User login
COPD care bundle curbs all-cause readmissions
at 30, 60, and 90 days, based on data from approximately 300 patients.
COPD remains a leading cause of mortality and a leading contributor to health care costs, but data suggest that adoption of an interdisciplinary care bundle could reduce hospital readmission for COPD patients, Sibyl Cherian, PharmD, BCPS, of Overlook Medical Center, Summit, N.J., and colleagues wrote. The Centers for Medicare & Medicaid Services has introduced both penalties and bundled payments for hospitals with excess all-cause readmission rates after hospitalizations, but more data are needed on the ability of a COPD care bundle to reduce readmission for COPD.
In a study published in the Journal of the American Pharmacists Association, the researchers assigned 127 individuals with COPD to a COPD care bundle arm and 189 to a control arm for treatment at a single center. The standard of care group was admitted between Jan. 1 and Dec. 31, 2017; the COPD care bundle group was admitted between Jan. 1 and Dec. 31, 2018. The mean age of the participants across both groups was 72 years, and more than 70% of patients in each group were White. The COPD care bundle was managed by a team including pulmonologists, hospitalists, care managers, advanced practice nurses, pharmacists, respiratory care practitioners, physical therapists, documentation specialists, quality improvement experts, social workers, and dietitians.
The primary outcome was 30-day all-cause readmission among adults with acute exacerbation of COPD.
Overall, the rate of 30-day all-cause readmissions was significantly lower in the COPD care bundle arm versus the control arm (11.8% vs. 21.7%; P = .017). Similar differences appeared between the care bundle group and control group for all-cause readmissions at 60 days (8.7% vs. 18%; P = .013) and 90 days (4.7% vs. 19.6%; P < .001).
Reasons for reduced readmissions after implementation of the COPD care bundle included pulmonary follow-up appointments of 7 days or less, significantly increased physical therapy consults, and significant escalation of COPD maintenance therapy, the researchers wrote.
Notably, pharmacists consulted with 68.5% of patients overall and assisted with access to outpatient medications for 45.7% of those in the care bundle arm, the researchers wrote. Patients in the COPD care bundle group were significantly more likely to have an escalation in maintenance therapy versus the control patients (44.9% vs. 22.2%; P < .001), which illustrates the importance of interventions by pharmacists in escalating therapy to reduce readmissions.
The study findings were limited by several factors including the retrospective design and use of data from a single center, the researchers noted. Other limitations included the lack of data on the need for therapy escalation in the control group and by the lack of controlling for socioeconomic status, which is a known risk factor for hospital readmission.
However, the results support the value of a COPD care bundle for reducing readmissions, and that such a bundle can be replicated at other hospitals, although more research is needed to evaluate the impact of other COPD care strategies, they emphasized.
The study received no outside funding. The researchers had no financial conflicts to disclose.
at 30, 60, and 90 days, based on data from approximately 300 patients.
COPD remains a leading cause of mortality and a leading contributor to health care costs, but data suggest that adoption of an interdisciplinary care bundle could reduce hospital readmission for COPD patients, Sibyl Cherian, PharmD, BCPS, of Overlook Medical Center, Summit, N.J., and colleagues wrote. The Centers for Medicare & Medicaid Services has introduced both penalties and bundled payments for hospitals with excess all-cause readmission rates after hospitalizations, but more data are needed on the ability of a COPD care bundle to reduce readmission for COPD.
In a study published in the Journal of the American Pharmacists Association, the researchers assigned 127 individuals with COPD to a COPD care bundle arm and 189 to a control arm for treatment at a single center. The standard of care group was admitted between Jan. 1 and Dec. 31, 2017; the COPD care bundle group was admitted between Jan. 1 and Dec. 31, 2018. The mean age of the participants across both groups was 72 years, and more than 70% of patients in each group were White. The COPD care bundle was managed by a team including pulmonologists, hospitalists, care managers, advanced practice nurses, pharmacists, respiratory care practitioners, physical therapists, documentation specialists, quality improvement experts, social workers, and dietitians.
The primary outcome was 30-day all-cause readmission among adults with acute exacerbation of COPD.
Overall, the rate of 30-day all-cause readmissions was significantly lower in the COPD care bundle arm versus the control arm (11.8% vs. 21.7%; P = .017). Similar differences appeared between the care bundle group and control group for all-cause readmissions at 60 days (8.7% vs. 18%; P = .013) and 90 days (4.7% vs. 19.6%; P < .001).
Reasons for reduced readmissions after implementation of the COPD care bundle included pulmonary follow-up appointments of 7 days or less, significantly increased physical therapy consults, and significant escalation of COPD maintenance therapy, the researchers wrote.
Notably, pharmacists consulted with 68.5% of patients overall and assisted with access to outpatient medications for 45.7% of those in the care bundle arm, the researchers wrote. Patients in the COPD care bundle group were significantly more likely to have an escalation in maintenance therapy versus the control patients (44.9% vs. 22.2%; P < .001), which illustrates the importance of interventions by pharmacists in escalating therapy to reduce readmissions.
The study findings were limited by several factors including the retrospective design and use of data from a single center, the researchers noted. Other limitations included the lack of data on the need for therapy escalation in the control group and by the lack of controlling for socioeconomic status, which is a known risk factor for hospital readmission.
However, the results support the value of a COPD care bundle for reducing readmissions, and that such a bundle can be replicated at other hospitals, although more research is needed to evaluate the impact of other COPD care strategies, they emphasized.
The study received no outside funding. The researchers had no financial conflicts to disclose.
at 30, 60, and 90 days, based on data from approximately 300 patients.
COPD remains a leading cause of mortality and a leading contributor to health care costs, but data suggest that adoption of an interdisciplinary care bundle could reduce hospital readmission for COPD patients, Sibyl Cherian, PharmD, BCPS, of Overlook Medical Center, Summit, N.J., and colleagues wrote. The Centers for Medicare & Medicaid Services has introduced both penalties and bundled payments for hospitals with excess all-cause readmission rates after hospitalizations, but more data are needed on the ability of a COPD care bundle to reduce readmission for COPD.
In a study published in the Journal of the American Pharmacists Association, the researchers assigned 127 individuals with COPD to a COPD care bundle arm and 189 to a control arm for treatment at a single center. The standard of care group was admitted between Jan. 1 and Dec. 31, 2017; the COPD care bundle group was admitted between Jan. 1 and Dec. 31, 2018. The mean age of the participants across both groups was 72 years, and more than 70% of patients in each group were White. The COPD care bundle was managed by a team including pulmonologists, hospitalists, care managers, advanced practice nurses, pharmacists, respiratory care practitioners, physical therapists, documentation specialists, quality improvement experts, social workers, and dietitians.
The primary outcome was 30-day all-cause readmission among adults with acute exacerbation of COPD.
Overall, the rate of 30-day all-cause readmissions was significantly lower in the COPD care bundle arm versus the control arm (11.8% vs. 21.7%; P = .017). Similar differences appeared between the care bundle group and control group for all-cause readmissions at 60 days (8.7% vs. 18%; P = .013) and 90 days (4.7% vs. 19.6%; P < .001).
Reasons for reduced readmissions after implementation of the COPD care bundle included pulmonary follow-up appointments of 7 days or less, significantly increased physical therapy consults, and significant escalation of COPD maintenance therapy, the researchers wrote.
Notably, pharmacists consulted with 68.5% of patients overall and assisted with access to outpatient medications for 45.7% of those in the care bundle arm, the researchers wrote. Patients in the COPD care bundle group were significantly more likely to have an escalation in maintenance therapy versus the control patients (44.9% vs. 22.2%; P < .001), which illustrates the importance of interventions by pharmacists in escalating therapy to reduce readmissions.
The study findings were limited by several factors including the retrospective design and use of data from a single center, the researchers noted. Other limitations included the lack of data on the need for therapy escalation in the control group and by the lack of controlling for socioeconomic status, which is a known risk factor for hospital readmission.
However, the results support the value of a COPD care bundle for reducing readmissions, and that such a bundle can be replicated at other hospitals, although more research is needed to evaluate the impact of other COPD care strategies, they emphasized.
The study received no outside funding. The researchers had no financial conflicts to disclose.
FROM THE JOURNAL OF THE AMERICAN PHARMACISTS ASSOCIATION
Nitrogen test predicts lung function decline
The slope of the alveolar plateau on the single-breath nitrogen test (SBN2) was a significant predictor of lung function decline and of chronic obstructive pulmonary disease (COPD), based on data from 907 adults.
In recent years, interest in small airways disease (SAD) has renewed, with research suggesting a link between SAD pathology and COPD progression, wrote Francesco Pistelli, MD, of the University of Pisa (Italy) and colleagues.
The SBN2 has been used to detect early SAD, but few studies have examined the relationship between SBN2 measures and lung function decline over time, they said.
In a study published in Pulmonology , the researchers reviewed data from adults aged 20 years and older who were enrolled in the Po River Delta prospective study in Italy. The study population included 907 individuals, with a mean age of 37.4 years; 56% were male.
The primary outcome was a change in lung function and incidence of COPD during an 8-year follow-up period.
COPD was defined using either the Global Initiative for Chronic Obstructive Lung Disease (GOLD) or ATS European Respiratory Society (ATS-ERS) criteria.
In a multinomial regression model, one SBN2 index, the slope of alveolar plateau (N2-slope) was significantly associated with rates of forced expiratory volume in 1 second (FEV1) decline, with a decrease of 7.93 mL/year for each one-unit change in N2-slope.
, with a relative risk of 1.81 for mild obstruction and 2.78 for severe obstruction based on GOLD criteria. The association was similar for COPD based on the ATS-ERS criteria, with a relative risk of 1.62 for mild obstruction and 3.40 for moderate to severe obstruction.
Age was associated with an increased COPD risk using the GOLD criteria, but not the ATS-ERS criteria; neither sex nor current or former smoking were associated with increased COPD risk for either measure.
The results are consistent with some previous longitudinal studies, but not others, possibly because of differences in sampling procedures, test techniques, or statistical approaches, the researchers wrote in their discussion.
The study findings were limited by several factors including incomplete data on closing capacity and vital capacity, and by the lack of bronchodilator for performing baseline spirometry, since bronchodilator testing was not recommended at the time of the study, the researchers noted.
However, the results support the role of SAD as a contributor to COPD, and the potential value of the SBN2 test, they said. “Large prospective studies are needed to evaluate whether new proposed functional or imaging tests that measure small airways impairment may be useful in the early detection of COPD,” they noted. In the meantime, “pulmonologists could rediscover an ‘old’ test, which could provide important information on their patients at risk for developing COPD,” they concluded.
The study was supported in part by the National Research Council, Targeted Project and the Italian Electric Power Authority (ENEL). The researchers had no financial conflicts to disclose.
The slope of the alveolar plateau on the single-breath nitrogen test (SBN2) was a significant predictor of lung function decline and of chronic obstructive pulmonary disease (COPD), based on data from 907 adults.
In recent years, interest in small airways disease (SAD) has renewed, with research suggesting a link between SAD pathology and COPD progression, wrote Francesco Pistelli, MD, of the University of Pisa (Italy) and colleagues.
The SBN2 has been used to detect early SAD, but few studies have examined the relationship between SBN2 measures and lung function decline over time, they said.
In a study published in Pulmonology , the researchers reviewed data from adults aged 20 years and older who were enrolled in the Po River Delta prospective study in Italy. The study population included 907 individuals, with a mean age of 37.4 years; 56% were male.
The primary outcome was a change in lung function and incidence of COPD during an 8-year follow-up period.
COPD was defined using either the Global Initiative for Chronic Obstructive Lung Disease (GOLD) or ATS European Respiratory Society (ATS-ERS) criteria.
In a multinomial regression model, one SBN2 index, the slope of alveolar plateau (N2-slope) was significantly associated with rates of forced expiratory volume in 1 second (FEV1) decline, with a decrease of 7.93 mL/year for each one-unit change in N2-slope.
, with a relative risk of 1.81 for mild obstruction and 2.78 for severe obstruction based on GOLD criteria. The association was similar for COPD based on the ATS-ERS criteria, with a relative risk of 1.62 for mild obstruction and 3.40 for moderate to severe obstruction.
Age was associated with an increased COPD risk using the GOLD criteria, but not the ATS-ERS criteria; neither sex nor current or former smoking were associated with increased COPD risk for either measure.
The results are consistent with some previous longitudinal studies, but not others, possibly because of differences in sampling procedures, test techniques, or statistical approaches, the researchers wrote in their discussion.
The study findings were limited by several factors including incomplete data on closing capacity and vital capacity, and by the lack of bronchodilator for performing baseline spirometry, since bronchodilator testing was not recommended at the time of the study, the researchers noted.
However, the results support the role of SAD as a contributor to COPD, and the potential value of the SBN2 test, they said. “Large prospective studies are needed to evaluate whether new proposed functional or imaging tests that measure small airways impairment may be useful in the early detection of COPD,” they noted. In the meantime, “pulmonologists could rediscover an ‘old’ test, which could provide important information on their patients at risk for developing COPD,” they concluded.
The study was supported in part by the National Research Council, Targeted Project and the Italian Electric Power Authority (ENEL). The researchers had no financial conflicts to disclose.
The slope of the alveolar plateau on the single-breath nitrogen test (SBN2) was a significant predictor of lung function decline and of chronic obstructive pulmonary disease (COPD), based on data from 907 adults.
In recent years, interest in small airways disease (SAD) has renewed, with research suggesting a link between SAD pathology and COPD progression, wrote Francesco Pistelli, MD, of the University of Pisa (Italy) and colleagues.
The SBN2 has been used to detect early SAD, but few studies have examined the relationship between SBN2 measures and lung function decline over time, they said.
In a study published in Pulmonology , the researchers reviewed data from adults aged 20 years and older who were enrolled in the Po River Delta prospective study in Italy. The study population included 907 individuals, with a mean age of 37.4 years; 56% were male.
The primary outcome was a change in lung function and incidence of COPD during an 8-year follow-up period.
COPD was defined using either the Global Initiative for Chronic Obstructive Lung Disease (GOLD) or ATS European Respiratory Society (ATS-ERS) criteria.
In a multinomial regression model, one SBN2 index, the slope of alveolar plateau (N2-slope) was significantly associated with rates of forced expiratory volume in 1 second (FEV1) decline, with a decrease of 7.93 mL/year for each one-unit change in N2-slope.
, with a relative risk of 1.81 for mild obstruction and 2.78 for severe obstruction based on GOLD criteria. The association was similar for COPD based on the ATS-ERS criteria, with a relative risk of 1.62 for mild obstruction and 3.40 for moderate to severe obstruction.
Age was associated with an increased COPD risk using the GOLD criteria, but not the ATS-ERS criteria; neither sex nor current or former smoking were associated with increased COPD risk for either measure.
The results are consistent with some previous longitudinal studies, but not others, possibly because of differences in sampling procedures, test techniques, or statistical approaches, the researchers wrote in their discussion.
The study findings were limited by several factors including incomplete data on closing capacity and vital capacity, and by the lack of bronchodilator for performing baseline spirometry, since bronchodilator testing was not recommended at the time of the study, the researchers noted.
However, the results support the role of SAD as a contributor to COPD, and the potential value of the SBN2 test, they said. “Large prospective studies are needed to evaluate whether new proposed functional or imaging tests that measure small airways impairment may be useful in the early detection of COPD,” they noted. In the meantime, “pulmonologists could rediscover an ‘old’ test, which could provide important information on their patients at risk for developing COPD,” they concluded.
The study was supported in part by the National Research Council, Targeted Project and the Italian Electric Power Authority (ENEL). The researchers had no financial conflicts to disclose.
FROM PULMONOLOGY
Pulmonologist consult at COPD admission reduces risk of return
according to a retrospective cohort review presented at the annual meeting of the American College of Chest Physicians (CHEST).
“When stratified by severity of COPD at the time of admission, the difference in the readmission rate was even greater,” reported Nakisa Hekmat-Joo, MD, a third-year resident at Staten Island University Hospital, New York.
Just as protocols have been developed for prompt initiation of antibiotics in patients with septicemia or prompt revascularization in patients with ST-segment elevated myocardial infarction (STEMI), Dr. Hekmat-Joo said the data from this study warrant a larger trial to evaluate whether an AECOPD admission protocol is warranted to improve outcomes and lower costs.
In this study, all AECOPD admissions were included from a recent 2-year period at two Staten Island hospitals. Of these, 198 patients received a pulmonologist consult within 24 hours. The remaining 92 patients were not evaluated by pulmonologists but were admitted and then managed by residents, internists, or others.
The primary outcome was length of stay (LOS). Although the slightly lower LOS in pulmonologist-treated group did not approach significance (4.16 vs. 4.21 days; P = .88), the readmission rate at 90 days, which was a secondary outcome, was reduced by almost half (30.1% vs. 57.6%; P < .0001).
At admission, there was no significant difference between those receiving a pulmonologist consult and those who did not. The average O2 saturation was lower in the group seen by a pulmonologist (93% vs. 95.4%; P < .0001), but the most striking difference was the low relative readmission rate, which remained significant after controlling for severity and pulmonary function.
“When we stratified patients for baseline severity, the advantage of a pulmonologist consult was even greater for those with the most severe disease,” Dr. Hekmat-Joo said. Among those with the greatest severity, the 90-day readmission rate was nearly three times greater in the absence of a pulmonologist consult (72% vs. 28%).
Although the comparison of outcomes for those receiving a pulmonologist consult vs. those who did not was adjusted for COPD severity, the potential for pulmonologist consults to be ordered for those patients who looked the sickest would have likely worked against the study result.
“We speculate that pulmonologists were more likely than internists to treat beyond standard guidelines, particularly in the event of greater severity,” Dr. Hekmat-Joo explained. These steps might include earlier use of noninvasive positive pressure ventilation or earlier initiation of rehabilitation strategies.
There were several signals that a pulmonologist consult led to more rigorous care.
“The average time to follow-up after hospitalization was 23 days for the pulmonologist group and 66 days for the nonpulmonologist group,” said Dr. Hekmat-Joo, noting this difference was highly significant (P = .0052).
Based on these results, Dr. Hekmat-Joo and her co-investigators are now working on a protocol for COPD admissions that involves a pulmonologist consult within 24 hours of admission. She hopes to test this protocol in a prospective trial.
“COPD remains a major cause of death and consumes enormous health care resources. About 30% of the cost of COPD care is due to readmissions,” she said, noting that readmissions adversely impact quality of life.
Asked if there was sufficient staff at her institution to allow for a pulmonologist consult with every COPD admission, Dr. Hekmat-Joo acknowledged that this has to be demonstrated, but compelling evidence of a benefit might prompt a redistribution of resources.
“If we can show that readmissions are substantially reduced, adding staff to perform these consults would be a good investment,” said Dr. Hekmat-Joo, indicating that improved outcomes could also attract the attention of third-party payers and those tracking quality-of-care metrics.
There is a strong rationale for a randomized prospective trial to confirm the value of a pulmonologist consultation following admission for an acute exacerbation of COPD, according to Nicola A. Hanania, MD, director, Airways Clinical Research Center, Baylor College of Medicine, Houston.
The potential for benefit as seen in this retrospective study is a rational expectation and might be related to more appropriate therapy upon discharge as well as to earlier and more rigorous follow-up, according to Dr. Hanania. Although he cautioned that there is a meaningful risk of selection bias in a retrospective study, he thinks this study “is certainly probing an important issue.”
“Mortality from a hospitalized COPD exacerbation exceeds that of a myocardial infarction,” Dr. Hanania pointed out. Noting that all patients with an MI are evaluated by a cardiologist, he sees the logic of a pulmonologist consult – although he acknowledged that evidence is needed.
“I strongly believe that a prospective study is feasible and will answer the question in an unbiased manner if done properly,” he said in an interview. If a multicenter, well-controlled study was positive, it could change practice.
In the event of a study showing major clinical benefits, particularly a reduction in mortality, “I believe it is feasible to have a pulmonary consult to see every COPD exacerbation patient admitted to the hospital,” Dr. Hanania said.
Dr. Hekmat-Joo reports no relevant financial relationships. Dr. Hanania has financial relationships with AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Mylan, Novartis, Regeneron, Sanofi, and Sunovion.
A version of this article first appeared on Medscape.com.
according to a retrospective cohort review presented at the annual meeting of the American College of Chest Physicians (CHEST).
“When stratified by severity of COPD at the time of admission, the difference in the readmission rate was even greater,” reported Nakisa Hekmat-Joo, MD, a third-year resident at Staten Island University Hospital, New York.
Just as protocols have been developed for prompt initiation of antibiotics in patients with septicemia or prompt revascularization in patients with ST-segment elevated myocardial infarction (STEMI), Dr. Hekmat-Joo said the data from this study warrant a larger trial to evaluate whether an AECOPD admission protocol is warranted to improve outcomes and lower costs.
In this study, all AECOPD admissions were included from a recent 2-year period at two Staten Island hospitals. Of these, 198 patients received a pulmonologist consult within 24 hours. The remaining 92 patients were not evaluated by pulmonologists but were admitted and then managed by residents, internists, or others.
The primary outcome was length of stay (LOS). Although the slightly lower LOS in pulmonologist-treated group did not approach significance (4.16 vs. 4.21 days; P = .88), the readmission rate at 90 days, which was a secondary outcome, was reduced by almost half (30.1% vs. 57.6%; P < .0001).
At admission, there was no significant difference between those receiving a pulmonologist consult and those who did not. The average O2 saturation was lower in the group seen by a pulmonologist (93% vs. 95.4%; P < .0001), but the most striking difference was the low relative readmission rate, which remained significant after controlling for severity and pulmonary function.
“When we stratified patients for baseline severity, the advantage of a pulmonologist consult was even greater for those with the most severe disease,” Dr. Hekmat-Joo said. Among those with the greatest severity, the 90-day readmission rate was nearly three times greater in the absence of a pulmonologist consult (72% vs. 28%).
Although the comparison of outcomes for those receiving a pulmonologist consult vs. those who did not was adjusted for COPD severity, the potential for pulmonologist consults to be ordered for those patients who looked the sickest would have likely worked against the study result.
“We speculate that pulmonologists were more likely than internists to treat beyond standard guidelines, particularly in the event of greater severity,” Dr. Hekmat-Joo explained. These steps might include earlier use of noninvasive positive pressure ventilation or earlier initiation of rehabilitation strategies.
There were several signals that a pulmonologist consult led to more rigorous care.
“The average time to follow-up after hospitalization was 23 days for the pulmonologist group and 66 days for the nonpulmonologist group,” said Dr. Hekmat-Joo, noting this difference was highly significant (P = .0052).
Based on these results, Dr. Hekmat-Joo and her co-investigators are now working on a protocol for COPD admissions that involves a pulmonologist consult within 24 hours of admission. She hopes to test this protocol in a prospective trial.
“COPD remains a major cause of death and consumes enormous health care resources. About 30% of the cost of COPD care is due to readmissions,” she said, noting that readmissions adversely impact quality of life.
Asked if there was sufficient staff at her institution to allow for a pulmonologist consult with every COPD admission, Dr. Hekmat-Joo acknowledged that this has to be demonstrated, but compelling evidence of a benefit might prompt a redistribution of resources.
“If we can show that readmissions are substantially reduced, adding staff to perform these consults would be a good investment,” said Dr. Hekmat-Joo, indicating that improved outcomes could also attract the attention of third-party payers and those tracking quality-of-care metrics.
There is a strong rationale for a randomized prospective trial to confirm the value of a pulmonologist consultation following admission for an acute exacerbation of COPD, according to Nicola A. Hanania, MD, director, Airways Clinical Research Center, Baylor College of Medicine, Houston.
The potential for benefit as seen in this retrospective study is a rational expectation and might be related to more appropriate therapy upon discharge as well as to earlier and more rigorous follow-up, according to Dr. Hanania. Although he cautioned that there is a meaningful risk of selection bias in a retrospective study, he thinks this study “is certainly probing an important issue.”
“Mortality from a hospitalized COPD exacerbation exceeds that of a myocardial infarction,” Dr. Hanania pointed out. Noting that all patients with an MI are evaluated by a cardiologist, he sees the logic of a pulmonologist consult – although he acknowledged that evidence is needed.
“I strongly believe that a prospective study is feasible and will answer the question in an unbiased manner if done properly,” he said in an interview. If a multicenter, well-controlled study was positive, it could change practice.
In the event of a study showing major clinical benefits, particularly a reduction in mortality, “I believe it is feasible to have a pulmonary consult to see every COPD exacerbation patient admitted to the hospital,” Dr. Hanania said.
Dr. Hekmat-Joo reports no relevant financial relationships. Dr. Hanania has financial relationships with AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Mylan, Novartis, Regeneron, Sanofi, and Sunovion.
A version of this article first appeared on Medscape.com.
according to a retrospective cohort review presented at the annual meeting of the American College of Chest Physicians (CHEST).
“When stratified by severity of COPD at the time of admission, the difference in the readmission rate was even greater,” reported Nakisa Hekmat-Joo, MD, a third-year resident at Staten Island University Hospital, New York.
Just as protocols have been developed for prompt initiation of antibiotics in patients with septicemia or prompt revascularization in patients with ST-segment elevated myocardial infarction (STEMI), Dr. Hekmat-Joo said the data from this study warrant a larger trial to evaluate whether an AECOPD admission protocol is warranted to improve outcomes and lower costs.
In this study, all AECOPD admissions were included from a recent 2-year period at two Staten Island hospitals. Of these, 198 patients received a pulmonologist consult within 24 hours. The remaining 92 patients were not evaluated by pulmonologists but were admitted and then managed by residents, internists, or others.
The primary outcome was length of stay (LOS). Although the slightly lower LOS in pulmonologist-treated group did not approach significance (4.16 vs. 4.21 days; P = .88), the readmission rate at 90 days, which was a secondary outcome, was reduced by almost half (30.1% vs. 57.6%; P < .0001).
At admission, there was no significant difference between those receiving a pulmonologist consult and those who did not. The average O2 saturation was lower in the group seen by a pulmonologist (93% vs. 95.4%; P < .0001), but the most striking difference was the low relative readmission rate, which remained significant after controlling for severity and pulmonary function.
“When we stratified patients for baseline severity, the advantage of a pulmonologist consult was even greater for those with the most severe disease,” Dr. Hekmat-Joo said. Among those with the greatest severity, the 90-day readmission rate was nearly three times greater in the absence of a pulmonologist consult (72% vs. 28%).
Although the comparison of outcomes for those receiving a pulmonologist consult vs. those who did not was adjusted for COPD severity, the potential for pulmonologist consults to be ordered for those patients who looked the sickest would have likely worked against the study result.
“We speculate that pulmonologists were more likely than internists to treat beyond standard guidelines, particularly in the event of greater severity,” Dr. Hekmat-Joo explained. These steps might include earlier use of noninvasive positive pressure ventilation or earlier initiation of rehabilitation strategies.
There were several signals that a pulmonologist consult led to more rigorous care.
“The average time to follow-up after hospitalization was 23 days for the pulmonologist group and 66 days for the nonpulmonologist group,” said Dr. Hekmat-Joo, noting this difference was highly significant (P = .0052).
Based on these results, Dr. Hekmat-Joo and her co-investigators are now working on a protocol for COPD admissions that involves a pulmonologist consult within 24 hours of admission. She hopes to test this protocol in a prospective trial.
“COPD remains a major cause of death and consumes enormous health care resources. About 30% of the cost of COPD care is due to readmissions,” she said, noting that readmissions adversely impact quality of life.
Asked if there was sufficient staff at her institution to allow for a pulmonologist consult with every COPD admission, Dr. Hekmat-Joo acknowledged that this has to be demonstrated, but compelling evidence of a benefit might prompt a redistribution of resources.
“If we can show that readmissions are substantially reduced, adding staff to perform these consults would be a good investment,” said Dr. Hekmat-Joo, indicating that improved outcomes could also attract the attention of third-party payers and those tracking quality-of-care metrics.
There is a strong rationale for a randomized prospective trial to confirm the value of a pulmonologist consultation following admission for an acute exacerbation of COPD, according to Nicola A. Hanania, MD, director, Airways Clinical Research Center, Baylor College of Medicine, Houston.
The potential for benefit as seen in this retrospective study is a rational expectation and might be related to more appropriate therapy upon discharge as well as to earlier and more rigorous follow-up, according to Dr. Hanania. Although he cautioned that there is a meaningful risk of selection bias in a retrospective study, he thinks this study “is certainly probing an important issue.”
“Mortality from a hospitalized COPD exacerbation exceeds that of a myocardial infarction,” Dr. Hanania pointed out. Noting that all patients with an MI are evaluated by a cardiologist, he sees the logic of a pulmonologist consult – although he acknowledged that evidence is needed.
“I strongly believe that a prospective study is feasible and will answer the question in an unbiased manner if done properly,” he said in an interview. If a multicenter, well-controlled study was positive, it could change practice.
In the event of a study showing major clinical benefits, particularly a reduction in mortality, “I believe it is feasible to have a pulmonary consult to see every COPD exacerbation patient admitted to the hospital,” Dr. Hanania said.
Dr. Hekmat-Joo reports no relevant financial relationships. Dr. Hanania has financial relationships with AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Mylan, Novartis, Regeneron, Sanofi, and Sunovion.
A version of this article first appeared on Medscape.com.
FROM CHEST 2022
Global Initiative for Chronic Obstructive Lung Disease guidelines 2022: Management and treatment
In the United States and around the globe, chronic obstructive pulmonary disease (COPD) remains one of the leading causes of death. In addition to new diagnostic guidelines, the Global Initiative for Chronic Obstructive Lung Disease 2022 Report, or GOLD report, sets forth recommendations for management and treatment.
According to the GOLD report, initial management of COPD should aim at reducing exposure to risk factors such as smoking or other chemical exposures. In addition to medications, stable COPD patients should be evaluated for inhaler technique, adherence to prescribed therapies, smoking status, and continued exposure to other risk factors. Also, physical activity should be advised and pulmonary rehabilitation should be considered. Spirometry should be performed annually.
These guidelines offer very practical advice but often are difficult to implement in clinical practice. Everyone knows smoking is harmful and quitting provides huge health benefits, not only regarding COPD. However, nicotine is very addictive, and most smokers cannot just quit. Many need smoking cessation aids and counseling. Additionally, some smokers just don’t want to quit. Regarding workplace exposures, it often is not easy for someone just to change their job. Many are afraid to speak because they are afraid of losing their jobs. Everyone, not just patients with COPD, can benefit from increased physical activity, and all doctors know how difficult it is to motivate patients to do this.
The decision to initiate medications should be based on an individual patient’s symptoms and risk of exacerbations. In general, long-acting bronchodilators, including long-acting beta agonists (LABA) and long-acting muscarinic antagonists (LAMA), are preferred except when immediate relief of dyspnea is needed, and then short-acting bronchodilators should be used. Either a single long-acting or dual long-acting bronchodilator can be initiated. If a patient continues to have dyspnea on a single long-acting bronchodilator, treatment should be switched to a dual therapy.
In general, inhaled corticosteroids (ICS) are not recommended for stable COPD patients. If a patient has exacerbations despite appropriate treatment with LABAs, an ICS may be added to the LABA, the GOLD guidelines say. Oral corticosteroids are not recommended for long-term use. PDE4 inhibitors should be considered in patents with severe to very severe airflow obstruction, chronic bronchitis, and exacerbations. Macrolide antibiotics, especially azithromycin, can be considered in acute exacerbations. There is no evidence to support the use of antitussives and mucolytics are advised in only certain patients. Inhaled bronchodilators are advised over oral ones and theophylline is recommended when long-acting bronchodilators are unavailable or unaffordable.
In clinical practice, I see many patients treated based on symptomatology with spirometry testing not being done. This may help control many symptoms, but unless my patient has an accurate diagnosis, I won’t know if my patient is receiving the correct treatment.
It is important to keep in mind that COPD is a progressive disease and without appropriate treatment and monitoring, it will just get worse, and this is most likely to be irreversible.
Medications and treatment goals for patients with COPD
Patients with alpha-1 antitrypsin deficiency may benefit from the addition of alpha-1 antitrypsin augmentation therapy, the new guidelines say. In patients with severe disease experiencing dyspnea, oral and parental opioids can be considered. Medications that are used to treat primary pulmonary hypertension are not advised to treat pulmonary hypertension secondary to COPD.
The treatment goals of COPD should be to decrease severity of symptoms, reduce the occurrence of exacerbations, and improve exercise tolerance. Peripheral eosinophil counts can be used to guide the use of ICS to prevent exacerbations. However, the best predictor of exacerbations is previous exacerbations. Frequent exacerbations are defined as two or more annually. Additionally, deteriorating airflow is correlated with increased risk of exacerbations, hospitalizations, and death. Forced expiratory volume in 1 second (FEV1) alone lacks precision to predict exacerbations or death.
Vaccines and pulmonary rehabilitation recommended
The Centers for Disease Control and Prevention and World Health Organization recommend several vaccines for stable patients with COPD. Influenza vaccine was shown to reduce serious complications in COPD patients. Pneumococcal vaccines (PCV13 and PPSV23) reduced the likelihood of COPD exacerbations. The COVID-19 vaccine also has been effective at reducing hospitalizations, in particular ICU admissions, and death in patients with COPD. The CDC also recommends TdaP and Zoster vaccines.
An acute exacerbation of COPD occurs when a patient experiences worsening of respiratory symptoms that requires additional treatment, according to the updated GOLD guidelines. They are usually associated with increased airway inflammation, mucous productions, and trapping of gases. They are often triggered by viral infections, but bacterial and environment factors play a role as well. Less commonly, fungi such as Aspergillus can be observed as well. COPD exacerbations contribute to overall progression of the disease.
In patients with hypoxemia, supplemental oxygen should be titrated to a target O2 saturation of 88%-92%. It is important to follow blood gases to be sure adequate oxygenation is taking place while at the same time avoiding carbon dioxide retention and/or worsening acidosis. In patients with severe exacerbations whose dyspnea does not respond to initial emergency therapy, ICU admission is warranted. Other factors indicating the need for ICU admission include mental status changes, persistent or worsening hypoxemia, severe or worsening respiratory acidosis, the need for mechanical ventilation, and hemodynamic instability. Following an acute exacerbation, steps to prevent further exacerbations should be initiated.
Systemic glucocorticoids are indicated during acute exacerbations. They have been shown to hasten recovery time and improve functioning of the lungs as well as oxygenation. It is recommended to give prednisone 40 mg per day for 5 days. Antibiotics should be used in exacerbations if patients have dyspnea, sputum production, and purulence of the sputum or require mechanical ventilation. The choice of which antibiotic to use should be based on local bacterial resistance.
Pulmonary rehabilitation is an important component of COPD management. It incorporates exercise, education, and self-management aimed to change behavior and improve conditioning. The benefits of rehab have been shown to be considerable. The optimal length is 6-8 weeks. Palliative and end-of-life care are also very important factors to consider when treating COPD patients, according to the GOLD guidelines.
COPD is a very common disease and cause of mortality seen by family physicians. The GOLD report is an extensive document providing very clear guidelines and evidence to support these guidelines in every level of the treatment of COPD patients. As primary care doctors, we are often the first to treat patients with COPD and it is important to know the latest guidelines.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at fpnews@mdedge.com.
In the United States and around the globe, chronic obstructive pulmonary disease (COPD) remains one of the leading causes of death. In addition to new diagnostic guidelines, the Global Initiative for Chronic Obstructive Lung Disease 2022 Report, or GOLD report, sets forth recommendations for management and treatment.
According to the GOLD report, initial management of COPD should aim at reducing exposure to risk factors such as smoking or other chemical exposures. In addition to medications, stable COPD patients should be evaluated for inhaler technique, adherence to prescribed therapies, smoking status, and continued exposure to other risk factors. Also, physical activity should be advised and pulmonary rehabilitation should be considered. Spirometry should be performed annually.
These guidelines offer very practical advice but often are difficult to implement in clinical practice. Everyone knows smoking is harmful and quitting provides huge health benefits, not only regarding COPD. However, nicotine is very addictive, and most smokers cannot just quit. Many need smoking cessation aids and counseling. Additionally, some smokers just don’t want to quit. Regarding workplace exposures, it often is not easy for someone just to change their job. Many are afraid to speak because they are afraid of losing their jobs. Everyone, not just patients with COPD, can benefit from increased physical activity, and all doctors know how difficult it is to motivate patients to do this.
The decision to initiate medications should be based on an individual patient’s symptoms and risk of exacerbations. In general, long-acting bronchodilators, including long-acting beta agonists (LABA) and long-acting muscarinic antagonists (LAMA), are preferred except when immediate relief of dyspnea is needed, and then short-acting bronchodilators should be used. Either a single long-acting or dual long-acting bronchodilator can be initiated. If a patient continues to have dyspnea on a single long-acting bronchodilator, treatment should be switched to a dual therapy.
In general, inhaled corticosteroids (ICS) are not recommended for stable COPD patients. If a patient has exacerbations despite appropriate treatment with LABAs, an ICS may be added to the LABA, the GOLD guidelines say. Oral corticosteroids are not recommended for long-term use. PDE4 inhibitors should be considered in patents with severe to very severe airflow obstruction, chronic bronchitis, and exacerbations. Macrolide antibiotics, especially azithromycin, can be considered in acute exacerbations. There is no evidence to support the use of antitussives and mucolytics are advised in only certain patients. Inhaled bronchodilators are advised over oral ones and theophylline is recommended when long-acting bronchodilators are unavailable or unaffordable.
In clinical practice, I see many patients treated based on symptomatology with spirometry testing not being done. This may help control many symptoms, but unless my patient has an accurate diagnosis, I won’t know if my patient is receiving the correct treatment.
It is important to keep in mind that COPD is a progressive disease and without appropriate treatment and monitoring, it will just get worse, and this is most likely to be irreversible.
Medications and treatment goals for patients with COPD
Patients with alpha-1 antitrypsin deficiency may benefit from the addition of alpha-1 antitrypsin augmentation therapy, the new guidelines say. In patients with severe disease experiencing dyspnea, oral and parental opioids can be considered. Medications that are used to treat primary pulmonary hypertension are not advised to treat pulmonary hypertension secondary to COPD.
The treatment goals of COPD should be to decrease severity of symptoms, reduce the occurrence of exacerbations, and improve exercise tolerance. Peripheral eosinophil counts can be used to guide the use of ICS to prevent exacerbations. However, the best predictor of exacerbations is previous exacerbations. Frequent exacerbations are defined as two or more annually. Additionally, deteriorating airflow is correlated with increased risk of exacerbations, hospitalizations, and death. Forced expiratory volume in 1 second (FEV1) alone lacks precision to predict exacerbations or death.
Vaccines and pulmonary rehabilitation recommended
The Centers for Disease Control and Prevention and World Health Organization recommend several vaccines for stable patients with COPD. Influenza vaccine was shown to reduce serious complications in COPD patients. Pneumococcal vaccines (PCV13 and PPSV23) reduced the likelihood of COPD exacerbations. The COVID-19 vaccine also has been effective at reducing hospitalizations, in particular ICU admissions, and death in patients with COPD. The CDC also recommends TdaP and Zoster vaccines.
An acute exacerbation of COPD occurs when a patient experiences worsening of respiratory symptoms that requires additional treatment, according to the updated GOLD guidelines. They are usually associated with increased airway inflammation, mucous productions, and trapping of gases. They are often triggered by viral infections, but bacterial and environment factors play a role as well. Less commonly, fungi such as Aspergillus can be observed as well. COPD exacerbations contribute to overall progression of the disease.
In patients with hypoxemia, supplemental oxygen should be titrated to a target O2 saturation of 88%-92%. It is important to follow blood gases to be sure adequate oxygenation is taking place while at the same time avoiding carbon dioxide retention and/or worsening acidosis. In patients with severe exacerbations whose dyspnea does not respond to initial emergency therapy, ICU admission is warranted. Other factors indicating the need for ICU admission include mental status changes, persistent or worsening hypoxemia, severe or worsening respiratory acidosis, the need for mechanical ventilation, and hemodynamic instability. Following an acute exacerbation, steps to prevent further exacerbations should be initiated.
Systemic glucocorticoids are indicated during acute exacerbations. They have been shown to hasten recovery time and improve functioning of the lungs as well as oxygenation. It is recommended to give prednisone 40 mg per day for 5 days. Antibiotics should be used in exacerbations if patients have dyspnea, sputum production, and purulence of the sputum or require mechanical ventilation. The choice of which antibiotic to use should be based on local bacterial resistance.
Pulmonary rehabilitation is an important component of COPD management. It incorporates exercise, education, and self-management aimed to change behavior and improve conditioning. The benefits of rehab have been shown to be considerable. The optimal length is 6-8 weeks. Palliative and end-of-life care are also very important factors to consider when treating COPD patients, according to the GOLD guidelines.
COPD is a very common disease and cause of mortality seen by family physicians. The GOLD report is an extensive document providing very clear guidelines and evidence to support these guidelines in every level of the treatment of COPD patients. As primary care doctors, we are often the first to treat patients with COPD and it is important to know the latest guidelines.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at fpnews@mdedge.com.
In the United States and around the globe, chronic obstructive pulmonary disease (COPD) remains one of the leading causes of death. In addition to new diagnostic guidelines, the Global Initiative for Chronic Obstructive Lung Disease 2022 Report, or GOLD report, sets forth recommendations for management and treatment.
According to the GOLD report, initial management of COPD should aim at reducing exposure to risk factors such as smoking or other chemical exposures. In addition to medications, stable COPD patients should be evaluated for inhaler technique, adherence to prescribed therapies, smoking status, and continued exposure to other risk factors. Also, physical activity should be advised and pulmonary rehabilitation should be considered. Spirometry should be performed annually.
These guidelines offer very practical advice but often are difficult to implement in clinical practice. Everyone knows smoking is harmful and quitting provides huge health benefits, not only regarding COPD. However, nicotine is very addictive, and most smokers cannot just quit. Many need smoking cessation aids and counseling. Additionally, some smokers just don’t want to quit. Regarding workplace exposures, it often is not easy for someone just to change their job. Many are afraid to speak because they are afraid of losing their jobs. Everyone, not just patients with COPD, can benefit from increased physical activity, and all doctors know how difficult it is to motivate patients to do this.
The decision to initiate medications should be based on an individual patient’s symptoms and risk of exacerbations. In general, long-acting bronchodilators, including long-acting beta agonists (LABA) and long-acting muscarinic antagonists (LAMA), are preferred except when immediate relief of dyspnea is needed, and then short-acting bronchodilators should be used. Either a single long-acting or dual long-acting bronchodilator can be initiated. If a patient continues to have dyspnea on a single long-acting bronchodilator, treatment should be switched to a dual therapy.
In general, inhaled corticosteroids (ICS) are not recommended for stable COPD patients. If a patient has exacerbations despite appropriate treatment with LABAs, an ICS may be added to the LABA, the GOLD guidelines say. Oral corticosteroids are not recommended for long-term use. PDE4 inhibitors should be considered in patents with severe to very severe airflow obstruction, chronic bronchitis, and exacerbations. Macrolide antibiotics, especially azithromycin, can be considered in acute exacerbations. There is no evidence to support the use of antitussives and mucolytics are advised in only certain patients. Inhaled bronchodilators are advised over oral ones and theophylline is recommended when long-acting bronchodilators are unavailable or unaffordable.
In clinical practice, I see many patients treated based on symptomatology with spirometry testing not being done. This may help control many symptoms, but unless my patient has an accurate diagnosis, I won’t know if my patient is receiving the correct treatment.
It is important to keep in mind that COPD is a progressive disease and without appropriate treatment and monitoring, it will just get worse, and this is most likely to be irreversible.
Medications and treatment goals for patients with COPD
Patients with alpha-1 antitrypsin deficiency may benefit from the addition of alpha-1 antitrypsin augmentation therapy, the new guidelines say. In patients with severe disease experiencing dyspnea, oral and parental opioids can be considered. Medications that are used to treat primary pulmonary hypertension are not advised to treat pulmonary hypertension secondary to COPD.
The treatment goals of COPD should be to decrease severity of symptoms, reduce the occurrence of exacerbations, and improve exercise tolerance. Peripheral eosinophil counts can be used to guide the use of ICS to prevent exacerbations. However, the best predictor of exacerbations is previous exacerbations. Frequent exacerbations are defined as two or more annually. Additionally, deteriorating airflow is correlated with increased risk of exacerbations, hospitalizations, and death. Forced expiratory volume in 1 second (FEV1) alone lacks precision to predict exacerbations or death.
Vaccines and pulmonary rehabilitation recommended
The Centers for Disease Control and Prevention and World Health Organization recommend several vaccines for stable patients with COPD. Influenza vaccine was shown to reduce serious complications in COPD patients. Pneumococcal vaccines (PCV13 and PPSV23) reduced the likelihood of COPD exacerbations. The COVID-19 vaccine also has been effective at reducing hospitalizations, in particular ICU admissions, and death in patients with COPD. The CDC also recommends TdaP and Zoster vaccines.
An acute exacerbation of COPD occurs when a patient experiences worsening of respiratory symptoms that requires additional treatment, according to the updated GOLD guidelines. They are usually associated with increased airway inflammation, mucous productions, and trapping of gases. They are often triggered by viral infections, but bacterial and environment factors play a role as well. Less commonly, fungi such as Aspergillus can be observed as well. COPD exacerbations contribute to overall progression of the disease.
In patients with hypoxemia, supplemental oxygen should be titrated to a target O2 saturation of 88%-92%. It is important to follow blood gases to be sure adequate oxygenation is taking place while at the same time avoiding carbon dioxide retention and/or worsening acidosis. In patients with severe exacerbations whose dyspnea does not respond to initial emergency therapy, ICU admission is warranted. Other factors indicating the need for ICU admission include mental status changes, persistent or worsening hypoxemia, severe or worsening respiratory acidosis, the need for mechanical ventilation, and hemodynamic instability. Following an acute exacerbation, steps to prevent further exacerbations should be initiated.
Systemic glucocorticoids are indicated during acute exacerbations. They have been shown to hasten recovery time and improve functioning of the lungs as well as oxygenation. It is recommended to give prednisone 40 mg per day for 5 days. Antibiotics should be used in exacerbations if patients have dyspnea, sputum production, and purulence of the sputum or require mechanical ventilation. The choice of which antibiotic to use should be based on local bacterial resistance.
Pulmonary rehabilitation is an important component of COPD management. It incorporates exercise, education, and self-management aimed to change behavior and improve conditioning. The benefits of rehab have been shown to be considerable. The optimal length is 6-8 weeks. Palliative and end-of-life care are also very important factors to consider when treating COPD patients, according to the GOLD guidelines.
COPD is a very common disease and cause of mortality seen by family physicians. The GOLD report is an extensive document providing very clear guidelines and evidence to support these guidelines in every level of the treatment of COPD patients. As primary care doctors, we are often the first to treat patients with COPD and it is important to know the latest guidelines.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at fpnews@mdedge.com.
Mucus unplugged
Just uttering the word “mucus” is often sufficient to elicit amusement from those within earshot, but to patients with chronic inflammatory airway diseases, mucus is no laughing matter.
, which are then moved by cilia out of the airways for expulsion through coughing.
But in cystic fibrosis (CF), for example, mucus hypersecretion can be deadly. The underlying pathology of CF – a mutation in the CFTR gene, which codes for the protein CF transmembrane conductance regulator – leads to buildup in the lungs of abnormally viscous and sticky mucus, resulting in frequent, severe infections (particularly with Pseudomonas aeruginosa), progressive lung damage, and prior to the development of effective disease management, significantly premature death.
Mucus hypersecretion is also a feature of chronic obstructive pulmonary disease (COPD), noted Victor Kim, MD, from Temple University, Philadelphia, Christopher M. Evans, PhD, from the University of Colorado at Denver, Aurora, and Burton F. Dickey, MD, from the University of Texas MD Anderson Cancer Center, Houston.
In COPD, “mucus dysfunction arises from several mechanisms, including excess production due to inflammation, decreased elimination due to impaired ciliary clearance and reduced cough efficiency, and excessive concentration due to smoke-induced dysfunction of transepithelial anion transport resembling CF,” they wrote in an editorial published in the American Journal of Respiratory and Critical Care Medicine.
In patients with idiopathic pulmonary fibrosis, a polymorphism in the enhancer region of MUC5B, a gene that encodes for mucin glycoproteins, results in a 20-fold overexpression of the gene and prominent mucus production that has been shown to parallel lung inflammation and decline in forced vital capacity (FVC).
In patients with asthma, up-regulation of MUC5AC and stimulated mucus secretion conspire to obstruct airways, which can in extreme cases lead to death.
‘Short shrift’
Yet until recently, the role of mucus hypersecretion in diseases such as COPD has been largely overlooked, or as Dr. Kim and colleagues put it, “airway mucus often receives short shrift from clinicians.”
“It’s a pretty hot topic in pulmonary medicine today because it has been so neglected for so long,” Dr. Dickey said in an interview with CHEST Physician. “As clinicians we haven’t had a way to identify who needs treatment, which is ridiculous, because many of the people who expectorate a lot, like those with chronic bronchitis, don’t actually have small airway obstruction, and conversely, a lot of asthmatics, who have very serious small airway obstruction, don’t expectorate, so you can’t really tell from symptoms.”
What has changed in recent years is the use of chest CT to image muco-obstructive pathology, commonly called “mucus plugging” in the peripheral airways of patients with COPD and asthma.
“In the last decade or so, we’ve seen the emergence in obstructive lung diseases such as asthma and COPD the use of more objective measures on CT scans, including the problem of mucus plugging, which is unfortunately very common,” Dr. Kim said in an interview.
The discovery of the extent and severity of mucus in obstructive lung diseases has led to new strategies to combat mucus overconcentration, such as hydration, mucolytics, and an intriguing investigational approach to decrease calcium-induced hypersecretion with designer peptides.
Mighty mucins
Under normal physiologic conditions mucus is composed largely of water (97%) and salts (2%), with the remainder consisting of entrapped globular proteins (0.7%) and mucins (0.3%), Dr. Dickey explains.
Yet those meager mucins pack a real punch, with the ability to absorb 300 times their mass of water after secretion, creating mucus of optimal consistency and viscoelasticity.
“Personally, I’ve never understood – maybe I should have paid more attention in physics – how a compound can absorb 300-fold its mass, but it does,” he said.
In a recent review article in the journal Clinical and Translational Medicine, Dr. Dickey and colleagues described how good mucus can go bad.
“[H]igh levels of mucin production from inflammatory stimulation (termed ‘mucous metaplasia’), followed by rapid release (together, termed ‘mucus hypersecretion’), can plug airways due to mucus volume expansion. In addition, if available lumenal liquid is insufficient, concentrated mucus of excessive viscoelasticity and adhesivity can cause mucus stasis,” they wrote.
Therapeutic strategies
In patients with CF, CFTR modulator therapy has markedly reduced but not eliminated the need for some patients to have mucolytic therapy, which may include dornase alfa, a recombinant human deoxyribonuclease that reduces the viscosity of lung secretions, hypertonic saline inhaled twice daily (for patients 12 and older), mannitol, and physical manipulations to help patients clear mucus. The manipulations can include both manual percussion and the use of devices for high-frequency chest wall oscillation.
Unlike in CF, where treating the underlying genetic pathology can help to resolve the thick, sticky mucus problems and thereby significantly reduce risk of infections and progressive lung damage, treatment of mucus metaplasia or hypersecretion in other diseases is aimed at symptomatic relief; it is still unclear whether symptomatic improvement of mucus overproduction would correlate with other disease-related outcomes, Dr. Kim and Dr. Dickey noted.
Potential therapeutic strategies to reduce excess mucus in the lungs include the use of mucolytic agents to thin secretions for more effective expulsion, decreasing mucus production through the use of an interleukin-13 (IL-13) inhibitor such as the anti-asthma agent dupilumab (Dupixent), and a novel strategy, still in the experimental phase, aimed at “disrupting the fusion of mucin storage granules with the cell membrane, thereby blocking secretion,” wrote Irina Gitlin, PhD, and John Fahy, MD, from the University of California, San Francisco, in Nature.
They were referring to research by Dr. Dickey and colleagues described in the same issue of Nature focusing on the inhibition of calcium-triggered mucus secretion by the use of hydrocarbon-stapled peptides, short chains of amino acids stabilized with a chemical bridge to a hydrocarbon molecule.
Knocking secretion down, but not out
The work has centered on decreasing overproduction of mucins with a focus on the signals for mucin production, including IL-13 and interleukin-1 beta, and on the signals for rapid release of mucins, including adenosine 5’-triphosphate (ATP), best known as an intracellular energy-storage module.
“But ATP is also steadily released by ciliated cells in response to the shear stress of tidal breathing, and it tells the neighboring secretory cells to slowly and steadily release mucin. But if the ciliated cells get stressed by any of a number of mechanisms, it can release a lot of ATP, and then the secretory cell can explosively release essentially all of its mucin content,” Dr. Dickey explained.
Other important signals for rapid release of mucins are acetylcholine and histamine, and all three of these agonists – ATP, acetylcholine, and histamine – cause a rise in intracellular calcium, which triggers calcium sensors that then lead to calcium-triggered membrane fusion and secretion.
Working as a postdoc in the Dickey laboratory, Dr. Evans had previously shown that deleting MUC5B in mice led to early development of serious lung abnormalities, some of which were fatal, indicating that MUC5B, a gene that is highly preserved in evolution, is essential for respiratory health.
This observation was later supported by a study of a family with a pattern of hereditary mucin deficiency caused by a homozygous loss-of-function mutation in MUC5B. The main subject in this study was an adult woman with unexplained bronchiectasis, impaired pulmonary function, and repeated Staphylococcus aureus infections. Her sibling, who also had the biallelic mutation, had extensive sinus disease with nasal polyps. Other siblings who were heterozygous for the mutation were asymptomatic but had mild functional lung impairment.
The trick for the investigators, then, was to figure out how to reduce stimulated release of stored mucins while still preserving normal release of mucins to allow for ciliary clearance of mucus, and Dr. Dickey and colleagues appear to have accomplished this, at least in mice.
They first validated as a potential therapeutic target a protein labeled synaptotagmin-2 (Syt2). Syt2 is a calcium sensor that is an essential part of the system that triggers calcium-triggered secretion. In a model for allergic asthma, mice with Syt2 deleted from airway epithelia had marked reductions in both stimulated mucin secretion and in mucus occlusion in airway lumens, but remained otherwise healthy with normal lung function.
Working with structural biologist Axel Brunger, PhD, from Stanford (Calif.) University, Dr. Dickey and coinvestigators developed and validated a peptide that could specifically inhibit Syt2, and found that it mimicked the action of the Syt2 deletion, preventing mucus occlusion in the allergic asthma model without adversely effecting normal production.
Not ready for prime time
Dr. Dickey and colleagues are now working to translate the therapy into a form that can be used in humans, most likely as an aerosol that could be used for acute treatment of patients with mucus plugging from asthma and COPD, and also as a therapy for patients with chronic disease.
“In the chronic situation, what we would hope to do is identify patients with muco-obstructive lung disease – asthma, COPD, cystic fibrosis – who have airway mucus obstruction and then use the inhaled peptide on a regular basis as one part of a program to try to prevent this chronic mucus occlusion,” Dr. Dickey said.
As Dr. Gitlin and Dr. Fahy wrote in their editorial, “by confirming that it is possible to block calcium-regulated mucin secretion, Lai and colleagues have shown the potential of such an approach as a new therapeutic strategy for lung illnesses associated with mucus pathology, including diseases such as asthma and COPD, for which there is a large unmet medical need.”
The study by Dr. Dickey and colleagues was supported by grants from the German Research Foundation, National Institutes of Health and the Cystic Fibrosis Foundation. Dr. Dickey disclosed consulting for Arrowhead Pharmaceuticals. Dr. Kim disclosed personal fees from Medscape and others. Dr. Evans reported no relevant disclosures. Dr. Fahy and Dr. Gitlin are named inventors on patents for mucolytic drugs, and shareholders in Aer Therapeutics.
Just uttering the word “mucus” is often sufficient to elicit amusement from those within earshot, but to patients with chronic inflammatory airway diseases, mucus is no laughing matter.
, which are then moved by cilia out of the airways for expulsion through coughing.
But in cystic fibrosis (CF), for example, mucus hypersecretion can be deadly. The underlying pathology of CF – a mutation in the CFTR gene, which codes for the protein CF transmembrane conductance regulator – leads to buildup in the lungs of abnormally viscous and sticky mucus, resulting in frequent, severe infections (particularly with Pseudomonas aeruginosa), progressive lung damage, and prior to the development of effective disease management, significantly premature death.
Mucus hypersecretion is also a feature of chronic obstructive pulmonary disease (COPD), noted Victor Kim, MD, from Temple University, Philadelphia, Christopher M. Evans, PhD, from the University of Colorado at Denver, Aurora, and Burton F. Dickey, MD, from the University of Texas MD Anderson Cancer Center, Houston.
In COPD, “mucus dysfunction arises from several mechanisms, including excess production due to inflammation, decreased elimination due to impaired ciliary clearance and reduced cough efficiency, and excessive concentration due to smoke-induced dysfunction of transepithelial anion transport resembling CF,” they wrote in an editorial published in the American Journal of Respiratory and Critical Care Medicine.
In patients with idiopathic pulmonary fibrosis, a polymorphism in the enhancer region of MUC5B, a gene that encodes for mucin glycoproteins, results in a 20-fold overexpression of the gene and prominent mucus production that has been shown to parallel lung inflammation and decline in forced vital capacity (FVC).
In patients with asthma, up-regulation of MUC5AC and stimulated mucus secretion conspire to obstruct airways, which can in extreme cases lead to death.
‘Short shrift’
Yet until recently, the role of mucus hypersecretion in diseases such as COPD has been largely overlooked, or as Dr. Kim and colleagues put it, “airway mucus often receives short shrift from clinicians.”
“It’s a pretty hot topic in pulmonary medicine today because it has been so neglected for so long,” Dr. Dickey said in an interview with CHEST Physician. “As clinicians we haven’t had a way to identify who needs treatment, which is ridiculous, because many of the people who expectorate a lot, like those with chronic bronchitis, don’t actually have small airway obstruction, and conversely, a lot of asthmatics, who have very serious small airway obstruction, don’t expectorate, so you can’t really tell from symptoms.”
What has changed in recent years is the use of chest CT to image muco-obstructive pathology, commonly called “mucus plugging” in the peripheral airways of patients with COPD and asthma.
“In the last decade or so, we’ve seen the emergence in obstructive lung diseases such as asthma and COPD the use of more objective measures on CT scans, including the problem of mucus plugging, which is unfortunately very common,” Dr. Kim said in an interview.
The discovery of the extent and severity of mucus in obstructive lung diseases has led to new strategies to combat mucus overconcentration, such as hydration, mucolytics, and an intriguing investigational approach to decrease calcium-induced hypersecretion with designer peptides.
Mighty mucins
Under normal physiologic conditions mucus is composed largely of water (97%) and salts (2%), with the remainder consisting of entrapped globular proteins (0.7%) and mucins (0.3%), Dr. Dickey explains.
Yet those meager mucins pack a real punch, with the ability to absorb 300 times their mass of water after secretion, creating mucus of optimal consistency and viscoelasticity.
“Personally, I’ve never understood – maybe I should have paid more attention in physics – how a compound can absorb 300-fold its mass, but it does,” he said.
In a recent review article in the journal Clinical and Translational Medicine, Dr. Dickey and colleagues described how good mucus can go bad.
“[H]igh levels of mucin production from inflammatory stimulation (termed ‘mucous metaplasia’), followed by rapid release (together, termed ‘mucus hypersecretion’), can plug airways due to mucus volume expansion. In addition, if available lumenal liquid is insufficient, concentrated mucus of excessive viscoelasticity and adhesivity can cause mucus stasis,” they wrote.
Therapeutic strategies
In patients with CF, CFTR modulator therapy has markedly reduced but not eliminated the need for some patients to have mucolytic therapy, which may include dornase alfa, a recombinant human deoxyribonuclease that reduces the viscosity of lung secretions, hypertonic saline inhaled twice daily (for patients 12 and older), mannitol, and physical manipulations to help patients clear mucus. The manipulations can include both manual percussion and the use of devices for high-frequency chest wall oscillation.
Unlike in CF, where treating the underlying genetic pathology can help to resolve the thick, sticky mucus problems and thereby significantly reduce risk of infections and progressive lung damage, treatment of mucus metaplasia or hypersecretion in other diseases is aimed at symptomatic relief; it is still unclear whether symptomatic improvement of mucus overproduction would correlate with other disease-related outcomes, Dr. Kim and Dr. Dickey noted.
Potential therapeutic strategies to reduce excess mucus in the lungs include the use of mucolytic agents to thin secretions for more effective expulsion, decreasing mucus production through the use of an interleukin-13 (IL-13) inhibitor such as the anti-asthma agent dupilumab (Dupixent), and a novel strategy, still in the experimental phase, aimed at “disrupting the fusion of mucin storage granules with the cell membrane, thereby blocking secretion,” wrote Irina Gitlin, PhD, and John Fahy, MD, from the University of California, San Francisco, in Nature.
They were referring to research by Dr. Dickey and colleagues described in the same issue of Nature focusing on the inhibition of calcium-triggered mucus secretion by the use of hydrocarbon-stapled peptides, short chains of amino acids stabilized with a chemical bridge to a hydrocarbon molecule.
Knocking secretion down, but not out
The work has centered on decreasing overproduction of mucins with a focus on the signals for mucin production, including IL-13 and interleukin-1 beta, and on the signals for rapid release of mucins, including adenosine 5’-triphosphate (ATP), best known as an intracellular energy-storage module.
“But ATP is also steadily released by ciliated cells in response to the shear stress of tidal breathing, and it tells the neighboring secretory cells to slowly and steadily release mucin. But if the ciliated cells get stressed by any of a number of mechanisms, it can release a lot of ATP, and then the secretory cell can explosively release essentially all of its mucin content,” Dr. Dickey explained.
Other important signals for rapid release of mucins are acetylcholine and histamine, and all three of these agonists – ATP, acetylcholine, and histamine – cause a rise in intracellular calcium, which triggers calcium sensors that then lead to calcium-triggered membrane fusion and secretion.
Working as a postdoc in the Dickey laboratory, Dr. Evans had previously shown that deleting MUC5B in mice led to early development of serious lung abnormalities, some of which were fatal, indicating that MUC5B, a gene that is highly preserved in evolution, is essential for respiratory health.
This observation was later supported by a study of a family with a pattern of hereditary mucin deficiency caused by a homozygous loss-of-function mutation in MUC5B. The main subject in this study was an adult woman with unexplained bronchiectasis, impaired pulmonary function, and repeated Staphylococcus aureus infections. Her sibling, who also had the biallelic mutation, had extensive sinus disease with nasal polyps. Other siblings who were heterozygous for the mutation were asymptomatic but had mild functional lung impairment.
The trick for the investigators, then, was to figure out how to reduce stimulated release of stored mucins while still preserving normal release of mucins to allow for ciliary clearance of mucus, and Dr. Dickey and colleagues appear to have accomplished this, at least in mice.
They first validated as a potential therapeutic target a protein labeled synaptotagmin-2 (Syt2). Syt2 is a calcium sensor that is an essential part of the system that triggers calcium-triggered secretion. In a model for allergic asthma, mice with Syt2 deleted from airway epithelia had marked reductions in both stimulated mucin secretion and in mucus occlusion in airway lumens, but remained otherwise healthy with normal lung function.
Working with structural biologist Axel Brunger, PhD, from Stanford (Calif.) University, Dr. Dickey and coinvestigators developed and validated a peptide that could specifically inhibit Syt2, and found that it mimicked the action of the Syt2 deletion, preventing mucus occlusion in the allergic asthma model without adversely effecting normal production.
Not ready for prime time
Dr. Dickey and colleagues are now working to translate the therapy into a form that can be used in humans, most likely as an aerosol that could be used for acute treatment of patients with mucus plugging from asthma and COPD, and also as a therapy for patients with chronic disease.
“In the chronic situation, what we would hope to do is identify patients with muco-obstructive lung disease – asthma, COPD, cystic fibrosis – who have airway mucus obstruction and then use the inhaled peptide on a regular basis as one part of a program to try to prevent this chronic mucus occlusion,” Dr. Dickey said.
As Dr. Gitlin and Dr. Fahy wrote in their editorial, “by confirming that it is possible to block calcium-regulated mucin secretion, Lai and colleagues have shown the potential of such an approach as a new therapeutic strategy for lung illnesses associated with mucus pathology, including diseases such as asthma and COPD, for which there is a large unmet medical need.”
The study by Dr. Dickey and colleagues was supported by grants from the German Research Foundation, National Institutes of Health and the Cystic Fibrosis Foundation. Dr. Dickey disclosed consulting for Arrowhead Pharmaceuticals. Dr. Kim disclosed personal fees from Medscape and others. Dr. Evans reported no relevant disclosures. Dr. Fahy and Dr. Gitlin are named inventors on patents for mucolytic drugs, and shareholders in Aer Therapeutics.
Just uttering the word “mucus” is often sufficient to elicit amusement from those within earshot, but to patients with chronic inflammatory airway diseases, mucus is no laughing matter.
, which are then moved by cilia out of the airways for expulsion through coughing.
But in cystic fibrosis (CF), for example, mucus hypersecretion can be deadly. The underlying pathology of CF – a mutation in the CFTR gene, which codes for the protein CF transmembrane conductance regulator – leads to buildup in the lungs of abnormally viscous and sticky mucus, resulting in frequent, severe infections (particularly with Pseudomonas aeruginosa), progressive lung damage, and prior to the development of effective disease management, significantly premature death.
Mucus hypersecretion is also a feature of chronic obstructive pulmonary disease (COPD), noted Victor Kim, MD, from Temple University, Philadelphia, Christopher M. Evans, PhD, from the University of Colorado at Denver, Aurora, and Burton F. Dickey, MD, from the University of Texas MD Anderson Cancer Center, Houston.
In COPD, “mucus dysfunction arises from several mechanisms, including excess production due to inflammation, decreased elimination due to impaired ciliary clearance and reduced cough efficiency, and excessive concentration due to smoke-induced dysfunction of transepithelial anion transport resembling CF,” they wrote in an editorial published in the American Journal of Respiratory and Critical Care Medicine.
In patients with idiopathic pulmonary fibrosis, a polymorphism in the enhancer region of MUC5B, a gene that encodes for mucin glycoproteins, results in a 20-fold overexpression of the gene and prominent mucus production that has been shown to parallel lung inflammation and decline in forced vital capacity (FVC).
In patients with asthma, up-regulation of MUC5AC and stimulated mucus secretion conspire to obstruct airways, which can in extreme cases lead to death.
‘Short shrift’
Yet until recently, the role of mucus hypersecretion in diseases such as COPD has been largely overlooked, or as Dr. Kim and colleagues put it, “airway mucus often receives short shrift from clinicians.”
“It’s a pretty hot topic in pulmonary medicine today because it has been so neglected for so long,” Dr. Dickey said in an interview with CHEST Physician. “As clinicians we haven’t had a way to identify who needs treatment, which is ridiculous, because many of the people who expectorate a lot, like those with chronic bronchitis, don’t actually have small airway obstruction, and conversely, a lot of asthmatics, who have very serious small airway obstruction, don’t expectorate, so you can’t really tell from symptoms.”
What has changed in recent years is the use of chest CT to image muco-obstructive pathology, commonly called “mucus plugging” in the peripheral airways of patients with COPD and asthma.
“In the last decade or so, we’ve seen the emergence in obstructive lung diseases such as asthma and COPD the use of more objective measures on CT scans, including the problem of mucus plugging, which is unfortunately very common,” Dr. Kim said in an interview.
The discovery of the extent and severity of mucus in obstructive lung diseases has led to new strategies to combat mucus overconcentration, such as hydration, mucolytics, and an intriguing investigational approach to decrease calcium-induced hypersecretion with designer peptides.
Mighty mucins
Under normal physiologic conditions mucus is composed largely of water (97%) and salts (2%), with the remainder consisting of entrapped globular proteins (0.7%) and mucins (0.3%), Dr. Dickey explains.
Yet those meager mucins pack a real punch, with the ability to absorb 300 times their mass of water after secretion, creating mucus of optimal consistency and viscoelasticity.
“Personally, I’ve never understood – maybe I should have paid more attention in physics – how a compound can absorb 300-fold its mass, but it does,” he said.
In a recent review article in the journal Clinical and Translational Medicine, Dr. Dickey and colleagues described how good mucus can go bad.
“[H]igh levels of mucin production from inflammatory stimulation (termed ‘mucous metaplasia’), followed by rapid release (together, termed ‘mucus hypersecretion’), can plug airways due to mucus volume expansion. In addition, if available lumenal liquid is insufficient, concentrated mucus of excessive viscoelasticity and adhesivity can cause mucus stasis,” they wrote.
Therapeutic strategies
In patients with CF, CFTR modulator therapy has markedly reduced but not eliminated the need for some patients to have mucolytic therapy, which may include dornase alfa, a recombinant human deoxyribonuclease that reduces the viscosity of lung secretions, hypertonic saline inhaled twice daily (for patients 12 and older), mannitol, and physical manipulations to help patients clear mucus. The manipulations can include both manual percussion and the use of devices for high-frequency chest wall oscillation.
Unlike in CF, where treating the underlying genetic pathology can help to resolve the thick, sticky mucus problems and thereby significantly reduce risk of infections and progressive lung damage, treatment of mucus metaplasia or hypersecretion in other diseases is aimed at symptomatic relief; it is still unclear whether symptomatic improvement of mucus overproduction would correlate with other disease-related outcomes, Dr. Kim and Dr. Dickey noted.
Potential therapeutic strategies to reduce excess mucus in the lungs include the use of mucolytic agents to thin secretions for more effective expulsion, decreasing mucus production through the use of an interleukin-13 (IL-13) inhibitor such as the anti-asthma agent dupilumab (Dupixent), and a novel strategy, still in the experimental phase, aimed at “disrupting the fusion of mucin storage granules with the cell membrane, thereby blocking secretion,” wrote Irina Gitlin, PhD, and John Fahy, MD, from the University of California, San Francisco, in Nature.
They were referring to research by Dr. Dickey and colleagues described in the same issue of Nature focusing on the inhibition of calcium-triggered mucus secretion by the use of hydrocarbon-stapled peptides, short chains of amino acids stabilized with a chemical bridge to a hydrocarbon molecule.
Knocking secretion down, but not out
The work has centered on decreasing overproduction of mucins with a focus on the signals for mucin production, including IL-13 and interleukin-1 beta, and on the signals for rapid release of mucins, including adenosine 5’-triphosphate (ATP), best known as an intracellular energy-storage module.
“But ATP is also steadily released by ciliated cells in response to the shear stress of tidal breathing, and it tells the neighboring secretory cells to slowly and steadily release mucin. But if the ciliated cells get stressed by any of a number of mechanisms, it can release a lot of ATP, and then the secretory cell can explosively release essentially all of its mucin content,” Dr. Dickey explained.
Other important signals for rapid release of mucins are acetylcholine and histamine, and all three of these agonists – ATP, acetylcholine, and histamine – cause a rise in intracellular calcium, which triggers calcium sensors that then lead to calcium-triggered membrane fusion and secretion.
Working as a postdoc in the Dickey laboratory, Dr. Evans had previously shown that deleting MUC5B in mice led to early development of serious lung abnormalities, some of which were fatal, indicating that MUC5B, a gene that is highly preserved in evolution, is essential for respiratory health.
This observation was later supported by a study of a family with a pattern of hereditary mucin deficiency caused by a homozygous loss-of-function mutation in MUC5B. The main subject in this study was an adult woman with unexplained bronchiectasis, impaired pulmonary function, and repeated Staphylococcus aureus infections. Her sibling, who also had the biallelic mutation, had extensive sinus disease with nasal polyps. Other siblings who were heterozygous for the mutation were asymptomatic but had mild functional lung impairment.
The trick for the investigators, then, was to figure out how to reduce stimulated release of stored mucins while still preserving normal release of mucins to allow for ciliary clearance of mucus, and Dr. Dickey and colleagues appear to have accomplished this, at least in mice.
They first validated as a potential therapeutic target a protein labeled synaptotagmin-2 (Syt2). Syt2 is a calcium sensor that is an essential part of the system that triggers calcium-triggered secretion. In a model for allergic asthma, mice with Syt2 deleted from airway epithelia had marked reductions in both stimulated mucin secretion and in mucus occlusion in airway lumens, but remained otherwise healthy with normal lung function.
Working with structural biologist Axel Brunger, PhD, from Stanford (Calif.) University, Dr. Dickey and coinvestigators developed and validated a peptide that could specifically inhibit Syt2, and found that it mimicked the action of the Syt2 deletion, preventing mucus occlusion in the allergic asthma model without adversely effecting normal production.
Not ready for prime time
Dr. Dickey and colleagues are now working to translate the therapy into a form that can be used in humans, most likely as an aerosol that could be used for acute treatment of patients with mucus plugging from asthma and COPD, and also as a therapy for patients with chronic disease.
“In the chronic situation, what we would hope to do is identify patients with muco-obstructive lung disease – asthma, COPD, cystic fibrosis – who have airway mucus obstruction and then use the inhaled peptide on a regular basis as one part of a program to try to prevent this chronic mucus occlusion,” Dr. Dickey said.
As Dr. Gitlin and Dr. Fahy wrote in their editorial, “by confirming that it is possible to block calcium-regulated mucin secretion, Lai and colleagues have shown the potential of such an approach as a new therapeutic strategy for lung illnesses associated with mucus pathology, including diseases such as asthma and COPD, for which there is a large unmet medical need.”
The study by Dr. Dickey and colleagues was supported by grants from the German Research Foundation, National Institutes of Health and the Cystic Fibrosis Foundation. Dr. Dickey disclosed consulting for Arrowhead Pharmaceuticals. Dr. Kim disclosed personal fees from Medscape and others. Dr. Evans reported no relevant disclosures. Dr. Fahy and Dr. Gitlin are named inventors on patents for mucolytic drugs, and shareholders in Aer Therapeutics.
Large trial of home-based COPD rehab shows positive results
NASHVILLE – The first multicenter randomized controlled trial of a home-based rehabilitation program for patients with chronic obstructive pulmonary disease (COPD) showed highly positive results, according to findings presented at the annual meeting of the American College of Chest Physicians (CHEST).
At the end of 12 weeks, those randomly assigned to the intervention had a significant and clinically meaningful improvement in all domains of the Chronic Respiratory Questionnaire (CRQ), including activity levels and emotional well-being, reported Roberto P. Benzo, MD, a consultant in the division of pulmonary and critical care medicine, Mayo Clinic, Rochester, Minn.
Presenting soon-to-be-published data, Dr. Benzo said that the intervention is based on a tablet-based app. The tablet is programmed to upload data captured from an activity monitor and pulse oximeter. Along with documentation of app usage, this information can then be downloaded for the remote coach to review with the patient.
The primary outcome of the randomized study were the physical and emotional domains of the CRQ quality of life, but a long list of secondary outcomes – including physical activity, symptoms of depression, sleep quality, and health care utilization, such as emergency room visits – was also analyzed.
In addition to the significant benefit on the primary outcomes, the home-based rehabilitation program relative to a wait list for intervention was associated with benefit or a trend for benefit on essentially every outcome measured. Health care utilization was a possible exception, but even then, the absolute number of visits was lower in the treatment arm.
“With a study period of only 12 weeks, we were limited to our ability to show a difference in emergency room visits,” said Dr. Benzo, who also noted that the study was conducted during the COVID-19 pandemic, when hospital visits were already occurring at a lower than usual rate. Based on the other findings, he suspects that a reduction in health care utilization could also be shown in more typical circumstances, particularly with a longer follow-up.
In the study, 375 patients with COPD were randomly assigned to a home health care regimen delivered by an app with remote coaching or to a wait list and usual care. The median age was 69 years. Fifty-nine percent were women. The median FEV1 at enrollment was 45% of predicted.
The patients were able to access their own data to monitor their progress at any time, not just at the time of coaching, but contact with the remote coach occurred on a weekly basis. Patients rated their level of energy, how they felt generally, and their progress toward daily goals, which was also captured on the app and could be discussed with the coach during the review of the previous week’s activity.
At 12 weeks, the favorable 0.54-point change (P < .001) and 0.51 change (P < .001) in the physical and emotional summary scores, respectively, met the criteria for a clinically meaningful change, Dr. Benzo reported. There were also significantly favorable changes from baseline and relative to controls in CRQ domains of self-management, sleep quality, and depression (all P ≤ .01).
Other data collected are supportive. For example, Dr. Benzo reported that those in the rehabilitation group took 624 more steps on average per day than those in the control group. The experimental group also spent nearly an hour more performing moderate or greater levels of activity.
“The app promotes behavioral change,” said Dr. Benzo, who said that this “completely home-based model” of rehabilitation is likely to be cost-effective given the relatively low costs of remote coaching and reasonable costs of the activity monitor, tablet, and other equipment.
Importantly, home-based rehabilitation is a billable practice under currently available CPT codes, according to Dr. Benzo, who believes this approach is not only effective but “feasible and practical.”
Two clinicians active in the care of patients with COPD believe this approach could fulfill an unmet need if further validated. Andrew Berman, MD, professor of medicine, New Jersey Medical School, Newark, thinks the premise is sound.
“Digital competency is still a big issue as is access to adequate quality Internet, but this could be a very useful approach for many individuals, and it avoids visits to a center, which could be a big advantage for patients,” Dr. Berman said.
Abebaw M. Johannes, PhD, a professor of physical therapy at Azusa Pacific University, Azusa, Calif., agreed. He said that home-based remote coaching could be a way of overcoming the current hurdles of participating in institutional-based programs
“This is clearly an unmet need in COPD,” he said.
The development of more effective and patient-friendly programs is what was driving this research, according to Dr. Benzo. He cited data suggesting that only about 30% of patients with COPD are participating in rehabilitation programs once discharged from the hospital despite the evidence that they can improve quality of life. For many of these patients, a home-based program might be the answer.
Dr. Benzo, Dr. Berman, and Dr. Johannes reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
NASHVILLE – The first multicenter randomized controlled trial of a home-based rehabilitation program for patients with chronic obstructive pulmonary disease (COPD) showed highly positive results, according to findings presented at the annual meeting of the American College of Chest Physicians (CHEST).
At the end of 12 weeks, those randomly assigned to the intervention had a significant and clinically meaningful improvement in all domains of the Chronic Respiratory Questionnaire (CRQ), including activity levels and emotional well-being, reported Roberto P. Benzo, MD, a consultant in the division of pulmonary and critical care medicine, Mayo Clinic, Rochester, Minn.
Presenting soon-to-be-published data, Dr. Benzo said that the intervention is based on a tablet-based app. The tablet is programmed to upload data captured from an activity monitor and pulse oximeter. Along with documentation of app usage, this information can then be downloaded for the remote coach to review with the patient.
The primary outcome of the randomized study were the physical and emotional domains of the CRQ quality of life, but a long list of secondary outcomes – including physical activity, symptoms of depression, sleep quality, and health care utilization, such as emergency room visits – was also analyzed.
In addition to the significant benefit on the primary outcomes, the home-based rehabilitation program relative to a wait list for intervention was associated with benefit or a trend for benefit on essentially every outcome measured. Health care utilization was a possible exception, but even then, the absolute number of visits was lower in the treatment arm.
“With a study period of only 12 weeks, we were limited to our ability to show a difference in emergency room visits,” said Dr. Benzo, who also noted that the study was conducted during the COVID-19 pandemic, when hospital visits were already occurring at a lower than usual rate. Based on the other findings, he suspects that a reduction in health care utilization could also be shown in more typical circumstances, particularly with a longer follow-up.
In the study, 375 patients with COPD were randomly assigned to a home health care regimen delivered by an app with remote coaching or to a wait list and usual care. The median age was 69 years. Fifty-nine percent were women. The median FEV1 at enrollment was 45% of predicted.
The patients were able to access their own data to monitor their progress at any time, not just at the time of coaching, but contact with the remote coach occurred on a weekly basis. Patients rated their level of energy, how they felt generally, and their progress toward daily goals, which was also captured on the app and could be discussed with the coach during the review of the previous week’s activity.
At 12 weeks, the favorable 0.54-point change (P < .001) and 0.51 change (P < .001) in the physical and emotional summary scores, respectively, met the criteria for a clinically meaningful change, Dr. Benzo reported. There were also significantly favorable changes from baseline and relative to controls in CRQ domains of self-management, sleep quality, and depression (all P ≤ .01).
Other data collected are supportive. For example, Dr. Benzo reported that those in the rehabilitation group took 624 more steps on average per day than those in the control group. The experimental group also spent nearly an hour more performing moderate or greater levels of activity.
“The app promotes behavioral change,” said Dr. Benzo, who said that this “completely home-based model” of rehabilitation is likely to be cost-effective given the relatively low costs of remote coaching and reasonable costs of the activity monitor, tablet, and other equipment.
Importantly, home-based rehabilitation is a billable practice under currently available CPT codes, according to Dr. Benzo, who believes this approach is not only effective but “feasible and practical.”
Two clinicians active in the care of patients with COPD believe this approach could fulfill an unmet need if further validated. Andrew Berman, MD, professor of medicine, New Jersey Medical School, Newark, thinks the premise is sound.
“Digital competency is still a big issue as is access to adequate quality Internet, but this could be a very useful approach for many individuals, and it avoids visits to a center, which could be a big advantage for patients,” Dr. Berman said.
Abebaw M. Johannes, PhD, a professor of physical therapy at Azusa Pacific University, Azusa, Calif., agreed. He said that home-based remote coaching could be a way of overcoming the current hurdles of participating in institutional-based programs
“This is clearly an unmet need in COPD,” he said.
The development of more effective and patient-friendly programs is what was driving this research, according to Dr. Benzo. He cited data suggesting that only about 30% of patients with COPD are participating in rehabilitation programs once discharged from the hospital despite the evidence that they can improve quality of life. For many of these patients, a home-based program might be the answer.
Dr. Benzo, Dr. Berman, and Dr. Johannes reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
NASHVILLE – The first multicenter randomized controlled trial of a home-based rehabilitation program for patients with chronic obstructive pulmonary disease (COPD) showed highly positive results, according to findings presented at the annual meeting of the American College of Chest Physicians (CHEST).
At the end of 12 weeks, those randomly assigned to the intervention had a significant and clinically meaningful improvement in all domains of the Chronic Respiratory Questionnaire (CRQ), including activity levels and emotional well-being, reported Roberto P. Benzo, MD, a consultant in the division of pulmonary and critical care medicine, Mayo Clinic, Rochester, Minn.
Presenting soon-to-be-published data, Dr. Benzo said that the intervention is based on a tablet-based app. The tablet is programmed to upload data captured from an activity monitor and pulse oximeter. Along with documentation of app usage, this information can then be downloaded for the remote coach to review with the patient.
The primary outcome of the randomized study were the physical and emotional domains of the CRQ quality of life, but a long list of secondary outcomes – including physical activity, symptoms of depression, sleep quality, and health care utilization, such as emergency room visits – was also analyzed.
In addition to the significant benefit on the primary outcomes, the home-based rehabilitation program relative to a wait list for intervention was associated with benefit or a trend for benefit on essentially every outcome measured. Health care utilization was a possible exception, but even then, the absolute number of visits was lower in the treatment arm.
“With a study period of only 12 weeks, we were limited to our ability to show a difference in emergency room visits,” said Dr. Benzo, who also noted that the study was conducted during the COVID-19 pandemic, when hospital visits were already occurring at a lower than usual rate. Based on the other findings, he suspects that a reduction in health care utilization could also be shown in more typical circumstances, particularly with a longer follow-up.
In the study, 375 patients with COPD were randomly assigned to a home health care regimen delivered by an app with remote coaching or to a wait list and usual care. The median age was 69 years. Fifty-nine percent were women. The median FEV1 at enrollment was 45% of predicted.
The patients were able to access their own data to monitor their progress at any time, not just at the time of coaching, but contact with the remote coach occurred on a weekly basis. Patients rated their level of energy, how they felt generally, and their progress toward daily goals, which was also captured on the app and could be discussed with the coach during the review of the previous week’s activity.
At 12 weeks, the favorable 0.54-point change (P < .001) and 0.51 change (P < .001) in the physical and emotional summary scores, respectively, met the criteria for a clinically meaningful change, Dr. Benzo reported. There were also significantly favorable changes from baseline and relative to controls in CRQ domains of self-management, sleep quality, and depression (all P ≤ .01).
Other data collected are supportive. For example, Dr. Benzo reported that those in the rehabilitation group took 624 more steps on average per day than those in the control group. The experimental group also spent nearly an hour more performing moderate or greater levels of activity.
“The app promotes behavioral change,” said Dr. Benzo, who said that this “completely home-based model” of rehabilitation is likely to be cost-effective given the relatively low costs of remote coaching and reasonable costs of the activity monitor, tablet, and other equipment.
Importantly, home-based rehabilitation is a billable practice under currently available CPT codes, according to Dr. Benzo, who believes this approach is not only effective but “feasible and practical.”
Two clinicians active in the care of patients with COPD believe this approach could fulfill an unmet need if further validated. Andrew Berman, MD, professor of medicine, New Jersey Medical School, Newark, thinks the premise is sound.
“Digital competency is still a big issue as is access to adequate quality Internet, but this could be a very useful approach for many individuals, and it avoids visits to a center, which could be a big advantage for patients,” Dr. Berman said.
Abebaw M. Johannes, PhD, a professor of physical therapy at Azusa Pacific University, Azusa, Calif., agreed. He said that home-based remote coaching could be a way of overcoming the current hurdles of participating in institutional-based programs
“This is clearly an unmet need in COPD,” he said.
The development of more effective and patient-friendly programs is what was driving this research, according to Dr. Benzo. He cited data suggesting that only about 30% of patients with COPD are participating in rehabilitation programs once discharged from the hospital despite the evidence that they can improve quality of life. For many of these patients, a home-based program might be the answer.
Dr. Benzo, Dr. Berman, and Dr. Johannes reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CHEST 2022
Climate change magnifies health effects of wildfire smoke in care deserts
DRESSLERVILLE, NEV. – Smoke began billowing into the skies of northwestern Nevada in September, clouding the mountains, dimming the sun – and quashing residents’ hopes that they would be spared from wildfires and the awful air quality the blazes produce.
The lung-irritating particles were blowing in from burning forests in California and settling in Douglas County, Nevada, home to nearly 50,000 people, prompting warnings that air quality had reached hazardous levels.
Those levels meant the air was very unhealthy, bad enough to raise alarms about people’s immediate health care needs and questions about whether worsening pollution could result in long-term health issues. People could increasingly face such risks as climate change makes wildfires, drought, dust storms, and floods more frequent across the United States and the world.
Some people simply feel powerless.
“There’s not much we could do about it,” said Serrell Smokey, chairman of the Washoe Tribe of Nevada and California. The tribe’s land straddles the border between California and Nevada near Lake Tahoe and extends into Douglas County, about 60 miles south of Reno.
Tribe members and other area residents are among millions of people nationwide who this year will experience poor air quality because of wildfires. In September, as smoke settled over Nevada, fire-related air quality alerts were dispatched in six other states: California, Idaho, Montana, Oregon, Washington, and Wyoming.
Yet, by one measure, people who live in Douglas County are better off than those in some other hard-hit areas. Douglas County residents must drive 30 minutes, on average, for medical care from lung specialists called pulmonologists. In other parts of the West and Upper Midwest, however, patients must drive an hour or more, according to data analyzed by GoodRx, a website that tracks prescription drug prices and conducts research.
Specifically, the research found that about 5.5 million Americans live in the 488 counties where drive times to pulmonologists are an hour or more. Much of Nevada and large parts of Montana fall into those gaps between specialists – places that have recently grappled with wildfires that fill the air with smoke and ash, which can cause lung problems or exacerbate existing ones.
Data from the Association of American Medical Colleges shows the number of pulmonary disease specialists in the United States dropped nearly 11% from 2014 to 2019. The group, which is based in Washington, D.C., and represents the academic medicine community, noted that the decline might not be as high as it appears because some physicians are opting to practice pulmonary critical care rather than just pulmonology. Many of those types of pulmonologists work in hospital intensive care units.
About 15,000 pulmonologists are practicing in the United States, according to the GoodRx report. Yet vast swaths of the country have few or none.
“New Mexico has one pulmonologist for the entire southeastern part of state, not counting Las Cruces, which is closer to El Paso,” said Victor Test, MD, a pulmonologist at Texas Tech Physicians.
Dr. Test, one of 13 pulmonologists in the Lubbock, Tex., region, said that his patients from within Texas sometimes drive 4 hours for an appointment and that other people travel from “New Mexico, Oklahoma, even far western Kansas.”
Increases in wildfires and their intensity will likely expand the need for pulmonologists.
“Climate change is going to affect lung disease,” said Nicholas Kenyon, MD, a professor of pulmonary, critical care, and sleep medicine at the University of California, Davis, where he and several other researchers are tracking the effects of wildfires. At his Sacramento practice, Dr. Kenyon said, he sees patients from far northern parts of California, including Eureka, a 5-hour drive from the state capital.
The short-term effects of breathing smoke are pretty well known. People show up in emergency rooms with asthma attacks, exacerbation of COPD, bronchitis, and even pneumonia, Dr. Kenyon said. Some have chest pain or other cardiac concerns.
“But we have very little understanding of what happens over the longer term,” he said. “If people get 2 or 3 weeks of wildfire exposure for 2 or 3 years, does that lead to worsening of asthma or COPD? We just don’t know.”
Fires release multiple pollutants, including carbon dioxide, carbon monoxide, and chemicals like benzene. All fires send particles into the air. Health researchers and air quality experts are most concerned about tiny pieces referred to as particulate matter 2.5. Far smaller than a human hair, the particles can lodge deep in the lungs and have been linked to heart and lung conditions.
Increases in those tiny particles are associated with a greater risk of death from all causes, excluding accidents, homicides, and other nonaccidental causes, for up to 4 days after a population is exposed, according to a 2020 New England Journal of Medicine overview.
The concentration of fine particulate matter is one of five gauges used to calculate the Air Quality Index, a numerical and color-coded index used to let the public know about local air pollution levels. Green denotes good air quality and is given if the total index is 50 or less. When the measurement exceeds 100, the air quality gets an orange label and may be bad for certain groups. Levels over 200 get a red label and are considered unhealthy for everyone.
Government agencies track those levels, as do people who use apps or websites to determine whether it’s safe to go outside.
When the AQI rises above 150, Farah Madhani-Lovely, MD, a pulmonologist, said, Renown Regional Medical Center in Reno shuts its outpatient pulmonary rehabilitation clinic because it doesn’t want to encourage patients to drive in. Some patients from Douglas County opt for care near home, about an hour away. “We don’t want these patients exposed outside because just 1 minute of exposure to the smoke can trigger an exacerbation of their chronic disease,” Dr. Madhani-Lovely said.
Mr. Smokey said connecting with pulmonologists can be difficult for Washoe Tribe members, particularly those who live on the California side of the reservation. “We cannot find providers for them,” he said. “We end up referring them out and sending them hundreds of miles out of their way just to get care that we should be able to provide here.”
Recruiting specialists to rural areas or smaller cities has long been difficult. For one thing, a specialist might be the only one for miles around, “so there’s a tremendous burden in terms of coverage and days off,” Dr. Test said.
Another concern is that physicians tend to train in larger cities and often want to practice in similar places. Even recruiting pulmonary physicians to Lubbock, a city of 260,000 in West Texas, is a challenge, Dr. Test said.
“I love Lubbock,” he said. “But I tell people who have never been here, I say, ‘It’s really flat.’ They don’t understand flat until they get here.”
In Nevada, on days when the air quality is bad, Washoe tribal members try to protect themselves with makeshift air purifiers created from fans, duct tape, and air filters, Mr. Smokey said.
Longer term, Mr. Smokey and other tribal leaders are pushing the Indian Health Service to establish a specialty care hospital in northern Nevada. The closest specialty care hospital for Washoe tribal members is more than 700 miles away, in Phoenix.
It’s difficult because “there’s a need we should be taking care of,” Mr. Smokey said. “But we have to fight for it. And sometimes that fight takes years, years, and years to accomplish.”
A version of this article first appeared on Medscape.com.
DRESSLERVILLE, NEV. – Smoke began billowing into the skies of northwestern Nevada in September, clouding the mountains, dimming the sun – and quashing residents’ hopes that they would be spared from wildfires and the awful air quality the blazes produce.
The lung-irritating particles were blowing in from burning forests in California and settling in Douglas County, Nevada, home to nearly 50,000 people, prompting warnings that air quality had reached hazardous levels.
Those levels meant the air was very unhealthy, bad enough to raise alarms about people’s immediate health care needs and questions about whether worsening pollution could result in long-term health issues. People could increasingly face such risks as climate change makes wildfires, drought, dust storms, and floods more frequent across the United States and the world.
Some people simply feel powerless.
“There’s not much we could do about it,” said Serrell Smokey, chairman of the Washoe Tribe of Nevada and California. The tribe’s land straddles the border between California and Nevada near Lake Tahoe and extends into Douglas County, about 60 miles south of Reno.
Tribe members and other area residents are among millions of people nationwide who this year will experience poor air quality because of wildfires. In September, as smoke settled over Nevada, fire-related air quality alerts were dispatched in six other states: California, Idaho, Montana, Oregon, Washington, and Wyoming.
Yet, by one measure, people who live in Douglas County are better off than those in some other hard-hit areas. Douglas County residents must drive 30 minutes, on average, for medical care from lung specialists called pulmonologists. In other parts of the West and Upper Midwest, however, patients must drive an hour or more, according to data analyzed by GoodRx, a website that tracks prescription drug prices and conducts research.
Specifically, the research found that about 5.5 million Americans live in the 488 counties where drive times to pulmonologists are an hour or more. Much of Nevada and large parts of Montana fall into those gaps between specialists – places that have recently grappled with wildfires that fill the air with smoke and ash, which can cause lung problems or exacerbate existing ones.
Data from the Association of American Medical Colleges shows the number of pulmonary disease specialists in the United States dropped nearly 11% from 2014 to 2019. The group, which is based in Washington, D.C., and represents the academic medicine community, noted that the decline might not be as high as it appears because some physicians are opting to practice pulmonary critical care rather than just pulmonology. Many of those types of pulmonologists work in hospital intensive care units.
About 15,000 pulmonologists are practicing in the United States, according to the GoodRx report. Yet vast swaths of the country have few or none.
“New Mexico has one pulmonologist for the entire southeastern part of state, not counting Las Cruces, which is closer to El Paso,” said Victor Test, MD, a pulmonologist at Texas Tech Physicians.
Dr. Test, one of 13 pulmonologists in the Lubbock, Tex., region, said that his patients from within Texas sometimes drive 4 hours for an appointment and that other people travel from “New Mexico, Oklahoma, even far western Kansas.”
Increases in wildfires and their intensity will likely expand the need for pulmonologists.
“Climate change is going to affect lung disease,” said Nicholas Kenyon, MD, a professor of pulmonary, critical care, and sleep medicine at the University of California, Davis, where he and several other researchers are tracking the effects of wildfires. At his Sacramento practice, Dr. Kenyon said, he sees patients from far northern parts of California, including Eureka, a 5-hour drive from the state capital.
The short-term effects of breathing smoke are pretty well known. People show up in emergency rooms with asthma attacks, exacerbation of COPD, bronchitis, and even pneumonia, Dr. Kenyon said. Some have chest pain or other cardiac concerns.
“But we have very little understanding of what happens over the longer term,” he said. “If people get 2 or 3 weeks of wildfire exposure for 2 or 3 years, does that lead to worsening of asthma or COPD? We just don’t know.”
Fires release multiple pollutants, including carbon dioxide, carbon monoxide, and chemicals like benzene. All fires send particles into the air. Health researchers and air quality experts are most concerned about tiny pieces referred to as particulate matter 2.5. Far smaller than a human hair, the particles can lodge deep in the lungs and have been linked to heart and lung conditions.
Increases in those tiny particles are associated with a greater risk of death from all causes, excluding accidents, homicides, and other nonaccidental causes, for up to 4 days after a population is exposed, according to a 2020 New England Journal of Medicine overview.
The concentration of fine particulate matter is one of five gauges used to calculate the Air Quality Index, a numerical and color-coded index used to let the public know about local air pollution levels. Green denotes good air quality and is given if the total index is 50 or less. When the measurement exceeds 100, the air quality gets an orange label and may be bad for certain groups. Levels over 200 get a red label and are considered unhealthy for everyone.
Government agencies track those levels, as do people who use apps or websites to determine whether it’s safe to go outside.
When the AQI rises above 150, Farah Madhani-Lovely, MD, a pulmonologist, said, Renown Regional Medical Center in Reno shuts its outpatient pulmonary rehabilitation clinic because it doesn’t want to encourage patients to drive in. Some patients from Douglas County opt for care near home, about an hour away. “We don’t want these patients exposed outside because just 1 minute of exposure to the smoke can trigger an exacerbation of their chronic disease,” Dr. Madhani-Lovely said.
Mr. Smokey said connecting with pulmonologists can be difficult for Washoe Tribe members, particularly those who live on the California side of the reservation. “We cannot find providers for them,” he said. “We end up referring them out and sending them hundreds of miles out of their way just to get care that we should be able to provide here.”
Recruiting specialists to rural areas or smaller cities has long been difficult. For one thing, a specialist might be the only one for miles around, “so there’s a tremendous burden in terms of coverage and days off,” Dr. Test said.
Another concern is that physicians tend to train in larger cities and often want to practice in similar places. Even recruiting pulmonary physicians to Lubbock, a city of 260,000 in West Texas, is a challenge, Dr. Test said.
“I love Lubbock,” he said. “But I tell people who have never been here, I say, ‘It’s really flat.’ They don’t understand flat until they get here.”
In Nevada, on days when the air quality is bad, Washoe tribal members try to protect themselves with makeshift air purifiers created from fans, duct tape, and air filters, Mr. Smokey said.
Longer term, Mr. Smokey and other tribal leaders are pushing the Indian Health Service to establish a specialty care hospital in northern Nevada. The closest specialty care hospital for Washoe tribal members is more than 700 miles away, in Phoenix.
It’s difficult because “there’s a need we should be taking care of,” Mr. Smokey said. “But we have to fight for it. And sometimes that fight takes years, years, and years to accomplish.”
A version of this article first appeared on Medscape.com.
DRESSLERVILLE, NEV. – Smoke began billowing into the skies of northwestern Nevada in September, clouding the mountains, dimming the sun – and quashing residents’ hopes that they would be spared from wildfires and the awful air quality the blazes produce.
The lung-irritating particles were blowing in from burning forests in California and settling in Douglas County, Nevada, home to nearly 50,000 people, prompting warnings that air quality had reached hazardous levels.
Those levels meant the air was very unhealthy, bad enough to raise alarms about people’s immediate health care needs and questions about whether worsening pollution could result in long-term health issues. People could increasingly face such risks as climate change makes wildfires, drought, dust storms, and floods more frequent across the United States and the world.
Some people simply feel powerless.
“There’s not much we could do about it,” said Serrell Smokey, chairman of the Washoe Tribe of Nevada and California. The tribe’s land straddles the border between California and Nevada near Lake Tahoe and extends into Douglas County, about 60 miles south of Reno.
Tribe members and other area residents are among millions of people nationwide who this year will experience poor air quality because of wildfires. In September, as smoke settled over Nevada, fire-related air quality alerts were dispatched in six other states: California, Idaho, Montana, Oregon, Washington, and Wyoming.
Yet, by one measure, people who live in Douglas County are better off than those in some other hard-hit areas. Douglas County residents must drive 30 minutes, on average, for medical care from lung specialists called pulmonologists. In other parts of the West and Upper Midwest, however, patients must drive an hour or more, according to data analyzed by GoodRx, a website that tracks prescription drug prices and conducts research.
Specifically, the research found that about 5.5 million Americans live in the 488 counties where drive times to pulmonologists are an hour or more. Much of Nevada and large parts of Montana fall into those gaps between specialists – places that have recently grappled with wildfires that fill the air with smoke and ash, which can cause lung problems or exacerbate existing ones.
Data from the Association of American Medical Colleges shows the number of pulmonary disease specialists in the United States dropped nearly 11% from 2014 to 2019. The group, which is based in Washington, D.C., and represents the academic medicine community, noted that the decline might not be as high as it appears because some physicians are opting to practice pulmonary critical care rather than just pulmonology. Many of those types of pulmonologists work in hospital intensive care units.
About 15,000 pulmonologists are practicing in the United States, according to the GoodRx report. Yet vast swaths of the country have few or none.
“New Mexico has one pulmonologist for the entire southeastern part of state, not counting Las Cruces, which is closer to El Paso,” said Victor Test, MD, a pulmonologist at Texas Tech Physicians.
Dr. Test, one of 13 pulmonologists in the Lubbock, Tex., region, said that his patients from within Texas sometimes drive 4 hours for an appointment and that other people travel from “New Mexico, Oklahoma, even far western Kansas.”
Increases in wildfires and their intensity will likely expand the need for pulmonologists.
“Climate change is going to affect lung disease,” said Nicholas Kenyon, MD, a professor of pulmonary, critical care, and sleep medicine at the University of California, Davis, where he and several other researchers are tracking the effects of wildfires. At his Sacramento practice, Dr. Kenyon said, he sees patients from far northern parts of California, including Eureka, a 5-hour drive from the state capital.
The short-term effects of breathing smoke are pretty well known. People show up in emergency rooms with asthma attacks, exacerbation of COPD, bronchitis, and even pneumonia, Dr. Kenyon said. Some have chest pain or other cardiac concerns.
“But we have very little understanding of what happens over the longer term,” he said. “If people get 2 or 3 weeks of wildfire exposure for 2 or 3 years, does that lead to worsening of asthma or COPD? We just don’t know.”
Fires release multiple pollutants, including carbon dioxide, carbon monoxide, and chemicals like benzene. All fires send particles into the air. Health researchers and air quality experts are most concerned about tiny pieces referred to as particulate matter 2.5. Far smaller than a human hair, the particles can lodge deep in the lungs and have been linked to heart and lung conditions.
Increases in those tiny particles are associated with a greater risk of death from all causes, excluding accidents, homicides, and other nonaccidental causes, for up to 4 days after a population is exposed, according to a 2020 New England Journal of Medicine overview.
The concentration of fine particulate matter is one of five gauges used to calculate the Air Quality Index, a numerical and color-coded index used to let the public know about local air pollution levels. Green denotes good air quality and is given if the total index is 50 or less. When the measurement exceeds 100, the air quality gets an orange label and may be bad for certain groups. Levels over 200 get a red label and are considered unhealthy for everyone.
Government agencies track those levels, as do people who use apps or websites to determine whether it’s safe to go outside.
When the AQI rises above 150, Farah Madhani-Lovely, MD, a pulmonologist, said, Renown Regional Medical Center in Reno shuts its outpatient pulmonary rehabilitation clinic because it doesn’t want to encourage patients to drive in. Some patients from Douglas County opt for care near home, about an hour away. “We don’t want these patients exposed outside because just 1 minute of exposure to the smoke can trigger an exacerbation of their chronic disease,” Dr. Madhani-Lovely said.
Mr. Smokey said connecting with pulmonologists can be difficult for Washoe Tribe members, particularly those who live on the California side of the reservation. “We cannot find providers for them,” he said. “We end up referring them out and sending them hundreds of miles out of their way just to get care that we should be able to provide here.”
Recruiting specialists to rural areas or smaller cities has long been difficult. For one thing, a specialist might be the only one for miles around, “so there’s a tremendous burden in terms of coverage and days off,” Dr. Test said.
Another concern is that physicians tend to train in larger cities and often want to practice in similar places. Even recruiting pulmonary physicians to Lubbock, a city of 260,000 in West Texas, is a challenge, Dr. Test said.
“I love Lubbock,” he said. “But I tell people who have never been here, I say, ‘It’s really flat.’ They don’t understand flat until they get here.”
In Nevada, on days when the air quality is bad, Washoe tribal members try to protect themselves with makeshift air purifiers created from fans, duct tape, and air filters, Mr. Smokey said.
Longer term, Mr. Smokey and other tribal leaders are pushing the Indian Health Service to establish a specialty care hospital in northern Nevada. The closest specialty care hospital for Washoe tribal members is more than 700 miles away, in Phoenix.
It’s difficult because “there’s a need we should be taking care of,” Mr. Smokey said. “But we have to fight for it. And sometimes that fight takes years, years, and years to accomplish.”
A version of this article first appeared on Medscape.com.
Lung volume reduction methods show similar results for emphysema
BARCELONA – For patients with emphysema who are suitable candidates for lung volume reduction surgery, in a randomized trial.
Among patients with emphysema amenable to surgery, there were similar improvements between the treatment groups at 12-month follow-up as assessed by the iBODE score, a composite disease severity measure incorporating body mass index, airflow obstruction, dyspnea, and exercise capacity (incremental shuttle walk test), reported Sara Buttery, BSc, a research physiotherapist and PhD candidate at the National Heart and Lung Institute at Imperial College London.
“Until now there had been no direct comparison of the two to inform decision-making when a person seems to be suitable for either. Bronchoscopic lung volume reduction is a less invasive option and is thought to be ‘less risky’ but, until now, there has not been substantial research to support this,” she said at the annual congress of the European Respiratory Society.
Ms. Buttery and colleagues conducted a randomized, controlled, single-blinded superiority trial to see whether LVRS could be superior to BLVR with valves. They enrolled 88 patients (52% male) with a mean age of 64, and randomly assigned them to receive either LVRS (41 patients) or the less-invasive BLVR (47 patients).
As noted before, there were no significant differences in outcomes at 1 year, with similar degrees of improvement between the surgical techniques for both the composite iBODE score (–1.10 for LVRS vs. –0.82 for BLVR, nonsignificant), and for the individual components of the score.
In addition, the treatments were associated with similar reductions in gas trapping, with residual volume percentage predicted –36.1 with LVRS versus –30.5 with BLVR (nonsignificant).
One patient in each group died during the 12 months of follow-up. The death of the patient in the BLVR group was deemed to be treatment related; the death of the patient in the LVRS group was related to a noninfective exacerbation of chronic obstructive pulmonary disease.
Invited discussant Isabelle Opitz, MD, from University Hospital Zürich told Ms. Buttery: “I have to congratulate you for this very first randomized controlled trial comparing both procedures in a superiority design.”
She pointed out, however, that the number of patients lost to follow-up and crossover of some patients randomized to bronchoscopy raised questions about the powering of the study.
“We did a sensitivity analysis to have a look to see if there was any difference between the patients who did return and the ones who didn’t, and there was no difference at baseline between those patients.” Ms. Buttery said.
She noted that follow-up visits were hampered by the COVID-19 pandemic and the inability of many patients to come into the clinic.
Dr. Opitz also asked about COPD Assessment Test (CAT) scores that were included in the trial design but not reported in the presentation. Ms. Buttery said that the CAT results favored the LVRS group, and that the results would be included in a future economic analysis.
“The results from this first randomized controlled trial suggest that BLVR may be a good therapeutic option for those patients for whom either procedure is suitable,” said Alexander Mathioudakis, MD, PhD, from the University of Manchester (England), who was not involved with this study but commented on it in a press statement. “Lung volume reduction surgery is an invasive operation as it requires a small incision to be made in the chest, which is stitched up after the procedure. As such, it has risks associated with surgery and it takes longer to recover from than bronchoscopic lung volume reduction. On the other hand, endobronchial valves placement is also associated with side effects, such as pneumonia, or valve displacement. Therefore, both the safety and effectiveness of the two procedures need to be investigated further, in larger groups of patients, but the results from this trial are very encouraging.”
The study is supported by the U.K. National Institute of Health Research. Ms. Buttery, Dr. Opitz, and Dr. Mathioudakis reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BARCELONA – For patients with emphysema who are suitable candidates for lung volume reduction surgery, in a randomized trial.
Among patients with emphysema amenable to surgery, there were similar improvements between the treatment groups at 12-month follow-up as assessed by the iBODE score, a composite disease severity measure incorporating body mass index, airflow obstruction, dyspnea, and exercise capacity (incremental shuttle walk test), reported Sara Buttery, BSc, a research physiotherapist and PhD candidate at the National Heart and Lung Institute at Imperial College London.
“Until now there had been no direct comparison of the two to inform decision-making when a person seems to be suitable for either. Bronchoscopic lung volume reduction is a less invasive option and is thought to be ‘less risky’ but, until now, there has not been substantial research to support this,” she said at the annual congress of the European Respiratory Society.
Ms. Buttery and colleagues conducted a randomized, controlled, single-blinded superiority trial to see whether LVRS could be superior to BLVR with valves. They enrolled 88 patients (52% male) with a mean age of 64, and randomly assigned them to receive either LVRS (41 patients) or the less-invasive BLVR (47 patients).
As noted before, there were no significant differences in outcomes at 1 year, with similar degrees of improvement between the surgical techniques for both the composite iBODE score (–1.10 for LVRS vs. –0.82 for BLVR, nonsignificant), and for the individual components of the score.
In addition, the treatments were associated with similar reductions in gas trapping, with residual volume percentage predicted –36.1 with LVRS versus –30.5 with BLVR (nonsignificant).
One patient in each group died during the 12 months of follow-up. The death of the patient in the BLVR group was deemed to be treatment related; the death of the patient in the LVRS group was related to a noninfective exacerbation of chronic obstructive pulmonary disease.
Invited discussant Isabelle Opitz, MD, from University Hospital Zürich told Ms. Buttery: “I have to congratulate you for this very first randomized controlled trial comparing both procedures in a superiority design.”
She pointed out, however, that the number of patients lost to follow-up and crossover of some patients randomized to bronchoscopy raised questions about the powering of the study.
“We did a sensitivity analysis to have a look to see if there was any difference between the patients who did return and the ones who didn’t, and there was no difference at baseline between those patients.” Ms. Buttery said.
She noted that follow-up visits were hampered by the COVID-19 pandemic and the inability of many patients to come into the clinic.
Dr. Opitz also asked about COPD Assessment Test (CAT) scores that were included in the trial design but not reported in the presentation. Ms. Buttery said that the CAT results favored the LVRS group, and that the results would be included in a future economic analysis.
“The results from this first randomized controlled trial suggest that BLVR may be a good therapeutic option for those patients for whom either procedure is suitable,” said Alexander Mathioudakis, MD, PhD, from the University of Manchester (England), who was not involved with this study but commented on it in a press statement. “Lung volume reduction surgery is an invasive operation as it requires a small incision to be made in the chest, which is stitched up after the procedure. As such, it has risks associated with surgery and it takes longer to recover from than bronchoscopic lung volume reduction. On the other hand, endobronchial valves placement is also associated with side effects, such as pneumonia, or valve displacement. Therefore, both the safety and effectiveness of the two procedures need to be investigated further, in larger groups of patients, but the results from this trial are very encouraging.”
The study is supported by the U.K. National Institute of Health Research. Ms. Buttery, Dr. Opitz, and Dr. Mathioudakis reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BARCELONA – For patients with emphysema who are suitable candidates for lung volume reduction surgery, in a randomized trial.
Among patients with emphysema amenable to surgery, there were similar improvements between the treatment groups at 12-month follow-up as assessed by the iBODE score, a composite disease severity measure incorporating body mass index, airflow obstruction, dyspnea, and exercise capacity (incremental shuttle walk test), reported Sara Buttery, BSc, a research physiotherapist and PhD candidate at the National Heart and Lung Institute at Imperial College London.
“Until now there had been no direct comparison of the two to inform decision-making when a person seems to be suitable for either. Bronchoscopic lung volume reduction is a less invasive option and is thought to be ‘less risky’ but, until now, there has not been substantial research to support this,” she said at the annual congress of the European Respiratory Society.
Ms. Buttery and colleagues conducted a randomized, controlled, single-blinded superiority trial to see whether LVRS could be superior to BLVR with valves. They enrolled 88 patients (52% male) with a mean age of 64, and randomly assigned them to receive either LVRS (41 patients) or the less-invasive BLVR (47 patients).
As noted before, there were no significant differences in outcomes at 1 year, with similar degrees of improvement between the surgical techniques for both the composite iBODE score (–1.10 for LVRS vs. –0.82 for BLVR, nonsignificant), and for the individual components of the score.
In addition, the treatments were associated with similar reductions in gas trapping, with residual volume percentage predicted –36.1 with LVRS versus –30.5 with BLVR (nonsignificant).
One patient in each group died during the 12 months of follow-up. The death of the patient in the BLVR group was deemed to be treatment related; the death of the patient in the LVRS group was related to a noninfective exacerbation of chronic obstructive pulmonary disease.
Invited discussant Isabelle Opitz, MD, from University Hospital Zürich told Ms. Buttery: “I have to congratulate you for this very first randomized controlled trial comparing both procedures in a superiority design.”
She pointed out, however, that the number of patients lost to follow-up and crossover of some patients randomized to bronchoscopy raised questions about the powering of the study.
“We did a sensitivity analysis to have a look to see if there was any difference between the patients who did return and the ones who didn’t, and there was no difference at baseline between those patients.” Ms. Buttery said.
She noted that follow-up visits were hampered by the COVID-19 pandemic and the inability of many patients to come into the clinic.
Dr. Opitz also asked about COPD Assessment Test (CAT) scores that were included in the trial design but not reported in the presentation. Ms. Buttery said that the CAT results favored the LVRS group, and that the results would be included in a future economic analysis.
“The results from this first randomized controlled trial suggest that BLVR may be a good therapeutic option for those patients for whom either procedure is suitable,” said Alexander Mathioudakis, MD, PhD, from the University of Manchester (England), who was not involved with this study but commented on it in a press statement. “Lung volume reduction surgery is an invasive operation as it requires a small incision to be made in the chest, which is stitched up after the procedure. As such, it has risks associated with surgery and it takes longer to recover from than bronchoscopic lung volume reduction. On the other hand, endobronchial valves placement is also associated with side effects, such as pneumonia, or valve displacement. Therefore, both the safety and effectiveness of the two procedures need to be investigated further, in larger groups of patients, but the results from this trial are very encouraging.”
The study is supported by the U.K. National Institute of Health Research. Ms. Buttery, Dr. Opitz, and Dr. Mathioudakis reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ERS 2022 CONGRESS
Biomarker-guided steroid therapy shown safe for COPD
Eosinophil-guided corticosteroid therapy for patients with chronic obstructive pulmonary disease (COPD) is equivalent in efficacy to standard of care therapy, but the eosinophil-guided therapy may help mitigate the harmful side effects associated with even short courses of corticosteroids, investigators said in a primary care–based randomized trial.
Among patients in 14 primary care practices in the United Kingdom who experienced COPD exacerbations, the proportion of patients who experienced treatment failure at day 28 was 27% for those who were randomized to receive prednisolone only when blood eosinophil counts on a point-of-care assay equaled or exceeded 2%, compared with 34% of all patients randomized to standard of care.
The relative risk for treatment failure using the eosinophil-guided approach was 0.82, which did not reach statistical significance, but indicated noninferiority for the biomarker-based dosing method, Mona Bafadhel, MD, of King’s College London, reported on behalf of colleagues in the Stratified Treatment to Reduce Risk in COPD (STARR2) trial.
This is the largest primary care multicenter trial, and probably adds another 20% to the literature base for exacerbations in COPD,” she said in an oral abstract presentation at the European Respiratory Society 2022 Congress.
“A personalized endotype-based treatment with oral prednisolone is possible in patients with COPD and I think should be now part of clinical guidelines,” she added.
Too much of a good thing
Although systemic corticosteroids are the universal treatment for COPD exacerbations, the drugs are also known to increase harm, with studies showing that cumulative doses of oral corticosteroids in COPD patients is associated with an increased risk for death. In addition, systemic corticosteroids are the third most common cause of adverse events leading to hospitalization, behind only chemotherapy and antibiotic use leading to Clostridioides difficile infections, Dr. Bafadhel said.
“And of course, corticosteroids are associated with significant harmful effects, including a five-times increased risk of sepsis, three-times increased risk of [venous thromboembolism], and a twice-increased risk of fracture,” she said.
Dr. Bafadhel and colleagues had previously shown in the single-center BEAT-COPD study that peripheral blood eosinophils at the time of a moderate COPD exacerbation could be used to safely direct oral corticosteroid therapy. She also pointed to a 2019 multicenter open-label study showing that eosinophil-guided care was noninferior to standard prescribing of oral corticosteroids for patients with severe exacerbations.
Primary care study
The investigators conducted the current study to test whether eosinophil-guided therapy at the point of care in a primary practice setting was efficacious, with the ultimate goal of encouraging changes in guidelines.
They recruited patients with COPD exacerbations from 14 general practices in Oxfordshire and Buckinghamshire in the Thames Valley.
The patients were randomly assigned to receive either standard of care or the biomarker-guided intervention for 14 days. In this arm, patients with eosinophil counts of 2% or greater received matched prednisolone, while patients with counts below 2% received placebo. The patients were blinded to the assigned drug.
A total of 203 exacerbations among 152 patients were evenly allocated to treatment or control groups. The mean patient age was 71. Of the 102 exacerbations allocated to eosinophil-guided therapy, 34 were treated with placebo.
As noted before, in the intention-to-treat analysis the primary outcome of the treatment failure rate, defined as any need for antibiotics and/or steroids at one month, was 27% in the biomarker-guided arm and 34% in the standard care arm.
“In the per-protocol analysis we also demonstrated that there was a suggestion that there is possible superiority of using blood eosinophil-directed oral corticosteroid prescriptions at the time of acute exacerbation using the point-of-care eosinophil test,” Dr. Bafadhel said.
There were no significant differences in the secondary outcomes of mean change in forced expiratory volume in 1 second (FEV1), COPD Assessment Test scores from exacerbation to follow-up, and symptoms according to a visual analog scale.
Invited discussant Dave Singh, MD, of the University of Manchester, England, asked Dr. Bafadhel how the data she presented supported her conclusions about the potential benefits of eosinophil-guided therapy, given that the P values were nonsignificant.
“The primary outcome was powered on noninferiority, and of course what we’ve shown is that it’s not any worse, it’s not any better, but of course it’s the effect of how many courses of steroids you can reduce in that population,” Dr. Bafadhel replied.
She noted that although the investigators have not performed an economic analysis to determine how many adverse events might be avoided using the biomarker-guided approach, “we do know that some of these patients who are given prednisolone, their comorbidities of diabetes worsened, for example.”
In the online Q&A for the presentation, Sohail Ansari, MD, from the Mid and South Essex NHS Foundation Trust in the United Kingdom, said that many patients in primary care practices receive “rescue packs” containing antibiotics and steroids, but may not be equipped to know when they should use the steroids and therefore may overuse them.
“Perhaps community-based, adequately resourced respiratory teams [may] be a way forward, but it will need adequate investment and commitment,” he wrote.
The trial was supported by the University of Oxford and National Institute for Health and Care Research, UK. Dr. Bafadhel reported grant and research support from the National Institute for Health and Care Research, Asthma & Lung UK, AstraZeneca, and Roche, and honoraria or fees from others. Dr. Singh reported speaking fees, honoraria, and research grants from multiple companies. Dr. Ansari reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
Eosinophil-guided corticosteroid therapy for patients with chronic obstructive pulmonary disease (COPD) is equivalent in efficacy to standard of care therapy, but the eosinophil-guided therapy may help mitigate the harmful side effects associated with even short courses of corticosteroids, investigators said in a primary care–based randomized trial.
Among patients in 14 primary care practices in the United Kingdom who experienced COPD exacerbations, the proportion of patients who experienced treatment failure at day 28 was 27% for those who were randomized to receive prednisolone only when blood eosinophil counts on a point-of-care assay equaled or exceeded 2%, compared with 34% of all patients randomized to standard of care.
The relative risk for treatment failure using the eosinophil-guided approach was 0.82, which did not reach statistical significance, but indicated noninferiority for the biomarker-based dosing method, Mona Bafadhel, MD, of King’s College London, reported on behalf of colleagues in the Stratified Treatment to Reduce Risk in COPD (STARR2) trial.
This is the largest primary care multicenter trial, and probably adds another 20% to the literature base for exacerbations in COPD,” she said in an oral abstract presentation at the European Respiratory Society 2022 Congress.
“A personalized endotype-based treatment with oral prednisolone is possible in patients with COPD and I think should be now part of clinical guidelines,” she added.
Too much of a good thing
Although systemic corticosteroids are the universal treatment for COPD exacerbations, the drugs are also known to increase harm, with studies showing that cumulative doses of oral corticosteroids in COPD patients is associated with an increased risk for death. In addition, systemic corticosteroids are the third most common cause of adverse events leading to hospitalization, behind only chemotherapy and antibiotic use leading to Clostridioides difficile infections, Dr. Bafadhel said.
“And of course, corticosteroids are associated with significant harmful effects, including a five-times increased risk of sepsis, three-times increased risk of [venous thromboembolism], and a twice-increased risk of fracture,” she said.
Dr. Bafadhel and colleagues had previously shown in the single-center BEAT-COPD study that peripheral blood eosinophils at the time of a moderate COPD exacerbation could be used to safely direct oral corticosteroid therapy. She also pointed to a 2019 multicenter open-label study showing that eosinophil-guided care was noninferior to standard prescribing of oral corticosteroids for patients with severe exacerbations.
Primary care study
The investigators conducted the current study to test whether eosinophil-guided therapy at the point of care in a primary practice setting was efficacious, with the ultimate goal of encouraging changes in guidelines.
They recruited patients with COPD exacerbations from 14 general practices in Oxfordshire and Buckinghamshire in the Thames Valley.
The patients were randomly assigned to receive either standard of care or the biomarker-guided intervention for 14 days. In this arm, patients with eosinophil counts of 2% or greater received matched prednisolone, while patients with counts below 2% received placebo. The patients were blinded to the assigned drug.
A total of 203 exacerbations among 152 patients were evenly allocated to treatment or control groups. The mean patient age was 71. Of the 102 exacerbations allocated to eosinophil-guided therapy, 34 were treated with placebo.
As noted before, in the intention-to-treat analysis the primary outcome of the treatment failure rate, defined as any need for antibiotics and/or steroids at one month, was 27% in the biomarker-guided arm and 34% in the standard care arm.
“In the per-protocol analysis we also demonstrated that there was a suggestion that there is possible superiority of using blood eosinophil-directed oral corticosteroid prescriptions at the time of acute exacerbation using the point-of-care eosinophil test,” Dr. Bafadhel said.
There were no significant differences in the secondary outcomes of mean change in forced expiratory volume in 1 second (FEV1), COPD Assessment Test scores from exacerbation to follow-up, and symptoms according to a visual analog scale.
Invited discussant Dave Singh, MD, of the University of Manchester, England, asked Dr. Bafadhel how the data she presented supported her conclusions about the potential benefits of eosinophil-guided therapy, given that the P values were nonsignificant.
“The primary outcome was powered on noninferiority, and of course what we’ve shown is that it’s not any worse, it’s not any better, but of course it’s the effect of how many courses of steroids you can reduce in that population,” Dr. Bafadhel replied.
She noted that although the investigators have not performed an economic analysis to determine how many adverse events might be avoided using the biomarker-guided approach, “we do know that some of these patients who are given prednisolone, their comorbidities of diabetes worsened, for example.”
In the online Q&A for the presentation, Sohail Ansari, MD, from the Mid and South Essex NHS Foundation Trust in the United Kingdom, said that many patients in primary care practices receive “rescue packs” containing antibiotics and steroids, but may not be equipped to know when they should use the steroids and therefore may overuse them.
“Perhaps community-based, adequately resourced respiratory teams [may] be a way forward, but it will need adequate investment and commitment,” he wrote.
The trial was supported by the University of Oxford and National Institute for Health and Care Research, UK. Dr. Bafadhel reported grant and research support from the National Institute for Health and Care Research, Asthma & Lung UK, AstraZeneca, and Roche, and honoraria or fees from others. Dr. Singh reported speaking fees, honoraria, and research grants from multiple companies. Dr. Ansari reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
Eosinophil-guided corticosteroid therapy for patients with chronic obstructive pulmonary disease (COPD) is equivalent in efficacy to standard of care therapy, but the eosinophil-guided therapy may help mitigate the harmful side effects associated with even short courses of corticosteroids, investigators said in a primary care–based randomized trial.
Among patients in 14 primary care practices in the United Kingdom who experienced COPD exacerbations, the proportion of patients who experienced treatment failure at day 28 was 27% for those who were randomized to receive prednisolone only when blood eosinophil counts on a point-of-care assay equaled or exceeded 2%, compared with 34% of all patients randomized to standard of care.
The relative risk for treatment failure using the eosinophil-guided approach was 0.82, which did not reach statistical significance, but indicated noninferiority for the biomarker-based dosing method, Mona Bafadhel, MD, of King’s College London, reported on behalf of colleagues in the Stratified Treatment to Reduce Risk in COPD (STARR2) trial.
This is the largest primary care multicenter trial, and probably adds another 20% to the literature base for exacerbations in COPD,” she said in an oral abstract presentation at the European Respiratory Society 2022 Congress.
“A personalized endotype-based treatment with oral prednisolone is possible in patients with COPD and I think should be now part of clinical guidelines,” she added.
Too much of a good thing
Although systemic corticosteroids are the universal treatment for COPD exacerbations, the drugs are also known to increase harm, with studies showing that cumulative doses of oral corticosteroids in COPD patients is associated with an increased risk for death. In addition, systemic corticosteroids are the third most common cause of adverse events leading to hospitalization, behind only chemotherapy and antibiotic use leading to Clostridioides difficile infections, Dr. Bafadhel said.
“And of course, corticosteroids are associated with significant harmful effects, including a five-times increased risk of sepsis, three-times increased risk of [venous thromboembolism], and a twice-increased risk of fracture,” she said.
Dr. Bafadhel and colleagues had previously shown in the single-center BEAT-COPD study that peripheral blood eosinophils at the time of a moderate COPD exacerbation could be used to safely direct oral corticosteroid therapy. She also pointed to a 2019 multicenter open-label study showing that eosinophil-guided care was noninferior to standard prescribing of oral corticosteroids for patients with severe exacerbations.
Primary care study
The investigators conducted the current study to test whether eosinophil-guided therapy at the point of care in a primary practice setting was efficacious, with the ultimate goal of encouraging changes in guidelines.
They recruited patients with COPD exacerbations from 14 general practices in Oxfordshire and Buckinghamshire in the Thames Valley.
The patients were randomly assigned to receive either standard of care or the biomarker-guided intervention for 14 days. In this arm, patients with eosinophil counts of 2% or greater received matched prednisolone, while patients with counts below 2% received placebo. The patients were blinded to the assigned drug.
A total of 203 exacerbations among 152 patients were evenly allocated to treatment or control groups. The mean patient age was 71. Of the 102 exacerbations allocated to eosinophil-guided therapy, 34 were treated with placebo.
As noted before, in the intention-to-treat analysis the primary outcome of the treatment failure rate, defined as any need for antibiotics and/or steroids at one month, was 27% in the biomarker-guided arm and 34% in the standard care arm.
“In the per-protocol analysis we also demonstrated that there was a suggestion that there is possible superiority of using blood eosinophil-directed oral corticosteroid prescriptions at the time of acute exacerbation using the point-of-care eosinophil test,” Dr. Bafadhel said.
There were no significant differences in the secondary outcomes of mean change in forced expiratory volume in 1 second (FEV1), COPD Assessment Test scores from exacerbation to follow-up, and symptoms according to a visual analog scale.
Invited discussant Dave Singh, MD, of the University of Manchester, England, asked Dr. Bafadhel how the data she presented supported her conclusions about the potential benefits of eosinophil-guided therapy, given that the P values were nonsignificant.
“The primary outcome was powered on noninferiority, and of course what we’ve shown is that it’s not any worse, it’s not any better, but of course it’s the effect of how many courses of steroids you can reduce in that population,” Dr. Bafadhel replied.
She noted that although the investigators have not performed an economic analysis to determine how many adverse events might be avoided using the biomarker-guided approach, “we do know that some of these patients who are given prednisolone, their comorbidities of diabetes worsened, for example.”
In the online Q&A for the presentation, Sohail Ansari, MD, from the Mid and South Essex NHS Foundation Trust in the United Kingdom, said that many patients in primary care practices receive “rescue packs” containing antibiotics and steroids, but may not be equipped to know when they should use the steroids and therefore may overuse them.
“Perhaps community-based, adequately resourced respiratory teams [may] be a way forward, but it will need adequate investment and commitment,” he wrote.
The trial was supported by the University of Oxford and National Institute for Health and Care Research, UK. Dr. Bafadhel reported grant and research support from the National Institute for Health and Care Research, Asthma & Lung UK, AstraZeneca, and Roche, and honoraria or fees from others. Dr. Singh reported speaking fees, honoraria, and research grants from multiple companies. Dr. Ansari reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM ERS 2022 CONGRESS
RETHINC takes air out of COPD-like therapy for smokers
Current or former smokers who have clinically significant respiratory symptoms but no spirometric evidence of airway obstruction are often treated with dual bronchodilators commonly prescribed for patients with chronic obstructive pulmonary disease (COPD).
But as results of the randomized RETHINC (Redefining Therapy In Early COPD for the Pulmonary Trials Cooperative) trial showed, bronchodilator therapy was no better than placebo at reducing respiratory symptoms in smokers, reported MeiLan K. Han, MD, from the University of Michigan, Ann Arbor, on behalf of colleagues in the RETHINC study group.
“Many tobacco-exposed symptomatic individuals are currently being treated. We don’t know if this is because physicians just aren’t doing spirometry and assuming COPD or they strongly believe that there’s a benefit, but the bottom line is that we really need to do spirometry to understand who benefits from bronchodilators, and we need further research to understand how to treat this specific group of patients because there truly is pathogenesis and disease burden,” Dr. Han said in an oral abstract presentation at the annual congress of the European Respiratory Society.
The study results were also published online in the New England Journal of Medicine to coincide with the presentation.
In an editorial accompanying the study, Don D. Sin, MD, MPH, from the University of British Columbia, Vancouver, commented that these medications should most likely be reserved for patients with COPD who have clinically significant airflow limitation,” and that “respiratory symptoms in tobacco-exposed persons are common but are highly variable over time.”
Dave Singh, MD, from the University of Manchester (England), the invited discussant, called it “a very important negative study.”
Not up to GOLD standard
Current or former smokers who are symptomatic, with COPD Assessment Test (CAT) scores of at least 10 despite having preserved function on spirometry, have been shown to have higher prospective rates of respiratory disease exacerbations and increased sputum total mucin concentrations. Approximately 43% of such patients are treated with bronchodilators, and 23% are treated with inhaled corticosteroids (ICS), Dr. Han noted.
Her group hypothesized that ever-smokers with spirometric values that fall within the normal range – that is, a postbronchodilator FEV1/FVC ratio of 70 or greater – would still derive benefit from long-acting bronchodilator therapy, even though these patients are currently excluded from Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations.
To test this, they conducted a 12-week, multicenter, randomized, parallel-group study in which patients were assigned to receive either indacaterol (27.5 mcg) and glycopyrrolate (15.6 mcg) inhaled twice daily or placebo.
They enrolled adults aged 40-80 years with a minimum of 10 pack-years of smoking history, postbronchodilator FEV1/FVC ratio of 70 or greater, and CAT scores of 10 or greater. Patients with known concomitant lung disease, a primary diagnosis of asthma, or body mass index lower than 15 or higher than 40 and those being concomitantly treated with long-acting beta2-agonists or muscarinic antagonists or a short-acting combination were excluded, although patients were allowed to be on a short-acting beta-agonist.
A total of 535 participants were randomized, but COVID-19 pandemic–imposed obstacles resulted in a modified intention-to-treat population of 277 patients assigned to receive the active treatment and 244 assigned to receive placebo.
There was no difference between the groups for the primary outcome of an at least 4-point decrease in St. George’s Respiratory Questionnaire scores in patients who did not experience treatment failure, defined as an increase in respiratory symptoms requiring treatment with active long-acting bronchodilators or ICS.
The primary endpoint was seen in 56.4% of patients in the bronchodilator group, and 59% of controls.
Although there was greater improvement in pulmonary function from baseline in the treatment group, compared with the placebo group, the improvements did not correlate with similar improvements in symptoms, Dr. Han said.
There were 4 serious adverse events in the bronchodilator group and 11 in the placebo group, but none of the events were deemed to be related to the assigned treatments.
Dr. Han acknowledged limitations of the study, which may have included symptoms driven by other factors such as cardiac disease, suggesting that if such patients had been identified and excluded, a stronger effect might have been seen for the active treatment.
In addition, the study was underpowered to look at the subgroup of participants with chronic bronchitis, and the 12 weeks of the study may have been too short to see improvements in symptoms.
In his editorial, Dr. Sin noted that the study showed that cough and sputum production rather than exertion dyspnea are the primary symptoms among ever-smokers.
“Although bronchodilators are effective in ameliorating breathlessness and improving exercise tolerance, they are generally ineffective for cough,” he wrote. “Existing drugs for the treatment of COPD, such as inhaled glucocorticoids or phosphodiesterase-4 inhibitors, or new therapeutics such as P2X3 receptor antagonists may be more effective for the treatment of cough and sputum production related to smoking and could be considered for future evaluations in this patient population.”
The study was supported by the National Heart, Lung, and Blood Institute, the National Center for Advancing Translational Sciences, and Sunovion Pharmaceuticals. Novartis Pharmaceuticals donated the trial medication and placebo. Dr. Han disclosed grant/research support and honoraria or consulting fees from various companies. Dr. Singh reported speaking fees, honoraria, and research grants from multiple companies. Dr. Sin reported having no conflicts of interest to disclose.
A version of this article first appeared on Medscape.com.
Current or former smokers who have clinically significant respiratory symptoms but no spirometric evidence of airway obstruction are often treated with dual bronchodilators commonly prescribed for patients with chronic obstructive pulmonary disease (COPD).
But as results of the randomized RETHINC (Redefining Therapy In Early COPD for the Pulmonary Trials Cooperative) trial showed, bronchodilator therapy was no better than placebo at reducing respiratory symptoms in smokers, reported MeiLan K. Han, MD, from the University of Michigan, Ann Arbor, on behalf of colleagues in the RETHINC study group.
“Many tobacco-exposed symptomatic individuals are currently being treated. We don’t know if this is because physicians just aren’t doing spirometry and assuming COPD or they strongly believe that there’s a benefit, but the bottom line is that we really need to do spirometry to understand who benefits from bronchodilators, and we need further research to understand how to treat this specific group of patients because there truly is pathogenesis and disease burden,” Dr. Han said in an oral abstract presentation at the annual congress of the European Respiratory Society.
The study results were also published online in the New England Journal of Medicine to coincide with the presentation.
In an editorial accompanying the study, Don D. Sin, MD, MPH, from the University of British Columbia, Vancouver, commented that these medications should most likely be reserved for patients with COPD who have clinically significant airflow limitation,” and that “respiratory symptoms in tobacco-exposed persons are common but are highly variable over time.”
Dave Singh, MD, from the University of Manchester (England), the invited discussant, called it “a very important negative study.”
Not up to GOLD standard
Current or former smokers who are symptomatic, with COPD Assessment Test (CAT) scores of at least 10 despite having preserved function on spirometry, have been shown to have higher prospective rates of respiratory disease exacerbations and increased sputum total mucin concentrations. Approximately 43% of such patients are treated with bronchodilators, and 23% are treated with inhaled corticosteroids (ICS), Dr. Han noted.
Her group hypothesized that ever-smokers with spirometric values that fall within the normal range – that is, a postbronchodilator FEV1/FVC ratio of 70 or greater – would still derive benefit from long-acting bronchodilator therapy, even though these patients are currently excluded from Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations.
To test this, they conducted a 12-week, multicenter, randomized, parallel-group study in which patients were assigned to receive either indacaterol (27.5 mcg) and glycopyrrolate (15.6 mcg) inhaled twice daily or placebo.
They enrolled adults aged 40-80 years with a minimum of 10 pack-years of smoking history, postbronchodilator FEV1/FVC ratio of 70 or greater, and CAT scores of 10 or greater. Patients with known concomitant lung disease, a primary diagnosis of asthma, or body mass index lower than 15 or higher than 40 and those being concomitantly treated with long-acting beta2-agonists or muscarinic antagonists or a short-acting combination were excluded, although patients were allowed to be on a short-acting beta-agonist.
A total of 535 participants were randomized, but COVID-19 pandemic–imposed obstacles resulted in a modified intention-to-treat population of 277 patients assigned to receive the active treatment and 244 assigned to receive placebo.
There was no difference between the groups for the primary outcome of an at least 4-point decrease in St. George’s Respiratory Questionnaire scores in patients who did not experience treatment failure, defined as an increase in respiratory symptoms requiring treatment with active long-acting bronchodilators or ICS.
The primary endpoint was seen in 56.4% of patients in the bronchodilator group, and 59% of controls.
Although there was greater improvement in pulmonary function from baseline in the treatment group, compared with the placebo group, the improvements did not correlate with similar improvements in symptoms, Dr. Han said.
There were 4 serious adverse events in the bronchodilator group and 11 in the placebo group, but none of the events were deemed to be related to the assigned treatments.
Dr. Han acknowledged limitations of the study, which may have included symptoms driven by other factors such as cardiac disease, suggesting that if such patients had been identified and excluded, a stronger effect might have been seen for the active treatment.
In addition, the study was underpowered to look at the subgroup of participants with chronic bronchitis, and the 12 weeks of the study may have been too short to see improvements in symptoms.
In his editorial, Dr. Sin noted that the study showed that cough and sputum production rather than exertion dyspnea are the primary symptoms among ever-smokers.
“Although bronchodilators are effective in ameliorating breathlessness and improving exercise tolerance, they are generally ineffective for cough,” he wrote. “Existing drugs for the treatment of COPD, such as inhaled glucocorticoids or phosphodiesterase-4 inhibitors, or new therapeutics such as P2X3 receptor antagonists may be more effective for the treatment of cough and sputum production related to smoking and could be considered for future evaluations in this patient population.”
The study was supported by the National Heart, Lung, and Blood Institute, the National Center for Advancing Translational Sciences, and Sunovion Pharmaceuticals. Novartis Pharmaceuticals donated the trial medication and placebo. Dr. Han disclosed grant/research support and honoraria or consulting fees from various companies. Dr. Singh reported speaking fees, honoraria, and research grants from multiple companies. Dr. Sin reported having no conflicts of interest to disclose.
A version of this article first appeared on Medscape.com.
Current or former smokers who have clinically significant respiratory symptoms but no spirometric evidence of airway obstruction are often treated with dual bronchodilators commonly prescribed for patients with chronic obstructive pulmonary disease (COPD).
But as results of the randomized RETHINC (Redefining Therapy In Early COPD for the Pulmonary Trials Cooperative) trial showed, bronchodilator therapy was no better than placebo at reducing respiratory symptoms in smokers, reported MeiLan K. Han, MD, from the University of Michigan, Ann Arbor, on behalf of colleagues in the RETHINC study group.
“Many tobacco-exposed symptomatic individuals are currently being treated. We don’t know if this is because physicians just aren’t doing spirometry and assuming COPD or they strongly believe that there’s a benefit, but the bottom line is that we really need to do spirometry to understand who benefits from bronchodilators, and we need further research to understand how to treat this specific group of patients because there truly is pathogenesis and disease burden,” Dr. Han said in an oral abstract presentation at the annual congress of the European Respiratory Society.
The study results were also published online in the New England Journal of Medicine to coincide with the presentation.
In an editorial accompanying the study, Don D. Sin, MD, MPH, from the University of British Columbia, Vancouver, commented that these medications should most likely be reserved for patients with COPD who have clinically significant airflow limitation,” and that “respiratory symptoms in tobacco-exposed persons are common but are highly variable over time.”
Dave Singh, MD, from the University of Manchester (England), the invited discussant, called it “a very important negative study.”
Not up to GOLD standard
Current or former smokers who are symptomatic, with COPD Assessment Test (CAT) scores of at least 10 despite having preserved function on spirometry, have been shown to have higher prospective rates of respiratory disease exacerbations and increased sputum total mucin concentrations. Approximately 43% of such patients are treated with bronchodilators, and 23% are treated with inhaled corticosteroids (ICS), Dr. Han noted.
Her group hypothesized that ever-smokers with spirometric values that fall within the normal range – that is, a postbronchodilator FEV1/FVC ratio of 70 or greater – would still derive benefit from long-acting bronchodilator therapy, even though these patients are currently excluded from Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations.
To test this, they conducted a 12-week, multicenter, randomized, parallel-group study in which patients were assigned to receive either indacaterol (27.5 mcg) and glycopyrrolate (15.6 mcg) inhaled twice daily or placebo.
They enrolled adults aged 40-80 years with a minimum of 10 pack-years of smoking history, postbronchodilator FEV1/FVC ratio of 70 or greater, and CAT scores of 10 or greater. Patients with known concomitant lung disease, a primary diagnosis of asthma, or body mass index lower than 15 or higher than 40 and those being concomitantly treated with long-acting beta2-agonists or muscarinic antagonists or a short-acting combination were excluded, although patients were allowed to be on a short-acting beta-agonist.
A total of 535 participants were randomized, but COVID-19 pandemic–imposed obstacles resulted in a modified intention-to-treat population of 277 patients assigned to receive the active treatment and 244 assigned to receive placebo.
There was no difference between the groups for the primary outcome of an at least 4-point decrease in St. George’s Respiratory Questionnaire scores in patients who did not experience treatment failure, defined as an increase in respiratory symptoms requiring treatment with active long-acting bronchodilators or ICS.
The primary endpoint was seen in 56.4% of patients in the bronchodilator group, and 59% of controls.
Although there was greater improvement in pulmonary function from baseline in the treatment group, compared with the placebo group, the improvements did not correlate with similar improvements in symptoms, Dr. Han said.
There were 4 serious adverse events in the bronchodilator group and 11 in the placebo group, but none of the events were deemed to be related to the assigned treatments.
Dr. Han acknowledged limitations of the study, which may have included symptoms driven by other factors such as cardiac disease, suggesting that if such patients had been identified and excluded, a stronger effect might have been seen for the active treatment.
In addition, the study was underpowered to look at the subgroup of participants with chronic bronchitis, and the 12 weeks of the study may have been too short to see improvements in symptoms.
In his editorial, Dr. Sin noted that the study showed that cough and sputum production rather than exertion dyspnea are the primary symptoms among ever-smokers.
“Although bronchodilators are effective in ameliorating breathlessness and improving exercise tolerance, they are generally ineffective for cough,” he wrote. “Existing drugs for the treatment of COPD, such as inhaled glucocorticoids or phosphodiesterase-4 inhibitors, or new therapeutics such as P2X3 receptor antagonists may be more effective for the treatment of cough and sputum production related to smoking and could be considered for future evaluations in this patient population.”
The study was supported by the National Heart, Lung, and Blood Institute, the National Center for Advancing Translational Sciences, and Sunovion Pharmaceuticals. Novartis Pharmaceuticals donated the trial medication and placebo. Dr. Han disclosed grant/research support and honoraria or consulting fees from various companies. Dr. Singh reported speaking fees, honoraria, and research grants from multiple companies. Dr. Sin reported having no conflicts of interest to disclose.
A version of this article first appeared on Medscape.com.
FROM ERS 2022