Pulmonology

COVID-19 hospitalizations continue their steady summer march upward, and now a new variant has perched atop the list of the most prevalent forms of the virus.

Called “Eris” among avid COVID trackers, the strain EG.5 now accounts for 17% of all U.S. COVID infections, according to the latest Centers for Disease Control and Prevention estimates. That’s up from 12% the week prior. 

EG.5 has been rising worldwide, just weeks after the World Health Organization added the strain to its official monitoring list. In the United Kingdom, it now accounts for 1 in 10 COVID cases, The Independent reported.

EG.5 is a descendant of the XBB strains that have dominated tracking lists in recent months. It has the same makeup as XBB.1.9.2 but carries an extra spike mutation, according to a summary published by the Center for Infectious Disease Research and Policy at the University of Minnesota. The spike protein is the part of the virus that allows it to enter human cells. But there’s no indication so far that EG.5 is more contagious or severe than other recent variants, according to the CIDRAP summary and a recent podcast from the American Medical Association. The CDC said that current vaccines protect against the variant.

U.S. hospitals saw a 12% increase in COVID admissions during the week ending on July 22, with 8,047 people being admitted because of the virus, up from an all-time low of 6,306 the week of June 24. In 17 states, the past-week increase in hospitalizations was 20% or greater. In Minnesota, the rate jumped by 50%, and in West Virginia, it jumped by 63%. Meanwhile, deaths reached their lowest weekly rate ever for the week of data ending July 29, with just 176 deaths reported by the CDC.

A version of this article first appeared on WebMD.com.

COVID-19 hospitalizations continue their steady summer march upward, and now a new variant has perched atop the list of the most prevalent forms of the virus.

Called “Eris” among avid COVID trackers, the strain EG.5 now accounts for 17% of all U.S. COVID infections, according to the latest Centers for Disease Control and Prevention estimates. That’s up from 12% the week prior. 

EG.5 has been rising worldwide, just weeks after the World Health Organization added the strain to its official monitoring list. In the United Kingdom, it now accounts for 1 in 10 COVID cases, The Independent reported.

EG.5 is a descendant of the XBB strains that have dominated tracking lists in recent months. It has the same makeup as XBB.1.9.2 but carries an extra spike mutation, according to a summary published by the Center for Infectious Disease Research and Policy at the University of Minnesota. The spike protein is the part of the virus that allows it to enter human cells. But there’s no indication so far that EG.5 is more contagious or severe than other recent variants, according to the CIDRAP summary and a recent podcast from the American Medical Association. The CDC said that current vaccines protect against the variant.

U.S. hospitals saw a 12% increase in COVID admissions during the week ending on July 22, with 8,047 people being admitted because of the virus, up from an all-time low of 6,306 the week of June 24. In 17 states, the past-week increase in hospitalizations was 20% or greater. In Minnesota, the rate jumped by 50%, and in West Virginia, it jumped by 63%. Meanwhile, deaths reached their lowest weekly rate ever for the week of data ending July 29, with just 176 deaths reported by the CDC.

A version of this article first appeared on WebMD.com.

COVID-19 hospitalizations continue their steady summer march upward, and now a new variant has perched atop the list of the most prevalent forms of the virus.

Called “Eris” among avid COVID trackers, the strain EG.5 now accounts for 17% of all U.S. COVID infections, according to the latest Centers for Disease Control and Prevention estimates. That’s up from 12% the week prior. 

EG.5 has been rising worldwide, just weeks after the World Health Organization added the strain to its official monitoring list. In the United Kingdom, it now accounts for 1 in 10 COVID cases, The Independent reported.

EG.5 is a descendant of the XBB strains that have dominated tracking lists in recent months. It has the same makeup as XBB.1.9.2 but carries an extra spike mutation, according to a summary published by the Center for Infectious Disease Research and Policy at the University of Minnesota. The spike protein is the part of the virus that allows it to enter human cells. But there’s no indication so far that EG.5 is more contagious or severe than other recent variants, according to the CIDRAP summary and a recent podcast from the American Medical Association. The CDC said that current vaccines protect against the variant.

U.S. hospitals saw a 12% increase in COVID admissions during the week ending on July 22, with 8,047 people being admitted because of the virus, up from an all-time low of 6,306 the week of June 24. In 17 states, the past-week increase in hospitalizations was 20% or greater. In Minnesota, the rate jumped by 50%, and in West Virginia, it jumped by 63%. Meanwhile, deaths reached their lowest weekly rate ever for the week of data ending July 29, with just 176 deaths reported by the CDC.

A version of this article first appeared on WebMD.com.

The recent statement on interpretive strategies for lung testing uses the acronym PRISm for preserved ratio impaired spirometry. PRISm identifies patients with a normal forced expiratory volume in 1 second/forced vital capacity ratio but abnormal FEV₁ and/or FVC (usually both). Most medical students are taught to call this a “restrictive pattern,” and every first-year pulmonary fellow orders full lung volumes when they see it. If total lung capacity (TLC) is normal, PRISm becomes the nonspecific pattern. If TLC is low, then the patient has “true” restriction, and if it’s elevated, then hyperinflation may be present.

The traditional classification scheme for basic spirometry interpretation (normal, restricted, obstructed, or mixed) is simple and conceptually clear. Because this simplicity is achieved at the expense of precision, the “restrictive pattern” label is due for retirement. It turns out that many with this pattern won’t have an abnormal TLC, so the name is, in some ways, a misnomer and can be misleading. Enter PRISm, a more descriptive and inclusive term. The phrase also lends itself to a phonetic acronym that is fun to say, easy to remember, and likely to catch on with learners.

Information on occurrence and clinical behavior comes from large cohorts with basic spirometry, but without full lung volumes because PRISm no longer applies once TLC is determined. As may be expected, prevalence varies by the population studied. Estimates for general populations have been in the 7%-12% range; however, one study examining a database of patients with clinical spirometry referrals found a prevalence of 22.3%. Rates may be far higher in low- and middle-income countries. Identified risk factors include sex, tobacco use, and body mass index; the presence of PRISm is associated with respiratory symptoms and mortality. Thus, PRISm is common and it matters.

Along with PRISm, the nonspecific pattern is a new addition, if not a new concept, to the 2022 interpretative strategies statement. As with PRISm, the title is necessarily broad, though far less imaginative. Defined by reductions in FEV₁ and FVC and a normal TLC, the nonspecific pattern has classically been considered a marker of early airway disease. The idea is that early, heterogeneous closure of distal segments of the bronchial tree can reduce total volume during a forced expiration before affecting the FEV₁/FVC. The fact that the TLC is not a forced maneuver means there is proportionately less effect from more collapsible/susceptible smaller units. More recent data suggest that there are additional causes.

Because the nonspecific pattern requires full lung volumes, we have less population-level data than for PRISm. Estimated prevalence is approximately 9.5% in patients with complete test results. The two most common causes are obesity and airway obstruction, and the pattern is relatively stable over time. Notably, an increase in specific airway resistance or TLC minus alveolar volume difference predicts progression to frank obstruction on spirometry.

The physiologic changes that obesity inflicts on the lung have been well described. Patients with obesity breathe at lower lung volumes and are therefore susceptible to small airway closure at rest and during forced expiration. There is no doubt that the increased recognition of PRISm and the nonspecific pattern is in part related to the worldwide rise in obesity rates.
 

Key takeaways

In summary, PRISm and the nonspecific pattern are now part of the classification scheme we use for spirometry and full lung volumes, respectively. They should be included in interpretations given their diagnostic and predictive value. Airway disease and obesity are common causes and often coexist with either pattern. Many will not have a true, restrictive lung deficit, and a reductionist approach to interpretation is likely to lead to erroneous diagnoses. There were many important updates included in the 2022 iteration on lung testing interpretation that should not fly under the radar.

Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington. He disclosed ties with CHEST College, Metapharm, and WebMD.

A version of this article appeared on Medscape.com.

The recent statement on interpretive strategies for lung testing uses the acronym PRISm for preserved ratio impaired spirometry. PRISm identifies patients with a normal forced expiratory volume in 1 second/forced vital capacity ratio but abnormal FEV₁ and/or FVC (usually both). Most medical students are taught to call this a “restrictive pattern,” and every first-year pulmonary fellow orders full lung volumes when they see it. If total lung capacity (TLC) is normal, PRISm becomes the nonspecific pattern. If TLC is low, then the patient has “true” restriction, and if it’s elevated, then hyperinflation may be present.

The traditional classification scheme for basic spirometry interpretation (normal, restricted, obstructed, or mixed) is simple and conceptually clear. Because this simplicity is achieved at the expense of precision, the “restrictive pattern” label is due for retirement. It turns out that many with this pattern won’t have an abnormal TLC, so the name is, in some ways, a misnomer and can be misleading. Enter PRISm, a more descriptive and inclusive term. The phrase also lends itself to a phonetic acronym that is fun to say, easy to remember, and likely to catch on with learners.

Information on occurrence and clinical behavior comes from large cohorts with basic spirometry, but without full lung volumes because PRISm no longer applies once TLC is determined. As may be expected, prevalence varies by the population studied. Estimates for general populations have been in the 7%-12% range; however, one study examining a database of patients with clinical spirometry referrals found a prevalence of 22.3%. Rates may be far higher in low- and middle-income countries. Identified risk factors include sex, tobacco use, and body mass index; the presence of PRISm is associated with respiratory symptoms and mortality. Thus, PRISm is common and it matters.

Along with PRISm, the nonspecific pattern is a new addition, if not a new concept, to the 2022 interpretative strategies statement. As with PRISm, the title is necessarily broad, though far less imaginative. Defined by reductions in FEV₁ and FVC and a normal TLC, the nonspecific pattern has classically been considered a marker of early airway disease. The idea is that early, heterogeneous closure of distal segments of the bronchial tree can reduce total volume during a forced expiration before affecting the FEV₁/FVC. The fact that the TLC is not a forced maneuver means there is proportionately less effect from more collapsible/susceptible smaller units. More recent data suggest that there are additional causes.

Because the nonspecific pattern requires full lung volumes, we have less population-level data than for PRISm. Estimated prevalence is approximately 9.5% in patients with complete test results. The two most common causes are obesity and airway obstruction, and the pattern is relatively stable over time. Notably, an increase in specific airway resistance or TLC minus alveolar volume difference predicts progression to frank obstruction on spirometry.

The physiologic changes that obesity inflicts on the lung have been well described. Patients with obesity breathe at lower lung volumes and are therefore susceptible to small airway closure at rest and during forced expiration. There is no doubt that the increased recognition of PRISm and the nonspecific pattern is in part related to the worldwide rise in obesity rates.
 

Key takeaways

In summary, PRISm and the nonspecific pattern are now part of the classification scheme we use for spirometry and full lung volumes, respectively. They should be included in interpretations given their diagnostic and predictive value. Airway disease and obesity are common causes and often coexist with either pattern. Many will not have a true, restrictive lung deficit, and a reductionist approach to interpretation is likely to lead to erroneous diagnoses. There were many important updates included in the 2022 iteration on lung testing interpretation that should not fly under the radar.

Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington. He disclosed ties with CHEST College, Metapharm, and WebMD.

A version of this article appeared on Medscape.com.

The recent statement on interpretive strategies for lung testing uses the acronym PRISm for preserved ratio impaired spirometry. PRISm identifies patients with a normal forced expiratory volume in 1 second/forced vital capacity ratio but abnormal FEV₁ and/or FVC (usually both). Most medical students are taught to call this a “restrictive pattern,” and every first-year pulmonary fellow orders full lung volumes when they see it. If total lung capacity (TLC) is normal, PRISm becomes the nonspecific pattern. If TLC is low, then the patient has “true” restriction, and if it’s elevated, then hyperinflation may be present.

The traditional classification scheme for basic spirometry interpretation (normal, restricted, obstructed, or mixed) is simple and conceptually clear. Because this simplicity is achieved at the expense of precision, the “restrictive pattern” label is due for retirement. It turns out that many with this pattern won’t have an abnormal TLC, so the name is, in some ways, a misnomer and can be misleading. Enter PRISm, a more descriptive and inclusive term. The phrase also lends itself to a phonetic acronym that is fun to say, easy to remember, and likely to catch on with learners.

Information on occurrence and clinical behavior comes from large cohorts with basic spirometry, but without full lung volumes because PRISm no longer applies once TLC is determined. As may be expected, prevalence varies by the population studied. Estimates for general populations have been in the 7%-12% range; however, one study examining a database of patients with clinical spirometry referrals found a prevalence of 22.3%. Rates may be far higher in low- and middle-income countries. Identified risk factors include sex, tobacco use, and body mass index; the presence of PRISm is associated with respiratory symptoms and mortality. Thus, PRISm is common and it matters.

Along with PRISm, the nonspecific pattern is a new addition, if not a new concept, to the 2022 interpretative strategies statement. As with PRISm, the title is necessarily broad, though far less imaginative. Defined by reductions in FEV₁ and FVC and a normal TLC, the nonspecific pattern has classically been considered a marker of early airway disease. The idea is that early, heterogeneous closure of distal segments of the bronchial tree can reduce total volume during a forced expiration before affecting the FEV₁/FVC. The fact that the TLC is not a forced maneuver means there is proportionately less effect from more collapsible/susceptible smaller units. More recent data suggest that there are additional causes.

Because the nonspecific pattern requires full lung volumes, we have less population-level data than for PRISm. Estimated prevalence is approximately 9.5% in patients with complete test results. The two most common causes are obesity and airway obstruction, and the pattern is relatively stable over time. Notably, an increase in specific airway resistance or TLC minus alveolar volume difference predicts progression to frank obstruction on spirometry.

The physiologic changes that obesity inflicts on the lung have been well described. Patients with obesity breathe at lower lung volumes and are therefore susceptible to small airway closure at rest and during forced expiration. There is no doubt that the increased recognition of PRISm and the nonspecific pattern is in part related to the worldwide rise in obesity rates.
 

Key takeaways

In summary, PRISm and the nonspecific pattern are now part of the classification scheme we use for spirometry and full lung volumes, respectively. They should be included in interpretations given their diagnostic and predictive value. Airway disease and obesity are common causes and often coexist with either pattern. Many will not have a true, restrictive lung deficit, and a reductionist approach to interpretation is likely to lead to erroneous diagnoses. There were many important updates included in the 2022 iteration on lung testing interpretation that should not fly under the radar.

Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington. He disclosed ties with CHEST College, Metapharm, and WebMD.

A version of this article appeared on Medscape.com.

NEW YORK – When data were combined from two parallel phase 3 bronchiectasis treatment trials, inhaled colistimethate sodium failed to significantly reduce the rate of exacerbations associated with Pseudomonas aeruginosa infection, but the disparity in the findings from the two trials, presented at the 6th World Bronchiectasis & NTM Conference (WBC) 2023, strongly suggests that this therapy is effective after all.

“The totality of the evidence supports a consistent and clinically meaningful benefit [of this therapy] outside of pandemic conditions,” reported Charles Haworth, MD, director, Cambridge Centre for Lung Infection, Royal Papworth Hospital, Cambridge, England.

The key phrase is “outside of pandemic conditions.” PROMIS I, which was fully enrolled before the COVID-19 pandemic descended, associated the inhaled therapy with highly significant benefits. PROMIS II, which was initiated later and enrolled 40% of its participants during the pandemic, did not.

The difference between these two trials, which were essentially identical, was the timing, according to Dr. Haworth. By starting later, PROMIS II caught the onset of the pandemic, which he believes introduced numerous problems that defeated the opportunity to show an advantage for the inhaled antibiotic.

Injectable colistimethate sodium, a decades-old formulation of colistin, is already approved in the United States for gram-negative infections and is considered helpful even in challenging diseases, such as cystic fibrosis. Positive results from a phase 2 trial with inhaled colistimethate sodium in bronchiectasis patients with P. aeruginosa infection provided the rationale for the phase 3 PROMIS program.

The key entry criterion of PROMIS I and PROMIS II, each with nearly 90 participating study sites, was a history of bronchiectasis and ≥ two P. aeruginosa infections requiring oral therapy or ≥ 1 infection requiring intravenous therapy in the prior 12 months. Patients were randomly assigned to receive colistimethate sodium delivered in the proprietary I-neb nebulizer (CMS I-neb) or a matching placebo.

On the primary endpoint of annualized rate of exacerbations, the figures per year were 0.58 for CMS I-neb and 0.95 for placebo in the PROMIS I trial. This produced a rate ratio of 0.65, signaling a significant 35% (P = .00101) reduction in risk. In PROMIS II, the annualized rates of exacerbation were essentially identical in the experimental and control arms (0.089 vs. 0.088; P = .97).

With “no signal of benefit” in the PROMIS II trial, the numerical advantage of CMS I-neb for the combined data did not reach statistical significance, Dr. Haworth reported.

Other endpoints told the same story. For example, the time to first exacerbation was reduced by 41% in PROMIS I (HR, 0.59; P = .0074) but was not reduced significantly (P = .603) in PROMIS II. In PROMIS I, there was a nearly 60% reduction in the risk of severe exacerbations associated with CMS I-neb, but the risk ratio of severe infections was slightly but not significantly higher on CMS I-neb in PROMIS II.

There were signals of benefit in PROMIS II. For example, the reductions in P. aeruginosa density were similar in the two studies (P < .00001 in both), and assessment with the Severe Exacerbations and Quality of Life (SQOL) tool associated CMS I-neb with end-of-study improvement in QOL for the experimental arm in both studies.

While Dr. Haworth acknowledged that he recognizes the “issues of post hoc analysis with any data,” he argued that there is compelling evidence that the pandemic “severely disrupted the conduct of the trial,” obscuring a benefit that would have been otherwise shown.

Besides the dramatic reduction in rates of hospitalization during the pandemic, an obstacle for showing differences in exacerbations, and other COVID-related factors with the potential to skew results, Dr. Haworth also provided several sets of objective data to make his point.

Most importantly, Dr. Haworth and his coinvestigators conducted a meta-analysis that combined data from the phase 2 trial, data from PROMIS I, and data from the patients enrolled in PROMIS II prior to the COVID pandemic. In this analysis the rate ratio for annualized exacerbations was a “pretty impressive” 0.65 favoring CMS I-neb. Moreover, in contrast to data from the PROMIS II patients enrolled during the COVID pandemic, the other three sets of data were “remarkably consistent.”

If PROMIS II data collected from patients enrolled during COVID are compared with the other sets of data, they are “the clear outlier,” he asserted.

Many guidelines in Europe, including those from the European Respiratory Society and the British Thoracic Society, already recommend inhaled colistin in patients with bronchiectasis for the treatment of P. aeruginosa. Although Dr. Haworth believes that the preponderance of controlled data now argue that CMS I-neb is effective as well as safe (adverse events in the experimental and placebo arms of PROMIS I and II were similar), he is not sure what steps will be taken to confirm a benefit to regulatory authorities. According to Dr. Haworth, there are no approved inhaled antibiotics in the United States.

Referring to Zambon, which funded the trials and is developing CMS I-neb, Dr. Haworth said, “This will be a company decision. There are some logistical hurdles to doing another trial.”

Not least of these hurdles is that clinicians and patients already consider inhalational antibiotics in general and inhaled colistin specifically to be effective for several types of infections, including P. aeruginosa, according to Eva Polverino, MD, PhD, a pulmonologist associated with the Hospital Clinic of Barcelona. She said that these drugs are already a standard of care in her own country as well as in many other countries in Europe.

“There has been a loss of equipoise needed to conduct a randomized placebo-controlled trial,” Dr. Polverino said. In her opinion, the U.S. FDA “should start thinking of other pathways to approval.” She thinks that enrollment in a placebo-controlled trial is no longer appropriate.

Dr. Haworth and Dr. Polverino have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NEW YORK – When data were combined from two parallel phase 3 bronchiectasis treatment trials, inhaled colistimethate sodium failed to significantly reduce the rate of exacerbations associated with Pseudomonas aeruginosa infection, but the disparity in the findings from the two trials, presented at the 6th World Bronchiectasis & NTM Conference (WBC) 2023, strongly suggests that this therapy is effective after all.

“The totality of the evidence supports a consistent and clinically meaningful benefit [of this therapy] outside of pandemic conditions,” reported Charles Haworth, MD, director, Cambridge Centre for Lung Infection, Royal Papworth Hospital, Cambridge, England.

The key phrase is “outside of pandemic conditions.” PROMIS I, which was fully enrolled before the COVID-19 pandemic descended, associated the inhaled therapy with highly significant benefits. PROMIS II, which was initiated later and enrolled 40% of its participants during the pandemic, did not.

The difference between these two trials, which were essentially identical, was the timing, according to Dr. Haworth. By starting later, PROMIS II caught the onset of the pandemic, which he believes introduced numerous problems that defeated the opportunity to show an advantage for the inhaled antibiotic.

Injectable colistimethate sodium, a decades-old formulation of colistin, is already approved in the United States for gram-negative infections and is considered helpful even in challenging diseases, such as cystic fibrosis. Positive results from a phase 2 trial with inhaled colistimethate sodium in bronchiectasis patients with P. aeruginosa infection provided the rationale for the phase 3 PROMIS program.

The key entry criterion of PROMIS I and PROMIS II, each with nearly 90 participating study sites, was a history of bronchiectasis and ≥ two P. aeruginosa infections requiring oral therapy or ≥ 1 infection requiring intravenous therapy in the prior 12 months. Patients were randomly assigned to receive colistimethate sodium delivered in the proprietary I-neb nebulizer (CMS I-neb) or a matching placebo.

On the primary endpoint of annualized rate of exacerbations, the figures per year were 0.58 for CMS I-neb and 0.95 for placebo in the PROMIS I trial. This produced a rate ratio of 0.65, signaling a significant 35% (P = .00101) reduction in risk. In PROMIS II, the annualized rates of exacerbation were essentially identical in the experimental and control arms (0.089 vs. 0.088; P = .97).

With “no signal of benefit” in the PROMIS II trial, the numerical advantage of CMS I-neb for the combined data did not reach statistical significance, Dr. Haworth reported.

Other endpoints told the same story. For example, the time to first exacerbation was reduced by 41% in PROMIS I (HR, 0.59; P = .0074) but was not reduced significantly (P = .603) in PROMIS II. In PROMIS I, there was a nearly 60% reduction in the risk of severe exacerbations associated with CMS I-neb, but the risk ratio of severe infections was slightly but not significantly higher on CMS I-neb in PROMIS II.

There were signals of benefit in PROMIS II. For example, the reductions in P. aeruginosa density were similar in the two studies (P < .00001 in both), and assessment with the Severe Exacerbations and Quality of Life (SQOL) tool associated CMS I-neb with end-of-study improvement in QOL for the experimental arm in both studies.

While Dr. Haworth acknowledged that he recognizes the “issues of post hoc analysis with any data,” he argued that there is compelling evidence that the pandemic “severely disrupted the conduct of the trial,” obscuring a benefit that would have been otherwise shown.

Besides the dramatic reduction in rates of hospitalization during the pandemic, an obstacle for showing differences in exacerbations, and other COVID-related factors with the potential to skew results, Dr. Haworth also provided several sets of objective data to make his point.

Most importantly, Dr. Haworth and his coinvestigators conducted a meta-analysis that combined data from the phase 2 trial, data from PROMIS I, and data from the patients enrolled in PROMIS II prior to the COVID pandemic. In this analysis the rate ratio for annualized exacerbations was a “pretty impressive” 0.65 favoring CMS I-neb. Moreover, in contrast to data from the PROMIS II patients enrolled during the COVID pandemic, the other three sets of data were “remarkably consistent.”

If PROMIS II data collected from patients enrolled during COVID are compared with the other sets of data, they are “the clear outlier,” he asserted.

Many guidelines in Europe, including those from the European Respiratory Society and the British Thoracic Society, already recommend inhaled colistin in patients with bronchiectasis for the treatment of P. aeruginosa. Although Dr. Haworth believes that the preponderance of controlled data now argue that CMS I-neb is effective as well as safe (adverse events in the experimental and placebo arms of PROMIS I and II were similar), he is not sure what steps will be taken to confirm a benefit to regulatory authorities. According to Dr. Haworth, there are no approved inhaled antibiotics in the United States.

Referring to Zambon, which funded the trials and is developing CMS I-neb, Dr. Haworth said, “This will be a company decision. There are some logistical hurdles to doing another trial.”

Not least of these hurdles is that clinicians and patients already consider inhalational antibiotics in general and inhaled colistin specifically to be effective for several types of infections, including P. aeruginosa, according to Eva Polverino, MD, PhD, a pulmonologist associated with the Hospital Clinic of Barcelona. She said that these drugs are already a standard of care in her own country as well as in many other countries in Europe.

“There has been a loss of equipoise needed to conduct a randomized placebo-controlled trial,” Dr. Polverino said. In her opinion, the U.S. FDA “should start thinking of other pathways to approval.” She thinks that enrollment in a placebo-controlled trial is no longer appropriate.

Dr. Haworth and Dr. Polverino have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NEW YORK – When data were combined from two parallel phase 3 bronchiectasis treatment trials, inhaled colistimethate sodium failed to significantly reduce the rate of exacerbations associated with Pseudomonas aeruginosa infection, but the disparity in the findings from the two trials, presented at the 6th World Bronchiectasis & NTM Conference (WBC) 2023, strongly suggests that this therapy is effective after all.

“The totality of the evidence supports a consistent and clinically meaningful benefit [of this therapy] outside of pandemic conditions,” reported Charles Haworth, MD, director, Cambridge Centre for Lung Infection, Royal Papworth Hospital, Cambridge, England.

The key phrase is “outside of pandemic conditions.” PROMIS I, which was fully enrolled before the COVID-19 pandemic descended, associated the inhaled therapy with highly significant benefits. PROMIS II, which was initiated later and enrolled 40% of its participants during the pandemic, did not.

The difference between these two trials, which were essentially identical, was the timing, according to Dr. Haworth. By starting later, PROMIS II caught the onset of the pandemic, which he believes introduced numerous problems that defeated the opportunity to show an advantage for the inhaled antibiotic.

Injectable colistimethate sodium, a decades-old formulation of colistin, is already approved in the United States for gram-negative infections and is considered helpful even in challenging diseases, such as cystic fibrosis. Positive results from a phase 2 trial with inhaled colistimethate sodium in bronchiectasis patients with P. aeruginosa infection provided the rationale for the phase 3 PROMIS program.

The key entry criterion of PROMIS I and PROMIS II, each with nearly 90 participating study sites, was a history of bronchiectasis and ≥ two P. aeruginosa infections requiring oral therapy or ≥ 1 infection requiring intravenous therapy in the prior 12 months. Patients were randomly assigned to receive colistimethate sodium delivered in the proprietary I-neb nebulizer (CMS I-neb) or a matching placebo.

On the primary endpoint of annualized rate of exacerbations, the figures per year were 0.58 for CMS I-neb and 0.95 for placebo in the PROMIS I trial. This produced a rate ratio of 0.65, signaling a significant 35% (P = .00101) reduction in risk. In PROMIS II, the annualized rates of exacerbation were essentially identical in the experimental and control arms (0.089 vs. 0.088; P = .97).

With “no signal of benefit” in the PROMIS II trial, the numerical advantage of CMS I-neb for the combined data did not reach statistical significance, Dr. Haworth reported.

Other endpoints told the same story. For example, the time to first exacerbation was reduced by 41% in PROMIS I (HR, 0.59; P = .0074) but was not reduced significantly (P = .603) in PROMIS II. In PROMIS I, there was a nearly 60% reduction in the risk of severe exacerbations associated with CMS I-neb, but the risk ratio of severe infections was slightly but not significantly higher on CMS I-neb in PROMIS II.

There were signals of benefit in PROMIS II. For example, the reductions in P. aeruginosa density were similar in the two studies (P < .00001 in both), and assessment with the Severe Exacerbations and Quality of Life (SQOL) tool associated CMS I-neb with end-of-study improvement in QOL for the experimental arm in both studies.

While Dr. Haworth acknowledged that he recognizes the “issues of post hoc analysis with any data,” he argued that there is compelling evidence that the pandemic “severely disrupted the conduct of the trial,” obscuring a benefit that would have been otherwise shown.

Besides the dramatic reduction in rates of hospitalization during the pandemic, an obstacle for showing differences in exacerbations, and other COVID-related factors with the potential to skew results, Dr. Haworth also provided several sets of objective data to make his point.

Most importantly, Dr. Haworth and his coinvestigators conducted a meta-analysis that combined data from the phase 2 trial, data from PROMIS I, and data from the patients enrolled in PROMIS II prior to the COVID pandemic. In this analysis the rate ratio for annualized exacerbations was a “pretty impressive” 0.65 favoring CMS I-neb. Moreover, in contrast to data from the PROMIS II patients enrolled during the COVID pandemic, the other three sets of data were “remarkably consistent.”

If PROMIS II data collected from patients enrolled during COVID are compared with the other sets of data, they are “the clear outlier,” he asserted.

Many guidelines in Europe, including those from the European Respiratory Society and the British Thoracic Society, already recommend inhaled colistin in patients with bronchiectasis for the treatment of P. aeruginosa. Although Dr. Haworth believes that the preponderance of controlled data now argue that CMS I-neb is effective as well as safe (adverse events in the experimental and placebo arms of PROMIS I and II were similar), he is not sure what steps will be taken to confirm a benefit to regulatory authorities. According to Dr. Haworth, there are no approved inhaled antibiotics in the United States.

Referring to Zambon, which funded the trials and is developing CMS I-neb, Dr. Haworth said, “This will be a company decision. There are some logistical hurdles to doing another trial.”

Not least of these hurdles is that clinicians and patients already consider inhalational antibiotics in general and inhaled colistin specifically to be effective for several types of infections, including P. aeruginosa, according to Eva Polverino, MD, PhD, a pulmonologist associated with the Hospital Clinic of Barcelona. She said that these drugs are already a standard of care in her own country as well as in many other countries in Europe.

“There has been a loss of equipoise needed to conduct a randomized placebo-controlled trial,” Dr. Polverino said. In her opinion, the U.S. FDA “should start thinking of other pathways to approval.” She thinks that enrollment in a placebo-controlled trial is no longer appropriate.

Dr. Haworth and Dr. Polverino have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Lower doses of initial vasopressin were associated with lower mortality when used as an adjunct in patients with septic shock, according to a review of three recent studies.

“Patients with septic shock require vasoactive agents to restore adequate tissue perfusion,” writes Gretchen L. Sacha, PharmD, of the Cleveland Clinic and colleagues.

Vasopressin is an attractive alternative to norepinephrine because it avoids the adverse effects associated with catecholamines, the researchers say. Although vasopressin is the recommended second-line adjunct after norepinephrine for patients with septic shock, findings to guide its use are inconsistent and data on the timing are limited, they note.

In a review published in the journal CHEST, the researchers summarize the three large, randomized trials to date examining the use of norepinephrine and vasopressin in patients with septic shock.

In the Vasopressin in Septic Shock Trial (VASST), 382 patients with septic shock were randomized to open-label norepinephrine with blinded norepinephrine, and 382 were randomized to open-label norepinephrine with blinded adjunctive vasopressin.

After initiation of the study drug, patients randomized to vasopressin had significantly lower requirements for open-label norepinephrine (P < .001). Although no differences occurred in the primary outcome of 28-day mortality, 90-day mortality was lower in the vasopressin group.

In the Vasopressin vs Norepinephrine as Initial Therapy in Septic Shock (VANISH) trial, 204 patients with septic shock were randomized to norepinephrine and 204 to vasopressin as an initial vasoactive agent. Although no differences appeared between the groups for the two primary outcomes of 28-day mortality and days free of kidney failure, the vasopressin group had a lower frequency of the use of kidney replacement therapy (absolute difference –9.9% vs. –0.6%).

The VANISH study was limited by the fact that 85% of the patients were receiving norepinephrine when they were randomized; “therefore, this study is best described as evaluating catecholamine-adjunctive vasopressin,” the researchers say.

The third clinical trial, published only as an abstract, randomized 387 patients with septic shock who were already receiving low doses of norepinephrine to either norepinephrine with adjunctive vasopressin or norepinephrine alone. Rates of 28-day mortality were significantly lower in the vasopressin group (34.0% vs. 42.3%; P = .03).

Several meta-analyses involving multiple vasopressin receptor agonists have shown an association between reduced mortality and their use. In addition, recent observational studies have shown an association between lower mortality and the initiation of vasopressors at a lower norepinephrine-equivalent dose or lower lactate concentration.

As for clinical implications, the 2021 version of the Surviving Sepsis Campaign (SSC) guidelines included a meta-analysis of 10 randomized, controlled trials that showed improved mortality associated with vasopressin use. This version of the guidelines was the first to address the timing of vasopressin initiation.

Because of insufficient evidence, the guidance was worded as “in our practice, vasopressin is usually started when the dose of norepinephrine is in the range of 0.25-0.5 mcg/kg/min,” the researchers write. “Although this is not a recommendation by the SSC for a specific threshold of catecholamine dose where vasopressin should be initiated, this statement represents clinician interest and the need for further research on the topic,” they note.

“Future studies of vasopressin should focus on the timing of its initiation at various clinical thresholds and patient selection for receipt of vasopressin,” they conclude.

The study was supported by the National Institutes of Health, National Institute of General Medical Sciences. Dr. Sacha has disclosed consulting for Wolters Kluwer.

A version of this article first appeared on Medscape.com.

Lower doses of initial vasopressin were associated with lower mortality when used as an adjunct in patients with septic shock, according to a review of three recent studies.

“Patients with septic shock require vasoactive agents to restore adequate tissue perfusion,” writes Gretchen L. Sacha, PharmD, of the Cleveland Clinic and colleagues.

Vasopressin is an attractive alternative to norepinephrine because it avoids the adverse effects associated with catecholamines, the researchers say. Although vasopressin is the recommended second-line adjunct after norepinephrine for patients with septic shock, findings to guide its use are inconsistent and data on the timing are limited, they note.

In a review published in the journal CHEST, the researchers summarize the three large, randomized trials to date examining the use of norepinephrine and vasopressin in patients with septic shock.

In the Vasopressin in Septic Shock Trial (VASST), 382 patients with septic shock were randomized to open-label norepinephrine with blinded norepinephrine, and 382 were randomized to open-label norepinephrine with blinded adjunctive vasopressin.

After initiation of the study drug, patients randomized to vasopressin had significantly lower requirements for open-label norepinephrine (P < .001). Although no differences occurred in the primary outcome of 28-day mortality, 90-day mortality was lower in the vasopressin group.

In the Vasopressin vs Norepinephrine as Initial Therapy in Septic Shock (VANISH) trial, 204 patients with septic shock were randomized to norepinephrine and 204 to vasopressin as an initial vasoactive agent. Although no differences appeared between the groups for the two primary outcomes of 28-day mortality and days free of kidney failure, the vasopressin group had a lower frequency of the use of kidney replacement therapy (absolute difference –9.9% vs. –0.6%).

The VANISH study was limited by the fact that 85% of the patients were receiving norepinephrine when they were randomized; “therefore, this study is best described as evaluating catecholamine-adjunctive vasopressin,” the researchers say.

The third clinical trial, published only as an abstract, randomized 387 patients with septic shock who were already receiving low doses of norepinephrine to either norepinephrine with adjunctive vasopressin or norepinephrine alone. Rates of 28-day mortality were significantly lower in the vasopressin group (34.0% vs. 42.3%; P = .03).

Several meta-analyses involving multiple vasopressin receptor agonists have shown an association between reduced mortality and their use. In addition, recent observational studies have shown an association between lower mortality and the initiation of vasopressors at a lower norepinephrine-equivalent dose or lower lactate concentration.

As for clinical implications, the 2021 version of the Surviving Sepsis Campaign (SSC) guidelines included a meta-analysis of 10 randomized, controlled trials that showed improved mortality associated with vasopressin use. This version of the guidelines was the first to address the timing of vasopressin initiation.

Because of insufficient evidence, the guidance was worded as “in our practice, vasopressin is usually started when the dose of norepinephrine is in the range of 0.25-0.5 mcg/kg/min,” the researchers write. “Although this is not a recommendation by the SSC for a specific threshold of catecholamine dose where vasopressin should be initiated, this statement represents clinician interest and the need for further research on the topic,” they note.

“Future studies of vasopressin should focus on the timing of its initiation at various clinical thresholds and patient selection for receipt of vasopressin,” they conclude.

The study was supported by the National Institutes of Health, National Institute of General Medical Sciences. Dr. Sacha has disclosed consulting for Wolters Kluwer.

A version of this article first appeared on Medscape.com.

Lower doses of initial vasopressin were associated with lower mortality when used as an adjunct in patients with septic shock, according to a review of three recent studies.

“Patients with septic shock require vasoactive agents to restore adequate tissue perfusion,” writes Gretchen L. Sacha, PharmD, of the Cleveland Clinic and colleagues.

Vasopressin is an attractive alternative to norepinephrine because it avoids the adverse effects associated with catecholamines, the researchers say. Although vasopressin is the recommended second-line adjunct after norepinephrine for patients with septic shock, findings to guide its use are inconsistent and data on the timing are limited, they note.

In a review published in the journal CHEST, the researchers summarize the three large, randomized trials to date examining the use of norepinephrine and vasopressin in patients with septic shock.

In the Vasopressin in Septic Shock Trial (VASST), 382 patients with septic shock were randomized to open-label norepinephrine with blinded norepinephrine, and 382 were randomized to open-label norepinephrine with blinded adjunctive vasopressin.

After initiation of the study drug, patients randomized to vasopressin had significantly lower requirements for open-label norepinephrine (P < .001). Although no differences occurred in the primary outcome of 28-day mortality, 90-day mortality was lower in the vasopressin group.

In the Vasopressin vs Norepinephrine as Initial Therapy in Septic Shock (VANISH) trial, 204 patients with septic shock were randomized to norepinephrine and 204 to vasopressin as an initial vasoactive agent. Although no differences appeared between the groups for the two primary outcomes of 28-day mortality and days free of kidney failure, the vasopressin group had a lower frequency of the use of kidney replacement therapy (absolute difference –9.9% vs. –0.6%).

The VANISH study was limited by the fact that 85% of the patients were receiving norepinephrine when they were randomized; “therefore, this study is best described as evaluating catecholamine-adjunctive vasopressin,” the researchers say.

The third clinical trial, published only as an abstract, randomized 387 patients with septic shock who were already receiving low doses of norepinephrine to either norepinephrine with adjunctive vasopressin or norepinephrine alone. Rates of 28-day mortality were significantly lower in the vasopressin group (34.0% vs. 42.3%; P = .03).

Several meta-analyses involving multiple vasopressin receptor agonists have shown an association between reduced mortality and their use. In addition, recent observational studies have shown an association between lower mortality and the initiation of vasopressors at a lower norepinephrine-equivalent dose or lower lactate concentration.

As for clinical implications, the 2021 version of the Surviving Sepsis Campaign (SSC) guidelines included a meta-analysis of 10 randomized, controlled trials that showed improved mortality associated with vasopressin use. This version of the guidelines was the first to address the timing of vasopressin initiation.

Because of insufficient evidence, the guidance was worded as “in our practice, vasopressin is usually started when the dose of norepinephrine is in the range of 0.25-0.5 mcg/kg/min,” the researchers write. “Although this is not a recommendation by the SSC for a specific threshold of catecholamine dose where vasopressin should be initiated, this statement represents clinician interest and the need for further research on the topic,” they note.

“Future studies of vasopressin should focus on the timing of its initiation at various clinical thresholds and patient selection for receipt of vasopressin,” they conclude.

The study was supported by the National Institutes of Health, National Institute of General Medical Sciences. Dr. Sacha has disclosed consulting for Wolters Kluwer.

A version of this article first appeared on Medscape.com.

Researchers in Texas are developing a “green light” technology they hope will solve a crucial problem highlighted by the pandemic: the limits of pulse oximeters in patients with darker skin.

A recent study adds weight to earlier findings that their device works. 

“It is a new, first-in-class technology,” said Sanjay Gokhale, MD, the bioengineer who is leading this research at the University of Texas at Arlington. “The team conducted extensive preclinical work and carried out phase 1 studies in human volunteers, demonstrating sensitivity and accuracy.”

It’s one of several projects underway to update pulse oximetry, a technology based on research in lighter-skinned people that has not changed much in 50 years. 

The pulse oximeter, or “pulse ox,” measures the saturation of oxygen in your hemoglobin (a protein in red blood cells). But it tends to overestimate the oxygen saturation in patients with darker skin by about 2%-3%. That may not sound like a lot, but it’s enough to delay major treatment for respiratory issues like COVID-19. 

“Falsely elevated readings from commercial oximeters have delayed treatment of Black COVID-19 patients for hours in some cases,” said Divya Chander, MD, PhD, an anesthesiologist in Oakland, Calif., and chair of neuroscience at The Singularity Group. (Dr. Chander was not involved in the UT Arlington research.)

Early research happening separately at Brown University and Tufts University aims to redesign the pulse oximeter to get accurate readings in patients of all skin tones. University of California, San Diego, researchers are looking into a method that measures blood oxygen using sound in combination with light.  Other solutions try to correct for skin tone with algorithms. 

The device from UT Arlington uses an algorithm too, but its main innovation is that it replaces red light with green light. 
 

Red light, green light

Traditional oximetry devices, which typically clip on to the patient’s fingertip, use LEDs to beam light through the skin at two wavelengths: one in the red part of the spectrum, the other in the infrared. The light transmits from one side of the clip to the other, passing through arterial blood as it pulses.

The device calculates a patient’s oxygenation based on how much light of each wavelength is absorbed by hemoglobin in the blood. Oxygenated hemoglobin absorbs the light differently than deoxygenated hemoglobin, so oxygenation can be represented as a percentage; 100% means all hemoglobin is completely oxygenated.  But the melanin in skin can interfere with the absorption of light and affect the results. 

The green light strategy measures not absorption but reflectance – how much of the light bounces back. As with traditional oximetry, the green-light method uses two wavelengths. Each is a different shade of green, and the two forms of hemoglobin reflect them differently. 

Using an algorithm developed by the researchers, the device can capture readings in patients of all skin tones, the researchers say. And because it works on the wrist rather than a finger, the device also eliminates issues with cold fingers and dark nail polish – both known to reduce accuracy in traditional oximetry.

In the latest experiments, the researchers tested the technology on synthetic skin samples with varying amounts of melanin, Dr. Gokhale said. The device picked up changes in blood oxygen saturation even in samples with high melanin levels. 

In a study published last year, the technology was tested in 16 people against an invasive handheld blood analyzer and a noninvasive commercial pulse oximeter, and found to be comparable to the invasive method. 
 

A drawback 

The green light approach could be “game changing,” Dr. Chander said. But there is a drawback. 

Since green light doesn’t penetrate as deeply, this approach measures blood oxygen saturation in capillary beds (small blood vessels very close to the skin surface). By contrast, traditional oximetry measures oxygen saturation in an artery as it pulses – thus the name pulse oximetry. 

Valuable information can be obtained from an arterial pulse.

Changes in arterial pulse, known as the waveforms, “can tell us about a patient’s hydration status [for instance],” Dr. Chander said. “In a mechanically ventilated patient, this variation with a patient’s respiratory cycle can give us feedback about how responsive the patient will be to fluid resuscitation if their blood pressure is too low.” 

Given such considerations, the green light method may be useful as an adjunct, not a full replacement, to a standard pulse ox, Dr. Chander noted.

A version of this article appeared on WebMD.com.

Researchers in Texas are developing a “green light” technology they hope will solve a crucial problem highlighted by the pandemic: the limits of pulse oximeters in patients with darker skin.

A recent study adds weight to earlier findings that their device works. 

“It is a new, first-in-class technology,” said Sanjay Gokhale, MD, the bioengineer who is leading this research at the University of Texas at Arlington. “The team conducted extensive preclinical work and carried out phase 1 studies in human volunteers, demonstrating sensitivity and accuracy.”

It’s one of several projects underway to update pulse oximetry, a technology based on research in lighter-skinned people that has not changed much in 50 years. 

The pulse oximeter, or “pulse ox,” measures the saturation of oxygen in your hemoglobin (a protein in red blood cells). But it tends to overestimate the oxygen saturation in patients with darker skin by about 2%-3%. That may not sound like a lot, but it’s enough to delay major treatment for respiratory issues like COVID-19. 

“Falsely elevated readings from commercial oximeters have delayed treatment of Black COVID-19 patients for hours in some cases,” said Divya Chander, MD, PhD, an anesthesiologist in Oakland, Calif., and chair of neuroscience at The Singularity Group. (Dr. Chander was not involved in the UT Arlington research.)

Early research happening separately at Brown University and Tufts University aims to redesign the pulse oximeter to get accurate readings in patients of all skin tones. University of California, San Diego, researchers are looking into a method that measures blood oxygen using sound in combination with light.  Other solutions try to correct for skin tone with algorithms. 

The device from UT Arlington uses an algorithm too, but its main innovation is that it replaces red light with green light. 
 

Red light, green light

Traditional oximetry devices, which typically clip on to the patient’s fingertip, use LEDs to beam light through the skin at two wavelengths: one in the red part of the spectrum, the other in the infrared. The light transmits from one side of the clip to the other, passing through arterial blood as it pulses.

The device calculates a patient’s oxygenation based on how much light of each wavelength is absorbed by hemoglobin in the blood. Oxygenated hemoglobin absorbs the light differently than deoxygenated hemoglobin, so oxygenation can be represented as a percentage; 100% means all hemoglobin is completely oxygenated.  But the melanin in skin can interfere with the absorption of light and affect the results. 

The green light strategy measures not absorption but reflectance – how much of the light bounces back. As with traditional oximetry, the green-light method uses two wavelengths. Each is a different shade of green, and the two forms of hemoglobin reflect them differently. 

Using an algorithm developed by the researchers, the device can capture readings in patients of all skin tones, the researchers say. And because it works on the wrist rather than a finger, the device also eliminates issues with cold fingers and dark nail polish – both known to reduce accuracy in traditional oximetry.

In the latest experiments, the researchers tested the technology on synthetic skin samples with varying amounts of melanin, Dr. Gokhale said. The device picked up changes in blood oxygen saturation even in samples with high melanin levels. 

In a study published last year, the technology was tested in 16 people against an invasive handheld blood analyzer and a noninvasive commercial pulse oximeter, and found to be comparable to the invasive method. 
 

A drawback 

The green light approach could be “game changing,” Dr. Chander said. But there is a drawback. 

Since green light doesn’t penetrate as deeply, this approach measures blood oxygen saturation in capillary beds (small blood vessels very close to the skin surface). By contrast, traditional oximetry measures oxygen saturation in an artery as it pulses – thus the name pulse oximetry. 

Valuable information can be obtained from an arterial pulse.

Changes in arterial pulse, known as the waveforms, “can tell us about a patient’s hydration status [for instance],” Dr. Chander said. “In a mechanically ventilated patient, this variation with a patient’s respiratory cycle can give us feedback about how responsive the patient will be to fluid resuscitation if their blood pressure is too low.” 

Given such considerations, the green light method may be useful as an adjunct, not a full replacement, to a standard pulse ox, Dr. Chander noted.

A version of this article appeared on WebMD.com.

Researchers in Texas are developing a “green light” technology they hope will solve a crucial problem highlighted by the pandemic: the limits of pulse oximeters in patients with darker skin.

A recent study adds weight to earlier findings that their device works. 

“It is a new, first-in-class technology,” said Sanjay Gokhale, MD, the bioengineer who is leading this research at the University of Texas at Arlington. “The team conducted extensive preclinical work and carried out phase 1 studies in human volunteers, demonstrating sensitivity and accuracy.”

It’s one of several projects underway to update pulse oximetry, a technology based on research in lighter-skinned people that has not changed much in 50 years. 

The pulse oximeter, or “pulse ox,” measures the saturation of oxygen in your hemoglobin (a protein in red blood cells). But it tends to overestimate the oxygen saturation in patients with darker skin by about 2%-3%. That may not sound like a lot, but it’s enough to delay major treatment for respiratory issues like COVID-19. 

“Falsely elevated readings from commercial oximeters have delayed treatment of Black COVID-19 patients for hours in some cases,” said Divya Chander, MD, PhD, an anesthesiologist in Oakland, Calif., and chair of neuroscience at The Singularity Group. (Dr. Chander was not involved in the UT Arlington research.)

Early research happening separately at Brown University and Tufts University aims to redesign the pulse oximeter to get accurate readings in patients of all skin tones. University of California, San Diego, researchers are looking into a method that measures blood oxygen using sound in combination with light.  Other solutions try to correct for skin tone with algorithms. 

The device from UT Arlington uses an algorithm too, but its main innovation is that it replaces red light with green light. 
 

Red light, green light

Traditional oximetry devices, which typically clip on to the patient’s fingertip, use LEDs to beam light through the skin at two wavelengths: one in the red part of the spectrum, the other in the infrared. The light transmits from one side of the clip to the other, passing through arterial blood as it pulses.

The device calculates a patient’s oxygenation based on how much light of each wavelength is absorbed by hemoglobin in the blood. Oxygenated hemoglobin absorbs the light differently than deoxygenated hemoglobin, so oxygenation can be represented as a percentage; 100% means all hemoglobin is completely oxygenated.  But the melanin in skin can interfere with the absorption of light and affect the results. 

The green light strategy measures not absorption but reflectance – how much of the light bounces back. As with traditional oximetry, the green-light method uses two wavelengths. Each is a different shade of green, and the two forms of hemoglobin reflect them differently. 

Using an algorithm developed by the researchers, the device can capture readings in patients of all skin tones, the researchers say. And because it works on the wrist rather than a finger, the device also eliminates issues with cold fingers and dark nail polish – both known to reduce accuracy in traditional oximetry.

In the latest experiments, the researchers tested the technology on synthetic skin samples with varying amounts of melanin, Dr. Gokhale said. The device picked up changes in blood oxygen saturation even in samples with high melanin levels. 

In a study published last year, the technology was tested in 16 people against an invasive handheld blood analyzer and a noninvasive commercial pulse oximeter, and found to be comparable to the invasive method. 
 

A drawback 

The green light approach could be “game changing,” Dr. Chander said. But there is a drawback. 

Since green light doesn’t penetrate as deeply, this approach measures blood oxygen saturation in capillary beds (small blood vessels very close to the skin surface). By contrast, traditional oximetry measures oxygen saturation in an artery as it pulses – thus the name pulse oximetry. 

Valuable information can be obtained from an arterial pulse.

Changes in arterial pulse, known as the waveforms, “can tell us about a patient’s hydration status [for instance],” Dr. Chander said. “In a mechanically ventilated patient, this variation with a patient’s respiratory cycle can give us feedback about how responsive the patient will be to fluid resuscitation if their blood pressure is too low.” 

Given such considerations, the green light method may be useful as an adjunct, not a full replacement, to a standard pulse ox, Dr. Chander noted.

A version of this article appeared on WebMD.com.

The combination of heat waves and poor air quality is associated with double the risk of fatal myocardial infarction (MI), with women and older adults at greatest risk, a study from China suggests.

rottadana/Thinkstock

The researchers estimate that up to 3% of all deaths due to MI could be attributed to the combination of extreme temperatures and high levels of ambient fine particulate matter (PM2.5).

“Our findings provide evidence that reducing exposure to both extreme temperatures and fine particulate pollution may be useful to prevent premature deaths from heart attack,” senior author Yuewei Liu, MD, PhD, with Sun Yat-sen University in Guangzhou, China, said in a statement.

There is “long-standing evidence” of the harmful cardiovascular effects of air pollution, Jonathan Newman, MD, MPH, cardiologist at NYU Langone Heart in New York, who wasn’t involved in the study, said in an interview.

The added value of this study was finding an interaction between extreme hot temperatures and air pollution, “which is worrisome with global warming,” said Dr. Newman, assistant professor, department of medicine, the Leon H. Charney Division of Cardiology at NYU Langone Health.

The study was published online in Circulation.
 

Intensity and duration matter

The researchers analyzed data on 202,678 adults (mean age, 77.6 years; 52% male) who suffered fatal MI between 2015 and 2020 in Jiangsu province, a region with four distinct seasons and a wide range of temperatures and ambient PM2.5.

They evaluated the association of exposure to extreme temperature events, including both hot and cold spells, and PM2.5 with MI mortality, and their interactive effects.

Among the key findings:

• The risk of fatal MI was 18% higher during 2-day heat waves with heat indexes at or above the 90th percentile (ranging from 82.6° to 97.9° F) and 74% higher during 4-day heat waves with heat indexes at or above the 97.5th percentile (ranging from 94.8° to 109.4° F), compared with control days.
• The risk of fatal MI was 4% higher during 2-day cold snaps with temperatures at or below the 10th percentile (ranging from 33.3° to 40.5° F) and 12% higher during 3-day cold snaps with temperatures at or below the 2.5th percentile (ranging from 27.0° to 37.2° F).
• The risk of fatal MI was twice as high during 4-day heat waves that had PM2.5 above 37.5 mcg/m³. Days with high levels of PM2.5 during cold snaps did not have an equivalent increase in the risk of fatal MI.
• Up to 2.8% of MI deaths during the 5-year study period may be attributable to the combination of extreme temperature exposure and PM2.5 at levels exceeding World Health Organization air quality guidelines (37.5 mcg/m³).
• The risk of fatal MI was generally higher among women than men during heat waves and was higher among adults 80 years old and older than in younger adults during heat waves, cold snaps, or days with high levels of PM2.5.

The finding that adults over age 80 are particularly susceptible to the effects of heat and air pollution and the interaction of the two is “notable and particularly relevant given the aging of the population,” Dr. Newman told this news organization.

Mitigating both extreme temperature events and PM2.5 exposures “may bring health cobenefits in preventing premature deaths from MI,” the researchers write.

“To improve public health, it is important to take fine particulate pollution into consideration when providing extreme temperature warnings to the public,” Dr. Liu adds in the statement.

In an earlier study, Dr. Liu and colleagues showed that exposure to both large and small particulate matter, as well as nitrogen dioxide, was significantly associated with increased odds of death from MI.

This study was funded by China’s Ministry of Science and Technology. The authors and Dr. Newman have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The combination of heat waves and poor air quality is associated with double the risk of fatal myocardial infarction (MI), with women and older adults at greatest risk, a study from China suggests.

rottadana/Thinkstock

The researchers estimate that up to 3% of all deaths due to MI could be attributed to the combination of extreme temperatures and high levels of ambient fine particulate matter (PM2.5).

“Our findings provide evidence that reducing exposure to both extreme temperatures and fine particulate pollution may be useful to prevent premature deaths from heart attack,” senior author Yuewei Liu, MD, PhD, with Sun Yat-sen University in Guangzhou, China, said in a statement.

There is “long-standing evidence” of the harmful cardiovascular effects of air pollution, Jonathan Newman, MD, MPH, cardiologist at NYU Langone Heart in New York, who wasn’t involved in the study, said in an interview.

The added value of this study was finding an interaction between extreme hot temperatures and air pollution, “which is worrisome with global warming,” said Dr. Newman, assistant professor, department of medicine, the Leon H. Charney Division of Cardiology at NYU Langone Health.

The study was published online in Circulation.
 

Intensity and duration matter

The researchers analyzed data on 202,678 adults (mean age, 77.6 years; 52% male) who suffered fatal MI between 2015 and 2020 in Jiangsu province, a region with four distinct seasons and a wide range of temperatures and ambient PM2.5.

They evaluated the association of exposure to extreme temperature events, including both hot and cold spells, and PM2.5 with MI mortality, and their interactive effects.

Among the key findings:

• The risk of fatal MI was 18% higher during 2-day heat waves with heat indexes at or above the 90th percentile (ranging from 82.6° to 97.9° F) and 74% higher during 4-day heat waves with heat indexes at or above the 97.5th percentile (ranging from 94.8° to 109.4° F), compared with control days.
• The risk of fatal MI was 4% higher during 2-day cold snaps with temperatures at or below the 10th percentile (ranging from 33.3° to 40.5° F) and 12% higher during 3-day cold snaps with temperatures at or below the 2.5th percentile (ranging from 27.0° to 37.2° F).
• The risk of fatal MI was twice as high during 4-day heat waves that had PM2.5 above 37.5 mcg/m³. Days with high levels of PM2.5 during cold snaps did not have an equivalent increase in the risk of fatal MI.
• Up to 2.8% of MI deaths during the 5-year study period may be attributable to the combination of extreme temperature exposure and PM2.5 at levels exceeding World Health Organization air quality guidelines (37.5 mcg/m³).
• The risk of fatal MI was generally higher among women than men during heat waves and was higher among adults 80 years old and older than in younger adults during heat waves, cold snaps, or days with high levels of PM2.5.

The finding that adults over age 80 are particularly susceptible to the effects of heat and air pollution and the interaction of the two is “notable and particularly relevant given the aging of the population,” Dr. Newman told this news organization.

Mitigating both extreme temperature events and PM2.5 exposures “may bring health cobenefits in preventing premature deaths from MI,” the researchers write.

“To improve public health, it is important to take fine particulate pollution into consideration when providing extreme temperature warnings to the public,” Dr. Liu adds in the statement.

In an earlier study, Dr. Liu and colleagues showed that exposure to both large and small particulate matter, as well as nitrogen dioxide, was significantly associated with increased odds of death from MI.

This study was funded by China’s Ministry of Science and Technology. The authors and Dr. Newman have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The combination of heat waves and poor air quality is associated with double the risk of fatal myocardial infarction (MI), with women and older adults at greatest risk, a study from China suggests.

rottadana/Thinkstock

The researchers estimate that up to 3% of all deaths due to MI could be attributed to the combination of extreme temperatures and high levels of ambient fine particulate matter (PM2.5).

“Our findings provide evidence that reducing exposure to both extreme temperatures and fine particulate pollution may be useful to prevent premature deaths from heart attack,” senior author Yuewei Liu, MD, PhD, with Sun Yat-sen University in Guangzhou, China, said in a statement.

There is “long-standing evidence” of the harmful cardiovascular effects of air pollution, Jonathan Newman, MD, MPH, cardiologist at NYU Langone Heart in New York, who wasn’t involved in the study, said in an interview.

The added value of this study was finding an interaction between extreme hot temperatures and air pollution, “which is worrisome with global warming,” said Dr. Newman, assistant professor, department of medicine, the Leon H. Charney Division of Cardiology at NYU Langone Health.

The study was published online in Circulation.
 

Intensity and duration matter

The researchers analyzed data on 202,678 adults (mean age, 77.6 years; 52% male) who suffered fatal MI between 2015 and 2020 in Jiangsu province, a region with four distinct seasons and a wide range of temperatures and ambient PM2.5.

They evaluated the association of exposure to extreme temperature events, including both hot and cold spells, and PM2.5 with MI mortality, and their interactive effects.

Among the key findings:

• The risk of fatal MI was 18% higher during 2-day heat waves with heat indexes at or above the 90th percentile (ranging from 82.6° to 97.9° F) and 74% higher during 4-day heat waves with heat indexes at or above the 97.5th percentile (ranging from 94.8° to 109.4° F), compared with control days.
• The risk of fatal MI was 4% higher during 2-day cold snaps with temperatures at or below the 10th percentile (ranging from 33.3° to 40.5° F) and 12% higher during 3-day cold snaps with temperatures at or below the 2.5th percentile (ranging from 27.0° to 37.2° F).
• The risk of fatal MI was twice as high during 4-day heat waves that had PM2.5 above 37.5 mcg/m³. Days with high levels of PM2.5 during cold snaps did not have an equivalent increase in the risk of fatal MI.
• Up to 2.8% of MI deaths during the 5-year study period may be attributable to the combination of extreme temperature exposure and PM2.5 at levels exceeding World Health Organization air quality guidelines (37.5 mcg/m³).
• The risk of fatal MI was generally higher among women than men during heat waves and was higher among adults 80 years old and older than in younger adults during heat waves, cold snaps, or days with high levels of PM2.5.

The finding that adults over age 80 are particularly susceptible to the effects of heat and air pollution and the interaction of the two is “notable and particularly relevant given the aging of the population,” Dr. Newman told this news organization.

Mitigating both extreme temperature events and PM2.5 exposures “may bring health cobenefits in preventing premature deaths from MI,” the researchers write.

“To improve public health, it is important to take fine particulate pollution into consideration when providing extreme temperature warnings to the public,” Dr. Liu adds in the statement.

In an earlier study, Dr. Liu and colleagues showed that exposure to both large and small particulate matter, as well as nitrogen dioxide, was significantly associated with increased odds of death from MI.

This study was funded by China’s Ministry of Science and Technology. The authors and Dr. Newman have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Family members with pulmonary fibrosis showed correlations for predicted forced vital capacity trajectories and computed tomography patterns, based on data from 101 individuals in 45 families.

Patients with familial pulmonary fibrosis (FPF), defined as fibrotic interstitial lung disease among two or more first-degree or second-degree relatives, have worse survival than that of patients with sporadic pulmonary fibrosis, wrote Tinne Goos, MD, of KU Leuven, Belgium, and colleagues. Diagnosis of FPF diagnosis is mainly based on family history, and data on intrafamilial correlations are lacking, they said.

In a study published in the journal Chest, the researchers identified FPF patients treated at a single center. The study population included 101 patients from 45 families; most of these (34) were siblings. Overall, 61.4% of the participants were men, 69.3% were ever-smokers, and 84.2% had idiopathic pulmonary fibrosis.

The analysis included data on computed tomography (CT) scanning and predicted forced vital capacity (FVC%), as well as age at diagnosis, treatment type, gender, smoking history, and date of diagnosis.

Overall, FVC%predicted was significantly correlated within families, with a correlation of 0.75. The annual change in FVC was –158.2 mL, and the annual change in FVC%predicted was –6.3%.

Sixty-five patients received antifibrotic treatment, and 18 received immunosuppressive treatment. Immunosuppressive treatment remained significantly correlated among families in a multivariate analysis, with a correlation of 0.77.

“Age at diagnosis correlated within a generation, while patients from a second generation were diagnosed younger,” the researchers noted. The current study findings and results from other studies suggest a genetic basis for FPF age of onset, and determining an age range for screening unaffected relatives based on the age at diagnosis of affected relatives might be useful, they said.

In addition, 42.2% of families showed concordance of CT scan patterns. Typical usual interstitial pneumonia (UIP) appeared in 35 patients, atypical UIP in 36 patients, UIP with emphysema in 9 patients, and findings incompatible with UIP in 21 patients.

The study findings were limited by several factors including the retrospective design and use of data from a single center, as well as by the changes in clinical practice guidelines between 2004 and 2019, with increases in genetic testing, the researchers noted.

However, the current study is the first known to report on FVC evolution within families in FPF, they said. Future studies of both intra- and interfamilial correlation and variability are needed to identify the genetic and environmental factors that may affect disease manifestation and progression, they concluded.

The study was supported by Research Foundation-Flanders. Dr. Goos had no financial conflicts to disclose.

Family members with pulmonary fibrosis showed correlations for predicted forced vital capacity trajectories and computed tomography patterns, based on data from 101 individuals in 45 families.

Patients with familial pulmonary fibrosis (FPF), defined as fibrotic interstitial lung disease among two or more first-degree or second-degree relatives, have worse survival than that of patients with sporadic pulmonary fibrosis, wrote Tinne Goos, MD, of KU Leuven, Belgium, and colleagues. Diagnosis of FPF diagnosis is mainly based on family history, and data on intrafamilial correlations are lacking, they said.

In a study published in the journal Chest, the researchers identified FPF patients treated at a single center. The study population included 101 patients from 45 families; most of these (34) were siblings. Overall, 61.4% of the participants were men, 69.3% were ever-smokers, and 84.2% had idiopathic pulmonary fibrosis.

The analysis included data on computed tomography (CT) scanning and predicted forced vital capacity (FVC%), as well as age at diagnosis, treatment type, gender, smoking history, and date of diagnosis.

Overall, FVC%predicted was significantly correlated within families, with a correlation of 0.75. The annual change in FVC was –158.2 mL, and the annual change in FVC%predicted was –6.3%.

Sixty-five patients received antifibrotic treatment, and 18 received immunosuppressive treatment. Immunosuppressive treatment remained significantly correlated among families in a multivariate analysis, with a correlation of 0.77.

“Age at diagnosis correlated within a generation, while patients from a second generation were diagnosed younger,” the researchers noted. The current study findings and results from other studies suggest a genetic basis for FPF age of onset, and determining an age range for screening unaffected relatives based on the age at diagnosis of affected relatives might be useful, they said.

In addition, 42.2% of families showed concordance of CT scan patterns. Typical usual interstitial pneumonia (UIP) appeared in 35 patients, atypical UIP in 36 patients, UIP with emphysema in 9 patients, and findings incompatible with UIP in 21 patients.

The study findings were limited by several factors including the retrospective design and use of data from a single center, as well as by the changes in clinical practice guidelines between 2004 and 2019, with increases in genetic testing, the researchers noted.

However, the current study is the first known to report on FVC evolution within families in FPF, they said. Future studies of both intra- and interfamilial correlation and variability are needed to identify the genetic and environmental factors that may affect disease manifestation and progression, they concluded.

The study was supported by Research Foundation-Flanders. Dr. Goos had no financial conflicts to disclose.

Family members with pulmonary fibrosis showed correlations for predicted forced vital capacity trajectories and computed tomography patterns, based on data from 101 individuals in 45 families.

Patients with familial pulmonary fibrosis (FPF), defined as fibrotic interstitial lung disease among two or more first-degree or second-degree relatives, have worse survival than that of patients with sporadic pulmonary fibrosis, wrote Tinne Goos, MD, of KU Leuven, Belgium, and colleagues. Diagnosis of FPF diagnosis is mainly based on family history, and data on intrafamilial correlations are lacking, they said.

In a study published in the journal Chest, the researchers identified FPF patients treated at a single center. The study population included 101 patients from 45 families; most of these (34) were siblings. Overall, 61.4% of the participants were men, 69.3% were ever-smokers, and 84.2% had idiopathic pulmonary fibrosis.

The analysis included data on computed tomography (CT) scanning and predicted forced vital capacity (FVC%), as well as age at diagnosis, treatment type, gender, smoking history, and date of diagnosis.

Overall, FVC%predicted was significantly correlated within families, with a correlation of 0.75. The annual change in FVC was –158.2 mL, and the annual change in FVC%predicted was –6.3%.

Sixty-five patients received antifibrotic treatment, and 18 received immunosuppressive treatment. Immunosuppressive treatment remained significantly correlated among families in a multivariate analysis, with a correlation of 0.77.

“Age at diagnosis correlated within a generation, while patients from a second generation were diagnosed younger,” the researchers noted. The current study findings and results from other studies suggest a genetic basis for FPF age of onset, and determining an age range for screening unaffected relatives based on the age at diagnosis of affected relatives might be useful, they said.

In addition, 42.2% of families showed concordance of CT scan patterns. Typical usual interstitial pneumonia (UIP) appeared in 35 patients, atypical UIP in 36 patients, UIP with emphysema in 9 patients, and findings incompatible with UIP in 21 patients.

The study findings were limited by several factors including the retrospective design and use of data from a single center, as well as by the changes in clinical practice guidelines between 2004 and 2019, with increases in genetic testing, the researchers noted.

However, the current study is the first known to report on FVC evolution within families in FPF, they said. Future studies of both intra- and interfamilial correlation and variability are needed to identify the genetic and environmental factors that may affect disease manifestation and progression, they concluded.

The study was supported by Research Foundation-Flanders. Dr. Goos had no financial conflicts to disclose.

On July 13, the Food and Drug Administration approved the first over-the-counter (OTC) norgestrel birth control pill (Opill). The daily oral contraceptive was approved for prescription use 5 decades ago, providing regulators with a half-century of data to show that the progestin-only drug can be used safely without a prescription. 

The drug is the latest in a series of medications that have made the switch from behind the pharmacy counter to retail shelves. 

Experts say several more classes of drugs to treat high cholesterol, asthma, and other common health problems could be next.
 

Why switch?

When a drug manufacturer submits a proposal for a switch to OTC, the key question that the FDA considers is patient safety. Some risks can be mitigated by approving OTC drugs at lower doses than what is available as the prescription version. 

“There is no drug that doesn’t have risks,” said Almut G. Winterstein, RPh, PhD, a distinguished professor in pharmaceutical outcomes and policy and director of the Center for Drug Evaluation and Safety at the University of Florida, Gainesville. “Risks are mitigated by putting specific constraints around access to those medications.”

Dr. Winterstein, a former chair of the FDA’s Drug Safety and Risk Management Advisory Committee, said that nonprescription drugs are unnecessary in a functional health care system. 

Many patients may struggle with accessing health clinicians, so making medications available OTC fills gaps left by not being able to get a prescription, according to Dr. Winterstein. 

A 2012 paper funded by the Consumer Healthcare Products Association (CHPA), the organization representing manufacturers and distributors of OTC medications, estimated that one quarter of people who bought OTC drugs would not otherwise seek treatment if these treatments were available only via prescription. The CHPA notes that the number of those who experience allergies who use nonprescription antihistamines and allergy-relief drugs increased by about 10% between 2009 and 2015. 
 

Cholesterol drugs

Approximately 80 million U.S. adults are eligible for cholesterol-lowering medications, particularly statins, but nearly half don’t take them, according to the Centers for Disease Control and Prevention. 

Fear of side effects is the most common reason people might avoid taking these drugs. But eliminating the need for a refill may encourage uptake of the statins. 

“It’s refill, refill, refill,” said Allen J. Taylor, MD, chairman of cardiology at MedStar Heart and Vascular Institute, in Washington. “We spend a ton of time refilling statins and it’s a headache for patients, too.” 

The need to secure regular prescriptions for the drug, “doesn’t put enough trust and faith in pharmacists and doesn’t put enough trust and faith in patients,” Dr. Taylor said. 

Moving statins to the front end of a pharmacy might not be the best move given the potential for drug interactions, but a nonprescription behind-the-counter approach could work, according to Dr. Taylor. 

“The concerns are modest at most, to where they can be monitored by a pharmacist,” he said. “There’s probably more people that would take a statin if they had that kind of access.” 

Many statin manufacturers have attempted to make the prescription-to-OTC switch. In 2005, an FDA advisory panel rejected Merck’s proposal for OTC sales of lovastatin after reviewing a study that found only 55% of OTC purchases would have been medically appropriate. 

In 2015, Pfizer pulled its application to make the cholesterol drug atorvastatin available to patients OTC because patients were not using the drug correctly. AstraZeneca is investigating an online platform that would allow patients to self-assess their eligibility for rosuvastatin. 
 

Asthma inhalers 

Inhalers are the main rescue therapy for asthma aside from a visit to the ED. 

The only inhaler available OTC is epinephrine sold under the brand name Primatene Mist, but this type of medicine device is not recommended as a first-line therapy for acute asthma symptoms, according to the American Medical Association. 

“It’s been around for a long time and has stayed over the counter even though newer, safer agents have come onto the market which aren’t available over the counter,” said William B. Feldman, MD, DPhil, MPH, a pulmonologist at Brigham and Women’s Hospital, Boston. 

Patients who have a hard time getting to a doctor or patients who lack insurance often face barriers accessing albuterol inhalers and beta agonist–corticosteroid combinations, according to Dr. Feldman. A switch to OTC distribution would widen access. 

“What we’re advocating is, if they’re going to have access to Primatene Mist, wouldn’t it be sensible to have access to a safer and more effective therapy?” Dr. Feldman said. 
 

Triptans

Migraines affect an estimated 39 million people in the United States, according to the American Migraine Foundation. Several drugs to treat migraine are available OTC, including nonsteroidal anti-inflammatory drugs, aspirin, and acetaminophen. Triptans, drugs used for the short-term treatment of acute symptoms, are prescription-only in the United States. 

But in the United Kingdom, triptans first became available in retail stores in 2006, leading to reduced costs for patients, employers, and the government. One study found that government health expenditures would be reduced by $84 million annually if the OTC switch were made in six European countries. 

However, overuse of the drug and potential contraindications have been cited as concerns with OTC access. 

For Dr. Winterstein, the decision to switch isn’t just about the freedom to buy a drug; it comes down to weighing potential risks and benefits. 

“Drugs are only as good as if they’re used in the context of how they should be used,” Dr. Winterstein said. “It’s not candy.”
 

A version of this article first appeared on Medscape.com.

On July 13, the Food and Drug Administration approved the first over-the-counter (OTC) norgestrel birth control pill (Opill). The daily oral contraceptive was approved for prescription use 5 decades ago, providing regulators with a half-century of data to show that the progestin-only drug can be used safely without a prescription. 

The drug is the latest in a series of medications that have made the switch from behind the pharmacy counter to retail shelves. 

Experts say several more classes of drugs to treat high cholesterol, asthma, and other common health problems could be next.
 

Why switch?

When a drug manufacturer submits a proposal for a switch to OTC, the key question that the FDA considers is patient safety. Some risks can be mitigated by approving OTC drugs at lower doses than what is available as the prescription version. 

“There is no drug that doesn’t have risks,” said Almut G. Winterstein, RPh, PhD, a distinguished professor in pharmaceutical outcomes and policy and director of the Center for Drug Evaluation and Safety at the University of Florida, Gainesville. “Risks are mitigated by putting specific constraints around access to those medications.”

Dr. Winterstein, a former chair of the FDA’s Drug Safety and Risk Management Advisory Committee, said that nonprescription drugs are unnecessary in a functional health care system. 

Many patients may struggle with accessing health clinicians, so making medications available OTC fills gaps left by not being able to get a prescription, according to Dr. Winterstein. 

A 2012 paper funded by the Consumer Healthcare Products Association (CHPA), the organization representing manufacturers and distributors of OTC medications, estimated that one quarter of people who bought OTC drugs would not otherwise seek treatment if these treatments were available only via prescription. The CHPA notes that the number of those who experience allergies who use nonprescription antihistamines and allergy-relief drugs increased by about 10% between 2009 and 2015. 
 

Cholesterol drugs

Approximately 80 million U.S. adults are eligible for cholesterol-lowering medications, particularly statins, but nearly half don’t take them, according to the Centers for Disease Control and Prevention. 

Fear of side effects is the most common reason people might avoid taking these drugs. But eliminating the need for a refill may encourage uptake of the statins. 

“It’s refill, refill, refill,” said Allen J. Taylor, MD, chairman of cardiology at MedStar Heart and Vascular Institute, in Washington. “We spend a ton of time refilling statins and it’s a headache for patients, too.” 

The need to secure regular prescriptions for the drug, “doesn’t put enough trust and faith in pharmacists and doesn’t put enough trust and faith in patients,” Dr. Taylor said. 

Moving statins to the front end of a pharmacy might not be the best move given the potential for drug interactions, but a nonprescription behind-the-counter approach could work, according to Dr. Taylor. 

“The concerns are modest at most, to where they can be monitored by a pharmacist,” he said. “There’s probably more people that would take a statin if they had that kind of access.” 

Many statin manufacturers have attempted to make the prescription-to-OTC switch. In 2005, an FDA advisory panel rejected Merck’s proposal for OTC sales of lovastatin after reviewing a study that found only 55% of OTC purchases would have been medically appropriate. 

In 2015, Pfizer pulled its application to make the cholesterol drug atorvastatin available to patients OTC because patients were not using the drug correctly. AstraZeneca is investigating an online platform that would allow patients to self-assess their eligibility for rosuvastatin. 
 

Asthma inhalers 

Inhalers are the main rescue therapy for asthma aside from a visit to the ED. 

The only inhaler available OTC is epinephrine sold under the brand name Primatene Mist, but this type of medicine device is not recommended as a first-line therapy for acute asthma symptoms, according to the American Medical Association. 

“It’s been around for a long time and has stayed over the counter even though newer, safer agents have come onto the market which aren’t available over the counter,” said William B. Feldman, MD, DPhil, MPH, a pulmonologist at Brigham and Women’s Hospital, Boston. 

Patients who have a hard time getting to a doctor or patients who lack insurance often face barriers accessing albuterol inhalers and beta agonist–corticosteroid combinations, according to Dr. Feldman. A switch to OTC distribution would widen access. 

“What we’re advocating is, if they’re going to have access to Primatene Mist, wouldn’t it be sensible to have access to a safer and more effective therapy?” Dr. Feldman said. 
 

Triptans

Migraines affect an estimated 39 million people in the United States, according to the American Migraine Foundation. Several drugs to treat migraine are available OTC, including nonsteroidal anti-inflammatory drugs, aspirin, and acetaminophen. Triptans, drugs used for the short-term treatment of acute symptoms, are prescription-only in the United States. 

But in the United Kingdom, triptans first became available in retail stores in 2006, leading to reduced costs for patients, employers, and the government. One study found that government health expenditures would be reduced by $84 million annually if the OTC switch were made in six European countries. 

However, overuse of the drug and potential contraindications have been cited as concerns with OTC access. 

For Dr. Winterstein, the decision to switch isn’t just about the freedom to buy a drug; it comes down to weighing potential risks and benefits. 

“Drugs are only as good as if they’re used in the context of how they should be used,” Dr. Winterstein said. “It’s not candy.”
 

A version of this article first appeared on Medscape.com.

On July 13, the Food and Drug Administration approved the first over-the-counter (OTC) norgestrel birth control pill (Opill). The daily oral contraceptive was approved for prescription use 5 decades ago, providing regulators with a half-century of data to show that the progestin-only drug can be used safely without a prescription. 

The drug is the latest in a series of medications that have made the switch from behind the pharmacy counter to retail shelves. 

Experts say several more classes of drugs to treat high cholesterol, asthma, and other common health problems could be next.
 

Why switch?

When a drug manufacturer submits a proposal for a switch to OTC, the key question that the FDA considers is patient safety. Some risks can be mitigated by approving OTC drugs at lower doses than what is available as the prescription version. 

“There is no drug that doesn’t have risks,” said Almut G. Winterstein, RPh, PhD, a distinguished professor in pharmaceutical outcomes and policy and director of the Center for Drug Evaluation and Safety at the University of Florida, Gainesville. “Risks are mitigated by putting specific constraints around access to those medications.”

Dr. Winterstein, a former chair of the FDA’s Drug Safety and Risk Management Advisory Committee, said that nonprescription drugs are unnecessary in a functional health care system. 

Many patients may struggle with accessing health clinicians, so making medications available OTC fills gaps left by not being able to get a prescription, according to Dr. Winterstein. 

A 2012 paper funded by the Consumer Healthcare Products Association (CHPA), the organization representing manufacturers and distributors of OTC medications, estimated that one quarter of people who bought OTC drugs would not otherwise seek treatment if these treatments were available only via prescription. The CHPA notes that the number of those who experience allergies who use nonprescription antihistamines and allergy-relief drugs increased by about 10% between 2009 and 2015. 
 

Cholesterol drugs

Approximately 80 million U.S. adults are eligible for cholesterol-lowering medications, particularly statins, but nearly half don’t take them, according to the Centers for Disease Control and Prevention. 

Fear of side effects is the most common reason people might avoid taking these drugs. But eliminating the need for a refill may encourage uptake of the statins. 

“It’s refill, refill, refill,” said Allen J. Taylor, MD, chairman of cardiology at MedStar Heart and Vascular Institute, in Washington. “We spend a ton of time refilling statins and it’s a headache for patients, too.” 

The need to secure regular prescriptions for the drug, “doesn’t put enough trust and faith in pharmacists and doesn’t put enough trust and faith in patients,” Dr. Taylor said. 

Moving statins to the front end of a pharmacy might not be the best move given the potential for drug interactions, but a nonprescription behind-the-counter approach could work, according to Dr. Taylor. 

“The concerns are modest at most, to where they can be monitored by a pharmacist,” he said. “There’s probably more people that would take a statin if they had that kind of access.” 

Many statin manufacturers have attempted to make the prescription-to-OTC switch. In 2005, an FDA advisory panel rejected Merck’s proposal for OTC sales of lovastatin after reviewing a study that found only 55% of OTC purchases would have been medically appropriate. 

In 2015, Pfizer pulled its application to make the cholesterol drug atorvastatin available to patients OTC because patients were not using the drug correctly. AstraZeneca is investigating an online platform that would allow patients to self-assess their eligibility for rosuvastatin. 
 

Asthma inhalers 

Inhalers are the main rescue therapy for asthma aside from a visit to the ED. 

The only inhaler available OTC is epinephrine sold under the brand name Primatene Mist, but this type of medicine device is not recommended as a first-line therapy for acute asthma symptoms, according to the American Medical Association. 

“It’s been around for a long time and has stayed over the counter even though newer, safer agents have come onto the market which aren’t available over the counter,” said William B. Feldman, MD, DPhil, MPH, a pulmonologist at Brigham and Women’s Hospital, Boston. 

Patients who have a hard time getting to a doctor or patients who lack insurance often face barriers accessing albuterol inhalers and beta agonist–corticosteroid combinations, according to Dr. Feldman. A switch to OTC distribution would widen access. 

“What we’re advocating is, if they’re going to have access to Primatene Mist, wouldn’t it be sensible to have access to a safer and more effective therapy?” Dr. Feldman said. 
 

Triptans

Migraines affect an estimated 39 million people in the United States, according to the American Migraine Foundation. Several drugs to treat migraine are available OTC, including nonsteroidal anti-inflammatory drugs, aspirin, and acetaminophen. Triptans, drugs used for the short-term treatment of acute symptoms, are prescription-only in the United States. 

But in the United Kingdom, triptans first became available in retail stores in 2006, leading to reduced costs for patients, employers, and the government. One study found that government health expenditures would be reduced by $84 million annually if the OTC switch were made in six European countries. 

However, overuse of the drug and potential contraindications have been cited as concerns with OTC access. 

For Dr. Winterstein, the decision to switch isn’t just about the freedom to buy a drug; it comes down to weighing potential risks and benefits. 

“Drugs are only as good as if they’re used in the context of how they should be used,” Dr. Winterstein said. “It’s not candy.”
 

A version of this article first appeared on Medscape.com.

The presence of a positive fungal culture in patients with bronchiectasis does not appear to correlate with disease severity or any increased risk of an adverse outcome, according to data pulled from the Bronchiectasis and NTM Registry and presented at the 6th World Bronchiectasis & NTM Conference.

“The question we were asking is whether there is some signal that suggests we need to take care of these patients differently, and the answer is no,” reported Pamela J. McShane, MD, a pulmonologist on the faculty at the University of Texas Health Science Center at Tyler.

When compared for outcome over time, those with a positive fungal culture at initial evaluation did not have more exacerbations, more hospitalizations, or other signs of a more severe disease or more complex course than did those without a positive fungal culture.

When fungal infections are detected in an initial microbiologic evaluation of patients with bronchiectasis or other lung diseases, first-line clinicians generally assume that coverage is needed. Dr. McShane noted that many of the patients referred to her with bronchiectasis and a positive fungal culture were already on an antifungal.

These data are not supportive of treatment in the absence of fungal-related complications. Dr. McShane suggested they even raise questions about the value of culturing beyond bacterial pathogens in the absence of suspicion that fungal organisms are playing a role in symptoms. She cautioned, however, that more studies specifically studying this possibility are needed.
 

Study details

The data were drawn in December 2022 from the U.S.-based Bronchiectasis and NTM Registry, which at that time had 22 participating sites. Of the more than 5,000 patients enrolled, the study looked at 2,230 after several exclusions, such as a diagnosis of allergic bronchopulmonary aspergillosis (ABPA).

Of these 2,230 patients, 949 had a fungal infection at the time of diagnosis and 1,281 did not. Those with a fungal infection were further subdivided into those with an aspergillosis (331 patients) and those with a nonaspergillosis fungal infection (751 patients). The total of these two numbers is greater than the total number of fungal infections because these were not mutually exclusive.

At enrollment into the registry, there were no statistical differences between groups for age. Some statistical differences were observed among groups stratified by race, but Dr. McShane doubted that these were clinically significant with the exception of a potential disparity among Asians that might deserve further analysis.
 

Infection results

Of clinical features evaluated for their association with fungal infection, there was no correlation with either body mass index or history of asthma. Eosinophilia was associated significantly with positive fungal cultures.

Baseline FEV₁ was slightly lower among those with a positive fungal culture even if the difference was highly significant (P = .0006). Again, Dr. McShane questioned the clinical significance of values that varied by only a few percentage points, even though she was willing to acknowledge that higher is always preferable to a lower FEV₁.

In the context of other pathogens, “generally speaking, those with a positive bacterial culture were more likely to have a fungal infection,” Dr. McShane reported, although there was some variation when looking at pathogenicity of the bacteria and other variables.

“Whether this [higher rate of fungal infection] just involves the environment or our antibiotics are driving the opportunity to permit the fungi to exist, we do not have the answer,” she added.

Nontuberculosis mycobacteria (NTM) infection was similarly represented in those with or without a fungal infection, according to Dr. McShane. Noting the high use of antibiotics in an NTM population, Dr. McShane conceded that this challenges the theory that antibiotic use is driving the risk of fungal infection, but these are what the data say.  

Steroid use was associated with a statistically significant risk of fungal infection, but Dr. McShane said it is unclear whether steroid use drives the risk or is an epiphenomenon.

“We looked at this a lot of different ways: oral vs. inhaled and oral vs. inhaled and oral, and it did not make much difference. Generally speaking, the fungal cultures were more likely to be positive in patients on any kind of steroid,” she said.

Finally, with the exception of the slightly lower FEV₁ in patients with fungal infections, Dr. McShane said that there was no discernible relationship between the presence of a fungal infection and severity of bronchiectasis.

Because of this evidence, Dr. McShane concluded that the presence of fungus in the culture of patients with bronchiectasis does not appear to correlate with outcome or severity. Since completing the study, she said she is now using these data to reassure patients who have a positive fungal culture.

While these data do not affect the need to diagnosis fungal infections in patients who are not responding typically to therapy or otherwise have an abnormal course of bronchiectasis, raising suspicion that fungal infection is participating in the disease course, the data provide a basis for questioning whether routine cultures are needed, according to the discussion that followed Dr. McShane’s presentation.
 

Expert opinion

Several of the experts at the presentation provided an opinion. Some reported that they would continue to order fungal cultures on a routine basis, while others said that they now, on the basis of these data, plan to order cultures only at the first visit or when fungal infection is suspected of exacerbating the disease.

Of this latter group, which seemed to be dominant, Juzar Ali, MD, professor of medicine, Louisiana State University, New Orleans, said that he has not been ordering fungal cultures on every visit. Rather, he has been doing so selectively. Examples include those who are on steroids or those with an unusual pattern of exacerbations.

“The value of these data is that they have now provided some data to support this approach,” Dr. Ali said in an interview. Noting that this is the first large study to address this question in a systematic way, he considers this to be a valuable contribution for approaching a common clinical issue.

Dr. McShane reports no relevant financial relationships. Dr. Ali reports a financial relationship with Insmed.
 

A version of this article first appeared on Medscape.com.

The presence of a positive fungal culture in patients with bronchiectasis does not appear to correlate with disease severity or any increased risk of an adverse outcome, according to data pulled from the Bronchiectasis and NTM Registry and presented at the 6th World Bronchiectasis & NTM Conference.

“The question we were asking is whether there is some signal that suggests we need to take care of these patients differently, and the answer is no,” reported Pamela J. McShane, MD, a pulmonologist on the faculty at the University of Texas Health Science Center at Tyler.

When compared for outcome over time, those with a positive fungal culture at initial evaluation did not have more exacerbations, more hospitalizations, or other signs of a more severe disease or more complex course than did those without a positive fungal culture.

When fungal infections are detected in an initial microbiologic evaluation of patients with bronchiectasis or other lung diseases, first-line clinicians generally assume that coverage is needed. Dr. McShane noted that many of the patients referred to her with bronchiectasis and a positive fungal culture were already on an antifungal.

These data are not supportive of treatment in the absence of fungal-related complications. Dr. McShane suggested they even raise questions about the value of culturing beyond bacterial pathogens in the absence of suspicion that fungal organisms are playing a role in symptoms. She cautioned, however, that more studies specifically studying this possibility are needed.
 

Study details

The data were drawn in December 2022 from the U.S.-based Bronchiectasis and NTM Registry, which at that time had 22 participating sites. Of the more than 5,000 patients enrolled, the study looked at 2,230 after several exclusions, such as a diagnosis of allergic bronchopulmonary aspergillosis (ABPA).

Of these 2,230 patients, 949 had a fungal infection at the time of diagnosis and 1,281 did not. Those with a fungal infection were further subdivided into those with an aspergillosis (331 patients) and those with a nonaspergillosis fungal infection (751 patients). The total of these two numbers is greater than the total number of fungal infections because these were not mutually exclusive.

At enrollment into the registry, there were no statistical differences between groups for age. Some statistical differences were observed among groups stratified by race, but Dr. McShane doubted that these were clinically significant with the exception of a potential disparity among Asians that might deserve further analysis.
 

Infection results

Of clinical features evaluated for their association with fungal infection, there was no correlation with either body mass index or history of asthma. Eosinophilia was associated significantly with positive fungal cultures.

Baseline FEV₁ was slightly lower among those with a positive fungal culture even if the difference was highly significant (P = .0006). Again, Dr. McShane questioned the clinical significance of values that varied by only a few percentage points, even though she was willing to acknowledge that higher is always preferable to a lower FEV₁.

In the context of other pathogens, “generally speaking, those with a positive bacterial culture were more likely to have a fungal infection,” Dr. McShane reported, although there was some variation when looking at pathogenicity of the bacteria and other variables.

“Whether this [higher rate of fungal infection] just involves the environment or our antibiotics are driving the opportunity to permit the fungi to exist, we do not have the answer,” she added.

Nontuberculosis mycobacteria (NTM) infection was similarly represented in those with or without a fungal infection, according to Dr. McShane. Noting the high use of antibiotics in an NTM population, Dr. McShane conceded that this challenges the theory that antibiotic use is driving the risk of fungal infection, but these are what the data say.  

Steroid use was associated with a statistically significant risk of fungal infection, but Dr. McShane said it is unclear whether steroid use drives the risk or is an epiphenomenon.

“We looked at this a lot of different ways: oral vs. inhaled and oral vs. inhaled and oral, and it did not make much difference. Generally speaking, the fungal cultures were more likely to be positive in patients on any kind of steroid,” she said.

Finally, with the exception of the slightly lower FEV₁ in patients with fungal infections, Dr. McShane said that there was no discernible relationship between the presence of a fungal infection and severity of bronchiectasis.

Because of this evidence, Dr. McShane concluded that the presence of fungus in the culture of patients with bronchiectasis does not appear to correlate with outcome or severity. Since completing the study, she said she is now using these data to reassure patients who have a positive fungal culture.

While these data do not affect the need to diagnosis fungal infections in patients who are not responding typically to therapy or otherwise have an abnormal course of bronchiectasis, raising suspicion that fungal infection is participating in the disease course, the data provide a basis for questioning whether routine cultures are needed, according to the discussion that followed Dr. McShane’s presentation.
 

Expert opinion

Several of the experts at the presentation provided an opinion. Some reported that they would continue to order fungal cultures on a routine basis, while others said that they now, on the basis of these data, plan to order cultures only at the first visit or when fungal infection is suspected of exacerbating the disease.

Of this latter group, which seemed to be dominant, Juzar Ali, MD, professor of medicine, Louisiana State University, New Orleans, said that he has not been ordering fungal cultures on every visit. Rather, he has been doing so selectively. Examples include those who are on steroids or those with an unusual pattern of exacerbations.

“The value of these data is that they have now provided some data to support this approach,” Dr. Ali said in an interview. Noting that this is the first large study to address this question in a systematic way, he considers this to be a valuable contribution for approaching a common clinical issue.

Dr. McShane reports no relevant financial relationships. Dr. Ali reports a financial relationship with Insmed.
 

A version of this article first appeared on Medscape.com.

The presence of a positive fungal culture in patients with bronchiectasis does not appear to correlate with disease severity or any increased risk of an adverse outcome, according to data pulled from the Bronchiectasis and NTM Registry and presented at the 6th World Bronchiectasis & NTM Conference.

“The question we were asking is whether there is some signal that suggests we need to take care of these patients differently, and the answer is no,” reported Pamela J. McShane, MD, a pulmonologist on the faculty at the University of Texas Health Science Center at Tyler.

When compared for outcome over time, those with a positive fungal culture at initial evaluation did not have more exacerbations, more hospitalizations, or other signs of a more severe disease or more complex course than did those without a positive fungal culture.

When fungal infections are detected in an initial microbiologic evaluation of patients with bronchiectasis or other lung diseases, first-line clinicians generally assume that coverage is needed. Dr. McShane noted that many of the patients referred to her with bronchiectasis and a positive fungal culture were already on an antifungal.

These data are not supportive of treatment in the absence of fungal-related complications. Dr. McShane suggested they even raise questions about the value of culturing beyond bacterial pathogens in the absence of suspicion that fungal organisms are playing a role in symptoms. She cautioned, however, that more studies specifically studying this possibility are needed.
 

Study details

The data were drawn in December 2022 from the U.S.-based Bronchiectasis and NTM Registry, which at that time had 22 participating sites. Of the more than 5,000 patients enrolled, the study looked at 2,230 after several exclusions, such as a diagnosis of allergic bronchopulmonary aspergillosis (ABPA).

Of these 2,230 patients, 949 had a fungal infection at the time of diagnosis and 1,281 did not. Those with a fungal infection were further subdivided into those with an aspergillosis (331 patients) and those with a nonaspergillosis fungal infection (751 patients). The total of these two numbers is greater than the total number of fungal infections because these were not mutually exclusive.

At enrollment into the registry, there were no statistical differences between groups for age. Some statistical differences were observed among groups stratified by race, but Dr. McShane doubted that these were clinically significant with the exception of a potential disparity among Asians that might deserve further analysis.
 

Infection results

Of clinical features evaluated for their association with fungal infection, there was no correlation with either body mass index or history of asthma. Eosinophilia was associated significantly with positive fungal cultures.

Baseline FEV₁ was slightly lower among those with a positive fungal culture even if the difference was highly significant (P = .0006). Again, Dr. McShane questioned the clinical significance of values that varied by only a few percentage points, even though she was willing to acknowledge that higher is always preferable to a lower FEV₁.

In the context of other pathogens, “generally speaking, those with a positive bacterial culture were more likely to have a fungal infection,” Dr. McShane reported, although there was some variation when looking at pathogenicity of the bacteria and other variables.

“Whether this [higher rate of fungal infection] just involves the environment or our antibiotics are driving the opportunity to permit the fungi to exist, we do not have the answer,” she added.

Nontuberculosis mycobacteria (NTM) infection was similarly represented in those with or without a fungal infection, according to Dr. McShane. Noting the high use of antibiotics in an NTM population, Dr. McShane conceded that this challenges the theory that antibiotic use is driving the risk of fungal infection, but these are what the data say.  

Steroid use was associated with a statistically significant risk of fungal infection, but Dr. McShane said it is unclear whether steroid use drives the risk or is an epiphenomenon.

“We looked at this a lot of different ways: oral vs. inhaled and oral vs. inhaled and oral, and it did not make much difference. Generally speaking, the fungal cultures were more likely to be positive in patients on any kind of steroid,” she said.

Finally, with the exception of the slightly lower FEV₁ in patients with fungal infections, Dr. McShane said that there was no discernible relationship between the presence of a fungal infection and severity of bronchiectasis.

Because of this evidence, Dr. McShane concluded that the presence of fungus in the culture of patients with bronchiectasis does not appear to correlate with outcome or severity. Since completing the study, she said she is now using these data to reassure patients who have a positive fungal culture.

While these data do not affect the need to diagnosis fungal infections in patients who are not responding typically to therapy or otherwise have an abnormal course of bronchiectasis, raising suspicion that fungal infection is participating in the disease course, the data provide a basis for questioning whether routine cultures are needed, according to the discussion that followed Dr. McShane’s presentation.
 

Expert opinion

Several of the experts at the presentation provided an opinion. Some reported that they would continue to order fungal cultures on a routine basis, while others said that they now, on the basis of these data, plan to order cultures only at the first visit or when fungal infection is suspected of exacerbating the disease.

Of this latter group, which seemed to be dominant, Juzar Ali, MD, professor of medicine, Louisiana State University, New Orleans, said that he has not been ordering fungal cultures on every visit. Rather, he has been doing so selectively. Examples include those who are on steroids or those with an unusual pattern of exacerbations.

“The value of these data is that they have now provided some data to support this approach,” Dr. Ali said in an interview. Noting that this is the first large study to address this question in a systematic way, he considers this to be a valuable contribution for approaching a common clinical issue.

Dr. McShane reports no relevant financial relationships. Dr. Ali reports a financial relationship with Insmed.
 

A version of this article first appeared on Medscape.com.

Indigenous children or children with new abnormal auscultatory findings were significantly more likely than children in other categories to respond to oral antibiotics for exacerbations related to bronchiectasis, based on data from more than 200 individuals in New Zealand.

Children and adolescents with bronchiectasis are often treated with antibiotics for respiratory exacerbations, but the effects of antibiotics can vary among individuals, and phenotypic features associated with greater symptom resolution have not been identified, wrote Vikas Goyal, PhD, of the Centre for Children’s Health Research, Brisbane, Australia, and colleagues.

Previous studies have suggested that nearly half of exacerbations in children and adolescents resolve spontaneously after 14 days, and more data are needed to identify which patients are mostly likely to benefit from antibiotics, they noted.

In a study published in the journal Chest, the researchers reviewed secondary data from 217 children and adolescents aged 1-18 years with bronchiectasis enrolled in a pair of randomized, controlled trials comparing oral antibiotics with placebo (known as BEST-1 and BEST-2). The median age of the participants was 6.6 years, 52% were boys, and 41% were Indigenous (defined as Australian First Nations, New Zealand Maori, or Pacific Islander). All participants in the analysis received at least 14 days of oral antibiotics for treatment of nonhospitalized respiratory exacerbations.

Overall, 130 children had resolution of symptoms by day 14, and 87 were nonresponders.

In a multivariate analysis, children who were Indigenous or who had new abnormal auscultatory findings were significantly more likely to respond than children in other categories (odds ratios, 3.59 and 3.85, respectively).

Patients with multiple bronchiectatic lobes at the time of diagnosis and those with higher cough scores at the start of treatment were significantly less likely to respond to antibiotics than patients without these features (OR, 0.66 and 0.55, respectively).

The researchers conducted a further analysis to examine the association between Indigenous ethnicity and treatment response. They found no differences in the other response variables of number of affected lobes at diagnosis and cough scores at the start of treatment between Indigenous and non-Indigenous children.

Given the strong response to antibiotics among Indigenous children, the researchers also conducted a mediation analysis. “Respiratory bacterial pathogens were mediated by Indigenous ethnicity and associated with being an antibiotic ‘responder,’ ” they wrote. For new abnormal chest auscultatory findings, both direct and indirect effects on day 14 response to oral antibiotics were mediated by Indigenous ethnicity. However, neither cough scores at the start of treatment nor the number of affected lobes at diagnosis showed a mediation effect from Indigenous ethnicity.

Among the nonresponders, 59 of 87 resolved symptoms with continuing oral antibiotics over the next 2-4 weeks, and 21 improved without antibiotics.

Additionally, the detection of a respiratory virus at the start of an exacerbation was not associated with antibiotic failure at 14 days, the researchers noted.

The findings were limited by several factors including the use of data from randomized trials that were not designed to address the question in the current study, the researchers noted. Other limitations included incomplete clinical data and lack of data on inflammatory indices, potential antibiotic-resistant pathogens in nonresponders, and the follow-up period of only 14 days, they said.

However, the results suggest a role for patient and exacerbation phenotypes in management of bronchiectasis in clinical practice and promoting antimicrobial stewardship, the researchers wrote. “Although there is benefit in treating exacerbations early to avoid treatment failure and subsequent intravenous antibiotics, future research also needs to identify exacerbations that can be managed without antibiotics,” they concluded.

The BEST-1 and BEST-2 studies were supported by the Australian National Health and Medical Research Council and the NHMRC Centre for Research Excellence in Lung Health of Aboriginal and Torres Strait Islander Children. Dr. Goyal had no financial conflicts to disclose.
 

Indigenous children or children with new abnormal auscultatory findings were significantly more likely than children in other categories to respond to oral antibiotics for exacerbations related to bronchiectasis, based on data from more than 200 individuals in New Zealand.

Children and adolescents with bronchiectasis are often treated with antibiotics for respiratory exacerbations, but the effects of antibiotics can vary among individuals, and phenotypic features associated with greater symptom resolution have not been identified, wrote Vikas Goyal, PhD, of the Centre for Children’s Health Research, Brisbane, Australia, and colleagues.

Previous studies have suggested that nearly half of exacerbations in children and adolescents resolve spontaneously after 14 days, and more data are needed to identify which patients are mostly likely to benefit from antibiotics, they noted.

In a study published in the journal Chest, the researchers reviewed secondary data from 217 children and adolescents aged 1-18 years with bronchiectasis enrolled in a pair of randomized, controlled trials comparing oral antibiotics with placebo (known as BEST-1 and BEST-2). The median age of the participants was 6.6 years, 52% were boys, and 41% were Indigenous (defined as Australian First Nations, New Zealand Maori, or Pacific Islander). All participants in the analysis received at least 14 days of oral antibiotics for treatment of nonhospitalized respiratory exacerbations.

Overall, 130 children had resolution of symptoms by day 14, and 87 were nonresponders.

In a multivariate analysis, children who were Indigenous or who had new abnormal auscultatory findings were significantly more likely to respond than children in other categories (odds ratios, 3.59 and 3.85, respectively).

Patients with multiple bronchiectatic lobes at the time of diagnosis and those with higher cough scores at the start of treatment were significantly less likely to respond to antibiotics than patients without these features (OR, 0.66 and 0.55, respectively).

The researchers conducted a further analysis to examine the association between Indigenous ethnicity and treatment response. They found no differences in the other response variables of number of affected lobes at diagnosis and cough scores at the start of treatment between Indigenous and non-Indigenous children.

Given the strong response to antibiotics among Indigenous children, the researchers also conducted a mediation analysis. “Respiratory bacterial pathogens were mediated by Indigenous ethnicity and associated with being an antibiotic ‘responder,’ ” they wrote. For new abnormal chest auscultatory findings, both direct and indirect effects on day 14 response to oral antibiotics were mediated by Indigenous ethnicity. However, neither cough scores at the start of treatment nor the number of affected lobes at diagnosis showed a mediation effect from Indigenous ethnicity.

Among the nonresponders, 59 of 87 resolved symptoms with continuing oral antibiotics over the next 2-4 weeks, and 21 improved without antibiotics.

Additionally, the detection of a respiratory virus at the start of an exacerbation was not associated with antibiotic failure at 14 days, the researchers noted.

The findings were limited by several factors including the use of data from randomized trials that were not designed to address the question in the current study, the researchers noted. Other limitations included incomplete clinical data and lack of data on inflammatory indices, potential antibiotic-resistant pathogens in nonresponders, and the follow-up period of only 14 days, they said.

However, the results suggest a role for patient and exacerbation phenotypes in management of bronchiectasis in clinical practice and promoting antimicrobial stewardship, the researchers wrote. “Although there is benefit in treating exacerbations early to avoid treatment failure and subsequent intravenous antibiotics, future research also needs to identify exacerbations that can be managed without antibiotics,” they concluded.

The BEST-1 and BEST-2 studies were supported by the Australian National Health and Medical Research Council and the NHMRC Centre for Research Excellence in Lung Health of Aboriginal and Torres Strait Islander Children. Dr. Goyal had no financial conflicts to disclose.
 

Indigenous children or children with new abnormal auscultatory findings were significantly more likely than children in other categories to respond to oral antibiotics for exacerbations related to bronchiectasis, based on data from more than 200 individuals in New Zealand.

Children and adolescents with bronchiectasis are often treated with antibiotics for respiratory exacerbations, but the effects of antibiotics can vary among individuals, and phenotypic features associated with greater symptom resolution have not been identified, wrote Vikas Goyal, PhD, of the Centre for Children’s Health Research, Brisbane, Australia, and colleagues.

Previous studies have suggested that nearly half of exacerbations in children and adolescents resolve spontaneously after 14 days, and more data are needed to identify which patients are mostly likely to benefit from antibiotics, they noted.

In a study published in the journal Chest, the researchers reviewed secondary data from 217 children and adolescents aged 1-18 years with bronchiectasis enrolled in a pair of randomized, controlled trials comparing oral antibiotics with placebo (known as BEST-1 and BEST-2). The median age of the participants was 6.6 years, 52% were boys, and 41% were Indigenous (defined as Australian First Nations, New Zealand Maori, or Pacific Islander). All participants in the analysis received at least 14 days of oral antibiotics for treatment of nonhospitalized respiratory exacerbations.

Overall, 130 children had resolution of symptoms by day 14, and 87 were nonresponders.

In a multivariate analysis, children who were Indigenous or who had new abnormal auscultatory findings were significantly more likely to respond than children in other categories (odds ratios, 3.59 and 3.85, respectively).

Patients with multiple bronchiectatic lobes at the time of diagnosis and those with higher cough scores at the start of treatment were significantly less likely to respond to antibiotics than patients without these features (OR, 0.66 and 0.55, respectively).

The researchers conducted a further analysis to examine the association between Indigenous ethnicity and treatment response. They found no differences in the other response variables of number of affected lobes at diagnosis and cough scores at the start of treatment between Indigenous and non-Indigenous children.

Given the strong response to antibiotics among Indigenous children, the researchers also conducted a mediation analysis. “Respiratory bacterial pathogens were mediated by Indigenous ethnicity and associated with being an antibiotic ‘responder,’ ” they wrote. For new abnormal chest auscultatory findings, both direct and indirect effects on day 14 response to oral antibiotics were mediated by Indigenous ethnicity. However, neither cough scores at the start of treatment nor the number of affected lobes at diagnosis showed a mediation effect from Indigenous ethnicity.

Among the nonresponders, 59 of 87 resolved symptoms with continuing oral antibiotics over the next 2-4 weeks, and 21 improved without antibiotics.

Additionally, the detection of a respiratory virus at the start of an exacerbation was not associated with antibiotic failure at 14 days, the researchers noted.

The findings were limited by several factors including the use of data from randomized trials that were not designed to address the question in the current study, the researchers noted. Other limitations included incomplete clinical data and lack of data on inflammatory indices, potential antibiotic-resistant pathogens in nonresponders, and the follow-up period of only 14 days, they said.

However, the results suggest a role for patient and exacerbation phenotypes in management of bronchiectasis in clinical practice and promoting antimicrobial stewardship, the researchers wrote. “Although there is benefit in treating exacerbations early to avoid treatment failure and subsequent intravenous antibiotics, future research also needs to identify exacerbations that can be managed without antibiotics,” they concluded.

The BEST-1 and BEST-2 studies were supported by the Australian National Health and Medical Research Council and the NHMRC Centre for Research Excellence in Lung Health of Aboriginal and Torres Strait Islander Children. Dr. Goyal had no financial conflicts to disclose.