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Nasal Cannula Dislodgement During Sleep in Veterans Receiving Long-term Oxygen Therapy for Hypoxemic Chronic Respiratory Failure
The prevalence of chronic obstructive pulmonary disease (COPD) among male US veterans is higher than in the general population.1 Veterans with COPD have higher rates of comorbidities and increased respiratory-related and all-cause health care use, including the use of long-term oxygen therapy (LTOT).2-5 It has been well established that LTOT reduces all-cause mortality in patients with COPD and
Delivery of domiciliary LTOT entails placing a nasal cannula into both nostrils and loosely securing it around both ears throughout the wake-sleep cycle. Several veterans with hypoxemic CRF due to COPD at the Jesse Brown Veterans Affairs Medical Center (JBVAMC) in Chicago, Illinois, who were receiving LTOT reported nasal cannula dislodgement (NCD) while they slept. However, the clinical significance and impact of these repeated episodes on respiratory-related health care utilization, such as frequent COPD exacerbations with hospitalization, were not recognized.
The purpose of this study was to determine whether veterans with hypoxemic CRF due to COPD and receiving 24-hour LTOT at JBVAMC were experiencing NCD during sleep and, if so, its impact on
METHODS
We reviewed electronic health records (EHRs) of veterans with hypoxemic CRF from COPD who received 24-hour LTOT administered through nasal cannula and were followed
Pertinent patient demographics, clinical and physiologic variables, and hospitalizations with length of JBVAMC stay for each physician-diagnosed COPD exacerbation in the preceding year from the date last seen in the clinic were abstracted from EHRs. Overall hospital cost, defined as a veteran overnight stay in either the medical intensive care unit (MICU) or a general acute medicine bed in a US Department of Veterans Affairs (VA) facility, was calculated for each hospitalization for physician-diagnosed COPD exacerbation using VA Managerial Cost Accounting System National Cost Extracts for inpatient encounters.15 We then contacted each veteran by telephone and asked whether they had experienced NCD and, if so, its weekly frequency ranging from once to nightly.
Data Analysis
Data were reported as mean (SD) where appropriate. The t test and Fisher exact test were used as indicated. P < .05 was considered statistically significant. The study protocol
RESULTS
During the study period,
Of the 75 patients, 66 (88%) responded to the telephone survey and 22 patients (33%) reported weekly episodes of NCD while they slept (median, 4 dislodgments per week). (Table 1). Eight patients (36%) reported nightly NCDs (Figure). All 66 respondents were male and 14 of 22 in the NCD group as well as 21 of 44 in the no NCD group were Black veterans. The mean age was similar in both groups: 71 years in the NCD group and 72 years in the no NCD group. There were no statistically significant differences in demographics, including prevalence of obstructive sleep apnea (OSA), supplemental oxygen flow rate, and duration of LTOT, or in pulmonary function test results between patients who did and did not experience NCD while sleeping (Table 2).
Ten of 22 patients (45%) with NCD and 9 of 44 patients (20%) without NCD were hospitalized at the JBVAMC for ≥ 1 COPD exacerbation in the preceding year that was diagnosed by a physician (P = .045). Three of 22 patients (14%) with NCD and no patients in the no NCD group were admitted to the MICU. No patients required intubation and mechanical ventilation during hospitalization, and no patients died. Overall hospital costs were 25% ($64,342) higher in NCD group compared with the no NCD group and were attributed to the MICU admissions in the NCD group (Table 3). Nine veterans did not respond to repeated telephone calls. One physician-diagnosed COPD exacerbation requiring hospitalization was documented in the nonresponder group; the patient was hospitalized for 2 days. One veteran died before being contacted.
DISCUSSION
There are 3 new findings in this study.
Nocturnal arterial oxygen desaturation in patients with COPD without evidence of OSA may contribute to the frequency of exacerbations.16 Although the mechanism(s) underlying this phenomenon is uncertain, we posit that prolonged nocturnal airway wall hypoxia could amplify underlying chronic inflammation through local generation of reactive oxygen species, thereby predisposing patients to exacerbations. Frequent COPD exacerbations promote disease progression and health status decline and are associated with increased mortality.11,13 Moreover, hospitalization of patients with COPD is the largest contributor to the annual direct cost of COPD per patient.10,12 The higher hospitalization rate observed in the NCD group in our study suggests that interruption of supplemental oxygen delivery while asleep may be a risk factor for COPD exacerbation. Alternatively, an independent factor or factors may have contributed to both NCD during sleep and COPD exacerbation in these patients or an impending exacerbation resulted in sleep disturbances that led to NCD. Additional research is warranted on veterans with hypoxemic CRF from COPD who are receiving LTOT and report frequent NCD during sleep that may support or refute these hypotheses.
To the best of our knowledge, NCD during sleep has not been previously reported in patients
Limitations
This was a small, single-site study, comprised entirely of male patients who are predominantly Black veterans. The telephone interviews with veterans self-reporting NCD during their sleep are prone to recall bias. In addition, the validity and reproducibility of NCD during sleep were not addressed in this study. Missing data from 9 nonresponders may have introduced a nonresponse bias in data analysis and interpretation. The overall hospital cost for a COPD exacerbation at JBVAMC was derived from VA data; US Centers for Medicare & Medicaid Services or commercial carrier data may be different.15,21 Lastly, access to LTOT for veterans with hypoxemic CRF from COPD is regulated and supervised at VA medical facilities.14 This process may be different for patients outside the VA. Taken together, it is difficult to generalize our initial observations to non-VA patients with hypoxemic CRF from COPD who are receiving LTOT. We suggest a large, prospective study of veterans be conducted to determine the prevalence of NCD during sleep and its relationship with COPD exacerbations in veterans receiving LTOT with hypoxemic CRF due to COPD.
CONCLUSIONS
Acknowledgments
We thank Yolanda Davis, RRT, and George Adam for their assistance with this project.
1. Boersma P, Cohen RA, Zelaya CE, Moy E. Multiple chronic conditions among veterans and nonveterans: United States, 2015-2018. Natl Health Stat Report. 2021;(153):1-13. doi:10.15620/cdc:101659
2. Sharafkhaneh A, Petersen NJ, Yu H-J, Dalal AA, Johnson ML, Hanania NA. Burden of COPD in a government health care system: a retrospective observational study using data from the US Veterans Affairs population. Int J Chron Obstruct Pulmon Dis. 2010;5:125-132. doi:10.2147/copd.s8047
3. LaBedz SL, Krishnan JA, Chung Y-C, et al. Chronic obstructive pulmonary disease outcomes at Veterans Affairs versus non-Veterans Affairs hospitals. Chronic Obstr Pulm Dis. 2021;8(3):306-313. doi:10.15326/jcopdf.2021.0201
4. Darnell K, Dwivedi AK, Weng Z, Panos RJ. Disproportionate utilization of healthcare resources among veterans with COPD: a retrospective analysis of factors associated with COPD healthcare cost. Cost Eff Resour Alloc. 2013;11:13. doi:10.1186/1478-7547-11-13
5. Bamonti PM, Robinson SA, Wan ES, Moy ML. Improving physiological, physical, and psychological health outcomes: a narrative review in US Veterans with COPD. Int J Chron Obstruct Pulmon Dis. 2022;17:1269-1283. doi:10.2147/COPD.S339323
6. Cranston JM, Crockett AJ, Moss JR, Alpers JH. Domiciliary oxygen for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2005;2005(4):CD001744. doi:10.1002/14651858.CD001744.pub2
7. Lacasse Y, Tan AM, Maltais F, Krishnan JA. Home oxygen in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2018;197(10):1254-1264. doi:10.1164/rccm.201802-0382CI
8. Jacobs SS, Krishnan JA, Lederer DJ, et al. Home oxygen therapy for adults with chronic lung disease. An official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020;202(10):e121-e141. doi:10.1164/rccm.202009-3608ST
9. AARC. AARC clinical practice guideline. Oxygen therapy in the home or alternate site health care facility--2007 revision & update. Respir Care. 2007;52(8):1063-1068.
10. Foo J, Landis SH, Maskell J, et al. Continuing to confront COPD international patient survey: economic impact of COPD in 12 countries. PLoS One. 2016;11(4):e0152618. doi:10.1371/journal.pone.0152618
11. Rothnie KJ, Müllerová H, Smeeth L, Quint JK. Natural history of chronic obstructive pulmonary disease exacerbations in a general practice-based population with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2018;198(4):464-471. doi:10.1164/rccm.201710-2029OC
12. Stanford RH, Engel-Nitz NM, Bancroft T, Essoi B. The identification and cost of acute chronic obstructive pulmonary disease exacerbations in a United States population healthcare claims database. COPD. 2020;17(5):499-508. doi:10.1080/15412555.2020.1817357
13. Hurst JR, Han MK, Singh B, et al. Prognostic risk factors for moderate-to-severe exacerbations in patients with chronic obstructive pulmonary disease: a systematic literature review. Respir Res. 2022;23(1):213. doi:10.1186/s12931-022-02123-5
14. US Department of Veterans Affairs, Veterans Health Administration. Home oxygen program. VHA Directive 1173.13(1). Published August 5, 2020. Accessed February 28, 2024. https://www.va.gov/vhapublications/ViewPublication.asp?pub_ID=8947
15. Phibbs CS, Barnett PG, Fan A, Harden C, King SS, Scott JY. Research guide to decision support system national cost extracts. Health Economics Resource Center of Health Service R&D Services, US Department of Veterans Affairs. September 2010. Accessed February 14, 2024. https://www.herc.research.va.gov/files/book_621.pdf
16. Agusti A, Hedner J, Marin JM, Barbé F, Cazzola M, Rennard S. Night-time symptoms: a forgotten dimension of COPD. Eur Respir Rev. 2011;20(121):183-194. doi:10.1183/09059180.00004311
17. Croxton TL, Bailey WC. Long-term oxygen treatment in chronic obstructive pulmonary disease: recommendations for future research: an NHLBI workshop report. Am J Respir Crit Care Med. 2006;174(4):373-378. doi:10.1164/rccm.200507-1161WS
18. Melani AS, Sestini P, Rottoli P. Home oxygen therapy: re-thinking the role of devices. Expert Rev Clin Pharmacol. 2018;11(3):279-289. doi:10.1080/17512433.2018.1421457
19. Sculley JA, Corbridge SJ, Prieto-Centurion V, et al. Home oxygen therapy for patients with COPD: time for a reboot. Respir Care. 2019;64(12):1574-1585. doi:10.4187/respcare.07135
20. Jacobs SS, Lindell KO, Collins EG, et al. Patient perceptions of the adequacy of supplemental oxygen therapy. Results of the American Thoracic Society Nursing Assembly Oxygen Working Group Survey. Ann Am Thorac Soc. 2018;15:24-32. doi:10.1513/AnnalsATS.201703-209OC
21. US Centers for Medicare & Medicaid Services. Home use of oxygen. Publication number 100-3. January 3, 2023. Accessed February 14, 2024. https://www.cms.gov/medicare-coverage-database/view/ncd.aspx?NCDId=169
The prevalence of chronic obstructive pulmonary disease (COPD) among male US veterans is higher than in the general population.1 Veterans with COPD have higher rates of comorbidities and increased respiratory-related and all-cause health care use, including the use of long-term oxygen therapy (LTOT).2-5 It has been well established that LTOT reduces all-cause mortality in patients with COPD and
Delivery of domiciliary LTOT entails placing a nasal cannula into both nostrils and loosely securing it around both ears throughout the wake-sleep cycle. Several veterans with hypoxemic CRF due to COPD at the Jesse Brown Veterans Affairs Medical Center (JBVAMC) in Chicago, Illinois, who were receiving LTOT reported nasal cannula dislodgement (NCD) while they slept. However, the clinical significance and impact of these repeated episodes on respiratory-related health care utilization, such as frequent COPD exacerbations with hospitalization, were not recognized.
The purpose of this study was to determine whether veterans with hypoxemic CRF due to COPD and receiving 24-hour LTOT at JBVAMC were experiencing NCD during sleep and, if so, its impact on
METHODS
We reviewed electronic health records (EHRs) of veterans with hypoxemic CRF from COPD who received 24-hour LTOT administered through nasal cannula and were followed
Pertinent patient demographics, clinical and physiologic variables, and hospitalizations with length of JBVAMC stay for each physician-diagnosed COPD exacerbation in the preceding year from the date last seen in the clinic were abstracted from EHRs. Overall hospital cost, defined as a veteran overnight stay in either the medical intensive care unit (MICU) or a general acute medicine bed in a US Department of Veterans Affairs (VA) facility, was calculated for each hospitalization for physician-diagnosed COPD exacerbation using VA Managerial Cost Accounting System National Cost Extracts for inpatient encounters.15 We then contacted each veteran by telephone and asked whether they had experienced NCD and, if so, its weekly frequency ranging from once to nightly.
Data Analysis
Data were reported as mean (SD) where appropriate. The t test and Fisher exact test were used as indicated. P < .05 was considered statistically significant. The study protocol
RESULTS
During the study period,
Of the 75 patients, 66 (88%) responded to the telephone survey and 22 patients (33%) reported weekly episodes of NCD while they slept (median, 4 dislodgments per week). (Table 1). Eight patients (36%) reported nightly NCDs (Figure). All 66 respondents were male and 14 of 22 in the NCD group as well as 21 of 44 in the no NCD group were Black veterans. The mean age was similar in both groups: 71 years in the NCD group and 72 years in the no NCD group. There were no statistically significant differences in demographics, including prevalence of obstructive sleep apnea (OSA), supplemental oxygen flow rate, and duration of LTOT, or in pulmonary function test results between patients who did and did not experience NCD while sleeping (Table 2).
Ten of 22 patients (45%) with NCD and 9 of 44 patients (20%) without NCD were hospitalized at the JBVAMC for ≥ 1 COPD exacerbation in the preceding year that was diagnosed by a physician (P = .045). Three of 22 patients (14%) with NCD and no patients in the no NCD group were admitted to the MICU. No patients required intubation and mechanical ventilation during hospitalization, and no patients died. Overall hospital costs were 25% ($64,342) higher in NCD group compared with the no NCD group and were attributed to the MICU admissions in the NCD group (Table 3). Nine veterans did not respond to repeated telephone calls. One physician-diagnosed COPD exacerbation requiring hospitalization was documented in the nonresponder group; the patient was hospitalized for 2 days. One veteran died before being contacted.
DISCUSSION
There are 3 new findings in this study.
Nocturnal arterial oxygen desaturation in patients with COPD without evidence of OSA may contribute to the frequency of exacerbations.16 Although the mechanism(s) underlying this phenomenon is uncertain, we posit that prolonged nocturnal airway wall hypoxia could amplify underlying chronic inflammation through local generation of reactive oxygen species, thereby predisposing patients to exacerbations. Frequent COPD exacerbations promote disease progression and health status decline and are associated with increased mortality.11,13 Moreover, hospitalization of patients with COPD is the largest contributor to the annual direct cost of COPD per patient.10,12 The higher hospitalization rate observed in the NCD group in our study suggests that interruption of supplemental oxygen delivery while asleep may be a risk factor for COPD exacerbation. Alternatively, an independent factor or factors may have contributed to both NCD during sleep and COPD exacerbation in these patients or an impending exacerbation resulted in sleep disturbances that led to NCD. Additional research is warranted on veterans with hypoxemic CRF from COPD who are receiving LTOT and report frequent NCD during sleep that may support or refute these hypotheses.
To the best of our knowledge, NCD during sleep has not been previously reported in patients
Limitations
This was a small, single-site study, comprised entirely of male patients who are predominantly Black veterans. The telephone interviews with veterans self-reporting NCD during their sleep are prone to recall bias. In addition, the validity and reproducibility of NCD during sleep were not addressed in this study. Missing data from 9 nonresponders may have introduced a nonresponse bias in data analysis and interpretation. The overall hospital cost for a COPD exacerbation at JBVAMC was derived from VA data; US Centers for Medicare & Medicaid Services or commercial carrier data may be different.15,21 Lastly, access to LTOT for veterans with hypoxemic CRF from COPD is regulated and supervised at VA medical facilities.14 This process may be different for patients outside the VA. Taken together, it is difficult to generalize our initial observations to non-VA patients with hypoxemic CRF from COPD who are receiving LTOT. We suggest a large, prospective study of veterans be conducted to determine the prevalence of NCD during sleep and its relationship with COPD exacerbations in veterans receiving LTOT with hypoxemic CRF due to COPD.
CONCLUSIONS
Acknowledgments
We thank Yolanda Davis, RRT, and George Adam for their assistance with this project.
The prevalence of chronic obstructive pulmonary disease (COPD) among male US veterans is higher than in the general population.1 Veterans with COPD have higher rates of comorbidities and increased respiratory-related and all-cause health care use, including the use of long-term oxygen therapy (LTOT).2-5 It has been well established that LTOT reduces all-cause mortality in patients with COPD and
Delivery of domiciliary LTOT entails placing a nasal cannula into both nostrils and loosely securing it around both ears throughout the wake-sleep cycle. Several veterans with hypoxemic CRF due to COPD at the Jesse Brown Veterans Affairs Medical Center (JBVAMC) in Chicago, Illinois, who were receiving LTOT reported nasal cannula dislodgement (NCD) while they slept. However, the clinical significance and impact of these repeated episodes on respiratory-related health care utilization, such as frequent COPD exacerbations with hospitalization, were not recognized.
The purpose of this study was to determine whether veterans with hypoxemic CRF due to COPD and receiving 24-hour LTOT at JBVAMC were experiencing NCD during sleep and, if so, its impact on
METHODS
We reviewed electronic health records (EHRs) of veterans with hypoxemic CRF from COPD who received 24-hour LTOT administered through nasal cannula and were followed
Pertinent patient demographics, clinical and physiologic variables, and hospitalizations with length of JBVAMC stay for each physician-diagnosed COPD exacerbation in the preceding year from the date last seen in the clinic were abstracted from EHRs. Overall hospital cost, defined as a veteran overnight stay in either the medical intensive care unit (MICU) or a general acute medicine bed in a US Department of Veterans Affairs (VA) facility, was calculated for each hospitalization for physician-diagnosed COPD exacerbation using VA Managerial Cost Accounting System National Cost Extracts for inpatient encounters.15 We then contacted each veteran by telephone and asked whether they had experienced NCD and, if so, its weekly frequency ranging from once to nightly.
Data Analysis
Data were reported as mean (SD) where appropriate. The t test and Fisher exact test were used as indicated. P < .05 was considered statistically significant. The study protocol
RESULTS
During the study period,
Of the 75 patients, 66 (88%) responded to the telephone survey and 22 patients (33%) reported weekly episodes of NCD while they slept (median, 4 dislodgments per week). (Table 1). Eight patients (36%) reported nightly NCDs (Figure). All 66 respondents were male and 14 of 22 in the NCD group as well as 21 of 44 in the no NCD group were Black veterans. The mean age was similar in both groups: 71 years in the NCD group and 72 years in the no NCD group. There were no statistically significant differences in demographics, including prevalence of obstructive sleep apnea (OSA), supplemental oxygen flow rate, and duration of LTOT, or in pulmonary function test results between patients who did and did not experience NCD while sleeping (Table 2).
Ten of 22 patients (45%) with NCD and 9 of 44 patients (20%) without NCD were hospitalized at the JBVAMC for ≥ 1 COPD exacerbation in the preceding year that was diagnosed by a physician (P = .045). Three of 22 patients (14%) with NCD and no patients in the no NCD group were admitted to the MICU. No patients required intubation and mechanical ventilation during hospitalization, and no patients died. Overall hospital costs were 25% ($64,342) higher in NCD group compared with the no NCD group and were attributed to the MICU admissions in the NCD group (Table 3). Nine veterans did not respond to repeated telephone calls. One physician-diagnosed COPD exacerbation requiring hospitalization was documented in the nonresponder group; the patient was hospitalized for 2 days. One veteran died before being contacted.
DISCUSSION
There are 3 new findings in this study.
Nocturnal arterial oxygen desaturation in patients with COPD without evidence of OSA may contribute to the frequency of exacerbations.16 Although the mechanism(s) underlying this phenomenon is uncertain, we posit that prolonged nocturnal airway wall hypoxia could amplify underlying chronic inflammation through local generation of reactive oxygen species, thereby predisposing patients to exacerbations. Frequent COPD exacerbations promote disease progression and health status decline and are associated with increased mortality.11,13 Moreover, hospitalization of patients with COPD is the largest contributor to the annual direct cost of COPD per patient.10,12 The higher hospitalization rate observed in the NCD group in our study suggests that interruption of supplemental oxygen delivery while asleep may be a risk factor for COPD exacerbation. Alternatively, an independent factor or factors may have contributed to both NCD during sleep and COPD exacerbation in these patients or an impending exacerbation resulted in sleep disturbances that led to NCD. Additional research is warranted on veterans with hypoxemic CRF from COPD who are receiving LTOT and report frequent NCD during sleep that may support or refute these hypotheses.
To the best of our knowledge, NCD during sleep has not been previously reported in patients
Limitations
This was a small, single-site study, comprised entirely of male patients who are predominantly Black veterans. The telephone interviews with veterans self-reporting NCD during their sleep are prone to recall bias. In addition, the validity and reproducibility of NCD during sleep were not addressed in this study. Missing data from 9 nonresponders may have introduced a nonresponse bias in data analysis and interpretation. The overall hospital cost for a COPD exacerbation at JBVAMC was derived from VA data; US Centers for Medicare & Medicaid Services or commercial carrier data may be different.15,21 Lastly, access to LTOT for veterans with hypoxemic CRF from COPD is regulated and supervised at VA medical facilities.14 This process may be different for patients outside the VA. Taken together, it is difficult to generalize our initial observations to non-VA patients with hypoxemic CRF from COPD who are receiving LTOT. We suggest a large, prospective study of veterans be conducted to determine the prevalence of NCD during sleep and its relationship with COPD exacerbations in veterans receiving LTOT with hypoxemic CRF due to COPD.
CONCLUSIONS
Acknowledgments
We thank Yolanda Davis, RRT, and George Adam for their assistance with this project.
1. Boersma P, Cohen RA, Zelaya CE, Moy E. Multiple chronic conditions among veterans and nonveterans: United States, 2015-2018. Natl Health Stat Report. 2021;(153):1-13. doi:10.15620/cdc:101659
2. Sharafkhaneh A, Petersen NJ, Yu H-J, Dalal AA, Johnson ML, Hanania NA. Burden of COPD in a government health care system: a retrospective observational study using data from the US Veterans Affairs population. Int J Chron Obstruct Pulmon Dis. 2010;5:125-132. doi:10.2147/copd.s8047
3. LaBedz SL, Krishnan JA, Chung Y-C, et al. Chronic obstructive pulmonary disease outcomes at Veterans Affairs versus non-Veterans Affairs hospitals. Chronic Obstr Pulm Dis. 2021;8(3):306-313. doi:10.15326/jcopdf.2021.0201
4. Darnell K, Dwivedi AK, Weng Z, Panos RJ. Disproportionate utilization of healthcare resources among veterans with COPD: a retrospective analysis of factors associated with COPD healthcare cost. Cost Eff Resour Alloc. 2013;11:13. doi:10.1186/1478-7547-11-13
5. Bamonti PM, Robinson SA, Wan ES, Moy ML. Improving physiological, physical, and psychological health outcomes: a narrative review in US Veterans with COPD. Int J Chron Obstruct Pulmon Dis. 2022;17:1269-1283. doi:10.2147/COPD.S339323
6. Cranston JM, Crockett AJ, Moss JR, Alpers JH. Domiciliary oxygen for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2005;2005(4):CD001744. doi:10.1002/14651858.CD001744.pub2
7. Lacasse Y, Tan AM, Maltais F, Krishnan JA. Home oxygen in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2018;197(10):1254-1264. doi:10.1164/rccm.201802-0382CI
8. Jacobs SS, Krishnan JA, Lederer DJ, et al. Home oxygen therapy for adults with chronic lung disease. An official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020;202(10):e121-e141. doi:10.1164/rccm.202009-3608ST
9. AARC. AARC clinical practice guideline. Oxygen therapy in the home or alternate site health care facility--2007 revision & update. Respir Care. 2007;52(8):1063-1068.
10. Foo J, Landis SH, Maskell J, et al. Continuing to confront COPD international patient survey: economic impact of COPD in 12 countries. PLoS One. 2016;11(4):e0152618. doi:10.1371/journal.pone.0152618
11. Rothnie KJ, Müllerová H, Smeeth L, Quint JK. Natural history of chronic obstructive pulmonary disease exacerbations in a general practice-based population with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2018;198(4):464-471. doi:10.1164/rccm.201710-2029OC
12. Stanford RH, Engel-Nitz NM, Bancroft T, Essoi B. The identification and cost of acute chronic obstructive pulmonary disease exacerbations in a United States population healthcare claims database. COPD. 2020;17(5):499-508. doi:10.1080/15412555.2020.1817357
13. Hurst JR, Han MK, Singh B, et al. Prognostic risk factors for moderate-to-severe exacerbations in patients with chronic obstructive pulmonary disease: a systematic literature review. Respir Res. 2022;23(1):213. doi:10.1186/s12931-022-02123-5
14. US Department of Veterans Affairs, Veterans Health Administration. Home oxygen program. VHA Directive 1173.13(1). Published August 5, 2020. Accessed February 28, 2024. https://www.va.gov/vhapublications/ViewPublication.asp?pub_ID=8947
15. Phibbs CS, Barnett PG, Fan A, Harden C, King SS, Scott JY. Research guide to decision support system national cost extracts. Health Economics Resource Center of Health Service R&D Services, US Department of Veterans Affairs. September 2010. Accessed February 14, 2024. https://www.herc.research.va.gov/files/book_621.pdf
16. Agusti A, Hedner J, Marin JM, Barbé F, Cazzola M, Rennard S. Night-time symptoms: a forgotten dimension of COPD. Eur Respir Rev. 2011;20(121):183-194. doi:10.1183/09059180.00004311
17. Croxton TL, Bailey WC. Long-term oxygen treatment in chronic obstructive pulmonary disease: recommendations for future research: an NHLBI workshop report. Am J Respir Crit Care Med. 2006;174(4):373-378. doi:10.1164/rccm.200507-1161WS
18. Melani AS, Sestini P, Rottoli P. Home oxygen therapy: re-thinking the role of devices. Expert Rev Clin Pharmacol. 2018;11(3):279-289. doi:10.1080/17512433.2018.1421457
19. Sculley JA, Corbridge SJ, Prieto-Centurion V, et al. Home oxygen therapy for patients with COPD: time for a reboot. Respir Care. 2019;64(12):1574-1585. doi:10.4187/respcare.07135
20. Jacobs SS, Lindell KO, Collins EG, et al. Patient perceptions of the adequacy of supplemental oxygen therapy. Results of the American Thoracic Society Nursing Assembly Oxygen Working Group Survey. Ann Am Thorac Soc. 2018;15:24-32. doi:10.1513/AnnalsATS.201703-209OC
21. US Centers for Medicare & Medicaid Services. Home use of oxygen. Publication number 100-3. January 3, 2023. Accessed February 14, 2024. https://www.cms.gov/medicare-coverage-database/view/ncd.aspx?NCDId=169
1. Boersma P, Cohen RA, Zelaya CE, Moy E. Multiple chronic conditions among veterans and nonveterans: United States, 2015-2018. Natl Health Stat Report. 2021;(153):1-13. doi:10.15620/cdc:101659
2. Sharafkhaneh A, Petersen NJ, Yu H-J, Dalal AA, Johnson ML, Hanania NA. Burden of COPD in a government health care system: a retrospective observational study using data from the US Veterans Affairs population. Int J Chron Obstruct Pulmon Dis. 2010;5:125-132. doi:10.2147/copd.s8047
3. LaBedz SL, Krishnan JA, Chung Y-C, et al. Chronic obstructive pulmonary disease outcomes at Veterans Affairs versus non-Veterans Affairs hospitals. Chronic Obstr Pulm Dis. 2021;8(3):306-313. doi:10.15326/jcopdf.2021.0201
4. Darnell K, Dwivedi AK, Weng Z, Panos RJ. Disproportionate utilization of healthcare resources among veterans with COPD: a retrospective analysis of factors associated with COPD healthcare cost. Cost Eff Resour Alloc. 2013;11:13. doi:10.1186/1478-7547-11-13
5. Bamonti PM, Robinson SA, Wan ES, Moy ML. Improving physiological, physical, and psychological health outcomes: a narrative review in US Veterans with COPD. Int J Chron Obstruct Pulmon Dis. 2022;17:1269-1283. doi:10.2147/COPD.S339323
6. Cranston JM, Crockett AJ, Moss JR, Alpers JH. Domiciliary oxygen for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2005;2005(4):CD001744. doi:10.1002/14651858.CD001744.pub2
7. Lacasse Y, Tan AM, Maltais F, Krishnan JA. Home oxygen in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2018;197(10):1254-1264. doi:10.1164/rccm.201802-0382CI
8. Jacobs SS, Krishnan JA, Lederer DJ, et al. Home oxygen therapy for adults with chronic lung disease. An official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020;202(10):e121-e141. doi:10.1164/rccm.202009-3608ST
9. AARC. AARC clinical practice guideline. Oxygen therapy in the home or alternate site health care facility--2007 revision & update. Respir Care. 2007;52(8):1063-1068.
10. Foo J, Landis SH, Maskell J, et al. Continuing to confront COPD international patient survey: economic impact of COPD in 12 countries. PLoS One. 2016;11(4):e0152618. doi:10.1371/journal.pone.0152618
11. Rothnie KJ, Müllerová H, Smeeth L, Quint JK. Natural history of chronic obstructive pulmonary disease exacerbations in a general practice-based population with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2018;198(4):464-471. doi:10.1164/rccm.201710-2029OC
12. Stanford RH, Engel-Nitz NM, Bancroft T, Essoi B. The identification and cost of acute chronic obstructive pulmonary disease exacerbations in a United States population healthcare claims database. COPD. 2020;17(5):499-508. doi:10.1080/15412555.2020.1817357
13. Hurst JR, Han MK, Singh B, et al. Prognostic risk factors for moderate-to-severe exacerbations in patients with chronic obstructive pulmonary disease: a systematic literature review. Respir Res. 2022;23(1):213. doi:10.1186/s12931-022-02123-5
14. US Department of Veterans Affairs, Veterans Health Administration. Home oxygen program. VHA Directive 1173.13(1). Published August 5, 2020. Accessed February 28, 2024. https://www.va.gov/vhapublications/ViewPublication.asp?pub_ID=8947
15. Phibbs CS, Barnett PG, Fan A, Harden C, King SS, Scott JY. Research guide to decision support system national cost extracts. Health Economics Resource Center of Health Service R&D Services, US Department of Veterans Affairs. September 2010. Accessed February 14, 2024. https://www.herc.research.va.gov/files/book_621.pdf
16. Agusti A, Hedner J, Marin JM, Barbé F, Cazzola M, Rennard S. Night-time symptoms: a forgotten dimension of COPD. Eur Respir Rev. 2011;20(121):183-194. doi:10.1183/09059180.00004311
17. Croxton TL, Bailey WC. Long-term oxygen treatment in chronic obstructive pulmonary disease: recommendations for future research: an NHLBI workshop report. Am J Respir Crit Care Med. 2006;174(4):373-378. doi:10.1164/rccm.200507-1161WS
18. Melani AS, Sestini P, Rottoli P. Home oxygen therapy: re-thinking the role of devices. Expert Rev Clin Pharmacol. 2018;11(3):279-289. doi:10.1080/17512433.2018.1421457
19. Sculley JA, Corbridge SJ, Prieto-Centurion V, et al. Home oxygen therapy for patients with COPD: time for a reboot. Respir Care. 2019;64(12):1574-1585. doi:10.4187/respcare.07135
20. Jacobs SS, Lindell KO, Collins EG, et al. Patient perceptions of the adequacy of supplemental oxygen therapy. Results of the American Thoracic Society Nursing Assembly Oxygen Working Group Survey. Ann Am Thorac Soc. 2018;15:24-32. doi:10.1513/AnnalsATS.201703-209OC
21. US Centers for Medicare & Medicaid Services. Home use of oxygen. Publication number 100-3. January 3, 2023. Accessed February 14, 2024. https://www.cms.gov/medicare-coverage-database/view/ncd.aspx?NCDId=169
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>0424 FED O2 Therapy</fileName> <TBEID>0C02F3C0.SIG</TBEID> <TBUniqueIdentifier>NJ_0C02F3C0</TBUniqueIdentifier> <newsOrJournal>Journal</newsOrJournal> <publisherName>Frontline Medical Communications Inc.</publisherName> <storyname/> <articleType>1</articleType> <TBLocation>Copyfitting-FED</TBLocation> <QCDate/> <firstPublished>20240408T155151</firstPublished> <LastPublished>20240408T155151</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240408T155151</CMSDate> <articleSource/> <facebookInfo/> <meetingNumber/> <byline/> <bylineText>Zane Elfessi, PharmD, BCPS, BCCCPa,b; Ahmed Mahgoub, MDa; Emily Tran, PharmDa,b; Grace McGeeb; Israel Rubinstein, MDa,b</bylineText> <bylineFull/> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType/> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:"> <name/> <rightsInfo> <copyrightHolder> <name/> </copyrightHolder> <copyrightNotice/> </rightsInfo> </provider> <abstract/> <metaDescription>The prevalence of chronic obstructive pulmonary disease (COPD) among male US veterans is higher than in the general population.1 Veterans with COPD have higher </metaDescription> <articlePDF/> <teaserImage/> <title>Nasal Cannula Dislodgement During Sleep in Veterans Receiving Long-term Oxygen Therapy for Hypoxemic Chronic Respiratory Failure</title> <deck/> <eyebrow>Original Study</eyebrow> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear>2024</pubPubdateYear> <pubPubdateMonth>April</pubPubdateMonth> <pubPubdateDay/> <pubVolume>41</pubVolume> <pubNumber>4</pubNumber> <wireChannels/> <primaryCMSID/> <CMSIDs> <CMSID>2951</CMSID> <CMSID>3639</CMSID> </CMSIDs> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>FED</publicationCode> <pubIssueName>April 2024</pubIssueName> <pubArticleType>Feature Articles | 3639</pubArticleType> <pubTopics/> <pubCategories/> <pubSections> <pubSection>Feature | 2951<pubSubsection/></pubSection> </pubSections> <journalTitle>Fed Pract</journalTitle> <journalFullTitle>Federal Practitioner</journalFullTitle> <copyrightStatement>Copyright 2017 Frontline Medical Communications Inc., Parsippany, NJ, USA. All rights reserved.</copyrightStatement> </publicationData> </publications_g> <publications> <term canonical="true">16</term> </publications> <sections> <term canonical="true">104</term> </sections> <topics> <term canonical="true">284</term> <term>27442</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Nasal Cannula Dislodgement During Sleep in Veterans Receiving Long-term Oxygen Therapy for Hypoxemic Chronic Respiratory Failure</title> <deck/> </itemMeta> <itemContent> <p class="abstract"><b>B</b><b>ackground: </b>Chronic obstructive pulmonary disease (COPD) is highly prevalent in male veterans. Long-term oxygen therapy (LTOT) can effectively reduce all-cause mortality in these patients, but the effects of nasal cannula dislodgement (NCD) during sleep have not been well studied. <hl name="33679"/><br/><br/><b>Methods: </b>This study sought<b> </b>to determine whether veterans receiving LTOT for hypoxemic chronic respiratory failure (CRF) due to COPD reported NCD while they slept and, if so, its impact on hospitalizations for COPD exacerbations. Electronic health records were reviewed of veterans with hypoxemic CRF due to COPD who received LTOT and were followed in the pulmonary clinic at the Jesse Brown Veterans Affairs Medical Center between February 1, 2022, and December 31, 2022. Overall hospital cost was calculated for each hospitalized veteran with diagnosed COPD exacerbation. Veterans reported whether they experienced NCD during sleep and, if so, its frequency. <br/><br/><b>Results<hl name="33680"/>:</b> <hl name="33681"/>Interviews were conducted with 66 veterans with a mean age of 71 years. Twenty-two veterans (33%) reported NCD ≥ 1 weekly (median, 4). There were no statistically significant differences in demographics, supplemental oxygen flow rate, duration of LTOT, and pulmonary function tests between patients with and without NCD. Ten patients (45%) with NCD and 9 patients (20%) without NCD were hospitalized for ≥ 1 COPD exacerbation (<i>P</i> = .045). Three patients (14%) with NCD were admitted to the medical intensive care unit. Overall hospital costs were 25% higher in the NCD group compared with the no NCD group.<br/><br/><b>Conclusions<hl name="33682"/>:</b> Veterans receiving LTOT for hypoxemic CRF due to COPD who report frequent NCD during sleep have higher hospitalization rates for COPD exacerbation and higher hospital costs.</p> <p><span class="Drop">T</span>he prevalence of chronic obstructive pulmonary disease (COPD) among male US veterans is higher than in the general population.<sup>1</sup> Veterans with COPD have higher rates of comorbidities and increased respiratory-related and all-cause health care use, including the use of long-term oxygen therapy (LTOT).<sup>2-5</sup> It has been well established that LTOT reduces all-cause mortality in patients with COPD and <hl name="33683"/>resting hypoxemic chronic respiratory failure (CRF) when used for ≥ 15 hours per day.<sup>6-8</sup> </p> <p>Delivery of domiciliary LTOT entails placing a nasal cannula into both nostrils and loosely securing it around both ears throughout the wake-sleep cycle. Several veterans with hypoxemic CRF due to COPD at the Jesse Brown Veterans Affairs Medical Center (JBVAMC) in Chicago, Illinois, who were receiving LTOT reported nasal cannula dislodgement (NCD) while they slept. However, the clinical significance and impact of these repeated episodes on respiratory-related health care utilization, such as frequent COPD exacerbations with hospitalization, were not recognized. <hl name="7"/>Moreover, we found no published reports or clinical practice guidelines alluding to similar events reported by patients with hypoxemic CRF due to COPD receiving LTOT either at home or in an acute care setting.<sup>8,9</sup> Nonetheless, frequent COPD exacerbations are associated with increased hospital admissions and account for a large portion of health care costs attributed to COPD.<sup>10-13</sup>The purpose of this study was to determine whether veterans with hypoxemic CRF due to COPD and receiving 24-hour LTOT at JBVAMC were experiencing NCD during sleep and, if so, its impact on <hl name="8"/>their hospitalizations for COPD exacerbations. </p> <h2>METHODS</h2> <p>We reviewed electronic health records (EHRs) of veterans with hypoxemic CRF from COPD who received 24-hour LTOT administered through nasal cannula and were followed <hl name="9"/>in the JBVAMC pulmonary outpatient clinic between February 1, 2022, and December 31, 2022. In each case, LTOT was prescribed by a board-certified pulmonologist based on Veterans Health Administration clinical practice guidelines.<sup>14</sup> A licensed durable medical equipment company contracted by the JBVAMC delivered and established home oxygen equipment at each veteran’s residence. </p> <p>Pertinent patient demographics, clinical and physiologic variables, and hospitalizations with length of JBVAMC stay for each physician-diagnosed COPD exacerbation in the preceding year from the date last seen in the clinic were abstracted from EHRs. Overall hospital cost, defined as a veteran overnight stay in either the medical intensive care unit (MICU) or a general acute medicine bed in a US Department of Veterans Affairs (VA) facility, was calculated for each hospitalization for physician-diagnosed COPD exacerbation using VA Managerial Cost Accounting System National Cost Extracts for inpatient encounters.<sup>15</sup> We then contacted each veteran by telephone and asked whether they had experienced NCD and, if so, its weekly frequency ranging from once to nightly.</p> <h3>Data Analysis</h3> <p>Data were reported as mean (SD) where appropriate. The<i> t</i> test and Fisher exact test were used as indicated. <i>P</i> < .05 was considered statistically significant.<b> </b>The study protocol <hl name="10"/>was determined to be exempt by the JBVAMC Institutional Review Board (Protocol #1725748).</p> <h2>RESULTS</h2> <p>During the study period, <hl name="11"/><hl name="12"/>75 patients with hypoxemic CRF from COPD received LTOT and were followed at the JBVAMC. No patients were hospitalized outside the JBVAMC for COPD exacerbation during this time frame. We also found no documentation in the EHRs indicating that the clinicians managing these patients at the JBVAMC inquired about NCD during sleep.</p> <p>Of the 75 patients, 66 (88%) responded to the telephone survey and 22 patients (33%) reported weekly episodes of NCD while they slept (median, 4 dislodgments per week). (Table 1). Eight patients (36%) reported nightly NCDs (Figure). All 66 respondents were male and 14 of 22 in the NCD group as well as 21 of 44 in the no NCD group were Black veterans. The mean age was similar in both groups: 71 years in the NCD group and 72 years in the no NCD group. There were no statistically significant differences in demographics, including prevalence of obstructive sleep apnea (OSA), supplemental oxygen flow rate, and duration of LTOT, or in pulmonary function test results between patients who did and did not experience NCD while sleeping (Table 2). <br/><br/>Ten of 22 patients (45%) with NCD and 9 of 44 patients (20%) without NCD were hospitalized at the JBVAMC for ≥ 1 COPD exacerbation in the preceding year that was diagnosed by a physician (<i>P</i> = .045). Three of 22 patients (14%) with NCD and no patients in the no NCD group were admitted to the MICU. No patients required intubation and mechanical ventilation during hospitalization, and no patients died. Overall hospital costs were 25% ($64,342) higher in NCD group compared with the no NCD group and were attributed to the MICU admissions in the NCD group (Table 3). Nine veterans did not respond to repeated telephone calls. One physician-diagnosed COPD exacerbation requiring hospitalization was documented in the nonresponder group; the patient was hospitalized for 2 days. One veteran died before being contacted.</p> <h2>DISCUSSION</h2> <p>There are 3 new findings in this study. <hl name="13"/><hl name="14"/>First, health care practitioners at JBVAMC did not document the presence of NCD during sleep in patients with <hl name="15"/>hypoxemic CRF due to COPD and receiving LTOT. Second, one-third of these patients reported frequent NCD during sleep when interviewed. Third, the nocturnal events were associated with a higher hospitalization rate for physician-diagnosed COPD exacerbation and higher overall hospital costs. These findings are unlikely to be explained by differences in COPD severity and/or known triggers that lead to COPD exacerbation and require hospitalization because baseline physiologic and LTOT parameters were similar in both groups. Conceivably, patients with untreated OSA could be restless while asleep, leading to NCD. However, this explanation seems unlikely because the frequency of OSA was similar in both groups. </p> <p>Nocturnal arterial oxygen desaturation in patients with COPD without evidence of OSA may contribute to the frequency of exacerbations.<sup>16</sup> Although the mechanism(s) underlying this phenomenon is uncertain, we posit that prolonged nocturnal airway wall hypoxia could amplify underlying chronic inflammation through local generation of reactive oxygen species, thereby predisposing patients to exacerbations. Frequent COPD exacerbations promote disease progression and health status decline and are associated with increased mortality.<sup>11,13</sup> Moreover, hospitalization of patients with COPD is the largest contributor to the annual direct cost of COPD per patient.<sup>10,12</sup> The higher hospitalization rate observed in the NCD group in our study suggests that interruption of supplemental oxygen delivery while asleep may be a risk factor for COPD exacerbation. Alternatively, an independent factor or factors may have contributed to both NCD during sleep and COPD exacerbation in these patients or an impending exacerbation resulted in sleep disturbances that led to NCD. Additional research is warranted on veterans with hypoxemic CRF from COPD who are receiving LTOT and report frequent NCD during sleep that may support or refute these hypotheses.<br/><br/>To the best of our knowledge, NCD during sleep has not been previously reported in patients <hl name="16"/>with hypoxemic CRF due to COPD who are receiving LTOT at home or in an acute care setting.<sup>17-20</sup> Several layperson proposals to secure nasal cannulas to the face while sleeping are posted online. These include wearing a commercially available headband with 2 Velcro loops that fix the cannula tube, using fabric medical tape on both cheeks, and wearing a sleep mask. Conceivably, the efficacy and safety of these inexpensive interventions to mitigate NCD during sleep in patients receiving LTOT with hypoxemic CRF from COPD could be tested in clinical trials.</p> <h3>Limitations</h3> <p>This was a small, single-site study, comprised entirely of male patients who are predominantly Black veterans. The telephone interviews with veterans self-reporting NCD during their sleep are prone to recall bias. In addition, the validity and reproducibility of NCD during sleep were not addressed in this study. Missing data from 9 nonresponders may have introduced a nonresponse bias in data analysis and interpretation. The overall hospital cost for a COPD exacerbation at JBVAMC was derived from VA data; US Centers for Medicare & Medicaid Services or commercial carrier data may be different.<sup>15,21</sup> Lastly, access to LTOT for veterans with hypoxemic CRF from COPD is regulated and supervised at VA medical facilities.<sup>14</sup> This process may be different for patients outside the VA. Taken together, it is difficult to generalize our initial observations to non-VA patients with hypoxemic CRF from COPD who are receiving LTOT. We suggest a large, prospective study of veterans be conducted to determine the prevalence of NCD during sleep and its relationship with COPD exacerbations in veterans receiving LTOT with hypoxemic CRF due to COPD. </p> <h2>CONCLUSIONS</h2> <p><hl name="17"/>Clinicians at the JBVAMC did not document the presence of NCD during sleep in patients with hypoxemic CRF from COPD who received LTOT. However, self-reported, weekly nocturnal NCD episodes were associated with a higher hospitalization rate for COPD exacerbation and higher hospital costs. Accordingly, user-friendly devices to mitigate NCD during sleep should be developed.</p> <p class="isub">Acknowledgments</p> <p> <em>We thank Yolanda Davis, RRT, and George Adam for their assistance with this project. </em> </p> <p class="isub">Author affiliations</p> <p> <em><sup>a</sup>Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois<br/><br/><sup>b</sup>University of Illinois Chicago College of Pharmacy</em> </p> <p class="isub">Author roles</p> <p> <em>All authors were involved in the conception, study design, data acquisition, analysis, writing, and editing of the manuscript. </em> </p> <p class="isub">Disclosures</p> <p> <em>This material is the result of work supported with resources and the use of facilities at the Jesse Brown Veterans Affairs Medical Center. The authors report no actual or potential conflicts of interest or outside sources of funding with regard to this article.</em> </p> <p class="isub">Disclaimer</p> <p> <em>The opinions expressed herein are those of the authors and do not necessarily reflect those of <i>Federal Practitioner</i>, Frontline Medical Communications Inc., the US Government, or any of its agencies.</em> </p> <p class="isub">Ethics and consent</p> <p> <em>The study protocol was determined to be exempt by Jesse Brown Veterans Affairs Medical Center Institutional Review Board (Protocol #1725748).</em> </p> <h2><hl name="18"/>References</h2> <p class="reference"> 1. Boersma P, Cohen RA, Zelaya CE, Moy E. Multiple chronic conditions among veterans and nonveterans: United States, 2015-2018. <i>Natl Health Stat Report</i>. 2021;(153):1-13. doi:10.15620/cdc:101659<br/><br/> 2. Sharafkhaneh A, Petersen NJ, Yu H-J, Dalal AA, Johnson ML, Hanania NA. Burden of COPD in a government health care system: a retrospective observational study using data from the US Veterans Affairs population. <i>Int J Chron Obstruct Pulmon Dis</i>. 2010;5:125-132. doi:10.2147/copd.s8047<br/><br/> 3. LaBedz SL, Krishnan JA, Chung Y-C, et al. Chronic obstructive pulmonary disease outcomes at Veterans Affairs versus non-Veterans Affairs hospitals. <i>Chronic Obstr Pulm Dis</i>. 2021;8(3):306-313. doi:10.15326/jcopdf.2021.0201<br/><br/> 4. Darnell K, Dwivedi AK, Weng Z, Panos RJ. Disproportionate utilization of healthcare resources among veterans with COPD: a retrospective analysis of factors associated with COPD healthcare cost. <i>Cost Eff Resour Alloc</i>. 2013;11:13. doi:10.1186/1478-7547-11-13<br/><br/> 5. Bamonti PM, Robinson SA, Wan ES, Moy ML. Improving physiological, physical, and psychological health outcomes: a narrative review in US Veterans with COPD. <i>Int J Chron Obstruct Pulmon Dis</i>. 2022;17:1269-1283. doi:10.2147/COPD.S339323<br/><br/> 6. Cranston JM, Crockett AJ, Moss JR, Alpers JH. Domiciliary oxygen for chronic obstructive pulmonary disease. <i>Cochrane Database Syst Rev</i>. 2005;2005(4):CD001744. doi:10.1002/14651858.CD001744.pub2<br/><br/> 7. Lacasse Y, Tan AM, Maltais F, Krishnan JA. Home oxygen in chronic obstructive pulmonary disease. <i>Am J Respir Crit Care Med</i>. 2018;197(10):1254-1264. doi:10.1164/rccm.201802-0382CI<br/><br/> 8. Jacobs SS, Krishnan JA, Lederer DJ, et al. Home oxygen therapy for adults with chronic lung disease. An official American Thoracic Society Clinical Practice Guideline. <i>Am J Respir Crit Care Med</i>. 2020;202(10):e121-e141. doi:10.1164/rccm.202009-3608ST<br/><br/> 9. AARC. AARC clinical practice guideline. Oxygen therapy in the home or alternate site health care facility--2007 revision & update. <i>Respir Care</i>. 2007;52(8):1063-1068. <br/><br/>10. Foo J, Landis SH, Maskell J, et al. Continuing to confront COPD international patient survey: economic impact of COPD in 12 countries. <i>PLoS One.</i> 2016;11(4):e0152618. doi:10.1371/journal.pone.0152618<br/><br/>11. Rothnie KJ, Müllerová H, Smeeth L, Quint JK. Natural history of chronic obstructive pulmonary disease exacerbations in a general practice-based population with chronic obstructive pulmonary disease. <i>Am J Respir Crit Care Med</i>. 2018;198(4):464-471. doi:10.1164/rccm.201710-2029OC<br/><br/>12. Stanford RH, Engel-Nitz NM, Bancroft T, Essoi B. The identification and cost of acute chronic obstructive pulmonary disease exacerbations in a United States population healthcare claims database. <i>COPD</i>. 2020;17(5):499-508. doi:10.1080/15412555.2020.1817357<br/><br/>13. Hurst JR, Han MK, Singh B, et al. Prognostic risk factors for moderate-to-severe exacerbations in patients with chronic obstructive pulmonary disease: a systematic literature review. <i>Respir Res</i>. 2022;23(1):213. doi:10.1186/s12931-022-02123-5<br/><br/>14. US Department of Veterans Affairs, Veterans Health Administration. Home oxygen program. VHA Directive 1173.13(1). Published August 5, 2020. Accessed February 28, 2024. https://www.va.gov/vhapublications/ViewPublication.asp?pub_ID=8947<br/><br/>15. Phibbs CS, Barnett PG, Fan A, Harden C, King SS, Scott JY. Research guide to decision support system national cost extracts. Health Economics Resource Center of Health Service R&D Services, US Department of Veterans Affairs. September 2010. Accessed February 14, 2024. https://www.herc.research.va.gov/files/book_621.pdf<br/><br/>16. Agusti A, Hedner J, Marin JM, Barbé F, Cazzola M, Rennard S. Night-time symptoms: a forgotten dimension of COPD. <i>Eur Respir Rev</i>. 2011;20(121):183-194. doi:10.1183/09059180.00004311<br/><br/>17. Croxton TL, Bailey WC. Long-term oxygen treatment in chronic obstructive pulmonary disease: recommendations for future research: an NHLBI workshop report. <i>Am J Respir Crit Care Med</i>. 2006;174(4):373-378. doi:10.1164/rccm.200507-1161WS<br/><br/>18. Melani AS, Sestini P, Rottoli P. Home oxygen therapy: re-thinking the role of devices. <i>Expert Rev Clin Pharmacol</i>. 2018;11(3):279-289. doi:10.1080/17512433.2018.1421457<br/><br/>19. Sculley JA, Corbridge SJ, Prieto-Centurion V, et al. Home oxygen therapy for patients with COPD: time for a reboot. <i>Respir Care</i>. 2019;64(12):1574-1585. doi:10.4187/respcare.07135<br/><br/>20. Jacobs SS, Lindell KO, Collins EG, et al. Patient perceptions of the adequacy of supplemental oxygen therapy. Results of the American Thoracic Society Nursing Assembly Oxygen Working Group Survey. <i>Ann Am Thorac Soc</i>. 2018;15:24-32. doi:10.1513/AnnalsATS.201703-209OC<br/><br/>21. US Centers for Medicare & Medicaid Services. Home use of oxygen. Publication number 100-3. January 3, 2023. Accessed February 14, 2024. https://www.cms.gov/medicare-coverage-database/view/ncd.aspx?NCDId=169</p> </itemContent> </newsItem> </itemSet></root>
Diagnosis of Indolent Clonorchis sinensis and Opisthorchis viverrini Infections as Risk Factors for Cholangiocarcinoma: An Unmet Medical Need
Cholangiocarcinoma is a heterogeneous, highly aggressive cancer of the biliary tract epithelium with an overall 5-year relative survival rate of only 9%.1,2 Although surgical resection of localized, intrahepatic cholangiocarcinoma is associated with improved overall survival, most patients present with advanced disease not amenable to surgery due to a late onset of symptoms.2 Recently, an increased incidence of cholangiocarcinoma has been reported in the United States.3 Although relatively rare in the US, cholangiocarcinoma is prevalent across large parts of Asia, including China, Vietnam, Thailand, South Korea, and Taiwan.2
Risk Factors
To date, risk factors for developing cholangiocarcinoma have not been elucidated. 4,5 However, a growing body of literature suggests that chronic infection of genetically susceptible human subjects with Clonorchis sinensis ( C sinensis ) and Opisthorchis viverrini ( O viverrini ) plays a role. 6,7 The life cycle of these food-borne zoonotic trematodes involves eggs discharged in the stool of infected humans, the definitive host. 6,7 In nature, these eggs are ingested by freshwater snails, the intermediate host, where they undergo several developmental stages to form cercariae. Once released from snails into the water, free-swimming cercariae come in contact and penetrate freshwater fish where they encyst as metacercariae. Infection of humans occurs by ingesting undercooked, salted, pickled, or smoked freshwater fish infested with metacercariae. After ingestion, metacercariae excyst in the duodenum and ascend the biliary tract through the ampulla of Vater. They then mature into adult flukes that reside in small- and medium-sized intrahepatic biliary ducts. 6,7
Although most infected people remain asymptomatic, untreated indolent infections with C sinensis and O viverrini may persist in peripheral intrahepatic bile ducts for as long as 30 years, which is the lifespan of the trematodes.6,7 During this prolonged period, C sinensis and O viverrini feeding activities and their excretory-secretory products may damage bile duct epithelium and promote intense local inflammation.6,7 Conceivably, these pathological processes could then provoke the epithelial desquamation, adenomatous hyperplasia, goblet cell metaplasia, periductal fibrosis, and granuloma formation that are conducive to initiation and progression of cholangiocarcinoma in genetically susceptible people.8 Accordingly, the International Agency for Research on Cancer (IARC) has determined that there is sufficient evidence for the carcinogenicity of chronic infections with C sinensis and O viverrini in humans and that chronic infections with these trematodes cause cholangiocarcinoma.9 The IARC concluded that chronic infections with C sinensis and O viverrini are carcinogenic to humans (Group 1).9
Diagnosis
Presently, the diagnosis of C sinensis and O viverrini infection is based on microscopic identification and enumeration of the parasites’ eggs in weighted stool specimens using a formalin-ethyl acetate sedimentation concentration technique. 6,7 This approach requires a labor-intensive test that is conducted by an experienced technician. The test has low specificity and sensitivity because eggs could be confused with those of nonpathogenic intestinal flukes that are morphologically similar and because eggs are not present in feces during all stages of the infection. Although diffuse dilatation of intrahepatic bile ducts by screening sonography is used to diagnose clonorchiasis in endemic areas, it has low sensitivity, particularly in patients with low-level C sinensis and O viverrin i infections. 10
To address the current diagnostic gap, several enzyme-linked immunosorbent assays (ELISA) have been developed for the diagnosis of C sinensis, including monoclonal antibody-based (mAb) ELISA and indirect antibody ELISA.11,12 However, both have important limitations. The mAb ELISA detects only active infections while indirect antibody ELISA cross-reacts with other liver flukes.11,12 Taken together, these data illustrate the difficulties in diagnosing asymptomatic individuals with low-burden C sinensis or O viverrini infections by existing laboratory methods.
Timely serodiagnosis of indolent C sinensis and O viverrini infections is important because these parasites have recently been raised as a risk factor for cholangiocarcinoma in veterans who served in Vietnam.13 The American War Library estimates that as of February 28, 2019, about 610,000 Americans who served on land in Vietnam or in the air over Vietnam between 1954 and 1975 are alive, and about 164,000 Americans who served at sea in Vietnam waters are alive.14 To that end, Psevdos and colleagues screened 97 US veterans who served in Vietnam and identified 50 who reported exposure to raw or undercooked fish while there.13 None had evidence of active C sinensis or O viverrini infection. Blood samples obtained from these veterans were analyzed for circulating C sinensis and O viverrini antibodies using an ELISA developed in South Korea and 12 blood samples tested positive for the trematodes. Imaging of extrahepatic and intrahepatic bile ducts was unyielding in all cases. One veteran diagnosed with cholangiocarcinoma had repeated negative tests. However, the results of this study were challenged by several experts in this field because the authors did not report the sensitivity and specificity of the ELISA assay used.15
Serologic testing of US veterans who served in C sinensis and O viverrini–endemic countries for indolent infections with these parasites is not recommended at present.15 Nevertheless, there is an urgent need to develop sensitive and specific serologic assays, such as ELISA tests with recombinant antigens, to detect both acute and indolent infections caused by each biliary liver fluke in the US, including in patients diagnosed with cholangiocarcinoma. We posit that testing and treatment of high-risk populations could lead to earlier detection and treatment of cholangiocarcinoma, leading to improved overall survival in the population at risk.
1. American Cancer Society. Survival rates for bile duct cancer. Updated March 1, 2023. Accessed March 17, 2023. https://www.cancer.org/cancer/bile-duct-cancer/detection-diagnosis-staging/survival-by-stage.html
2. Vij M, Puri Y, Rammohan A, et al. Pathological, molecular, and clinical characteristics of cholangiocarcinoma: A comprehensive review. World J Gastrointest Oncol. 2022;14(3):607-627. doi:10.4251/wjgo.v14.i3.607
3. Yao KJ, Jabbour S, Parekh N, Lin Y, Moss RA. Increasing mortality in the United States from cholangiocarcinoma: an analysis of the National Center for Health Statistics Database. BMC Gastroenterol. 2016;16(1):117. Published 2016 Sep 21. doi:10.1186/s12876-016-0527-z
4. Rustagi T, Dasanu CA. Risk factors for gallbladder cancer and cholangiocarcinoma: similarities, differences and updates. J Gastrointest Cancer. 2012;43(2):137-147. doi:10.1007/s12029-011-9284-y
5. Maemura K, Natsugoe S, Takao S. Molecular mechanism of cholangiocarcinoma carcinogenesis. J Hepatobiliary Pancreat Sci. 2014;21(10):754-760. doi:10.1002/jhbp.126
6. Steele JA, Richter CH, Echaubard P, et al. Thinking beyond Opisthorchis viverrini for risk of cholangiocarcinoma in the lower Mekong region: a systematic review and meta-analysis. Infect Dis Poverty. 2018;7(1):44. Published 2018 May 17. doi:10.1186/s40249-018-0434-3.
7. Kim TS, Pak JH, Kim JB, Bahk YY. Clonorchis sinensis, an oriental liver fluke, as a human biological agent of cholangiocarcinoma: a brief review. BMB Rep. 2016;49(11):590-597. doi:10.5483/bmbrep.2016.49.11.109
8. Murata M. Inflammation and cancer. Environ Health Prev Med. 2018;23(1):50. Published 2018 Oct 20. doi:10.1186/s12199-018-0740-1
9. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Biological agents. IARC Monogr Eval Carcinog Risks Hum. 2012;100(pt B):1-441.
10. Mairiang E, Laha T, Bethony JM, et al. Ultrasonography assessment of hepatobiliary abnormalities in 3359 subjects with Opisthorchis viverrini infection in endemic areas of Thailand. Parasitol Int. 2012;61(1):208-211. doi:10.1016/j.parint.2011.07.009
11. Li HM, Qian MB, Yang YC, et al. Performance evaluation of existing immunoassays for Clonorchis sinensis infection in China. Parasit Vectors. 2018;11(1):35. Published 2018 Jan 15. doi:10.1186/s13071-018-2612-3
12. Hughes T, O’Connor T, Techasen A, et al. Opisthorchiasis and cholangiocarcinoma in Southeast Asia: an unresolved problem. Int J Gen Med. 2017;10:227-237. Published 2017 Aug 10. doi:10.2147/IJGM.S133292
13. Psevdos G, Ford FM, Hong ST. Screening US Vietnam veterans for liver fluke exposure 5 decades after the end of the war. Infect Dis Clin Pract (Baltim Md). 2018;26(4):208-210. doi:10.1097/IPC.0000000000000611
14. American War Library. In harm’s way... How many real Vietnam vets are alive today? Updated February 28, 2019. Accessed March 17, 2023. https://www.americanwarlibrary.com/personnel/vietvet.htm
15. Nash TE, Sullivan D, Mitre E, et al. Comments on “Screening US Vietnam veterans for liver fluke exposure 5 decades after the end of the war”. Infect Dis Clin Pract (Baltim Md). 2018;26(4):240-241. doi:10.1097/IPC.0000000000000659
Cholangiocarcinoma is a heterogeneous, highly aggressive cancer of the biliary tract epithelium with an overall 5-year relative survival rate of only 9%.1,2 Although surgical resection of localized, intrahepatic cholangiocarcinoma is associated with improved overall survival, most patients present with advanced disease not amenable to surgery due to a late onset of symptoms.2 Recently, an increased incidence of cholangiocarcinoma has been reported in the United States.3 Although relatively rare in the US, cholangiocarcinoma is prevalent across large parts of Asia, including China, Vietnam, Thailand, South Korea, and Taiwan.2
Risk Factors
To date, risk factors for developing cholangiocarcinoma have not been elucidated. 4,5 However, a growing body of literature suggests that chronic infection of genetically susceptible human subjects with Clonorchis sinensis ( C sinensis ) and Opisthorchis viverrini ( O viverrini ) plays a role. 6,7 The life cycle of these food-borne zoonotic trematodes involves eggs discharged in the stool of infected humans, the definitive host. 6,7 In nature, these eggs are ingested by freshwater snails, the intermediate host, where they undergo several developmental stages to form cercariae. Once released from snails into the water, free-swimming cercariae come in contact and penetrate freshwater fish where they encyst as metacercariae. Infection of humans occurs by ingesting undercooked, salted, pickled, or smoked freshwater fish infested with metacercariae. After ingestion, metacercariae excyst in the duodenum and ascend the biliary tract through the ampulla of Vater. They then mature into adult flukes that reside in small- and medium-sized intrahepatic biliary ducts. 6,7
Although most infected people remain asymptomatic, untreated indolent infections with C sinensis and O viverrini may persist in peripheral intrahepatic bile ducts for as long as 30 years, which is the lifespan of the trematodes.6,7 During this prolonged period, C sinensis and O viverrini feeding activities and their excretory-secretory products may damage bile duct epithelium and promote intense local inflammation.6,7 Conceivably, these pathological processes could then provoke the epithelial desquamation, adenomatous hyperplasia, goblet cell metaplasia, periductal fibrosis, and granuloma formation that are conducive to initiation and progression of cholangiocarcinoma in genetically susceptible people.8 Accordingly, the International Agency for Research on Cancer (IARC) has determined that there is sufficient evidence for the carcinogenicity of chronic infections with C sinensis and O viverrini in humans and that chronic infections with these trematodes cause cholangiocarcinoma.9 The IARC concluded that chronic infections with C sinensis and O viverrini are carcinogenic to humans (Group 1).9
Diagnosis
Presently, the diagnosis of C sinensis and O viverrini infection is based on microscopic identification and enumeration of the parasites’ eggs in weighted stool specimens using a formalin-ethyl acetate sedimentation concentration technique. 6,7 This approach requires a labor-intensive test that is conducted by an experienced technician. The test has low specificity and sensitivity because eggs could be confused with those of nonpathogenic intestinal flukes that are morphologically similar and because eggs are not present in feces during all stages of the infection. Although diffuse dilatation of intrahepatic bile ducts by screening sonography is used to diagnose clonorchiasis in endemic areas, it has low sensitivity, particularly in patients with low-level C sinensis and O viverrin i infections. 10
To address the current diagnostic gap, several enzyme-linked immunosorbent assays (ELISA) have been developed for the diagnosis of C sinensis, including monoclonal antibody-based (mAb) ELISA and indirect antibody ELISA.11,12 However, both have important limitations. The mAb ELISA detects only active infections while indirect antibody ELISA cross-reacts with other liver flukes.11,12 Taken together, these data illustrate the difficulties in diagnosing asymptomatic individuals with low-burden C sinensis or O viverrini infections by existing laboratory methods.
Timely serodiagnosis of indolent C sinensis and O viverrini infections is important because these parasites have recently been raised as a risk factor for cholangiocarcinoma in veterans who served in Vietnam.13 The American War Library estimates that as of February 28, 2019, about 610,000 Americans who served on land in Vietnam or in the air over Vietnam between 1954 and 1975 are alive, and about 164,000 Americans who served at sea in Vietnam waters are alive.14 To that end, Psevdos and colleagues screened 97 US veterans who served in Vietnam and identified 50 who reported exposure to raw or undercooked fish while there.13 None had evidence of active C sinensis or O viverrini infection. Blood samples obtained from these veterans were analyzed for circulating C sinensis and O viverrini antibodies using an ELISA developed in South Korea and 12 blood samples tested positive for the trematodes. Imaging of extrahepatic and intrahepatic bile ducts was unyielding in all cases. One veteran diagnosed with cholangiocarcinoma had repeated negative tests. However, the results of this study were challenged by several experts in this field because the authors did not report the sensitivity and specificity of the ELISA assay used.15
Serologic testing of US veterans who served in C sinensis and O viverrini–endemic countries for indolent infections with these parasites is not recommended at present.15 Nevertheless, there is an urgent need to develop sensitive and specific serologic assays, such as ELISA tests with recombinant antigens, to detect both acute and indolent infections caused by each biliary liver fluke in the US, including in patients diagnosed with cholangiocarcinoma. We posit that testing and treatment of high-risk populations could lead to earlier detection and treatment of cholangiocarcinoma, leading to improved overall survival in the population at risk.
Cholangiocarcinoma is a heterogeneous, highly aggressive cancer of the biliary tract epithelium with an overall 5-year relative survival rate of only 9%.1,2 Although surgical resection of localized, intrahepatic cholangiocarcinoma is associated with improved overall survival, most patients present with advanced disease not amenable to surgery due to a late onset of symptoms.2 Recently, an increased incidence of cholangiocarcinoma has been reported in the United States.3 Although relatively rare in the US, cholangiocarcinoma is prevalent across large parts of Asia, including China, Vietnam, Thailand, South Korea, and Taiwan.2
Risk Factors
To date, risk factors for developing cholangiocarcinoma have not been elucidated. 4,5 However, a growing body of literature suggests that chronic infection of genetically susceptible human subjects with Clonorchis sinensis ( C sinensis ) and Opisthorchis viverrini ( O viverrini ) plays a role. 6,7 The life cycle of these food-borne zoonotic trematodes involves eggs discharged in the stool of infected humans, the definitive host. 6,7 In nature, these eggs are ingested by freshwater snails, the intermediate host, where they undergo several developmental stages to form cercariae. Once released from snails into the water, free-swimming cercariae come in contact and penetrate freshwater fish where they encyst as metacercariae. Infection of humans occurs by ingesting undercooked, salted, pickled, or smoked freshwater fish infested with metacercariae. After ingestion, metacercariae excyst in the duodenum and ascend the biliary tract through the ampulla of Vater. They then mature into adult flukes that reside in small- and medium-sized intrahepatic biliary ducts. 6,7
Although most infected people remain asymptomatic, untreated indolent infections with C sinensis and O viverrini may persist in peripheral intrahepatic bile ducts for as long as 30 years, which is the lifespan of the trematodes.6,7 During this prolonged period, C sinensis and O viverrini feeding activities and their excretory-secretory products may damage bile duct epithelium and promote intense local inflammation.6,7 Conceivably, these pathological processes could then provoke the epithelial desquamation, adenomatous hyperplasia, goblet cell metaplasia, periductal fibrosis, and granuloma formation that are conducive to initiation and progression of cholangiocarcinoma in genetically susceptible people.8 Accordingly, the International Agency for Research on Cancer (IARC) has determined that there is sufficient evidence for the carcinogenicity of chronic infections with C sinensis and O viverrini in humans and that chronic infections with these trematodes cause cholangiocarcinoma.9 The IARC concluded that chronic infections with C sinensis and O viverrini are carcinogenic to humans (Group 1).9
Diagnosis
Presently, the diagnosis of C sinensis and O viverrini infection is based on microscopic identification and enumeration of the parasites’ eggs in weighted stool specimens using a formalin-ethyl acetate sedimentation concentration technique. 6,7 This approach requires a labor-intensive test that is conducted by an experienced technician. The test has low specificity and sensitivity because eggs could be confused with those of nonpathogenic intestinal flukes that are morphologically similar and because eggs are not present in feces during all stages of the infection. Although diffuse dilatation of intrahepatic bile ducts by screening sonography is used to diagnose clonorchiasis in endemic areas, it has low sensitivity, particularly in patients with low-level C sinensis and O viverrin i infections. 10
To address the current diagnostic gap, several enzyme-linked immunosorbent assays (ELISA) have been developed for the diagnosis of C sinensis, including monoclonal antibody-based (mAb) ELISA and indirect antibody ELISA.11,12 However, both have important limitations. The mAb ELISA detects only active infections while indirect antibody ELISA cross-reacts with other liver flukes.11,12 Taken together, these data illustrate the difficulties in diagnosing asymptomatic individuals with low-burden C sinensis or O viverrini infections by existing laboratory methods.
Timely serodiagnosis of indolent C sinensis and O viverrini infections is important because these parasites have recently been raised as a risk factor for cholangiocarcinoma in veterans who served in Vietnam.13 The American War Library estimates that as of February 28, 2019, about 610,000 Americans who served on land in Vietnam or in the air over Vietnam between 1954 and 1975 are alive, and about 164,000 Americans who served at sea in Vietnam waters are alive.14 To that end, Psevdos and colleagues screened 97 US veterans who served in Vietnam and identified 50 who reported exposure to raw or undercooked fish while there.13 None had evidence of active C sinensis or O viverrini infection. Blood samples obtained from these veterans were analyzed for circulating C sinensis and O viverrini antibodies using an ELISA developed in South Korea and 12 blood samples tested positive for the trematodes. Imaging of extrahepatic and intrahepatic bile ducts was unyielding in all cases. One veteran diagnosed with cholangiocarcinoma had repeated negative tests. However, the results of this study were challenged by several experts in this field because the authors did not report the sensitivity and specificity of the ELISA assay used.15
Serologic testing of US veterans who served in C sinensis and O viverrini–endemic countries for indolent infections with these parasites is not recommended at present.15 Nevertheless, there is an urgent need to develop sensitive and specific serologic assays, such as ELISA tests with recombinant antigens, to detect both acute and indolent infections caused by each biliary liver fluke in the US, including in patients diagnosed with cholangiocarcinoma. We posit that testing and treatment of high-risk populations could lead to earlier detection and treatment of cholangiocarcinoma, leading to improved overall survival in the population at risk.
1. American Cancer Society. Survival rates for bile duct cancer. Updated March 1, 2023. Accessed March 17, 2023. https://www.cancer.org/cancer/bile-duct-cancer/detection-diagnosis-staging/survival-by-stage.html
2. Vij M, Puri Y, Rammohan A, et al. Pathological, molecular, and clinical characteristics of cholangiocarcinoma: A comprehensive review. World J Gastrointest Oncol. 2022;14(3):607-627. doi:10.4251/wjgo.v14.i3.607
3. Yao KJ, Jabbour S, Parekh N, Lin Y, Moss RA. Increasing mortality in the United States from cholangiocarcinoma: an analysis of the National Center for Health Statistics Database. BMC Gastroenterol. 2016;16(1):117. Published 2016 Sep 21. doi:10.1186/s12876-016-0527-z
4. Rustagi T, Dasanu CA. Risk factors for gallbladder cancer and cholangiocarcinoma: similarities, differences and updates. J Gastrointest Cancer. 2012;43(2):137-147. doi:10.1007/s12029-011-9284-y
5. Maemura K, Natsugoe S, Takao S. Molecular mechanism of cholangiocarcinoma carcinogenesis. J Hepatobiliary Pancreat Sci. 2014;21(10):754-760. doi:10.1002/jhbp.126
6. Steele JA, Richter CH, Echaubard P, et al. Thinking beyond Opisthorchis viverrini for risk of cholangiocarcinoma in the lower Mekong region: a systematic review and meta-analysis. Infect Dis Poverty. 2018;7(1):44. Published 2018 May 17. doi:10.1186/s40249-018-0434-3.
7. Kim TS, Pak JH, Kim JB, Bahk YY. Clonorchis sinensis, an oriental liver fluke, as a human biological agent of cholangiocarcinoma: a brief review. BMB Rep. 2016;49(11):590-597. doi:10.5483/bmbrep.2016.49.11.109
8. Murata M. Inflammation and cancer. Environ Health Prev Med. 2018;23(1):50. Published 2018 Oct 20. doi:10.1186/s12199-018-0740-1
9. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Biological agents. IARC Monogr Eval Carcinog Risks Hum. 2012;100(pt B):1-441.
10. Mairiang E, Laha T, Bethony JM, et al. Ultrasonography assessment of hepatobiliary abnormalities in 3359 subjects with Opisthorchis viverrini infection in endemic areas of Thailand. Parasitol Int. 2012;61(1):208-211. doi:10.1016/j.parint.2011.07.009
11. Li HM, Qian MB, Yang YC, et al. Performance evaluation of existing immunoassays for Clonorchis sinensis infection in China. Parasit Vectors. 2018;11(1):35. Published 2018 Jan 15. doi:10.1186/s13071-018-2612-3
12. Hughes T, O’Connor T, Techasen A, et al. Opisthorchiasis and cholangiocarcinoma in Southeast Asia: an unresolved problem. Int J Gen Med. 2017;10:227-237. Published 2017 Aug 10. doi:10.2147/IJGM.S133292
13. Psevdos G, Ford FM, Hong ST. Screening US Vietnam veterans for liver fluke exposure 5 decades after the end of the war. Infect Dis Clin Pract (Baltim Md). 2018;26(4):208-210. doi:10.1097/IPC.0000000000000611
14. American War Library. In harm’s way... How many real Vietnam vets are alive today? Updated February 28, 2019. Accessed March 17, 2023. https://www.americanwarlibrary.com/personnel/vietvet.htm
15. Nash TE, Sullivan D, Mitre E, et al. Comments on “Screening US Vietnam veterans for liver fluke exposure 5 decades after the end of the war”. Infect Dis Clin Pract (Baltim Md). 2018;26(4):240-241. doi:10.1097/IPC.0000000000000659
1. American Cancer Society. Survival rates for bile duct cancer. Updated March 1, 2023. Accessed March 17, 2023. https://www.cancer.org/cancer/bile-duct-cancer/detection-diagnosis-staging/survival-by-stage.html
2. Vij M, Puri Y, Rammohan A, et al. Pathological, molecular, and clinical characteristics of cholangiocarcinoma: A comprehensive review. World J Gastrointest Oncol. 2022;14(3):607-627. doi:10.4251/wjgo.v14.i3.607
3. Yao KJ, Jabbour S, Parekh N, Lin Y, Moss RA. Increasing mortality in the United States from cholangiocarcinoma: an analysis of the National Center for Health Statistics Database. BMC Gastroenterol. 2016;16(1):117. Published 2016 Sep 21. doi:10.1186/s12876-016-0527-z
4. Rustagi T, Dasanu CA. Risk factors for gallbladder cancer and cholangiocarcinoma: similarities, differences and updates. J Gastrointest Cancer. 2012;43(2):137-147. doi:10.1007/s12029-011-9284-y
5. Maemura K, Natsugoe S, Takao S. Molecular mechanism of cholangiocarcinoma carcinogenesis. J Hepatobiliary Pancreat Sci. 2014;21(10):754-760. doi:10.1002/jhbp.126
6. Steele JA, Richter CH, Echaubard P, et al. Thinking beyond Opisthorchis viverrini for risk of cholangiocarcinoma in the lower Mekong region: a systematic review and meta-analysis. Infect Dis Poverty. 2018;7(1):44. Published 2018 May 17. doi:10.1186/s40249-018-0434-3.
7. Kim TS, Pak JH, Kim JB, Bahk YY. Clonorchis sinensis, an oriental liver fluke, as a human biological agent of cholangiocarcinoma: a brief review. BMB Rep. 2016;49(11):590-597. doi:10.5483/bmbrep.2016.49.11.109
8. Murata M. Inflammation and cancer. Environ Health Prev Med. 2018;23(1):50. Published 2018 Oct 20. doi:10.1186/s12199-018-0740-1
9. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Biological agents. IARC Monogr Eval Carcinog Risks Hum. 2012;100(pt B):1-441.
10. Mairiang E, Laha T, Bethony JM, et al. Ultrasonography assessment of hepatobiliary abnormalities in 3359 subjects with Opisthorchis viverrini infection in endemic areas of Thailand. Parasitol Int. 2012;61(1):208-211. doi:10.1016/j.parint.2011.07.009
11. Li HM, Qian MB, Yang YC, et al. Performance evaluation of existing immunoassays for Clonorchis sinensis infection in China. Parasit Vectors. 2018;11(1):35. Published 2018 Jan 15. doi:10.1186/s13071-018-2612-3
12. Hughes T, O’Connor T, Techasen A, et al. Opisthorchiasis and cholangiocarcinoma in Southeast Asia: an unresolved problem. Int J Gen Med. 2017;10:227-237. Published 2017 Aug 10. doi:10.2147/IJGM.S133292
13. Psevdos G, Ford FM, Hong ST. Screening US Vietnam veterans for liver fluke exposure 5 decades after the end of the war. Infect Dis Clin Pract (Baltim Md). 2018;26(4):208-210. doi:10.1097/IPC.0000000000000611
14. American War Library. In harm’s way... How many real Vietnam vets are alive today? Updated February 28, 2019. Accessed March 17, 2023. https://www.americanwarlibrary.com/personnel/vietvet.htm
15. Nash TE, Sullivan D, Mitre E, et al. Comments on “Screening US Vietnam veterans for liver fluke exposure 5 decades after the end of the war”. Infect Dis Clin Pract (Baltim Md). 2018;26(4):240-241. doi:10.1097/IPC.0000000000000659
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>0523 FED AVAHO Cholangio</fileName> <TBEID>0C02CB16.SIG</TBEID> <TBUniqueIdentifier>NJ_0C02CB16</TBUniqueIdentifier> <newsOrJournal>Journal</newsOrJournal> <publisherName>Frontline Medical Communications Inc.</publisherName> <storyname/> <articleType>1</articleType> <TBLocation>Copyfitting-FED</TBLocation> <QCDate/> <firstPublished>20230509T163432</firstPublished> <LastPublished>20230509T163432</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20230509T163431</CMSDate> <articleSource/> <facebookInfo/> <meetingNumber/> <byline/> <bylineText>Jesica A. Herrick, MD, MSa,b; Israel Rubinstein, MDa,b</bylineText> <bylineFull/> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType/> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:"> <name/> <rightsInfo> <copyrightHolder> <name/> </copyrightHolder> <copyrightNotice/> </rightsInfo> </provider> <abstract/> <metaDescription>Cholangiocarcinoma is a heterogeneous, highly aggressive cancer of the biliary tract epithelium with an overall 5-year relative survival rate of only 9%.1,2 Alt</metaDescription> <articlePDF/> <teaserImage/> <title>Diagnosis of Indolent Clonorchis sinensis and Opisthorchis viverrini Infections as Risk Factors for Cholangiocarcinoma: An Unmet Medical Need</title> <deck/> <eyebrow>Commentary</eyebrow> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear>2023</pubPubdateYear> <pubPubdateMonth>May</pubPubdateMonth> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>fed</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">16</term> </publications> <sections> <term canonical="true">52</term> </sections> <topics> <term canonical="true">263</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Diagnosis of Indolent Clonorchis sinensis and Opisthorchis viverrini Infections as Risk Factors for Cholangiocarcinoma: An Unmet Medical Need</title> <deck/> </itemMeta> <itemContent> <p class="abstract"><b>Background:</b> Cholangiocarcinoma is a highly aggressive cancer of the biliary tract epithelium. This form of cancer is prevalent in Asia, and recent reports show that its incidence is relatively rare but increasing in the United States. Although risk factors for cholangiocarcinoma have yet to be elucidated, a growing body of literature suggests chronic infection of genetically susceptible individuals with the food-borne zoonotic trematodes<i> Clonorchis sinensis </i>(<i>C sinensis</i>)<i> </i>and <i>Opisthorchis viverrini </i>(<i>O viverrini</i>) may play a role.<br/><br/><b>Observations:</b> Although most infected people remain asymptomatic, untreated indolent infections with <i>C sinensis </i>and <i>O viverrini</i> may persist in peripheral intrahepatic bile ducts for almost 30 years. During this period, the trematodes’ feeding activities and their excretory-secretory products may damage the bile duct epithelium and promote local inflammation. These pathological processes could then provoke epithelial desquamation, adenomatous hyperplasia, goblet cell metaplasia, periductal fibrosis, and granuloma formation that are conducive to the initiation and progression of cholangiocarcinoma in genetically susceptible people. The International Agency for Research on Cancer has determined that there is sufficient evidence in humans for the carcinogenicity of chronic infections with <i>C sinensis </i>and <i>O viverrini</i>.<br/><br/><b>Conclusions:</b> Timely serodiagnosis of indolent <i>C sinensis </i>and <i>O viverrini</i> infections is important as these parasites may be a risk factor for cholangiocarcinoma in veterans who served in Vietnam. About 774,000 living Americans served in Vietnam and there is an urgent need to develop sensitive and specific serologic assays to detect both acute and indolent infections. We posit that testing and treatment of high-risk populations could lead to earlier detection and treatment of cholangiocarcinoma, leading to improved overall survival. </p> <p><span class="Drop">C</span>holangiocarcinoma is a heterogeneous, highly aggressive cancer of the biliary tract epithelium with an overall 5-year relative survival rate of only 9%.<sup>1,2</sup> Although surgical resection of localized, intrahepatic cholangiocarcinoma is associated with improved overall survival, most patients present with advanced disease not amenable to surgery due to a late onset of symptoms.<sup>2</sup> Recently, an increased incidence of cholangiocarcinoma has been reported in the United States.<sup>3</sup> Although relatively rare in the US, cholangiocarcinoma is prevalent across large parts of Asia, including China, Vietnam, Thailand, South Korea, and Taiwan.<sup>2</sup> </p> <h2>Risk Factors</h2> <p> To date, risk factors for developing cholangiocarcinoma have not been elucidated. <sup>4,5</sup> However, a growing body of literature suggests that chronic infection of genetically susceptible human subjects with <i>Clonorchis sinensis </i> ( <i>C sinensis</i> ) and <i>Opisthorchis viverrini</i> ( <i>O viverrini</i> ) plays a role. <sup>6,7</sup> The life cycle of these food-borne zoonotic trematodes involves eggs discharged in the stool of infected humans, the definitive host. <sup>6,7</sup> In nature, these eggs are ingested by freshwater snails, the intermediate host, where they undergo several developmental stages to form cercariae. Once released from snails into the water, free-swimming cercariae come in contact and penetrate freshwater fish where they encyst as metacercariae. Infection of humans occurs by ingesting undercooked, salted, pickled, or smoked freshwater fish infested with metacercariae. After ingestion, metacercariae excyst in the duodenum and ascend the biliary tract through the ampulla of Vater. They then mature into adult flukes that reside in small- and medium-sized intrahepatic biliary ducts. <sup>6,7 </sup> </p> <p>Although most infected people remain asymptomatic, untreated indolent infections with <i>C sinensis</i> and <i>O viverrini</i> may persist in peripheral intrahepatic bile ducts for as long as 30 years, which is the lifespan of the trematodes.<sup>6,7</sup> During this prolonged period, <i>C sinensis </i>and <i>O viverrini</i> feeding activities and their excretory-secretory products may damage bile duct epithelium and promote intense local inflammation.<sup>6,7</sup> Conceivably, these pathological processes could then provoke the epithelial desquamation, adenomatous hyperplasia, goblet cell metaplasia, periductal fibrosis, and granuloma formation that are conducive to initiation and progression of cholangiocarcinoma in genetically susceptible people.<sup>8</sup> Accordingly, the International Agency for Research on Cancer (IARC) has determined that there is sufficient evidence for the carcinogenicity of chronic infections with <i>C sinensis </i>and <i>O viverrini</i> in humans and that chronic infections with these trematodes cause cholangiocarcinoma.<sup>9</sup> The IARC concluded that chronic infections with <i>C sinensis</i> and <i>O viverrini </i>are carcinogenic to humans (Group 1).<sup>9</sup></p> <h2>Diagnosis</h2> <p> Presently, the diagnosis of <i>C sinensis</i> and <i>O viverrini</i> infection is based on microscopic identification and enumeration of the parasites’ eggs in weighted stool specimens using a formalin-ethyl acetate sedimentation concentration technique. <sup> 6,7 </sup> This approach requires a labor-intensive test that is conducted by an experienced technician. The test has low specificity and sensitivity because eggs could be confused with those of nonpathogenic intestinal flukes that are morphologically similar and because eggs are not present in feces during all stages of the infection. Although diffuse dilatation of intrahepatic bile ducts by screening sonography is used to diagnose clonorchiasis in endemic areas, it has low sensitivity, particularly in patients with low-level <i>C sinensis</i> and <i>O viverrin</i> i infections. <sup> 10 </sup> </p> <p>To address the current diagnostic gap, several enzyme-linked immunosorbent assays (ELISA) have been developed for the diagnosis of <i>C sinensis</i>, including monoclonal antibody-based (mAb) ELISA and indirect antibody ELISA.<sup>11,12</sup> However, both have important limitations. The mAb ELISA detects only active infections while indirect antibody ELISA cross-reacts with other liver flukes.<sup>11,12</sup> Taken together, these data illustrate the difficulties in diagnosing asymptomatic individuals with low-burden <i>C sinensis</i> or <i>O viverrini</i> infections by existing laboratory methods.<br/><br/>Timely serodiagnosis of indolent <i>C sinensis</i><i> </i>and <i>O viverrini</i> infections is important because these parasites have recently been raised as a risk factor for cholangiocarcinoma in veterans who served in Vietnam.<sup>13</sup> The American War Library estimates that as of February 28, 2019, about 610,000 Americans who served on land in Vietnam or in the air over Vietnam between 1954 and 1975 are alive, and about 164,000 Americans who served at sea in Vietnam waters are alive.<sup>14</sup> To that end, Psevdos and colleagues screened 97 US veterans who served in Vietnam and identified 50 who reported exposure to raw or undercooked fish while there.<sup>13</sup> None had evidence of active <i>C sinensis</i> or <i>O viverrini</i> infection. Blood samples obtained from these veterans were analyzed for circulating <i>C sinensis</i> and <i>O viverrini</i> antibodies using an ELISA developed in South Korea and 12 blood samples tested positive for the trematodes. Imaging of extrahepatic and intrahepatic bile ducts was unyielding in all cases. One veteran diagnosed with cholangiocarcinoma had repeated negative tests. However, the results of this study were challenged by several experts in this field because the authors did not report the sensitivity and specificity of the ELISA assay used.<sup>15</sup> <br/><br/>Serologic testing of US veterans who served in <i>C sinensis </i>and <i>O viverrini</i>–endemic countries for indolent infections with these parasites is not recommended at present.<sup>15</sup> Nevertheless, there is an urgent need to develop sensitive and specific serologic assays, such as ELISA tests with recombinant antigens, to detect both acute and indolent infections caused by each biliary liver fluke in the US, including in patients diagnosed with cholangiocarcinoma. We posit that testing and treatment of high-risk populations could lead to earlier detection and treatment of cholangiocarcinoma, leading to improved overall survival in the population at risk. </p> <h3> Author affiliations </h3> <p> <em><sup>a</sup>Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois<br/><br/><sup>b</sup>University of Illinois College of Medicine at Chicago</em> </p> <h3> Author disclosures </h3> <p> <em>The authors report no actual or potential conflicts of interest or outside sources of funding with regard to this article.</em> </p> <h3> Disclaimer </h3> <p> <em>The opinions expressed herein are those of the authors and do not necessarily reflect those of <i>Federal Practitioner</i>, Frontline Medical Communications Inc., the US Government, or any of its agencies. </em> </p> <h3> References </h3> <p class="reference"> 1. American Cancer Society. Survival rates for bile duct cancer. Updated March 1, 2023. Accessed March 17, 2023. https://www.cancer.org/cancer/bile-duct-cancer/detection-diagnosis-staging/survival-by-stage.html<br/><br/> 2. Vij M, Puri Y, Rammohan A, et al. Pathological, molecular, and clinical characteristics of cholangiocarcinoma: A comprehensive review. <i>World J Gastrointest Oncol</i>. 2022;14(3):607-627. doi:10.4251/wjgo.v14.i3.607<br/><br/> 3. Yao KJ, Jabbour S, Parekh N, Lin Y, Moss RA. Increasing mortality in the United States from cholangiocarcinoma: an analysis of the National Center for Health Statistics Database. <i>BMC Gastroenterol</i>. 2016;16(1):117. Published 2016 Sep 21. doi:10.1186/s12876-016-0527-z<br/><br/> 4. Rustagi T, Dasanu CA. Risk factors for gallbladder cancer and cholangiocarcinoma: similarities, differences and updates. <i>J Gastrointest Cancer</i>. 2012;43(2):137-147. doi:10.1007/s12029-011-9284-y<br/><br/> 5. Maemura K, Natsugoe S, Takao S. Molecular mechanism of cholangiocarcinoma carcinogenesis. <i>J Hepatobiliary Pancreat Sci</i>. 2014;21(10):754-760. doi:10.1002/jhbp.126<br/><br/> 6. Steele JA, Richter CH, Echaubard P, et al. Thinking beyond Opisthorchis viverrini for risk of cholangiocarcinoma in the lower Mekong region: a systematic review and meta-analysis. <i>Infect Dis Poverty</i>. 2018;7(1):44. Published 2018 May 17. doi:10.1186/s40249-018-0434-3.<br/><br/> 7. Kim TS, Pak JH, Kim JB, Bahk YY. Clonorchis sinensis, an oriental liver fluke, as a human biological agent of cholangiocarcinoma: a brief review. <i>BMB Rep</i>. 2016;49(11):590-597. doi:10.5483/bmbrep.2016.49.11.109<br/><br/> 8. Murata M. Inflammation and cancer. <i>Environ Health Prev Med</i>. 2018;23(1):50. Published 2018 Oct 20. doi:10.1186/s12199-018-0740-1<br/><br/> 9. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Biological agents. <i>IARC Monogr Eval Carcinog Risks Hum</i>. 2012;100(pt B):1-441.<br/><br/>10. Mairiang E, Laha T, Bethony JM, et al. Ultrasonography assessment of hepatobiliary abnormalities in 3359 subjects with Opisthorchis viverrini infection in endemic areas of Thailand. <i>Parasitol Int</i>. 2012;61(1):208-211. doi:10.1016/j.parint.2011.07.009<br/><br/>11. Li HM, Qian MB, Yang YC, et al. Performance evaluation of existing immunoassays for Clonorchis sinensis infection in China. <i>Parasit Vectors</i>. 2018;11(1):35. Published 2018 Jan 15. doi:10.1186/s13071-018-2612-3<br/><br/>12. Hughes T, O’Connor T, Techasen A, et al. Opisthorchiasis and cholangiocarcinoma in Southeast Asia: an unresolved problem. <i>Int J Gen Med</i>. 2017;10:227-237. Published 2017 Aug 10. doi:10.2147/IJGM.S133292<br/><br/>13. Psevdos G, Ford FM, Hong ST. Screening US Vietnam veterans for liver fluke exposure 5 decades after the end of the war. <i>Infect Dis Clin Pract (Baltim Md)</i>. 2018;26(4):208-210. doi:10.1097/IPC.0000000000000611<br/><br/>14. American War Library. In harm’s way... How many real Vietnam vets are alive today? Updated February 28, 2019. Accessed March 17, 2023. https://www.americanwarlibrary.com/personnel/vietvet.htm<br/><br/>15. Nash TE, Sullivan D, Mitre E, et al. Comments on “Screening US Vietnam veterans for liver fluke exposure 5 decades after the end of the war”. <i>Infect Dis Clin Pract (Baltim Md)</i>. 2018;26(4):240-241. doi:10.1097/IPC.0000000000000659</p> </itemContent> </newsItem> </itemSet></root>
Preliminary Observations of Veterans Without HIV Who Have Mycobacterium avium Complex Pulmonary Disease
Nontuberculous Mycobacterium (NTM) is a ubiquitous organism known to cause a variety of infections in susceptible hosts; however, pulmonary infection is the most common. Mycobacterium avium complex (MAC) is the most prevalent cause of NTM-related pulmonary disease (NTM-PD) and is associated with underlying structural lung disease, such as chronic obstructive pulmonary disease (COPD) and noncystic fibrosis bronchiectasis.1-3
Diagnosis of NTM-PD requires (1) symptoms or radiographic abnormality; and (2) at least 2 sputum cultures positive with the same organism or at least 1 positive culture result on bronchoscopy (wash, lavage, or biopsy).1 Notably, the natural history of untreated NTM-PD varies, though even mild disease may progress substantially.4-6 Progressive disease is more likely to occur in those with a positive smear or more extensive radiographic findings at the initial diagnosis.7 A nationwide Medicare-based study showed that patients with NTM-PD had a higher rate of all-cause mortality than did patients without NTM-PD.8 In a study of 123 patients from Taiwan with MAC-PD, lack of treatment was an independent predictor of mortality.9 Given the risk of progressive morbidity and mortality, recent guidelines recommend initiation of a susceptibility driven, macrolide-based, 3-drug treatment regimen over watchful waiting.10
MAC-PD is increasingly recognized among US veterans.11,12 The Jesse Brown Veterans Affairs Medical Center (JBVAMC) in south/west Chicago serves a large, predominantly Black male population of veterans many of whom are socioeconomically underresourced, and half are aged ≥ 65 years. We observed that initiation of guideline-directed therapy in veterans with MAC-PD at JBVAMC varied among health care professionals (HCPs) in the pulmonary clinic. Therefore, the purpose of this retrospective study was to describe and compare the characteristics of veterans without HIV were diagnosed with MAC-PD and managed at JBVAMC.
Methods
The hospital microbiology department identified veterans diagnosed with NTM at JBVAMC between October 2008 and July 2019. Veterans included in the study were considered to have MAC-PD per American Thoracic Society (ATS)/Infectious Diseases Society of America (ISDA) guidelines and those diagnosed with HIV were excluded from analysis. The electronic health record (EHR) was queried for pertinent demographics, smoking history, comorbidities, and symptoms at the time of a positive mycobacterial culture. Computed tomography (CT) and pulmonary function tests (PFTs) performed within 1 year of diagnosis were included. PFTs were assessed in accordance with Global Initiative for Obstructive Lung Disease (GOLD) criteria, with normal forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) values defined as ≥ 80% and a normal FEV1/FVC ratio defined as ≥ 70. The diffusion capacity of lung for carbon monoxide (DLCO) was assessed per 2017 European Respiratory Society (ERS) technical standards and was considered reduced if below the lower limit of normal.13 Information regarding treatment decisions, initiation, and cessation were collected. All-cause mortality was recorded if available in the EHR at the time of data collection.
Statistical analysis was performed using Mann-Whitney U and Fisher exact tests where appropriate. P < .05 was considered statistically significant. The study was approved by the JBVAMC Institutional Review Board.
Results
We identified 43 veterans who had a positive culture for MAC; however, only 19 veterans met the diagnostic criteria for MAC-PD and were included in the study (Table). The cohort included predominantly Black and male veterans with a median age of 74 years at time of diagnosis (range, 45-92). Sixteen veterans had underlying lung disease (84.2%), and 16 (84.2%) were current or former smokers. Common comorbidities included COPD, obstructive sleep apnea, gastroesophageal reflux disease, and lung cancer. Respiratory symptoms were reported in 17 veterans (89.5%), 15 (78.9%) had a chronic cough, and 10 (52.6%) had dyspnea. Fifteen veterans had a chest CT scan within 1 year of diagnosis: A nodular and tree-in-bud pattern was most commonly found in 13 (86.7%) of veterans. Thirteen veterans had PFTs within 1 year of MAC-PD diagnosis, of whom 6 had a restrictive pattern with percent predicted FVC < 80%, and 9 had evidence of obstruction with FEV1/FVC < 70. DLCO was below the lower limit of normal in 18 veterans. Finally, 6 veterans were deceased at the time of the study.
Of the 19 veterans, guideline-directed, combination antimycobacterial therapy for MAC-PD was initiated in only 10 (52.6%) patients due to presence of symptoms and/or imaging abnormalities. Treatment was deferred due to improved symptoms, concern for adverse events (AEs), or lost to follow-up. Five veterans stopped treatment prematurely due to AEs, lost to follow-up, or all-cause mortality. Assessment of differences between treated and untreated groups revealed no significant difference in race, sex, age, body mass index (BMI), symptom presence, or chest CT abnormalities. There was no statistically significant difference in all-cause mortality (40% and 22.2% in treated and untreated group, respectively).
To further understand the differences of this cohort, the 13 veterans alive at time of the study were compared with the 6 who had since died of all-cause mortality. No statistically significant differences were found.
Discussion
Consistent with previous reports in the literature, veterans in our cohort were predominantly current or former smoking males with underlying COPD and bronchiectasis.1-3,11,12 Chest CT findings varied: Most veterans presented not only with nodules and tree-in-bud opacities, but also a high frequency of fibrosis and emphysema. PFTs revealed a variety of obstruction and restrictive patterns, and most veterans had a reduced DLCO, though it is unclear whether this is reflective of underlying emphysema, fibrosis, or an alternative cardiopulmonary disease.13,14
While underlying structural lung disease may have been a risk factor for MAC-PD in this cohort, the contribution of environmental and domiciliary factors in metropolitan Chicago neighborhoods is unknown. JBVAMC serves an underresourced population who live in the west and south Chicago neighborhoods. Household factors, ambient and indoor air pollution, and potential contamination of the water supply and surface soil may contribute to the prevalence of MAC-PD in this group.15-19 Further studies are warranted to characterize MAC-PD and its treatment in veterans without HIV who reside in underresourced urban communities in the US.
Recent ATS, European Society of Clinical Microbiology and Infectious Diseases, and IDSA guidelines recommend combination antimycobacterial therapy for patients who meet clinical, radiographic, and microbiologic criteria for the diagnosis of MAC-PD.10 Patients who meet these diagnostic criteria, particularly patients with smear positivity or fibrocavitary disease, should be treated because of risk of unfavorable outcomes.15,20-22 However, we found that the initiation of guideline-recommended antimycobacterial therapy in veterans without HIV with MAC-PD were inconsistent among HCPs. The reasons underlying this phenomenon were not apparent beyond cited reasons for treatment initiation or deference. Despite this inconsistency, there was no clear difference in age, BMI, symptom burden, radiographic abnormality, or all-cause mortality between treatment groups. Existing studies support slow but substantial progression of untreated MAC-PD, and while treatment prevents deterioration of the disease, it does not prevent progression of bronchiectasis.6 The natural history of MAC-PD in this veteran cohort has yet to be fully elucidated. Furthermore, the 50% treatment dropout rate was higher than previously reported rates (11-33%).5 However, the small number of veterans in this study precludes meaningful comparison with similar reports in the literature.
Limitations
The limitations of this small, single-center, retrospective study prevent a robust, generalizable comparison between groups. Further studies are warranted to characterize MAC-PD and its treatment in veterans without HIV who reside in underresourced urban communities in the US.24-26
Conclusions
These data suggest that clinical, imaging, and treatment attributes of MAC-PD in veterans without HIV who reside in metropolitan Chicago are heterogeneous and are associated with a relatively high mortality rate. Although there was no difference in the attributes or outcomes of veterans who did and did not initiate treatment despite current recommendations, further studies are needed to better explore these relationships.
1. Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/ IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases [published correction appears in Am J Respir Crit Care Med. 2007 Apr 1;175(7):744-5. Dosage error in article text]. Am J Respir Crit Care Med. 2007;175(4):367-416. doi:10.1164/rccm.200604-571ST
2. Prevots DR, Shaw PA, Strickland D, et al. Nontuberculous mycobacterial lung disease prevalence at four integrated health care delivery systems. Am J Respir Crit Care Med. 2010;182(7):970-976. doi:10.1164/rccm.201002-0310OC
3. Winthrop KL, Marras TK, Adjemian J, Zhang H, Wang P, Zhang Q. Incidence and prevalence of nontuberculous mycobacterial lung disease in a large U.S. managed care health plan, 2008-2015. Ann Am Thorac Soc. 2020;17(2):178-185. doi:10.1513/AnnalsATS.201804-236OC
4. Field SK, Fisher D, Cowie RL. Mycobacterium avium complex pulmonary disease in patients without HIV infection. Chest. 2004;126(2):566-581. doi:10.1378/chest.126.2.566
5. Kimizuka Y, Hoshino Y, Nishimura T, et al. Retrospective evaluation of natural course in mild cases of Mycobacterium avium complex pulmonary disease. PLoS One. 2019;14(4):e0216034. Published 2019 Apr 25. doi:10.1371/journal.pone.0216034
6. Kotilainen H, Valtonen V, Tukiainen P, Poussa T, Eskola J, Järvinen A. Clinical findings in relation to mortality in nontuberculous mycobacterial infections: patients with Mycobacterium avium complex have better survival than patients with other mycobacteria. Eur J Clin Microbiol Infect Dis. 2015;34(9):1909-1918. doi:10.1007/s10096-015-2432-8.
7. Hwang JA, Kim S, Jo KW, Shim TS. Natural history of Mycobacterium avium complex lung disease in untreated patients with stable course. Eur Respir J. 2017;49(3):1600537. Published 2017 Mar 8. doi:10.1183/13993003.00537-2016
8. Adjemian J, Olivier KN, Seitz AE, Holland SM, Prevots DR. Prevalence of nontuberculous mycobacterial lung disease in U.S. Medicare beneficiaries. Am J Respir Crit Care Med. 2012;185(8):881-886. doi:10.1164/rccm.201111-2016OC
9. Wang PH, Pan SW, Shu CC, et al. Clinical course and risk factors of mortality in Mycobacterium avium complex lung disease without initial treatment. Respir Med. 2020;171:106070. doi:10.1016/j.rmed.2020.106070
10. Daley CL, Iaccarino JM, Lange C, et al. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ ERS/ESCMID/IDSA Clinical Practice Guideline [published correction appears in Clin Infect Dis. 2020 Dec 31;71(11):3023]. Clin Infect Dis. 2020;71(4):e1-e36. doi:10.1093/cid/ciaa241
11. Mirsaeidi M, Hadid W, Ericsoussi B, Rodgers D, Sadikot RT. Non-tuberculous mycobacterial disease is common in patients with non-cystic fibrosis bronchiectasis. Int J Infect Dis. 2013;17(11):e1000-e1004. doi:10.1016/j.ijid.2013.03.018
12. Oda G, Winters MA, Pacheco SM, et al. Clusters of nontuberculous mycobacteria linked to water sources at three Veterans Affairs medical centers. Infect Control Hosp Epidemiol. 2020;41(3):320-330. doi:10.1017/ice.2019.342
13. Stanojevic S, Graham BL, Cooper BG, et al. Official ERS technical standards: Global Lung Function Initiative reference values for the carbon monoxide transfer factor for Caucasians [published correction appears in Eur Respir J. 2020 Oct 15;56(4):]. Eur Respir J. 2017;50(3):1700010. Published 2017 Sep 11. doi:10.1183/13993003.00010-2017
14. Macintyre N, Crapo RO, Viegi G, et al. Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur Respir J. 2005;26(4):720-735. doi:10.1183/09031936.05.00034905
15. Chalmers JD, Balavoine C, Castellotti PF, et al. European Respiratory Society International Congress, Madrid, 2019: nontuberculous mycobacterial pulmonary disease highlights. ERJ Open Res. 2020;6(4):00317-2020. Published 2020 Oct 19. doi:10.1183/23120541.00317-2020
16. Hamilton LA, Falkinham JO. Aerosolization of Mycobacterium avium and Mycobacterium abscessus from a household ultrasonic humidifier. J Med Microbiol. 2018;67(10):1491-1495. doi:10.1099/jmm.0.000822
17. Hannah CE, Ford BA, Chung J, Ince D, Wanat KA. Characteristics of nontuberculous mycobacterial infections at a midwestern tertiary hospital: a retrospective study of 365 patients. Open Forum Infect Dis. 2020;7(6):ofaa173. Published 2020 May 25. doi:10.1093/ofid/ofaa173
18. Rautiala S, Torvinen E, Torkko P, et al. Potentially pathogenic, slow-growing mycobacteria released into workplace air during the remediation of buildings. J Occup Environ Hyg. 2004;1(1):1-6. doi:10.1080/15459620490250008
19. Tzou CL, Dirac MA, Becker AL, et al. Association between Mycobacterium avium complex pulmonary disease and mycobacteria in home water and soil. Ann Am Thorac Soc. 2020;17(1):57-62. doi:10.1513/AnnalsATS.201812-915OC
20. Daley CL, Winthrop KL. Mycobacterium avium complex: addressing gaps in diagnosis and management. J Infect Dis. 2020;222(suppl 4):S199-S211. doi:10.1093/infdis/jiaa354 21. Kwon BS, Lee JH, Koh Y, et al. The natural history of noncavitary nodular bronchiectatic Mycobacterium avium complex lung disease. Respir Med. 2019;150:45-50. doi:10.1016/j.rmed.2019.02.007
22. Nasiri MJ, Ebrahimi G, Arefzadeh S, Zamani S, Nikpor Z, Mirsaeidi M. Antibiotic therapy success rate in pulmonary Mycobacterium avium complex: a systematic review and meta-analysis. Expert Rev Anti Infect Ther. 2020;18(3):263- 273. doi:10.1080/14787210.2020.1720650
23. Diel R, Lipman M, Hoefsloot W. High mortality in patients with Mycobacterium avium complex lung disease: a systematic review. BMC Infect Dis. 2018;18(1):206. Published 2018 May 3. doi:10.1186/s12879-018-3113-x
24. Marras TK, Prevots DR, Jamieson FB, Winthrop KL; Pulmonary MAC Outcomes Group. Opinions differ by expertise in Mycobacterium avium complex disease. Ann Am Thorac Soc. 2014;11(1):17-22. doi:10.1513/AnnalsATS.201305-136OC
25. Plotinsky RN, Talbot EA, von Reyn CF. Proposed definitions for epidemiologic and clinical studies of Mycobacterium avium complex pulmonary disease. PLoS One. 2013;8(11):e77385. Published 2013 Nov 12. doi:10.1371/journal.pone.0077385
26. Swenson C, Zerbe CS, Fennelly K. Host variability in NTM disease: implications for research needs. Front Microbiol. 2018;9:2901. Published 2018 Dec 3. doi:10.3389/fmicb.2018.02901
Nontuberculous Mycobacterium (NTM) is a ubiquitous organism known to cause a variety of infections in susceptible hosts; however, pulmonary infection is the most common. Mycobacterium avium complex (MAC) is the most prevalent cause of NTM-related pulmonary disease (NTM-PD) and is associated with underlying structural lung disease, such as chronic obstructive pulmonary disease (COPD) and noncystic fibrosis bronchiectasis.1-3
Diagnosis of NTM-PD requires (1) symptoms or radiographic abnormality; and (2) at least 2 sputum cultures positive with the same organism or at least 1 positive culture result on bronchoscopy (wash, lavage, or biopsy).1 Notably, the natural history of untreated NTM-PD varies, though even mild disease may progress substantially.4-6 Progressive disease is more likely to occur in those with a positive smear or more extensive radiographic findings at the initial diagnosis.7 A nationwide Medicare-based study showed that patients with NTM-PD had a higher rate of all-cause mortality than did patients without NTM-PD.8 In a study of 123 patients from Taiwan with MAC-PD, lack of treatment was an independent predictor of mortality.9 Given the risk of progressive morbidity and mortality, recent guidelines recommend initiation of a susceptibility driven, macrolide-based, 3-drug treatment regimen over watchful waiting.10
MAC-PD is increasingly recognized among US veterans.11,12 The Jesse Brown Veterans Affairs Medical Center (JBVAMC) in south/west Chicago serves a large, predominantly Black male population of veterans many of whom are socioeconomically underresourced, and half are aged ≥ 65 years. We observed that initiation of guideline-directed therapy in veterans with MAC-PD at JBVAMC varied among health care professionals (HCPs) in the pulmonary clinic. Therefore, the purpose of this retrospective study was to describe and compare the characteristics of veterans without HIV were diagnosed with MAC-PD and managed at JBVAMC.
Methods
The hospital microbiology department identified veterans diagnosed with NTM at JBVAMC between October 2008 and July 2019. Veterans included in the study were considered to have MAC-PD per American Thoracic Society (ATS)/Infectious Diseases Society of America (ISDA) guidelines and those diagnosed with HIV were excluded from analysis. The electronic health record (EHR) was queried for pertinent demographics, smoking history, comorbidities, and symptoms at the time of a positive mycobacterial culture. Computed tomography (CT) and pulmonary function tests (PFTs) performed within 1 year of diagnosis were included. PFTs were assessed in accordance with Global Initiative for Obstructive Lung Disease (GOLD) criteria, with normal forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) values defined as ≥ 80% and a normal FEV1/FVC ratio defined as ≥ 70. The diffusion capacity of lung for carbon monoxide (DLCO) was assessed per 2017 European Respiratory Society (ERS) technical standards and was considered reduced if below the lower limit of normal.13 Information regarding treatment decisions, initiation, and cessation were collected. All-cause mortality was recorded if available in the EHR at the time of data collection.
Statistical analysis was performed using Mann-Whitney U and Fisher exact tests where appropriate. P < .05 was considered statistically significant. The study was approved by the JBVAMC Institutional Review Board.
Results
We identified 43 veterans who had a positive culture for MAC; however, only 19 veterans met the diagnostic criteria for MAC-PD and were included in the study (Table). The cohort included predominantly Black and male veterans with a median age of 74 years at time of diagnosis (range, 45-92). Sixteen veterans had underlying lung disease (84.2%), and 16 (84.2%) were current or former smokers. Common comorbidities included COPD, obstructive sleep apnea, gastroesophageal reflux disease, and lung cancer. Respiratory symptoms were reported in 17 veterans (89.5%), 15 (78.9%) had a chronic cough, and 10 (52.6%) had dyspnea. Fifteen veterans had a chest CT scan within 1 year of diagnosis: A nodular and tree-in-bud pattern was most commonly found in 13 (86.7%) of veterans. Thirteen veterans had PFTs within 1 year of MAC-PD diagnosis, of whom 6 had a restrictive pattern with percent predicted FVC < 80%, and 9 had evidence of obstruction with FEV1/FVC < 70. DLCO was below the lower limit of normal in 18 veterans. Finally, 6 veterans were deceased at the time of the study.
Of the 19 veterans, guideline-directed, combination antimycobacterial therapy for MAC-PD was initiated in only 10 (52.6%) patients due to presence of symptoms and/or imaging abnormalities. Treatment was deferred due to improved symptoms, concern for adverse events (AEs), or lost to follow-up. Five veterans stopped treatment prematurely due to AEs, lost to follow-up, or all-cause mortality. Assessment of differences between treated and untreated groups revealed no significant difference in race, sex, age, body mass index (BMI), symptom presence, or chest CT abnormalities. There was no statistically significant difference in all-cause mortality (40% and 22.2% in treated and untreated group, respectively).
To further understand the differences of this cohort, the 13 veterans alive at time of the study were compared with the 6 who had since died of all-cause mortality. No statistically significant differences were found.
Discussion
Consistent with previous reports in the literature, veterans in our cohort were predominantly current or former smoking males with underlying COPD and bronchiectasis.1-3,11,12 Chest CT findings varied: Most veterans presented not only with nodules and tree-in-bud opacities, but also a high frequency of fibrosis and emphysema. PFTs revealed a variety of obstruction and restrictive patterns, and most veterans had a reduced DLCO, though it is unclear whether this is reflective of underlying emphysema, fibrosis, or an alternative cardiopulmonary disease.13,14
While underlying structural lung disease may have been a risk factor for MAC-PD in this cohort, the contribution of environmental and domiciliary factors in metropolitan Chicago neighborhoods is unknown. JBVAMC serves an underresourced population who live in the west and south Chicago neighborhoods. Household factors, ambient and indoor air pollution, and potential contamination of the water supply and surface soil may contribute to the prevalence of MAC-PD in this group.15-19 Further studies are warranted to characterize MAC-PD and its treatment in veterans without HIV who reside in underresourced urban communities in the US.
Recent ATS, European Society of Clinical Microbiology and Infectious Diseases, and IDSA guidelines recommend combination antimycobacterial therapy for patients who meet clinical, radiographic, and microbiologic criteria for the diagnosis of MAC-PD.10 Patients who meet these diagnostic criteria, particularly patients with smear positivity or fibrocavitary disease, should be treated because of risk of unfavorable outcomes.15,20-22 However, we found that the initiation of guideline-recommended antimycobacterial therapy in veterans without HIV with MAC-PD were inconsistent among HCPs. The reasons underlying this phenomenon were not apparent beyond cited reasons for treatment initiation or deference. Despite this inconsistency, there was no clear difference in age, BMI, symptom burden, radiographic abnormality, or all-cause mortality between treatment groups. Existing studies support slow but substantial progression of untreated MAC-PD, and while treatment prevents deterioration of the disease, it does not prevent progression of bronchiectasis.6 The natural history of MAC-PD in this veteran cohort has yet to be fully elucidated. Furthermore, the 50% treatment dropout rate was higher than previously reported rates (11-33%).5 However, the small number of veterans in this study precludes meaningful comparison with similar reports in the literature.
Limitations
The limitations of this small, single-center, retrospective study prevent a robust, generalizable comparison between groups. Further studies are warranted to characterize MAC-PD and its treatment in veterans without HIV who reside in underresourced urban communities in the US.24-26
Conclusions
These data suggest that clinical, imaging, and treatment attributes of MAC-PD in veterans without HIV who reside in metropolitan Chicago are heterogeneous and are associated with a relatively high mortality rate. Although there was no difference in the attributes or outcomes of veterans who did and did not initiate treatment despite current recommendations, further studies are needed to better explore these relationships.
Nontuberculous Mycobacterium (NTM) is a ubiquitous organism known to cause a variety of infections in susceptible hosts; however, pulmonary infection is the most common. Mycobacterium avium complex (MAC) is the most prevalent cause of NTM-related pulmonary disease (NTM-PD) and is associated with underlying structural lung disease, such as chronic obstructive pulmonary disease (COPD) and noncystic fibrosis bronchiectasis.1-3
Diagnosis of NTM-PD requires (1) symptoms or radiographic abnormality; and (2) at least 2 sputum cultures positive with the same organism or at least 1 positive culture result on bronchoscopy (wash, lavage, or biopsy).1 Notably, the natural history of untreated NTM-PD varies, though even mild disease may progress substantially.4-6 Progressive disease is more likely to occur in those with a positive smear or more extensive radiographic findings at the initial diagnosis.7 A nationwide Medicare-based study showed that patients with NTM-PD had a higher rate of all-cause mortality than did patients without NTM-PD.8 In a study of 123 patients from Taiwan with MAC-PD, lack of treatment was an independent predictor of mortality.9 Given the risk of progressive morbidity and mortality, recent guidelines recommend initiation of a susceptibility driven, macrolide-based, 3-drug treatment regimen over watchful waiting.10
MAC-PD is increasingly recognized among US veterans.11,12 The Jesse Brown Veterans Affairs Medical Center (JBVAMC) in south/west Chicago serves a large, predominantly Black male population of veterans many of whom are socioeconomically underresourced, and half are aged ≥ 65 years. We observed that initiation of guideline-directed therapy in veterans with MAC-PD at JBVAMC varied among health care professionals (HCPs) in the pulmonary clinic. Therefore, the purpose of this retrospective study was to describe and compare the characteristics of veterans without HIV were diagnosed with MAC-PD and managed at JBVAMC.
Methods
The hospital microbiology department identified veterans diagnosed with NTM at JBVAMC between October 2008 and July 2019. Veterans included in the study were considered to have MAC-PD per American Thoracic Society (ATS)/Infectious Diseases Society of America (ISDA) guidelines and those diagnosed with HIV were excluded from analysis. The electronic health record (EHR) was queried for pertinent demographics, smoking history, comorbidities, and symptoms at the time of a positive mycobacterial culture. Computed tomography (CT) and pulmonary function tests (PFTs) performed within 1 year of diagnosis were included. PFTs were assessed in accordance with Global Initiative for Obstructive Lung Disease (GOLD) criteria, with normal forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) values defined as ≥ 80% and a normal FEV1/FVC ratio defined as ≥ 70. The diffusion capacity of lung for carbon monoxide (DLCO) was assessed per 2017 European Respiratory Society (ERS) technical standards and was considered reduced if below the lower limit of normal.13 Information regarding treatment decisions, initiation, and cessation were collected. All-cause mortality was recorded if available in the EHR at the time of data collection.
Statistical analysis was performed using Mann-Whitney U and Fisher exact tests where appropriate. P < .05 was considered statistically significant. The study was approved by the JBVAMC Institutional Review Board.
Results
We identified 43 veterans who had a positive culture for MAC; however, only 19 veterans met the diagnostic criteria for MAC-PD and were included in the study (Table). The cohort included predominantly Black and male veterans with a median age of 74 years at time of diagnosis (range, 45-92). Sixteen veterans had underlying lung disease (84.2%), and 16 (84.2%) were current or former smokers. Common comorbidities included COPD, obstructive sleep apnea, gastroesophageal reflux disease, and lung cancer. Respiratory symptoms were reported in 17 veterans (89.5%), 15 (78.9%) had a chronic cough, and 10 (52.6%) had dyspnea. Fifteen veterans had a chest CT scan within 1 year of diagnosis: A nodular and tree-in-bud pattern was most commonly found in 13 (86.7%) of veterans. Thirteen veterans had PFTs within 1 year of MAC-PD diagnosis, of whom 6 had a restrictive pattern with percent predicted FVC < 80%, and 9 had evidence of obstruction with FEV1/FVC < 70. DLCO was below the lower limit of normal in 18 veterans. Finally, 6 veterans were deceased at the time of the study.
Of the 19 veterans, guideline-directed, combination antimycobacterial therapy for MAC-PD was initiated in only 10 (52.6%) patients due to presence of symptoms and/or imaging abnormalities. Treatment was deferred due to improved symptoms, concern for adverse events (AEs), or lost to follow-up. Five veterans stopped treatment prematurely due to AEs, lost to follow-up, or all-cause mortality. Assessment of differences between treated and untreated groups revealed no significant difference in race, sex, age, body mass index (BMI), symptom presence, or chest CT abnormalities. There was no statistically significant difference in all-cause mortality (40% and 22.2% in treated and untreated group, respectively).
To further understand the differences of this cohort, the 13 veterans alive at time of the study were compared with the 6 who had since died of all-cause mortality. No statistically significant differences were found.
Discussion
Consistent with previous reports in the literature, veterans in our cohort were predominantly current or former smoking males with underlying COPD and bronchiectasis.1-3,11,12 Chest CT findings varied: Most veterans presented not only with nodules and tree-in-bud opacities, but also a high frequency of fibrosis and emphysema. PFTs revealed a variety of obstruction and restrictive patterns, and most veterans had a reduced DLCO, though it is unclear whether this is reflective of underlying emphysema, fibrosis, or an alternative cardiopulmonary disease.13,14
While underlying structural lung disease may have been a risk factor for MAC-PD in this cohort, the contribution of environmental and domiciliary factors in metropolitan Chicago neighborhoods is unknown. JBVAMC serves an underresourced population who live in the west and south Chicago neighborhoods. Household factors, ambient and indoor air pollution, and potential contamination of the water supply and surface soil may contribute to the prevalence of MAC-PD in this group.15-19 Further studies are warranted to characterize MAC-PD and its treatment in veterans without HIV who reside in underresourced urban communities in the US.
Recent ATS, European Society of Clinical Microbiology and Infectious Diseases, and IDSA guidelines recommend combination antimycobacterial therapy for patients who meet clinical, radiographic, and microbiologic criteria for the diagnosis of MAC-PD.10 Patients who meet these diagnostic criteria, particularly patients with smear positivity or fibrocavitary disease, should be treated because of risk of unfavorable outcomes.15,20-22 However, we found that the initiation of guideline-recommended antimycobacterial therapy in veterans without HIV with MAC-PD were inconsistent among HCPs. The reasons underlying this phenomenon were not apparent beyond cited reasons for treatment initiation or deference. Despite this inconsistency, there was no clear difference in age, BMI, symptom burden, radiographic abnormality, or all-cause mortality between treatment groups. Existing studies support slow but substantial progression of untreated MAC-PD, and while treatment prevents deterioration of the disease, it does not prevent progression of bronchiectasis.6 The natural history of MAC-PD in this veteran cohort has yet to be fully elucidated. Furthermore, the 50% treatment dropout rate was higher than previously reported rates (11-33%).5 However, the small number of veterans in this study precludes meaningful comparison with similar reports in the literature.
Limitations
The limitations of this small, single-center, retrospective study prevent a robust, generalizable comparison between groups. Further studies are warranted to characterize MAC-PD and its treatment in veterans without HIV who reside in underresourced urban communities in the US.24-26
Conclusions
These data suggest that clinical, imaging, and treatment attributes of MAC-PD in veterans without HIV who reside in metropolitan Chicago are heterogeneous and are associated with a relatively high mortality rate. Although there was no difference in the attributes or outcomes of veterans who did and did not initiate treatment despite current recommendations, further studies are needed to better explore these relationships.
1. Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/ IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases [published correction appears in Am J Respir Crit Care Med. 2007 Apr 1;175(7):744-5. Dosage error in article text]. Am J Respir Crit Care Med. 2007;175(4):367-416. doi:10.1164/rccm.200604-571ST
2. Prevots DR, Shaw PA, Strickland D, et al. Nontuberculous mycobacterial lung disease prevalence at four integrated health care delivery systems. Am J Respir Crit Care Med. 2010;182(7):970-976. doi:10.1164/rccm.201002-0310OC
3. Winthrop KL, Marras TK, Adjemian J, Zhang H, Wang P, Zhang Q. Incidence and prevalence of nontuberculous mycobacterial lung disease in a large U.S. managed care health plan, 2008-2015. Ann Am Thorac Soc. 2020;17(2):178-185. doi:10.1513/AnnalsATS.201804-236OC
4. Field SK, Fisher D, Cowie RL. Mycobacterium avium complex pulmonary disease in patients without HIV infection. Chest. 2004;126(2):566-581. doi:10.1378/chest.126.2.566
5. Kimizuka Y, Hoshino Y, Nishimura T, et al. Retrospective evaluation of natural course in mild cases of Mycobacterium avium complex pulmonary disease. PLoS One. 2019;14(4):e0216034. Published 2019 Apr 25. doi:10.1371/journal.pone.0216034
6. Kotilainen H, Valtonen V, Tukiainen P, Poussa T, Eskola J, Järvinen A. Clinical findings in relation to mortality in nontuberculous mycobacterial infections: patients with Mycobacterium avium complex have better survival than patients with other mycobacteria. Eur J Clin Microbiol Infect Dis. 2015;34(9):1909-1918. doi:10.1007/s10096-015-2432-8.
7. Hwang JA, Kim S, Jo KW, Shim TS. Natural history of Mycobacterium avium complex lung disease in untreated patients with stable course. Eur Respir J. 2017;49(3):1600537. Published 2017 Mar 8. doi:10.1183/13993003.00537-2016
8. Adjemian J, Olivier KN, Seitz AE, Holland SM, Prevots DR. Prevalence of nontuberculous mycobacterial lung disease in U.S. Medicare beneficiaries. Am J Respir Crit Care Med. 2012;185(8):881-886. doi:10.1164/rccm.201111-2016OC
9. Wang PH, Pan SW, Shu CC, et al. Clinical course and risk factors of mortality in Mycobacterium avium complex lung disease without initial treatment. Respir Med. 2020;171:106070. doi:10.1016/j.rmed.2020.106070
10. Daley CL, Iaccarino JM, Lange C, et al. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ ERS/ESCMID/IDSA Clinical Practice Guideline [published correction appears in Clin Infect Dis. 2020 Dec 31;71(11):3023]. Clin Infect Dis. 2020;71(4):e1-e36. doi:10.1093/cid/ciaa241
11. Mirsaeidi M, Hadid W, Ericsoussi B, Rodgers D, Sadikot RT. Non-tuberculous mycobacterial disease is common in patients with non-cystic fibrosis bronchiectasis. Int J Infect Dis. 2013;17(11):e1000-e1004. doi:10.1016/j.ijid.2013.03.018
12. Oda G, Winters MA, Pacheco SM, et al. Clusters of nontuberculous mycobacteria linked to water sources at three Veterans Affairs medical centers. Infect Control Hosp Epidemiol. 2020;41(3):320-330. doi:10.1017/ice.2019.342
13. Stanojevic S, Graham BL, Cooper BG, et al. Official ERS technical standards: Global Lung Function Initiative reference values for the carbon monoxide transfer factor for Caucasians [published correction appears in Eur Respir J. 2020 Oct 15;56(4):]. Eur Respir J. 2017;50(3):1700010. Published 2017 Sep 11. doi:10.1183/13993003.00010-2017
14. Macintyre N, Crapo RO, Viegi G, et al. Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur Respir J. 2005;26(4):720-735. doi:10.1183/09031936.05.00034905
15. Chalmers JD, Balavoine C, Castellotti PF, et al. European Respiratory Society International Congress, Madrid, 2019: nontuberculous mycobacterial pulmonary disease highlights. ERJ Open Res. 2020;6(4):00317-2020. Published 2020 Oct 19. doi:10.1183/23120541.00317-2020
16. Hamilton LA, Falkinham JO. Aerosolization of Mycobacterium avium and Mycobacterium abscessus from a household ultrasonic humidifier. J Med Microbiol. 2018;67(10):1491-1495. doi:10.1099/jmm.0.000822
17. Hannah CE, Ford BA, Chung J, Ince D, Wanat KA. Characteristics of nontuberculous mycobacterial infections at a midwestern tertiary hospital: a retrospective study of 365 patients. Open Forum Infect Dis. 2020;7(6):ofaa173. Published 2020 May 25. doi:10.1093/ofid/ofaa173
18. Rautiala S, Torvinen E, Torkko P, et al. Potentially pathogenic, slow-growing mycobacteria released into workplace air during the remediation of buildings. J Occup Environ Hyg. 2004;1(1):1-6. doi:10.1080/15459620490250008
19. Tzou CL, Dirac MA, Becker AL, et al. Association between Mycobacterium avium complex pulmonary disease and mycobacteria in home water and soil. Ann Am Thorac Soc. 2020;17(1):57-62. doi:10.1513/AnnalsATS.201812-915OC
20. Daley CL, Winthrop KL. Mycobacterium avium complex: addressing gaps in diagnosis and management. J Infect Dis. 2020;222(suppl 4):S199-S211. doi:10.1093/infdis/jiaa354 21. Kwon BS, Lee JH, Koh Y, et al. The natural history of noncavitary nodular bronchiectatic Mycobacterium avium complex lung disease. Respir Med. 2019;150:45-50. doi:10.1016/j.rmed.2019.02.007
22. Nasiri MJ, Ebrahimi G, Arefzadeh S, Zamani S, Nikpor Z, Mirsaeidi M. Antibiotic therapy success rate in pulmonary Mycobacterium avium complex: a systematic review and meta-analysis. Expert Rev Anti Infect Ther. 2020;18(3):263- 273. doi:10.1080/14787210.2020.1720650
23. Diel R, Lipman M, Hoefsloot W. High mortality in patients with Mycobacterium avium complex lung disease: a systematic review. BMC Infect Dis. 2018;18(1):206. Published 2018 May 3. doi:10.1186/s12879-018-3113-x
24. Marras TK, Prevots DR, Jamieson FB, Winthrop KL; Pulmonary MAC Outcomes Group. Opinions differ by expertise in Mycobacterium avium complex disease. Ann Am Thorac Soc. 2014;11(1):17-22. doi:10.1513/AnnalsATS.201305-136OC
25. Plotinsky RN, Talbot EA, von Reyn CF. Proposed definitions for epidemiologic and clinical studies of Mycobacterium avium complex pulmonary disease. PLoS One. 2013;8(11):e77385. Published 2013 Nov 12. doi:10.1371/journal.pone.0077385
26. Swenson C, Zerbe CS, Fennelly K. Host variability in NTM disease: implications for research needs. Front Microbiol. 2018;9:2901. Published 2018 Dec 3. doi:10.3389/fmicb.2018.02901
1. Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/ IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases [published correction appears in Am J Respir Crit Care Med. 2007 Apr 1;175(7):744-5. Dosage error in article text]. Am J Respir Crit Care Med. 2007;175(4):367-416. doi:10.1164/rccm.200604-571ST
2. Prevots DR, Shaw PA, Strickland D, et al. Nontuberculous mycobacterial lung disease prevalence at four integrated health care delivery systems. Am J Respir Crit Care Med. 2010;182(7):970-976. doi:10.1164/rccm.201002-0310OC
3. Winthrop KL, Marras TK, Adjemian J, Zhang H, Wang P, Zhang Q. Incidence and prevalence of nontuberculous mycobacterial lung disease in a large U.S. managed care health plan, 2008-2015. Ann Am Thorac Soc. 2020;17(2):178-185. doi:10.1513/AnnalsATS.201804-236OC
4. Field SK, Fisher D, Cowie RL. Mycobacterium avium complex pulmonary disease in patients without HIV infection. Chest. 2004;126(2):566-581. doi:10.1378/chest.126.2.566
5. Kimizuka Y, Hoshino Y, Nishimura T, et al. Retrospective evaluation of natural course in mild cases of Mycobacterium avium complex pulmonary disease. PLoS One. 2019;14(4):e0216034. Published 2019 Apr 25. doi:10.1371/journal.pone.0216034
6. Kotilainen H, Valtonen V, Tukiainen P, Poussa T, Eskola J, Järvinen A. Clinical findings in relation to mortality in nontuberculous mycobacterial infections: patients with Mycobacterium avium complex have better survival than patients with other mycobacteria. Eur J Clin Microbiol Infect Dis. 2015;34(9):1909-1918. doi:10.1007/s10096-015-2432-8.
7. Hwang JA, Kim S, Jo KW, Shim TS. Natural history of Mycobacterium avium complex lung disease in untreated patients with stable course. Eur Respir J. 2017;49(3):1600537. Published 2017 Mar 8. doi:10.1183/13993003.00537-2016
8. Adjemian J, Olivier KN, Seitz AE, Holland SM, Prevots DR. Prevalence of nontuberculous mycobacterial lung disease in U.S. Medicare beneficiaries. Am J Respir Crit Care Med. 2012;185(8):881-886. doi:10.1164/rccm.201111-2016OC
9. Wang PH, Pan SW, Shu CC, et al. Clinical course and risk factors of mortality in Mycobacterium avium complex lung disease without initial treatment. Respir Med. 2020;171:106070. doi:10.1016/j.rmed.2020.106070
10. Daley CL, Iaccarino JM, Lange C, et al. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ ERS/ESCMID/IDSA Clinical Practice Guideline [published correction appears in Clin Infect Dis. 2020 Dec 31;71(11):3023]. Clin Infect Dis. 2020;71(4):e1-e36. doi:10.1093/cid/ciaa241
11. Mirsaeidi M, Hadid W, Ericsoussi B, Rodgers D, Sadikot RT. Non-tuberculous mycobacterial disease is common in patients with non-cystic fibrosis bronchiectasis. Int J Infect Dis. 2013;17(11):e1000-e1004. doi:10.1016/j.ijid.2013.03.018
12. Oda G, Winters MA, Pacheco SM, et al. Clusters of nontuberculous mycobacteria linked to water sources at three Veterans Affairs medical centers. Infect Control Hosp Epidemiol. 2020;41(3):320-330. doi:10.1017/ice.2019.342
13. Stanojevic S, Graham BL, Cooper BG, et al. Official ERS technical standards: Global Lung Function Initiative reference values for the carbon monoxide transfer factor for Caucasians [published correction appears in Eur Respir J. 2020 Oct 15;56(4):]. Eur Respir J. 2017;50(3):1700010. Published 2017 Sep 11. doi:10.1183/13993003.00010-2017
14. Macintyre N, Crapo RO, Viegi G, et al. Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur Respir J. 2005;26(4):720-735. doi:10.1183/09031936.05.00034905
15. Chalmers JD, Balavoine C, Castellotti PF, et al. European Respiratory Society International Congress, Madrid, 2019: nontuberculous mycobacterial pulmonary disease highlights. ERJ Open Res. 2020;6(4):00317-2020. Published 2020 Oct 19. doi:10.1183/23120541.00317-2020
16. Hamilton LA, Falkinham JO. Aerosolization of Mycobacterium avium and Mycobacterium abscessus from a household ultrasonic humidifier. J Med Microbiol. 2018;67(10):1491-1495. doi:10.1099/jmm.0.000822
17. Hannah CE, Ford BA, Chung J, Ince D, Wanat KA. Characteristics of nontuberculous mycobacterial infections at a midwestern tertiary hospital: a retrospective study of 365 patients. Open Forum Infect Dis. 2020;7(6):ofaa173. Published 2020 May 25. doi:10.1093/ofid/ofaa173
18. Rautiala S, Torvinen E, Torkko P, et al. Potentially pathogenic, slow-growing mycobacteria released into workplace air during the remediation of buildings. J Occup Environ Hyg. 2004;1(1):1-6. doi:10.1080/15459620490250008
19. Tzou CL, Dirac MA, Becker AL, et al. Association between Mycobacterium avium complex pulmonary disease and mycobacteria in home water and soil. Ann Am Thorac Soc. 2020;17(1):57-62. doi:10.1513/AnnalsATS.201812-915OC
20. Daley CL, Winthrop KL. Mycobacterium avium complex: addressing gaps in diagnosis and management. J Infect Dis. 2020;222(suppl 4):S199-S211. doi:10.1093/infdis/jiaa354 21. Kwon BS, Lee JH, Koh Y, et al. The natural history of noncavitary nodular bronchiectatic Mycobacterium avium complex lung disease. Respir Med. 2019;150:45-50. doi:10.1016/j.rmed.2019.02.007
22. Nasiri MJ, Ebrahimi G, Arefzadeh S, Zamani S, Nikpor Z, Mirsaeidi M. Antibiotic therapy success rate in pulmonary Mycobacterium avium complex: a systematic review and meta-analysis. Expert Rev Anti Infect Ther. 2020;18(3):263- 273. doi:10.1080/14787210.2020.1720650
23. Diel R, Lipman M, Hoefsloot W. High mortality in patients with Mycobacterium avium complex lung disease: a systematic review. BMC Infect Dis. 2018;18(1):206. Published 2018 May 3. doi:10.1186/s12879-018-3113-x
24. Marras TK, Prevots DR, Jamieson FB, Winthrop KL; Pulmonary MAC Outcomes Group. Opinions differ by expertise in Mycobacterium avium complex disease. Ann Am Thorac Soc. 2014;11(1):17-22. doi:10.1513/AnnalsATS.201305-136OC
25. Plotinsky RN, Talbot EA, von Reyn CF. Proposed definitions for epidemiologic and clinical studies of Mycobacterium avium complex pulmonary disease. PLoS One. 2013;8(11):e77385. Published 2013 Nov 12. doi:10.1371/journal.pone.0077385
26. Swenson C, Zerbe CS, Fennelly K. Host variability in NTM disease: implications for research needs. Front Microbiol. 2018;9:2901. Published 2018 Dec 3. doi:10.3389/fmicb.2018.02901