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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