Mortality among patients with pulmonary non-tuberculous mycobacteria disease

Fleshner, Monika; Olivier, Kenneth N.; Shaw, Pamela A.; Adjemian, Jennifer; Strollo, Sara; Claypool, Reginald J.; Folio, Les; Zelazny, Adrian M.; Holland, Steven M.; Prevots, D. Rebecca

doi:10.5588/ijtld.15.0807

Cited by 75 publications

(58 citation statements)

References 30 publications

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“…In addition, most prior studies comprised patients from NTM clinics, which permitted careful clinical characterization but most likely led to substantial bias in patient selection ( 7 , 8 , 10 ). Although our 5-year mortality estimates (26.6% for NTM-PI and 36.9% for NTM-PD) were of generally similar magnitude to prior studies ( 7 – 11 ), parsing those studies by cohort type reveals that those comprising single NTM clinics tended to report lower rates of death ( 7 , 8 , 10 ). In the single-clinic study from the United States, which had the lowest 5-year death rate of 18% ( 10 ), the median age at diagnosis was 55 years, compared with 70 years in our study, which probably explains much of the difference in death.…”

Section: Discussionmentioning

confidence: 99%

“…At the population level, patients with NTM-PD have been poorly characterized in general, and their survival is not well studied. Studies from individual clinical programs have identified prognostic factors ( 7 – 10 ), but estimates of survival are undoubtedly affected by referral bias and therefore cannot be generalized to all NTM-PD patients. One population-based study of survival in NTM-PD patients has been reported, but it did not include controls without NTM, so NTM-attributable death could not be determined ( 11 ).…”

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confidence: 99%

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Pulmonary Nontuberculous Mycobacteria–Associated Deaths, Ontario, Canada, 2001–2013

Marras

Campitelli

et al. 2017

Emerg. Infect. Dis.

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Survival implications of nontuberculous mycobacterial pulmonary disease (NTM-PD) and NTM pulmonary isolation without disease (NTM-PI) are unclear. To study deaths associated with NTM-PD and NTM-PI and differences in survival between them, we conducted a population-based cohort study of persons with microbiologically defined NTM-PD or NTM-PI diagnosed during 2001–2013 in Ontario, Canada. We used propensity score matching and Cox proportional hazards models to compare survival. Among 9,681 NTM-PD patients and 10,936 NTM-PI patients, 87% and 91%, respectively, were successfully matched with unexposed controls. Both NTM-PD and NTM-PI were associated with higher rates of death for all species combined and for most individual species. Compared with NTM-PI, NTM-PD was associated with higher death rates for all species combined, Mycobacterium avium complex, and M. xenopi. NTM-PD and NTM-PI were significantly associated with death, NTM-PD more so than NTM-PI.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Pulmonary Nontuberculous Mycobacteria–Associated Deaths, Ontario, Canada, 2001–2013

Marras

Campitelli

et al. 2017

Emerg. Infect. Dis.

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“…Impaired innate immunity due to lung parenchyma damage is believed to be the major predisposing factor for PNTM infection. PNTM disease is a serious cause of morbidity and mortality and has a rising incidence across populations [6, 7]. In cases with no past medical or family history suggestive of immunodeficiency, a deficiency in the production of IFN- γ has previously been noted prompting the adjuvant use of IFN- γ therapy [8–10].…”

Section: Discussionmentioning

confidence: 99%

Differential Impairment of Interferon-γ Responses in Two Cases of Pulmonary Nontuberculous Mycobacterial Disease

Rae

Gao

Eren

et al. 2016

Case Reports in Immunology

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Nontuberculous mycobacteria (NTMs) are weakly virulent intracellular pathogens that are common in food and water supplies. The persistent culture of these organisms in the setting of clinical infection warrants investigation of immune function. In cases of isolated pulmonary NTM (PNTM) disease, underlying immune defects have not been clearly identified. We present two patients with isolated PNTM infection who demonstrated differentially impaired IFN-γ production across a range of stimuli. These cases show that cellular IFN-γ responses may be defective in a proportion of patient suffering PNTM disease and that when assessing responses, the stimulant used in the testing is important to delineate defective cell populations. Impaired IFN-γ responses to IL-12 + BCG seem to be a poor prognostic indicator in PNTM disease and in these cases were not improved by adjuvant IFN-γ.

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“…From a pathophysiologic perspective, this recognition has changed the way that many NTM experts view the development of NTM lung disease. Specifically, because NTM exposure is universal but NTM disease is relatively rare, it is increasingly accepted that patients require not only exposure to NTM but also likely some type of predisposition, such as the structural lung abnormalities most often associated with bronchiectasis or obstructive lung disease 38 . This hypothesis has been dubbed the “two-hit” theory of NTM lung disease acquisition.…”

Section: Pathophysiologymentioning

confidence: 99%

Understanding nontuberculous mycobacterial lung disease: it’s been a long time coming

Griffith

Aksamit

2016

F1000Res

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With a surprising predictability, most studies and reviews addressing therapy for nontuberculous mycobacterial (NTM) lung disease either start or end by mentioning the paucity of data from randomized and controlled trials. That is a legitimate criticism for NTM lung disease therapy, but it also somehow seems to influence attitudes toward all aspects of NTM investigation. Certainly the study of NTM diseases in general and NTM lung disease in particular is a recent development. Previously, NTM were viewed as minor, if inconvenient, pathogens similar to Mycobacterium tuberculosis. However, over the last three decades, NTM have emerged as increasingly important pathogens that are clearly different compared with tuberculosis. Although there has been frustratingly slow progress in the treatment of NTM diseases, in contrast there has unquestionably been impressive progress in almost every other realm of investigation into NTM disease. Our understanding of NTM lung disease a) pathophysiology, including mechanisms of organism acquisition, b) epidemiology, including estimates of disease prevalence, c) mycobacteriology, including application of molecular laboratory techniques and matrix-assisted laser desorption ionization–time of flight (MALDI–TOF) mass spectrometry, and d) even treatment strategies, including the recognition of innate drug resistance mechanisms, has immeasurably and permanently changed and advanced the landscape for NTM lung disease. It is no longer necessary to apologize for the state of NTM lung disease knowledge and understanding, but rather it is time to recognize the great distance we have travelled over the last 30 years.

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Mortality among patients with pulmonary non-tuberculous mycobacteria disease

Cited by 75 publications

References 30 publications

Pulmonary Nontuberculous Mycobacteria–Associated Deaths, Ontario, Canada, 2001–2013

Pulmonary Nontuberculous Mycobacteria–Associated Deaths, Ontario, Canada, 2001–2013

Differential Impairment of Interferon-γ Responses in Two Cases of Pulmonary Nontuberculous Mycobacterial Disease

Understanding nontuberculous mycobacterial lung disease: it’s been a long time coming

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