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May 25, 2015 - 1Department of Internal Medicine, Schulich School of Medicine and Dentistry – Western ... and Mount Sinai Hospital, Department of Medicine, University of Toronto, and ... lung disease: (i) normal (no chronic obstructive pul-.
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ORIGINAL ARTICLE

Impact of pulmonary nontuberculous mycobacterial treatment on pulmonary function tests in patients with and without established obstructive lung disease MAULI MEHTA,1 KENNETH R. CHAPMAN,2 MATTHEW HEFFER3 AND THEODORE K. MARRAS2 1

Department of Internal Medicine, Schulich School of Medicine and Dentistry – Western University, London, 2Joint Division of Respirology, University Health Network and Mount Sinai Hospital, Department of Medicine, University of Toronto, and 3 Division of Respirology and Medicine, St. Joseph’s Health Centre, Toronto, Ontario, Canada

ABSTRACT Background and objective: There is relatively little data regarding pulmonary function test (PFT) findings and impact of treatment on PFT in pulmonary nontuberculous mycobacterial (pNTM) disease. Methods: We performed a retrospective study on pNTM patients. Clinical, radiographical, microbiological and PFT data were reviewed. Patients were divided into three groups based on pre-existing obstructive lung disease: (i) normal (no chronic obstructive pulmonary disease (COPD) or asthma); (ii) asthma; and (iii) COPD. We studied pre-treatment PFT and assessed for PFT changes after anti-mycobacterial therapy. Results: A total of 96 patients fulfilled ATS disease criteria and had pre-treatment PFT (54 ‘normal’, 18 asthma, 24 COPD). Most common causative NTM was Mycobacterium avium complex (76%), and radiographical disease type was nodular bronchiectasis (71%). Before therapy, all groups had PFT abnormalities, including obstruction, gas trapping and at least mildly low diffusion capacity of carbon monoxide (DLCO). Pre-treatment PFT abnormalities were more pronounced among patients with asthma and COPD. A total of 44 patients had >12 months anti-mycobacterial therapy and post-treatment PFT. There tended to be small and generally not statistically significant reductions in spirometry and DLCO in most groups. Among the nine asthmatic patients, there was a small reduction in residual volume (RV) (1.5% predicted, P = 0.01) and RV/total lung capacity (by 7% predicted, P = 0.06). Conclusions: Patients with pNTM have abnormal PFT, and treatment was not associated with substantial changes therein. Asthmatics may experience some improvements in gas trapping after NTM therapy, but because the sample size and the observed change were both small, this requires further investigation.

Correspondence: Theodore K. Marras, Toronto Western Hospital, Rm. 7E-452 East, 399 Bathurst Street, Toronto, ON M5T 2S8, Canada. Email: [email protected] Received 8 February 2014; invited to revise 9 May and 3 November 2014, 27 February 2015; revised 4 September and 20 November 2014, 1 March 2015; accepted 1 March 2015 (Associate Editor: Paul Thomas).

Article first published online: 25 May 2015 © 2015 Asian Pacific Society of Respirology

SUMMARY AT A GLANCE Does treating nontuberculous mycobacterial disease improve pulmonary function? Pretreatment, patients with NTM had obstruction and gas trapping. Post-treatment, patients with coexisting asthma had small improvements in gas trapping, whereas no improvements were noted in other patient groups. Further research is needed to explore possible physiological benefits of NTM therapy.

Key words: infections atypical, mycobacterial infections atypical, nontuberculous mycobacterial infection, obstructive lung disease, pulmonary function test. Abbreviations: ATS, American Thoracic Society; COPD, chronic obstructive pulmonary disease; CT, computed tomography; DLCO, diffusion capacity of carbon monoxide; FC, fibrocavitary; FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; MAC, Mycobacterium avium-intracellulare complex; NB, nodular bronchiectasis; PFT, pulmonary function test; pNTM, pulmonary nontuberculous mycobacterial; RV, residual volume; TLC, total lung capacity.

INTRODUCTION Pulmonary nontuberculous mycobacterium (pNTM) infection is an increasingly common problem requiring complex assessment and management.1–4 Current guidelines suggest treatment with multiple antibiotics for at least 12 months, with culture conversion as an indicator of treatment success.1 Disease is frequently chronic despite prolonged multi-drug therapy, secondary to difficulty in tolerating intensive therapy, an inability to eradicate the infection (sometimes due to drug resistance), and recurrence after apparently successful therapy.1,5 It is therefore important to identify patients at greater risk for clinical deterioration and provide optimal therapy to those patients.1,6 Respirology (2015) 20, 987–993 doi: 10.1111/resp.12565

988 Pulmonary function tests (PFT) have demonstrated value in the assessment and monitoring of common respiratory diseases, but few studies have examined PFT changes in patients with NTM lung disease.7,8 Patients with pre-existing chronic obstructive pulmonary disease (COPD) or bronchiectasis are particularly predisposed to pulmonary NTM disease, and the infection may play a role in progression of preexisting lung disease and deterioration of the preinfection lung function.9,10 In patients without known pre-existing lung disease, pulmonary NTM could initiate the development of PFT abnormalities. A rapid decrease of forced expiratory volume in 1 s (FEV1) has been described in younger pNTM patients with good baseline lung function in the presence of abronchiectatic radiological pattern and worse radiographical scores.6 Gas trapping and gas exchange abnormalities have been reported in patients with pulmonary Mycobacterium avium-intracellulare complex (MAC) infection and no known predisposing lung disease.11 Impairment in pulmonary function has been shown following treatment for Mycobacterium tuberculosis, but few data have examined PFT pre- and post-NTM treatments.12,13 To our knowledge, the impact of anti-pNTM therapy in patients with prior established obstructive lung disease has not been evaluated in a large population of patients. Understanding the impact of pNTM treatment on PFT will improve the use of PFT in monitoring pNTM patients and provide a method to evaluate effects of therapy. In patients with pNTM, we sought to assess for the presence of PFT abnormalities and changes after antimycobacterial therapy.

METHODS We performed a retrospective study of patients with at least one pNTM isolate and a PFT measured before treatment, between August 2003 and July 2010, in our clinics at a tertiary care centre. Medical records of all subjects including clinical notes were used to gather data on clinical symptoms, presence of underlying lung disease, co-morbidities, microbiological burden of infection, and nature and distribution of abnormalities on computed tomography (CT) scans. One author (TKM) reviewed all CT scans in addition to reports and categorised the predominant radiographical disease type (nodular bronchiectasis, fibrocavitary (FC), random nodules, consolidation and unclassifiable). Patients were considered as having pNTM disease if they fulfilled American Thoracic Society (ATS) criteria for disease.1 Patients were classified as ‘normal’ (no pre-existing COPD or asthma), ‘COPD’ or ‘asthma’. Patients were classified using a combination of clinical, PFT and radiological criteria from clinical records of two respirologists (authors TKM and KRC), PFT (historical and/or those used in the current investigation) and review of CT scans. Asthma was defined by the presence of all of: at least partially reversible obstruction or a positive methacholine challenge, the absence of emphysema on CT scan, and in the setting of some fixed obstrucRespirology (2015) 20, 987–993

M Mehta et al.

tion, the absence of a significant smoking history. COPD was defined by the presence of at least some fixed obstruction and either emphysema on CT or significant smoking history. Patients with features suggesting an overlap of COPD and asthma were classified as COPD. PFT used in this study were all conducted in a single laboratory at the University Health Network, with consistent predicted equations over the study period for spirometry,14 lung volumes15 and diffusion capacity of carbon monoxide (DLCO).16 Pulmonary function values obtained prior to pNTM antibiotic treatment were reviewed and recorded as absolute values and percent of predicted. Among patients in the cohort who received greater than 12 months of pNTM antibiotic treatment that was consistent with ATS guidelines,1 we reviewed posttreatment PFT and compared pre- and posttreatment values. The study was reviewed and approved by the Research Ethics Board of the University Health Network. Proportions or means (standard deviations) were used to describe baseline PFT, demographic, clinical and radiographical characteristics. Baseline PFT and clinical characteristics were reported and compared according to the study classification (normal, COPD or asthma). Because much smaller groups of patients had data before and after treatment, nonparametric methods were used for assessing PFT changes after pNTM treatment. Post-treatment PFT changes are presented as median (interquartile range) and compared within groups (before vs after treatment) using Wilcoxon signed rank sum tests. Statistical analyses were performed using Microsoft Office XL 2007 (Microsoft, Redmond, WA, USA), StatCalc (Centers for Disease Control and Prevention, Atlanta, GA, USA), GraphPad online calculator (http://www.graphpad .com, accessed 20 May 2013) and SAS 9.3 (SAS Institute, Cary, NC, USA). A P value of