Predictors of Exacerbation of Japanese Bronchiectasis and Nontuberculous Mycobacterial Pulmonary Disease: A Multicenter Prospective Study

Abstract RATIONALE: Recent large-scale registries of patients with bronchiectasis across countries have revealed regional differences in disease characteristics. Although factors associated with exacerbations have been identified, limited data are available on bronchiectasis cohorts with a high nontuberculous mycobacterial (NTM) infection prevalence. We identified the risk factors for exacerbation, including nontuberculous mycobacterial pulmonary disease (NTM-PD), in a Japanese bronchiectasis registry. METHODS: The Japanese Nontuberculous Mycobacteriosis-Bronchiectasis Registry is a prospective, multicenter observational registry of patients with bronchiectasis and NTM-PD aged ≥20 years. We analyzed patients with bronchiectasis registered at 12 facilities between November 2017 and December 2019. The primary outcome was exacerbation within one year of follow-up (Hill AT, et al., ERJ 2017), where severe exacerbation required hospitalization. Multivariate logistic regression analyses were conducted using a backward elimination method based on the corrected Akaike information criterion (AICc), excluding factors with multicollinearity. The mycobacterial burden was categorized as high (acid-fast bacilli [AFB] smear-positive), low (AFB smear-negative but culture-positive), or none (both smear- and culture-negative). RESULTS: We enrolled 902 patients [mean age, 68 years; 731 women (81.0%); 701 diagnosed with NTM-PD (77.7%). In the NTM-PD group, the number of M. avium, M. intracellulare, and M. abscessus was 475 (67.8%), 127 (18.1%), and 49 (7.0%), respectively. The proportion of chronic Pseudomonas aeruginosa infection was lower in the NTM-PD group than in the non-NTM-PD group [55 (7.8%) vs. 34 (16.9%), respectively, P <0.001]. A one-year follow-up revealed that 166 cases (18.4%) exhibited exacerbation, including 79 (8.8%) with severe exacerbation. The exacerbation rates were comparable between patients with bronchiectasis with and without NTM-PD. Multivariable logistic regression analyses revealed that a history of hemoptysis requiring hospitalization (aOR 2.2, 95%CI 1.2―4.1), history of exacerbation in the previous year (aOR 1.9, 95%CI 1.2―3.0), high C-reactive protein (CRP) levels (aOR 1.3, 95%CI 1.1―1.6), and Quality of Life-Bronchiectasis (QOL-B) Respiratory Score (aOR 0.97, 95%CI 0.96―0.99), none (aOR 2.2, 95%CI 1.1―4.3) or high (aOR 2.6, 95%CI 1.3―5.3) mycobacterial burden were significantly associated with exacerbation. Severe exacerbation was associated with age (aOR 1.0, 95%CI 1.0―1.1), body mass index (aOR 0.86, 95%CI 0.77―0.97), presence of chronic infection (aOR 2.1, 95%CI 1.1―4.1), respiratory symptoms (aOR 0.97, 95%CI 0.95―0.99), history of exacerbation in the previous year (aOR 2.4, 95%CI 1.3―4.8), CRP (aOR 1.3, 95%CI 1.1―1.6), and high (aOR 4.8, 95%CI 1.4―16.3) mycobacterial burden. CONCLUSIONS: We identified factors associated with exacerbation in patients with Japanese bronchiectasis, particularly those with a high prevalence of NTM-PD.