Risk Factors and Long-Term Prognosis for Coinfection of Nontuberculous Mycobacterial Pulmonary Disease and Chronic Pulmonary Aspergillosis: A Multicentre Observational Study in Japan

Abstract

Background: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic respiratory infection with increasing prevalence and mortality worldwide. Coinfection with chronic pulmonary aspergillosis (CPA) is a significant complication of NTM-PD, often complicating treatment and resulting in poor prognosis.

Objective: In this multicentre, retrospective cohort study, we examined the epidemiology, comorbidities, risk factors for CPA coinfection and long-term prognosis of patients with NTM-PD infected with CPA in Japan.

Methods: Patients aged ≥ 18 years with newly diagnosed NTM-PD who visited 18 hospitals between 2010 and 2017 in Kyushu, Japan, were included. Medical records were reviewed for patient characteristics, mycobacterial species, laboratory data, radiological features, Aspergillus coinfection and all-cause mortality rates. Risk factors for CPA coinfection were analysed using multiple logistic regression, and survival analysis was performed before and after propensity score matching with risk factors.

Results: Among 1304 patients with NTM-PD, 45 (3.5%) were diagnosed with CPA, including 42 with chronic progressive pulmonary aspergillosis. The risk factors for CPA coinfection included male sex, chronic obstructive pulmonary disease, oral corticosteroid use and cavity formation. All-cause mortality was significantly higher in patients with NTM-PD with CPA than in those without CPA (log-rank test, p < 0.001; crude hazard ratio [HR], 3.98). Survival analysis after propensity score matching suggested CPA was an independent poor prognostic factor (log-rank test, p = 0.036; adjusted HR, 1.59).

Conclusion: CPA is an independent poor prognostic factor in patients with NTM-PD. Clinicians must consider CPA when treating patients with NTM-PD, particularly those with high-risk factors, to ensure timely diagnosis and management.

Keywords: Aspergillus; Mycobacterium avium complex; Mycobacterium infections; coinfection; nontuberculous mycobacteria; propensity score; pulmonary aspergillosis; retrospective studies.

FIGURE 1

Flowchart of study patients. During the study period, 1317 patients were newly diagnosed with NTM‐PD, and 1304 were evaluated. The median observation period was 59 months (IQR: 19–95 months). Of these, 45 patients (3.5%) were diagnosed with CPA, and there were three cases of simple aspergilloma and 42 cases of CPPA, including CCPA, CFPA, and SAIA. CCPA, chronic cavitary pulmonary aspergillosis; CFPA, chronic fibrosing pulmonary aspergillosis; CPA, chronic pulmonary aspergillosis; CPPA, chronic progressive pulmonary aspergillosis; IQR, interquartile range; JSTNM, The Japanese Society for Tuberculosis and Nontuberculous Mycobacteriosis; NTM‐PD, nontuberculous mycobacterial pulmonary disease; SAIA, subacute invasive pulmonary aspergillosis.

FIGURE 2

Duration from nontuberculous mycobacterial pulmonary disease diagnosis to chronic pulmonary aspergillosis diagnosis. The median duration from NTM‐PD diagnosis to CPA diagnosis was 26 months (IQR, 12–58 months), with a mean of 38.4 ± 32.6 months. CPA, chronic pulmonary aspergillosis; IQR, interquartile range; NTM‐PD, nontuberculous mycobacterial pulmonary disease.

FIGURE 3

Kaplan–Meier analysis for patients with NTM‐PD with or without CPA, before (A) and after (B) propensity score matching. Patients with NTM‐PD infected with CPA had significantly worse prognoses than those without CPA (A). Analysis after propensity score matching for age, male sex, COPD, oral corticosteroid use, and cavity formation showed that CPA was a significantly poor prognostic factor (B). COPD, chronic obstructive pulmonary disease; CPA, chronic pulmonary aspergillosis; NTM‐PD, nontuberculous mycobacterial pulmonary disease.