Chronic Fungi Infection Tied to Poor Outcomes in NTM Lung Disease

Chronic Fungi Infection Tied to Poor Outcomes in NTM Lung Disease

Early identification and prompt treatment of chronic pulmonary aspergillosis — a lung infection caused by fungi belonging to the Aspergillus genus — are needed to improve outcomes for people with pulmonary disease caused by non-tuberculous mycobacteria (NTM), a Japanese study reported.

The study, “New/Different Look at the Presence of Aspergillus in Mycobacterial Pulmonary Diseases. Long-Term Retrospective Cohort Study,” was published in the journal Microorganisms.

NTM and Aspergillus are both microorganisms that can cause disease, including chronic lung infections that result in NTM pulmonary disease (NTM-PD) and chronic pulmonary aspergillosis (CPA).

Both types of infections are known to increase the chances of developing bronchiectasis, a lung disease characterized by excessive mucus production and enlargement of the lungs’ airways due to recurrent infections.

Although the exact relationship between these two types of infections is unclear, it is thought that patients with NTM-PD, particularly those who also have bronchiectasis, may be at a higher risk of CPA for several reasons.

One has to do with treatment. The broad spectrum antibiotics normally used to destroy NTM raises the risk of patients’ lungs being colonized by fungi, potentially leading to CPA onset.

Another is particular to bronchiectasis. Patients’ excessive mucus production can trap fungi inside the airways, further increasing the risk of CPA.

Previous studies have indicated poorer outcomes in people with NTM-PD who develop CPA.

“However, whether isolation of Aspergillus species is associated with poor outcome or mostly just the reflection of colonization is a widely debated issue and a yet unsolved question,” the researchers wrote.

To clarify this, researchers evaluated the prevalence and impact of Aspergillus lung colonization for CPA development in NTM pulmonary disease patients.

They reviewed the medical records of 409 people with NTM-PD (264 women and 145 men, mean age of 62), who were followed at the National Hospital Organization Osaka Toneyama Medical Center between January 2008 and October 2019.

All patients in the analyses had at least one respiratory fungal exam during follow-up, including fungal cultures grown from lung samples. All were followed for a median of 85 months (around seven years) following NTM-PD diagnosis.

Fungi species belonging to the Aspergillus genus were found in 79 (19.3%) patients over those years. Twenty-three people, who made up 29.1% of those with Aspergillus in the lungs and 5.6% of the overall population, ended up developing CPA.

A total of 73 people died during follow-up. Most deaths were due to NTM-PD progression (47.9%), followed by pneumonia (17.8%), lung cancer (12.3%), and other respiratory conditions (11.0%). CPA was identified as the cause of death in three (4.1%) patients.

Statistical analyses showed no association between the presence of Aspergillus in the lungs and a higher risk of death in NTM-PD, suggesting “that isolation of Aspergillus species alone was not associated with poor prognosis” for this group.

In contrast, the presence of CPA was found to significantly affect survival.

Subsequent analyses also identified the use of systemic steroids and the presence of lung cavities associated with NTM infection as independent risk factors for CPA.

Based on these observations, the researchers proposed that “Aspergillus-related conditions in NTM-PD can be classified as totally different subgroups: Aspergillus colonization and chronic infection such as CPA development.”

The presence of Aspergillus in the lungs is likely “a consequence of airway clearance defects,”  they added, and is not, by itself, associated with poor outcomes in these patients. Yet, “considering the high mortality rate of CPA in NTM-PD, early diagnosis and treatment are essential to improve outcomes for NTM-PD patients,” they concluded.