Research Article: Retrospective evaluation of natural course in mild cases of Mycobacterium avium complex pulmonary disease

Date Published: April 25, 2019

Publisher: Public Library of Science

Author(s): Yoshifumi Kimizuka, Yoshihiko Hoshino, Tomoyasu Nishimura, Takahiro Asami, Yumi Sakakibara, Kozo Morimoto, Shinji Maeda, Noboru Nakata, Takayuki Abe, Shunsuke Uno, Ho Namkoong, Hiroshi Fujiwara, Yohei Funatsu, Kazuma Yagi, Toshihide Fujie, Makoto Ishii, Naohiko Inase, Satoshi Iwata, Atsuyuki Kurashima, Tomoko Betsuyaku, Naoki Hasegawa, Atsushi Miyamoto.


There is no proven management for mild cases of Mycobacterium avium complex (MAC) pulmonary disease, who do not immediately receive treatment and are managed with observation alone, because its long term-natural course, factors predictive of deterioration, and the effect of treating the disease remain unclear. Thus, we sought to investigate the natural course of mild cases of MAC pulmonary disease.

We conducted a multicenter retrospective study. Sixty-five patients with mild MAC pulmonary disease in whom treatment was withheld for at least 6 months after diagnosis were retrospectively recruited after a review of 747 medical records. Longitudinal changes in clinical features were evaluated by using a mixed effects model.

Mean follow-up was 6.9 ± 5.7 years. During the follow-up period, 15 patients (23%) required treatment and 50 (77%) were managed with observation alone. At diagnosis, 65 patients had nodular bronchiectatic disease without fibrocavitary lesions. Among clinical features, mean body mass index (BMI), forced expiratory volume in 1 second as percent of forced vital capacity (%FEV1), nodular lung lesions, and bronchiectasis worsened significantly in the observation group during follow-up. In the treatment group, BMI, and %FEV1 were stable, but bronchiectasis significantly worsened. At diagnosis, the polyclonal MAC infection rate in the treatment group was higher than that in the observation group. Other microbiological factors, such as insertion sequences, did not differ significantly between the groups.

Mild MAC pulmonary disease progresses slowly but substantially without treatment. Treatment prevents the deterioration of the disease but not the progression of bronchiectasis. Polyclonal MAC infection is a predictor of disease progression.

Partial Text

The prevalence of nontuberculous mycobacterial (NTM) pulmonary disease is increasing around the world, especially in developed countries [1–8]. Although substantial geographic differences are seen in the distribution of the pathogens responsible for NTM pulmonary disease, the Mycobacterium avium complex (MAC) is the most common pathogen in Japan and in other developed, pan-Pacific countries [1–9]. Radiographic features of MAC pulmonary disease (pMAC) are classified into two main types, fibrocavitary and nodular bronchiectatic. A large proportion of patients with the nodular bronchiectatic form of pMAC are middle-aged or elderly female patients without pulmonary comorbidities or history of smoking [10].

There is no established strategy for the management of patients with mild pMAC who do not immediately receive treatment and are managed by observation alone because the long-term natural clinical course and the effects of that treatment remain unclear. Our multicentre, retrospective study describes both the clinical course and the bacterial profiles of mild pMAC at diagnosis and without treatment. We show that polyclonal MAC infection could become a predictor of deterioration in mild pMAC, that mild pMAC slowly but substantially progresses over several years without treatment and that treatment may slow deterioration in pulmonary function, perhaps by improving reversible pulmonary lesions.

Polyclonal MAC infection is a predictive of clinical deterioration that may eventually require treatment. Mild pMAC without anti-microbial treatment showed slow but significant clinical and radiologic deterioration. Treatment can prevent deterioration due to disease but not progression of bronchiectasis.