Mycobacterium avium complex pulmonary disease, often abbreviated MAC-PD, belongs to a family of infections caused by non-tuberculous mycobacteria, organisms that are widespread in soil and water and that can colonize the lungs of susceptible individuals, particularly older women with certain structural lung characteristics and people with compromised immune defenses. Unlike tuberculosis, MAC-PD is not generally transmitted from person to person, but it shares a troubling feature with its more famous cousin: treatment is long, burdensome, and frequently followed by relapse. Patients typically endure multidrug antibiotic regimens lasting many months or years, and even those who achieve conversion of their sputum cultures to negative face a substantial probability that the infection will reappear. The recurrence rate is high enough that clinicians increasingly describe MAC-PD not as an acute infection to be eradicated but as a chronic disease requiring long-term management strategies, yet no intervention has ever been prospectively proven to reduce the risk of recurrence after cure.

It is this therapeutic vacuum that the new trial aims to fill, and the choice of candidate is deliberate. Bailing capsule is a fermented preparation of Cordyceps sinensis, a fungus that has been used in Chinese medicine for centuries and that has already been granted approval in China for the treatment of chronic bronchitis and chronic obstructive pulmonary disease. The research team points to previous studies suggesting that the preparation exerts immunomodulatory effects, meaning that rather than attacking bacteria directly, it may help recalibrate the host immune system that failed to clear the mycobacteria in the first place. This concept, known as host-directed therapy, has attracted growing interest in infectious disease research because it offers a way to bolster the body’s own defenses in situations where antibiotics alone are insufficient, toxic, or undermined by resistance. If the immune environment of the lung can be shifted toward one that resists re-infection or reactivation, the logic goes, the cycle of cure and relapse might finally be broken.

The design of the study reflects an unusually high standard of rigor for research in complementary medicine. The investigators plan to recruit 300 participants who have achieved microbiologically cured MAC-PD, confirmed by laboratory testing, and to assign them randomly in a one-to-one ratio to receive either Bailing capsule or an indistinguishable placebo. Neither the patients nor the treating clinicians and assessors will know who is receiving the active preparation, a double-blind arrangement that guards against bias in symptom reporting and outcome assessment. Both groups will take four capsules three times per day by mouth for twelve consecutive months, a dosing schedule and duration chosen to provide sustained exposure while remaining feasible for patients to adhere to over the long treatment period.

Monitoring during the trial will be intensive. Participants will return for follow-up visits every month, at which they will complete quality-of-life questionnaires, undergo blood analyses, and receive radiologic examinations of the chest. The primary outcome measure is the rate of MAC-PD recurrence within twelve months, and the investigators have specified a demanding diagnostic standard for detecting it: recurrence must be confirmed either by culture of mycobacteria or by sequencing-based detection, ensuring that the endpoint rests on objective microbiological evidence rather than on clinical impression alone. This matters because respiratory symptoms in patients with prior MAC-PD can fluctuate for many reasons, and attributing worsening to recurrence without laboratory confirmation risks overstating both disease activity and treatment effects.

Beyond the primary endpoint, the trial will track a battery of secondary outcomes designed to capture the fuller clinical picture. These include the time it takes for recurrence to occur, the rate of other respiratory tract infections, quality of life as measured by validated instruments, respiratory symptoms, and adverse events. The inclusion of adverse event surveillance is particularly important for a widely used over-the-counter-style preparation, since large randomized cohorts are among the best settings in which to detect side effects that smaller or shorter studies might miss. The parallel-group design, in which the two arms proceed simultaneously under identical conditions, further strengthens the trial’s ability to isolate the effect of the capsule from seasonal variation in respiratory infections and from differences in care across the participating hospitals.

The scale and structure of the study also speak to a broader ambition. According to the investigators, this is the first trial to prospectively evaluate any specific intervention for reducing the recurrence of MAC-PD, a claim that underscores how little evidence-based guidance currently exists for the post-cure phase of this disease. The authors describe the rigid design and large sample size as key features boosting the statistical power of the study, and they frame the project as an effort to establish traditional Chinese medicine as a legitimate form of host-directed therapy in the long-term management of chronic infectious disease. They also acknowledge that questions will remain even if the trial succeeds, noting that further research will be needed to determine the optimal duration of treatment, since twelve months of capsules may represent only one point on a longer dosing curve.

The institutional backing behind the study lends it additional weight. The trial is coordinated through the National Center for Respiratory Medicine and the State Key Laboratory of Respiratory Health and Multimorbidity at the China-Japan Friendship Hospital, one of China’s leading respiratory institutions, and draws co-investigators from Capital Medical University, Shanghai University of Traditional Chinese Medicine’s Longhua Hospital, Shanghai Pulmonary Hospital affiliated with Tongji University, Guangzhou Chest Hospital, Beijing Chest Hospital, Anhui Chest Hospital, and Jiangxi Provincial Chest Hospital. The protocol has received ethics approval from the ethics committee of the China-Japan Friendship Hospital under approval number 2025-KY-004-2, and the investigators state that the trial will be conducted in accordance with the Good Clinical Practice guideline and the Declaration of Helsinki. The authors declare no competing interests, and the work is supported by a grant from the National Science and Technology Major Project.

For patients, the stakes are considerable. MAC-PD predominantly affects people who already carry significant respiratory burden, and each episode of recurrence can mean another round of toxic multidrug antibiotic therapy, repeated hospital visits, and mounting anxiety about a disease that seems to keep returning. A safe, orally administered adjunct that meaningfully reduced recurrence would transform the outlook for this population, shifting the post-cure period from watchful waiting to active prevention. It would also represent a notable milestone for the scientific evaluation of traditional Chinese medicine, demonstrating that a classical fungal preparation can be tested against the same gold-standard criteria applied to any modern pharmaceutical.

Caution remains warranted, as it always does at the protocol stage. A published trial design is a promise of evidence to come, not a result, and the history of medicine is littered with promising hypotheses that dissolved under the scrutiny of randomized data. The true test will arrive when the 300 participants have completed their twelve months of capsules and monthly follow-ups, and when the culture and sequencing results reveal whether the Bailing group truly experienced fewer recurrences than those receiving placebo. Until then, the study stands as a carefully constructed experiment at the intersection of ancient pharmacology and modern immunology, one whose outcome could reshape how clinicians think about preventing relapse not only in MAC-PD but potentially in chronic infections more broadly. If the fungus that has been a fixture of Chinese apothecaries for centuries does prove its worth in a double-blind trial, it will do so not on the strength of tradition, but on the strength of data.

Subject of Research: A randomized controlled trial of Bailing (Cordyceps sinensis) capsule for preventing recurrence of Mycobacterium avium complex pulmonary disease

Article Title: The effect of Bailing (Cordyceps sinesis) capsule in preventing recurrence of mycobacterium avium complex pulmonary disease: a protocol of multicenter, randomized, double-blind, placebo-controlled trial

Article References: The effect of Bailing (Cordyceps sinesis) capsule in preventing recurrence of mycobacterium avium complex pulmonary disease: a protocol of multicenter, randomized, double-blind, placebo-controlled trial. (n.d.). https://doi.org/10.1186/s12906-026-05614-w

Image Credits: AI Generated

DOI: 10.1186/s12906-026-05614-w

Keywords: Mycobacterium avium complex, non-tuberculous mycobacteria, Cordyceps sinensis, Bailing capsule, traditional Chinese medicine, host-directed therapy, pulmonary disease recurrence, randomized controlled trial, immunomodulation, respiratory medicine, clinical trial protocol, placebo-controlled