Non-pharmacological therapies for patients with lymphangioleiomyomatosis: a systematic review and meta-analysis

This study aims to systematically review non-pharmacological therapies for patients with lymphangioleiomyomatosis (LAM), and synthesize the effects of non-pharmacological therapies on 6-minute walking distance test (6MWDT), pulmonary function (FEV₁), and quality of life in LAM patients.

The systematic review and meta-analysis design was used. Data were searched on Scopus, Web of Science, PubMed, Embase, OVID, CINAHL, CNKI and Wang Fang for studies published from August 2015 to August 2025 on non-pharmacological therapies for patients with LAM. Studies were screened using rigorous inclusion and exclusion criteria. Study quality was assessed using JBI study quality evaluation tools, and a stratified narrative synthesis was conducted based on intervention types, supplemented with a meta-analysis (excluding single-case report).

Five studies were eligible to be included in this study. Narrative synthesis showed that interventions with multicomponent, including high intensity aerobic and strength training, yoga, pulmonary rehabilitation and telemonitoring exercise, are beneficial for patients with LAM. Meta-analysis results (excluding the case report) showed that non-pharmacological therapies, particularly structured exercise programs, significantly increased physical activity tolerance of patients with LAM (p < 0.00001) by 37.39 meters using 6MWDT, compared to the pre-intervention or comparison group (95% CI: 27.29, 46.98). Non-pharmacological therapies increased pulmonary function FEV₁ (MD: 0.20, 95% CI: -0.02, 0.42) and quality of life (SMD: -0.19; 95%CI: -0.56, 0.18) of the patients with LAM, compared to the pre-intervention or comparison group, however, the results were not significant (p = 0.08 and 0.32, respectively). No serious adverse events were reported in the included studies, indicating good safety of non-pharmacological interventions.

Non-pharmacological therapies, especially physiotherapy, can improve patients with LAM's physical activity tolerance, enhancing their physical fitness and daily activity capacity. Compared with other alveolar and parenchymal diseases (e.g., tuberculosis, COPD), LAM patients show similar improvements in exercise tolerance but less significant improvements in lung function, which may be related to the unique cystic lung pathology of LAM. More effectively and innovatively designed research is needed to improve patients with LAM's pulmonary function and quality of life.

This study not only demonstrates the potential value of non-pharmacological therapies in the management of patients with LAM, but also points the directions for future research. By further optimizing the interventions and expanding the sample size, we can achieve a comprehensive understanding of the long-term effects of non-pharmacological therapies in patients with LAM, eventually providing more effective treatment options for patients.

https://www.crd.york.ac.uk/prospero/, PROSPERO system ID: CRD42024548486.