Introduction:
Pneumothorax is the presence of air in the pleural cavity, often resulting in respiratory distress and impaired lung function. Although clinical observations have shown that high intensity physical activity and frail state affect respiratory health, their causal role in pneumothorax development is unclear. This study is the first to use a two-sample Mendelian randomization method (TSMR) to investigate the causal relationship between physical activity and frailty and the risk of pneumothorax, with a view to providing new insights into the pathogenesis of pneumothorax and preventive strategies.

Material and methods:
Using Mendelian randomization (MR) analyses, we examined the potential causal relationship between physical activity, frailty, and the risk of pneumothorax. Genetic instrumental variables (IVs) for relevant exposure factors were selected from genome wide association studies (GWAS). The study was analyzed using five different methods, mainly using inverse variance weighted (IVW) to draw causal inferences. Sensitivity analyses were performed to ensure the validity of the MR results. Sensitivity analyses included the detection of horizontal pleiotropy, i.e., genetic variants affecting the outcome through pathways other than the target exposure, which may lead to biased causal inference. Heterogeneity between genetic instrumental variables was also assessed and used to detect variability in effect estimates, which may reflect violations of MR assumptions or differences between populations.

Results:
Our analyses found that light DIY reduced the risk of pneumothorax, but did not identify a causal association between other levels of physical activity and pneumothorax. In addition, frailty index (FI) showed a positive association with the risk of developing spontaneous pneumothorax, and this causal relationship persisted after adjustment for body mass index (BMI) and light DIY. Sensitivity analyses further validate the robustness of our findings.

Conclusions:
Our findings support the ability of light DIY to reduce the risk of pneumothorax development. It also emphasizes the need for frail individuals to be more aware of the need to protect against pneumothorax in their daily lives. We encourage appropriate exercise to improve fitness and reduce the risk of pneumothorax.