Our study showed significant improvements in patients with lung cancer who underwent PR. PR significantly improved exercise capacity, exertional symptoms, and HRQL. Although lung function parameters did not change significantly, there was a significant improvement in MIP, suggesting enhanced respiratory muscle function. Cardiovascular parameters, including the SVI, CI, WE, O2P, and AT, improved during exercise, highlighting the cardiovascular benefits of the PR program. These results suggest that an enhanced cardiopulmonary response to exercise improves exercise capacity and exertional symptoms, ultimately leading to reduced symptom burden.
The current study shows distinct demographic features of patients, including a predominance of early-stage lung cancer, a higher incidence in female and a low smoking rate. Lung cancer generally occurs more often in males than in females and is more prevalent among smokers. In Taiwan, the trend of lung cancer incidence might differ from global patterns due to various factors such as environmental influences, genetic predispositions, or lifestyle [17]. Chinese-food chefs have a 2.3-fold higher risk than non-chefs, and female not using fume extractors while cooking have a 3.5–12-fold higher lung cancer risk [17]. Recently, there has been a significant increase in lung cancer cases among Taiwanese female, particularly in early-stage lung adenocarcinoma. This trend might be linked to more nonsmokers undergoing low-dose computed tomography screening [17].
An important finding of this study was that PR resulted in improvements in MIP, VT, and VEQ during exercise. Respiratory muscles generate the pressure differences driving ventilation [18]. Respiratory muscle weakness can lead to poor ventilation efficiency, exercise capacity, and HRQL. Improved respiratory muscle strength is needed to increase VT [19]. In a previous study [19], we showed that PR improves respiratory muscle strength and VT, especially in patients with reduced respiratory muscle strength. Another notable finding was the improvement in VEQ following PR. VEQ represents the ability of the respiratory system to maintain a balance between ventilation and metabolism during exercise [14]. The improvement in VEQ suggests that PR enhances gas exchange efficiency and respiratory function during exercise. This may be attributed to improved cardiovascular fitness, better respiratory muscle coordination, and reduced respiratory effort, which contribute to more efficient ventilation and carbon dioxide removal [14]. The improvements in MIP, VT, and VEQ observed in this study provide evidence of the beneficial effects of PR on respiratory function in patients with lung cancer. These improvements likely contributed to improved exercise capacity and reduced exertional dyspnea following PR.
The observed improvement exclusively in MIP could be attributed to several factors. MIP is a direct measure of respiratory muscle strength, particularly the muscles involved in inspiration such as the diaphragm. The breathing exercises such as diaphragmatic breathing, are designed to strengthen these muscles [20]. Additionally, the measurement of MIP is sensitive and can detect even small changes in the strength of respiratory muscles [21]. MEP is the effort-dependent nature measurements can introduce bias, as maximal effort during measurements may be challenging to achieve [21]. Previous studies also showed that MIP but not MEP was associated with COPD severity [21]. Additionally, if participants had relatively well-preserved inspiratory muscle strength at baseline, the potential for improvement might be limited [19]. The effectiveness of PR in improving lung function parameters such as FEV1, FVC, and FEV1/FVC ratio is controversial [22, 23]. Previous studies have shown that PR improved these parameters in patients with poor lung function [23]. However, in our study, the patients' lung function were already above normal values, and we did not observe significant improvements in these parameters.
This study also showed that PR had a positive effect on cardiovascular parameters, including SVI, CI, WE, O2P and AT, during exercise. This suggests that PR not only improves respiratory function but also enhances cardiovascular performance. A previous study [24] reported that patients with cancer experience cardiac wasting, with structural and hemodynamic changes due to cancer-related cardiac wasting. Exercise training has been shown to improve cardiac function during exercise in patients with cancer [25]. A PR program incorporating exercise training and cardiovascular conditioning improves cardiac contractility and stroke volume, resulting in better oxygen delivery to tissues during exercise [12, 25].
O2P, WE, and AT not only serve as indicators of cardiac function, but also reflect the oxygen extraction capacity of peripheral muscles [12]. Exercise training is widely recognized for its ability to stimulate skeletal muscle growth, enhance mitochondrial function, and improve the oxygen extraction capacity of peripheral muscles [26]. Exercise training contributes to more efficient oxygen utilization in the peripheral muscles. Delayed anaerobic metabolism during exercise was observed after PR. In this study, we observed a significant reduction in leg soreness during exercise. Leg soreness is a common symptom experienced during physical activity that is often associated with muscle strain and fatigue. This suggests that exercise training can enhance muscular endurance and reduce discomfort during exercise.
Patients with lung cancer often experience cardiac or pulmonary comorbidities, which can diminish exercise performance, decrease physical activity levels, exacerbate muscle weakness, and increase symptoms [5]. A previous study demonstrated that an improvement in physical activity level was observed following PR [27]. Physical activity is also considered as an intervention for improving psychological well-being, anxiety and depression and maintaining the ability to perform daily activities [28]. Considering these significant benefits, physical activity is increasingly as a vital element of comprehensive cancer care [28].
Assessment of HRQL in lung cancer is important. Although there are several questionnaires about cancers in the past, many questionnaires are time-consuming and not easy to use. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) is commonly used in cancer research that it comprehensively encompasses physiological, respiratory, gastrointestinal, sleep functions, and financial concerns [29]. However, the EORTC QLQ-C30 is not specifically tailored for respiratory symptoms and is time-consuming, leading to its primary use in research rather than clinical practice. While the CAT was initially designed for COPD, it encompasses most respiratory symptoms, making it applicable to other pulmonary diseases such as pulmonary fibrosis [30] and coronavirus disease 2019 [31]. In our previous study, we showed that CAT also significantly reflected the changes in HRQL of lung cancer [4].
Clinical implications
This study has important clinical implications as it demonstrates that PR can significantly improve cardiopulmonary function, exercise capacity, exertional symptoms, and HRQL in patients with lung cancer. Incorporating PR into the management of patients with lung cancer can improve overall physical well-being, activities of daily living, and HRQL.
Study limitations
This study has several limitations. First, the sample size is relatively small. Its single-center design may have introduced selection bias. Multicenter studies with larger sample sizes are needed to confirm our findings. Second, this was a retrospective study. Prospective randomized controlled trials are needed to provide stronger evidence. Despite these limitations, we provide real-world evidence of the effectiveness of PR. Third, the relatively short 12-week follow-up period may not have been sufficient to determine the long-term effects of PR. Longer follow-up studies are needed to confirm the long-term effects of PR. Finally, all patients received PR in this study had non-small cell lung cancer (NSCLC), with no cases of small cell lung cancer (SCLC). Treatment strategies and prognoses significantly differ between SCLC and NSCLC. Therefore, the conclusions of this study are applicable exclusively to NSCLC and should not be generalized to SCLC.
