Based on the risk factors associated with COPD mortality, R software was developed for use in predicting the risk of COPD mortality in lung cancer patients at 5, 8, and 10 years (Fig. 3). As shown in Fig. 4, the AUC values of the model in the training cohort were 0.886, 0.870, and 0.873, respectively, and in the validation cohort, the AUC values were 0.901, 0.888, and 0.879, respectively. As shown in Fig. 5, there was a high degree of consistency between the model's predicted survival and the actual observed values, which indicated that the model had an excellent predictive performance. DCA showed that the model had a significant positive net benefit over a wide range of mortality risks, further demonstrating the high clinical utility of the model for lung cancer patients (Fig. 6).

In this large population-based study using the SEER database, we characterize for the first time the distribution of mortality in COPD patients in a population with different characteristics. Meanwhile, factors associated with COPD mortality in lung cancer patients were identified by retrospective analysis of a large cohort and validated using different statistical methods. It was successfully verified that bone metastasis had a significant effect on COPD mortality in different characterized lung cancer populations, which provided a clinical basis for the interaction between COPD and bone metastasis. In addition, this study further constructed and validated a clinical prediction model for predicting the risk of COPD mortality in lung cancer patients, and the model demonstrated high predictive accuracy, which provides a strong reference for clinicians to make treatment decisions.

This study demonstrates that sex is an independent prognostic factor for COPD mortality and that female patients have a better prognosis than males. We suggest that this difference involves multiple factors, including biological, behavioral, environmental, and medical aspects. First, gender differences in biological characteristics are a contributing factor. Several studies have shown that women have relatively smaller lung volumes and larger airways, which may make them somewhat more adaptable or resistant to the pathologic changes of COPD. In addition, estrogen may play a role in protecting lung function in women. Although the mechanism is not fully understood, some studies have shown that estrogen has a protective effect on the inflammatory response and repair of the lungs. Second, even though smoking is increasing among women, overall, men continue to smoke at higher rates than women. And since smoking is a major risk factor for COPD, the difference may be reflected in disease severity and mortality. It is also worth noting that women are usually more focused on health screening and early intervention than men, which may lead to earlier detection and treatment of the disease, thus improving prognosis. Notably, factors affecting mortality in patients with COPD differed in the presence or absence of coexisting lung cancer. In patients with COPD alone, the main risk factors for mortality include advanced age, severe airflow limitation (FEV < 50% predicted), frequency of acute exacerbations, comorbid cardiovascular disease, and low body mass index. In contrast, the present study demonstrated that when lung cancer coexisted, tumor-specific factors (e.g., histological type, T/N stage, bone metastasis) and anticancer treatments (surgery, chemotherapy) significantly increased the complexity of COPD deaths, in addition to covariates such as age and gender. For example, bone metastases act as a risk amplifier for COPD mortality specific to lung cancer coexistence by exacerbating systemic inflammation, limiting respiratory function, and increasing treatment conflict. This discrepancy highlights the specificity of managing lung cancer-colonial lung co-morbidity and the need to integrate dual strategies of tumor control and maintenance of respiratory function.

It is now generally recognized that when patients are accompanied by multiple organ metastases, the prognosis is usually poor. Among them, bone, lung, liver, and brain are the most common sites of metastasis in lung cancer patients. Surprisingly, however, this study demonstrated that bone metastasis alone was a risk factor for COPD mortality, significantly affecting lung cancer patients, and this result was further validated in a subgroup analysis of populations with different characteristics. The association between bone metastasis and COPD has been described at the mechanistic level in several previous studies. The results of the present study, however, provide evidence supporting the interaction between bone metastasis and COPD from a clinical perspective. We believe that this phenomenon can be explained from multiple perspectives, including disease progression, comorbidity control, systemic effects, and overall health status. Both COPD and cancer can cause systemic inflammatory responses. Bone metastases further activate inflammatory mediators, leading to an increased systemic inflammatory burden, which in turn exacerbates the progression and deterioration of COPD. At the same time, patients with advanced cancer are often accompanied by severe immune suppression, making them more susceptible to infections and other complications, which is particularly fatal in COPD patients. Once bone metastasis occurs in lung cancer patients, it is usually accompanied by severe bone pain, which may lead to shallow breathing and reluctance to take deep breaths, thus decreasing the ventilation of the lungs and promoting the development of infections and pulmonary complications. As a result of the pain and anxiety, patients may experience a further decrease in lung ventilation and lung gas exchange due to their reluctance to move, exacerbating COPD symptoms. It is also worth noting that the treatment of bone metastases may require potent painkillers and bone repair medications, which may interact with medications used for the treatment of COPD (e.g., steroids, bronchodilators, etc.), compromising efficacy and safety. Patients with cancer bone metastases are usually in a state of generalized weakness, with significantly reduced physical capacity and resistance. This makes them less able to cope with acute exacerbations of COPD and worsening of the chronic course. Overall, the higher risk of death from COPD in patients with lung cancer with bone metastases reflects a combination of complex causes. These causes include increased systemic inflammation, decreased respiratory function due to pain, treatment conflicts, management difficulties, and significant deterioration in physical status.

Consistent with previous reports and perceptions that older lung cancer patients are at greater risk of mortality from period COPD. Lung function naturally declines in the elderly as they age. Reduced lung tissue elasticity, decreased lung capacity, and increased airway resistance make elderly lung cancer patients more susceptible to respiratory failure due to COPD. The weakened immune system of the elderly makes them more susceptible to respiratory infections, which can exacerbate the symptoms and condition of COPD and lead to an increased risk of death. In addition, older patients are more likely to have multiple chronic conditions such as cardiovascular disease, diabetes, and hypertension. These comorbidities interact with COPD and lung cancer, increasing the complexity of managing the condition and the risk of death. In addition, older patients are less likely to tolerate conventional treatments, especially chemotherapy, radiotherapy, and surgery. Treatment for COPD may be less effective due to frailty and attenuation of cardiopulmonary function. Elderly lung cancer patients have a higher mortality rate due to COPD because of age-related decline in lung function, weakened immunity, multiple comorbidities, poor treatment tolerance, poor overall health, and psychological and social factors. These complex factors interact to increase the difficulty of managing the condition and the risk of death in elderly patients. This study demonstrates that histologic type has a significant effect on mortality associated with COPD, with SC having the most significant effect. We hypothesize that this is because SC usually originates in the larger bronchi and tends to invade the airways locally. This characteristic makes SC more likely to cause airway obstruction or narrowing, exacerbating symptoms of dyspnea and airflow limitation in COPD patients. In addition, patients with SC tend to produce more sputum, which may lead to airway obstruction and increase the risk of infection and inflammation, exacerbating the symptoms of COPD. Also, patients with squamous cancer may be less tolerant of some treatments (such as chemotherapy and radiation), and more complications and side effects may occur during treatment, exacerbating COPD symptoms. All of these reasons put these patients at a higher risk of facing complications such as respiratory infections, which can lead to an increased risk of mortality due to COPD.

The model and results constructed in this study are rigorous and reliable and can inform clinicians' clinical decisions. The COPD mortality prediction model constructed in this study is not only statistically significant but also provides actionable clinical decision support for individualized management of lung cancer patients. For example, individualized risk scores were calculated by the model to quickly screen out the 5/8/10-year COPD mortality high-risk groups. Secondly, patients with ≥ 30% 10-year risk predicted by the model can be included in the palliative support team at an early stage. However, the study has some limitations. First, as a multicenter retrospective study, selection bias is inevitable. The primary validation of our model was performed internally using a subset of the same SEER database. While this demonstrates robustness in the dataset, it does not guarantee performance in a completely external population or a different healthcare setting. External validation using an independent prospective cohort is essential to confirm the generalizability and portability of the model before widespread clinical application. Future studies should prioritize this step. Second, an important limitation inherent in the SEER database is the lack of detailed information on smoking history (e.g., smoking status, pack-years, duration, time to quit). However, this first large-scale cohort study focusing on COPD mortality in lung cancer provides insights into the distributional characteristics and risk factors of COPD mortality among lung cancer patients. The constructed predictive model allows physicians to make recommendations regarding the survival of lung cancer patients and to focus on the prevention of COPD mortality.