Symptoms and extra-pulmonary consequences in patients with acute exacerbations of COPD or lung cancer

Abstract

Chronic Obstructive Pulmonary Disease (COPD) and non-small cell lung cancer (NSCLC) are diseases characterized by symptoms of dyspnea and fatigue and extra-pulmonary consequences, such as impairments in physical status (inactivity, exercise limitation, and skeletal muscle dysfunction). These consequences can be assessed with patient-reported outcome measures (PROMs) and physical tests. Patients with COPD might experience an acute exacerbation of COPD (AECOPD) characterized by increased respiratory symptoms. An AECOPD is classified as severe when a patient requires hospitalization. A severe AECOPD is associated with a further deterioration in symptoms and physical status. Evaluation of symptoms and physical status involves the use of PROMs and physical tests to quantify the impact of hospitalization. However, it remains unclear to what extent physical tests accurately capture the patient's perspective on the impact of hospitalization, especially in severe AECOPD. Study 1 investigated the relationship between physical tests and PROMs in patients experiencing severe AECOPD and showed a generally weak correlation between physical tests and PROMs. Consequently, a comprehensive assessment combining physical tests and PROMs needs to be conducted on these patients to understand the impact of a severe AECOPD on symptoms and physical status. Previous research primarily focused on evaluating the impact of a severe AECOPD on symptoms and extra-pulmonary consequences during and after an AECOPD, making it difficult to determine the extent of recovery. Study 2 examined the recovery of symptoms and extra-pulmonary consequences in patients after a severe AECOPD and compared them with matched patients with stable COPD. The study showed that one month after experiencing a severe AECOPD, patients’ symptoms and physical status were similar to those with SCOPD, indicating that patients tend to improve. However, patients experiencing severe acute exacerbations of COPD have a high risk for readmission and mortality. Study 2 determined whether physical tests and PROMs at hospital discharge for a severe AECOPD could discriminate patients’ risk for exacerbation-related readmission or mortality at six months and found that the short physical performance battery (SPPB) and five times sit-to-stand test (5STS) could discriminate patients at risk for future events. Therefore, stratifying patients for readmission and mortality risk can help healthcare providers tailor post-discharge care to the patient's needs. In patients with NSCLC, treatment options include lung resection, with or without (neo-) adjuvant treatment, radiation therapy, chemotherapy, immunotherapy, targeted therapy or a combination, or best supportive care. In patients with NSCLC undergoing lung resection, postoperative complications can occur, particularly in patients with pre-existing cardiorespiratory impairment. A cardiopulmonary exercise test (CPET) is the golden standard to identify patients at risk for complications. However, their use may be limited by logistical and financial challenges. Alternatively, the 1-minute sit-to-stand test (1MSTS) can be used, which is quick, requires minimal space and equipment, and stresses the cardiorespiratory system. Study 3 explored the prognostic ability of the 1MSTS to predict postoperative complications in patients with NSCLC using a multi-center design. The study found that patients achieving 22 repetitions or less are at increased risk for complications. Therefore, risk stratification using the 1MSTS in the preoperative period may guide patients toward prehabilitation. As a result of the disease and the treatment, patients with NSCLC may experience high symptoms of dyspnea, fatigue, and impairments in physical status. However, studies including a comprehensive assessment combining physical tests and PROMs to assess the impact of treatment are scarce. In addition, current knowledge about the impact of different treatment regimens is limited, and conflicting evidence exists. Using a comprehensive assessment, study 4 quantified the impact of different treatment regimens on symptoms and extrapulmonary consequences in patients with NSCLC. Initial findings showed that patients experience a decline in symptoms and physical status after different types of treatment. However, individual patient data indicated varying trajectories in symptoms and physical status, with some patients not deteriorating while others did. Therefore, a comprehensive and individualized assessment is needed to identify patients for tailored interventions such as pulmonary rehabilitation. Physical activity after a cancer diagnosis is a prognostic factor for mortality and is, therefore, an important treatable trait. Interventions to enhance physical activity can potentially improve this behavior in cancer survivors. However, evidence about interventions delivered in the early trajectory after a cancer diagnosis on device-measured physical activity has never been systematically reviewed. Study 5 was a systematic review and meta-analysis summarizing the effectiveness of different non-pharmacological interventions on device-measured physical activity in patients within 12 months of cancer diagnosis. The study concluded that behavior change interventions increased device-measured moderate-to-vigorous physical activity in patients with cancer. Additionally, the study summarized the devices and methodologies used to objectively measure physical activity in adults with cancer. This thesis presents crucial insights into COPD and NSCLC, illustrating that these diseases extend their impact beyond the lungs, manifesting a wide range of symptoms and extra-pulmonary consequences. Considerable heterogeneity between patients is seen, resulting in the individual disease burden. The impairments seen in patients with COPD and NSCLC may be considered treatable traits and should be comprehensively and individually assessed. Treatable traits have prognostic value, and low scores on physical tests can identify patients at risk for morbidity and mortality. Identifying these traits and focusing on avoidance of future events can mitigate the burden of the disease. Individualized tailored interventions, such as pulmonary rehabilitation, are a way to move forward in secondary prevention strategies.