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Comorbidities complicate COPD management, but the underlying mechanisms driving both conditions present an opportunity for therapeutic advancements.
A better understanding of the mechanisms driving comorbidities associated with chronic obstructive pulmonary disease (COPD) may present opportunities for better clinical care and new therapeutic targets, according to a review published in the Journal of Clinical Medicine.
Comorbidities in patients with COPD may be caused by the “spillover” of systemic inflammation, primarily attributable to Interleukin (IL)-6, IL-1β, C-reactive protein (CRP), and Tumor Necrosis Factor (TNF)-α. Oxidative stress and shared risk factors also play a role.
“Considering that the number of patients with COPD is expected to rise, understanding the mechanisms linking COPD with its comorbidities may help to identify new targets for therapeutic purposes based on multi-dimensional assessments,” the review authors wrote.
Comorbidities & Their Underlying Mechanisms
Domenica Francesca Mariniello and colleagues explored the intersection between COPD and several comorbidities, including CVD, lung cancer, bronchiectasis, obstructive sleep apnea, and metabolic syndrome.
Cardiovascular Diseases
In patients with COPD, mortality is more often due to CVD than respiratory failure. Common CVDs include ischemic heart disease, arrhythmias, and heart failure. Smoking, aging, and physical inactivity are shared risk factors for both conditions. In addition, several pathophysiological links exist between CVD and COPD, including lung hyperinflation, pulmonary hypertension, hypoxemia, oxidative stress, and systemic inflammation.
Ongoing clinical trials aim to explore the efficacy of various treatments, including antiplatelet therapy, bronchodilators, beta-blockers, and statins, for improving outcomes for patients with COPD and cardiovascular comorbidities. The authors noted, however, that more research is needed to clarify the potential impact of these agents on cardiovascular mortality.
Lung Cancer
COPD is also strongly associated with lung cancer. Shared risk factors include tobacco exposure, occupational hazards, and particulate matter exposure. Patients with COPD are more susceptible to developing lung cancer if they are genetically predisposed to it or have epigenetic alterations.
COPD increases post-surgical complications and reduces survival rates in patients with lung cancer, especially in cases of severe COPD. Immune checkpoint inhibitors extend survival in lung cancer but may have varying impacts on patients with COPD, authors said.
“Lung cancer treatments in mild to moderate COPD seem to be potentially synergic, tackling both oncological and respiratory outcomes, while patients in more advanced COPD stages have a higher risk of adverse events,” the researchers explained.
Optimizing COPD management may improve surgical outcomes for patients with lung cancer. Clinical trials are underway to elucidate the relationship between pharmacological interventions and the tumor immune microenvironment, which could lead to targeted treatments for patients with lung cancer and COPD.
Bronchiectasis
Approximately 30% of patients with COPD have bronchiectasis, a chronic airway disease characterized by permanent bronchi dilation. It is more prevalent in advanced cases of COPD, and patients with both diseases typically have elevated serum levels of IL-6, IL-8, CRP, and cytokines.
Long-term macrolide therapy may be useful for both conditions, but there are concerns regarding adverse effects and antibiotic resistance. Inhaled antibiotics are recommended for bronchiectasis but not for COPD, although some patients with COPD and chronic P. aeruginosa infection may benefit from this treatment. In addition, inhaled corticosteroids are used in COPD with multiple exacerbations or peripheral eosinophilia, but the authors noted that it is unclear whether these agents benefit patients with bronchiectasis.
Obstructive Sleep Apnea
The association between COPD and obstructive sleep apnea is termed “overlap syndrome” and affects between 1% and 3.6% of the general population. Patients with overlap syndrome experience heightened risks for cardiovascular complications, hospitalizations, and mortality, the authors wrote.
Prolonged hypoxemia contributes to a higher incidence of pulmonary hypertension in patients with overlap syndrome. These patients also have lower PaO2 and higher PaCO2 levels compared with patients who only have obstructive sleep apnea.
Continuous positive airway pressure (CPAP) therapy’s efficacy in patients with overlap syndrome is not fully established. The authors wrote that noninvasive ventilation in biphasic positive airway pressure mode may be more effective in patients with severe emphysema and hypoventilation. Supplemental oxygen therapy during sleep can improve QOL for patients with persistent low oxygen saturation, even with CPAP therapy.
The authors added that recognizing and treating sleep-disorder breathing is crucial for improving clinical outcomes for patients with COPD.
Metabolic Syndrome
More than 30% of patients with COPD have at least one component of metabolic syndrome, such as abdominal obesity, dyslipidemia, hypertension, and hyperglycemia. Metabolic syndrome is more prevalent in patients with milder airflow obstruction and tends to impact women and those with higher BMI and FEV1 scores.
The authors noted that COPD and metabolic syndrome share features such as oxidative stress, systemic inflammation, and decreased physical activity. Proinflammatory cytokines in COPD promote insulin resistance. Adipose tissue inflammation and hormonal dysregulation also contribute to the link between COPD and metabolic syndrome.
The authors wrote that addressing low-grade systemic inflammation and adipose-tissue-related hormones is crucial when managing patients with COPD and metabolic syndrome. Studies are currently underway to investigate the efficacy of diet and exercise programs in this patient population.
Toward Holistic Clinical Care
The authors concluded that comorbidities make COPD management difficult. They called for both clinicians and researchers to devote more attention to comorbidities.
“Given the impact of these comorbidities on COPD progression, mortality, and resource use, it is crucial to have proper patient management and initiate the early treatment of these conditions,” the authors wrote. “The analysis of COPD comorbidities may offer the opportunity to select an approach based on treatable traits, prompting a pragmatical and holistic therapy approach.”
