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Systemic Effects of COPD Linked to Many Comorbidities, Affect Treatment Decisions, Increase Costs

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Chronic obstructive pulmonary disease (COPD) is often accompanied by other conditions that can potentiate its morbidity, leading to hospitalizations and increased healthcare costs. The systemic effects of COPD were examined at a Meet the Professor session at Chest 2010.

Systemic Manifestations Guide Treatment Decisions
“Airflow obstruction has profound effects on cardiac function and gas exchange, with systemic consequences,” said Paolo Palange, MD, Associate Professor of Internal Medicine, University of Rome, Italy.

COPD inflammation may initiate or worsen comorbid conditions, including ischemic heart disease, heart failure, osteoporosis, depression, and diabetes.

The systemic manifestations of COPD have been explained by 2 hypotheses:

  1. There is systemic spillover of the inflammatory and respiratory events occurring in the lungs of patients with COPD
  2. COPD is the expression of a systemic inflammatory state, with multiple organ compromise.

These hypotheses have important implications on treatment pathways, Dr Palange said. If one subscribes to the first hypothesis, therapy should be centered in the lungs. If the second hypothesis is more accurate, however, therapy should shift toward the systemic inflammatory state.

“Treatment of COPD inflammation may concomitantly treat systemic inflammation and associated comorbidities,” Dr Palange said. Broad-spectrum anti-inflammatory treatments—phosphodiesterase in hibitors, per oxisome proliferator-activated re ceptor agonists— may therefore provide unexpected benefits in patients with COPD.

Cardiovascular disease (CVD) is common in patients with COPD, and evidence suggests that anti-inflammatory treatments for COPD can also reduce CVD risk. Patients with COPD have a 2- to 3-fold higher risk for CVD mortality compared with those without COPD.

Low-dose inhaled corticosteroids have been shown to decrease the risk of acute heart attack in patients with COPD. Dr Palange speculated that acute reductions in the inflammatory marker C-reactive protein (CRP) with inhaled corticosteroids may partially explain reductions in CVD risk with these agents when used in patients with COPD.

In contrast, beta-agonists may have deleterious effects in patients with heart failure and COPD. This excess risk, however, appears to be confined to short-acting beta-agonists, where as the long-acting beta-agonists (LABAs) appear to have an acceptable safety profile; however, LABAs also should be used with caution in patients who also have CVD.

In an observational study, patients with COPD who were being treated with statins had a near halving of mortality compared with those not treated with statins, and statin therapy in combination with inhaled corticosteroids was associated with a lower rate of mortality than either therapy alone.

Skeletal muscle weakness is one of the main systemic effects of COPD. It leads to reduced exercise capacity independent of disease severity, worsening health status, increased mortality, and higher healthcare resource utilization.

Pulmonary rehabilitation improves the skeletal muscle dysfunction of patients with COPD, improves exercise capacity, and accelerates the speed of reoxygenation of skeletal muscle, Dr Palange noted.

Osteoporosis is another serious comorbidity in patients with COPD. Although therapy with inhaled corticosteroids had been thought to be a factor in the development of osteoporosis in patients with COPD, there were no significant changes in the rates of osteoporosis or osteopenia in men or women with COPD after treatment with inhaled cortico steroids in the TORCH (Towards a Revolution in COPD Health) study.

Anxiety disorders and depression in patients with COPD appear more frequently in women than in men. Women also have greater psychological distress and worse perceived control of COPD symptoms.

Anemia and obstructive sleep apnea syndrome are 2 other diseases that appear frequently in patients with COPD. Anemia with COPD is related to dyspnea, worse exercise capacity, and worse 3-year survival.

Evolving COPD Biomarkers
The search for systemic biomarkers to predict COPD worsening continues. CRP “may be the best biomarker,” Dr Palange said.

Other biomarkers with promise include an imbalance of leptin/ adiponectin, surfactant protein D, and plasma proadrenomedullin.

The coexistence of metabolic syndrome in patients with COPD is one obstacle in the search for biomarkers to predict COPD exacerbation, because the metabolic syndrome itself is a proinflammatory state associated with the release of many inflammatory proteins and molecules

Last modified: August 30, 2021