Study Tries to Understand Comorbidity of COPD, Anemia

Although anemia is associated with adverse outcomes in chronic obstructive pulmonary disease (COPD), its contribution to outcomes in individuals with other comorbid chronic diseases is not well understood.

A recent study examined the association of anemia with outcomes in a large group of patients with COPD in an effort to understand the contribution of anemia to outcomes and phenotypes in individuals with other comorbidities. It found that anemia is associated with worse exercise capacity, greater dyspnea, and greater disease severity among adults with COPD, particularly among those with comorbid chronic cardiac and metabolic diseases.

Possible pathways for the adverse correlations of anemia with outcomes in COPD could stem from the biomarkers found in anemic individuals, suggesting inflammation, lung tissue injury, and oxidative stress.

Participants with COPD from SPIROMICS (the Subpopulations and Intermediate Outcome Measures in COPD Study) were analyzed to determine the associations of normocytic anemia (a group of anemias where the average size and hemoglobin content are within normal limits) with clinical outcomes, computed tomographic measures, and biomarkers.

Additional analysis was performed to understand the independence and possible interactions related to cardiac and metabolic comorbidities.

SPIROMICS is a multicenter prospective study of current and former smokers (greater than 20 pack-years) with and without obstructive lung disease and of nonsmokers without obstructive lung disease, who were enrolled between November 2010 and July 2015 and monitored quarterly for up to 3 years. Patients were aged 40 to 80 years.

This study includes all individuals with COPD with mean forced expiratory volume in 1 second (FEV₁) less than 0.70 (FEV₁ >50% predicted, n = 1193; and FEV₁, 50% predicted, n = 596).

Generally speaking, estimates of anemia in patients with COPD have ranged from 7.5% and 33% in patients with COPD.

A total of 1789 individuals with COPD from SPIROMICS had data on hemoglobin, and of these 7.5% (n = 135) were found to have normocytic anemia. Anemic participants were older with worse airflow obstruction, a higher proportion of them were African American, and they had a higher burden of cardiac and metabolic comorbidities.

Anemia was strongly associated with 6-minute walk distance (ß, 261.43; 95% CI, 285.11-237.75), modified Medical Research Council dyspnea questionnaire (ß, 0.27; 95% CI, 0.11-0.44), and St. George’s Respiratory Questionnaire (ß, 3.90; 95% CI, 1.09-6.71).

These adjusted associations were stronger among those with 2 or more cardiac and metabolic comorbidities. Anemia was associated with higher levels of serum C-reactive protein, soluble receptor for advanced glycosylation end-products, and epithelial cadherin-1, findings that persisted in those with a high burden of comorbidities.

The biomarker analysis suggests a few possible mechanisms, such as increased systemic inflammation and airway epithelial injury.

More study is required to better understand these potential mechanisms, the authors wrote in the latest issue of the Annals of the American Thoracic Society. Randomized trials targeted at both identifying and treating anemia would be required to understand the importance of anemia and whether improving hemoglobin levels would impact these outcomes. Until then, it is difficult to know whether screening for or treating anemia would be of value to patients with COPD and should be incorporated in clinical practice guidelines.

However, anemia could be one of several independent factors for having worse outcomes in the subgroup of individuals with COPD who have high levels of systemic inflammation and comorbidity burden.

The study was funded by the National Institutes of Health's National Heart, Lung, and Blood Institute.

Reference

Putcha N, Fawzy A, Paul GG, et al. Anemia and adverse outcomes in a chronic obstructive pulmonary disease population with a high burden of comorbidities: an analysis from SPIROMICS. Ann Am Thorac Soc. 2018;15(6):710-777. doi: 10.1513/AnnalsATS.201708-687OC.