Anemia and Survival in Chronic Obstructive Pulmonary Disease: A Dichotomous rather than a Continuous Predictor

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a disorder characterized by high mortality. Hemoglobin (Hb) concentration has a prognostic impact on COPD patients receiving long-term oxygen treatment, but its value as an independent predictor of survival among stable COPD outpatients has not been fully clarified by previous studies. Objectives: To investigate the potential association between anemia and survival in a cohort of stable COPD outpatients. Methods: A cohort of stable COPD patients, who had had their first spirometry, blood count and serum chemistry profile done between October 1999 and November 2010 were retrospectively analyzed. Patients with heart failure, renal impairment, malignancy, recent hemorrhage and other causes of anemia were excluded. Variables that were found to be univariately associated with survival entered a multivariate stepwise Cox regression analysis model, to allow independent predictors of survival to be identified. Results: Of 294 patients (67.9 ± 9.8 years old, 64.6% male) 15.6% were anemic (Hb <13 g/dl). The median survival differed significantly between anemic [68.7 (18.1–91.5) months] and nonanemic [79.8 (57.5–98.4) months, p = 0.035] individuals. Independent predictors of mortality in the total population were anemia [hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.06–3.29], age (HR 1.08, 95% CI 1.04–1.12) and forced expiratory volume in 1 s (FEV₁) % predicted (HR 0.94, 95% CI 0.92–0.97); the Hb concentration was neither univariately nor multivariately associated with mortality. Conclusion: This is the first study to indicate that anemia (but not the Hb value) is independently associated with survival in stable COPD outpatients. It would be better to treat this as a categorical variable in future scoring systems.

Anaemia in chronic obstructive pulmonary disease: an insight into its prevalence and pathophysiology

“…Although patients with disorders that could be accompanied by low Hb levels, such as heart failure, gastrointestinal bleeding and malignancy were excluded, renal function was not investigated. Results of two more studies conducted in COPD hospital outpatients of various severities were comparable, with anaemia prevalence ranging between 15 % and 17.1 % [4,7]. The only study which used both clinical and laboratory criteria to exclude all potential causes of anaemia, apart from anaemia of chronic disease (ACD), estimated the prevalence of the latter to be 10.2 % among stable hospital outpatients [8].…”

“…Boutou [8] [2,4,[7][8][9]14,21], several have applied the ICD 9/10 codes [13,[22][23][24] or identified COPD patients from existing databases without describing the diagnostic criteria in detail [19]. Thus, it is possible that in these studies, patients with respiratory symptoms of airflow obstruction without fulfilling spirometric criteria for COPD were misclassified, creating more variation regarding anaemia prevalence.…”

“…According to current World Health Organization (WHO), anaemia in the general population is defined by Hb levels <13 g/dl in male and <12 g/dl in female [25] and these thresholds have been used by several authors in order to identify anaemic COPD patients [5,8,11,15,26]. However, the use of a Hb <12 g/dl threshold to define anaemia in postmenopausal women is currently under debate [27], so the 13 g/dl threshold for both male and female has also been applied [2,4,7,19]. Controversy is even more evident regarding COPD patients admitted in the ICU, since there is as yet no accepted definition of abnormal Hb values in the critically ill [18].…”

Association between hemoglobin and prognosis in patients admitted to hospital for COPD

“…Importantly, anemia might reflect iron deficiency, which has been linked to the development of pulmonary arterial hypertension14 and presence of chronic inflammation, which is associated with frailty 15. Concentrations of hemoglobin and hematocrit have been shown to provide prognostic information in different populations of COPD patients,16–25 but in many of these studies patients with diseases associated with chronic anemia were excluded 12. While this strategy provides estimates of the prevalence and prognostic importance of hemoglobin directly ascribable to COPD, it does not reflect the importance of hemoglobin in a real-life COPD population, where most patients have numerous chronic diseases 5.…”

Lung function indices for predicting mortality in COPD

“…Since COPD has impacts beyond the lung [4, 5], the prognostic impact of both pulmonary and extrapulmonary factors has been investigated. Parameters of lung function and, particularly, forced expiratory volume in 1 s (FEV 1 ) [6, 7], age [8], sex [6, 7], body mass index (BMI) [9, 10], quadriceps strength [11], arterial blood gases [12, 13], lung volumes [14], gas transfer [15, 16], severity of dyspnoea [17], anaemia [18, 19], presence of comorbidities [20] and reduced physical activity or exercise capacity [21] are only some of the factors that have been studied. However, several of these studies have been conducted in specific COPD populations, such as selected patients with severe emphysema [2], patients using long-term oxygen treatment (LTOT) or noninvasive mechanical ventilation [6, 22, 23], and patients during or immediately after hospitalisation for a COPD exacerbation [7, 12, 24].…”