Abnormal Pulmonary Function in Adults with Sickle Cell Anemia

Abstract

Rationale: Pulmonary complications of sickle cell anemia (Hb-SS) commonly cause morbidity, yet few large studies of pulmonary function tests (PFTs) in this population have been reported. Objectives: PFTs (spirometry, lung volumes, and diffusion capacity for carbon monoxide [DL CO ]) from 310 adults with Hb-SS were analyzed to determine the pattern of pulmonary dysfunction and their association with other systemic complications of sickle cell disease. Methods: Raw PFT data were compared with predicted values. Each subject was subclassified into one of five groups: obstructive physiology, restrictive physiology, mixed obstructive/restrictive physiology, isolated low DL CO , or normal. The association between laboratory data of patients with decreased DL CO Sickle cell anemia (Hb-SS) results from homozygosity for a point mutation in the ␤-globin gene (HBB; Glu6Val) causing the resultant sickle hemoglobin (Hb S) to be less soluble when deoxygenated than normal hemoglobin (1). Even with improved treatment, including the early use of prophylactic antibiotic regimens, judicious transfusions, and the administration of hydroxyurea in selected patients, mortality remains high for this population. The median age at death is 42 yr for males and 48 yr for females with Hb-SS. Pulmonary complications, including acute chest syndrome (ACS), pulmonary hypertension (PH), and pulmonary fibrosis, account for 20-30% of deaths in the Hb-SS population and are often underrecognized by the health care community (2, 3).Dyspnea is a frequent complaint amongst patients with sickle cell disease, the etiology of which is unclear and likely multifacto- 5). Studies of lung function to date in this population have been of modest size, often involving fewer than 50 patients (4, 6-11) and largely inconclusive. Their results have yielded a spectrum of abnormalities, including restrictive lung disease, abnormal diffusion capacity for carbon monoxide (Dl CO ), obstructive disease, and hypoxemia (4,6,7,9,12). No definitive profile for pulmonary function in sickle cell disease has emerged. As a result, clinicians find pulmonary function tests (PFTs) difficult to interpret in this population and their clinical utility for directing further investigation and therapy has not been well evaluated.Of growing concern is the link between obstructive lung disease and ACS, particularly in children (7,13,14). The few published studies suggest that obstructive lung disease, in some cases, plays a role in the pathogenesis of ACS (7,13,15). Moreover, obstructive lung disease could be a long-term sequela of recurrent episodes of ACS (6, 9). Larger scale studies are necessary to elucidate more clearly the interaction between lung function and ACS. In addition, certain findings on PFTs might be a marker of other complications of sickle vasculopathy. For example, isolated decreased Dl CO is a well-established finding associated with PH (16, 17). However, its role as a marker or predictor of PH in the Hb-SS population is unknown. The purpose of this study is to evalua...

Pulmonary Complications of Sickle Cell Disease

“…The prevalence of asthma among pediatric patients with SCD appears to be similar to that in children of African descent in the general population (57,60). As mentioned earlier, obstructive lung disease in adults with SCD is less common, occurring in less than 3% of patients (56).…”

“…High-resolution CT studies usually reveal a few scattered foci of lung scarring. In the historical SCD registry study, the Cooperative Study of Sickle Cell Disease, which was performed in the pre-hydroxyurea treatment era, pulmonary function studies were available for analysis in 310 patients with HbSS with SCD (56). Ninety percent of the population had abnormal pulmonary function studies, and the major abnormality was a mild restrictive pulmonary function defect (TLC of 70 6 15% predicted) and isolated reduction in the DL CO (57 6 20% predicted).…”

Mechanisms of Vasculopathy in Sickle Cell Disease and Thalassemia

“…Therefore, the induction of arginase may also promote aberrant vessel wall remodelling and neointima formation. 13 Proline is an amino acid that is also involved in lung fibrosis, airway remodeling, and asthma in addition to vascular smooth muscle proliferation, 12 common features of pulmonary dysfunction in SCD 14,15 and thalassemia. 16 In SCD, pulmonary complications compromise oxygenation and contribute to a vicious cycle of erythrocyte sickling.…”

Pulmonary Complications of Sickle Cell Disease in the Pregnant Patient

“…These abnormalities include thrombocytosis, increased tissue factor levels and plasma concentrations of procoagulant clotting factors [42]. Similarly, pregnancy increases the rate of VTE events through various different mecha-tion tests, with the majority of them exhibiting a mild restrictive disease pattern [49]. Advanced lung disease in patients with SCD has been previously described as sickle cell chronic lung disease [50].…”