Chest
Volume 149, Issue 5, May 2016, Pages 1313-1324
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Recent Advances in Chest Medicine
Chronic Pulmonary Complications of Sickle Cell Disease

https://doi.org/10.1016/j.chest.2015.11.016Get rights and content

Sickle cell disease (SCD), the most common genetic hemolytic anemia worldwide, affects 250,000 births annually. In the United States, SCD affects approximately 100,000 individuals, most of African descent. Hemoglobin S (HbS) results from a glutamate-to-valine mutation of the sixth codon of the β-hemoglobin allele; the homozygous genotype (HbSS) is associated with the most prevalent and severe form of the disease. Other SCD genotypes include HbSC, composed of one HbS allele and one HbC (glutamate-to-lysine mutation) allele; and HbS-β-thalassemia0 or HbS-β-thalassemia+, composed of one HbS allele and one β-thalassemia allele with absent or reduced β-chain production, respectively. Despite advances in care, median survival remains in the fifth decade, due in large part to chronic complications of the disease. Chronic pulmonary complications in SCD are major contributors to this early mortality. Although our understanding of these conditions has improved much over the past 10 to 15 years, there remains no specific treatment for pulmonary complications of SCD. It is unclear whether conventional treatment regimens directed at non-SCD populations have equivalent efficacy in patients with SCD. This represents a critical research need. In this review, the authors review the state-of-the-art understanding of the following pulmonary complications of SCD: (1) pulmonary hypertension; (2) venous thromboembolic disease; (3) sleep-disordered breathing; (4) asthma and recurrent wheezing; and (5) pulmonary function abnormalities. This review highlights the advances as well as the knowledge gaps in this field to update clinicians and other health care providers and to garner research interest from the medical community.

Section snippets

Definitions

Pulmonary hypertension (PH), defined hemodynamically as a mean pulmonary arterial pressure ≥ 25 mm Hg at rest, occurs in 6% to 10.4% of adults with SCD.3, 4, 5, 6 Right-sided heart catheterization is the gold standard for the diagnosis of PH3 and assessment of prognosis. The hemodynamics of PH in patients with SCD are heterogeneous (Table 1). PH may be precapillary (pulmonary arterial hypertension [PAH]), postcapillary (pulmonary venous hypertension), or have features of both.7 Clinical

Venous Thromboembolism in SCD

VTE (deep vein thrombosis and pulmonary embolism [PE]) affects about 25% of adults with SCD and is a risk factor for death.30, 31 Despite the known hypercoagulability of SCD, VTE is often overlooked as a major complication of SCD,30 in part because in situ microvascular thrombosis occurs in these patients and large-vessel thromboses have been recognized only with diagnostic advances.

The cause of increased VTE risk in SCD is multifactorial. Patients with SCD have traditional VTE risk factors and

Sleep-Disordered Breathing and Nocturnal Hypoxemia

SDB, particularly OSA and intermittent oxyhemoglobin desaturation, are potential contributors to cardiopulmonary compromise in SCD, possibly via increasing vaso-occlusion.47, 48 Despite this, SDB is underappreciated and, consequently, often undertreated; this is due, in part, to a lack of understanding of its prevalence and natural history in SCD.

Much of what is known about SDB in SCD stems from retrospective cohort studies in which up to 79% of symptomatic children and adolescents were

Asthma and Recurrent Wheezing

In the United States, African Americans and people of mixed race have a higher prevalence of asthma than do white individuals with an increased mortality rate.62 One of the difficulties in diagnosing asthma in SCD stems from the overlap of clinical features that may be due solely to SCD63, 64 and those of asthma in the non-SCD population (Table 5). Koumbourlis et al reported that 35% of 5- to 18-year-old patients with SCD had lower airway obstruction.64 In addition, up to 77% of children and

Adults

Pulmonary function testing (PFT) often produces abnormal results in adults with SCD.76, 77, 78 A cross-sectional analysis of 310 HbSS adults demonstrated abnormal pulmonary function in 90%, predominantly restrictive physiology (mildly decreased total lung capacity and diffusion capacity of the lung for carbon monoxide [Dlco]).77 Longitudinal studies of adults with SCD demonstrate an average decline in forced expiratory volume in 1 second of 49 mL/y (unrelated to smoking status) compared with 20

Summary and Future Directions

Pulmonary complications of SCD represent a diverse group of diseases affecting the large and small airways, parenchyma, and vasculature. Although pulmonary disease clearly has an adverse impact on outcomes in SCD, much needs to be learned about the natural history of these conditions across the life span of patients with SCD to better understand the potential impacts of screening and prevention. Moreover, clinical trials that target this population specifically are needed, because it is

Acknowledgment

Financial/nonfinancial disclosures: The authors have reported to CHEST the following: E. S. K. has received grant support from Actelion Pharmaceuticals and Pfizer. None declared (A. M.).

Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript.

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  • Cited by (0)

    FUNDING/SUPPORT: Dr Mehari is supported by National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number P50HL118006 and Department of Medicine Academic Enrichment Fund.

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