Progression and Prognostic Indicators of Bronchial Disease in Children with Sickle Cell Disease

Sophia N Williams,Inderpal Randhawa,Leila Yoonessi,Tricia Morphew,Eliezer Nussbaum

doi:10.1007/s00408-014-9572-y

Abstract

The pulmonary complications of sickle cell disease (SCD) are a leading cause of morbidity and mortality (MacLean et al. Am J Respir Crit Care Med 178:1055-1059, 2008; Klings et al. Am J Respir Crit Care Med 173:1264-1269, 2006; National Heart, Lung, and Blood Institute, 2009). Despite this recognition, predictive markers of lung dysfunction progression remain elusive (Klings et al. Am J Respir Crit Care Med 173:1264-1269, 2006; Platt et al. N Engl J Med 330:1639-1644, 1994; Caboot et al. Curr Opin Pediatr 20:279-287, 2008; Field et al. Am J Hematol 83:574-576, 2008; Shirlo et al. Peadiatr Respir Review 12:78-82, 2011). This study was designed describe the longitudinal progression and identify specific markers that influence bronchial disease in SCD. A retrospective, chart review of 89 patients with SCD was conducted. All patients underwent spirometry in conjunction with body plethysmography as part of routine care. Eleven lung function variables were assessed, five of which were selected to establish patterns of normal, obstructive, restrictive, or mixed obstructive-restrictive physiology (Klings et al. Am J Respir Crit Care Med 173:1264-1269, 2006; Field et al. Am J Hematol 83:574-576, 2008). In the unadjusted model, forced expiratory volume in one second (FEV1)% of predicted trended downward with age, while total lung capacity (TLC)% of predicted showed a bimodal distribution and carbon monoxide diffusion capacity corrected for hemoglobin (DLCOcor)% of predicted remained stable. Adjusting for acute chest syndrome (ACS) episodes, medication status, and growth velocity (GV), the final model demonstrated that the downward trend between FEV1% of predicted with age was further influenced by the latter two factors. Initial decline in FEV1% of predicted is associated with worsening pulmonary dysfunction over time. Independent of ACS episodes, the factors most influential on the progression of FEV1% predicted include the introduction of medications as well as the promotion of adequate prepubertal growth. Efforts to ensure normal prepubertal GV and treatment with bronchodilators, such as short-acting beta(2) agonists and inhaled corticosteroids (ICS), should be considered at an early age to delay progression of pulmonary dysfunction.

Highlights

Sickle cell disease (SCD) is a group of genetic disorders identified primarily by homozygosity of hemoglobin S (HbSS) [1,2,3]
Independent of acute chest syndrome (ACS) episodes, the factors most influential on the progression of FEV1% predicted include the introduction of medications as well as the promotion of adequate prepubertal growth
38 % of patients had a history of ACS, which increased to 48 % when evaluated through the last visit

Summary

Introduction

Sickle cell disease (SCD) is a group of genetic disorders identified primarily by homozygosity of hemoglobin S (HbSS) [1,2,3]. Pulmonary complications, including pulmonary hypertension (PH), acute chest syndrome (ACS), and sickle cell chronic lung disease (SCLD), remain a leading cause of morbidity and mortality in adults [4,5,6,7,8,9,10,11]. The presence of a restrictive lung pattern have been reported in adults [2, 6, 12,13,14,15,16]. An obstructive pattern has been reported in pediatric studies, with increased prevalence over time approximating a 3 % loss in forced expiratory volume in one second (FEV1)% of predicted/ year [7]. The data suggest SCD lung disease progresses from airway obstruction to a restrictive pattern of impairment. The underlying mechanisms of lung physiology and disease progression are not completely understood [2, 6, 7]

Methods

Results

Discussion

Conclusion