Pulmonary functions in children and adolescents with sickle cell disease

Abstract

BackgroundSickle cell disease (SCD) is relatively common in Bahrain, and airway inflammation in patients with SCD is usually multifactorial. This study aimed to evaluate lung function and induced sputum levels of interleukin‐6 (IL‐6) in Bahraini children and adolescents with SCD and assess their relationship with the recurrence of acute chest syndrome (ACS).MethodsA total of 139 children and adolescents with SCD and 123 healthy children (control group) were included in the present study. Patients were further stratified according to age and history of ACS. The patient and control groups underwent pulmonary function tests (PFTs), including spirometry and assessments of lung volume, diffusion of carbon monoxide (DLCO), and induced sputum IL‐6 levels.ResultsForced expiratory volume in 1 second (FEV1), force vital capacity (FVC), FEV1/FVC, total lung capacity, DLCO, and DLCOc (ie, hemoglobin‐corrected DLCO) were significantly lower, while residual volume and sputum IL‐6 levels were significantly higher in the patient group than in the control group. PFT parameters were more compromised in the patient subgroup with a history of ACS and older than 12 years compared with the subgroup without a history of ACS and the subgroup under 12 years of age. PFTs revealed significant negative correlations with age, number of ACS events, and sputum IL‐6 levels.ConclusionPulmonary function was observed to worsen with disease progression, and it worsened with older age and repeated occurrence of ACS. Induced sputum IL‐6 levels reflected the degree of lung inflammation in affected patients and were associated with more impairment in various PFT parameters.

Predictors of Diffusing Capacity in Children With Sickle Cell Disease: A Longitudinal Study

“…Despite its importance, very few studies have been evaluated DLCO in C-SCD. Biltagi et al (2) reported DLCO impairment in C-SCD compared to controls, and we previously reported an annual DLCO decline of 1.5% in C-SCD (12). Moreover, DLCO impairment in SCD may differ by race/ethnicity (13).…”

“…Sickle cell disease (SCD) is a hemoglobinopathy that leads to a chronic inflammatory state resulting in vasculitis, pulmonary fibrosis, and pulmonary hypertension (1). Children with SCD (C-SCD) often suffer from an impaired gas exchange (2), primarily due to chronic airway inflammation, and the association between DLCO and sputum IL-6 level has been reported (2). If untreated, gas exchange abnormalities in SCD may result in chronic hypoxemia, cardiopulmonary morbidity, and poor disease outcomes (3).…”

“…Thus, the association between DLCO and spirometric and IOS measures of OAD would be clinically relevant yet relatively unexplored domain. Unlike OAD, restrictive lung disease can be a late manifestation in C-SCD (19), and measures like total lung capacity (TLC) and vital capacity (VC) could be significant predictors of declining DLCO-which is more evident in older C-SCD (2).…”

IL-6 levels are dramatically high in the sputum from children with sickle cell disease during acute chest syndrome

“…Figure 1A). By contrast, median IL-6 level in sputum was dramatically elevated during ACS (3320 [1233-6459] pg/mL) compared with non-ACS patients (13 [11][12][13][14][15][16][17][18][19] pg/mL; P 5 .0009; Figure 1B). For the 5 patients who had concomitant sputum and plasma collections during ACS, median IL-6 level was .150-fold higher in sputum (6892 [6314-7114] pg/mL) than in plasma (42 [35-48] pg/mL; P 5 .0009; Figure 1C).…”

“…Moreover, reported levels of IL-6 in endotracheal fluid from non-SCD children with severe pneumonia requiring mechanical ventilation are much lower than those observed in our patients. 16 Sputum levels of IL-8, CCL2, and CCL3 chemokines are high during ACS Figure 1I), and CCL3 (62 [32-105] pg/mL vs 12 [9][10][11][12][13][14][15][16][17][18][19] pg/mL; P 5 .01; Figure 1J). These high chemokine levels could induce pulmonary recruitment of innate immune cells, including neutrophils and monocytes, which in turn may produce inflammatory mediators, thus contributing to a vicious cycle of local inflammation during ACS.…”