Age is a predictor of a small decrease in lung function in children with sickle cell anemia

Abstract

The longitudinal pattern of lung function in children with sickle cell anemia (SCA) has shown a decrease in FEV % predicted, a risk factor for death in adults with SCA, but predictors for this decline are poorly characterized. In a prospective longitudinal multi-center cohort of children with SCA, we tested the hypotheses that: (1) FEV % predicted declines over time; and (2) SCA-specific characteristics and therapy predict this decline. At three clinical centers, children with SCA (HbSS or HbSβ thalassemia), unselected for respiratory disease, were enrolled in the Sleep and Asthma Cohort (SAC) study. Study-certified pulmonary function technicians performed spirometry and lung volumes. Each assessment was reviewed centrally. Predicted values were determined for TLC, FEV , FVC, and FEV /FVC ratio. A total of 197 participants, mean age 11.0 years at first testing (range 4-19.3 years), had a minimum of three spirometry measurements, over an average of 4.4 years (range 1.1-6.5 years) from baseline to endpoint. In a multivariable model, FEV % predicted declines by 0.3% for every additional year of age (95% CI -0.56 to -0.05, P = .020). Sex, asthma history, hemoglobin, reticulocyte count, white blood cell count, incidence rate of severe acute pain and acute chest syndrome episodes, and hydroxyurea therapy were not associated with a decline in FEV % predicted. In a large, rigorously evaluated, prospective cohort of an unselected group of children with SCA, FEV % predicted declines minimally over an average of 4 years, and none of the examined disease features predict the decline.

Developmental Profile of Sleep and Its Potential Impact on Daytime Functioning from Childhood to Adulthood in Sickle Cell Anaemia

“…For the London site, ethical approval was granted by the Brent (05/Q0408/42) and East Midlands-Leicester (11/EM/0084) National Research Ethics Service Committees; and for the US sites, approval was gained from the Institutional Review Boards of Washington University School of Medicine, St. Louis, MO, Federal Fide Assurance (FWA) #00000163 and Case Western Reserve, Cleveland, OH (FWA #00004428). Details for ethical approval, recruitment and follow up of children and young adults with SCA to the Sleep Asthma Cohort (SAC), investigating the prevalence and importance of sleep disturbances and asthma, have been previously published [ 12 , 39 , 40 ]. Each child and adolescent with SCA aged 4–18 attending their routine hospital visits was eligible to take part regardless of past morbidity or sleep-disordered breathing symptoms.…”

A physicians survey assessing management of pulmonary airway involvement in sickle cell disease

“…Moreover, the number of ACS episodes has been directly correlated with AHR and negatively correlated with percent predicted FEV1 and FEV1/FVC ratio . However, another large prospective study of children with SCD reported disparate results suggesting that taking coefficient of variation into account, the decline in FEV1% is only minimal and episodes of pain crisis and ACS do not predict a decline in lung function . Lung volumes in patients with SCD are lower as compared to age matched normal controls but may not necessarily be in the restrictive range but older children and adults can have a restrictive pattern of lung disease …”

Identifying Clinical and Research Priorities in Sickle Cell Lung Disease. An Official American Thoracic Society Workshop Report

“…There are few longitudinal lung function studies in SCD, and most were retrospective. One pediatric cohort demonstrated a 2% to 3% annual decline in FVC, FEV 1 , and total lung capacity ( 62 ); however, this finding has not been replicated in other studies ( 63 , 64 ).…”