TORONTO — Lung function abnormalities are present at age 8 years in children with sickle cell disease, and the subsequent rate of decline is between 2% and 3% a year, according to new data.
“We were aware [of the lung function abnormalities] from cross-sectional studies, but they only look at one time point,” and not across childhood,” Dr. Joanna MacLean told an international conference of the American Thoracic Society.
The pattern of change, whether obstructive or restrictive, in pulmonary function also has not been well delineated in sickle cell disease. The researchers sought clarity because “there is a high mortality in early adulthood in sickle cell disease, with a major contributor being respiratory disease,” said Dr. MacLean of the Hospital for Sick Children, Toronto.
The hospital's sickle cell clinic began requiring pulmonary function testing in 1989. Data for an unselected cohort of 413 children from then until 2005, beginning at age 8 years, were collected and analyzed using linear mixed effects modeling and compared with data for race-matched predicted values and reference equations in the African American population from the third National Health and Nutrition Examination Survey (NHANES III).
The study examined the contributions of age, gender, serum hemoglobin levels, and β-globin genotype on longitudinal changes in spirometry and lung volumes.
The sample consisted of 1,357 pulmonary function test results and 1,129 total lung capacity measurements. About 46% of the records were for males, and the records were evenly distributed across age groups, with a mean age of 12.7 years.
Significant declines were seen in percent predicted values for forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), though not for the FEV1/FVC ratio. Total lung capacity (TLC) and residual volume/TLC ratios demonstrated a similar pattern of change.
There has been considerable interest in the relationship between sickle cell disease and asthma, but the spirometry data suggest a restrictive, rather than an obstructive, pattern. “It is possible that early in childhood, the pattern is more obstructive, as in asthma; but [toward] adulthood, the changes become fixed, showing a more restrictive pattern,” she said in a press conference.
Previous data suggested early adulthood mortality is worse in females, but the current results suggested boys and girls alike had a decline in FEV1 of 2.9% predicted per year.
The role of sickle cell genotype, hemoglobin SS or SC, was also evaluated. The SS genotype is more common and considered worse, but has never been examined in terms of lung function. “Children with the hemoglobin SS genotype had a rate of decline in lung function that was twice that of those with the SC genotype,” she said. This novel finding is to be investigated.