Pulmonary function declines early in sickle cell disease.

TORONTO -- Abnormalities in lung function already are present at age 8 years in children with sickle cell disease, and the subsequent rate of decline is between 2% and 3% per year, according to one study.

"We were aware from cross-sectional studies that children with sickle cell disease have lung function abnormalities, but cross-sectional studies only look at one time point and don't provide a sense of what happens across childhood," Dr. Joanna MacLean said at 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.

"We wanted to sort out exactly what the message is, and particularly 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 sickle cell clinic at the Hospital for Sick Children 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 contributory effects of age, gender, serum hemoglobin levels, and beta-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. A total of 45.8% 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 ([FEV.sub.1]) and forced vital capacity (FVC), though not for the [FEV.sub.1]/FVC ratio. Total lung capacity (TLC) and residual volume/TLC ratios demonstrated a similar pattern of change.

Recently, 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 is seen in asthma; but as [the children] progress to adulthood, the changes become fixed, showing a more restrictive pattern," she explained during a press conference.

Another surprising finding was that boys and girls alike had a decline in [FEV.sub.1] of 2.9% predicted per year. Previous data suggested that early adulthood mortality is much worse in females.

The investigators also evaluated the influence of sickle cell genotype. "We found that children with the hemoglobin SS genotype had a rate of decline in lung function that was twice that of those with the SC genotype. This was a novel finding, and we plan to continue investigating it."

BY NANCY WALSH

New York Bureau