Research presented at the American Thoracic Society’s 2008 International Conference in Toronto on Sunday, 18 May, show that children with sickle cell disease (SCD) have a significantly sharper decline in lung function with age when compared to other children of the same race and age.
Furthermore, that loss of function appears to be linked to a restrictive rather than obstructive pattern, contrary to previous research that has focused on obstructive or asthma-like patterns in loss of lung function with sickle cell disease.
To determine the patterns of lung function loss, the researchers analysed 1,357 lung function results completed between January 1989 and January 2005 from 413 children with SCD during routine sickle cell clinical visits. Lung volume measurements were also included for 1,129 records.
They found that over time, lung function significantly declined, as shown by a decline in the per cent predicted values for all spirometry measures except the FEV1/FVC ratio, a marker of airway obstruction. The decline in lung volume confirmed a restrictive pattern, with an average loss of 2 per cent per year of total lung capacity.
“The restrictive pattern of decline is supportive of early injury or inflammation resulting in progressive changes in lung volumes across age,” said lead researcher Joanna MacLean, M.D., of the department of respiratory medicine at Children’s Hospital at Westmead in Australia. “We expected that children with sickle cell disease would show greater loss of lung function than other children, but this had never been quantified, nor was the pattern of decline clear.”
This is the first study to examine loss of lung function in children with sickle cell disease over time in a large number of children. “Most studies of lung function in children with sickle cell disease are either cross-sectional or have limited longitudinal follow-up,” said Dr. MacLean. “The strength of our study is that data was collected from a large number of children with sickle cell disease across childhood.”
They also found that of children with SCD, hemoglobin-beta genotype SS was associated with an increased risk of loss of lung function across childhood. The haemoglobin SS genotype is more common than the haemoglobin SC genotype (one in 600 versus one in 800 life births) and is associated with more complications than haemoglobin SC disease. This pattern of decline in lung function may simply reflect a greater risk of lung injury in this group, but alternatively may also suggest differences in response to lung injury or lung repair with different genotypes of sickle cell disease.
“Our findings confirm that lung disease in SCD begins in childhood,” explained Dr. MacLean. “Using statistical modelling, we are able to predict the rate of decline of lung function. These results can be used as a baseline against which results from intervention studies can be compared.”
While changes in treatment over the last 20 years have led to a significant reduction in overall mortality and morbidity for children with SCD, prospective longitudinal studies focusing on the identification and treatment of sickle cell associated lung disease are needed to continue to improve the long term health of children and adults with sickle disease.
“The results of this project emphasise the need for further investigation into the pathophysiology and treatment of lung disease in children with sickle cell disease,” concluded Dr. MacLean.
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