Discussion
comorbidity, lung disease, asthma exacerbations, inflammation, asthma, airway inflammation, SCD, TLC.A, pulmonary injury
RESPIRATORY INFECTIONS, LUNG DISEASE, INFLAMMATION, DISEASE, SECONDARY, PULMONARY INVOLVEMENT, ASTHMA, ASTHMA
We compared lung function parameters and inflammatory markers in children with SCD with and without ACS.TLC was significantly lower for children with ACS at baseline and at 2 year follow up. Patients with ACS also showed changes in flow rates over a 2-year period, which was particularly seen in children with multiple episodes of ACS. Elevated concentrations of IL-5 and IL-13, which persisted at 2 years along with elevated TNFa at 2 years, suggested that Th1 and Th2 markers are elevated with ACS. There was a trend towards elevated IP10 for children with ACS at baseline. Changes in IP10 negatively correlated with changes in FVC for patients with ACS. Multivariable modeling found ACS to be a predictor of TLC. Taken together these findings suggest that inflammatory markers are elevated in patients with ACS, and ACS was a predictor for low lung function, particularly TLC.A decline in lung function over time in children with SCD has been previously reported in several studies [Few previous studies have correlated lung function deficits and inflammatory markers in SCD [There have only been a handful of human investigations studying underlying inflammatory pathways and lung disease in patients with SCD [Asthma has been frequently reported as a comorbidity in SCD [In our multivariate model, age was negatively related to FEV1 and FEV1/FVC as can be expected with the natural course of decline in lung function. Males had lower FEV1/FVC and higher TLC which is likely secondary to gender based differences in the biological and mechanical properties of the lungs, and the concept of dysanapsis [The limitations of this study are its exploratory nature, small sample size and the potential effects of an intervention in the clinical trial that may have influenced cytokine levels and lung function. Vitamin D therapy has been shown to have a beneficial effect on reducing asthma exacerbations and respiratory infections [Our present findings strengthen the association of ACS with lung function deficits and indicate that inflammatory mediators may be responsible. The current practice has been to associate most patients with SCD who have lung function defects and pulmonary involvement or ACS, with having asthma and managing them with standard asthma medications. A relationship of ACS with IFN induced cytokines such as IP10 and monocyte driven inflammation involving IL-6, is a step towards understanding airway inflammation in SCD patients following ACS, and its relationship with lung function changes. With more insight into the underlying mechanisms of ACS in SCD leading to pulmonary injury, future therapeutic targets can be directed toward more specific disease mechanisms.