Airway Inflammation in Children with Primary Ciliary Dyskinesia
Scott D. Sagel, Oren Kupfer, Brandie D. Wagner, Stephanie D. Davis, Sharon Dell, Thomas W. Ferkol, Jordana E. Hoppe, Margaret Rosenfeld, Kelli M. Sullivan, Harm A.W.M. Tiddens, Michael R. Knowles, Margaret W. Leigh
Abstract
Abstract Rationale The role of airway inflammation in disease pathogenesis in children with primary ciliary dyskinesia (PCD) is poorly understood. Objectives We investigated relationships between sputum inflammation measurements, age, lung function, bronchiectasis, airway infection, and ultrastructural defects in children with PCD. Methods Spontaneously expectorated sputum was collected from clinically stable children and adolescents with PCD ages 6 years and older participating in a multicenter, observational study. Sputum protease and inflammatory cytokine concentrations were correlated with age, lung function, and chest computed tomography measures of structural lung disease, whereas differences in concentrations were compared between ultrastructural defect categories and between those with and without detectable bacterial infection. Results Sputum from 77 children with PCD (39 females [51%]; mean [standard deviation] age, 13.9 [4.9] yr; mean [standard deviation] forced expiratory volume in 1 second [FEV1]% predicted, 80.8 [20.5]) was analyzed. Sputum inflammatory marker measurements, including neutrophil elastase activity, IL-1β (interleukin-1β), IL-8, and TNF-α (tumor necrosis factor α) concentrations, correlated positively with age, percentage of bronchiectasis, and percentage of total structural lung disease on computed tomography, and negatively with lung function. Correlations between neutrophil elastase concentrations and FEV1% predicted and percentage of bronchiectasis were −0.32 (95% confidence interval, −0.51 to −0.10) and 0.46 (0.14 to 0.69), respectively. Sputum neutrophil elastase, IL-1β, and TNF-α concentrations were higher in those with detectable bacterial pathogens. Participants with absent inner dynein arm and microtubular disorganization had similar inflammatory profiles compared with participants with outer dynein arm defects. Conclusions In this multicenter pediatric PCD cohort, elevated concentrations of sputum proteases and cytokines were associated with impaired lung function and structural damage as determined by chest computed tomography, suggesting that sputum inflammatory measurements could serve as biomarkers in PCD.