Airway inflammation linked to impaired lung function in primary ciliary dyskinesia
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Key takeaways:
- Elevated sputum inflammation markers were linked to lower lung function in primary ciliary dyskinesia.
- Inflammation measurements may potentially be employed as biomarkers for disease severity.
High sputum inflammatory concentrations in children with primary ciliary dyskinesia were linked to high structural lung injury percentages, according to study results published in Annals of the American Thoracic Society.
“We found that increased airway inflammation, demonstrated by higher concentrations of sputum proteases and cytokines, was associated with two important indicators of lung disease: impaired lung function and structural airway damage as determined by chest CT,” Scott D. Sagel, MD, PhD, professor of pediatrics-pulmonary medicine at University of Colorado School of Medicine, told Healio. “While this is not unexpected, since similar findings have been shown in people with cystic fibrosis (CF) and non-CF bronchiectasis, it was unknown and an important finding in this large diverse group of children with primary ciliary dyskinesia (PCD).”
In a multicenter observational cohort study, Sagel and colleagues assessed sputum samples from 77 children (mean age, 13.9 years; 51% female; FEV1 percent predicted, 80.8) aged 6 years to younger than 19 years with PCD to understand the impact airway inflammation has on lung disease development in this patient population.
To evaluate this impact, researchers looked for correlations between sputum inflammation measurements with age, lung function and structural lung disease found on chest CT.
Additionally, researchers looked for differences in measures of sputum inflammation between those with vs. without detectable bacterial infection and between various ciliary ultrastructural defects.
Researchers found positive correlations between sputum neutrophil elastase, interleukin-1B (IL-1B), IL-8 and tumor necrosis factor-alpha (TNF-alpha) with age, percentage of bronchiectasis and percentage of total structural lung disease. Further, researchers observed positive correlations between both sputum IL-1B and TNF-alpha concentrations and mucus plugging on the CT scans.
Looking specifically at concentrations of neutrophil elastase, researchers found a –0.32 (95% CI, –0.51 to –0.1) correlation coefficient with FEV1 percent predicted and a 0.46 (95% CI, 0.14-0.69) correlation coefficient with bronchiectasis percentage.
Negative correlations between sputum neutrophil elastase, IL-1B and TNF-alpha with FEV1 percent predicted were observed, signaling that increased inflammation is linked to decreased lung function, according to researchers.
Researchers further observed that children with detectable bacterial pathogens had increased concentrations of neutrophil elastase, IL-1B and TNF-alpha than patients without detectable infection.
Despite previous studies showing lower lung function and more lung function decline in children with absent inner dynein arm and microtubular disorganization ciliary defects vs. those with isolated outer dynein arm defects, Sagel and colleagues found no difference in airway inflammation between the two groups. Researchers noted that this was interesting considering that patients with absent inner dynein arm and microtubular disorganization defects had worse FEV1 percent predicted than patients with isolated outer dynein arm defects (mean, 71.5 vs. 89.5; P < .01).
Additionally, researchers compared these sputum inflammation measures with those of age-matched children with CF and found comparable measures of neutrophil elastase, IL-1B and IL-6. This analysis also found elevated measures of sputum IL-8 and TNF-alpha in patients with PCD than in patients with CF, which was surprising, according to Sagel.
“These results, which establish an important linkage between airway inflammation and lung disease in PCD, suggest that inflammation might be a treatment target in PCD clinical trials,” Sagel told Healio. “Our findings indicate that sputum measurements of inflammation can be used as biomarkers of PCD lung disease severity and activity and can be used to assess the efficacy of anti-inflammatory therapies.”
With these study findings by Sagel and colleagues, clinicians may have a new way to measure PCD severity through sputum samples, but further studies are necessary, according to an accompanying editorial by Dvir Gatt, MD, pediatric respiratory fellow, and Felix Ratjen, MD, PhD, pediatric respirologist, both of The Hospital for Sick Children in Canada.
“These findings show a linkage to disease progression and could serve as possible markers for disease trajectories and severity,” Gatt and Ratjen wrote. “Although the findings reported by Sagel and colleagues do not necessarily prove causation, such measurements may help to further our understanding of how lung damage occurs in PCD. Longitudinal studies are needed to better delineate the predictive role of biomarkers of airway inflammation for the subsequent course of lung disease.”
For more information:
Scott D. Sagel, MD, PhD, can be reached at scott.sagel@childrenscolorado.org.