Study identifies subphenotypes of cystic fibrosis pulmonary exacerbations

A new study published in Annals of the American Thoracic Society highlighted subphenotypes of cystic fibrosis pulmonary exacerbations and differences in biomarker profiles, clinical presentation and outcomes.

“Using a predefined method of classification for cystic fibrosis pulmonary exacerbations, differences in clinical outcomes and inflammatory profiles were detected in three cohorts of cystic fibrosis patients with acute pulmonary exacerbations,” Suzanne C. Carter, MD, from the National Referral Centre for Adult Cystic Fibrosis at St. Vincent’s University Hospital in Dublin and the University College Dublin School of Medicine, and colleagues wrote. “For the first time, we describe the pauci-inflammatory exacerbation subphenotype of cystic fibrosis exacerbation associated with reduced markers of systemic inflammation and lower loss of lung function at exacerbation onset, and more rapid response to treatment. Viral and non-viral inflammatory exacerbation subphenotypes also exist with differences in [C-reactive protein] and lung function drop at onset of exacerbation but similar responses to treatment.”

This observational cohort study included 59 patients with cystic fibrosis at the time of admission for a pulmonary exacerbation. Researchers collected nasal swabs and sputum samples and measured serum and plasma biomarkers. Pulmonary exacerbations were classified as the following:

• pauci-inflammatory if C-reactive protein (CRP) was less than 5 mg/L;
• nonviral with systemic inflammation if CRP was 5 mg/L or more with no viral infection detected by polymerase chain reaction (PCR); or
• viral with systemic inflammation if CRP was 5 mg/L or more with viral infection detected by PCR.

Overall, 37% of patients had the pauci-inflammatory subphenotype, 41% had the nonviral with systemic inflammation subphenotype and 22% had the viral with systemic inflammation subphenotype. Across phenotypes, immunoglobulin, immunoglobulin M, interleukin-10, interleukin-13, serum calprotectin and CRP levels differed.

FEV₁ percent predicted reduction from baseline at onset of pulmonary exacerbation was different between patients with the nonviral with systemic inflammation subphenotype and those with the viral with systemic inflammation subphenotype (–6.73 vs. –13.5; P = .025). Patients with nonviral systemic inflammation pulmonary exacerbations experienced a trend toward a longer duration of IV antibiotic use compared with patients with pauci-inflammation exacerbations (18.1 vs. 14.8 days; P = .057).

Researchers observed no differences in the percent of patients with lung function recovery to less than 10% of baseline FEV₁ percent predicted. Researchers reported similar results in local and external validation cohorts that compared pauci-inflammatory to viral and nonviral inflammatory pulmonary exacerbation phenotypes.

“In an era of increasing antimicrobial resistance and new cystic fibrosis therapeutics, a more personalized approach to treating cystic fibrosis pulmonary exacerbations may help reduce the significant morbidity and mortality associated with these events,” the researchers wrote.