Acute Pulmonary Exacerbation Phenotypes in Patients with Cystic Fibrosis.

The etiology of cystic fibrosis (CF) pulmonary exacerbations (PEx) is likely multifactorial with viral, bacterial, and non-infectious pathways contributing. To determine whether viral infection status and CRP (C-reactive protein) can classify subphenotypes of PEx that differ in outcomes and biomarker profiles. Patients were recruited at time of admission for a PEx. Nasal swabs and sputum samples were collected and processed using the respiratory panel of the FilmArray multiplex polymerase chain reaction (PCR). Serum and plasma biomarkers were measured. PEx were classified using serum CRP and viral PCR: "" if CRP < 5 mg/L, "" if CRP ⩾ 5 mg/L and no viral infection detected by PCR and "" if CRP ⩾ 5 mg/L and viral infection detected by PCR. Discovery cohort ( = 59) subphenotype frequencies were ) pauci-inflammatory (37%); ) non-viral with systemic inflammation (41%); and ) viral with systemic inflammation (22%). Immunoglobulin G, immunoglobulin M, interleukin-10, interleukin-13, serum calprotectin, and CRP levels differed across phenotypes. Reduction from baseline in forced expiratory volume in 1 second as percent predicted (FEVpp) at onset of exacerbation differed between and (-6.73 ± 1.78 vs. -13.5 ± 2.32%;  = 0.025). PEx had a trend toward longer duration of intravenous antibiotics versus (18.1 ± 1.17 vs. 14.8 ± 1.19 days,  = 0.057). There were no differences in percent with lung function recovery to <10% of baseline FEVpp. Similar results were seen in local and external validation cohorts comparing a to exacerbation phenotypes. Subphenotypes of CF PEx exist with differences in biomarker profile, clinical presentation, and outcomes.