Browsing by Subject "Pulmonary exacerbations"

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    Evaluating FEV1 decline in diagnosis and management of pulmonary exacerbations in children with cystic fibrosis
    (Wiley, 2022) Bouzek, Drake C.; Ren, Clement L.; Thompson, Misty; Slaven, James E.; Sanders, Don B.; Pediatrics, School of Medicine
    Rationale: Forced expiratory volume in 1 s (FEV1) decline (ΔFEV1) is associated with pulmonary exacerbation (PEx) diagnosis in cystic fibrosis (CF). Spirometry may not be available during telehealth visits and could impair clinician ability to diagnose PEx. This study aims to (1) identify the associations between degrees of ΔFEV1 (decrease of <5% predicted vs. 5%-9% predicted vs. ≥10% predicted from baseline), clinical symptoms, and clinician-diagnosed PEx and (2) evaluate the correlation between respiratory symptoms, ΔFEV1, and antibiotic treatment. Methods: Retrospective, descriptive study of PEx diagnosis and management in 628 outpatient clinical encounters with spirometry in 178 patients with CF ages 6-17 years at Riley Hospital for Children during 2019. Odds ratios (OR) of symptoms associated with clinician-defined PEx diagnosis and antibiotic management stratified by ΔFEV1 decline were determined. Results: Clinician-diagnosed PEx occurred at 199 (31.7%) visits; increased cough (77.4%) and sputum/wet cough (57.8%) were the most frequently reported symptoms. Compared to no ΔFEV1, the odds of a clinician-diagnosed PEx were increased when ΔFEV15%-9% and ΔFEV1≥10% was present with increased cough (OR 1.56, 95% confidence interval [CI] 1.25-1.94 and OR 1.82, 95% CI 1.52-2.19, respectively), increased sputum (OR 1.59, 95% CI 1.20-2.12 and OR 1.78, 95% CI 1.37-2.32, respectively), and increased cough and sputum together (OR 1.51, 95% CI 1.08-2.13 and OR 1.68, 95% CI 1.22-2.31, respectively). Conclusions: ΔFEV1 is associated with increased likelihood that cough and sputum are diagnosed as a PEx. Spirometry is essential for PEx diagnosis and treatment and is a necessary component of all clinical encounters.
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    Safety and efficacy of lenabasum in a phase 2 randomized, placebo-controlled trial in adults with cystic fibrosis
    (Elsevier, 2021) Chmiel, James F.; Flume, Patrick; Downey, Damian G.; Dozor, Allen J.; Colombo, Carla; Mazurek, Henryk; Sapiejka, Ewa; Rachel, Marta; Constantine, Scott; Conley, Brian; Dgetluck, Nancy; Dinh, Quinn; White, Barbara; Elborn, J. Stuart; Lenabasum JBT101-CF-001 Study Group; Pediatrics, School of Medicine
    Background: Few therapies specifically address the chronic airway inflammation in cystic fibrosis (CF) that contributes to progressive destruction of lung tissue and loss of lung function. Lenabasum is a cannabinoid type 2 receptor (CB2) agonist that resolves inflammation in a number of in vitro and in vivo models. Methods: A Phase 2 double-blind, randomized, placebo-controlled study assessed the safety and tolerability of lenabasum in adults with CF. Subjects with FEV1% (ppFEV1) ≥40% predicted were randomized to lenabasum 1 or 5 mg or placebo once daily (QD) (Weeks 1-4), then 20 mg QD, 20 mg twice daily (BID) or placebo (Weeks 5-12), with follow-up at Week 16. Pulmonary exacerbations (PEx) were recorded and biomarkers of blood and lung inflammation were measured. Results: Of 89 subjects randomized, 51 lenabasum and 23 placebo-only subjects completed the study. No deaths or serious or severe adverse events (AE) were considered related to lenabasum. Most AEs were mild/moderate, and the most common were PEx, hemoptysis, dry mouth, and upper respiratory infection. Three lenabasum and one placebo-only subjects discontinued the study for a treatment related AE. New PEx were treated with intravenous antibiotics in 4.0% of lenabasum-treated vs. 11.4% of placebo-treated subjects, during Weeks 1-4 and 5.2% compared to 13.0% during Weeks 5-12 (p<0.2). No significant differences in ppFEV1 were observed between treatment groups. Sputum neutrophils, eosinophils, and neutrophil elastase were numerically reduced, and significant (p<0.05) reductions in IL-8 and immunoglobulin G levels occurred with lenabasum. Conclusions: The safety findings of lenabasum, coupled with biomarker data, support further testing in a larger study with a longer duration.