Exercise ventilatory inefficiency in adults with Cystic Fibrosis with normal to moderate impairment in lung function

Introduction: Despite of being recognized as a hallmark and an independent prognostic factor in several respiratory and cardiovascular diseases, ventilatory efficiency (VE/VCO2 relationship) has never been systematically explored in Cystic Fibrosis (CF). Aim: To provide a comprehensive frame of reference regarding measures of ventilatory inefficiency in CF adults with normal to moderate impairment in lung function tests (LFT). Methods: 74 CF patients (age 31.4 ± 7.7 years, BMI 22.2 ± 2.6 kg/m2) and 36 age-sex-BMI matched healthy controls (HC) were recruited in a multicenter observational study. CF patients were divided into 3 groups according to their LFT impairment: normal (G1: FEV1/FVC ≥ 0.7, FEV1 > 80%; n = 16), mild (G2: FEV1/FVC < 0.7, FEV1 ≥ 70%; n = 23) and moderate (G3; FEV1/FVC < 0.7, FEV1 40-69%; n = 35). All participants underwent incremental cardiopulmonary exercise testing (CPET) on cycle-ergometer. Slope and intercept of the linear region of the VE/VCO2 relationship and the lowest VE/VCO2 ratio (nadir) were assessed. Results: Compared to HC, CF patients had significantly higher values of VE/VCO2 nadir and slope (24.2 ± 2.5 vs 29.3 ± 4.2, p < 0.001; 25.0 ± 2.9 vs 29.0 ± 4.6, p < 0.001, respectively). Subgroup analysis revealed a significant difference in VE/VCO2 nadir values even between HC and G1 (p = 0.017). Intercept was not different between groups. Conclusions: Ventilatory inefficiency is a clear feature of adults with CF, even among patients with normal spirometry. VE/VCO2 nadir could be used in CF to detect early impairment in lung function and could represent a valuable outcome for further prospective trials.