Reduced exercise ventilatory efficiency in adults with cystic fibrosis and normal to moderately impaired lung function

Despite being a hallmark and an independent prognostic factor in several cardiopulmonary diseases, ventilatory efficiency-i.e., minute ventilation/carbon dioxide output relationship ((V) over dot(E)/(V) over dot(CO2))-has never been systematically explored in cystic fibrosis (CF). To provide a comprehensive frame of reference regarding measures of ventilatory efficiency in CF adults with normal to moderately impaired lung function and to confirm the hypothesis that (V) over dot(E)/(V) over dot(CO2) is a sensitive marker of early lung disease. CF patients were divided into three groups, according to their spirometry: normal (G(1)), mild impairment (G(2)), and moderate impairment (G(3)) in lung function. All participants underwent incremental cardiopulmonary exercise testing on a cycle ergometer. Lowest (V) over dot(E)/(V) over dot(CO2) ratio (nadir) and the slope and the intercept of the linear region of the V-E/(V) over dot(CO2) relationship were contrasted in a two-center retrospective analysis, involving 72 CF patients and 36 healthy controls (HC). Compared with HC, CF patients had significantly higher (V) over dot(E)/(V) over dot(CO2) nadir, slope, and intercept (P < 0.001, P < 0.001, and P = 0.049, respectively). Subgroup analysis revealed significant differences in nadir (P = 0.001) and slope (P = 0.012) values even between HC and G(1). Dynamic hyperinflation related negatively with slope (P = 0.045) and positively with intercept (P = 0.001), while no impact on nadir was observed. Ventilatory inefficiency is a clear feature of adults with CF, even among patients with normal spirometry. (V) over dot(E)/(V) over dot(CO2) nadir seems to be the most reliable metric to describe ventilatory efficiency in CF adults. Further prospective studies are needed to clarify whether (V) over dot(E)/(V) over dot(CO2) could represent a useful marker in the evaluation of early lung disease in CF.NEW & NOTEWORTHY This is the first study to investigate ventilatory efficiency in a cohort of adult cystic fibrosis (CF) patients with nonsevere lung disease. The finding of impaired ventilatory efficiency in patients with normal lung function confirms the higher sensitivity of exercise testing in detecting early lung disease compared with spirometry. Dynamic hyperinflation plays a significant role in determining the behavior of (V) over dot(E)/(V) over dot(CO2) slope and intercept values with increasing lung function impairment. Apparently free from interference from mechanical constraints, (V) over dot(E)/(V) over dot(CO2) nadir seems the most reliable parameter to evaluate ventilatory efficiency in CF adults.