This study highlights the prevalence of adverse effects in a CF population newly exposed to lumacaftor/ivacaftor and demonstrates a relatively high rate of drug intolerance.

Nasal high flow (NHF) reduces minute ventilation and ventilatory loads during sleep but the mechanisms are not clear. We hypothesised NHF reduces ventilation in proportion to physiological but not anatomical dead space.11 subjects (five controls and six chronic obstructive pulmonary disease (COPD) patients) underwent polysomnography with transcutaneous carbon dioxide (CO) monitoring under a metabolic hood. During stable non-rapid eye movement stage 2 sleep, subjects received NHF (20 L·min) intermittently for periods of 5-10 min. We measured CO production and calculated dead space ventilation.Controls and COPD patients responded similarly to NHF. NHF reduced minute ventilation (from 5.6±0.4 to 4.8±0.4 L·min; p<0.05) and tidal volume (from 0.34±0.03 to 0.3±0.03 L; p<0.05) without a change in energy expenditure, transcutaneous CO or alveolar ventilation. There was a significant decrease in dead space ventilation (from 2.5±0.4 to 1.6±0.4 L·min; p<0.05), but not in respiratory rate. The reduction in dead space ventilation correlated with baseline physiological dead space fraction (r=0.36; p<0.05), but not with respiratory rate or anatomical dead space volume.During sleep, NHF decreases minute ventilation due to an overall reduction in dead space ventilation in proportion to the extent of baseline physiological dead space fraction.

BACKGROUND AND OBJECTIVES: Children with cystic fibrosis (CF) often report poor sleep, increased daytime sleepiness, and fatigue. The purpose of this study was to identify respiratory patterns over the spectrum of disease severity in children with CF. The overall hypothesis for the current study is that children with CF compared with snoring control subjects demonstrate gas exchange abnormalities and increased respiratory loads during sleep that are not reported or recognized by conventional polysomnography (PSG).METHODS: Analysis of breathing patterns and gas exchange on PSG was performed in children with CF and healthy controls matched by age and BMI. For all CF and control subjects, the indication for PSG was evaluation for obstructive sleep apnea based on a history of snoring.RESULTS: Children with CF, compared with age-and BMI-matched snoring controls, demonstrated lower oxyhemoglobin saturation (95% 6 1.6% vs 98% 6 0.6%, P = .005), higher respiratory rate (19.5 6 4.9 vs 16.5 6 1.2 breaths per minute, P = .03), and a higher proportion of inspiratory flow limitation (44.1% 6 24.7% vs 12.1% 6 13.5%, P = .007) during non-rapid eye movement sleep. The respiratory disturbance index did not differ between CF and snoring control groups (1.5 6 2.7 vs 0.6 6 0.6 events per hour, P = .11).CONCLUSIONS: Children with CF exhibited abnormalities in gas exchange and increased respiratory load during sleep compared with normal age-and BMI-matched snoring controls. Because these abnormalities were independent of weight and lung function, sleep state may serve as an opportunity for early detection of breathing abnormalities and possibly CF lung disease progression.