One year effect of tezacaftor and ivacaftor on functional exercise capacity and muscle strength in people with cystic fibrosis.

Background: The 1-min sit-to-stand test (1STST) is a practical tool to evaluate physical capacity. The aim of this study was to assess the impact of tezacaftor and ivacaftor on functional exercise capacity, muscle strength and symptoms in people with cystic fibrosis (PwCF). Methods: The assessments were performed during the first year of tezacaftor and ivacaftor using the 1STST, 6-min walk test (6MWT), MicroFET2 dynamometer®, CF Questionnaire-Revised (CFQ-R), Leicester Cough Questionnaire (LCQ). Forced expiratory volume in 1 s (FEV1), body mass index (BMI), pancreatic sufficiency status, genotype and microbiologic data were also collected. Results: Fifty-four PwCF participated to the study and took at least one dose of tezacaftor-ivacaftor. Mean age was 26y±10 (±SD), median BMI 20.9 kg/m2 (interquartile range) (19.4; 23.5) and mean FEV1 82 percent of predicted values (%PV) ± 21. Significant correlations were found at baseline between the 1STST and the 6MWT (r = 0.617, p < 0.0001), the quadriceps strength (r = 0.6556, p < 0.0001) and the FEV1 (r = 0.29, p = 0.03). After one year of treatment, the 1STST increased significantly in terms of number of repetitions (n) (median 50 versus 58.5, p < 0.0001), %PV (101.1 versus 115.2%PV, p = 0.0003) and n times weight in kg (2885 versus 3389nxkg, p < 0.0001). The 6MWT distance and quadriceps strength were not modified after treatment but during the 6MWT, oxygen desaturation decreased significantly. FEV1, BMI, CFQ-R, LCQ improved as previously demonstrated. Conclusion: After one year of tezacaftor and ivacaftor, the 1STST improves, suggesting that the 1STST seems more responsive than the 6MWT and the MicroFET2 dynamometer® to assess the effects of CFTR modulators.

Ex-vivo effects of intrapulmonary percussive ventilation on sputum rheological properties.

Intrapulmonary percussive ventilation (IPV) has been postulated to enhance mucociliary clearance by improving tracheobronchial sputum rheological properties. The IPV effects on linear (viscoelasticity) and non-linear (flowing) rheological properties of 40 sputum samples collected from 19 patients with muco-obstructive lung diseases were investigated ex-vivo. Each sputum sample was split into 4 aliquots. These aliquots were independently placed in a circuit connected on one side to an IPV device and on the other side to a lung model that simulated spontaneous adult breaths. IPV was superimposed on simulated breathing. Three aliquots were exposed to a different IPV setting, modifying either percussion frequency or amplitude (4 Hz-200 L/min, 10 Hz-200 L/min, 10 Hz-140 L/min). One aliquot was only exposed to breathing (IPV was switched off, control condition). Each aliquot underwent 5 min of the pre-fixed mechanical stimulation before being recollected to proceed to rheological analysis. Neither percussion frequencies nor amplitudes had a significant impact on any sputum rheological properties studied. These results need to be confirmed in vivo.