More Relaxation by Deep Breath on Methacholine- Than on Exercise-Induced bronchoconstriction during the Routine Testing of Asthmatic Children

Deep inspiration (DI) dilates normal airway precontracted with methacholine. The fact that this effect is diminished or absent in asthma could be explained by the presence of bronchial inflammation. The hypothesis was tested that DI induces more relaxation in methacholine induced bronchoconstriction—solely determined by the smooth muscle contraction—than in exercise induced bronchoconstriction, which is contributed to by both smooth muscle contraction and airway wall inflammation. The respiratory conductance (Grs) response to DI was monitored in asthmatic children presenting a moderately positive airway response to challenge by methacholine (n = 36) or exercise (n = 37), and expressed as the post- to pre-DI Grs ratio (GrsDI). Both groups showed similar change in FEV1 after challenge and performed a DI of similar amplitude. GrsDI however was significantly larger in methacholine than in exercise induced bronchoconstriction (p < 0.02). The bronchodilatory effect of DI is thus less during exercise- than methacholine-induced bronchoconstriction. The observation is consistent with airway wall inflammation—that characterizes exercise induced bronchoconstriction—rendering the airways less responsive to DI. More generally, it is surmised that less relief of bronchoconstriction by DI is to be expected during indirect than direct airway challenge. The current suggestion that airway smooth muscle constriction and airway wall inflammation may result in opposing effects on the bronchomotor action of DI opens important perspective to the routine testing of asthmatic children. New crossover research protocols comparing the mechanical consequences of the DI maneuver are warranted during direct and indirect bronchial challenges

Rapid Improvement after Starting Elexacaftor–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and Advanced Pulmonary Disease

International audienceRationale: Elexacaftor-tezacaftor-ivacaftor is a CFTR (cystic fibrosis [CF] transmembrane conductance regulator) modulator combination, developed for patients with CF with at least one Phe508del mutation. Objectives: To evaluate the effects of elexacaftor-tezacaftor- ivacaftor in patients with CF and advanced respiratory disease. Methods: A prospective observational study, including all patients aged ⩾12 years and with a percent-predicted FEV1 (ppFEV1) <40 who initiated elexacaftor-tezacaftor-ivacaftor from December 2019 to August 2020 in France was conducted. Clinical characteristics were collected at initiation and at 1 and 3 months. Safety and effectiveness were evaluated by September 2020. National-level transplantation and mortality figures for 2020 were obtained from the French CF and transplant centers and registries. Measurements and Main Results: Elexacaftor-tezacaftor- ivacaftor was initiated in 245 patients with a median (interquartile range) ppFEV1 = 29 (24-34). The mean (95% confidence interval) absolute increase in the ppFEV1 was +15.1 (+13.8 to +16.4; P < 0.0001), and the mean (95% confidence interval) in weight was +4.2 kg (+3.9 to +4.6; P < 0.0001). The number of patients requiring long-term oxygen, noninvasive ventilation, and/or enteral tube feeding decreased by 50%, 30%, and 50%, respectively (P < 0.01). Although 16 patients were on the transplant waiting list and 37 were undergoing transplantation evaluation at treatment initiation, only 2 received a transplant, and 1 died. By September 2020, only five patients were still on the transplantation path. Compared with the previous 2 years, a twofold decrease in the number of lung transplantations in patients with CF was observed in 2020, whereas the number of deaths without transplantation remained stable. Conclusions: In patients with advanced disease, elexacaftor-tezacaftor-ivacaftor is associated with rapid clinical improvement, often leading to the indication for lung transplantation being suspended