The combination of lumacaftor and ivacaftor (LUM/IVA) has been reported to induce a mean acute absolute drop of -4.1% predicted forced expiratory volume in 1 s (FEV 1 ) after a unique administration in healthy subjects. The aim of the present study was to assess acute FEV 1 changes after the first dose of LUM/IVA in CF patients. A total of 32 pediatric patients were included. Respiratory manifestations occurred in only 3 patients (9.4%), but FEV 1 consistently decreased (-10.4 ±4.6%, range: -1.5; -21.8%). FEV 1 only partially resumed after salbutamol inhalation. Patients with previously known significant reversible airway obstruction and low FEV 1 were more at risk of FEV 1 decrease.