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Background: The combination of the CFTR corrector lumacaftor (LUM) and potentiator ivacaftor (IVA) has been labeled in France since 2015 for F508del homozygote cystic fibrosis (CF) patients over 12 years. In this real-life study, we aimed (i) to compare the changes in lung function, clinical (e.g., body mass index and pulmonary exacerbations) and radiological parameters, and in sweat chloride concentration before and after initiation of LUM/IVA treatment; (ii) to identify factors associated with response to treatment; and (iii) to assess the tolerance to treatment.Materials and Methods: In this tri-center, non-interventional, and observational cohort study, children (12–18 years old) were assessed prospectively during the 2 years of therapy, and retrospectively during the 2 years preceding treatment. Data collected and analyzed for the study were exclusively extracted from the medical electronic system records of the patients.Results: Forty adolescents aged 12.0–17.4 years at LUM/IVA initiation were included. The lung function decreased significantly during and prior to treatment and increased after LUM/IVA initiation, becoming significant after 2 years of treatment. LUM/IVA significantly improved the BMI Z-score and sweat chloride concentration. By contrast, there was no significant change in exacerbation rates, antibiotic use, or CT scan scores. Age at LUM/IVA initiation was lower in good responders and associated with greater ppFEV1 change during the 2 years of treatment. LUM/IVA was well-tolerated.Conclusion: In F508del homozygote adolescents, real-life long-term LUM/IVA improved the ppFEV1 trajectory, particularly in the youngest patients, nutritional status, and sweat chloride concentration but not exacerbation rates or radiological scores. LUM/IVA was generally well-tolerated and safe.

Background Bacterial infection early in life may increase structural lung lesions in children with cystic fibrosis (CF). Methods A 9‐year monocentric (Bordeaux University Hospital, France) retrospective study in children with CF to evaluate the impact of the early‐onset (at 1 year of age, Y1) of chronic meticillin‐sensitive Staphylococcus aureus (MSSA) infection on the severity of bronchiectasis and Bhalla score on CT scan, clinical status, lung function tests, and serum immunoglobulins (IgG) at the age of 6 years (Y6). Results A total of 37 children were included: 10 had contracted chronic MSSA infection at Y1 and 27 at a later date. Children with MSSA infection at Y1 showed increased Y6 CT scan bronchiectasis severity scores vs late MSSA infection (mean ± SD: 4.7 ± 0.8 vs 2.5 ± 0.5, P < .05) and Bhalla scores (7.3 ± 1.1 vs 4.7 ± 0.8, P < .05), but no significant decrease in lung function ([% reference values] FEV1: 83.7 ± 6 vs 90.6 ± 2.2, P = .21; FEF25‐75: 67.8 ± 8.9 vs 76.3 ± 3.9, P = .18). In addition, Y6 serum IgG was greater in the early chronic Y1 MSSA group (11.3 ± 0.7 vs 8.9 ± 0.7 g/L, P < .05). Clinical symptoms or nutritional status were similar in both infection groups. Conclusion Early chronic MSSA infection may enhance the progression of structural lung disease in CF at 6 years.

Preschool wheezing and related hospitalization rates are increasing. Prenatal tobacco smoke exposure (PTSE) increases the risk of wheezing, yet >20% of French women smoke during pregnancy. In this observational retrospective monocentric study, we assessed the link between PTSE and hospital admissions. We included infants <2 years of age admitted for acute wheezing. A phone interview with mothers was completed by electronic records. The primary endpoint was the ratio of cumulative duration of the hospitalization stays (days)/age (months). 129 children were included (36.4% exposed to PTSE vs. 63.6% unexposed). There was a significant difference in the duration of hospitalization/age: 0.9 days/month (exposed) vs. 0.58 days/month (unexposed) (p = 0.008). Smoking one cigarette/day during pregnancy was associated with an increase in hospitalization duration of 0.055 days/month (r = 0.238, p = 0.006). In the multi-variable analysis, this positive association persisted (β = 0.04, p = 0.04; standardized b = 0.27, p = 0.03). There was a trend towards a dose-effect relationship between PTSE and other important parameters associated with hospital admissions. We have demonstrated a dose-effect relationship, without a threshold effect, between PTSE and duration of hospitalization for wheezing in non-premature infants during the first 2 years of life. Prevention campaigns for future mothers should be enforced.

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