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In cirrhotic patients, alveolar nitric oxide (NO) concentration is increased. This may be secondary to increased output of NO produced by the alveoli (V9A,NO) and/or to decreased lung transfer factor of NO. In advanced liver cirrhosis, NO produced by the alveoli may play a role in abnormalities of pulmonary haemodynamics and gas exchanges. In cirrhotic patients, we aimed to measure V9A,NO and to compare V9A,NO with pulmonary haemodynamics and gas exchange parameters.Measurements were performed in 22 healthy controls and in 29 cirrhotic patients, of whom eight had hepatopulmonary syndrome. Exhaled NO concentrations were measured at multiple expiratory flow rates to derive alveolar NO concentration. V9A,NO was the product of alveolar NO concentration by single breath lung transfer factor for NO.V9A,NO was increased in patients (median (range) 260 (177-341) nL?min) compared with controls (79 (60-90), p,0.0001). Alveolar-arterial oxygen tension difference failed to correlate with V9A,NO. However, cardiac index correlated positively and systemic vascular resistance correlated negatively with V9A, NO (r50.56, p50.004, respectively).In cirrhotic patients, NO was produced in excess by the alveolar compartment of the lungs. Alveolar NO production was associated with hyperdynamic circulatory syndrome but not with arterial oxygenation impairment.

A chronic intestinal inflammation may occur in patients with cystic fibrosis (CF), while no therapeutic management is proposed. Although Lumacaftor/Ivacaftor is well-known to modulate the defective cystic fibrosis transmembrane conductance regulator (CFTR) protein in lungs, no data are available on the impact of this treatment on CF intestinal disorders. We, therefore, investigated the evolution of intestinal inflammation after initiation of Lumacaftor/Ivacaftor in CF adolescents (median of follow-up: 336 days [IQR: 278;435]). Median fecal calprotectin concentrations decreased significantly after Lumacaftor/Ivacaftor initiation (102 μg/g [IQR: 69–210]) compared with the baseline (713 μg/g (IQR:148–852), P = 0.001). To our knowledge, this study showed for the first time that CF-related intestinal inflammation is improved by Lumacaftor/Ivacaftor treatment.

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.