Clinical studies with modulators of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) protein have demonstrated that functional restoration of the mutated CFTR can lead to substantial clinical benefit. However, studies have shown highly variable patient responses. The objective of this study was to determine a biomarker predictive of the clinical response. CFTR function was assessed in vivo via nasal potential difference (NPD) and in human nasal epithelial (HNE) cultures by the response to Forskolin/IBMX and the CFTR potentiator VX-770 in short-circuit-current (∆IscF/I+V) experiments. CFTR expression was evaluated by apical membrane fluorescence semi-quantification. Isc measurements discriminated CFTR function between controls, healthy heterozygotes, patients homozygous for the severe F508del mutation and patients with genotypes leading to absent or residual function. ∆IscF/I+V correlated with CFTR cellular apical expression and NPD measurements. The CFTR correctors lumacaftor and tezacaftor significantly increased the ∆IscF/I+V response to about 25% (SEM = 4.4) of the WT-CFTR level and the CFTR apical expression to about 22% (SEM = 4.6) of the WT-CFTR level in F508del/F508del HNE cells. The level of CFTR correction in HNE cultures significantly correlated with the FEV1 change at 6 months in 8 patients treated with CFTR modulators. We provide the first evidence that correction of CFTR function in HNE cell cultures can predict respiratory improvement by CFTR modulators.

SC is associated with poor prognosis and high rate of resistance to conventional first-line CT. New therapeutic strategies are needed, based on better knowledge of the carcinogenesis of SC.

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Severe pulmonary hypertension is a common feature in patients with end-stage PLCH. Given the good postransplant survival rate and despite a recurrence rate of the disease of approximately 20% after LT, we conclude that LT is a therapeutic option in this setting.

Background: Infection with Burkholderia cepacia complex (BCC) is a life threatening complication of cystic fibrosis (CF), often seen as a contraindication for lung transplantation. Methods: A long term retrospective study was conducted of all patients with CF undergoing lung transplants from January 1990 to October 2006 in two French centres allowing transplantation in patients colonised with BCC. Results: 22 of the 247 lung transplant patients with CF were infected with BCC (B cenocepacia genomovar III (n = 8), B multivorans genomovar II (n = 11), B vietnamiensis genomovar V (n = 2) and B stabilis genomovar IV (n = 1)). BCC colonisation was not associated with any significant excess mortality (HR 1.5, 95% CI 0.7 to 3.2; p = 0.58). However, early mortality rates tended to be higher in the BCC group than in the non-BCC group (3 month survival: 85% vs 95%, respectively; log rank p = 0.05). Univariate analysis showed that the risk of death was significantly higher for the eight patients infected with B cenocepacia than for the other 14 colonised patients (HR 3.2, 95% CI 1.1 to 5.9; p = 0.04). None of the other risk factors testedprimary graft failure, late extubation, septicaemia-had a significant effect. The 5 year cumulative incidence rate of bronchiolitis obliterans syndrome was not significantly higher in the BCC group than in the non-BCC group (38% vs 24%, respectively; p = 0.35). Conclusion: Our results suggest that BCC infection with a non-genomovar III organism may not be associated with excess mortality after lung transplantation in patients with CF and should not be seen as sufficient reason to exclude lung transplantation. However, colonisation with B cenocepacia remains potentially detrimental.Cystic fibrosis (CF) is the most common inherited lung disease. It frequently progresses to respiratory failure and death and the treatments currently available aim to slow progression through respiratory therapy, good nutritional support and the treatment of pulmonary exacerbations. In patients with end stage CF, lung transplantation may help to prolong survival and ensure that patients have an acceptable quality of life. Survival rates 1, 3 and 5 years after transplantation of 76%, 60% and 49%, respectively, have been reported. 1 Organ shortages have led some physicians to try to select the ''best candidates'' for lung transplantation.2 One of the criteria used in pretransplantation selection is the absence of infection with Burkholderia cepacia complex (BCC). This gram negative bacterium causes serious opportunistic infections and has emerged as a major pathogen in patients with CF, with the clinical outcome of infection varying from long term bronchial colonisation to life threatening necrotising pneumonia and sepsis, known as ''cepacia syndrome''. Global mortality rates for BCC colonisation may reach 50%, 3-9 depending on genomovar type. However, these rates were determined for patients who had not yet undergone transplantation. Conflicting results have been published concerning post-transplantation ...