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International audience; Rationale: Lumacaftor-ivacaftor is a CFTR (cystic fibrosis transmembrane conductance regulator) modulator combination recently approved for patients with cystic fibrosis (CF) homozygous for the Phe508del mutation.Objectives: To evaluate the safety and effectiveness of lumacaftor-ivacaftor in adolescents (≥12 yr) and adults (≥18 yr) in a real-life postapproval setting.Methods: The study was conducted in the 47 CF reference centers in France. All patients who initiated lumacaftor-ivacaftor from January 1 to December 31, 2016, were eligible. Patients were evaluated for lumacaftor-ivacaftor safety and effectiveness over the first year of treatment following the French CF Learning Society's recommendations.Measurements and Main Results: Among the 845 patients (292 adolescents and 553 adults) who initiated lumacaftor-ivacaftor, 18.2% (154 patients) discontinued treatment, often owing to respiratory (48.1%, 74 patients) or nonrespiratory (27.9%, 43 patients) adverse events. In multivariable logistic regression, factors associated with increased rates of discontinuation included adult age group, percent predicted FEV1 (ppFEV1) less than 40%, and numbers of intravenous antibiotic courses during the year before lumacaftor-ivacaftor initiation. Patients with continuous exposure to lumacaftor-ivacaftor showed an absolute increase in ppFEV1 (+3.67%), an increase in body mass index (+0.73 kg/m2), and a decrease in intravenous antibiotic courses by 35%. Patients who discontinued treatment had significant decrease in ppFEV1, without improvement in body mass index or decrease in intravenous antibiotic courses.Conclusions: Lumacaftor-ivacaftor was associated with improvement in lung disease and nutritional status in patients who tolerated treatment. Adults who discontinued lumacaftor-ivacaftor, often owing to adverse events, were found at high risk of clinical deterioration.

Background Allergic bronchopulmonary aspergillosis (ABPA) is a severe lung disease complication caused by an Aspergillus fumigatus-induced hypersensitivity that affects 2–15% of patients with cystic fibrosis (CF). The mainstay treatment consists of a combination of corticosteroids and antifungals. However, repeated or long-term corticosteroid therapies can lead to serious side effects. The monoclonal anti-IgE antibody, omalizumab, has demonstrated its efficacy in allergic asthma. As ABPA results from a hypersensitivity to a specific allergen, omalizumab might benefit CF patients with ABPA. Therefore, we conducted a retrospective study to investigate the effects of omalizumab on ABPA in CF patients. Methods We retrospectively analyzed the clinical records of young patients with CF treated with omalizumab for an ABPA in several French CF centers. The clinical data were collected 3 months before the start of omalizumab treatment, at initiation, and every 3 months up to 12 following initiation. These data comprised clinical, biological, nutritional, and functional parameters. Results Eighteen patients were included (mean age: 17.1 ± 5.2 yrs). Under omalizumab was observed a stabilization of the lung function decline associated with a significant decrease in the corticosteroid daily dose (p = 0.0007) and an improvement in the nutritional status (p = 0.01). No serious side effect of omalizumab was reported. Conclusions This study suggests that omalizumab might be an interesting therapeutic strategy in ABPA, associated with less side effects compared to long-term corticosteroids. Further randomized-controlled trials are needed to ascertain the efficacy of omalizumab in CF patients with ABPA.

Pasteurella multocida is a commensal of the upper respiratory tract of various animals. The spectrum of human diseases caused by P. multocida varies from soft-tissue infections fol- lowing bites and scratches to systemic infections, including res- piratory tract infections resulting from airborne contamination and/or chronic carriage. Antimicrobial resistance of Pasteurella strains originating from animals has been reported for many years. Human P. multocida isolates are usually susceptible to penicillins. We report a case in which a strain of b-lacta- mase-producing P. multocida was isolated from a lung abscess specimen and review related cases. A 75-year-old woman with chronic bronchitis was hospital- ized with fever (temperature, 407C), weight loss, increased pro- ductive cough, and dyspnea. A chest x-ray was unremarkable, whereas the WBC count was 13,900/mm 3 (89% neutrophils) and the one-hour erythrocyte sedimentation rate was 63 mm/h. The patient was treated for 8 days with intravenous amoxicillin (1.5 g/d). Because of persistent signs of infection, a new chest ra- diograph was obtained, which showed a left lung abscess; the abscess was confirmed by CT. Culture of specimens obtained by bronchoalveolar lavage yielded P. multocida subspecies mul- tocida (10 5 cfu/mL) and Haemophilus parainfluenzae (10 3 cfu/ mL). Production of b-lactamase by both isolates was detected by a chromogenic test using nitrocefin-impregnated disk and the synergic effect between clavulanate and amoxicillin by disk dif- fusion testing. Minimum inhibitory concentrations of amoxi- cillin and amoxicillin/clavulanate for the P. multocida strain were of 8 and 0.25 mg/mL, respectively. Consequently, amoxi- cillin was changed to intravenous amoxicillin/clavulanic acid (3 g/d). A favorable outcome was achieved, and the patient was discharged from the hospital; medication at the time of dis- charge was oral amoxicillin/clavulanic acid for 2 months. Our patient had no known exposure to animals other than her cat. Two different strains of P. multocida (subspecies multocida and septica) were isolated from the cat's saliva, but none of them was found to produce b-lactamase. A MEDLINE search of the literature revealed only 4 well- documented cases of human infections due to penicillin-resis- tant P. multocida (1-4). All 4 cases were respiratory tract in- fections. The principal features of these cases along with our case are presented in table 1. The respiratory tract is the most common site of pasteurella infections after soft tissues (5). Pre- vious studies have shown that impaired pulmonary defenses

Hydrogen as an energy carrier becomes more important in a future sustainable energy economy. One regenerative hydrogen production path is photobiological production by green algae “Chlamydomonas reinhardtii”. This organism is proven to produce small amounts of hydrogen under certain conditions only using sunlight and water [1] . To get into competition to other production technologies a new organism, called “Design Cell”, should overcome the handicaps of green algae leading to an improved organism.For cultivation of the microorganisms a photobioreactor system was developed in a laboratory scale. To collect first technical data a system analysis based on the methods of life cycle assessment was conducted to classify the current status of photobiological hydrogen, to identify potentials and to uncover weaknesses. The results were compared with other ways of hydrogen production. To develop the process to large scale applications, hydrogen production rates under sunlight illumination are estimated and a large scale reactor was designed.The assessment showed that the actual hydrogen production rates have to be increased at least by a factor of 100 to get into competition to other technologies. Scale up and sunlight illumination tests showed a lot of optimization potential, but also system limitations for large scale applications.