Boubou Camara

Real-life initiation of lumacaftor/ivacaftor combination in adults with cystic fibrosis homozygous for the Phe508del CFTR mutation and severe lung disease

OBJECTIVE To investigate the short-term adverse events and effectiveness of lumacaftor/ivacaftor combination treatment in adults with cystic fibrosis (CF) and severe lung disease in a real life setting. METHODS A multicentre observational study investigated adverse events, treatment discontinuation, FEV1 and body mass index (BMI) one month and three months after lumacaftor/ivacaftor initiation in adults with CF and FEV1 below 40% predicted. RESULTS Respiratory adverse events (AEs) were reported by 27 of 53 subjects (51%) and 16 (30%) discontinued treatment. The mean absolute change in FEV1 was +2.06% after one month of treatment (P=0.086) and +3.19% after 3 months (P=0.009). BMI was unchanged. CONCLUSIONS Treatment with lumacaftor/ivacaftor in patients with CF and severe lung disease was discontinued more frequently than reported in clinical trials, due to respiratory AEs. Nevertheless, the patients who continued treatment had an increase in lung function comparable to what was observed in pivotal trials.

Skeletal muscle contractility and fatigability in adults with cystic fibrosis

BACKGROUND Recent discovery of cystic fibrosis transmembrane conductance regulator expression in human skeletal muscle suggests that CF patients may have intrinsic skeletal muscle abnormalities potentially leading to functional impairments. The aim of the present study was to determine whether CF patients with mild to moderate lung disease have altered skeletal muscle contractility and greater muscle fatigability compared to healthy controls. METHODS Thirty adults (15 CF and 15 controls) performed a quadriceps neuromuscular evaluation using single and paired femoral nerve magnetic stimulations. Electromyographic and mechanical parameters during voluntary and magnetically-evoked contractions were recorded at rest, during and after a fatiguing isometric task. Quadriceps cross-sectional area was determined by magnetic resonance imaging. RESULTS Some indexes of muscle contractility tended to be reduced at rest in CF compared to controls (e.g., mechanical response to doublets stimulation at 100 Hz: 74±30 Nm vs. 97±28 Nm, P=0.06) but all tendencies disappeared when expressed relative to quadriceps cross-sectional area (P>0.5 for all parameters). CF and controls had similar alterations in muscle contractility with fatigue, similar endurance and post exercise recovery. CONCLUSIONS We found similar skeletal muscle endurance and fatigability in CF adults and controls and only trends for reduced muscle strength in CF which disappeared when normalized to muscle cross-sectional area. These results indicate small quantitative (reduced muscle mass) rather than qualitative (intrinsic skeletal muscle abnormalities) muscle alterations in CF with mild to moderate lung disease.

Direct Molecular Diagnosis of Aspergillosis and CYP51A Profiling from Respiratory Samples of French Patients

Background: Microbiological diagnosis of aspergillosis and triazole resistance is limited by poor culture yield. To better estimate this shortcoming, we compared culture and molecular detection of A. fumigatus in respiratory samples from French patients at risk for aspergillosis. Methods: A total of 97 respiratory samples including bronchoalveolar lavages (BAL), bronchial aspirates (BA), tracheal aspirates, sputa, pleural fluids, and lung biopsy were collected from 33 patients having invasive aspergillosis (n = 12), chronic pulmonary aspergillosis (n = 3), allergic bronchopulmonary aspergillosis (n = 7), or colonization (n = 11) and 28 controls. Each specimen was evaluated by culture, pan-Aspergillus qPCR, and CYP51A PCR and sequencing. Results: One A. flavus and 19 A. fumigatus with one multiazole resistant strain (5.3%) were cultured from 20 samples. Culture positivity was 62.5, 75, 42.9, and 15.8% in ABPA, CPA, IA, and colonized patients, respectively. Aspergillus detection rate was significantly higher by pan-Aspergillus qPCR than by culture in IA (90.5 vs. 42.9%; P < 0.05) and colonization group (73.7 vs. 15.8%; P < 0.05). The CYP51A PCR found one TR34/L98H along with 5 novel cyp51A mutations (4 non-synonymous and 1 promoter mutations), yet no association can be established currently between these novel mutations and azole resistance. The analysis of 11 matched pairs of BA and BAL samples found that 9/11 BA carried greater fungal load than BAL and CYP51A detection was more sensitive in BA than in BAL. Conclusion: Direct molecular detection of Aspergillus spp. and azole resistance markers are useful adjunct tools for comprehensive aspergillosis diagnosis. The observed superior diagnostic value of BAs to BAL fluids warrants more in-depth study.

Balloon pulmonary angioplasty in a patient with chronic thromboembolic pulmonary hypertension.

To the Editor: We report the first French case of percutaneous balloon pulmonary angioplasty (BPA) in a 78-year-old patient with chronic thromboembolic pulmonary hypertension (CTEPH). The patient had a history of acute pulmonary embolism in 2004 with recurrence in 2011. At the end of 2012, he complained of persistent dyspnoea and CTEPH was diagnosed on lung radionuclide perfusion scan, contrast chest computed tomography and right heart catheterisation. At the first evaluation, he was in New York Heart Association (NYHA) functional class III and his 6-min walk distance (6MWD) was 470 m. Mean pulmonary artery pressure (mPAP) was 45 mmHg, cardiac index 1.8 L·min−1·m−2 and pulmonary vascular resistance (PVR) 8 Wood units. He had used warfarin for 2 years, and combination therapy with bosentan and tadalafil was started (1 year before angioplasty) [1, 2]. Conventional pulmonary angiography showed that the main lesions were located in segmental pulmonary arteries of the lower lobes (fig. 1c). Webs, splits and occlusion were identified in A6, A8, A9 and A10 pulmonary arterial branches on the right lung, and A8, A9 and A10 …

Absence of calf muscle metabolism alterations in active cystic fibrosis adults with mild to moderate lung disease

BACKGROUND Specific alterations in skeletal muscle related to genetic defects may be present in adults with cystic fibrosis (CF). Limb muscle dysfunction may contribute to physical impairment in CF. AIMS AND OBJECTIVES We hypothesized that adults with CF would have altered calf muscle metabolism during exercise. METHODS Fifteen adults with CF and fifteen healthy controls matched for age, gender and physical activity performed a maximal cycling test and an evaluation of calf muscle energetics by 31P magnetic resonance spectroscopy before, during and after plantar flexions to exhaustion. RESULTS Maximal cycling test revealed lower exercise capacities in CF (VO2peak 2.44±0.11 vs. 3.44±0.23L·Min-1, P=0.03). At rest, calf muscle phosphorus metabolites and pHi were similar in CF and controls (P>0.05). Maximal power output during plantar flexions was significantly lower in CF compared to controls (7.8±1.2 vs. 6.6±2.4W; P=0.013). At exhaustion, PCr concentration was similarly reduced in both groups (CF -33±7%, controls -34±6%, P=0.44), while PCr degradation at identical absolute workload was greater in CF patients (P=0.04). These differences disappeared when power output was normalized for differences in calf size (maximal power output: 0.10±0.02 vs. 0.10±0.03W/cm2; P=0.87). Pi/PCr ratio and pHi during exercise as well as PCr recovery after exercise were similar between groups. CONCLUSION Similar metabolic calf muscle responses during exercise and recovery were found in CF adults and controls. Overall, muscle anabolism rather than specific metabolic dysfunction may be critical regarding muscle function in CF.

Phenotyping chronic pulmonary aspergillosis by cluster analysis.

Chronic pulmonary aspergillosis (CPA) is a complex disorder involving various underlying conditions and risk factors, clinical and radiological features, and natural histories or responses to treatment [1]. Untreated, patients with CPA have ≥50% 5-year mortality [2, 3]. Recently, it was proposed that CPA includes simple aspergilloma, chronic cavitary pulmonary aspergillosis (CCPA) and chronic necrotising pulmonary aspergillosis (CNPA) [1]. Cluster analysis based on clinical and radiological settings does not distinguish any specific phenotype of CPA http://ow.ly/QZq7V

Grouped Cases of Pulmonary Pneumocystosis After Solid Organ Transplantation: Advantages of Coordination by an Infectious Diseases Unit for Overall Management and Epidemiological Monitoring.

OBJECTIVE To determine the origin of grouped cases of Pneumocystis pneumonia in solid-organ transplant recipients at our institution. DESIGN A case series with clinical examinations, genotyping, and an epidemiological survey. SETTING A university hospital in France. PATIENTS We report 12 solid-organ transplant recipients with successive cases of Pneumocystis pneumonia that occurred over 3 years; 10 of these cases occurred in a single year. METHODS We used molecular typing of P. jirovecii strains by multilocus sequence typing and clinical epidemiological survey to determine potential dates and places of transmission. RESULTS Between May 2014 and March 2015, 10 solid-organ transplant recipients (5 kidney transplants, 4 heart transplants, and 1 lung transplant) presented with Pneumocystis pneumonia. Molecular genotyping revealed the same P. jirovecii strain in at least 6 patients. This Pneumocystis strain was not identified in control patients (ie, nontransplant patients presenting with pulmonary pneumocystosis) during this period. The epidemiological survey guided by sequencing results provided information on the probable or possible dates and places of contamination for 5 of these patients. The mobile infectious diseases unit played a coordination role in the clinical management (adaptation of the local guidelines) and epidemiological survey. CONCLUSION Our cardiac and kidney transplant units experienced grouped cases of pulmonary pneumocystosis. Genotyping and epidemiological surveying results suggested interhuman contamination, which was quickly eliminated thanks to multidisciplinary coordination. Infect Control Hosp Epidemiol 2017;38:179-185.

Comment j’explore une hypertension pulmonaire ?

Les hypertensions pulmonaires sont definies hemodynamiquement par une pression arterielle pulmonaire moyenne ≥ 25 mmHg au repos (tableau 1) [1]. On distingue cinq grands cadres nosologiques a visee clinique et therapeutique, mis a jour lors du cinquieme congres mondial sur l’hypertension pulmonaire a Nice en 2013 (tableau 2) [2]. Le groupe 1 correspond aux HTAP, maladies rares dont la prevalence est estimee entre 15 et 50 par million d’habitants [3], de pronostic redoutable mais [...]