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International audience; Introduction: Primary ciliary dyskinesia (PCD) is a genetic disease characterised by abnormalities in ciliary function, responsible for chronic pulmonary and sinonasal diseases. Adult clinical features and outcome are poorly described.Objectives: To assess the clinical characteristics and disease progression in adults with PCD.Methods: Bicentric retrospective study, focusing on adults (≥18 years) with an asserted diagnosis of PCD based on the presence of bronchiectasis with typical ultrastructural defect of cilia and/or situs inversus (SI). Clinical symptoms, respiratory function, extent of bronchiectasis, microbiology and molecular analysis were assessed. Results are expressed as median (25th; 75th centile).Results: 78 patients were included with a median follow-up of 8.1 years. 91% of patients had respiratory symptoms and 95% had chronic rhinosinusitis. Half of ultrastructural defects concerned dynein arms. Respiratory function was significantly lower in women (FEV1=60% predicted (50; 76), vs 77% (62; 95), p=0.009) and in patients with chronic airway Pseudomonas aeruginosa (PA, n=21) infection (FEV1=60% (48; 71) vs 75% (55; 89), p=0.04). FEV1 was associated with gender (regression coefficient for men =13.8, p=0.009), chest CT score (r=-0.42, p

Background The present study aimed to develop an automated computed tomography (CT) score based on the CT quantification of high-attenuating lung structures, in order to provide a quantitative assessment of lung structural abnormalities in patients with Primary Ciliary Dyskinesia (PCD). Methods Adult (≥18 years) PCD patients who underwent both chest CT and spirometry within a 6-month period were retrospectively included. Commercially available lung segmentation software was used to isolate the lungs from the mediastinum and chest wall and obtain histograms of lung density. CT-density scores were calculated using fixed and adapted thresholds based on various combinations of histogram characteristics, such as mean lung density (MLD), skewness, and standard deviation (SD). Additionally, visual scoring using the Bhalla score was performed by 2 independent radiologists. Correlations between CT scores, forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were evaluated. Results Sixty-two adult patients with PCD were included. Of all histogram characteristics, those showing good positive or negative correlations to both FEV1 and FVC were SD (R = − 0.63 and − 0.67; p

Objectives: Several studies, especially in Europe, have recently reported the emerging phenomenon of azole resistance in Aspergillus fumigatus, but very few data are available in France. Our study aimed to determine the resistance prevalence in A. fumigatus isolates recovered from clinical samples over a 1-year period in two university hospital centers. Methods :A llA. fumigatus isolates were screened for azole resistance using RPMI agar plates supplemented with itraconazole and voriconazole. Resistance was then confirmed by the EUCAST method. A part of the beta-tubulin gene was amplified for resistant isolates to confirm the A. fumigatus species, and the Cyp51A gene and its promoter were afterward sequenced to detect mutations potentially responsible for this resistance. Results: One hundred sixty-five A. fumigatus isolates were recovered from 134 patients. Three isolates recovered from three patients were found resistant with MICs of >8 mg/l, 4 mg/l, and 1 mg/l for itraconazole, voriconazole, and posaconazole, respectively. The TR34/L98H mutation, previously and largely described in other countries, was detected in the three isolates. Conclusion: Our study demonstrated the occurrence of azole resistance among unselected A. fumigatus clinical isolates, with an overall prevalence of 1.8%.

Infertility, observed in 75% of male and 61% of female PCD patients, is dependent on ultrastructural and gene defects http://ow.ly/P4K030fPnPp

Resume Les etiologies des syndromes cavitaires pulmonaires sont multiples, notamment neoplasiques, infectieuses ou inflammatoires. Une etiologie particuliere est celle d’infarctus pulmonaires multiples secondaires a des embolies pulmonaires. Ce diagnostic peut etre suspecte devant la localisation sous-pleurale des lesions et l’association avec un thrombus arteriel pulmonaire. Nous rapportons le cas d’une patiente atteinte d’une hypertension pulmonaire post-embolique (HTP PE) chronique associee a une thrombophilie familiale revelee par des infarctus pulmonaires excaves. L’HTP PE chronique est parfois diagnostiquee lors d’une recidive embolique sur des lesions anciennes passees inapercues. Parmi les conditions medicales associees au developpement d’une HTP PE, figurent certaines thrombophilies telles que l’elevation isolee du facteur VIII.

Mycobacterium chelonae (M. chelonae) is rarely responsible for respiratory infection. This report concerns the case of an 81-year-old man with previously asymptomatic bronchiectasis, colonised by M. chelonae for 3 years. He was hospitalised for acute dyspnoea and fever due to a right hydro-pneumothorax with cavitated alveolar opacities of the right lung. Pleural fluid and bronchial aspiration were positive for M. chelonae and no other microorganisms were detected. The effusion was drained and the patient treated with clarythromycin and amikacin. The radiological abnormalities improved but the patient's general condition remained poor. Treatment was continued for 11 months. Because of the absence of any other bacteria, clinical deterioration following broad-spectrum antibiotics and stabilisation of the lesions after anti-mycobacterial treatment, our diagnosis was severe M. chelonae pleuro-pneumonia in an immunocompetent patient.

We investigated whether mutations in the genes that code for the different subunits of the amiloride-sensitive epithelial sodium channel (ENaC) might result in cystic fibrosis (CF)-like disease. In a small fraction of the patients, the disease could be potentially explained by an ENaC mutation by a Mendelian mechanism, such as p.V114I and p.F61L in SCNN1A. More importantly, a more than three-fold significant increase in incidence of several rare ENaC polymorphisms was found in the patient group (30% vs. 9% in controls), indicating an involvement of ENaC in some patients by a polygenetic mechanism. Specifically, a significantly higher number of patients carried c.-55+5G>C or p.W493R in SCNN1A in the heterozygous state, with odds ratios (ORs) of 13.5 and 2.7, respectively.The p.W493R-SCNN1A polymorphism was even found to result in a four-fold more active ENaC channel when heterologously expressed in Xenopus laevis oocytes. About 1 in 975 individuals in the general population will be heterozygous for the hyperactive p.W493R-SCNN1A mutation and a cystic fibrosis transmembrane conductance regulator (CFTR) gene that results in very low amounts (0-10%) functional CFTR. These ENaC/CFTR genotypes may play a hitherto unrecognized role in lung diseases.

PURPOSE The clinical indications and economic consequences of human granulocyte colony-stimulating factor (G-CSF) prescription during small-cell lung cancer (SCLC) chemotherapy remain controversial. The aim of this study, based on a Markov model, was to assess the impact of routine G-CSF use in the treatment of SCLC on costs and patient comfort. Markov models allow the modeling SCLC chemotherapy, in which the risk of febrile neutropenia (FN) is continuous over time and may occur more than once. PATIENTS AND METHODS We used a Markov model to compare three strategies: a chemotherapy dose reduction after FN and nonuse of G-CSF ("never" strategy), secondary use of G-CSF ("CSF if FN" strategy) and primary use of G-CSF ("systematic CSF" strategy). Model baseline probabilities were based on a review of medical records for all patients (n = 39) treated for SCLC in our unit during 1993 (when G-CSF was not used) and on published reductions in the incidence of FN obtained by using G-CSF. Two different types of rewards were used: a cost-utility scale that took into account the costs of FN (CFN) episodes and G-CSF (CCSF) courses; and a comfort-utility scale that took into account the discomfort of FN and G-CSF therapy. Costs were analyzed from the health care payer's perspective and utilities were assessed prospectively in standardized interviews with treated SCLC patients. RESULTS The never strategy was the least costly ($4,875 [United States] versus $5,816 and $7,690 for CSF if FN and systematic CSF) and gave the highest comfort value (378 U v 365 and 327 for CSF if FN and systematic CSF). Sensitivity analyses showed that the never strategy remains the less costly when the probability of a first FN episode was less than 49%, the probability of FN recurrence was less than 60%, or the CFN was less than $6,077, or the CCSF was greater than $863. In terms of patient comfort, the never strategy was the best choice, except for patients who considered that a course of G-CSF caused little or no discomfort, whether or not it prevented FN. CONCLUSION Routine use of G-CSF during SCLC chemotherapy is not justified by clinical benefits, improved patient comfort, or economic considerations.

Resume Des etudes recentes ont montre que la prevalence de la coqueluche serait de l'ordre de 10 a 20 % chez les patients adultes souffrant d'une toux chronique d'une duree superieure a huit jours et inferieure a deux mois. Confronte a ce symptome tres banal, le clinicien doit penser a la coqueluche et tenter d'etayer ce diagnostic par cinq elements cles : 1) le caractere paroxystique et astheniant de la toux ; 2) la chronologie particuliere des symptomes, la toux s'aggravant apres une banale phase catarrhale initiale ; 3) la normalite de l'examen physique entre les acces de toux ; 4) l'identification dans l'entourage d'un possible contaminateur ; 5) la normalite de la radiographie thoracique. Une suspicion clinique renforcee doit en effet conduire a demander les examens biologiques susceptibles d'affirmer le diagnostic (PCR chez l'adulte vaccine, serologie par immunoempreinte) et a discuter une antibiotherapie adequate (macrolides).

Background Primary Ciliary Dyskinesia (PCD) is a inherited disorder characterized by abnormal ciliary structure/function, responsible for impaired muco-ciliary transport and infertility. The diagnosis is often delayed for several years though PCD is a rare (~1/20,000) and heterogeneous disease. We elaborated recommendations aiming at improving the quality and efficacy of PCD diagnosis. Methods A multicentric working group, created in 2009 within the French National Centre for Rare Respiratory Diseases, elaborated precise and practical algorithm for PCD diagnosis, based on their experience and the recent literature. It includes adults and paediatric physicians, biologists and technicians involved in PCD, dealing since many years with the difficulties to confirm this diagnosis.

Background Primary Ciliary Dyskinesia (PCD) is a rare inherited disease (~1/20,000), characterized by ciliary structure/function abnormalities, responsible for impaired muco-ciliary transport, leading to recurrent upper and lower airways infections early in life and infertility. The diagnosis is confirmed on ciliate cell samples, collected by nasal and/or bronchial endoscopy. Patients usually need several samples, due to difficulties to get reliable results, especially during respiratory tract infections which are frequent in PCD. We created national guidelines aimed at obtaining the more efficient quality of ciliate cell samples for children and adults.

International audience; BACKGROUND:The identification by CFTR mRNA studies of a new deep-intronic splicing mutation, c.870-1113_1110delGAAT, in one patient of our series with mild CF symptoms and in three CF patients of an Italian study, led us to evaluate the mutation frequency and phenotype/genotype correlations.METHODS:266 patients with CF and related disorders and having at least one undetected mutation, were tested at the gDNA level in three French reference laboratories.RESULTS:In total, the mutation was found in 13 unrelated patients (5% of those already carrying a mutation) plus 4 siblings, including one homozygote and 12 heterozygotes having a severe CF mutation. The sweat test was positive in 10/14 documented cases, the diagnosis was delayed after 20 years in 9/15 and pancreatic insufficiency was present in 5/16.CONCLUSION:c.870-1113_1110delGAAT should be considered as CF-causing with phenotype variability and overall delayed diagnosis. Its frequency highlights the potential of mRNA studies.

Mycotic aneurysm secondary to tuberculous infection of the aorta is a rare and life-threatening disease. We report a single-center experience of three patients treated with a combination of surgical aortic replacement and prolonged antituberculosis therapy. The first case is a 34-year-old woman with a suprarenal abdominal aortic aneurysm, the second case is a 77-year-old man with an infrarenal abdominal aortic aneurysm and a right psoas abscess, the third case is a 37-year-old woman with an infrarenal abdominal aortic aneurysm. All patients had a favorable outcome with a mean follow-up of 6.2 years (range, 6 months-10 years). Early diagnosis and a combination of surgical intervention (aortic reconstruction and extensive excision of the infected field) and prolonged antituberculous drug therapy provide long-term survival without evidence of recurrence after tuberculous aortic involvement.