Using chest computed tomography and unsupervised machine learning for predicting and evaluating response to lumacaftor-ivacaftor in people with cystic fibrosis.

Objectives: Lumacaftor-ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator known to improve clinical status in people with cystic fibrosis (CF). The aim of this study was to assess lung structural changes after 1 year of lumacaftor-ivacaftor treatment and to use unsupervised machine learning to identify morphological phenotypes of lung disease that are associated with response to lumacaftor-ivacaftor.

Methods: Adolescents and adults with CF from a French multicentre real-world prospective observational study evaluating the first year of treatment with lumacaftor-ivacaftor were included if they had pre-therapeutic and follow-up chest computed tomography (CT) scans available.

Nebulised liposomal amphotericin-B as maintenance therapy in allergic bronchopulmonary aspergillosis: a randomised, multicentre trial.

Background: In allergic bronchopulmonary aspergillosis (ABPA), prolonged nebulised antifungal treatment may be a strategy for maintaining remission.

Methods: We performed a randomised, single-blind, clinical trial in 30 centres. Patients with controlled ABPA after 4-month attack treatment (corticosteroids and itraconazole) were randomly assigned to nebulised liposomal amphotericin-B or placebo for 6 months.

Etiological Work-Up for Adults with Bronchiectasis: A Predictive Diagnostic Score for Primary Ciliary Dyskinesia and Cystic Fibrosis.

Background: etiological investigations are not done for all adult patients with bronchiectasis because of the availability and interpretation of tests. The aim of the study was to elaborate a score to identify patients at high risk of having cystic fibrosis or primary ciliary dyskinesia (CF/PCD), which require appropriate management.

Methods: diagnostic work-ups were carried out on a French monocenter cohort, and results were subjected to logistic-regression analyses to identify the independent factors associated with CF/PCD diagnosis and, thereby, elaborate a score to validate in a second cohort.

Follow-Up and Management of Chronic Rhinosinusitis in Adults with Primary Ciliary Dyskinesia: Review and Experience of Our Reference Centers.

Chronic rhinosinusitis is the foremost manifestation in adult patients with primary ciliary dyskinesia (PCD). We present a retrospective series of 41 adult patients with a confirmed diagnosis of PCD followed in our reference centers. As part of the diagnostic work up in our centers, sinus computed tomography scans (CTs) are systematically performed.

Critical Evaluation of Sinonasal Disease in 64 Adults with Primary Ciliary Dyskinesia.

To date, no study precisely described ear, nose and throat (ENT) disease in adults with primary ciliary dyskinesia (PCD) and its relationship with ciliary function/ultrastructure. A retrospective study of standardized ENT data (exam, audiogram, sinus Computed tomography (CT), and bacteriology) was conducted in 64 adults with confirmed PCD who were followed in two ENT reference centers. Rhinorrhoea and hearing loss were the main symptoms.

Computed Tomography Description of the Uncinate Process Angulation in Patients With Cystic Fibrosis and Comparison With Primary Ciliary Dyskinesia, Nasal Polyposis, and Controls.

Background:: There is a medial bulging of the lateral nasal wall in patients with cystic fibrosis (CF).

Aims:: Uncinate process (UP) angulation measurements in patients and controls to objectify this bulging.

Materials And Methods:: Thirty CF, 17 primary ciliary dyskinesia (PCD), 13 chronic rhinosinusitis with polyps (CRSwp), and 30 controls were included.

Automated computed tomographic scoring of lung disease in adults with primary ciliary dyskinesia.

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.

Omalizumab treatment for allergic bronchopulmonary aspergillosis in young patients with cystic fibrosis.

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.

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, FEV and body mass index (BMI) one month and three months after lumacaftor/ivacaftor initiation in adults with CF and FEV below 40% predicted.

Results: Respiratory adverse events (AEs) were reported by 27 of 53 subjects (51%) and 16 (30%) discontinued treatment.

Changes of CFTR functional measurements and clinical improvements in cystic fibrosis patients with non p.Gly551Asp gating mutations treated with ivacaftor.

Ivacaftor, a CFTR potentiator, has been found to improve CFTR function and clinical outcomes in patients with cystic fibrosis (CF) gating mutations. We investigated the effects of ivacaftor on CFTR functional measurement in CF patients carrying gating mutations other than p.Gly551Asp.

Clinical characteristics, functional respiratory decline and follow-up in adult patients with primary ciliary dyskinesia.

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.

Lessons from a French collaborative case-control study in cystic fibrosis patients during the 2009 A/H1N1 influenza pandemy.

Background: Viral infections such as influenza are thought to impact respiratory parameters and to promote infection with Pseudomonas aeruginosa in patients with cystic fibrosis (CF). However, the real morbidity of the influenza virus in CF needs to be further investigated because previous studies were only observational.

Methods: CF patients were included in a case-control study (n = 44 cases and n = 371 controls) during the 2009 pandemic A/H1N1 influenza.

Loss-of-function mutations in RSPH1 cause primary ciliary dyskinesia with central-complex and radial-spoke defects.

Primary ciliary dyskinesia (PCD) is a rare autosomal-recessive respiratory disorder resulting from defects of motile cilia. Various axonemal ultrastructural phenotypes have been observed, including one with so-called central-complex (CC) defects, whose molecular basis remains unexplained in most cases. To identify genes involved in this phenotype, whose diagnosis can be particularly difficult to establish, we combined homozygosity mapping and whole-exome sequencing in a consanguineous individual with CC defects.

Quantitative analysis of ciliary beating in primary ciliary dyskinesia: a pilot study.

Background: Primary ciliary dyskinesia (PCD) is a rare congenital respiratory disorder characterized by abnormal ciliary motility leading to chronic airway infections. Qualitative evaluation of ciliary beat pattern based on digital high-speed videomicroscopy analysis has been proposed in the diagnosis process of PCD. Although this evaluation is easy in typical cases, it becomes difficult when ciliary beating is partially maintained.

Determinants of refusal of A/H1N1 pandemic vaccination in a high risk population: a qualitative approach.

Background: Our study analyses the main determinants of refusal or acceptance of the 2009 A/H1N1 vaccine in patients with cystic fibrosis, a high-risk population for severe flu infection, usually very compliant for seasonal flu vaccine.

Methodology/principal Findings: We conducted a qualitative study based on semi-structured interviews in 3 cystic fibrosis referral centres in Paris, France. The study included 42 patients with cystic fibrosis: 24 who refused the vaccine and 18 who were vaccinated.

A recurrent deep-intronic splicing CF mutation emphasizes the importance of mRNA studies in clinical practice.

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.

Cystic fibrosis transmembrane conductance regulator channel dysfunction in non-cystic fibrosis bronchiectasis.

Rationale: Although in patients with diffuse bronchiectasis (DB) and a normal sweat test the presence of one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene is frequently observed, its pathogenic role in the development of DB remains unclear.

Objectives: To evaluate the association between CFTR heterozygosity and CFTR protein dysfunction in the airways of patients with DB.

Methods: Nasal potential difference was measured in 122 patients with DB of unknown origin and with a normal sweat test (Cl(-) < 60 mmol/L).

Mutations in the amiloride-sensitive epithelial sodium channel in patients with cystic fibrosis-like disease.

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.

Tuberculous aneurysms of the abdominal aorta.

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.

Health and economic consequences of an outbreak of pertussis among healthcare workers in a hospital in France.

Background: Bordetella pertussis is highly contagious, and because immunity wanes after vaccination, it continues to be a cause of cough among adults.

Objective: To describe the healthcare services used and productivity losses accrued by healthcare workers (HCWs) missing work due to pertussis.

Methods: After 3 pertussis cases were confirmed among HCWs, all hospital employees and patients with a cough were screened between November 2000 and March 2001.

Ultrastructural analysis of the interactions between Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica and human tracheal epithelial cells.

Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica are respiratory pathogens that colonize the respiratory tract of their host after adhesion to the respiratory epithelium. Presently, the intracellular fate of these bacteria in human tracheal epithelial cells was compared by use of transmission electron microscopy. The three species, even when cytotoxic, were taken-up by epithelial cells.

Nosocomial pertussis outbreak among adult patients and healthcare workers.

We describe a pertussis outbreak among adult patients in a French general hospital following transmission from a healthcare worker. This index case transmitted pertussis to other healthcare workers, who, in turn, contaminated other staff and two immunosuppressed patients. This raises questions about infection control.

Bordetella pertussis adenylate cyclase-hemolysin induces interleukin-6 secretion by human tracheal epithelial cells.

After interaction with tracheal epithelial cells, Bordetella pertussis induces the secretion of interleukin-6. This secretion is dependent on the expression of adenylate cyclase-hemolysin by the bacterium but not on the expression of other characterized bacterial toxins or adhesins. This finding confirms the important role of adenylate cyclase-hemolysin in the pathogenicity of the bacterium.