Search

Background : Some studies suggest that ACOS is associated with worse outcomes than COPD. The goal of this study was to further explore the clinical characteristics and survival of patients with ACOS identified in a real-life cohort of COPD patients. Methods : Data from the French COPD cohort “Initiatives BPCO” (n=998 patients) were analyzed to assess the frequency of ACOS defined as a physician diagnosis of asthma before the age of 40 years and to analyze its impact. Univariate analyses were performed to assess the relationship between ACOS and risk factors (smoking, occupational exposure, atopic diseases), symptoms (chronic bronchitis , dyspnea -modified Medical Research Council scale and baseline dyspnea index-), quality of life, mood disorders, exacerbations, comorbidities, lung function, prescribed treatment, and survival. Results : ACOS was diagnosed in 129 patients (13%). In multivariate analyses, ACOS was associated negatively with cumulative smoking (Odds Ratio –OR-: 0.992; 95%CI 0.984-1.000 per pack-year) and positively with obesity: OR: 1.97 [1.22-3.16], history of atopic disease (hay fever: OR: 5.50 [3.42-9.00] and atopic dermatitis: OR 3.76 [2.14-6.61]), and drug use (LABA+ ICS: 1.86 [1.27-2.74], anti-leukotrienes 4.83 [1.63-14.34], theophylline: 2.46; [1.23-4.91] and oral corticosteroids: [2.99;.1.26-7.08]). No independent association was found with dyspnea, QoL, exacerbations and mortality. Conclusions : Compared to “pure”COPD patients, patients with ACOS exhibit lower cumulative smoking, suffer more from obesity and atopic diseases and use more asthma treatments. Disease severity (dyspnea, QoL, exacerbations, comorbidities) and prognosis (mortality) are not different from “pure” COPD patients.

Allergic bronchopulmonary aspergillosis (ABPA) affects up to 15% of patients with cystic fibrosis (CF). Corticosteroids are used as first-line therapy, but relapse and adverse effects commonly occur. Case reports have suggested the efficacy of the anti-IgE recombinant humanized monoclonal antibody omalizumab. A retrospective multicenter observational French study retrieved 32 CF patients (11 children and 21 adults) who have received omalizumab for more than 3 months in the context of ABPA. Clinical characteristics, concomitant medications (inhaled and oral corticosteroids, antifungal drugs), lung function, body mass index (BMI), and serum IgE were compared at the start and during the first year of omalizumab therapy. Omalizumab-related adverse effects and costs were also evaluated. No significant difference with omalizumab could be demonstrated with regard to lung function, BMI, or the number of patients receiving oral corticosteroids. At the time of initiation of omalizumab, 56% of patients were receiving oral corticosteroids. Five patients were able to discontinue corticosteroids during follow-up and nine patients were able to reduce their daily dose. A total of 78% of the patients had received antifungal therapy at the time of the initiation of omalizumab. Treatment tolerance was good (12.5% of patients experienced side effects). The median cost of omalizumab treatment was €3,620 per patient per month. Omalizumab may represent a steroid-sparing therapy in CF patients with ABPA. A randomized-controlled trial is urgently required to provide higher level of evidence regarding the efficacy and cost-effectiveness of omalizumab in CF patients with ABPA. Pediatr Pulmonol. 2017;52:190-197. © 2016 Wiley Periodicals, Inc.

Background There are a growing number of adults in Europe with a projected increase of 75% over the next decade. There is concern that provision of care will not be sufficient to meet needs. We aimed to establish the level of CF service throughout Europe. Methods An online survey designed by clinicians and patient representatives to explore level of service. Results Training opportunities for clinicians and resources (physical and manpower) to provide care to adults with CF are limited in Europe. Although specific adult CF care has been identified, teams continue to be supported by paediatric colleagues and many adults are still being admitted to paediatric wards. In some centres, service delivery, particularly infection control and access to some CF medication is insufficient and in many places poor personnel resources limits access to comprehensive multidisciplinary teams. Conclusions This survey shows an urgent need for the development of resources for adult CF care, in both physical space and appropriately trained clinicians.

Background Little data exist on causes of death in cystic fibrosis (CF) patients in the era of lung transplantation. Methods Deaths in CF patients in France (2007–2010) were identified using the French CF Registry and causes of deaths were determined based on medical files by a mortality adjudication committee. Results Of 256 deaths, half occurred after lung transplantation and were related to early or late complications of transplantation, whereas half occurred in patients who did not receive lung transplantation and were primarily related to respiratory failure or massive hemoptysis. Among patients who did not receive lung transplantation, only 19% died while waiting on a lung transplantation list. Lack of listing for lung transplantation was primarily related to late, or to lack of transplantation referral, rather than to contraindication to transplantation. Conclusions These data suggest that improvement in transplantation referral strategies may result in transplantation-related survival benefits.

Pulmonary hypertension (PH) may affect survival in cystic fibrosis (CF) and can be assessed on echocardiographic measurement of the pulmonary acceleration time (PAT). The study aimed at evaluating PAT as a tool to optimize timing of lung transplant in CF patients. Prospective multicenter longitudinal study of patients with forced expiratory volume in 1 second (FEV1) ≤60% predicted. Echocardiography, spirometry and nocturnal oximetry were obtained as part of the routine evaluation. We included 67 patients (mean FEV1 42±12% predicted), among whom 8 underwent lung transplantation during the mean follow-up of 19±6 months. No patients died. PAT was determined in all patients and correlated negatively with systolic pulmonary artery pressure (sPAP, r=–0.36, P=0.01). Patients in the lowest PAT tertile (35 mmHg. By multivariate analysis, FEV1and nocturnal desaturation were the main determinants of reduced PAT. A PAT

Eosinophilic pleural effusions have multiple aetiologies. We report on the case of a 40-year-old man who experienced an eosinophilic pleural effusion with blood hypereosinophilia that occurred nine weeks after a treatment with valproic acid was introduced. Usual aetiologies of eosinophilic pleural effusion were excluded. Once valproic acid was discontinued, both pleural effusion and blood eosinophilia decreased rapidly. The persistence of a residual pleural effusion required the introduction of oral corticosteroids, which resulted in the effusion disappearing completely and rapidly. Valproic acid is a rare cause of eosinophilic pleural effusion. The effusion usually regresses when treatment is discontinued but short-term oral corticotherapy may be necessary in order to heal the patient.

Background & Aims Increased life expectancy in patients with cystic fibrosis (CF) allows better knowledge of non-pulmonary complications like liver disease (CFLD). However, few data have been published in large adult cohorts. The aim of this study was to estimate the prevalence and the prognosis of CFLD in adult CF patients. Methods A retrospective analysis of a monocentric cohort of adult CF patients prospectively followed, at least every year, was performed. CFLD was diagnosed using published composite criteria. If cirrhosis was suspected, upper digestive endoscopy was realized to assess the presence of portal hypertension. Results A cohort of 285 adult CF patients was followed during 4.8±3.6years. Among them, 90 had CFLD at the beginning of follow-up and 23 a suspicion of cirrhosis. Factors independently associated with liver disease at baseline were history of meconium ileus, pancreatic insufficiency, chronic colonization with Burkholderia cepacia and the number of IV antibiotic courses per year. Nine patients developed liver decompensation during follow-up, all with a suspicion of cirrhosis at baseline. Six patients underwent liver transplantation alone and three patients combined liver and lung transplantation. Factors independently associated with death or lung transplantation at baseline were liver disease, BMI, forced expiratory volume in 1second and number of IV antibiotic courses per year. Conclusions CFLD was present at baseline in one third of adult patients with CF with a marked risk of liver decompensation during follow-up. Moreover, CFLD at baseline appears as an independent factor associated with death or lung transplantation.

Inflammation plays a central role in the pathophysiology of chronic obstructive pulmonary disease (COPD). Exposure to cigarette smoke induces the recruitment of inflammatory cells in the airways and stimulates innate and adaptive immune mechanisms. Airway inflammation is involved in increased bronchial wall thickness, increased bronchial smooth muscle tone, mucus hypersecretion and loss of parenchymal elastic structures. Oxidative stress impairs tissue integrity, accelerates lung ageing and reduces the efficacy of corticosteroids by decreasing levels of histone deacetylase-2. Protease–antiprotease imbalance impairs tissues and is involved in inflammatory processes. Inflammation is also present in the pulmonary artery wall and at the systemic level in COPD patients, and may be involved in COPD-associated comorbidities.Proximal airways inflammation contributes to symptoms of chronic bronchitis while distal and parenchymal inflammation relates to airflow obstruction, emphysema and hyperinflation. Basal levels of airways and systemic inflammation are increased in frequent exacerbators.Inhaled corticosteroids are much less effective in COPD than in asthma, which relates to the intrinsically poor reversibility of COPD-related airflow obstruction and to molecular mechanisms of resistance relating to oxidative stress. Ongoing research aims at developing new drugs targeting more intimately COPD-specific mechanisms of inflammation, hypersecretion and tissue destruction and repair. Among new anti-inflammatory agents, phosphodiesterase-4 inhibitors have been the first to emerge.

IntroductionPrevious qualitative research analyzing social media and online community discussions highlighted the symptomatic burden of cough and mucus (sputum), alongside shortness of breath, in patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to determine the relative importance of these symptoms and their consequences (for example, disturbed sleep) to COPD patients, compared with conventional COPD endpoints (lung function and exacerbations).MethodsA total of 1,050 patients (at least 40 years of age) with moderate to severe COPD or chronic bronchitis, and regular symptoms of cough and excess mucus production, are to be recruited through patient advocacy groups (PAGs) from five countries (Australia, France, Japan, the United Kingdom, and the United States; 150 to 400 patients per country). A discrete choice experiment was designed with input from clinical experts and the PAGs, plus scientific advice from the National Institute for Health and Care Excellence (NICE) in the United Kingdom. Patients’ preferences for the conditional relative importance of symptoms and impact of COPD will be quantified based on trade-offs they are willing to make among hypothetical COPD disease state profiles, described by differing attributes and levels. Hierarchical Bayesian analysis with effect-coding parameterization will be undertaken on the choice data to estimate (using Gibbs sampling) the relative value each respondent places on an attribute level.ResultsThe feedback from NICE informed the selection of screening criteria and the statistical analysis plan, as well as the inclusion of a health status measure, the EQ-5D-3L. Qualitative patient interviews and pilot testing of the attributes and levels grid have been completed, informing finalization of the online survey design.ConclusionsPatient preference studies evaluating the relative importance of symptom burden through assessment of disease state preference values are an important new form of patient-based evidence for informing value-based decision making in HTA. The present study should facilitate a more patient-centered approach to developing new treatments for and improving the care of patients with COPD.

Whole-exome sequencing reveals activating STAT1 mutations in some patients with autosomal dominant chronic mucocutaneous candidiasis disease., Chronic mucocutaneous candidiasis disease (CMCD) may be caused by autosomal dominant (AD) IL-17F deficiency or autosomal recessive (AR) IL-17RA deficiency. Here, using whole-exome sequencing, we identified heterozygous germline mutations in STAT1 in 47 patients from 20 kindreds with AD CMCD. Previously described heterozygous STAT1 mutant alleles are loss-of-function and cause AD predisposition to mycobacterial disease caused by impaired STAT1-dependent cellular responses to IFN-γ. Other loss-of-function STAT1 alleles cause AR predisposition to intracellular bacterial and viral diseases, caused by impaired STAT1-dependent responses to IFN-α/β, IFN-γ, IFN-λ, and IL-27. In contrast, the 12 AD CMCD-inducing STAT1 mutant alleles described here are gain-of-function and increase STAT1-dependent cellular responses to these cytokines, and to cytokines that predominantly activate STAT3, such as IL-6 and IL-21. All of these mutations affect the coiled-coil domain and impair the nuclear dephosphorylation of activated STAT1, accounting for their gain-of-function and dominance. Stronger cellular responses to the STAT1-dependent IL-17 inhibitors IFN-α/β, IFN-γ, and IL-27, and stronger STAT1 activation in response to the STAT3-dependent IL-17 inducers IL-6 and IL-21, hinder the development of T cells producing IL-17A, IL-17F, and IL-22. Gain-of-function STAT1 alleles therefore cause AD CMCD by impairing IL-17 immunity.

Chronic obstructive pulmonary disease (COPD) pharmacological treatment aims to reduce symptoms, represented mostly by dyspnoea and its impact on daily life, and future risk, i.e. lung function decline, mortality and exacerbations [1]. Inhaled therapies, including long-acting bronchodilators (LABD) and inhaled corticosteroids (ICS), are the main treatments recommended for COPD patients. LABD have been found not only to improve lung function, decrease dyspnoea, increase exercise tolerance and improve health status, but also to reduce the rate of exacerbations. In that respect, some studies suggested that long-acting antimuscarinic agents (LAMA) could be more effective than long-acting β2-agonists (LABA) [2]. In most countries, ICS are indicated only as part of fixed-dose combinations (FDC) with LABA and are used mostly to decrease the risk of exacerbations, which is associated with health status improvement [3]. Therefore, it appeared logical to restrict their use to patients at high risk of exacerbations. The long-term benefit of combining LAMA and FDC (triple therapy) is not strongly documented [4]. Many studies in various countries found discrepancies between guidelines and real-life practice regarding long-term maintenance treatment in patients with COPD [5–7]. Although the impact of nonadherence to guidelines on efficacy outcomes is controversial [8], it increases healthcare costs [9] and, New agents for COPD treatment appear to increase overall treatment intensity in all severity categories [http://ow.ly/BS6Wq][1] [1]: http://ow.ly/C95Ue

To the Editors: Chronic obstructive pulmonary disease (COPD) is characterised by progressive and poorly reversible airflow obstruction due to small airway disease and emphysema. Cigarette smoking is the major cause of COPD, but the disease also occurs in nonsmokers. In nonsmokers, environmental factors ( e.g. second-hand smoking and inhalation of toxic gas), genetic factors ( e.g. the rare α1-antitrypsin deficiency) and infectious factors ( e.g. HIV infection) have been implicated in the pathogenesis of the disease. We report on two cases of COPD with emphysema in nonsmokers with long-standing undiagnosed coeliac disease. A 71-yr-old female was referred to our hospital (Hopital Cochin, Assistance Publique-Hopitaux de Paris, Paris, France) for dyspnoea and cough, which had evolved over 5 yrs. She had suffered from alternating diarrhoea and constipation for many years, ascribed to functional bowel disease. She had never been exposed to inhaled toxics and had never smoked. Examination revealed a body mass index (BMI) of 18 kg·m−2 and a chest computed tomography (CT) image revealed pulmonary distension and emphysema (fig. 1). Spirometry revealed severe airflow limitation (table 1). Serum α1-antitrypsin was normal. Treatment with long-acting bronchodilators was initiated. After 7 yrs of follow-up, the patient complained of progressive weight loss (BMI 15 kg·m−2 …

Hypertonic saline may be effective not only in cystic fibrosis but also in other chronic airway diseases http://ow.ly/dioH30jGXoa

Owing to its major and better recognised burden from both individual and societal perspectives, chronic obstructive pulmonary disease (COPD) is an area of intensive epidemiological, fundamental and clinical research, leading to the publication of more than 10,000 papers each year in the PubMed database. Among these, many report important advances in the understanding of and care for COPD. Epidemiological aspects are the topic of another manuscript in this issue of the European Respiratory Review [1], while the treatment of COPD and its exacerbations will be addressed in other reviews in upcoming issues. Thus, the present paper will focus on more fundamental aspects of pathophysiology, resting and exercise lung mechanics, respiratory muscles and gas exchange, together with more clinical topics, including respiratory symptoms and comorbidities. The purpose of the authors is clearly not to be exhaustive but to focus on points that are likely to have some impact on clinical practice in the relatively short term. Cigarette smoking is the leading cause of COPD in Western countries. Cigarette-associated noxious agents injure the airway epithelium and drive the key processes that lead to specific airway inflammation and structural changes [2]. Once these agents are removed, repair processes should, ideally, bring the airways back to their normal structure and function. In general, an inadequate repair process is thought to play a key role in the development of chronic airflow obstruction in some, but not all, smokers. Indeed, in many subjects most of the inflammatory changes continue despite smoking cessation [3]. This failure of bronchial inflammation to resolve might contribute to systemic changes and ongoing bronchial and lung matrix degradation. In addition to persistent airway inflammation, other major phenomena involved in the disease initiation and progression include increased oxidative stress and protease–antiprotease imbalance. Several studies have established that …

BACKGROUND: Epithelial damage and modifications of cell differentiation are frequent in airway diseases with chronic inflammation, in which transforming growth factor-beta1 (TGF-beta1) plays an important role. The aim of this study was to evaluate the differentiation of human nasal epithelial cells (HNEC) after wound healing and the potential effects of TGF-beta1. METHODS: Basal, mucus, and ciliated cells were characterized by cytokeratin-14, MUC5AC, and betaIV tubulin immunodetection, respectively. Their expression was evaluated in situ in nasal polyps and in an in vitro model of wound healing in primary cultures of HNEC after wound closure, under basal conditions and after TGF-beta1 supplementation. Using RT-PCR, the effects of TGF-beta1 on MUC5AC and DNAI1 genes, specifically transcribed in mucus and ciliated cells, were evaluated. RESULTS: In situ, high TGF-beta1 expression was associated with low MUC5AC and betaIV tubulin expression. In vitro, under basal conditions, MUC5AC expression remained stable, cytokeratin-14 expression was strong and decreased with time, while betaIV tubulin expression increased. Transforming growth factor-beta1 supplementation downregulated MUC5AC and betaIV tubulin expression as well as MUC5AC and DNAI1 transcripts. CONCLUSION: After a wound, differentiation into mucus and ciliated cells was possible and partially inhibited in vitro by TGF-beta1, a cytokine that may be involved in epithelial remodeling observed in chronic airway diseases.

Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by permanent and progressive airway obstruction. Cigarette smoking is the main cause responsible for COPD although only 15 to 25 % of smokers develop COPD. Mechanisms underlying COPD pathogenesis are not fully understood. Structural abnormalities in small airways (bronchioles < 2mm in diameter) are the main determinants of airway obstruction; obstruction of these bronchioles is related to increase in airway wall thickness (associated with peribronchiolar fibrosis) and to plugging by mucus exudates. Alveolar wall destruction (emphysema) also contributes to airway obstruction and to gas exchange abnormalities. Current knowledge related to molecular and cellular mechanisms responsible for these structural modifications are reviewed.

Resume La pleuresie eosinophile est definie par un taux de polynucleaires eosinophiles dans la plevre superieur a 10 %. Elle peut etre observee dans toutes les causes d’epanchement pleural, mais certaines etiologies, de par leur frequence ou leur potentiel de gravite, doivent systematiquement etre recherchees. La presence d’air ou de sang dans la cavite pleurale constitue la premiere cause a evoquer. Une pneumopathie bacterienne, une tuberculose et certaines parasitoses doivent etre recherchees, de meme que certaines prises medicamenteuses. Bien que souvent consideree comme marqueur de benignite, l’eosinophilie pleurale est frequemment associee a des neoplasies ou a des hemopathies. Enfin, la pleuresie eosinophile peut apparaitre dans l’evolution de certaines vascularites, comme le syndrome de Churg et Strauss, et parfois en etre une manifestation revelatrice. Nous rapportons l’observation d’un homme de 27 ans, asthmatique, qui a developpe un epanchement pleural eosinophile revelant un syndrome de Churg et Strauss devant l’association d’un asthme, d’une hypereosinophilie sanguine et sur le lavage bronchioloalveolaire, d’une myopericardite et d’anticorps anticytoplasme des polynucleaires neutrophiles (ANCA) positifs. Cette observation permet de discuter les differentes etiologies a rechercher devant un epanchement pleural eosinophile et illustre le fait qu’une pleuresie eosinophile peut etre une manifestation d’un syndrome de Churg et Strauss.

Background/objectives Currently, factors that promote the occurrence of pancreatitis episodes in patients affected with cystic fibrosis (CF) and pancreatic sufficiency (PS) are largely unknown. Methods Six genes involved in pancreatitis or in ion transport into the pancreatic duct were investigated by next generation sequencing in 59 adult CF-PS patients with two identified CF mutations. Data on predisposing environmental factors were also recorded. Results 19 experienced at least one episode of acute pancreatitis (AP) (AP+) and 40 patients did not (AP−). No influence of environmental factor was evidenced. No specific CFTR genotype was found predictive of pancreatitis. Patients sharing the same CFTR genotype may or may not experience AP episodes. Frequent and rare missense variants were found in 78.9% patients in group AP+ and 67.5% in group AP− but a few of them were pathogenic. Conclusions AP or recurrent AP (RAP) is a frequent complication in our series of adult CF-PS patients. The majority of mild CFTR mutations found in group AP+ were located in the first transmembrane region. No clear other genetic factor could be found predictive of AP/RAP. Further experiments in large homogenous cohorts of CF-PS patients, including whole genome sequencing, may identify genetic predisposing factors to pancreatitis.

Gaëtan Deslee,1 Pierre-Régis Burgel,2 Roger Escamilla,3 Pascal Chanez,4 Isabelle Court-Fortune,5 Pascale Nesme-Meyer,6 Graziella Brinchault-Rabin,7 Thierry Perez,8 Gilles Jebrak,9 Denis Caillaud,10 Jean-Louis Paillasseur,11 Nicolas Roche2On behalf of the Initiatives BPCO Scientific Committee 1Department of Respiratory Diseases, INSERM UMR 903, Maison Blanche Hospital, University Hospital of Reims, Reims, 2Department of Respiratory Diseases, Cochin Hospital, AP-HP and University Paris Descartes, Sorbonne Paris Cité, Paris, 3Department of Respiratory Diseases, Larrey Hospital, Toulouse, 4Department of Respiratory Diseases, APHM, INSERM U1077, CNRS UMR 7733 Aix Marseille Université, Marseille, 5Department of Respiratory Diseases, University Hospital of St Etienne, 6Department of Respiratory Diseases, La Croix Rousse Hospital, Lyon, 7Department of Respiratory Diseases, Pontchaillou Hospital, University Hospital of Rennes, Rennes, 8Department of Respiratory Diseases, Calmette Hospital, University Hospital of Lille, Lille, 9Department of Respiratory Diseases, Bichat Hospital, AP-HP, Paris, 10Department of Respiratory Diseases, Gabriel Montpied Hospital, University Hospital of Clermont-Ferrand, Clermont-Ferrand, 11EFFI-STAT, Paris,FranceBackground: Cough and sputum production are frequent in chronic obstructive pulmonary disease (COPD). The objective of this study was to examine the relationship between cough and sputum production and health-related quality of life in COPD.Methods: A cross-sectional study was conducted in the French Initiatives COPD cohort and assessed cough and sputum production within the past 7 days using the cough and sputum assessment questionnaire (CASA-Q), health-related quality of life, spirometry, smoking status, dyspnea, exacerbations, anxiety and depression, and comorbidities.Results: One hundred and seventy-eight stable COPD patients were included (age, 62 [56–69]years, 128 male, forced expiratory volume in 1 second [FEV1]: 57 [37–72] % predicted) (median [Q1–Q3]). In univariate analyses, health-related quality of life (Saint George’s respiratory questionnaire total score) was associated with each CASA-Q domain and with chronic bronchitis, exacerbations, dyspnea, FEV1, depression, and anxiety. All four domains introduced separately were independently associated with health-related quality of life. When introduced together in multivariate analyses, only the cough impact domain remained independently associated with health-related quality of life (R2=0.60). With chronic bronchitis (standard definition) instead of the CASA-Q, the R2 was lower (R2=0.54).Conclusion: This study provides evidence that current cough in the previous 7 days is an important determinant of health-related quality of life impairment in stable COPD patients.Keywords: signs and symptoms, respiratory, sputum, questionnaires, dyspnea, multivariate analysis

Rationale: Little knowledge exists on structural changes and plugging in small airways in cystic fibrosis. Objective: To characterise the extent of plugging and contribution of secreted mucins to the plugs. Methods: Small airways in patients with cystic fibrosis at transplantation (n = 18) were compared with control non-smokers (n = 10). Tissue sections were stained with Alcian blue (AB)/periodic acid-Schiff (PAS), for mucins MUC5B and MUC5AC, and for neutrophils and its chemoattractant interleukin (IL) 8. Epidermal growth factor receptor (EGFR) and its ligand pro-transforming growth factor α were also identified using immunohistochemical staining. Epithelial and luminal contents were assessed morphometrically. Results: Plugs occupying >50% of total luminal volume were found in 147 of 231 (63.6%) airways in patients with cystic fibrosis, but only in 1 of 39 (2.6%) airways in controls. In the epithelium of patients with cystic fibrosis, AB/PAS, MUC5B, and MUC5AC-stained volume densities were increased 10-fold (p

The improved survival in people with cystic fibrosis has led to an increasing number of patients reaching adulthood. This trend is likely to be maintained over the next decades, suggesting a need to increase the number of centres with expertise in the management of adult patients with cystic fibrosis. These centres should be capable of delivering multidisciplinary care addressing the complexity of the disease, in addition to addressing the psychological burden on patients and their families. Further issues that require attention are organ transplantation and end of life management.Lung disease in adults with cystic fibrosis drives most of the clinical care requirements, and major life-threatening complications, such as respiratory infection, respiratory failure, pneumothorax and haemoptysis, and the management of lung transplantation require expertise from trained respiratory physicians. The taskforce therefore strongly reccommends that medical leadership in multidisciplinary adult teams should be attributed to a respiratory physician adequately trained in cystic fibrosis management.The task force suggests the implementation of a core curriculum for trainees in adult respiratory medicine and the selection and accreditation of training centres that deliver postgraduate training to the standards of the HERMES programme.

Introduction: Primary ciliary dyskinesia (PCD) is a genetic disease characterized by anomalies in ciliary structure/function, responsible for chronic pulmonary and rhinosinus disease. To date, no study involving only adults has been published Aims and objectives: to assess the clinical characteristics and respiratory function in adults with PCD Methods: Retrospective study in two French tertiary hospitals, focusing on adults (≥18 yrs) with a diagnosis of PCD based on presence of bronchiectasis with typical ultrastructural defect of cilia and/or situs inversus (SI). We assessed clinical symptoms, respiratory function, extent of bronchiectasis on CT scans, sputum microbiology and molecular analysis. Results: 78 patients (18-77 yrs) were included. Median follow up was 8.1 yrs. 94.8% of patients had chronic rhinosinusitis. Median nasal NO was 18.9 nL/min (IQR 84.7) and half of ultrastructural defects were dynein arm defects. Respiratory function was significantly lower in women (median FEV1=60% pred, IQR=26 vs. 77.5%, IQR=33, p P. aeruginosa (PA, n=21) infection (median FEV 1 =60.5% vs. 75.5%, p 1 (% pred) correlated with age (r=-0.24, p=0.03), chest CT score (r=-0.46, p 1 decline was -11mL/year (IQR=62.3) and was greater in women (−28.3mL/ yr, IQR=43.4, vs -3.8mL/yr in men, IQR=85.7, p=0.01) although age and PA status were similar. FEV 1 decline was not different between patients with or without chronic PA (−22 mL/yr vs -9 mL/yr, p=0.14). Moreover 3 patients had severe chronic respiratory failure Conclusions: PCD in adults is more severe in women and in patients with chronic PA infection.

Median survival has increased in people with cystic fibrosis (CF) during the past six decades, which has led to an increased number of adults with CF. The future impact of changes in CF demographics has not been evaluated. The aim of this study was to estimate the number of children and adults with CF in 34 European countries by 2025.Data were obtained from the European Cystic Fibrosis Society Patient Registry. Population forecasts were performed for countries that have extensive CF population coverage and at least 4 years of longitudinal data by modelling future entering and exiting flows in registry cohorts. For the other countries, population projections were performed based on assumptions from knowledge of current CF epidemiology.Western European countries’ forecasts indicate that an increase in the overall number of CF patients by 2025, by approximately 50%, corresponds to an increase by 20% and by 75% in children and adults, respectively. In Eastern European countries the projections suggest a predominant increase in the CF child population, although the CF adult population would also increase.It was concluded that a large increase in the adult CF population is expected in the next decade. A significant increase in adult CF services throughout Europe is urgently required.

Objectifs. - Evaluer les criteres d'indications et les modalites du choix pour l'antibiotherapie d'une exacerbation de bronchopneumopathie chronique obstructive (BPCO) en France. Methodes. - Recherche bibliographique sur Medline et sur les references citees dans les articles identifies entre 1995 et 2005. Les etudes randomisees ouvertes ou en aveugle ont ete evaluees selon les criteres de l'Anaes. Resultats. - Environ 50 % des exacerbations de BPCO semblent liees a une infection bacterienne. Haemophilus influenzae, Moraxella catarrhalis et Streptococcus pneumoniae sont les trois principales bacteries responsables d'exacerbations. Chez les patients ayant une alteration importante de la fonction respiratoire, Pseudomonas aeruginosa et les enterobacteries sont frequemment responsables d'exacerbations. L'augmentation de la purulence de l'expectoration est utile pour predire le caractere bacterien d'une exacerbation de BPCO. L'antibiotherapie apporte un benefice d'autant plus important que les patients ont une atteinte respiratoire severe. Les nouvelles molecules antibiotiques ont un spectre d'action souvent plus large et des caracteristiques pharmacologiques optimisees, mais les donnees justifiant de preferer ces molecules aux antibiotiques classiques, restent insuffisantes. Conclusions. - Les futures etudes devront determiner les criteres permettant d'identifier plus precisement les sous-groupes de patients qui beneficient de l'antibiotherapie. L'apport des nouvelles molecules sur de nouveaux criteres de jugement comme la duree sans nouvelle exacerbation devra etre mieux precise.

We retrospectively studied the outcomes of adult patients with cystic fibrosis (CF) hospitalized for severe pulmonary exacerbations (69 cases) between January 1997 and June 2001. Cases were treated either in the Pulmonary Department (n = 46) or in the intensive care unit (ICU) (n = 23) depending on severity. Noninvasive mechanical ventilation was used in 61% (14 of 23) and 33% (15 of 46) of cases treated in the ICU and the Pulmonary Department groups, respectively. Invasive ventilation was necessary in 4 of 23 cases treated in the ICU. The 1-year survival rate was 52% (12 of 23) and 91% (42 of 46) in the ICU and the Pulmonary Department groups, respectively. Lung transplantation was performed in two patients from the ICU group and in five patients from the Pulmonary Department group after hospital discharge. Factors predictive of death were prior colonization with Burkholderia cepacia and rapid decline in FEV1 before admission and severity of exacerbations (severity of hypoxemia and hypercapnia, simplified acute physiology score II and logistic organ dysfunction (LOD) scores, requirement of noninvasive mechanical ventilation, and hospitalization in the ICU) in the univariate analysis and were prior colonization with B. cepacia, the severity of hypoxemia at admission, and hospitalization in the ICU in the multivariate analysis. In 1-year survivors, pulmonary exacerbation did not affect the progression of the disease.

To the Editor: Clinical trials in chronic obstructive pulmonary disease (COPD) patients have shown that the long-term use of inhaled corticosteroids (ICS) in COPD patients reduced the number of exacerbations per patient per year and improved health status [1]. Early studies have suggested increased ICS efficacy in patients with low lung function and frequent exacerbations [2]. The efficacy was reinforced when ICS was used in conjunction with long-acting β2-agonists (LABA) [3]. In most countries, health authorities approved ICS/LABA combinations in COPD patients with severe airflow impairment and frequent exacerbations, as also recommended in the Global Initiative for Obstructive Lung Disease (GOLD) 2007 document [4]. However, several surveys found poor adherence to this proposal among primary care physicians and pulmonologists in “real life”, ICS being often prescribed at a milder stage of the disease. The GOLD 2011 document proposed a new multidimensional system for the assessment and management of patients with COPD [5]. This system classifies COPD patients into four categories (A, B, C and D) based on the level of symptoms (dyspnoea or global clinical impact) and the risk of future exacerbations, as assessed using the severity of airflow limitation and the past history …

The epithelial cells lining the airways serve protective functions. The "barrier function" of the epithelium protects the individual from damage by inhaled irritants. The epithelium produces mucins which become hydrated and form a viscoelastic gel which spreads over the epithelial surface. In healthy individuals inhaled foreign materials become entrapped in the mucus and are cleared by mucociliary transport and by coughing. In many chronic inflammatory airway diseases, however, excessive mucus is produced and is inadequately cleared, leading to mucous obstruction and infection. At present there is no specific treatment for hypersecretion. However, the discovery that an epidermal growth factor receptor (EGFR) cascade is involved in mucin production by a wide variety of stimuli suggests that blockade may provide specific treatment for hypersecretory diseases. EGFR pathways have also been implicated in the repair of damaged airway epithelium. The roles of EGFR in airway epithelial cell hypersecretion and epithelial damage and repair are reviewed and future potential treatments are suggested.

More research to explore the newly proposed MOLT phenotype in COPD is welcome http://ow.ly/zkYR30hH4UP

Chronic obstructive pulmonary disease (COPD) is characterised by incompletely reversible airflow limitation and its severity has been categorised using the level of forced expiratory volume in 1 s (FEV1) [1]. Because marked heterogeneity existed between subjects with comparable FEV1 [2], it has been proposed that identification of subgroups of COPD subjects could represent an alternative to the current FEV1-based classification [3]. A consensus report proposed that COPD phenotypes, as defined by “a single or combination of disease attributes that describes differences between individuals with COPD as they relate to clinically meaningful outcomes (symptoms, exacerbations, response to therapy, rate of disease progression or death)”, could represent the future of COPD [4]. Chronic cough and sputum production (chronic bronchitis) have long been recognised as a consequence of tobacco smoking. In the 1960s, the British hypothesis proposed that chronic cough and sputum production encouraged bronchial infection, which promoted airway and alveolar damage and led to airflow limitation [5]. In their classical study reported in 1976, Fletcher and Peto [6] concluded that while chronic cough and sputum production and airflow limitation both occurred in smokers, they were largely unrelated disease processes. Almost 20 yrs later, Vestbo et al . [7] reported that chronic cough and sputum production were associated with an excess FEV1 decline and increased risk of hospitalisation because of COPD. Data from the Lung Health Study further indicated that chronic cough and sputum production were associated with increased lower respiratory illnesses (exacerbations) in subjects with mild airflow limitation [8]. These two studies shed new light on the potential importance of chronic cough and …

This article is the summary of a workshop, which took place in November 2013, on the roles of microorganisms in chronic respiratory diseases. Until recently, it was assumed that lower airways were sterile in healthy individuals. However, it has long been acknowledged that microorganisms could be identified in distal airway secretions from patients with various respiratory diseases, including cystic fibrosis (CF) and non-CF bronchiectasis, chronic obstructive pulmonary disease, asthma and other chronic airway diseases (e.g.post-transplantation bronchiolitis obliterans). These microorganisms were sometimes considered as infectious agents that triggered host immune responses and contributed to disease onset and/or progression; alternatively, microorganisms were often considered as colonisers, which were considered unlikely to play roles in disease pathophysiology. These concepts were developed at a time when the identification of microorganisms relied on culture-based methods. Importantly, the majority of microorganisms cannot be cultured using conventional methods, and the use of novel culture-independent methods that rely on the identification of microorganism genomes has revealed that healthy distal airways display a complex flora called the airway microbiota. The present article reviews some aspects of current literature on host–microbe (mostly bacteria and viruses) interactions in healthy and diseased airways, with a special focus on distal airways.

Previous work showed that the Th2 cytokine interleukin (IL)-13 induces goblet cell metaplasia via an indirect mechanism involving the expression and subsequent activation of epidermal growth factor receptor (EGFR). Because Clara cell secretory protein (CCSP) expression has been reported in cells that express mucins, we examined the effect of IL-13 on CCSP gene and protein expression in pathogen-free rat airways and in pulmonary mucoepidermoid NCI-H292 cells. Intratracheal instillation of IL-13 induced CCSP mRNA in epithelial cells without cilia within 8–16 h, maximal between 24 and 48 h; CCSP immunostaining increased in a time-dependent fashion, maximal at 48 h. The CCSP immunostaining was localized in nongranulated secretory cells and goblet cells and in the lumen. Pretreatment with the selective EGFR tyrosine kinase inhibitor BIBX1522, cyclophosphamide (an inhibitor of bone marrow leukocyte mobilization), or a blocking antibody to IL-8 prevented CCSP staining. Treatment of NCI-H292 cells with the EGFR ligand transforming growth factor-α, but not with IL-13 alone, induced CCSP gene and protein expression. Selective EGFR tyrosine kinase inhibitors, BIBX1522 and AG1478, prevented CCSP expression in NCI-H292 cells, but the platelet-derived growth factor receptor tyrosine kinase inhibitor AG1295 had no effect. These findings indicate that IL-13 induces CCSP expression via an EGFR- and leukocyte-dependent pathway.

Background Peripherally inserted central catheters (PICCs) are increasingly used in patients with cystic fibrosis (CF) or with non-CF bronchiectasis, but little data exist on catheter-related complications in this setting. Methods Prospective follow-up of consecutive PICCs inserted for intravenous (IV) antibiotics in adults with CF or with non-CF bronchiectasis at Cochin Hospital (Paris, France). Results Between March 2009 and December 2011, 182 PICCs were prescribed in 117 adults (67 CF and 50 non-CF patients). Ultrasound-guided placement of catheter was successful in 174/182 (95.6%) procedures; no insertion complication occurred. The mean ± SD catheter dwell time was 15 ± 9 days. No catheter-associated bloodstream infection occurred; main complications were symptomatic upper limb deep vein thrombosis (2%), catheter obstruction (18%) and persistent pain after catheter insertion (18%). Patients' satisfaction was high and PICC could be used to perform antibiotic courses in most patients. Conclusions PICCs were generally safe for performing IV antibiotic courses in patients with CF or non-CF bronchiectasis, but prolonged pain and/or catheter obstruction occurred in approximately 20% of cases.

International audience; Young cystic fibrosis (CF) patients' airways are mainly colonized by Staphylococcus aureus, while Pseudomonas aeruginosa predominates in adults. However, the mechanisms behind this infection switch are unclear. Here, we show that levels of type-IIA-secreted phospholipase A2 (sPLA2-IIA, a host enzyme with bactericidal activity) increase in expectorations of CF patients in an age-dependent manner. These levels are sufficient to kill S. aureus, with marginal effects on P. aeruginosa strains. P. aeruginosa laboratory strains and isolates from CF patients induce sPLA2-IIA expression in bronchial epithelial cells from CF patients (these cells are a major source of the enzyme). In an animal model of lung infection, P. aeruginosa induces sPLA2-IIA production that favours S. aureus killing. We suggest that sPLA2-IIA induction by P. aeruginosa contributes to S. aureus eradication in CF airways. Our results indicate that a bacterium can eradicate another bacterium by manipulating the host immunity.

COPD is characterized by incompletely reversible airflow limitation (FEV1/FVC70%). The historical classification of COPD, which was based on the severity of airflow limitation assessed by the level of FEV1, did not take into account the various aspects of COPD patients. At comparable levels of FEV1, COPD patients show marked heterogeneity in clinical manifestations (dyspnea, rates of exacerbations, exercise capacity, and quality of life), leading to the proposal of the current COPD classification based not only on FEV1, but also on symptoms (dyspnea or quality of life) and history of exacerbations. Limitations of this novel classification of COPD include its relative complexity and the absence of age and comorbidities. Recent identification of clinical COPD phenotypes (i.e., subgroups of COPD patients sharing not only clinical characteristics, but also natural history and/response to therapy) could result in progresses in the pathophysiology of the disease, in the development of specific biomarkers, and could facilitate evaluation of drugs in clinical trials. The development of simple algorithms, using easily available clinical data, will allow identification of phenotypes in clinical practice and may lead to individualized therapies.

60 Evaluation of twice-a-year antibiotic susceptibility testing for Pseudomonas aeruginosa in adult patients with cystic fibrosis P.C. Morand1,2, J. Chapron1,3, J. Loubinoux1,2, I. Honore1,3, H. Poupet2, R. Kanaan1,3, P.-R. Burgel1,3, C. Poyart1,2, D. Dusser1,3, D. Hubert3. 1Universite Paris Descartes, Sorbonne Paris Cite, Paris, France; 2Assistance PubliqueHopitaux de Paris, Hopital Cochin, Bacteriology, Paris, France; 3Assistance Publique-Hopitaux de Paris, Hopital Cochin, Service de Pneumologie and Adult CF Centre, Paris, France