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The aim of this study was to compare helical CT with fiberoptic bronchoscopy findings to appraise the medium-term results of proximal-airways stenting. Twenty-five patients with 28 endobronchial metallic stents inserted for local advanced malignancy ( n=13) or benign diseases ( n=12) underwent follow-up CT from 3 days to 50 months (mean 8 months). All studies were obtained using helical CT with subsequent multiplanar reformation and three-dimensional reconstruction including virtual bronchoscopy. The location, shape, and patency of stents and adjacent airway were assessed. The results of CT were compared with the results of fiberoptic bronchoscopy obtained with a mean delay of 2.5 days (SD 9 days) after CT scan. Twelve stents (43%) remained in their original position, patent and without deformity. Sixteen stents were associated with local complications: migration ( n=6); external compression with persistent stenosis ( n=4); local recurrence of malignancy ( n=4); fracture ( n=1); and non-congruence between the airway and the stent ( n=1). The CT demonstrated all the significant abnormalities demonstrated at fiberoptic bronchoscopy except two moderate stenoses (20%) related to granulomata at the origin of the stent. Ten of 14 stents inserted for benign conditions were without complications as compared with 2 of 14 in malignant conditions ( p=0.008). Computed tomography is an accurate noninvasive method for evaluating endobronchial stents. The CT is a useful technique for follow-up of patients who have undergone endobronchial stenting. [ABSTRACT FROM AUTHOR]

Lung transplantation (LTx) is the last-resort treatment for end-stage respiratory insufficiency, whatever its origin, and represents a steadily expanding field of endeavor. Major developments have been impelled over the years by painstaking efforts at LTx centers to improve donor and recipient selection, and multifaceted attempts have been made to meet the challenges raised by surgical management, perioperative care, and long-term medical complications. The number of procedures has increased, leading to improved post-LTx prognosis. One consequence of these multiple developments has been a pruning away of contraindications over time, which has, in some ways, complicated the patient selection process. With these considerations in mind, the Francophone Pulmonology Society (Société de Pneumology de Langue Française [SPLF]) has set up a task force to produce up-to-date working guidelines designed to assist pulmonologists in managing end-stage respiratory insufficiency, determining which patients may be eligible for LTx, and appropriately timing LTx-center referral. The task force has examined the most recent literature and evaluated the risk factors that continue to limit patient survival after LTx. Ideally, the objectives of LTx are to prolong life while improving quality of life. The guidelines developed by the task force apply to a limited resource and are consistent with the ethical principles described below., (Copyright © 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality in Europe; however, it is important to understand how clinical practice patterns differ between countries and how this might relate to disease outcomes, to identify ways of improving local disease management. We aimed to describe and compare the management of patients with COPD in the UK and France between 2008 and 2017., Methods: We used data from the Clinical Practice Research Datalink GOLD and Hospital Episode Statistics in the UK and the Echantillon Généraliste des Bénéficiaire in France to identify patients with COPD each year between 2008 and 2017. We compared patient characteristics, all-cause mortality and COPD exacerbations each year between 2008 and 2017 for patients in the UK and France separately. Health care utilisation and COPD exacerbations in 2017 were compared between France and the UK using t-tests and χ 2 tests., Results: Patients with COPD were similar in gender and comorbidities in both countries. Incidence of COPD exacerbations remained stable in the UK and France between 2007 and 2017. In 2017, the proportion of all-cause and COPD-related hospitalisations was greater in the UK than in France (43.9% vs 32.8% and 8.3% vs 4.9%, respectively; p<0.001) as was the proportion of patients visiting accident and emergency (A&E) (39.8% vs 16.2%, respectively; p<0.001). In addition, the mean length of stay in hospital for COPD-related causes was shorter in the UK than in France (6.2 days (SD 8.4) vs 10.5 days (SD 9.1), respectively; p<0.001)., Discussion: Overall, UK patients were more likely to go to A&E, be hospitalised for COPD-related causes and stay in hospital for fewer days after being admitted for COPD-related reasons compared with patients in France, illustrating a difference in health-seeking behaviours and access to healthcare., Competing Interests: Competing interests: HW reports grants from GSK, AZ and BI, outside the submitted work. JKQ reports grants and personal fees from British Lung Foundation, AZ, Asthma UK, BI, Bayer, GSK, MRC and Chiesi, outside the submitted work. MN, CM-M, MB and FD are employees of PELyon. EVG is the scientific advisor of PELyon. CP received support from AZ, BI, GSK, Chiesi and Novartis to attend medical meetings and fees for conferences., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background Pulmonary hypertension is a rare, chronic and life-threatening group of diseases. Recent advances in pulmonary hypertension management prolong survival and improve quality-of-life. However, highly complex drug therapy enhances the risk of drug-related problems. Objective To assess the impact of involving clinical pharmacists in the collaborative care of pulmonary hypertension patients. Setting Ten French University Hospital Pneumology departments, all members of the French Network for Pulmonary Hypertension. Methods This prospective multicenter randomized controlled trial included incident pulmonary hypertension patients who were followed-up for 18 months. Randomization using an adapted Zelen method allocated patients to collaborative care (n = 41) or usual care groups (n = 51). A collaborative care program involving clinical pharmacists was developed through a close partnership between with physicians, nurses and pharmacists. Besides usual care, the program includes regular one-to-one interviews between the pharmacist and the patient. These interviews had following objectives: to perform an exhaustive medication history review; to identify the patient' needs, knowledge and skills; to define educational objectives and to provide patients with relevant information when needed. Following each interview, a standardized report form containing the pharmacist's recommendations was provided to physicians and nurses and discussed collaboratively. An ancillary economic analysis was performed. Main outcome measure Number of drug-related problems and their outcomes. Results The number of drug-related problems was not significantly different between groups (1.6 ± 1.5 vs. 1.9 ± 2.4; p = 0.41). More problems were resolved in the collaborative care group than in the usual care group (86.5% vs. 66.7%, p = 0.01). Time to clinical worsening, therapeutic adherence, satisfaction or quality-of-life were not statistically different between groups. Collaborative care decreased costs of drug-related hospitalizations. Conclusion Including clinical pharmacists in the multidisciplinary care of hospitalized patients with pulmonary hypertension improved the outcome of drug-related problems and reduced the costs of related hospitalization. However, we observed no efficacy on medication errors, clinical outcomes or medication adherence. Clinical Trial Registration ClinicalTrials.gov Identifier NCT01038284.

Background: Lung cancer screening with low-dose chest CT (LDCT) reduces the mortality of eligible individuals. Blood signatures might act as a standalone screening tool, refine the selection of patients at risk, or help to classify undetermined nodules detected on LDCT. We previously showed that circulating tumour cells (CTCs) could be detected, using the isolation by size of epithelial tumour cell technique (ISET), long before the cancer was diagnosed radiologically. We aimed to test whether CTCs could be used as a biomarker for lung cancer screening., Methods: We did a prospective, multicentre, cohort study in 21 French university centres. Participants had to be eligible for lung cancer screening as per National Lung Screening Trial criteria and have chronic obstructive pulmonary disease with a fixed airflow limitation defined as post-bronchodilator FEV1/FVC ratio of less than 0·7. Any cancer, other than basocellular skin carcinomas, detected within the previous 5 years was the main exclusion criterion. Participants had three screening rounds at 1-year intervals (T0 [baseline], T1, and T2), which involved LDCT, clinical examination, and a blood test for CTCs detection. Participants and investigators were masked to the results of CTC detection, and cytopathologists were masked to clinical and radiological findings. Our primary objective was to test the diagnostic performance of CTC detection using the ISET technique in lung cancer screening, compared with cancers diagnosed by final pathology, or follow up if pathology was unavailable as the gold standard. This study is registered with ClinicalTrials.gov identifier, number NCT02500693., Findings: Between Oct 30, 2015, and Feb 2, 2017, we enrolled 614 participants, predominantly men (437 [71%]), aged 65·1 years (SD 6·5), and heavy smokers (52·7 pack-years [SD 21·5]). 81 (13%) participants dropped out between baseline and T1, and 56 (11%) did between T1 and T2. Nodules were detected on 178 (29%) of 614 baseline LDCTs. 19 participants (3%) were diagnosed with a prevalent lung cancer at T0 and 19 were diagnosed with incident lung cancer (15 (3%) of 533 at T1 and four (1%) of 477 at T2). Extrapulmonary cancers were diagnosed in 27 (4%) of participants. Overall 28 (2%) of 1187 blood samples were not analysable. At baseline, the sensitivity of CTC detection for lung cancer detection was 26·3% (95% CI 11·8-48·8). ISET was unable to predict lung cancer or extrapulmonary cancer development., Interpretation: CTC detection using ISET is not suitable for lung cancer screening., Funding: French Government, Conseil Départemental 06, Fondation UNICE, Fondation Aveni, Fondation de France, Ligue Contre le Cancer-Comité des Alpes-Maritimes, ARC (Canc'Air Genexposomics), Claire de Divonne-Pollner, Enca Faidhi, Basil Faidhi, Fabienne Mourou, Michel Mourou, Leonid Fridlyand, cogs4cancer, and the Fondation Masikini., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Mepolizumab was available in France as part of an early access programme for patients with severe eosinophilic asthma (nominative autorisation temporaire d'utilisation [temporary use authorisation] (nATU)) before its commercialisation. This study aimed to characterise patients who received mepolizumab in the nATU., Methods: This retrospective, observational study analysed data from the hospital medical records of patients up to 24 months after treatment initiation. Study objectives were to describe patient baseline characteristics, the evolution of disease severity and treatment modifications during follow-up; safety was also investigated., Findings: Overall, 146 patients who received ≥1 dose of mepolizumab were included. At inclusion, patients had a mean age of 58.2 years with a mean severe asthma duration of 13.4 years, and 37.0% had respiratory allergies. Patients experienced, on average, 5.8 exacerbations per patient per year at baseline, 0.6 and 0.5 of which required hospitalisation and emergency department visits, respectively. These values improved to 0.6, 0.1 and 0.1 exacerbations per patient per year, respectively, at 24 months of follow-up. Most patients (92.8%) were using oral corticosteroids at baseline, compared with 34.7% by 24 months of follow-up. Moreover, mean blood eosinophil counts improved from 722 cells·µL -1 at baseline to 92 cells·µL -1 at 24 months of follow-up; lung function and asthma control followed a similar trend., Interpretation: Results confirm findings from clinical trials, demonstrating that mepolizumab is associated with important improvements in several clinically meaningful outcomes and has a favourable safety profile in a population with severe eosinophilic asthma, outside of the controlled environment of a clinical trial., Competing Interests: Conflict of interest: C. Taillé reports that the study and manuscript preparation support was funded by GlaxoSmithKline; grants and personal fees for consultancy and lectures from GlaxoSmithKline, AstraZeneca, Novartis, Roche, Sanofi, Chiesi and TEVA, outside the submitted work. Conflict of interest: P. Chanez reports that the study and manuscript preparation support was funded by GlaxoSmithKline; personal fees for advisory board work from Almirall, grants and personal fees for lectures from Alk-Abello, Boston Scientific and Centocor, grants and personal fees for consultancy, advisory board work and lectures from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis and Teva, personal fees for consultancy and advisory board work from Johnson & Johnson and Sanofi, personal fees for consultancy from Merck Sharp & Dohme, grants from Roche, outside the submitted work. Conflict of interest: G. Devouassoux reports that the study and manuscript preparation support was funded by GlaxoSmithKline; grants and personal fees for consultancy and meeting participation from Novartis Pharma, AstraZeneca, GlaxoSmithKline, ALK, TEVA, personal fees for consultancy and meeting participation from MundiPharma, grants and personal fees for consultancy from Boehringer Ingelheim, personal fees for consultancy from Vivisol, grants from Sanofi, Vitalair, AB Science, Amgen, Lilly and Roche, grants and personal fees for meeting participation from Chiesi and MSD, personal fees for meeting participation from AGIR a dom, Orkyn, Stallergene and Takeda, outside the submitted work. Conflict of interest: A. Didier reports that the study and manuscript preparation support was funded by GlaxoSmithKline; personal fees for consultancy and meeting participation from Novartis Pharma, AstraZeneca and GlaxoSmithKline, personal fees for consultancy from Chiesi, Boehringer Ingelheim, Mundi Pharma, TEVA, ALK and Menarini, outside the submitted work. Conflict of interest: C. Pison reports that the study and manuscript preparation support was funded by GlaxoSmithKline; grants, personal fees for lectures and non-financial support for meeting attendance from Novartis, AstraZeneca, GlaxoSmithKline, Chiesi, Boehringer Ingelheim and Sanofi, grants and personal fees for consultancy and lectures from Mundi Pharma and MSD, outside the submitted work. Conflict of interest: G. Garcia reports that the study and manuscript preparation support was funded by GlaxoSmithKline; personal fees for advisory board work from Novartis and Sanofi, personal fees for advisory board work and consultancy from AstraZeneca, personal fees for consultancy from GlaxoSmithKline, non-financial support for travel from Oxyvie, outside the submitted work. Conflict of interest: J. Charriot reports that the study and manuscript preparation support was funded by GlaxoSmithKline. Conflict of interest: S. Bouée reports that the study and manuscript preparation support was funded by GlaxoSmithKline; is an employee of CEMKA, and reports grants from GlaxoSmithKline, outside the submitted work. Conflict of interest: A. Gruber reports that the study and manuscript preparation support was funded by GlaxoSmithKline; and is an employee and shareholder of GlaxoSmithKline, outside the submitted work. Conflict of interest: C. Pribil reports that the study and manuscript preparation support was funded by GlaxoSmithKline; and is an employee and shareholder of GlaxoSmithKline, outside the submitted work. Conflict of interest: A. Bourdin reports that the study and manuscript preparation support was funded by GlaxoSmithKline; personal fees for clinical trial work from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Chiesi, Novartis and Sanofi, outside the submitted work. Conflict of interest: M. Humbert reports that the study and manuscript preparation support was funded by GlaxoSmithKline; personal fees for consultancy, speaking at conferences, and participation in clinical research projects from AstraZeneca, GlaxoSmithKline, Novartis, Roche, Sanofi and TEVA, outside the submitted work., (Copyright ©ERS 2020.)

Introduction: In 2015, the International Society for Heart and Lung Transplantation (ISHLT) published a consensus document for the selection of lung transplant candidates. In the absence of recent French recommendations, this guideline is useful in order to send lung transplant candidates to the transplantation centers and to list them for lung transplantation at the right time., Background: The main indications for lung transplantation in adults are COPD and emphysema, idiopathic pulmonary fibrosis and interstitial diseases, cystic fibrosis and pulmonary arterial hypertension (PAH). The specific indications for each underlying disease as well as the general contraindications have been reviewed in 2015 by the ISHLT. For cystic fibrosis, the main factors are forced expiratory volume in one second, 6-MWD, PAH and clinical deterioration characterized by increased frequency of exacerbations; for emphysema progressive disease, the BODE score, hypercapnia and FEV1; for PAH progressive disease or the need of specific intravenous therapy and NYHA classification. Finally, the diagnosis of fibrosing interstitial lung disease is usually a sufficient indication for lung transplantation assessment., Outlook and Conclusion: These new recommendations, close to French practices, help clinicians to find the right time for referral of patients to transplantation centers. This is crucial for the prognosis of lung transplantation., (Copyright © 2019 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: This paper reports the French data from a post-hoc analysis of the international IDEAL study, which aimed to describe a recent cohort of patients with severe asthma, the impact of the disease on quality of life, as well as the population of patients eligible for treatment with omalizumab, mepolizumab and reslizumab., Methods: Eligible patients were≥12 years of age, with severe asthma (GINA steps 4 and 5)., Results: A total of 129 patients were included in this post-hoc analysis. Their mean age was 53 years, the majority were overweight, they were mainly women (64%) and had at least one medical comorbidity (85%). More than half had suffered from asthma for more than 25 years and were non-smokers. Lung function was moderately impaired. Blood eosinophil count was≥150 cells/μL in 66% of patients,≥300 cells/μL in 34% of patients, and≥500 cells/μL in 12% of patients. One out of three patients was currently treated with omalizumab and 24% had maintenance oral corticosteroids. Asthma was poorly controlled with a negative impact on quality of life (ACQ≥1.5) in 67% of patients. In this population 40% of patients were eligible for omalizumab, 27% for mepolizumab and 2% for reslizumab., Conclusions: These findings show that a considerable proportion of patients with severe asthma remain uncontrolled and are not eligible for any of the available biological treatments. This underlines the need for therapeutic innovations in this disease., (Copyright © 2018. Published by Elsevier Masson SAS.)

Endobronchial coil treatment (ECT) is a minimally invasive procedure developed for palliative care of patients with severe emphysema. ECT has demonstrated a decrease in hyperinflation, an improvement in quality of life, and an acceptable safety profile in randomized controlled trials (RCTs). Because alpha-1 antitrypsin deficiency (AATD) is a classical exclusion criterion in RCTs, there is no available data for ECT in AATD. In this post hoc analysis of the REVOLENS study (Réduction volumique endobronchique par spirales; ClinicalTrials.gov Identifier: NCT01822795), a multicenter 1:1 RCT which compared bilateral ECT with usual care in severe emphysema, we analyzed the efficacy and safety results at 1 year in six patients with AATD (five males, one female; mean age: 52±9 years) who underwent ECT. A significant decrease in hyperinflation (0.35 L decrease in residual volume [RV]) was observed in four out of six patients at 6 months and three out of six patients at 12 months, and an improvement in quality of life (improvement of 4 points in the St George's Respiratory Questionnaire [SGRQ]) was observed in four out of six patients at both 6 and 12 months. Efficacy results at 6 and 12 months from the six AATD patients were compared with 84 non-AATD patients who underwent ECT, and no statistically significant differences were found for FEV 1 , RV, 6MWT score and SGRQ score. Respiratory-related serious adverse event was limited to pneumonia in one AATD patient at 1 year post-ECT. This post hoc study suggests that AATD patients may have similar efficacy and safety outcomes at 1 year as non-AATD patients. Because of the paucity of available data, appropriately powered studies are needed to determine the effects of ECT in AATD., Competing Interests: Disclosure Gaëtan Deslee has been involved as an investigator in previous studies sponsored by BTG/PneumRx, and received travel reimbursements and speaker fees for educational sessions and consulting from BTG/PneumRx. Hervé Mal received honorarium from Boehringer, Bayer, Roche, Astellas, Chiesi, Actellion, Pfizer, Novartis, and GlaxoSmithKline outside the submitted work. Hervé Dutau received travel reimbursements and speaker fees for educational sessions and consulting from BTG/PneumRx. Arnaud Bourdin received honorarium from Astra Zeneca, GlaxoSmithKline, Boehringer, Novartis, Teva, Chiesi, Actellion, Gilead, and Roche outside the submitted work. Jean Michel Vergnon received travel reimbursements and speaker fees for educational sessions from BTG/PneumRx. Christophe Pison received honorarium from BTG/PneumRx and his hospital received funds to conduct trials from Holaira, PulmonX, and BTG/PneumRx. Charles Hugo Marquette has been involved as an investigator in previous studies sponsored by BTG/PneumRx, and received travel reimbursements and speaker fees for educational sessions and consulting from BTG/PneumRx. The authors report no other conflicts of interest in this work.

Background: With population aging, further asthma research is needed in the elderly., Objective: We assessed the relevance of the controller-to-total asthma medication ratio and its fluctuations over time to identify participants with a subsequent risk of poor asthma-related outcomes among well-characterized elderly women., Methods: We studied 4,328 women with ever asthma (69.6 ± 6.1 years) from the Asthma-E3N study (Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l'Education Nationale), which combined drug claims data since 2004 with prospective individual characteristics. The levels of the yearly controller-to-total asthma medication ratio from 2004 to 2011 were included in latent class analysis to identify groups of women characterized by specific long-term fluctuations of the ratio. Multiple regression models estimated the subsequent risk of uncontrolled asthma, asthma attacks, asthma exacerbations, and poor asthma-related quality of life associated with the level and the fluctuations of the ratio., Results: A short-term (12 months) ratio below 0.5 was associated with a higher risk of subsequent uncontrolled asthma, asthma attacks, asthma exacerbations (odds ratio [95% confidence interval (CI)] = 2.13 [1.41; 3.23], 1.51 [1.01; 2.26], and 2.18 [1.37; 3.44], respectively), and a lower total asthma quality of life questionnaire score (β [95% CI] = -0.49 [-0.68; -0.29]). The analysis of the long-term fluctuations of the ratio identified 5 profiles ("Never regular treatment," 53.2%; "Persistent high ratio," 21.8%; "Increasing ratio," 4.4%; "Initiating treatment," 8.8%; "Treatment discontinuation," 11.8%). The subsequent risk of poor asthma-related outcomes was significantly higher in profiles characterized by no or interrupted asthma maintenance therapy over time, compared with the "Persistent high ratio" group., Conclusions: The level and the long-term fluctuations of the controller-to-total asthma medication ratio predict poor asthma-related outcomes in elderly women., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Multimedication related to multimorbidity is common in the elderly with asthma. We aimed at comprehensively characterising medications used by elderly women and assessing how multimedication impacts on asthma prognosis.We performed network-based analyses on drug administrative databases to visualise the prevalence of drug classes and their interconnections among 17 458 elderly women from the Asthma-E3N study, including 4328 women with asthma. Asthma groups sharing similar medication profiles were identified by a clustering method relying on all medications and were studied in association with adverse asthma events (uncontrolled asthma, attacks/exacerbations and poor asthma-related quality of life).The network-based analysis showed more multimedication in women with asthma than in those without asthma. The clustering method identified three multimedication profiles in asthma: "Few multimorbidity-related medications" (43.5%), "Predominantly allergic multimorbidity-related medications" (32.8%) and "Predominantly metabolic multimorbidity-related medications" (23.7%). Compared with women belonging to the "Few multimorbidity-related medications" profile, women belonging to the two other profiles had an increased risk of uncontrolled asthma and asthma attacks/exacerbations, and had lower asthma-related quality of life.The integrative data-driven approach on drug administrative databases identified specific multimorbidity-related medication profiles that were associated with poor asthma prognosis. These findings support the importance of multimorbidity in the unmet needs in asthma management., Competing Interests: Conflict of interest: S. Chanoine reports personal fees (board membership) from AstraZeneca, and nonfinancial support (travel/accommodation/meeting expenses) from Boehringer Ingelheim, Actelion Pharmaceuticals and MSD, outside the submitted work. I. Pin reports travel grants and presentation fees from Novartis and AstraZeneca, and fees for training courses from Vertex, outside the submitted work. C. Pison has received grants and lectures fees from GlaxoSmithKline, AstraZeneca, Novartis and BIF, as well as speaker fees and fees for meeting participation from GlaxoSmithKline, AstraZeneca, Novartis, BIF and Teva. J. Bousquet reports personal fees (scientific and advisory boards) from Almirall, Meda, Merck, MSD, Novartis, Sanofi-Aventis, Takeda, Teva and Uriach, as well as personal fees (lecture fees) from Almirall, AstraZeneca, Chiesi, GlaxoSmithKline, Meda, Menarini, Merck, MSD, Novartis, Sanofi-Aventis, Takeda, Teva and Uriach, outside the submitted work. P. Bedouch reports fees for meeting expenses from Actelion Pharmaceuticals, outside the submitted work. R. Varraso reports grants from the Institut pour la Recherche en Santé Publique (IReSP), during the conduct of the study. V. Siroux reports personal fees (speakers honorarium) from Teva, AstraZeneca and Novartis, outside the submitted work., (Copyright ©ERS 2018.)

Studies reporting the effects of modern strategies with pulmonary arterial hypertension (PAH)-targeted therapies in sarcoidosis-associated pulmonary hypertension (S-APH) are limited.Clinical and haemodynamic data from newly diagnosed patients with severe S-APH (mean pulmonary artery pressure (mPAP) >35 mmHg or mPAP 25-35 mmHg with cardiac index <2.5 L·min -1 ·m -2 ) were collected from the French Pulmonary Hypertension Registry between 2004 and 2015.Data from 126 patients with severe S-APH were analysed (mean±sd age 57.5±11.6 years, 74% radiological stage IV). 97 patients (77%) received PAH-targeted therapy and immunosuppressive therapy was initiated or escalated in 33 patients at the time of pulmonary hypertension diagnosis. Four months after PAH-targeted therapy initiation, mean±sd pulmonary vascular resistance decreased from 9.7±4.4 to 6.9±3.0 Wood units (p<0.001), without significant improvement in exercise capacity. Among the 11 patients treated only with immunosuppressive therapy, a haemodynamic improvement was observed in four patients, including two with compressive lymph nodes. After a median follow-up of 28 months, 39 patients needed PAH-targeted therapy escalation, nine underwent lung transplantation and 42 had died. Survival at 1, 3 and 5 years was 93%, 74% and 55%, respectively.PAH-targeted therapy improved short-term pulmonary haemodynamics in severe S-APH without change in exercise capacity. Immunosuppressive therapy improved haemodynamics in selected patients. Pulmonary hypertension in sarcoidosis remains associated with a poor prognosis., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

Introduction and Methods: The EGEA study (epidemiological study on the genetics and environment of asthma, bronchial hyperresponsiveness and atopy), which combines a case-control and a family-based study of asthma case (n=2120 subjects) with three surveys over 20 years, aims to identify environmental and genetic factors associated with asthma and asthma-related phenotypes. We summarize the results of the phenotypic characterization and the investigation of environmental and genetic factors of asthma and asthma-related phenotypes obtained since 2007 in the EGEA study (42 articles)., Results: Both epidemiological and genetic results confirm the heterogeneity of asthma. These results strengthen the role of the age of disease onset, the allergic status and the level of disease activity in the identification of the different phenotypes of asthma. The deleterious role of active smoking, exposure to air pollution, occupational asthmogenic agents and cleaning products on the prevalence and/or activity of asthma has been confirmed. Accounting for gene-environment interactions allowed the identification of new genetic factors underlying asthma and asthma-related traits and better understanding of their mode of action., Conclusion: The EGEA study is contributing to the advances in respiratory research at the international level. The new phenotypic, environmental and biological data available in EGEA study will help characterizing the long-term evolution of asthma and the factors associated to this evolution., (Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

The French registry of patients with alpha-1 antitrypsin deficiency (AATD)-associated emphysema was launched in 2006. Here, we aimed to report on the baseline characteristics of these patients, their health-related quality of life (HRQoL) and factors associated with HRQoL. Another goal was to survey the practices of French physicians regarding augmentation therapy. We included 273 patients with AATD, emphysema, obstructive-pattern [forced expiratory volume in 1 sec/forced volume capacity (FEV1/FVC) < 0.7], FEV1 ≤ 80% predicted. Mean (SD) age was 51.8 (11.1) years, 240 (87.9%) of patients were smokers or ex-smokers, mean (SD) FEV1 was 40.5% (15.7) predicted. Mean (SD) SGRQ score was 49.0 (20.0) and was higher for females than males (52.7 [20.7] vs 46.8 [18.2]; p = 0.01). Dyspnea showed the strongest association with SGRQ score (r = 0.65; p < 0.0001), followed by chronic bronchitis (r = 0.33; p < 0.0001) and wheezing (r = 0.32; p < 0.0001). Number of exacerbations in the year before inclusion was also significantly associated with SGRQ score (r = 0.36; p < 0.0001). The SGRQ score was associated with the 6-min walking distance (r = -0.53, p < 0.0001), FEV1 (% predicted, r = -0.53, p < 0.0001) and DLCO (% predicted, r = -0.52, p < 0.0001). It was also associated with the GOLD 2006 (r = 0.53; p < 0.0001) and GOLD 2011 (r = 0.63; p< 0.0001) classifications and with the BODE index (r = 0.37; p < 0.0001). Age, history of tobacco smoking or current smoking did not show any association with SGRQ total scores. On multivariate analysis, a model including age, chronic bronchitis, dyspnea (MRC scale), diffusing lung capacity and 6-min walking distance explained 57% of the variation in the score. The French registry provides important insights into the clinical characteristics of French patients with AATD-related emphysema.

Background: After lung transplantation (LT), immunoglobulin (Ig) G plasma concentrations<6 g/L are common and correlate with an increased risk of chronic lung allograft dysfunction (CLAD) and a poorer survival., Methods: We conducted an open substitution intervention with nonspecific intravenous Ig (IVIg), in all patients with IgG plasma less than 6 g/L post-LT in 54 of 84 consecutive recipients since 1998 who survived more than 3 months. Pre-LT and post-LT events were retrospectively analyzed., Results: Both substituted and nonsubstituted groups demonstrated similar donor or recipient characteristics and events over a median follow-up of 2.8 years (Q1-Q3, 1.4-5.7], except for initial diagnosis with more chronic obstructive pulmonary disease patients and less cases of pulmonary arterial hypertension in NS group. Intravenous Ig substitution started 3.5 months (0.5-9.4) after transplantation and lasted 4.5 months after (1.0-17.7), mean cumulative dose was 52.8±47.7 g. In multivariate Cox regression model, hypogammaglobulinemic patients who were substituted with IVIg had actually a 5-year survival (hazard ratio, 0.63; 95% confidence interval, 0.26-1.49; P=0.29) and CLAD-free 5-year survival (hazard ratio, 0.51; 95% confidence interval, 0.15-1.67; P=0.27) really close to nonhypogammaglobulinemic and nonsubstituted patients. Complementary analysis using propensity score and time-dependent analysis showed that survival and CLAD-free survival were not different in both groups., Conclusion: Intravenous Ig post-LT achieved similar survival and CLAD-free survival in recipients with hypogammaglobulinemia as compared to those with normal IgG plasmatic rate. A randomized control trial is required to confirm benefic effects of IVIg and disentangle mechanisms, including protection from infections, acute cellular and humoral rejections in patients with hypogammaglobulinemia after LT.

The BODE (body mass index, airflow obstruction, dyspnoea and exercise capacity) index is used to decide on referral and transplantation of patients with chronic obstructive pulmonary disease (COPD). The BODE index has not been validated in patients with α1-antitrypsin deficiency, who account for 15% of COPD patients undergoing lung transplantation. We sought to validate the BODE index in α1-antitrypsin deficiency-related COPD. We assessed the prognostic value of the BODE index in 191 patients followed from 2006 to 2012 in a French prospective cohort of patients with α1-antitrypsin deficiency. 20 patients died during follow-up and 22 underwent lung transplantation. Survival (95% CI) was 93.0% (91.7-94.3%) at 3 years and 76.0% (72.9-79.1%) at 5 years. The 3-year survival was 97.4% (96.6-98.2%), 98.0% (96.7-99.3%), 87.7% (84.5-90.9%) and 75.3% (66.0-84.6%) for patients with BODE index 0-2, 3-4, 5-6 and 7-10, respectively. Survival discrimination of the BODE index was better than with both forced expiratory volume in 1 s and Global Initiative for Chronic Obstructive Lung Disease classification. Regarding calibration, expected survival by BODE index was noticeably lower than observed survival. The BODE index showed very good survival discrimination in patients with α1-antitrypsin deficiency-related COPD. Larger studies are needed to support its use to drive patient referral for lung transplantation., (©ERS 2014.)

Background: The associations between exposure to air pollution and asthma control are not well known. The objective of this study was to assess the association between long-term exposure to NO(2), O(3) and PM(10) and asthma control in the follow-up of the Epidemiological study on the Genetics and Environment of Asthma (EGEA2) (2003-2007)., Methods: Modelled outdoor NO(2), O(3) and PM(10) estimates were linked to each residential address using the 4 km grid air pollutant surface developed by the French Institute of Environment in 2004. Asthma control was assessed in 481 subjects with current asthma using a multidimensional approach following the 2006-2009 Global Initiative for Asthma guidelines. Multinomial and ordinal logistic regressions were conducted adjusted for sex, age, body mass index, education, smoking and use of inhaled corticosteroids. The association between air pollution and the three domains of asthma control (symptoms, exacerbations and lung function) was assessed. ORs are reported per IQR., Results: Median concentrations (in micrograms per cubic metre) were 32 (IQR 25-38) for NO(2) (n=465), 46 (41-52) for O(3) and 21 (18-21) for PM(10) (n=481). In total, 44%, 29% and 27% had controlled, partly controlled and uncontrolled asthma, respectively. The ordinal ORs for O(3) and PM(10) with asthma control were 1.69 (95% CI 1.22 to 2.34) and 1.35 (95% CI 1.13 to 1.64), respectively. When including both pollutants in the same model, both associations persisted. Associations were not modified by sex, smoking status, use of inhaled corticosteroids, atopy, season of examination or body mass index. Both pollutants were associated with each of the three main domains of control., Conclusions: The results suggest that long-term exposure to PM(10) and O(3) is associated with uncontrolled asthma in adults, defined by symptoms, exacerbations and lung function.

Background: The aims were to assess 1) the relationship of asthma control assessed by combining epidemiological survey questions and lung function to Health-Related Quality of Life (HRQL) and 2) whether individuals with controlled asthma reach similar generic HRQL levels as individuals without asthma., Methods: The analysis included 584 individuals without asthma and 498 with asthma who participated in the follow-up of the Epidemiological study on Genetics and Environment of Asthma (EGEA). Asthma control was assessed from survey questions and lung function, closely adapted from the 2006-2009 Global Initiative for Asthma guidelines. The Asthma Quality of Life Questionnaire (AQLQ, scores range:1-7) and the generic SF-36 (scores range: 0-100) were used., Results: Adjusted mean total AQLQ score decreased by 0.5 points for each asthma control steps (6.4, 5.9 and 5.4 for controlled, partly-controlled and uncontrolled asthma respectively, p < 0.0001). The differences in SF-36 scores between individuals with controlled asthma and those without asthma were minor and not significant for the PCS (-1, p = 0.09), borderline significant for the MCS (-1.6, p = 0.05) and small for the 8 domains (<5.1) although statistically significant for 4 domains., Conclusion: These results support the discriminative properties of the proposed asthma control grading system and its use in epidemiology., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Therapeutic drug monitoring of tacrolimus is a major support to patient management and could help improve the outcome of lung transplant recipients, by minimizing the risk of rejections and infections. However, despite the wide use of tacrolimus as part of maintenance immunosuppressive regimens after lung transplantation, little is known about its pharmacokinetics in this population. Better knowledge of the pharmacokinetics of tacrolimus in lung transplant recipients, and the development of tools dedicated to its therapeutic drug monitoring, could thus help improve their outcome., Objectives: The aims of this study were (i) to characterize the population pharmacokinetics of tacrolimus in lung transplant recipients, including the influence of biological and pharmacogenetic covariates; and (ii) to develop a Bayesian estimator of the tacrolimus area under the blood concentration-time curve from time zero to 12 hours (AUC(12)) for its therapeutic drug monitoring in lung transplant recipients., Methods: A population pharmacokinetic model was developed by nonlinear mixed-effects modelling using NONMEM® version VI, from 182 tacrolimus full concentration-time profiles collected in 78 lung transplant recipients within the first year post-transplantation. Patient genotypes for the cytochrome P450 3A5 (CYP3A5) A6986G single nucleotide polymorphism (SNP) were characterized by TaqMan allelic discrimination. Patients were divided into an index dataset (n = 125 profiles) and a validation dataset (n = 57 profiles). A Bayesian estimator was derived from the final model using the index dataset, in order to determine the tacrolimus AUC(12) on the basis of a limited number of samples. The predictive performance of the Bayesian estimator was evaluated in the validation dataset by comparing the estimated AUC(12) with the trapezoidal AUC(12)., Results: Tacrolimus pharmacokinetics were described using a two-compartment model with Erlang absorption and first-order elimination. The model included cystic fibrosis (CF) and CYP3A5 polymorphism as covariates. The relative bioavailability in patients with CF was approximately 60% of the relative bioavailability observed in patients without CF, and the transfer rate constant between the transit compartments was 2-fold smaller in patients with CF than in those without CF (3.32 vs 7.06 h-1). The apparent clearance was 40% faster in CYP3A5 expressers than in non-expressers (24.5 vs 17.5 L/h). Good predictive performance was obtained with the Bayesian estimator developed using the final model and concentrations measured at 40 minutes and at 2 and 4 hours post-dose, as shown by the mean bias (1.1%, 95% CI -1.4, 3.7) and imprecision (9.8%) between the estimated and the trapezoidal AUC(12). The bias was >20% in 1.8% of patients., Conclusion: Population pharmacokinetic analysis showed that lung transplant patients with CF displayed lower bioavailability and a smaller transfer rate constant between transit compartments than those without CF, while the apparent clearance was faster in CYP3A5 expressers than in non-expressers. The Bayesian estimator developed in this study provides an accurate prediction of tacrolimus exposure in lung transplant patients, with and without CF, throughout the first year post-transplantation. This tool may allow routine tacrolimus dose individualization and may be used to conduct clinical trials on therapeutic drug monitoring of tacrolimus after lung transplantation.

Patients with Pulmonary Arterial Hypertension (PAH) require multidisciplinary care. Involving pharmacists in PAH multidisciplinary care teams may enhance patient education and improve medication use. We describe the implementation of a Pharmacist Collaborative Care Program (PCCP) in a PAH referral centre in Grenoble, France. Initiated in 2007, the PCCP program includes a pharmacist intervention whose goals are educational, psychosocial, and technical. During patient interviews, pharmacists make an 'educational diagnosis' and provide a patient-specific education session. Patient skills are evaluated at the end of the session. Pharmacists provide feedback to nurses and physicians through a standardized report form and discussion during medical rounds and PAH group meetings. Pharmacists re-evaluate patients' skills every 3-6 months during multidisciplinary clinical evaluations. The PCCP program for PAH is an established practice in Grenoble and may inform future patient education programs involving pharmacists in France, where legislation has recently been passed to standardize patient education.

Introduction: Lung transplantation has experienced an increasing expansion with a significant improvement in results with the passage of time. Evaluation of these results consists of several domains: survival, function, quality of life and cost-effectiveness., Background: The success of lung transplantation is confirmed by a median survival that currently exceeds 5 years. Cystic fibrosis is the disease associated with the best results with, in France, a survival of 76% at 1 year, 56% at 5 years and 47% at 10 years and a median survival of 8 years. According to French data the 5-year survival is 46% for PAHT, 42% for COPD and 36% for pulmonary fibrosis. Studies have shown a survival benefit for cystic fibrosis and interstitial lung disease but definitive conclusions cannot be drawn for patients with COPD. Lung transplantation brings similar benefits in terms of quality of life and cost-effectiveness., Viewpoints: New statistical methods would allow a better estimate in terms of years of survival and quality of life to be made for each candidate on an individual basis., Conclusions: Lung transplantation improves survival and quality of life compared to medical treatment, at an acceptable cost. These outcomes should be assessed at both an individual and social level to justify the resources involved., (Copyright © 2010 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Background: Masitinib is a tyrosine kinase inhibitor targeting stem cell factor receptor (c-kit) and platelet-derived growth factor (PDGF) receptor, which are expressed on several cell types including mast cells and bronchial structural cells, respectively. We hypothesized that c-kit and PDGF receptor inhibition may decrease bronchial inflammation and interfere with airway remodeling, which are crucial features of severe asthma., Objectives: The primary endpoint was the percent change from baseline in oral corticosteroids after 16 weeks of treatment. Change in asthma control (asthma control questionnaire), exacerbation rate, pulmonary function tests, rescue medication requirement and safety were secondary endpoints., Methods: A 16-week randomized, dose-ranging (3, 4.5, and 6 mg/kg/day), placebo-controlled study was undertaken in 44 patients with severe corticosteroid-dependent asthma who remained poorly controlled despite optimal asthma management., Results: At 16 weeks of treatment, a comparable reduction in oral corticosteroids was achieved with masitinib and placebo (median reduction of -78% and -57% in the masitinib and placebo arms, respectively). Despite this similar reduction, the Asthma Control Questionnaire score was significantly better in the masitinib arm as compared to placebo with a reduction by 0.99 unit at week 16 (P < 0.001) vs 0.43 unit in the placebo arm. Masitinib therapy was associated with more transient skin rash and edema., Conclusions: Masitinib, a c-kit and PDGF-receptor tyrosine kinase inhibitor, may represent an innovative avenue of treatment in corticosteroid-dependent asthma. These preliminary results warrant further long-term clinical studies in severe asthma

Introduction: Alpha-1 antitrypsin deficiency is associated with the occurrence of pulmonary emphysema. The aim of this study is to describe the characteristics of patients with alpha-1 antitrypsin deficiency associated pulmonary emphysema., Methods: We describe a prospective cohort study including adult patients with alpha-1 antitrypsin deficiency associated pulmonary emphysema confirmed by CT scan living in France. Patients' clinical and functional characteristics, quality of life measures and management were recorded every 6 months during a five-year period., Results: 201 patients were included from 56 centres between 2005 and 2008. The characteristics of 110 patients have been analysed. Mean age was 50 years (SD:11.8), 62.7% were males, 90% were tobacco smokers. The main functional results (% predicted) were: FEV1: 42.8 (19.6), CPT: 128.3 (21.7), CRF: 167.0 (46.0), 6 minute walking distance (meters): 413 (130). 51 (46.4%) patients received augmentation therapy. Augmentation therapy was administered weekly (37.5%), twice a month (35.4%) or monthly (25.5%). Study centre was the only factor associated with the likelihood to received augmentation therapy., Conclusions: The clinical and functional characteristics as well as management of these patients varied markedly. There is a need for a standardization of the management of patients with alpha-1 antitrypsin deficiency associated pulmonary emphysema.

There is ongoing debate as to how asthma should be defined in order to forward understanding of the underlying mechanisms. The aim of the present study was to build quantitative scores of asthma and asthma severity and to assess whether refinement of disease phenotypes can facilitate the identification of chromosomal regions harbouring susceptibility genes. A genome-wide linkage scan was conducted in 110 families with at least two asthmatic siblings (n = 508) from the French Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA). The phenotypes studied were an asthma severity score (assessed among asthmatics by combining clinical data and treatment), forced expiratory volume in one second (FEV(1)) and an asthma score (including both asthmatics and nonasthmatics and representing the whole disease spectrum). This analysis showed genome-wide suggestive evidence of linkage of the asthma score to 18p11, a novel region undetected in a previous screen of dichotomous asthma. There was potential linkage of 2p23 to asthma severity score and of three regions (1p36, 2q36 and 6q14) to FEV(1). Moreover, FEV(1) appeared to have no genetic determinant in common with asthma severity and asthma scores. Asthma and asthma severity quantitative scores revealed new regions of linkage and thus provide support for considering these phenotypes in future genetic studies.

Introduction: EGEA (Epidemiological study on the genetics and environment of asthma, bronchial hyperresponsiveness and atopy), a case control and family study including 2048 individuals, was initiated to look for environmental and genetic risk factors for asthma. A synthesis of the results obtained since 2002 on phenotypic and environmental aspects of asthma severity and allergy are presented in this article., Methods and Results: The results support a role for hormonal factors in asthma severity and in various allergic markers of asthma. A greater body mass index was related to a more severe asthma in women with early menarche. Associations between markers of allergy (eosinophils, IgE and atopy) and hormonal dependent events in women (premenstrual asthma, menopause and oral contraceptive use) have been found. In asthmatics, exposure to agents known to be associated with occupational asthma, active and passive smoking were associated with an increased clinical asthma severity score. The study underlines the protective role of country living and exposure to pets in early life on allergy markers in adulthood, supporting the hygiene hypothesis., Conclusions: New hypothesis will be tested in the near future from the second stage of this survey.

Aging is associated with a progressive decrease in lung function. As a consequence of aging, individual's reserve is diminished, but this decrease is heterogeneous between individual subjects. Many factors are involved in the overall decline in lung function. The prevalence of asthma in the elderly is estimated between 6 and 10%. Mortality due to COPD is increasing, especially among older subjects. Older subjects are at an increased risk of developing chronic diseases such as Parkinson's disease, which can have consequences for lung function. Under-nutrition is also common in the elderly and can produce sarcopenia and skeletal muscle dysfunction. The presentation of respiratory disorders may differ in the elderly, especially because of a lack of perception of symptoms such as dyspnea. The impact of bronchodilatators or corticosteroids on respiratory function has not been studied in the elderly. Drugs usually used for the treatment of hypertension or arrhythmias, which are often observed with aging, can have pulmonary toxicity. There is no difference between functional evaluation in younger and older subjects but it is more difficult to find predicted values for older patients. Performing pulmonary function tests in older patients is often difficult because of a higher prevalence of cognitive impairment and/or poor coordination. When assessing pulmonary function in the elderly, the choice of tests will be depend on the circumstances, with the use of voluntary manoeuvres dependent on the condition of the patient.

Rationale: Pulmonary arterial hypertension (PAH) is an orphan disease for which the trend is for management in designated centers with multidisciplinary teams working in a shared-care approach., Objective: To describe clinical and hemodynamic parameters and to provide estimates for the prevalence of patients diagnosed for PAH according to a standardized definition., Methods: The registry was initiated in 17 university hospitals following at least five newly diagnosed patients per year. All consecutive adult (> or = 18 yr) patients seen between October 2002 and October 2003 were to be included., Main Results: A total of 674 patients (mean +/- SD age, 50 +/- 15 yr; range, 18-85 yr) were entered in the registry. Idiopathic, familial, anorexigen, connective tissue diseases, congenital heart diseases, portal hypertension, and HIV-associated PAH accounted for 39.2, 3.9, 9.5, 15.3, 11.3, 10.4, and 6.2% of the population, respectively. At diagnosis, 75% of patients were in New York Heart Association functional class III or IV. Six-minute walk test was 329 +/- 109 m. Mean pulmonary artery pressure, cardiac index, and pulmonary vascular resistance index were 55 +/- 15 mm Hg, 2.5 +/- 0.8 L/min/m(2), and 20.5 +/- 10.2 mm Hg/L/min/m(2), respectively. The low estimates of prevalence and incidence of PAH in France were 15.0 cases/million of adult inhabitants and 2.4 cases/million of adult inhabitants/yr. One-year survival was 88% in the incident cohort., Conclusions: This contemporary registry highlights current practice and shows that PAH is detected late in the course of the disease, with a majority of patients displaying severe functional and hemodynamic compromise.

A multidisciplinary working group devoted to epidemiological surveillance of invasive aspergillosis (IA) was created in January 2000 in Grenoble University Hospital. This article presents the results of a three-year IA surveillance. The multidisciplinary working group surveyed all hospitalized patients, and the mycology laboratory detected most suspected IA cases. Cases were reviewed monthly by the Aspergillosis Committee, and were classified according to international consensus criteria. Possible nosocomial acquisition was determined. Among the 490 alerts, 74 IA cases were observed: six proven cases (8%), 36 (49%) probable cases and 32 (43%) possible cases. The incidence was 4.4 (95% CI 3.4-5.4) IA/100 000 patient-days. Among the proven and probable IA cases, we observed 10 nosocomial cases and six cases of undetermined origin. No cases were noted in the protected rooms in the haematology unit. Only one cluster of cases (three nosocomial cases) was detected in the haematology unit. Forty-three percent of cases (N=32) were hospitalized in the haematology unit, and all other cases were hospitalized elsewhere. This three-year survey found a high rate of non-nosocomial IA cases and a high frequency of IA cases hospitalized in units other than haematology. Thus, this study shows the importance of IA surveillance in haematology units and all high-risk units.

Background: The liberalization of lung-donor criteria and the use of marginal donors have been advocated to face the current shortage of donors in lung transplantation. However, the impact of donor characteristics on the outcome of lung transplantation is still largely unknown. We aimed to determine, on a large cohort of patients, the effect of donors characteristics on short- and long-term outcome of lung transplantation, Methods: Between 1988 and 1998, a total of 785 adult patients underwent single-lung transplantation (n = 270), bilateral-lung transplantation (n = 251), and heart-lung transplantation (n = 264) in 7 centers in France. We constructed several multivariate models to assess the relationship between donor characteristics and early gas exchange, duration of mechanical ventilation, and long-term survival after lung transplantation., Results: Among donor characteristics, donor gas exchange before harvest was found to be significantly associated with recipient early gas exchange, duration of mechanical ventilation, and long-term survival after adjustment for potential confounding variables. Moreover, nonlinear modeling showed a steep increase in the relative risk of death when donor PaO2/FiO2 before harvest was below 350 (hazard ratio 1.43; 95% confidence interval 1.10-1.85; p = 0.01). Donor and recipient sex mismatch were also found to be significantly associated with long-term survival., Conclusions: Although liberalization of lung-donor criteria may be considered to overcome the shortage of lung donors, our data suggest that the violation of the gas-exchange criterion should be avoided.

Rationale: The effect of graft ischemic time on early graft function and long-term survival of patients who underwent lung transplantation remains controversial. Consequently, graft ischemic time has not been incorporated in the decision-making process at the time of graft acceptance., Objectives: To investigate the relationship between graft ischemic time and (1) early graft function and (2) long-term survival after lung transplantation., Measurements and Main Results: The data from 752 patients who underwent single lung transplantation (n = 258), bilateral lung transplantation (n = 247), and heart-lung transplantation (n = 247) in seven French transplantation centers during a 12-year period were reviewed. Independent data quality control was done to ensure the quality of the collected variables. Mean graft ischemic time was 245.8 +/- 96.4 minutes (range 50-660). After adjustment on 11 potential confounders, graft ischemic time was associated with the recipient Pa(O2)/FI(O2) ratio recorded within the first 6 hours and with long-term survival in patients undergoing single or double lung transplantation but not in patients undergoing heart-lung transplantation. The relationship between graft ischemic time and survival appears to be of cubic form with a cutoff value of 330 minutes. These results were unaffected by the preservation fluid employed., Conclusions: The results of this large cohort of patients suggest a close relationship between graft ischemic time and both early gas exchange and long-term survival after single and double lung transplantation. Such relationship was not found in patients undergoing heart-lung transplantation. The expected graft ischemic time should be incorporated in the decision-making process at the time of graft acceptance.

Rationale: The severity of asthma has been defined by various criteria in epidemiology, but their relationships have been rarely studied., Material and Methods: The interrelationships between various asthma severity criteria (clinical severity in the past 12 months) (score 0-7), functional (FEV1), therapy (inhaled steroids used in the past 12 months) and hospitalization during life were studied. Bivariate (OR) and multivariate (factorial analyses, log-linear models) analyses were applied in asthmatic children (n=135) and adults (n=213) recruited in chest clinics for the EGEA study (Epidemiological Study on the Genetics and Environment of Asthma)., Results: In asthmatics, the proportion of severe asthma was highly dependent on the definition used. Whatever the statistical method used, FEV1 in children was unrelated to treatment, hospitalization and the clinical score. In adults, the clinical score was not associated with hospitalization, treatment and FEV1, these last three criteria being highly related to each other., Conclusion: Results support the hypothesis of the multidimensional character of severity of asthma.

Background: The EGEA study combines a case-control study and a family study to assess genetic and environmental risk factors and their interactions for asthma, bronchial hyperresponsiveness and atopy. Information is scanty regarding potential selection biases, in particular regarding familial ressemblance in epidemiological surveys of this kind., Methods: Asthmatic probands (adult and paediatric) were recruited in chest clinics of six clinical centres. Controls were mostly population-based (electoral rolls) for adults and recruited in surgery departments for children., Results: The population examined includes 348 nuclear families ascertained by one asthmatic and 416 controls, totalling 1847 subjects (EGEA I) and an additional sample of 40 families ascertained by two asthmatic siblings (EGEA II). Potential biases for the various types of analyses have been studied. Quantification of the consequences of the greater participation of probands with a parental history of asthma shows it does not introduce a major bias in the estimates of familial resemblance. Cases and controls showed a good comparability regarding sex, age, area of residence and familial geographical origin, allowing proper associations studies for environmental and candidate genetic factors., Conclusions: The case-control component of the study will allow to perform studies on environmental factors and association studies for various genetic polymorphisms. Using the family base collected, segregation and genetic linkage/association analyses with DNA markers may be performed.

A genome-wide search was conducted in 107 nuclear families with at least two siblings with asthma, as part of the French EGEA study. A two-stage analysis strategy was applied to the 107 families divided into two independent subsets of 46 and 61 families, where all regions detected in the first set of families were tested for replication in the second set. In addition, all regions reported by published genome scans in different populations were examined in the total sample. A total of 254 markers were typed in the first set of families and 70% of them in the second set. Linkage was investigated by model-free methods for asthma and four asthma-related phenotypes: bronchial responsiveness (BR), skin test response, total immunoglobulin E (IgE) levels, and eosinophil count. The two-stage analysis led to the detection of three regions: 11p13 for IgE, 12q24 for eosinophils, and 17q12-21 for asthma and skin tests. Among the regions reported by published genome screens, seven were found in the 107 French EGEA families: three being already detected by the two-stage analysis, 11p13 (p = 0.005), 12q24 (p = 0.0008), and 17q12-21 (p = 0.001), and four additional ones, 1p31 (p = 0.005) for asthma, 11q13 (p = 0.006) for IgE, 13q31 (p = 0.001) for eosinophils, and 19q13 (p = 0.02) for BR.

Background: This study is part of the European Community Respiratory Health Survey (ECRHS), which uses a common methodology in different areas throughout the world. This paper describes the prevalences of reported asthma, asthma-like symptoms and nasal allergies, their relationships to age group and sex, and the relationships of asthma-like symptoms to current asthma, in the general population aged 20-44 years of three French urban areas., Methods: The study population of 2804 subjects in Grenoble, 3774 in Montpellier and 3152 in Paris (18th district), randomly selected from electoral rolls, answered a postal questionnaire (stage I of ECRHS). The response rates were 77.8%, 68.6% and 74.4%, respectively., Results: The prevalences were approximately 14% for wheezing, 16% for chest tightness and 4.5% for nocturnal shortness of breath in the three areas. Asthma attacks in the last 12 months were reported by 2.7% of subjects in Grenoble, 3.5% of subjects in Montpellier and 4.0% of subjects in Paris (P = 0.02). For nasal allergies, the prevalences were 28.0%, 34.3% and 30.8%, respectively (P < 0.001). Asthma was inversely correlated to age (higher prevalence in the youngest) but was not related to sex. Neither age distribution nor sex ratio explained the differences between areas. Among the asthma-like symptoms, wheezing and nocturnal shortness of breath correlated strongly with asthma, chest tightness correlated moderately and nocturnal coughing correlated poorly., Conclusion: The prevalences observed were higher than expected from previous comparable French studies in young adults. These results are consistent with the hypothesis of a recent increase of asthma and allergies.

Histiocytosis is a rare cause of diffuse interstitial pneumonia. Its aetiology is not known and the outcome is often unsatisfactory. In 10 subjects in whom the diagnosis of histiocytosis X was established at CHU in Grenoble, 7 could be followed up. We report the clinical, functional, radiological and high resolution tomographic data on these 7 subjects suffering from histiocytosis X and followed up for a period between 3 and 13 years (8 +/- 3 years). All the subjects were symptomatic at the time of diagnosis. The clinical outcome amongst the 10 subjects included 2 patients who died, 2 who stabilised, 1 worsened and there were 4 clinical cures, 1 patient was lost to follow up. The respiratory function tests of the 7 subjects who were followed up was characterised by the appearance of airflow obstruction and a significant fall in the DLCO/VA (KCO) of 68 +/- 17% of the predicted value to 43 +/- 13%. An analysis comparing the initial pulmonary radiography to the current films showed that the reticular nodular lesions tended to progress to a diminution in size, while there was an increase in the reticulation. The high resolution computed tomography was confirmed as better technique than pulmonary radiography in detailing the cystic and nodular lesions. This was the only examination which correlated with DLCO/VA (R: 0.8; p: 0.018). A progressive model for computed tomographic lesions is proposed. Computed tomography appears to be the key examination, orientating the diagnosis based on the association of the nodules and cysts and enabling a better appreciation of the severity of the pulmonary disease taking account of its excellent correlation with diffusion.