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Background: In allergic bronchopulmonary aspergillosis (ABPA), prolonged nebulised antifungal treatment may be a strategy for maintaining remission., Methods: We performed a randomised, single-blind, clinical trial in 30 centres. Patients with controlled ABPA after 4-month attack treatment (corticosteroids and itraconazole) were randomly assigned to nebulised liposomal amphotericin-B or placebo for 6 months. The primary outcome was occurrence of a first severe clinical exacerbation within 24 months following randomisation. Secondary outcomes included the median time to first severe clinical exacerbation, number of severe clinical exacerbations per patient, ABPA-related biological parameters., Results: Among 174 enrolled patients with ABPA from March 2015 through July 2017, 139 were controlled after 4-month attack treatment and were randomised. The primary outcome occurred in 33 (50.8%) out of 65 patients in the nebulised liposomal amphotericin-B group and 38 (51.3%) out of 74 in the placebo group (absolute difference -0.6%, 95% CI -16.8- +15.6%; OR 0.98, 95% CI 0.50-1.90; p=0.95). The median (interquartile range) time to first severe clinical exacerbation was longer in the liposomal amphotericin-B group: 337 days (168-476 days) versus 177 days (64-288 days). At the end of maintenance therapy, total immunoglobulin-E and Aspergillus precipitins were significantly decreased in the nebulised liposomal amphotericin-B group., Conclusions: In ABPA, maintenance therapy using nebulised liposomal amphotericin-B did not reduce the risk of severe clinical exacerbation. The presence of some positive secondary outcomes creates clinical equipoise for further research., Competing Interests: Conflict of interest: C. Godet reports having received speaker fees, travel support from Pfizer, MSD; fees for board memberships from SOS Oxygène and Pulmatrix; grant support from Ohre Pharma, Pfizer, MSD, SOS Oxygène, ISIS Medical and AstraZeneca. Conflict of interest: F. Couturaud reports having received research grant support from Bristol-Myers Squibb/Pfizer and fees for board memberships or symposia from Bayer, Bristol-Myers Squibb/Pfizer, Merck Sharp & Dohme and AstraZeneca, and having received travel support from Bayer, Bristol-Myers Squibb/Pfizer, Leo Pharma, Merck Sharp & Dohme and Actelion. Conflict of interest: S. Marchand-Adam reports having received consultancy for board membership, consultancy or speaker fees and travel support from AstraZeneca, Boehringer Ingelheim, Novartis and Roche. Conflict of interest: C. Pison reports having received, outside of the submitted work, consultancy for board membership, consultancy or speaker fees, travel support from AGIR à Dom, Chiesi, Boehringer Ingelheim, GSK, SOS Oxygène, AstraZeneca and Novartis. Conflict of interest: F. Gagnadoux reports having received grants and personal fees from Resmed; personal fees and non-financial support from Boehringer Ingelheim, Nyxoah, Sefam; personal fees from Actelion, Cidelec, Novartis, and non-financial support from Asten, unrelated to the submitted work. Conflict of interest: E. Blanchard reports having received consultancy or speaker fees, travel support from Pfizer, MSD, Novartis, Gilead, Roche, Boehringer Ingelheim, SOS Oxygene and ISIS Medical. Conflict of interest: C. Taillé reports having received consulting or advisory fees from Sanofi, GSK, AstraZeneca, Novartis and Chiesi, and research grants from Sanofi and GSK, outside the submitted work. Conflict of interest: B. Philippe reports having received speaker fees, travel support from Chiesi, Novartis and Oxyvie. Conflict of interest: S. Hirschi reports having received research grant support from CSL Behring and Adiral, and fees for board membership from Boehringer Ingelheim and Roche. Conflict of interest: C. Andréjak reports having received fees for board memberships or symposia and travel support from GSK, AstraZeneca, Zambon and Insmed. Conflict of interest: A. Bourdin reports having received grants from AstraZeneca, Boehringer Ingelheim, Cephalon/TEVA, GlaxoSmithKline, Novartis and Sanofi-Regeneron; has provided consultancy for Actelion, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, MedinCell, Merck, Novartis, Roche and Sanofi-Regeneron; and has acted as an investigator or co-investigator for trials sponsored by Actelion, AstraZeneca, Boehringer Ingelheim, Chiesi, Galapagos, GlaxoSmithKline, Merck, Novartis, Roche, Sanofi-Regeneron and Vertex. Conflict of interest: C. Chenivesse reports having received grants from AstraZeneca and Santelys outside the submitted work, personal fees from ALK-Abello, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKlein, Novartis, Sanofi-Regeneron and TEVA outside the submitted work and congress support from ALK-Abello, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Pierre Fabre, Pfizer, Roche and TEVA. Conflict of interest: S. Dominique reports having received consultancy for board membership, speaker fees, travel support from Roche, Chiesi, Boehringer Ingelheim, AstraZeneca, Novartis and Actelion, outside the submitted work. Conflict of interest: L. Bassinet has nothing to disclose. Conflict of interest: M. Murris-Espin reports having received consultancy for board membership or speaker fees, or travel support, from Insmed, MSD, Pfizer, Asten, LVL, Vertex, Vivisol and Zambon. Conflict of interest: F. Rivière reports having received consultancy fees from Roche and Boehringer Ingelheim. Conflict of interest: G. Garcia reports having received grants from AstraZeneca, GlaxoSmithKline, Novartis, Sanofi-Regeneron and Chiesi; has provided consultancy for AstraZeneca, GlaxoSmithKline, Novartis and Sanofi-Regeneron; and has acted as an investigator or co-investigator for trials sponsored by AstraZeneca, GlaxoSmithKline and Sanofi-Regeneron. Conflict of interest: D. Caillaud reports having received consultancy or speaker fees, travel support from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Menarini and Novartis. Conflict of interest: F-X. Blanc has nothing to disclose. Conflict of interest: F. Goupil reports having received travel support from Aliseo/Asten Santé, GSK, Chiesi, Novartis and Actelion. Conflict of interest: A. Bergeron reports having received consultancy or speaker fees, from Pfizer, Gilead, MSD, AstraZeneca and Takeda, and grants from SOS Oxygene. Conflict of interest: A. Gondouin reports having received consultancy or speaker fees, or travel support from Roche, Boehringer Ingelheim, Vitalaire, Actelion, LFB, GSK and Pfizer. Conflict of interest: J-P. Frat reports having received grants from the French Ministry of Health, outside the submitted work; grants, personal fees and non-financial support from Fisher & Paykel HealthCare, outside the submitted work; personal fees and non-financial support from SOS Oxygène, outside the submitted work. Conflict of interest: T. Flament has nothing to disclose. Conflict of interest: B. Camara reports having received outside of the submitted work, consultancy for speaker fees, travel supports from AGIR à Dom. Conflict of interest: P. Priou received travel support from Asten Santé. Conflict of interest: A-L. Brun has nothing to disclose. Conflict of interest: F. Laurent reports having received consultancy for board membership, consultancy or speaker fees, travel support from Bayer, Roche, Chiesi, Boehringer Ingelheim, SOS Oxygène, AstraZeneca, Basilea, Novartis and Actelion. Conflict of interest: S. Ragot has nothing to disclose. Conflict of interest: J. Cadranel reports having received speaker fees from MSD and Pfizer., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

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: Evidence is accumulating that Staphylococcus aureus plays an important role as disease modifier in upper and lower airway diseases. Sensitisation to S. aureus enterotoxins (SEs) was associated with an increased risk of severe asthma in previous cross-sectional studies, but evidence from longitudinal studies is lacking. We aimed to assess associations between SE-sensitisation and the subsequent risk for asthma severity and exacerbations., Methods: This is a nested case-control study from the 20-year Epidemiological Study of the Genetics and Environment of Asthma (EGEA) cohort, including 225 adults (75 without asthma, 76 with mild asthma and 74 with severe asthma) in EGEA2 (2003-2007). For 173 of these individuals, SE-sensitisation was measured on samples collected 11 years earlier (EGEA1). Cross-sectional associations were conducted for EGEA1 and EGEA2. Longitudinal analyses estimated the association between SE-sensitisation in EGEA1 and the risk of severe asthma and asthma exacerbations assessed in the follow-up. Models were adjusted for sex, age, smoking, parental asthma/allergy and skin-prick test to house dust mite., Results: SE-sensitisation varied between 39% in controls to 58% and 76% in mild and severe asthma, respectively, in EGEA1. An adjusted cross-sectional association showed that SE-sensitisation was associated with an increased risk of severe, but not for mild asthma. SE-sensitisation in EGEA1 was associated with severe asthma (adjusted OR 2.69, 95% CI 1.18-6.15) and asthma exacerbations (adjusted OR 4.59, 95% CI 1.40-15.07) assessed 10-20 years later., Conclusion: For the first time, this study shows that being sensitised to SEs is associated with an increased subsequent risk of severe asthma and asthma exacerbations., Competing Interests: Conflict of interest: V. Siroux reports personal fees for lecturing from AstraZeneca, outside the submitted work. Conflict of interest: G. Holtappels has nothing to disclose. Conflict of interest: C. Pison reports non-financial support for meeting attendance from GSK France, AZ France, Boehringer Ingelheim and Novartis, outside the submitted work. Conflict of interest: R. Nadif has nothing to disclose. Conflict of interest: J. Bousquet reports personal fees for advisory board work, consultancy and lecturing from Chiesi, Cipla, Hikma, Menarini, Mundipharma, Mylan, Novartis, Sanofi-Aventis, Takeda, Teva and Uriach, and owns shares in KYomed-INNOV, outside the submitted work. Conflict of interest: C. Bachert has nothing to disclose. Conflict of interest: I. Sintobin has nothing to disclose., (Copyright ©ERS 2019.)

The interpretation of pulmonary function tests (PFTs) to diagnose respiratory diseases is built on expert opinion that relies on the recognition of patterns and the clinical context for detection of specific diseases. In this study, we aimed to explore the accuracy and interrater variability of pulmonologists when interpreting PFTs compared with artificial intelligence (AI)-based software that was developed and validated in more than 1500 historical patient cases.120 pulmonologists from 16 European hospitals evaluated 50 cases with PFT and clinical information, resulting in 6000 independent interpretations. The AI software examined the same data. American Thoracic Society/European Respiratory Society guidelines were used as the gold standard for PFT pattern interpretation. The gold standard for diagnosis was derived from clinical history, PFT and all additional tests.The pattern recognition of PFTs by pulmonologists (senior 73%, junior 27%) matched the guidelines in 74.4±5.9% of the cases (range 56-88%). The interrater variability of κ=0.67 pointed to a common agreement. Pulmonologists made correct diagnoses in 44.6±8.7% of the cases (range 24-62%) with a large interrater variability (κ=0.35). The AI-based software perfectly matched the PFT pattern interpretations (100%) and assigned a correct diagnosis in 82% of all cases (p<0.0001 for both measures).The interpretation of PFTs by pulmonologists leads to marked variations and errors. AI-based software provides more accurate interpretations and may serve as a powerful decision support tool to improve clinical practice., Competing Interests: Conflict of interest: M. Topalovic has nothing to disclose. Conflict of interest: N. Das has nothing to disclose. Conflict of interest: P-R. Burgel reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Novartis, Teva and Vertex, outside the submitted work. Conflict of interest: M. Daenen has nothing to disclose. Conflict of interest: E. Derom has nothing to disclose. Conflict of interest: C. Haenebalcke reports personal fees from Novartis, Chiesi, GSK and AstraZeneca, outside the submitted work. Conflict of interest: R. Janssen has nothing to disclose. Conflict of interest: H.A.M. Kerstjens has nothing to disclose. Conflict of interest: G. Liistro has nothing to disclose. Conflict of interest: R. Louis reports grants and personal fees from GSK and Novartis, personal fees from AstraZeneca, and grants from Chiesi, outside the submitted work. Conflict of interest: V. Ninane has nothing to disclose. Conflict of interest: C. Pison has nothing to disclose. Conflict of interest: M. Schlesser has nothing to disclose. Conflict of interest: P. Vercauter has nothing to disclose. Conflict of interest: C.F. Vogelmeier reports personal fees from Almirall, Cipla, Berlin-Chemie/Menarini, CSL Behring and Teva, grants and personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Grifols, Mundipharma, Novartis and Takeda, grants from German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET), Bayer Schering Pharma AG, MSD and Pfizer, outside the submitted work. Conflict of interest: E. Wouters reports personal fees for board membership from Nycomed and Boehringer, grants from AstraZeneca and GSK, and personal fees for lectures from AstraZeneca, GSK, Novartis and Chiesi, outside the submitted work. Conflict of interest: J. Wynants has nothing to disclose. Conflict of interest: W. Janssens has nothing to disclose., (Copyright ©ERS 2019.)

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.)

An irreversible loss in lung function limits the long-term success in lung transplantation. We evaluated the role of chronic exposure to ambient air pollution on lung function levels in lung transplant recipients (LTRs).The lung function of 520 LTRs from the Cohort in Lung Transplantation (COLT) study was measured every 6 months. The levels of air pollutants (nitrogen dioxide (NO 2 ), particulate matter with an aerodynamic cut-off diameter of x µm (PM x ) and ozone (O 3 )) at the patients' home address were averaged in the 12 months before each spirometry test. The effects of air pollutants on forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) in % predicted were estimated using mixed linear regressions. We assessed the effect modification of macrolide antibiotics in this relationship.Increased 12-month levels of pollutants were associated with lower levels of FVC % pred (-2.56%, 95% CI -3.86--1.25 for 5 µg·m -3 of PM 10 ; -0.75%, 95% CI -1.38--0.12 for 2 µg·m -3 of PM 2.5 and -2.58%, 95% CI -4.63--0.53 for 10 µg·m -3 of NO 2 ). In patients not taking macrolides, the deleterious association between PM and FVC tended to be stronger and PM 10 was associated with lower FEV 1 Our study suggests a deleterious effect of chronic exposure to air pollutants on lung function levels in LTRs, which might be modified with macrolides., (Copyright ©ERS 2017.)

To what extent blood granulocyte patterns may predict asthma control remains under-studied. Our aim was to study associations between blood neutrophilia and eosinophilia and asthma control outcomes in adults.Analyses were conducted in 474 asthmatics from the first follow-up of the Epidemiological Study on the Genetics and Environment of Asthma (EGEA2), including 242 asthmatics who were adults a decade earlier (EGEA1). At EGEA2, asthma control was assessed using the Global Initiative for Asthma definition (2015), and asthma exacerbations by use of urgent care or courses of oral corticosteroids in the past year. Blood EOS lo /EOS hi was defined as -3 , respectively, and NEU lo /NEU hi as -3 , respectively. Estimates were adjusted for age, sex and smoking.At EGEA2, NEU hi was associated with asthma exacerbations and poor asthma control (OR >2.10). EOS hi was associated with higher bronchial hyperresponsiveness (BHR) (OR (95% CI) 2.21 (1.24-3.97)), poor lung function (p=0.02) and higher total IgE level (p=0.002). Almost 50% of asthmatics had a persistent pattern between surveys. Persistent NEU hi was associated with poor asthma control at EGEA2 (OR (95% CI) 3.09 (1.18-7.05)). EOS hi at EGEA1 and persistent EOS hi were associated with higher BHR (OR (95% CI) 2.36 (1.10-5.07) and 3.85 (1.11-13.34), respectively), poor lung function (p<0.06) and higher immunoglobulin E level (p<10 -4 ) at EGEA2.Granulocyte patterns were differently associated with asthma outcomes, suggesting specific roles for each one, which could be tested as predictive signatures., (Copyright ©ERS 2016.)

Nutrition and metabolism have been the topic of extensive scientific research in chronic obstructive pulmonary disease (COPD) but clinical awareness of the impact dietary habits, nutritional status and nutritional interventions may have on COPD incidence, progression and outcome is limited. A multidisciplinary Task Force was created by the European Respiratory Society to deliver a summary of the evidence and description of current practice in nutritional assessment and therapy in COPD, and to provide directions for future research. Task Force members conducted focused reviews of the literature on relevant topics, advised by a methodologist. It is well established that nutritional status, and in particular abnormal body composition, is an important independent determinant of COPD outcome. The Task Force identified different metabolic phenotypes of COPD as a basis for nutritional risk profile assessment that is useful in clinical trial design and patient counselling. Nutritional intervention is probably effective in undernourished patients and probably most when combined with an exercise programme. Providing evidence of cost-effectiveness of nutritional intervention is required to support reimbursement and thus increase access to nutritional intervention. Overall, the evidence indicates that a well-balanced diet is beneficial to all COPD patients, not only for its potential pulmonary benefits, but also for its proven benefits in metabolic and cardiovascular risk., (©ERS 2014.)

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.)

Benfluorex was marketed in France until 2009, despite its similar pharmacological properties with fenfluramine and its derivatives known to be a cause of pulmonary arterial hypertension (PAH). The aim of this study is to report clinical and haemodynamic characteristics for patients suffering from pulmonary hypertension (PH) associated with benfluorex exposure that had been identified by the French PAH Network. 85 cases of PH associated with benfluorex exposure were identified by the French PAH Network from June 1999 to March 2011. Of these, 70 patients had confirmed pre-capillary PH. The median duration of exposure was 30 months, with a median of 108 months between start of exposure and diagnosis of the pulmonary vascular disease. 33% of all patients also had prior exposure to fenfluramine or dexfenfluramine, and an additional risk factor for PH was identified in 20 (30%) out of 70 patients with pre-capillary PH. A quarter of patients in this current series showed coexisting PH and mild-to-moderate cardiac valve involvement. The results of our study, together with the accumulated data regarding the known toxic effects of fenfluramine and dexfenfluramine, strongly suggest that benfluorex exposure is a potent trigger for PAH.

The purpose of this study was to estimate the prevalence of malnutrition in outpatients on long-term oxygen therapy or home mechanical ventilation, to determine the relationships between malnutrition and impairment/disability and smoking and also to identify relevant tools for routine nutritional assessment. In 744 patients (M:F 1.68, aged 65+/-15 yrs) with chronic obstructive pulmonary disease (COPD, 40%), restrictive disorders (27%), mixed respiratory failure (15%), neuromuscular diseases (13%) and bronchiectasis (5%), body mass index (BMI), fat-free mass (FFM), serum albumin, transthyretin, 6-min walking test, forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and blood gases were recorded. FFM was the most sensitive parameter for detecting malnutrition, being abnormal in 53.6% of patients, while BMI was <20 in 23.2%, serum albumin <35 g x L(-1) in 20.7%, and serum transthyretin <200 mg x L(-1) in 20%. FFM depletion predominated in neuromuscular, bronchiectasis and restrictive disorders. BMI and FFM were correlated with FEV1, FVC and 6-min walking test. In multivariate analysis a BMI<20 was related to FEV1 and smoking habits, and a low FFM to smoking, FEV1 and female sex. Malnutrition is highly prevalent in home-assisted respiratory patients and is related to causal disease, forced expiratory volume in one second, smoking and disability. Fat-free mass appeared to be the most sensitive and relevant nutritional parameter according to impairment and disability.

Nutritional status was studied in lung transplant (LT) candidates. The hypotheses were that nutritional depletion was highly prevalent and lean body mass depletion was a risk factor for a higher mortality both before and after LT. Of 78 consecutive patients listed for LT, 16 (21%) died while on the waiting list, eight (10%) were alive awaiting LT, and 54 (69%) received a graft. Mean age was 42.3+/-4.4 (mean+/-SD). Thirty-eight per cent had a diagnosis of bronchiectasis or cystic fibrosis (BRO/CF), 33% of emphysema, 20% of idiopathic pulmonary fibrosis (IPF) and 8% of primary pulmonary hypertension. Body mass index (BMI) was 20.4+/-4.3 kg.m2, weight was 87.9+/-16.6% of ideal body weight (IBW). Patients were classed into four nutritional groups according to IBW and creatinine height index (CHI): 1: weight <90% IBW and CHI <60% of predicted (28% of cases); II: weight <90% IBW and CHI > or =60% (27%); III: weight > or =90% IBW and CHI <60% (17%); IV: weight > or =90% IBW and CHI > or =60% (28%). Overall, 72% were depleted corresponding to groups 1, II and III. Lean body mass depletion occurred despite normal weight in 17% of the cases (group III). Subjects with BRO/CF were mostly in groups 1, II, III whereas IPF were concentrated in group II. Lean body mass depletion was associated with more severe hypoxaemia, reduced 6-minute walking distance and a higher mortality while awaiting. After LT, duration of mechanical ventilation, time spent in intensive care unit (ICU) was related to initial body composition. Survival after LT was lowest in group III. To conclude, nutritional depletion in lung transplant candidates is highly prevalent and should be more precisely assessed with a special reference to lean body mass since it has specific consequences both while awaiting and after lung transplant. Attempts should be made to increase lean body mass before lung transplant.

Hypoxia is well known to affect carbohydrate metabolism through its action on liver function and thus on glucose homeostasis. The aim of this study was to examine the carbohydrate, lipid and protein metabolic responses to 48 h of hypoxia, as well as the hormonal adaptations using both normoxic controls and hypoxic animals in the fasted state to standardize for the marked hypophagia observed in response to hypoxia. Hypoxia exposure (inspiratory oxygen fraction (FI,O2) = 0.1) resulted in a greater weight loss (-23 +/- 3.6% versus -16 +/- 2% in controls, p<0.001). Hypoxia plus fasting led to a significant increase in plasma glucose, lactate, insulin and catecholamine concentrations, while the increase in free fatty acid and beta-hydroxybutyrate was abolished. Changes in plasma amino acid patterns were not affected by hypoxia. Liver glycogen depletion was significantly less pronounced in the hypoxic group, while phosphoenolpyruvate carboxykinase (a key enzyme of liver gluconeogenesis) activity and transcription enhancements were abolished by hypoxia. Overall, hypoxic exposure in rats fasted for 48 h resulted in a unique pattern that differed from responses to injury or fasting per se. Oxygen seems to play a central role in the metabolic adaptation to fasting, from gene expression to weight loss. Since hypoxaemia associated with fasting has detrimental effects on nutritional balance, the present observations may be clinically relevant in the setting of acute exacerbation with hypoxaemia for chronic respiratory disease.

Nine patients, 4 with chronic obstructive pulmonary disease (COPD) and 5 with obstructive sleep apnoea syndrome (OSAS) were monitored during sleep, rest and exercise. Left ventricular ejection fraction (LVEF) was investigated using gated equilibrium 99mtechnetium ventricular scintigraphy during rapid eye movement (REM) sleep, during exercise, and during wakeful rest. Control wakeful rest periods used for comparison with a study state (either REM sleep or exercise) were always selected during the same circadian segment as that state. Myocardial stress thallium-201 scintigraphy was performed during, and 4 h after, exercise, and results were compared to a daytime rest period. Several patients had myocardial hypoperfusion despite a normal electrocardiographic (ECG) treadmill test. During REM sleep, all patients exhibited a significant change in LVEF (greater than 5%) compared to wakefulness. During exercise, 5 subjects increased their LVEF normally (greater than 5%) and 4 (1 COPD, 3 OSAS) decreased it. All patients had a similar change (increase or decrease) during REM and at maximal exercise. Our results suggest that REM sleep in COPD and in OSAS can produce a myocardial stress as great as that produced by exercise. We conclude that REM sleep, like exercise, is a state in which morbidity may become higher and that it may account for mortality in COPD and OSAS patients with compromised myocardial circulation.