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Enterovirus D68 (EV-D68) has emerged as an agent of epidemic respiratory illness and acute flaccid myelitis in the paediatric population but data are lacking in adult patients. We performed a 4.5-year single-centre retrospective study of all patients who tested positive for EV-D68 and analysed full-length EV-D68 genomes of the predominant clades B3 and D1. Between 1 June 2014, and 31 December 2018, 73 of the 11,365 patients investigated for respiratory pathogens tested positive for EV-D68, of whom 20 (27%) were adults (median age 53.7 years [IQR 34.0-65.7]) and 53 (73%) were children (median age 1.9 years [IQR 0.2-4.0]). The proportion of adults increased from 12% in 2014 to 48% in 2018 ( p = 0.01). All adults had an underlying comorbidity factor, including chronic lung disease in 12 (60%), diabetes mellitus in six (30%), and chronic heart disease in five (25%). Clade D1 infected a higher proportion of adults than clades B3 and B2 ( p = 0.001). Clade D1 was more divergent than clade B3: 5 of 19 amino acid changes in the capsid proteins were located in putative antigenic sites. Adult patients with underlying conditions are more likely to present with severe complications associated with EV-D68, notably the emergent clade D1.

Background: Chronic respiratory failure may occur as a consequence of chronic obstructive pulmonary disease (COPD) and is associated with significant morbidity and mortality. Hypoxemia is determined by underlying disease characteristics and comorbidities. Severe hypoxemia is typically only found in subjects with severe airflow obstruction (FEV 1 <50% predicted). However, how hypoxemia relates to disease characteristics is not fully understood., Methods: In the French Initiatives BPCO real-life cohort, arterial blood gases were routinely collected in most patients. Relationships between severe hypoxemia, defined by a Pa0 2 <60 mmHg (8 kPa) and clinical/lung function features, comorbidities and mortality were assessed. In subjects with severe hypoxemia, clinical characteristics and comorbidities were compared between those with non-severe versus severe airflow limitation. Classification and regression trees (CART) were used to define clinically relevant subgroups (phenotypes)., Results: Arterial blood gases were available from 887 subjects, of which 146 (16%) exhibited severe hypoxemia. Compared to subjects with a PaO2≥60 mmHg, the severe hypoxemia group exhibited higher mMRC dyspnea score, lower FEV 1 , higher RV and RV/TLC, more impaired quality of life, lower 6-minute walking distance, less frequent history of asthma, more frequent diabetes and higher 3-year mortality rate (14% versus 8%, p=0.026). Compared to subjects with Pa0 2 <60 mmHg and FEV 1 <50% (n=115, 13%), those with severe hypoxemia but FEV1≥50% predicted (n=31) were older, had higher BMI, less hyperinflation, better quality of life and a higher rate of diabetes (29% versus 13%, p=0.02). Severe hypoxemia was better related to CART-defined phenotypes than to GOLD ABCD classification., Conclusion: In this cohort of stable COPD subjects, severe hypoxemia was associated with worse prognosis and more severe symptoms, airflow limitation and hyperinflation. Compared to subjects with severe hypoxemia and severe airflow limitation, subjects with severe hypoxemia despite non-severe airflow limitation were older, had higher BMI and more diagnosed diabetes., Trial Registration: 04-479., Competing Interests: MZ reports grants and personal fees from Boehringer Ingelheim, grants and personal fees from Novartis, personal fees from Chiesi, personal fees from Astra Zeneca and personal fees from GSK outside the submitted work. PRB reports personal fees from Aptalis, personal fees from Astra-Zeneca, grants and personal fees from Boehringer Ingelheim, personal fees from Chiesi, personal fees from GSK, personal fees from Novartis, personal fees from Pfizer, personal fees from Vertex, personal fees from Zambon, personal fees from Insmed, outside the submitted work. ICF reports grants and personal fees from Boehringer Ingelheim, grants and personal fees from Novartis, and GSK outside the submitted work. GBR reports grants and personal fees from Boehringer Ingelheim, grants and personal fees from Novartis, grants and personal fees from Astra Zeneca, personal fees and non-financial support from Chiesi, outside the submitted work. PNM reports grants and personal fees from Boehringer Ingelheim, grants and personal fees from NOVARTIS, personal fees and non-financial support from Chiesi, outside the submitted work. PS reports grants and personal fees from Boehringer Ingelheim outside the submitted work. GD reports personal fees from Novartis, personal fees and grants from Astra Zeneca, personal fees from BTG/PneumRx, personal fees from Chiesi, personal fees from Boehringer Ingelheim, personal fees from GSK, outside the submitted work. TP reports personal fees from Boehringer Ingelheim, personal fees from Novartis, personal fees from GSK, personal fees from Chiesi, personal fees from Pierre Fabre, outside the submitted work. OLR reports grants and personal fees personal fees and non-financial support from Astra Zeneca, Boehringer Ingelheim, Chiesi, Lilly and Novartis; non-financial support from Glaxo Smith Kline, Correvio, Mayoli, Mylan, MSD, PulmonX, Zambon, Novartis, MundiPharma, Pfizer, Teva, Santelys Association, Vertex and Vitalaire, all outside the submitted work. GJ reports personal fees from Boehringer Ingelheim, personal fees from GSK, personal fees from Novartis, personal fees from Menarini, personal fees from Astra Zeneca, personal fees from Chiesi, outside the submitted work. PC reports personal fees from Boehringer Ingelheim, personal fees from GSK, personal fees and grants from ALK, personal fees and grants from Almirall, personal fees and grants from Boehringer-Ingelheim, personal fees from Novartis, personal fees from Teva, personal fees from Astra Zeneca, grants and personal fees from Chiesi, personal fees from Sanofi, personal fees and non-financial support from SNCF, personal fees from GlaxoSmithKline, grants and personal fees from Sanofi-Aventis, grants from Amu, outside the submitted work. JLP reports grants from iBPCO association, during the conduct of the study. DC has nothing to disclose. NR reports grants and personal fees from Boehringer Ingelheim, grants and personal fees from Novartis, grant and personal fees from Pfizer, grants and personal fees from GSK, personal fees from AstraZeneca, personal fees from Chiesi, personal fees from Sanofi, personal fees from Zambon, personal fees and grants from Boehringer Ingelheim, outside the submitted work., (© 2021 Zysman et al.)

Although the vast majority of critically endangered Grauer's gorillas (Gorilla beringei graueri) inhabit low-elevation rain forests, current insights into this ape's life history and ecology stem predominantly from 2 small populations ranging in highland habitats. Here, we provide an initial and non-exhaustive overview of food items of Grauer's gorillas in the Nkuba Conservation Area (NCA), a lower-elevation (500-1,500 m) forest located between Kahuzi-Biega National Park and Maiko National Park in the Democratic Republic of the Congo. Community-based conservation efforts at the NCA aim to protect a population of unhabituated Grauer's gorillas, which we have studied since 2014. Between 2014 and 2020, we simultaneously tracked 1-3 gorilla groups and recorded a total of 10,514 feeding signs on at least 100 plant species, ants, termites, and fungi. Vegetative plant parts (plant stems, leaves, pith, bark, and roots), especially of Marantaceae and Fabaceae, made up close to 90% of recorded feeding signs, with fruit accounting for most of the remainder and a small (<1%) number of feeding signs on invertebrates and fungi. We found that the most frequently recorded food items were consumed year-round, though fruit intake seems to peak in the September-December wet season, possibly reflecting patterns in fruit phenology. The diet of Grauer's gorillas in the NCA differed from that of Grauer's gorillas in highland habitat and instead showed similarities with Grauer's gorillas at the lowland forest of Itebero and with western lowland gorillas (G. gorilla), which live under ecologically comparable conditions., (© 2021 S. Karger AG, Basel.)

To accurately determine the space use of animals, we need to follow animal movements over prolonged periods, which is especially challenging for the critically endangered Grauer's gorillas (Gorilla beringei graueri) in eastern Democratic Republic of the Congo (DRC). As a consequence, we know little about Grauer's gorillas, particularly from the lower elevational parts of their range. Between 2016 and 2018, we tracked unhabituated Grauer's gorillas in lowland forests (500-1,000 m a.s.l.), at the community-managed Nkuba Conservation Area in Nord Kivu (DRC) to provide estimates of daily travel distances (DTD), daily displacement distances (DDD), and the linearity of recorded paths expressed as the Linearity Index (LI): DDD/DTD. We found an average DTD of ∼1.3 km (range 0.05-5.0 km), with temporal variation among monthly averages; specifically, an increase in travel distance over the June-August dry season resulting in peak travel distances at the beginning of the September-December wet season. Daily displacements showed similar temporal variation, which resulted in a lack of obvious temporal patterns in LI. We conclude that the movement patterns of Grauer's gorillas in lowland forests, which are characterized by larger DTD than those of Grauer's gorillas that inhabit highland habitats, show similarity to travel distances of other predominantly frugivorous gorillas. Moreover, the observed temporal patterns in space use may be tentatively linked to temporal changes in fruit availability or consumption. These observations have consequences for our understanding of the ecological role that Grauer's gorillas play and provide baseline data to estimate current and future distributions, abundances, and carrying capacities of this highly threatened animal., (© 2021 S. Karger AG, Basel.)

Respiratory pathogens are expected to spread through social contacts, but outbreaks often occur quickly and unpredictably, making it challenging to simultaneously record social contact and disease incidence data, especially in wildlife. Thus, the role of social contacts in the spread of infectious disease is often treated as an assumption in disease simulation studies, and few studies have empirically demonstrated how pathogens spread through social networks. In July-August 2015, an outbreak of respiratory disease was observed in a wild chimpanzee community in Kibale National Park, Uganda, during an ongoing behavioral study of male chimpanzees, offering a rare opportunity to evaluate how social behavior affects individual exposure to socially transmissible diseases. From May to August 2015, we identified adult and adolescent male chimpanzees displaying coughs and rhinorrhea and recorded 5-m proximity data on males (N = 40). Using the network k-test, we found significant relationships between male network connectivity and the distribution of cases within the network, supporting the importance of short-distance contacts for the spread of the respiratory outbreak. Additionally, chimpanzees central to the network were more likely to display clinical signs than those with fewer connections. Although our analyses were limited to male chimpanzees, these findings underscore the value of social connectivity data in predicting disease outcomes and elucidate a potential evolutionary cost of being social.

Introduction: The obesity hypoventilation syndrome (OHS) has an increasing prevalence. Compliance with first-line non-invasive ventilation has not been evaluated, taking into account patients' initial comorbidities. This study consisted of identification of the factors associated with compliance with non-invasive ventilation during the first six months of use., Methods: A monocentric retrospective study, gathering patients from the pneumology department of Gabriel-Montpied hospital in Clermont-Ferrand, from April 2010 to October 2019. The analysis was carried-out through the collection of computerised medical records (age, mode of entry, patient comorbidities) and compliance reports (average daily hours of use) provided by the regional service provider for the Auvergne area (AIRRA)., Results: Being hospitalized for an acute exacerbation and being older than seventy-five years were factors associated with an improved compliance to non-invasive ventilation, with an increase of 1.47h/d and 2.73h/d (P value: 0.018 and 0.02, respectively). Moreover, patients with obstructive sleep apnea hypopnea syndrome and recipients of therapeutic education may prove more compliant over time., Conclusion: Age greater than seventy-five years and being hospitalized for an acute exacerbation are predictors of better use of non-invasive ventilation in OHS., (Copyright © 2020 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Density-dependent processes such as competition for resources, migration, predation, and disease outbreaks limit the growth of natural populations. The analysis of 50 years of mountain gorilla data reveals that social behavior changes observed at high group density may also affect population growth in social species. A sudden increase in social group density observed in 2007 caused a threefold increase in the rate of violent encounters between social units (groups and solitary males). A fivefold increase in the rate of infanticide and seven cases of lethal fights among mature males were subsequently recorded, and the annual subpopulation growth rate declined by half between 2000 and 2017. The increase in infanticide alone explains 57% of this decline. These findings highlight the complex relationship between population density and growth in social species and hold important implications for the management of island populations., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Background/objectives: Sarcopenia defined by the association of skeletal muscle mass depletion and a decreased physical performance is underdiagnosed in chronic obstructive pulmonary disease (COPD) patients. The objective was to assess prevalence of sarcopenia and malnutrition in hospitalized COPD patients during an acute exacerbation, after 6 months follow-up and the 1-year survival., Subjects/methods: Hospitalized COPD patients were recruited for the assessment of body composition, handgrip strength, respiratory function, and maximal inspiratory and expiratory pressures (MIP and MEP), during hospitalization and 6 months later. Sarcopenia was defined according to the criteria of the European Working Group on Sarcopenia in Older Adults, malnutrition was defined according to French criteria 2007. Survival data were collected 12 months after hospitalization., Results: We analyzed data from 54 patients, aged 68 ± 9 years and BMI 26.9 ± 7.8 kg/m 2 , with an average FEV1 of 1.13 ± 0.49 l (45 ± 16% predicted value). Sarcopenia and malnutrition prevalence were, respectively, 48% and 52% during hospitalization, 30% and 30% after 6 months. MIP and MEP were lower in sarcopenic patients (p = 0.01 and 0.009, respectively). In multivariate analysis, skeletal muscle mass index and MIP were positively correlated at 6 months' follow-up (r = 0.40, p = 0.04). The 1-year survival rate was lower in sarcopenic patients (65 vs 86%, p = 0.03), particularly when malnutrition was associated (p = 0.02)., Conclusions: Sarcopenia in COPD patients is highly prevalent during and after recovery of an acute exacerbation, exposing to lower survival. A multimodal management is required to treat sarcopenia and improve prognosis.

Accurately quantifying species' area requirements is a prerequisite for effective area-based conservation. This typically involves collecting tracking data on species of interest and then conducting home-range analyses. Problematically, autocorrelation in tracking data can result in space needs being severely underestimated. Based on the previous work, we hypothesized the magnitude of underestimation varies with body mass, a relationship that could have serious conservation implications. To evaluate this hypothesis for terrestrial mammals, we estimated home-range areas with global positioning system (GPS) locations from 757 individuals across 61 globally distributed mammalian species with body masses ranging from 0.4 to 4000 kg. We then applied block cross-validation to quantify bias in empirical home-range estimates. Area requirements of mammals <10 kg were underestimated by a mean approximately15%, and species weighing approximately100 kg were underestimated by approximately50% on average. Thus, we found area estimation was subject to autocorrelation-induced bias that was worse for large species. Combined with the fact that extinction risk increases as body mass increases, the allometric scaling of bias we observed suggests the most threatened species are also likely to be those with the least accurate home-range estimates. As a correction, we tested whether data thinning or autocorrelation-informed home-range estimation minimized the scaling effect of autocorrelation on area estimates. Data thinning required an approximately93% data loss to achieve statistical independence with 95% confidence and was, therefore, not a viable solution. In contrast, autocorrelation-informed home-range estimation resulted in consistently accurate estimates irrespective of mass. When relating body mass to home range size, we detected that correcting for autocorrelation resulted in a scaling exponent significantly >1, meaning the scaling of the relationship changed substantially at the upper end of the mass spectrum., (© 2020 The Authors. Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

Endothelial dysfunction is a hallmark of tissue injury and is believed to initiate the development of vascular diseases. Sphingosine-1 phosphate receptor-1 (S1P 1 ) plays fundamental physiological roles in endothelial function and lymphocyte homing. Currently available clinical molecules that target this receptor are desensitizing and are essentially S1P 1 functional antagonists that cause lymphopenia. They are clinically beneficial in autoimmune diseases such as multiple sclerosis. In patients, several side effects of S1P 1 desensitization have been attributed to endothelial damage, suggesting that drugs with the opposite effect, namely, the ability to activate S1P 1, could help to restore endothelial homeostasis. We found and characterized a biased agonist of S1P 1 , SAR247799, which preferentially activated downstream G protein signaling to a greater extent than β-arrestin and internalization signaling pathways. SAR247799 activated S1P 1 on endothelium without causing receptor desensitization and potently activated protection pathways in human endothelial cells. In a pig model of coronary endothelial damage, SAR247799 improved the microvascular hyperemic response without reducing lymphocyte numbers. Similarly, in a rat model of renal ischemia/reperfusion injury, SAR247799 preserved renal structure and function at doses that did not induce S1P 1 -desensitizing effects, such as lymphopenia and lung vascular leakage. In contrast, a clinically used S1P 1 functional antagonist, siponimod, conferred minimal renal protection and desensitized S1P 1 These findings demonstrate that sustained S1P 1 activation can occur pharmacologically without compromising the immune response, providing a new approach to treat diseases associated with endothelial dysfunction and vascular hyperpermeability., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Telomeres are nucleoprotein structures at the end of chromosomes. The telomerase complex, constituted of the catalytic subunit TERT, the RNA matrix hTR and several cofactors, including the H/ACA box ribonucleoproteins Dyskerin, NOP10, GAR1, NAF1 and NHP2, regulates telomere length. In humans, inherited defects in telomere length maintenance are responsible for a wide spectrum of clinical premature aging manifestations including pulmonary fibrosis (PF), dyskeratosis congenita (DC), bone marrow failure and predisposition to cancer. NHP2 mutations have been so far reported only in two patients with DC. Here, we report the first case of Høyeraal-Hreidarsson syndrome, the severe form of DC, caused by biallelic missense mutations in NHP2. Additionally, we identified three unrelated patients with PF carrying NHP2 heterozygous mutations. Strikingly, one of these patients acquired a somatic mutation in the promoter of TERT that likely conferred a selective advantage in a subset of blood cells. Finally, we demonstrate that a functional deficit of human NHP2 affects ribosomal RNA biogenesis. Together, our results broaden the functional consequences and clinical spectrum of NHP2 deficiency., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Humans and other apes represent magnitudes spatially, demonstrated by their responding faster and more accurately to one side of space when presented with small quantities and to the other side of space when presented with large quantities. This representation is flexible and shows substantial variability between cultural groups in humans and between and within individuals in great apes. In contrast, recent findings suggest that chicks show a spatial representation of magnitude that is highly lateralized and inflexible, implying a qualitatively different underlying representation than in primates. Using methods similar to those used with great apes and humans, we trained adult domestic pigeons ( Columba livia ) and blue jays ( Cyanocitta cristata ) to select the smaller (or larger) of two nonadjacent quantity arrays; later, this task was reversed. At test, birds were presented with novel probe pairs consisting of adjacent quantity pairs (e.g., 2 vs. 3). Both species showed robust evidence for a flexible spatial representation of magnitude with considerable individual variability in the orientation of this representation. These results are not consistent with an inflexible, lateralized, left-to-right representation of magnitude in birds, but are consistent with the flexible spatial representation of magnitude observed in apes and humans. We conclude that the tendency to organize quantities spatially may be a fundamental and evolutionarily ancient feature of cognition that is widespread among vertebrates. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Background: Temporal ecological studies have shown that outdoor moulds are associated with severe asthma exacerbations, as emergency department visits or hospitalisations. The aim of this was to assess the associations between daily sales of short-acting β2-agonists (SABA), a specific and frequent treatment for control of mild asthma exacerbations in children and young adults, and outdoor mould concentrations in the central France area over a 5 year period., Methods: The relationship between daily changes in mould (25 species) concentrations and daily SABA sales within a population of patients aged 6 to 39 years in a middle-size town of central France (approximately 127,000) was obtained from social security database and analysed with generalized additive models, taking into account confounding factors (air pollution, weather conditions, pollen counts and trend)., Results: Daily SABA sales (mean, SD) rose from 17.3 (9.7) in 2010 to 22.7 (12) in 2015. The relative risk (RR [95% CI]) of SABA sales associated with an interquartile increase in mould concentration was significant in the whole population for Alternaria 1.06 [1.002-1.12]. When the influence of age and sex was accounted for, the relationship was significant only in 6-12 years old males for Alternaria 1.21 [1.04-1.41] and Aspergillus - Penicillium 1.08 [1.04-1.12]., Conclusions: Daily SABA sales are positively associated with Alternaria spores in the general population of children and young adults. The association between daily SABA sales and temporal changes to Alternaria and Aspergillus - Penicillium in male children indicate that outdoor moulds contribute to asthma morbidity., Competing Interests: Competing interestsDC has received research grant support and/or speaker/consulting fees from ALK-Abello, Astra-Zeneca, Boehringer-Ingelheim, Chiesi, Novartis and GSK. DM has received speaker/consulting fees from Astra-Zeneca, Boehringer-Ingelheim, Chiesi, Mylan and Roche. CS, SM, ND and MT have no interest to declare., (© The Author(s) 2019.)

Risk of a fall is increased in individuals with chronic obstructive pulmonary disease (COPD), and is usually evaluated using the Berg Balance Scale (BBS), but this is difficult to perform in everyday clinical practice. We aimed to prospectively predict short-term fall recurrence in COPD patients using a predetermined cut-off value of the Timed Up and Go test (TUG). In stable COPD patients, we collected self-reported records of the number of falls in the previous year, and measured TUG and BBS scores for each individual. Records of fall recurrence were obtained prospectively at 6-months after the initial evaluation. Among the 50 patients recruited, 23 (46%) had at least one fall during the past year. The optimal diagnosis value for the TUG to detect a fall was 10.9 s with a sensitivity of 100% and a specificity of 97%. A cut-off of 11 s predicted fall recurrence with high sensitivity and specificity (93% and 74%, respectively). The TUG as well as the BBS score detected fallers, and a cut-off value of 11 s predicted fall recurrence. TUG could be easily incorporated into the scheduled functional evaluations of COPD patients, could predict the risk of a fall and when appropriate, could guide specific balance training exercises to prevent fall.

Introduction: Few investigations have related objective assessments of indoor air pollutants to respiratory health in farmers, in spite of the many rural environmental hazards to which they are exposed. Chemical air pollution has been particularly neglected., Objective: We investigated the relationships of indoor exposure to particulate matter (PM) and volatile organic compounds (VOCs) to respiratory health in farmers., Methods: Nineteen VOCs (5 families) and PM (from ultrafine to total suspended particles (TSP)) were objectively assessed in dwellings and workplaces in 109 French farmers during a week. To take into account multiple exposures, scores of exposure were computed for total VOCs and VOCs families. Individuals filled a standardized questionnaire and underwent spirometry with bronchodilation test., Results: On average, VOCs concentrations were higher in dwellings than in workplaces. The reverse was observed for PM. When considering the mean concentrations of air pollutants for the whole farm (dwellings + workplaces), asthma (9.3%) was positively associated with elevated exposure to benzene (adjusted odds-ratio (ORa) = 6.64, 95%CI: 1.56-28.27), trichloroethylene (4.80, 1.00-23.30) and halogenated hydrocarbons score (2.9, 95% 1.3-6.8). Early airway obstruction (FEF 25-75  < 80%, with normal FEV 1 and FVC and FEV/FVC ≥ 70%) (29.8%) was related to elevated exposure to 2-butoxyetylacetate (11.49, 1.55-85.37) and glycol ethers score (2.0; 1.0-4.1) in the whole farm and to PM 2.5 (ORa = 5.26, 95% CI: 1.09-25.28) in the granary/stable. The risk of Chronic Obstructive Pulmonary Diseases (FEV/FVC < 70%) (COPD) (4.26%) was found to be larger with elevated exposure to aldehydes (OR = 3.95, 1.09-14.26)., Conclusion: Indoor chemical air pollution is detrimental to farmers' respiratory health. More epidemiological investigations with detailed exposure assessments and clinical measures of respiratory effects are needed in rural settings to corroborate these findings., Competing Interests: Competing interestsThe authors report no conflicts of interest. IAM is Associate Editor of Multidisciplinary Respiratory Medicine., (© The Author(s). 2019.)

The African montane bamboo Yushania alpina provides both habitat and food for many species in the Albertine Rift region. In Volcanoes National Park (VNP), Rwanda, it is especially important as a key food resource for the Endangered mountain gorilla Gorilla beringei beringei and Endangered golden guenon Cercopithecus mitis kandti. We examined temporal and spatial variation in bamboo shoots regeneration and consumption by primates, monitored between 2013 and 2018 in 82 16-m 2 plots located along transects in VNP. Our analyses revealed a decline in vegetative regeneration of bamboo in recent years, which is mirrored by a decline in bamboo shoot consumption by primates; but an increase in proportional intake. Local declines in regeneration are potentially due to high intensities of herbivory, decreased amounts of rainfall during growing seasons, and natural processes that form part of the life cycle of bamboo. Moreover, spatial variation in bamboo regeneration can be explained by elevation, as well as by stand-level variation in soil acidity, vegetation density, and the density of dead bamboo culms. We discuss the potential mechanisms underlying observed temporal and spatial variations and outline possible effects of a decline in bamboo regeneration for primates and other aspects of biodiversity in VNP.

Background: The 6-min walk test (6MWT) allows exercise tolerance to be assessed, and it has a significant prognostic value in COPD. The goal of this study was to analyse the determinants (obtained in routine practice) of a low 6-min walking distance (6MWD) and exercise-induced desaturation (EID) in COPD, including comorbidities. Methods: Patients were recruited from the real-life French COPD cohort "Initiatives BPCO". A low 6MWD was defined as <350 m. EID was defined by a minimum pulse oxygen saturation (SpO2)<90% and delta SpO2≥4% from baseline. Multivariate logistic regression analyses assessed the influence on 6MWD and EID of age, sex, obesity (body mass index, BMI >30 kg/m 2 ), low BMI (BMI <18.5 kg/m 2 ), modified Medical Research Council (mMRC) dyspnea scale, FEV1% pred, FVC % pred, hyperinflation and comorbidities including cardiovascular diseases. Results: Among 440 patients with available 6MWT data, a 6MWD <350 m was found in 146 patients (33%), which was positively associated in multivariate analyses with age and mMRC and negatively with resting SpO2 and FVC % pred (rescaled r 2 =0.34), whereas no comorbidity was associated with a low 6WMD. EID was found in 155 patients (35%). This was positively associated with hypertension and negatively with age, obesity, FEV1% pred and resting SpO2 (rescaled r 2 =0.37). Conclusion: 6MWD and EID exhibit different determinants in COPD with a minor impact of comorbidities limited to hypertension in EID and to obesity, which was unexpectedly associated with less EID. Other variables including age, routine resting lung function and SpO2 were weakly associated with 6MWD and EID. Altogether, these results suggest that 6MWT performance remains difficult to predict with routine clinical/functional parameters., Competing Interests: Dr Thierry Perez reports personal fees from Boehringer Ingelheim, Novartis, GSK, and Chiesi, and grants from Astra Zeneca, outside the submitted work. Professor Gaétan Deslée reports grants and personal fees from BTG/PneumRx; grants from Nuvaira; personal fees from Chiesi, grants and personal fees from AstraZeneca, outside the submitted work. Professor Pierre Régis Burgel reports personal fees from Astra-Zeneca, Boehringer Ingelheim, Chiesi, GSK, Pfizer, Teva, Vertex, and Zambon, outside the submitted work. Professor Denis Caillaud has nothing to disclose. Dr Olivier Le Rouzic reports personal fees and non-financial support from AstraZeneca, Boehringer Ingelheim, Chiesi, Lilly, Novartis, and PulmonX; non-financial support from GlaxoSmithKlein,, outside the submitted work. Dr Maeva Zysman reports personal fees and non-financial support from Boehringer ingelheim, during the conduct of the study; grants and personal fees from Novartis, grants from Fondation pour la recherche medicale; grants from Astra Zeneca; personal fees from Chiesi, outside the submitted work. Dr Roger Escamilla has nothing to disclose. Dr Gilles Jebrak has nothing to disclose. Professor Pascal Chanez has nothing to disclose. Dr Isabelle Court-Fortune reports grants and personal fees from Boehringer Ingelheim, during the conduct of the study. Dr Graziella Brinchault-Rabin has nothing to disclose. Dr Pascale Nesme-Meyer reports personal fees from Boehringer Ingelheim, outside the submitted work. Mr Jean Louis Paillasseur reports grants from iBPCO association, during the conduct of the study. Professor Nicolas Roche reports grants from Boehringer Ingelheim (France), during the conduct of the study. The authors report no other conflicts of interest in this work.

Humans were once considered unique in having a concept of death but a growing number of observations of animal responses to dying and dead conspecifics suggests otherwise. Complex arrays of behaviors have been described ranging from corpse removal and burial among social insects to quiet attendance and caregiving among elephants and primates. Less frequently described, however, are behavioral responses of individuals from different age/sex classes or social position toward the death of conspecifics. We describe behavioral responses of mountain gorillas ( Gorilla beringei beringei ) to the deaths of a dominant silverback and a dominant adult female from the same social group in Volcanoes National Park in Rwanda and the responses of Grauer's gorillas ( Gorilla b. graueri ) to the corpse of an extra-group silverback in Kahuzi-Biega National Park, Democratic Republic of Congo. In gorillas, interactions between groups or with a lone silverback often result in avoidance or aggression. We predicted that: (i) more individuals should interact with the corpses of same-group members than with the corpse of the extra-group silverback; (ii) adult females with infants should avoid the corpse of the extra-group silverback; and (iii) in the mountain gorilla cases, individuals that shared close social relationships with the dead individual should spend more time with the corpse than other individuals in the group. We used a combination of detailed qualitative reports, photos, and videos to describe all occurrences of affiliative/investigative and agonistic behaviors observed at the corpses. We observed similar responses toward the corpses of group and extra-group individuals. Animals in all three cases showed a variety of affiliative/investigative and agonistic behaviors directed to the corpses. Animals of all age/sex classes interacted with the corpses in affiliative/investigative ways but there was a notable absence of all adult females at the corpse of the extra-group silverback. In all three cases, we observed only silverbacks and blackbacks being agonistic around and/or toward the corpses. In the mountain gorilla cases, the individuals who spent the most time with the corpses were animals who shared close social relationships with the deceased. We emphasize the similarity in the behavioral responses around the corpses of group and extra-group individuals, and suggest that the behavioral responses were influenced in part by close social relationships between the deceased and certain group members and by a general curiosity about death. We further discuss the implications close interactions with corpses have for disease transmission within and between gorilla social groups., Competing Interests: Amy Porter, Winnie Eckardt, Veronica Vecellio, Urbain Ngobobo and Tara Stoinski are employed by The Dian Fossey Gorilla Fund International. Damien Caillaud is affiliated with the Fossey Fund.

Introduction: Short peripheral intravenous catheters (PVCs) are the most frequently used invasive medical devices in hospitals. Unfortunately, PVCs often fail before the end of treatment due to the occurrence of mechanical, vascular or infectious complications, which prolongs hospitalisation and increases healthcare costs and mortality.Prevention of these complications is mainly based on the respect of hygiene rules and the use of biocompatible catheters. In critically ill patients, 2% chlorhexidine-alcohol is superior to 5% povidone iodine-alcohol for skin preparation before central venous and arterial catheters; whether this finding can be extended to PVC inserted in the wards remains speculative. Similarly, the use of new technologies such as catheters designed to minimise blood exposure, zero-reflux needleless connectors, disinfecting caps and flushing PVCs before and after each medication administration to maintain catheter patency are of theoretical interest to prevent PVC failure, but little scientific data support their routine use., Methods and Analysis: The CLEAN 3 study is an open-label, single-centre, randomised, two-by-two factorial trial. One thousand patients visiting our emergency department and requiring hospital admission in the wards will be randomised to one of four strategies according to skin preparation and devices used. The two primary endpoints will be (1) the incidence of infectious complications related to the catheters (colonisation, local infection or bloodstream infection) and (2) the time between catheter insertion and catheter failure defined as any premature removal of PVC before end of treatment, other than for routine replacement., Ethics and Dissemination: This protocol has been approved by an independent ethics committee and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals., Trial Registration Number: EudraCT 2018-A02535-50; NCT03757143., Competing Interests: Competing interests: OM received grant support and honoraria for giving lectures from Becton Dickinson., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The objective of this panel study was to document the relationship between exposure to cypress pollen and allergic symptoms., Methods: The study group included 47 patients with allergy to cypress pollen who completed a daily diary and a weekly evaluation of quality of life (QoL) during the cypress pollen season. Different patients were included in three consecutive pollen seasons: 2014-2015, 2015-2016, and 2016-2017. Daily cypress pollen counts were obtained from the National Aerobiological Network. Air pollution and meteorological data were recorded on a daily basis. The pollen-symptoms relationship was quantified by calculating odds ratios for an increase of 1 log of grains of pollen/m3, taking into account potential confounding factors. The QoL score was expressed with a beta coefficient that increased with 1 grain of pollen/m3., Results: There was a marked increase in rhinitis and ocular symptoms during the pollen season, with a plateau effect at high levels of exposure, but no relationship with bronchial symptoms. The QoL score had a linear and significant relationship with the cypress pollen count. We did not detect any threshold level., Conclusion: This panel study demonstrated a significant association between exposure to cypress pollens and allergic symptoms, with a plateau effect for high exposures., (© 2019 S. Karger AG, Basel.)

Background: Outdoor moulds are classically associated with exacerbations of asthma., Objective: The aim of this paper was to examine nasal allergy morbidity by studying the short-term relationship between mould spore exposure and daily sales of reimbursable anti-allergic treatment in central France., Methods: The relationship between daily changes in mould concentrations and daily sales obtained from the national healthcare database was analysed with generalized additive models, taking into account confounding factors such as air pollution, weather conditions, pollen counts, and days of the week., Results: During the study, the average total yearly number of treated people was around 10 000 over approximately 230 000 surveyed. The relative risk (95% CI confidence interval) of sales of oral antihistamines with topical treatment associated with an interquartile increase in mould concentration was significant for Cladosporium 1.079 [1.019-1.142] and Aspergillus-Penicillium (Asp-Pen) 1.051 [1.021-1.082] in the whole population. When the influence of age and sex was considered, the relationship was significant only in male children aged 0-12 years and those aged between 13 and 49 years for Cladosporium: 1.256 [1.081-1.460] and 1.151 [1.063-1.245], respectively. The relationship was also significant for Asp-Pen: 1.038 [1.003-1.075] for those aged between 13 and 49 years and 1.056 [1.007-1.108] for adults over 50 years of age., Conclusion: The association between prescribed daily sales of oral antihistamines with topical treatment sales is associated with temporal changes to Cladosporium and Aspergillus-Penicillium in the whole population. When the influence of age and sex was considered, these two moulds contributed to prescribed medication sales only in the male general population., (© 2018 John Wiley & Sons Ltd.)

The proportion of moldy housing in France is around 20%. It is not simple to establish that a health impact of mold is not allergic, because the identification of allergy is itself difficult. Moreover, exposure to molds and their metabolites may have a protective effect. Non-allergic health impacts may occur due to the multiple aerocontaminants found in damp or mold-containing dwellings: glucans, microbial volatile organic compounds, mycotoxins, bacteria and endotoxins. The heath impacts of indoor mold have been addressed by numerous toxicologic and epidemiologic investigations, the results of which have been summarized in three notable reports. These conclude that mold exposure is linked to a risk of ENT and bronchial symptoms, both the genesis and exacerbation of asthma and, lastly, hypersensitivity pneumonitis. Finally, other studies highlight the protective role of fungal metabolites with respect to asthma and allergy. Pulmonologists should be aware of these data, which can be useful in clinical practice and also in legal work., (Copyright © 2018 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Starting from the Institute of Medicine (IOM) and World Health Organization (WHO) reports, this review provides an overview of the literature published from 2006 to 2017 on the associations between indoor mould exposure and asthma and rhinitis separately in children and adults with a focus on longitudinal epidemiological studies.A systematic search of peer-reviewed literature was performed, including systematic reviews and meta-analyses, longitudinal, incident case-control and panel studies. 61 publications were identified reporting visible mould or mould odour or quantitative assessment of culturable fungi or mould species.In children, visible mould and mould odour were associated with the development and exacerbations of asthma, providing sufficient evidence of a causal relationship. Results from population-based studies in adults were too few and divergent to conclude at more than a limited level of evidence. Exposure to mould in a work building was associated with the incidence and exacerbations of occupational asthma, and we concluded at a sufficient evidence for an association. Systematic reviews, meta-analyses and longitudinal studies on the relationships between mould exposure and allergic rhinitis provide sufficient evidence of an association.This review extended the conclusions of the IOM and WHO reports, and highlighted the need for further longitudinal studies on asthma in adults, and on rhinitis., Competing Interests: Conflict of interest: None declared., (Copyright ©ERS 2018.)

Species and populations are disappearing at an alarming rate as a direct result of human activities. Loss of genetic diversity associated with population decline directly impacts species' long-term survival. Therefore, preserving genetic diversity is of considerable conservation importance. However, to assist in conservation efforts, it is important to understand how genetic diversity is spatially distributed and how it changes due to anthropogenic pressures. In this study, we use historical museum and modern faecal samples of two critically endangered eastern gorilla taxa, Grauer's (Gorilla beringei graueri) and mountain gorillas (Gorilla beringei beringei), to directly infer temporal changes in genetic diversity within the last century. Using over 100 complete mitochondrial genomes, we observe a significant decline in haplotype and nucleotide diversity in Grauer's gorillas. By including historical samples from now extinct populations we show that this decline can be attributed to the loss of peripheral populations rather than a decrease in genetic diversity within the core range of the species. By directly quantifying genetic changes in the recent past, our study shows that human activities have severely impacted eastern gorilla genetic diversity within only four to five generations. This rapid loss calls for dedicated conservation actions, which should include preservation of the remaining peripheral populations.

Objectives: The critically endangered Grauer's gorilla (Gorilla beringei graueri) has experienced an estimated 77% population decline within a single generation. Although crucial for informed conservation decisions, there is no clear understanding about population structure and distribution of genetic diversity across the species' highly fragmented range. We fill this gap by studying several core and peripheral Grauer's gorilla populations throughout their distribution range., Materials and Methods: We generated genetic profiles for a sampling of an unstudied population of Grauer's gorillas from within the species' core range at 13 autosomal microsatellite loci and combined them with previously published and newly generated data from four other Grauer's gorilla populations, two mountain gorilla populations, and one western lowland gorilla population., Results: In agreement with previous studies, the genetic diversity of Grauer's gorillas is intermediate, falling between western lowland and mountain gorillas. Among Grauer's gorilla populations, we observe lower genetic diversity and high differentiation in peripheral compared with central populations, indicating a strong effect of genetic drift and limited gene flow among small, isolated forest fragments., Discussion: Although genetically less diverse, peripheral populations are frequently essential for the long-term persistence of a species and migration between peripheral and core populations may significantly enrich the overall species genetic diversity. Thus, in addition to central Grauer's gorilla populations from the core of the distribution range that clearly deserve conservation attention, we argue that conservation strategies aiming to ensure long-term species viability should include preserving peripheral populations and enhancing habitat connectivity., (© 2018 Wiley Periodicals, Inc.)

Mould spores constitute the largest portion of biologic particulate matter suspended in the outdoor atmosphere. There is no universal method for collecting airborne mould spores. The most used sampler, Hirst's apparatus, operates continuously and gives results in individual spores per cubic metre of air. Spore concentrations depend on available substrates, human activities such as agriculture, season, diurnal meteorological variations and climate changes. Under natural conditions, concentrations of over 100,000 spores per cubic metre are not exceptional. Cladosporium is the most commonly identified outdoor mould. The association between respiratory health and outdoor mould spore exposure has been assessed in clinical studies, and also by cross-sectional, and less often longitudinal, epidemiological studies. The relationship between asthma exacerbations and specific mould spores has been demonstrated in longitudinal studies. Cross sectional studies have related measurements of mould spore concentrations to severity of bronchial symptoms, drug consumption and peak-flow measurements in groups of asthmatic subjects. Ecological time-series studies use daily indicators of asthma exacerbations (emergency room visits, hospitalizations) within the general population. The moulds mainly incriminated are Cladosporium and Alternaria. They are associated with seasonal, but also perennial, asthma and rhinitis. Further studies are needed to better assess the impact of outdoor moulds on health, particularly basidiomycetes. Studies with molecular biology tools are probably a way forward., (Copyright © 2018 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

The overarching goals of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) are to enable European citizens to lead healthy, active and independent lives whilst ageing. The EIP on AHA includes 74 Reference Sites. The aim of this study was to transfer innovation from an app developed by the MACVIA-France EIP on AHA reference site (Allergy Diary) to other reference sites. The phenotypic characteristics of rhinitis and asthma multimorbidity in adults and the elderly will be compared using validated information and communication technology (ICT) tools (i.e. the Allergy Diary and CARAT: Control of Allergic Rhinitis and Asthma Test) in 22 Reference Sites or regions across Europe. This will improve the understanding, assessment of burden, diagnosis and management of rhinitis in the elderly by comparison with an adult population. Specific objectives will be: (i) to assess the percentage of adults and elderly who are able to use the Allergy Diary, (ii) to study the phenotypic characteristics and treatment over a 1-year period of rhinitis and asthma multimorbidity at baseline (cross-sectional study) and (iii) to follow-up using visual analogue scale (VAS). This part of the study may provide some insight into the differences between the elderly and adults in terms of response to treatment and practice. Finally (iv) work productivity will be examined in adults., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Humans mentally represent magnitudes spatially; we respond faster to one side of space when processing small quantities and to the other side of space when processing large quantities. We determined whether spatial representation of magnitude is a fundamental feature of primate cognition by testing for such space-magnitude correspondence in gorillas and orangutans. Subjects picked the larger quantity in a pair of dot arrays in one condition, and the smaller in another. Response latencies to the left and right sides of the screen were compared across the magnitude range. Apes showed evidence of spatial representation of magnitude. While all subjects did not adopt the same orientation, apes showed consistent tendencies for spatial representations within individuals and systematically reversed these orientations in response to reversal of the task instruction. Results suggest that spatial representation of magnitude is phylogenetically ancient and that consistency in the orientation of these representations in humans is likely culturally mediated., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In patients with COPD, there is controversy regarding the association of blood eosinophil (Eos) levels with 1) exacerbation frequency and 2) the effect of inhaled corticosteroids for prevention of exacerbations. To determine whether Eos define subgroups of patients exhibiting attributes of COPD clinical phenotypes, we compared clinical features and mortality rates in COPD patients from the Initiatives BPCO French cohort categorized using different thresholds of blood Eos levels. The following data were collected at inclusion: medical and smoking history, occupational exposures, dyspnea, cough and sputum production, exacerbations in the previous year, history of allergy and asthma, nasal symptoms, body mass index, St George Respiratory Questionnaire (SGRQ) total score, post-bronchodilator spirometry, comorbidities, and medications. Three-year survival between groups was compared using Kaplan-Meier analysis. Three sets of analyses were performed to compare patients with ≥2% versus <2%, ≥3% versus <3%, and ≥4% versus <4% Eos. Eos was available in 458 patients (mean age: 62 years, 72% male, mean forced expiratory volume in 1 second: 51% pred), including 235 patients with Eos ≥2% (49%), 149 with Eos ≥3% (33%), and 90 with Eos ≥4% (20%). For all cutoffs, there was no difference between Eos+ and Eos- groups in univariate analyses except for diabetes and SGRQ score (more frequent and more impaired, respectively, in lower Eos categories). In particular, there was no difference in exacerbation rate, history of asthma, or three-year survival. In conclusion, regardless of the cutoff, Eos+ COPD patients exhibited no specific characteristic in terms of symptoms, lung function, exacerbation rate, and prognosis. These findings suggest that the association of higher Eos with exacerbations reported in previous studies could be population specific, which does not support generalizing the use of Eos as a biomarker for COPD phenotyping., Competing Interests: Disclosure Dr Zysman reports grants and personal fees from Boehringer Ingelheim and personal fees from Novartis, Chiesi, AGEvie outside the submitted work. Dr Deslee reports personal fees from Novartis, AstraZeneca, BTG/PneumRx, Chiesi, and Boehringer Ingelheim, outside the submitted work. Dr Caillaud reports grants and personal fees from Boehringer Ingelheim, personal fees from Novartis, Bayer, and grants from AstraZeneca, ALK-Abello, and Stallergenes, outside the submitted work. Dr Chanez does not report any conflicts of interest. Dr Escamilla reports grants and personal fees from Boehringer Ingelheim, Novartis, personal fees from AstraZeneca, Mundipharma, ALK, and Chiesi, and nonfinancial support from TEVA, outside the submitted work. Dr Court-Fortune reports grants and personal fees from Boehringer Ingelheim and Novartis. Dr Nesme-Meyer reports grants and personal fees from Boehringer Ingelheim. Dr Perez reports personal fees from Boehringer Ingelheim, Novartis, GSK, Chiesi, and Pierre Fabre, outside the submitted work. Dr Paillasseur reports grants from Initiative BPCO Association, during the conduct of the study. Dr Pinet reports grants and personal fees from Boehringer Ingelheim and Novartis. Dr Jebrak reports grants and personal fees from Boerhringer, Novartis, and Pfizer and personal fees from AstraZeneca during the conduct of the study. Dr Roche reports grants and personal fees from Boehringer Ingelheim, Novartis, and Pfizer and personal fees from Teva, GSK, AstraZeneca, Chiesi, Mundipharma, Cipla, Sanofi, Sandoz, Zambon, 3M, and BRAHMS/Thermo Fischer scientific, outside the submitted work. Dr Burgel reports grants and personal fees from Boehringer Ingelheim and personal fees from Aptalis, Astra-Zeneca, Chiesi, GSK, Novartis, Pfizer, Vertex, and Zambon, outside the submitted work.

Serological data are one of the primary sources of information for disease monitoring in wildlife. However, the duration of the seropositive status of exposed individuals is almost always unknown for many free-ranging host species. Directly estimating rates of antibody loss typically requires difficult longitudinal sampling of individuals following seroconversion. Instead, we propose a Bayesian statistical approach linking age and serological data to a mechanistic epidemiological model to infer brucellosis infection, the probability of antibody loss, and recovery rates of elk (Cervus canadensis) in the Greater Yellowstone Ecosystem. We found that seroprevalence declined above the age of ten, with no evidence of disease-induced mortality. The probability of antibody loss was estimated to be 0.70 per year after a five-year period of seropositivity and the basic reproduction number for brucellosis to 2.13. Our results suggest that individuals are unlikely to become re-infected because models with this mechanism were unable to reproduce a significant decline in seroprevalence in older individuals. This study highlights the possible implications of antibody loss, which could bias our estimation of critical epidemiological parameters for wildlife disease management based on serological data.

Chronic obstructive pulmonary disease (COPD) most often results from the inhalation of toxic agents. Cigarette smoking still remains the principal cause but the pertinence of occupational COPD is now clearly established. After a brief overview of the epidemiology of this "other COPD", the clinical and functional characteristics are summarized, taking into account recent advances in this field. The combined effects of occupational exposure and tobacco are also considered, providing evidence of the need to continuously reinforce campaigns of education and prevention in occupational COPD., (Copyright © 2017 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Although French farmers smoke less on average than individuals from the general population, they suffer more from COPD. Exposure to biological and chemical air pollutants in the farm may be the cause of these higher COPD rates. This study investigates the role of bio-contaminants, including the relationship of exposure to volatile organic compounds (VOCs) and fine particulate matter (of diameter of 2.5 µm [PM 2.5 ]) objectively measured in the farm settings (dwellings and workplaces) to serum cytokines involved in COPD, in a sample of 72 farmers from 50 farms in the Auvergne region, France. Mean concentrations of VOCs were highest inside the home, while levels of PM 2.5 were highest in workplaces (stables and granaries). After adjusting for confounders, high exposure to PM 2.5 was significantly associated with a decreased level of serum cytokines (among others, IL13: β: -0.94, CI: -1.5 to -0.2, P -value =0.004; IL8: β: -0.82, CI: -1.4 to -0.2, P -value =0.005) and high exposure to VOCs according to a VOC global score with a decreased IL13 level (β: -0.5, CI: -0.9 to -0.1, P -value =0.01). Moreover, respiratory symptoms and diseases, including COPD, were associated with a decreased level of serum cytokines significantly in the case of IL5. An alteration of immune response balance in terms of cytokine levels in relation to indoor chemical air pollution exposure may contribute to respiratory health impairment in farmers., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Introduction: We studied the pattern changes over time of medication prescriptions for COPD and their conformity with French and international recommendations using data from patients in the prospective French cohort "Initiatives BPCO"., Method: Eight hundred and forty-six patients have been included during a first period from August, 2001 till May 2006 (n=425) and a second period from June, 2006 till June, 2012 (n=421). The pivotal date was based on the tiotropium availability in France., Results: During period 1, we recruited older patients (average 65 vs 64 years), less often women (19 vs 26 %) and having less severe airflow obstruction (mean FEV1 48 vs 54 %). The ICS prescriptions decreased in mild COPD, but there was no change for inhaled long-acting beta-2 agonist (LABA) (68 %). The use of LABA+LAMA association without ICS increased from 0.9 to 7 %, but remained lower than the fixed LABA+ICS association (26 %), less often prescribed than the triple association LABA+ICS+LAMA (32.5 % in period 2). The use of long-acting bronchodilators increased from 68 to 80 % between both periods. Vaccinations and rehabilitation remained insufficiently prescribed. LAMA had been added but did not appear to replace other drugs., (Copyright © 2017 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Background: It is known that asthma is related to obesity but also to small birthweight. The objective of this study was to clarify this issue by assessing the putative relationship between the changes in corpulence between birth and childhood as assessed by body mass index (BMI) and asthma phenotypes., Methods: The following status in corpulence was assessed in 7781 schoolchildren using quartile of BMI at birth and at around 10 (9-11 years): underweight at birth and at around 10, underweight at birth and overweight at around 10, overweight at birth and underweight at around 10, overweight at birth and at around 10, and the reference group constituted by all the other children in whom corpulence changes were not extreme. Determination of asthma phenotypes (allergic, non-allergic, and exercise-induced asthma) was based on a clinical examination including skin prick tests, an exercise challenge test, and a questionnaire., Results: The risk of allergic asthma was higher in children with persistent underweight, children with persistent overweight, and children becoming markedly more corpulent. In boys, the risk of allergic asthma was significantly higher for the less corpulent children at birth, regardless of whether they remained so or become overweight. In girls, the risk of allergic asthma was significantly higher in those with persistent overweight. There were no significant associations between BMI changes and non-allergic and exercise-induced asthma., Conclusions: We observed that some extreme changes in BMI, persistent underweight, and persistent overweight in childhood increased the risk of allergic asthma., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The results of international epidemiological surveys show large geographical variations in skin test reactivity but do not provide a rationale for such variations., Objective: To assess the relationship between climate and allergic sensitization in schoolchildren., Methods: In the present study, we analyzed data from a multicenter, epidemiological survey that included 6,461 schoolchildren, aged 9-11 years, living in 6 French cities scattered around France. The protocol also included a battery of skin prick tests to common airborne allergens. The crude prevalence of sensitization to each allergen was estimated for each city and then adjusted for potential confounding factors. This analysis was repeated for monosensitization and for allergens grouped into 2 categories: indoor allergens, i.e., house dust mite (HDM), cat, and cockroach allergens, and outdoor allergens, i.e., birch pollen, grass pollen, and Alternaria. We also grouped cities according to their location on the coast, i.e., Marseille and Bordeaux, or inland, i.e., Créteil, Clermont-Ferrand, Reims, and Strasbourg., Results: A difference in prevalence of sensitization to each airborne allergen or allergens grouped into indoor and outdoor categories was found between cities, even after adjusting for potential confounding factors. Also, a higher prevalence of sensitization to HDM, cat dander, and, broadly speaking, indoor allergens, was found in children living on the coast than in those living inland, whereas they showed a lower prevalence of sensitization to birch pollen. Between-city differences in the prevalence of monosensitization were also statistically significant. Children living in coastal cities had a higher rate of monosensitization to indoor allergens and a lower prevalence of sensitization to birch pollen. The higher prevalence of allergic sensitization in children from coastal cities is most likely due to climatic conditions, such as proximity from sea and humidity. Differences in sensitization to birch allergens could be due to differential exposure to these pollen., Conclusion: These results indicate a role of environmental exposure in sensitization to perennial as well as seasonal allergens., (© 2017 S. Karger AG, Basel.)

Background: Some studies suggest that asthma-COPD overlap syndrome (ACOS) is associated with worse outcomes than chronic obstructive pulmonary disease (COPD). The goal of this study was to further explore the clinical characteristics and survival of patients with ACOS identified in a real-life cohort of patients with COPD., Methods: Data from the French COPD cohort 'INITIATIVES BronchoPneumopathie Chronique Obstructive' (n = 998 patients) were analyzed to assess the frequency of ACOS defined as a physician diagnosis of asthma before the age of 40 years and to analyze its impact. Univariate analyses were performed to assess the relationship between ACOS and sociodemographic characteristics, risk factors (smoking, occupational exposure, atopic diseases), symptoms (chronic bronchitis, dyspnea-modified Medical Research Council scale and baseline dyspnea index), quality of life (QoL), mood disorders, exacerbations, comorbidities, lung function, prescribed treatment, and survival., Results: ACOS was diagnosed in 129 patients (13%). In multivariate analyses, ACOS was associated negatively with cumulative smoking (odds ratio [OR]: 0.992; 95% CI 0.984-1.000 per pack-year) and positively with obesity: OR: 1.97 [1.22-3.16], history of atopic disease (hay fever: OR: 5.50 [3.42-9.00] and atopic dermatitis: OR 3.76 [2.14-6.61]), and drug use (LABA + ICS: 1.86 [1.27-2.74], antileukotrienes 4.83 [1.63-14.34], theophylline: 2.46 [1.23-4.91], and oral corticosteroids: [2.99;.1.26-7.08]). No independent association was found with dyspnea, QoL, exacerbations, and mortality., Conclusions: Compared to 'pure' COPD patients, patients with ACOS exhibit lower cumulative smoking, suffer more from obesity and atopic diseases, and use more asthma treatments. Disease severity (dyspnea, QoL, exacerbations, comorbidities) and prognosis (mortality) are not different from 'pure' COPD patients., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Cough and sputum production are frequent in chronic obstructive pulmonary disease (COPD). The objective of this study was to examine the relationship between cough and sputum production and health-related quality of life in COPD., Methods: A cross-sectional study was conducted in the French Initiatives COPD cohort and assessed cough and sputum production within the past 7 days using the cough and sputum assessment questionnaire (CASA-Q), health-related quality of life, spirometry, smoking status, dyspnea, exacerbations, anxiety and depression, and comorbidities., Results: One hundred and seventy-eight stable COPD patients were included (age, 62 [56-69] years, 128 male, forced expiratory volume in 1 second [FEV 1 ]: 57 [37-72] % predicted) (median [Q1-Q3]). In univariate analyses, health-related quality of life (Saint George's respiratory questionnaire total score) was associated with each CASA-Q domain and with chronic bronchitis, exacerbations, dyspnea, FEV 1 , depression, and anxiety. All four domains introduced separately were independently associated with health-related quality of life. When introduced together in multivariate analyses, only the cough impact domain remained independently associated with health-related quality of life ( R 2 =0.60). With chronic bronchitis (standard definition) instead of the CASA-Q, the R 2 was lower ( R 2 =0.54)., Conclusion: This study provides evidence that current cough in the previous 7 days is an important determinant of health-related quality of life impairment in stable COPD patients.

The use of recombinant antigens has been shown to improve both the sensitivity and the standardization of the serological diagnosis of Farmer's lung disease (FLD). The aim of this study was to complete the panel of recombinant antigens available for FLD serodiagnosis with antigens of Lichtheimia corymbifera, known to be involved in FLD. L. corymbifera proteins were thus separated by 2D electrophoresis and subjected to western blotting with sera from 7 patients with FLD and 9 healthy exposed controls (HEC). FLD-associated immunoreactive proteins were identified by mass spectrometry based on a protein database specifically created for this study and subsequently produced as recombinant antigens. The ability of recombinant antigens to discriminate patients with FLD from controls was assessed by ELISA performed with sera from FLD patients (n = 41) and controls (n = 43) recruited from five university hospital pneumology departments of France and Switzerland. Forty-one FLD-associated immunoreactive proteins from L. corymbifera were identified. Six of them were produced as recombinant antigens. With a sensitivity and specificity of 81.4 and 77.3% respectively, dihydrolipoyl dehydrogenase was the most effective antigen for discriminating FLD patients from HEC. ELISA performed with the putative proteasome subunit alpha type as an antigen was especially specific (88.6%) and could thus be used for FLD confirmation. The production of recombinant antigens from L. corymbifera represents an additional step towards the development of a standardized ELISA kit for FLD diagnosis.

Introduction: With an aging population and an increase in the prevalence of asthma, this disease is becoming more common in the elderly. Nevertheless, the management of severe asthma can be complex, due to an increased risk of uncontrolled disease in patients over 65 years old and partly to the inherent characteristics of old age: comorbidities, underestimation of the role of allergies, poor adherence, difficulties with inhalation devices, etc., Case Reports: We report two cases of women over 75 with severe persistent allergic asthma not controlled by high doses of inhaled corticosteroids and long-acting beta-2-agonists in whom treatment with omalizumab was initiated. Following treatment with omalizumab a decrease in the number and severity of exacerbations, improved asthma control and dose reduction or discontinuation of systemic corticosteroids were observed. The tolerance of omalizumab was good in both cases., Conclusions: Omalizumab is to be considered an effective and well-tolerated therapeutic option for elderly patients with inadequately controlled severe allergic asthma., (Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Background: The prevalence of asthma and allergy has recently risen among children. This increase in prevalence might be related to various factors, particularly diet. The aim of this study is to assess the prevalence and association of asthma and allergic sensitization with dietary factors in the French Six Cities Study., Methods: Cross-sectional studies were performed among 7432 schoolchildren aged 9-11 years in Bordeaux, Clermont-Ferrand, Créteil, Marseille, Reims, and Strasbourg. Parental questionnaires, based on the International Study on Asthma and Allergies in Childhood (ISAAC), were used to collect information on allergic diseases and potential exposure factors including a food frequency questionnaire to evaluate dietary habits. Skin prick testing to common allergens for allergic sensitization and bronchial hyper-responsiveness (BHR) testing to exercise were performed. Confounders control was performed with multiple logistic regressions., Results: Asthma symptoms, asthma and allergic sensitization were more prevalent in boys than in girls and were more prevalent in the South than in the North of France. After adjustment for confounders, fruit juice intake was associated with a low prevalence of lifetime asthma (ORa [95 % CI]; 0.73 [0.56-0.97]), butter intake was positively associated with atopic wheeze (1.48 [1.07-2.05]) and having lunch at the canteen 1-2 times/week compared to never or occasionally was associated with a lower prevalence of past year wheeze (0.71 [0.52-0.96]), lifetime asthma (0.76 [0.60-0.96]) and allergic sensitization (0.80 [0.67-0.95]). Meat intake was inversely related to past year wheeze among atopic children (0.68 [0.50-0.98]) while fast food consumption and butter intake were associated with an increase prevalence of asthma (2.39 [1.47-3.93] and 1.51 [1.17-2.00] respectively). Fish intake was associated with a lower prevalence of asthma among non-atopic children (0.61 [0.43-0.87]. None of the dietary factors was associated with BHR., Conclusions: Diet is associated with wheeze, asthma and allergic sensitization but not with BHR in children. These results provide further evidence that adherence to a healthy diet including fruits, meat and fish seems to have a protective effect on asthma and allergy in childhood. However, prospective and experimental studies are needed to provide causal evidence concerning the effect of diet on asthma and atopy.

Background: Assessment of dyspnea in COPD patients relies in clinical practice on the modified Medical Research Council (mMRC) scale, whereas the Baseline Dyspnea Index (BDI) is mainly used in clinical trials. Little is known on the correspondence between the two methods., Methods: Cross-sectional analysis was carried out on data from the French COPD cohort Initiatives BPCO. Dyspnea was assessed by the mMRC scale and the BDI. Spirometry, plethysmography, Hospital Anxiety-Depression Scale, St George's Respiratory Questionnaire, exacerbation rates, and physician-diagnosed comorbidities were obtained. Correlations between mMRC and BDI scores were assessed using Spearman's correlation coefficient. An ordinal response model was used to examine the contribution of clinical data and lung function parameters to mMRC and BDI scores., Results: Data are given as median (interquartile ranges, [IQR]). Two-hundred thirty-nine COPD subjects were analyzed (men 78%, age 65.0 years [57.0; 73.0], forced expiratory volume in 1 second [FEV1] 48% predicted [34; 67]). The mMRC grade and BDI score were, respectively, 1 [1-3] and 6 [4-8]. Both BDI and mMRC scores were significantly correlated at the group level (rho =-0.67; P<0.0001), but analysis of individual data revealed a large scatter of BDI scores for any given mMRC grade. In multivariate analysis, both mMRC grade and BDI score were independently associated with lower FEV1% pred, higher exacerbation rate, obesity, depression, heart failure, and hyperinflation, as assessed by the inspiratory capacity/total lung capacity ratio. The mMRC dyspnea grade was also associated with the thromboembolic history and low body mass index., Conclusion: Dyspnea is a complex symptom with multiple determinants in COPD patients. Although related to similar factors (including hyperinflation, depression, and heart failure), BDI and mMRC scores likely explore differently the dyspnea intensity in COPD patients and are clearly not interchangeable.

Objective: The purpose of this study was to examine the association between pre and post environmental tobacco smoke (ETS) exposure and behavioral problems in schoolchildren., Methods: In the cross-sectional 6 cities Study conducted in France, 5221 primary school children were investigated. Pre- and postnatal exposure to secondhand tobacco smoke at home was assessed using a parent questionnaire. Child's behavioral outcomes (emotional symptoms and conduct problems) were evaluated by the Strengths and Difficulties Questionnaire (SDQ) completed by the parents., Results: ETS exposure during the postnatal period and during both pre- and postnatal periods was associated with behavioral problems in children. Abnormal emotional symptoms (internalizing problems) were related to ETS exposure in children who were exposed during the pre- and postnatal periods with an OR of 1.72 (95% Confidence Interval (CI)= 1.36-2.17), whereas the OR was estimated to be 1.38 (95% CI= 1.12-1.69) in the case of postnatal exposure only. Abnormal conduct problems (externalizing problems) were related to ETS exposure in children who were exposed during the pre- and postnatal periods with an OR of 1.94 (95% CI= 1.51-2.50), whereas the OR was estimated to be 1.47 (95% CI=1.17-1.84) in the case of postnatal exposure only. Effect estimates were adjusted for gender, study center, ethnic origin, child age, low parental education, current physician diagnosed asthma, siblings, preterm birth and single parenthood., Conclusion: Postnatal ETS exposure, alone or in association with prenatal exposure, increases the risk of behavioral problems in school-age children.