TY  - JOUR
AB  - OBJECTIVES: To investigate the associations of physical activity (PA) and sedentary behaviour in early childhood with asthma and reduced lung function in later childhood within a large collaborative study. DESIGN: Pooling of longitudinal data from collaborating birth cohorts using meta-analysis of separate cohort-specific estimates and analysis of individual participant data of all cohorts combined. SETTING: Children aged 0-18 years from 26 European birth cohorts. PARTICIPANTS: 136 071 individual children from 26 cohorts, with information on PA and/or sedentary behaviour in early childhood and asthma assessment in later childhood. MAIN OUTCOME MEASURE: Questionnaire-based current asthma and lung function measured by spirometry (forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity) at age 6-18 years. RESULTS: Questionnaire-based and accelerometry-based PA and sedentary behaviour at age 3-5 years was not associated with asthma at age 6-18 years (PA in hours/day adjusted OR 1.01, 95% CI 0.98 to 1.04; sedentary behaviour in hours/day adjusted OR 1.03, 95% CI 0.99 to 1.07). PA was not associated with lung function at any age. Analyses of sedentary behaviour and lung function showed inconsistent results. CONCLUSIONS: Reduced PA and increased sedentary behaviour before 6 years of age were not associated with the presence of asthma later in childhood.
AU  - Eijkemans, M.*
AU  - Mommers, M.*
AU  - Harskamp-van Ginkel, M.W.*
AU  - Vrijkotte, T.G.M.*
AU  - Ludvigsson, J.*
AU  - Faresjö, Å.*
AU  - Bergström, A.*
AU  - Ekström, S.*
AU  - Grote, V.*
AU  - Koletzko, B.*
AU  - Bønnelykke, K.*
AU  - Eliasen, A.U.*
AU  - Bager, P.*
AU  - Melbye, M.*
AU  - Annesi-Maesano, I.*
AU  - Baïz, N.*
AU  - Barros, H.*
AU  - Santos, A.C.*
AU  - Duijts, L.*
AU  - Mensink-Bout, S.M.*
AU  - Flexeder, C.
AU  - Koletzko, S.*
AU  - Schikowski, T.*
AU  - Eggesbø, M.*
AU  - Lenters, V.*
AU  - Fernández-Tardón, G.*
AU  - Subiza-Perez, M.*
AU  - Garcia-Aymerich, J.*
AU  - López-Vicente, M.*
AU  - Sunyer, J.*
AU  - Torrent, M.*
AU  - Ballester, F.*
AU  - Kelleher, C.*
AU  - Mehegan, J.*
AU  - Berg, A.V.*
AU  - Herberth, G.*
AU  - Standl, M.
AU  - Kuehni, C.E.*
AU  - Pedersen, E.S.L.*
AU  - Jansen, M.*
AU  - Gehring, U.*
AU  - Boer, J.M.A.*
AU  - Devereux, G.*
AU  - Turner, S.*
AU  - Peltola, V.*
AU  - Lagström, H.*
AU  - Inskip, H.M.*
AU  - Pike, K.C.*
AU  - Dalmeijer, G.W.*
AU  - Ent, C.K.V.*
AU  - Thijs, C.*
C1  - 71490
C2  - 56098
CY  - British Med Assoc House, Tavistock Square, London Wc1h 9jr, England
TI  - Physical activity, sedentary behaviour, and childhood asthma: A European collaborative analysis.
JO  - BMJ Open Respir. Res.
VL  - 11
IS  - 1
PB  - Bmj Publishing Group
PY  - 2024
SN  - 2052-4439
ER  - 

TY  - JOUR
AB  - INTRODUCTION: The emergence of new SARS-CoV-2 variants, capable of escaping the humoral immunity acquired by the available vaccines, together with waning immunity and vaccine hesitancy, challenges the efficacy of the vaccination strategy in fighting COVID-19. Improved therapeutic strategies are urgently needed to better intervene particularly in severe cases of the disease. They should aim at controlling the hyperinflammatory state generated on infection, reducing lung tissue pathology and inhibiting viral replication. Previous research has pointed to a possible role for the chaperone HSP90 in SARS-CoV-2 replication and COVID-19 pathogenesis. Pharmacological intervention through HSP90 inhibitors was shown to be beneficial in the treatment of inflammatory diseases, infections and reducing replication of diverse viruses. METHODS: In this study, we investigated the effects of the potent HSP90 inhibitor Ganetespib (STA-9090) in vitro on alveolar epithelial cells and alveolar macrophages to characterise its effects on cell activation and viral replication. Additionally, the Syrian hamster animal model was used to evaluate its efficacy in controlling systemic inflammation and viral burden after infection. RESULTS: In vitro, STA-9090 reduced viral replication on alveolar epithelial cells in a dose-dependent manner and lowered significantly the expression of proinflammatory genes, in both alveolar epithelial cells and alveolar macrophages. In vivo, although no reduction in viral load was observed, administration of STA-9090 led to an overall improvement of the clinical condition of infected animals, with reduced oedema formation and lung tissue pathology. CONCLUSION: Altogether, we show that HSP90 inhibition could serve as a potential treatment option for moderate and severe cases of COVID-19.
AU  - Teixeira Alves, L.G.*
AU  - Baumgardt, M.*
AU  - Langner, C.*
AU  - Fischer, M.*
AU  - Maria Adler, J.*
AU  - Bushe, J.
AU  - Firsching, T.C.*
AU  - Mastrobuoni, G.*
AU  - Grobe, J.*
AU  - Hoenzke, K.*
AU  - Kempa, S.*
AU  - Gruber, A.D.*
AU  - Hocke, A.C.*
AU  - Trimpert, J.*
AU  - Wyler, E.*
AU  - Landthaler, M.*
C1  - 70101
C2  - 55421
CY  - British Med Assoc House, Tavistock Square, London Wc1h 9jr, England
TI  - Protective role of the HSP90 inhibitor, STA-9090, in lungs of SARS-CoV-2-infected Syrian golden hamsters.
JO  - BMJ Open Respir. Res.
VL  - 11
IS  - 1
PB  - Bmj Publishing Group
PY  - 2024
SN  - 2052-4439
ER  - 

TY  - JOUR
AB  - Introduction: To understand the puberty-related sex shift in the prevalence of asthma and rhinitis as single entities and as respiratory multimorbidities, we investigated if there is also a sex-specific and puberty-related pattern of their incidences. Methods: We used harmonised questionnaire data from 18 451 participants in five prospective observational European birth cohorts within the collaborative MeDALL (Mechanisms of the Development of Allergy) project. Outcome definitions for IgE-associated and non-IgE-associated asthma, rhinitis and respiratory multimorbidity (first occurrence of coexisting asthma and rhinitis) were based on questionnaires and the presence of specific antibodies (IgE) against common allergens in serum. For each outcome, we used proportional hazard models with sex-puberty interaction terms and conducted a one-stage individual participant data meta-analysis. Results: Girls had a lower risk of incident asthma (adjusted HR 0.67, 95% CI 0.61 to 0.74), rhinitis (0.73, 0.69 to 0.78) and respiratory multimorbidity (0.58, 0.51 to 0.66) before puberty compared with boys. After puberty onset, these incidences became more balanced across the sexes (asthma 0.84, 0.64 to 1.10; rhinitis 0.90, 0.80 to 1.02; respiratory multimorbidity 0.84, 0.63 to 1.13). The incidence sex shift was slightly more distinct for non-IgE-associated respiratory diseases (asthma 0.74, 0.63 to 0.87 before vs 1.23, 0.75 to 2.00 after puberty onset; rhinitis 0.88, 0.79 to 0.98 vs 1.20, 0.98 to 1.47; respiratory multimorbidity 0.66, 0.49 to 0.88 vs 0.96, 0.54 to 1.71) than for IgE-associated respiratory diseases. Discussion: We found an incidence 'sex shift' in chronic respiratory diseases from a male predominance before puberty to a more sex-balanced incidence after puberty onset, which may partly explain the previously reported sex shift in prevalence. These differences need to be considered in public health to enable effective diagnoses and timely treatment in adolescent girls.
AU  - Hohmann, C.*
AU  - Keller, T.*
AU  - Gehring, U.*
AU  - Wijga, A.*
AU  - Standl, M.
AU  - Kull, I.*
AU  - Bergstrom, A.*
AU  - Lehmann, I.*
AU  - von Berg, A.*
AU  - Heinrich, J.
AU  - Lau, S.*
AU  - Wahn, U.*
AU  - Maier, D.*
AU  - Anto, J.*
AU  - Bousquet, J.*
AU  - Smit, H.*
AU  - Keil, T.*
AU  - Roll, S.*
C1  - 56975
C2  - 47464
TI  - Sex-specific incidence of asthma, rhinitis and respiratory multimorbidity before and after puberty onset: individual participant meta-analysis of five birth cohorts collaborating in MeDALL.
JO  - BMJ Open Respir. Res.
VL  - 6
IS  - 1
PY  - 2019
SN  - 2052-4439
ER  - 

TY  - JOUR
AB  - INTRODUCTION: Sleep length has been associated with obesity and various adverse health outcomes. The possible association of sleep length and respiratory symptoms has not been previously described. The aim of this study was to investigate the association between sleep length and respiratory symptoms and whether such an association existed independent of obesity. METHODS: This is a multicentre, cross-sectional, population-based study performed in 23 centres in 10 different countries. Participants (n=5079, 52.3% males) were adults in the third follow-up of the European Community Respiratory Health Survey III. The mean±SD age was 54.2±7.1 (age range 39-67 years). Information was collected on general and respiratory health and sleep characteristics. RESULTS: The mean reported nighttime sleep duration was 6.9±1.0 hours. Short sleepers (<6 hours per night) were n=387 (7.6%) and long sleepers (≥9 hours per night) were n=271 (4.3%). Short sleepers were significantly more likely to report all respiratory symptoms (wheezing, waking up with chest tightness, shortness of breath, coughing, phlegm and bronchitis) except asthma after adjusting for age, gender, body mass index (BMI), centre, marital status, exercise and smoking. Excluding BMI from the model covariates did not affect the results. Short sleep was related to 11 out of 16 respiratory and nasal symptoms among subjects with BMI ≥30 and 9 out of 16 symptoms among subjects with BMI <30. Much fewer symptoms were related to long sleep, both for subjects with BMI <30 and ≥30. CONCLUSIONS: Our results show that short sleep duration is associated with many common respiratory symptoms, and this relationship is independent of obesity.
AU  - Björnsdóttir, E.*
AU  - Janson, C.*
AU  - Lindberg, E.*
AU  - Arnardottir, E.S.*
AU  - Benediktsdóttir, B.*
AU  - Garcia-Aymerich, J.*
AU  - Carsin, A.E.*
AU  - Real, F.G.*
AU  - Torén, K.*
AU  - Heinrich, J.
AU  - Nowak, D.*
AU  - Sánchez-Ramos, J.L.*
AU  - Demoly, P.*
AU  - Arenas, S.D.*
AU  - Navarro, R.C.*
AU  - Schlünssen, V.*
AU  - Raherison, C.*
AU  - Jarvis, D.L.*
AU  - Gislason, T.*
C1  - 52322
C2  - 43864
TI  - Respiratory symptoms are more common among short sleepers independent of obesity.
JO  - BMJ Open Respir. Res.
VL  - 4
IS  - 1
PY  - 2017
SN  - 2052-4439
ER  -