Should flow-volume loop be monitored in sleep apnea patients treated with continuous positive airway pressure?

AbstractNasal continuous positive airway pressure (nCPAP) has been widely established in the treatment of obstructive sleep apnea syndrome (OSAS). However, only few studies have evaluated long-term effects of this treatment on lung function. This study assesses the effect of nCPAP on lung function parameters and response to bronchodilators in 50 OSAS patients. Spirometry and arterial blood gas measurements were performed before starting nCPAP and after 16.8±8 months of treatment. Of the 50 study patients (55±12 years, with an apnea/hypopnea index of 47±34h−1), 15 had asthma, 13 had chronic obstructive pulmonary disease (COPD) and 22 had no obstructive airway disease (NOAD). In the entire population, significant decreases in FEF50 (from 69±38% to 61±30%, P<0.005), FEF25 (from 53±34% to 46±28%, P<0.05) and FEF25−75 (from 65±33% to 57±27%, P<0.005) were observed after treatment. No impairment of lung function was found in COPD and asthmatic patients. In contrast, lung function was changed in the NOAD group where FEF50, FEF25 and FEF25−75 as well as FEV1 and FEV1/VC ratio were significantly reduced. Moreover, bronchial hyperresponsiveness occurred in five of 22 patients of this group. These results suggest that tolerance of nCPAP should be handled by long-term follow-up of flow-volume loops

Editorial: Exercise intervention for prevention, management of and rehabilitation from COVID-19

exercise, prevention, rehabilitation, infection, COVID-1

Induction of Heme Oxygenase-1, Biliverdin Reductase and H-Ferritin in Lung Macrophage in Smokers with Primary Spontaneous Pneumothorax: Role of HIF-1α

Few data concern the pathophysiology of primary spontaneous pneumothorax (PSP), which is associated with alveolar hypoxia/reoxygenation. This study tested the hypothesis that PSP is associated with oxidative stress in lung macrophages. We analysed expression of the oxidative stress marker 4-HNE; the antioxidant and anti-inflammatory proteins heme oxygenase-1 (HO-1), biliverdin reductase (BVR) and heavy chain of ferritin (H-ferritin); and the transcription factors controlling their expression Nrf2 and HIF-1alpha, in lung samples from smoker and nonsmoker patients with PSP (PSP-S and PSP-NS), cigarette smoke being a risk factor of recurrence of the disease.mRNA was assessed by RT-PCR and proteins by western blot, immunohistochemistry and confocal laser analysis. 4-HNE, HO-1, BVR and H-ferritin were increased in macrophages from PSP-S as compared to PSP-NS and controls (C). HO-1 increase was associated with increased expression of HIF-1alpha mRNA and protein in alveolar macrophages in PSP-S patients, whereas Nrf2 was not modified. To understand the regulation of HO-1, BVR and H-ferritin, THP-1 macrophages were exposed to conditions mimicking conditions in C, PSP-S and PSP-NS patients: cigarette smoke condensate (CS) or air exposure followed or not by hypoxia/reoxygenation. Silencing RNA experiments confirmed that HIF-1alpha nuclear translocation was responsible for HO-1, BVR and H-ferritin induction mediated by CS and hypoxia/reoxygenation.PSP in smokers is associated with lung macrophage oxidative stress. The response to this condition involves HIF-1alpha-mediated induction of HO-1, BVR and H-ferritin

Hepatocyte and keratinocyte growth factors and their receptors in human lung emphysema

BACKGROUND: Hepatocyte and keratinocyte growth factors are key growth factors in the process of alveolar repair. We hypothesized that excessive alveolar destruction observed in lung emphysema involves impaired expression of hepatocyte and keratinocyte growth factors or their respective receptors, c-met and keratinocyte growth factor receptor. The aim of our study was to compare the expression of hepatocyte and keratinocyte growth factors and their receptors in lung samples from 3 groups of patients: emphysema; smokers without emphysema and non-smokers without emphysema. METHODS: Hepatocyte and keratinocyte growth factor proteins were analysed by immunoassay and western blot; mRNA expression was measured by real time quantitative polymerase chain reaction. RESULTS: Hepatocyte and keratinocyte growth factors, c-met and keratinocyte growth factor receptor mRNA levels were similar in emphysema and non-emphysema patients. Hepatocyte growth factor mRNA correlated negatively with FEV1 and the FEV1/FVC ratio both in emphysema patients and in smokers with or without emphysema. Hepatocyte and keratinocyte growth factor protein concentrations were similar in all patients' groups. CONCLUSION: The expression of hepatocyte and keratinocyte growth factors and their receptors is preserved in patients with lung emphysema as compared to patients without emphysema. Hepatocyte growth factor mRNA correlates with the severity of airflow obstruction in smokers

Research priorities to address the global burden of chronic obstructive pulmonary disease (COPD) in the next decade

Background The global prevalence of chronic obstructive pulmonary disease (COPD) has increased markedly in recent decades. Given the scarcity of resources available to address global health challenges and respiratory medicine being relatively under-invested in, it is important to define research priorities for COPD globally. In this paper, we aim to identify a ranked set of COPD research priorities that need to be addressed in the next 10 years to substantially reduce the global impact of COPD. Methods We adapted the Child Health and Nutrition Research Initiative (CHNRI) methodology to identify global COPD research priorities. Results 62 experts contributed 230 research ideas, which were scored by 34 researchers according to six pre-defined criteria: answerability, effectiveness, feasibility, deliverability, burden reduction, and equity. The top-ranked research priority was the need for new effective strategies to support smoking cessation. Of the top 20 overall research priorities, six were focused on feasible and cost-effective pulmonary rehabilitation delivery and access, particularly in primary/community care and low-resource settings. Three of the top 10 overall priorities called for research on improved screening and accurate diagnostic methods for COPD in low-resource primary care settings. Further ideas that drew support involved a better understanding of risk factors for COPD, development of effective training programmes for health workers and physicians in low resource settings, and evaluation of novel interventions to encourage physical activity. Conclusions The experts agreed that the most pressing feasible research questions to address in the next decade for COPD reduction were on prevention, diagnosis and rehabilitation of COPD, especially in low resource settings. The largest gains should be expected in low- and middle-income countries (LMIC) settings, as the large majority of COPD deaths occur in those settings. Research priorities identified by this systematic international process should inform and motivate policymakers, funders, and researchers to support and conduct research to reduce the global burden of COPD

Pollution atmosphérique et maladies respiratoires allergiques

Les particules diesel (PDi) exercent une activité adjuvante sur la production d’IgE (animal sensibilisé à un allergène et injection simultanée de l’allergène et des PDi), et cela quelle que soit la voie d’administration utilisée. Chez l’homme, l’instillation nasale de PDi chez des volontaires sains provoque une augmentation de la production de cytokines pro-Th2, caractéristiques de la réponse allergique. À partir des études réalisées chez l’homme et chez l’animal, on peut donc proposer une hypothèse expliquant la recrudescence des pathologies respiratoires, et notamment des crises d’asthme, observée lors des épisodes de pollution particulaire

Régulation de l'hème oxygénase-1 dans les macrophages au cours des pathologies pulmonaires liées à l'exposition de la fumée de cigarette

L intoxication tabagique, source d oxydants, est un facteur de risque important de développement de l emphysème pulmonaire et du pneumothorax spontané primitif. Les macrophages alvéolaires contribuent pour une large part à l inflammation pulmonaire au cours de ces pathologies en produisant des métalloprotéases et des espèces réactives de l oxygène à l origine du déséquilibre des balances protéase/anti-protéase et oxydant/antioxydant. L'hème oxygénase-1 (HO-1), exprimée principalement par les macrophages, est une enzyme clé des défenses anti-oxydantes pulmonaires. Nous avons initialement étudié l expression et la localisation cellulaire de l HO-1 et de ses régulateurs potentiels (Nrf2, Keap1, Bach1 et HIF-1a) dans les macrophages alvéolaires au cours de l emphysème pulmonaire post-tabagique et du pneumothorax spontané primitif. Les voies de régulation de l expression de ces protéines ont été analysées in vitro sur des macrophages dérivés de la lignée THP-1 exposés ou non au condensat de fumée de cigarette et à l hypoxieréoxygénation visant à mimer une partie des effets de l atélectasie-réexpansion observée lors de la prise en charge thérapeutique des pneumothorax récidivants. Les travaux présentés dans cette thèse nous ont permis de mettre en évidence une altération de l expression de la voie Nrf2/Keap1-Bach1 associée à une diminution de l expression des enzymes anti-oxydantes, dont l HO-1, dans les macrophages alvéolaires au cours de l emphysème pulmonaire sévère post-tabagique, malgré un stress oxydant important. In vitro, ces altérations pourraient être liées à une activation spécifique des MAPKinases ERK1/2 et JNK par le condensat de fumée de cigarette. Nous avons également montré que la stimulation du système de l HO-1 était probablement orchestrée par la voie du facteur HIF-1a, et non par celle de Nrf2, dans les macrophages alvéolaires au cours du pneumothorax spontané primitif récidivant du sujet fumeur. Ces résultats pourraient contribuer à une meilleure connaissance de la physiopathologie de l emphysème pulmonaire et permettre d envisager de nouvelles approches thérapeutiques basées sur la préservation et/ou la restauration de l équilibre Nrf2/Keap1-Bach1. Nos travaux suggèrent également que la physiopathologie du pneumothorax spontané primitif est différente chez les patients fumeurs et non fumeurs. Le pneumothorax du sujet fumeur est associé à un stress oxydant pulmonaire et à une induction de l HO-1 probablement orchestrée par HIF-1a. Ces résultats, confirmés in vitro, mettent en évidence une interaction potentielle entre le stress oxydant et l hypoxie-réoxygénationChronic cigarette smoking, a source of oxidants, is an important risk factor for lung emphysema and primary spontaneous pneumothorax development. Alveolar macrophages are mainly involved in lung inflammation observed in these pathologies through the production of metalloproteases and reactive oxygen species resulting to protease/anti-protease and oxidant/anti-oxidant imbalances. Heme oxygenase-1 (HO-1), mainly expressed in macrophages, is a key enzyme in pulmonary anti-oxidant defences. Therefore, the first aim of our studies was to investigate the expression and cellular localisation of HO-1 and its potential regulators (Nrf2, Keap1, Bach1 and HIF-1a) in alveolar macrophages from smoking related lung emphysema and primary spontaneous pneumothorax. Regulation pathways involved in expression of these proteins were assessed in vitro in macrophage cell line THP-1 exposed or not to cigarette smoke condensate and with or without hypoxia-reoxygenation mimicking parts of events induced by atelectasia-reexpansion during recurrent pneumothorax constitution and treatment. In these studies, we showed an altered expression of Nrf2/Keap1- Bach1 pathway associated with a reduced expression of anti-oxidants enzymes, like HO-1, in alveolar macrophages from smoking related lung emphysema patients, despite an important oxidative stress. These alterations might be related to cigarette smoke condensate activated ERK1/2 and JNK MAPKinases as observed in THP-1 cells. Furthermore, we showed that HO- 1 system induction was mediated by HIF-1a instead of Nrf2 pathway in alveolar macrophages from smoking related recurrent primary spontaneous pneumothorax. These findings may contribute to a better knowledge of the pathophysiology of lung emphysema and could provide new therapeutic approaches based on preservation and/or restoration of Nrf2/Keap1-Bach1 equilibrium. Our results also suggest that the pathophysiology of primary spontaneous pneumothorax could be different in smokers and non smokers. Spontaneous pneumothorax in smokers is associated with lung oxidative stress and the orchestrated induction of HO-1 probably via HIF-1a. These results provide a new link between oxidative stress and hypoxia/reoxygenationPARIS-EST-Université (770839901) / SudocSudocFranceF