Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Chronic obstructive pulmonary disease secondary to organic dust exposure : pulmonary and systemic characterization.

La broncho-pneumopathie chronique obstructive (BPCO) est caractérisée par l’existence de symptômes respiratoires et d’une obstruction permanente des voies aériennes. Le tabagisme reste le principal facteur de risque bien que des causes environnementales et professionnelles comme l’exposition aux poussières organiques aient été identifiées.La prévalence de la BPCO secondaire à l’exposition aux poussières organiques est de 8% et est similaire à celle de la BPCO tabagique malgré une prévalence du tabagisme beaucoup plus faible. Les facteurs liés à l’hôte tel que l’atopie semblent être des déterminants de son développement plus que l’importance de l’exposition aux poussières organiques. Par rapport à la BPCO tabagique, la BPCO secondaire aux poussières organiques est caractérisée par une moindre dyspnée d’effort, une meilleure qualité de vie, une capacité de diffusion alvéolo-capillaire moins altérée suggérant une moindre destruction parenchymateuse et une meilleure tolérance à l’exercice. Les comorbidités notamment cardiovasculaires sont moins fréquentes et sont liés au tabagisme plus qu’à l’existence d’une BPCO. L’inflammation systémique est également moins importante avec un profil de type Th2.Un suivi longitudinal de ces patients est actuellement en cours (NCT03468101). Par ailleurs, la prise en charge thérapeutique et le pronostic de cette BPCO reste à déterminer.Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and airflow limitation. The main risk factor for COPD is tobacco smoking but other environmental exposures such as organic dust exposure may contribute.The prevalence of COPD secondary to organic dust exposure is similar (8%) to those of COPD related to tobacco smoking although prevalence of tobacco smoking is lower. Host factors like atopy appear to be important determinants for its development rather than the magnitude of organic dust exposure. Compared to COPD related to tobacco smoking, COPD secondary to organic dust exposure is associated with less dyspnoea, better quality of life, less impaired exercise capacity and diffusing capacity suggesting a lower emphysema burden. In addition, comorbidities including cardio-vascular diseases are less frequent and are related to tobacco smoking rather than COPD. Systemic inflammation is at a lower level and has a predominantly Th2 profile.Longitudinal follow-up of these patients is currently underway (NCT03468101). Therapeutic management and prognosis of this COPD remain to be determined

Broncho-pneumopathie chronique obstructive secondaire à l’exposition aux poussières organiques : caractérisation pulmonaire et systémique.

Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and airflow limitation. The main risk factor for COPD is tobacco smoking but other environmental exposures such as organic dust exposure may contribute.The prevalence of COPD secondary to organic dust exposure is similar (8%) to those of COPD related to tobacco smoking although prevalence of tobacco smoking is lower. Host factors like atopy appear to be important determinants for its development rather than the magnitude of organic dust exposure. Compared to COPD related to tobacco smoking, COPD secondary to organic dust exposure is associated with less dyspnoea, better quality of life, less impaired exercise capacity and diffusing capacity suggesting a lower emphysema burden. In addition, comorbidities including cardio-vascular diseases are less frequent and are related to tobacco smoking rather than COPD. Systemic inflammation is at a lower level and has a predominantly Th2 profile.Longitudinal follow-up of these patients is currently underway (NCT03468101). Therapeutic management and prognosis of this COPD remain to be determined.La broncho-pneumopathie chronique obstructive (BPCO) est caractérisée par l’existence de symptômes respiratoires et d’une obstruction permanente des voies aériennes. Le tabagisme reste le principal facteur de risque bien que des causes environnementales et professionnelles comme l’exposition aux poussières organiques aient été identifiées.La prévalence de la BPCO secondaire à l’exposition aux poussières organiques est de 8% et est similaire à celle de la BPCO tabagique malgré une prévalence du tabagisme beaucoup plus faible. Les facteurs liés à l’hôte tel que l’atopie semblent être des déterminants de son développement plus que l’importance de l’exposition aux poussières organiques. Par rapport à la BPCO tabagique, la BPCO secondaire aux poussières organiques est caractérisée par une moindre dyspnée d’effort, une meilleure qualité de vie, une capacité de diffusion alvéolo-capillaire moins altérée suggérant une moindre destruction parenchymateuse et une meilleure tolérance à l’exercice. Les comorbidités notamment cardiovasculaires sont moins fréquentes et sont liés au tabagisme plus qu’à l’existence d’une BPCO. L’inflammation systémique est également moins importante avec un profil de type Th2.Un suivi longitudinal de ces patients est actuellement en cours (NCT03468101). Par ailleurs, la prise en charge thérapeutique et le pronostic de cette BPCO reste à déterminer

COPD, airflow limitation and chronic bronchitis in farmers: a systematic review and meta-analysis

Introduction The current definition of chronic obstructive pulmonary disease (COPD) associates persistent airflow limitation and chronic respiratory symptoms. Agricultural work has been associated with an increased risk of developing COPD, but the prevalence and definition of the disease vary greatly between studies. This meta-analysis aimed to assess the association between agricultural work and COPD using the most widely used definitions of the disease. Methods Inclusion criteria were: (1) design: cross-sectional or longitudinal, (2) groups: at least one group of farmers and a control group of non-farmers, (3) outcome: prevalence or unadjusted OR of COPD, airflow limitation and/or chronic bronchitis, (4) study subjects: groups of exposed subjects comprising ≥30 individuals and with a mean age ≥40 years and (5) language: English and French language, full-length, original publications in peer-reviewed journals. Results In total, 22 manuscripts were included in the meta-analysis. Eight studies assessed only the prevalence of airflow limitation, nine assessed only the prevalence of chronic bronchitis and four assessed the prevalence of both these parameters. Only one assessed the prevalence of COPD according to its current definition, and this study also provided the prevalence of airflow limitation. Ten studies showed a positive association between farming exposure and airflow limitation or chronic bronchitis, and 12 showed no association (OR (95% CI)=1.77 (1.50 to 2.08), p<0.001). Cattle, swine, poultry and crop farming were associated with either airflow limitation or chronic bronchitis. Conclusion Although some features of COPD are associated with some agricultural work, well-designed studies with appropriate diagnostic criteria should be conducted to draw strong conclusions about the relationship between COPD and farming

Combined pulmonary fibrosis and emphysema in hypersensitivity pneumonitis.

International audienceCombined pulmonary fibrosis and emphysema is a distinct syndrome reported in patients who smoke. A 72-year-old, never-smoking female dairy farmer was referred for progressive dyspnoea on exertion, basal crackles on auscultation, normal spirometry and normal lung volumes but decreased diffusing capacity of the lung for carbon monoxide, centrilobular emphysema in the upper zones of the lungs and diffuse infiltrative lung disease in the lower zones on high-resolution CT scan. Bronchoalveolar lavage differential cell count showed 35% lymphocytosis, and precipitating antibodies for Wallemia sebi, Trichoderma species and Cladosporium sphaerospermum were identified. The diagnosis of farmer's lung disease with combined pulmonary fibrosis and emphysema was retained. This case highlights for the first time that hypersensitivity pneumonitis should be suspected in the setting of combined pulmonary fibrosis and emphysema in non-smoking patients

Hypersensitivity pneumonitis in a beautician.

International audienceA radioimmunoassay for guanosine-5'-diphosphate-3'-diphosphate (ppGpp) and adenosine-5'-triphosphate-3'-diphosphate (pppApp) has been developed. The assay method is based on competition of an unlabeled highly phosphorylated nucleotide with 3H-labeled highly phosphorylated nucleotide for binding sites on a specific antibody. Antibodies to ppGpp and pppApp were obtained by immunizing rabbits with the antigen prepared by conjugating ppGpp with human serum albumin using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, and with the antigen prepared by conjugating 8-(6-aminohexyl)amino-adenosine-5'-triphosphate-3'-diphosphate with human serum albumin using glutaraldehyde, respectively. Antibody-bound 3H-labeled highly phosphorylated nucleotides were separated from the free 3H-labeled highly phosphorylated nucleotides by selective adsorption on dextran-coated charcoal. Displacement plots were linear over a concentration range of 5-1,000 pmol/assay tube in a log-probit percentage plot. Application of this method to biological systems offers improved accuracy and convenience compared with the previous 32PO4-labeling technique

Never-smokers with occupational COPD have better exercise capacities and ventilatory efficiency than matched smokers with COPD

Chronic obstructive pulmonary disease (COPD) in never-smokers exposed to organic dusts is still poorly characterized. Therapeutic strategies in COPD are only evaluated in smoking-related COPD. Understanding how never-smokers with COPD behave during exercise is an important prerequisite for optimal management. The objective of this study was to compare physiological parameters measured during exercise between never-smokers with COPD exposed to organic dusts and patients with smoking-related COPD matched for age, sex, and severity of airway obstruction. Healthy control subjects were also studied. Dyspnea (Borg scale), exercise tolerance, and ventilatory constraints were assessed during incremental cycle cardiopulmonary exercise testing in COPD patients at mild to moderate stages [22 exposed to organic dusts: postbronchodilator forced expiratory volume in 1 s (FEV 1)/forced vital capacity (FVC) z score À2.44 ± 0.72 and FEV 1 z score À1.45 ± 0.78; 22 with smokingrelated COPD: FEV 1 /FVC z score À2.45 ± 0.61 and FEV 1 z score À1.43 ± 0.69] and 44 healthy control subjects (including 22 neversmokers). Despite the occurrence of similar significant dynamic hyperinflation, never-smoker COPD patients exposed to organic dusts had lower dyspnea ratings than those with smoking-related COPD. They also had better ventilatory efficiency, higher peak oxygen consumption and peak power output than smoking-related COPD patients, all these parameters being similar to control subjects. Differences in exercise capacity between the two COPD groups were mainly driven by better ventilatory efficiency stemming from preserved diffusion capacity. Never-smokers exposed to organic dusts with mild to moderate COPD have better exercise capacities, better ventilatory efficiency, and better diffusion capacity than matched patients with smoking-related COPD. NEW & NOTEWORTHY It is unknown whether or not neversmokers with chronic obstructive pulmonary disease (COPD) behave like their smoking counterparts during exercise. This is the first study showing that never-smokers with mild to moderate COPD [defined by a postbronchodilator forced expiratory volume in 1 s (FEV 1)/forced vital capacity (FVC) < lower limit of normal] have preserved exercise capacities. They also have lower exertional dyspnea than patients with smoking-related COPD. This suggests that the two COPD groups should not be managed in the same way. chronic obstructive pulmonary disease; exercise tolerance; nonsmoker