Estrogen replacement therapy (ERT) is frequently prescribed for postmenopausal women. Epidemiological data suggest that sex hormones may play a role in the expression of asthma, but the mechanism(s) whereby this influence is mediated remain(s) unclear. To better understand the role of physiologic doses of estrogens in airway function, we tested the hypothesis that 17beta-estradiol (E(2), 10 microg/kg per d for 21 d) given to oophorectomized female rats modifies airway responsiveness to cholinergic agonists, compared with oophorectomized rats given placebo. In vivo, the concentration of inhaled acetylcholine (ACh) required to double pulmonary resistance (EC(200)RL) in anesthetized spontaneously breathing tracheotomized rats was calculated as an index of airway responsiveness. E(2)-treated rats were less responsive to ACh than placebo-treated rats (EC(200)RL, 9.40 +/- 1.48 vs. 1.52 +/- 0.85 mg. ml(-1), respectively). Ex vivo airway responsiveness was evaluated with the cumulative concentration-response curve (CCRC) of isolated tracheal segments. Compared with placebo, E(2) treatment significantly increased the EC(50) of ACh (p = 0.01) but did not alter the CCRC to carbachol. Removing the epithelium or treatment with physostigmine abolished the difference in EC(50) of ACh between the groups. Acetylcholinesterase (AChE) activity of homogenized whole trachea was 1.4-fold greater in the E(2)-treated group compared with placebo (p = 0.02), whereas no difference was found in homogenized epithelium-free trachea. We conclude that E(2) treatment decreases airway responsiveness to ACh in ovariectomized rats at least in part by increasing AChE activity dependent on the presence of the epithelium.

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Introduction: Given the pathophysiology of coronavirus disease 19 (COVID-19), persistent pulmonary abnormalities are likely. Methods:We conducted a prospective cohort study in severe COVID-19 patients who had oxygen saturation <94% and were primarily admitted to hospital. We aimed to describe persistent gas exchange abnormalities at 4 months, defined as decreased diffusing capacity of the lungs for carbon monoxide (DLco) and/or desaturation on the 6-minute walk test (6MWT), along with associated mechanisms and risk factors Results: Of the 72 patients included, 76.1% required admission to the intensive care unit (ICU), while 68.5% required invasive mechanical ventilation (MV). 39.1% developed venous thromboembolism (VTE). At 4 months, 61.4% were still symptomatic. Functionally, 39.1% had abnormal carbon monoxide test results and/or desaturation on 6MWT; high-flow oxygen, MV, and VTE during the acute phase were significantly associated. Restrictive lung disease was observed in 23.6% of cases, obstructive lung disease in 16.7%, and respiratory muscle dysfunction in 18.1%. A severe initial presentation with admission to ICU (p=.0181), and VTE occurrence during the acute phase (p=.0089) were associated with these abnormalities. 41% had interstitial lung disease in computed tomography (CT) of the chest. Four patients (5.5%) displayed residual defects on lung scintigraphy, only one of whom had developed VTE during the acute phase (5.5%). The main functional respiratory abnormality (31.9%) was reduced capillary volume (Vc<70%). Conclusion: Among patients with severe COVID-19 pneumonia who were admitted to hospital, 61% were still symptomatic, 39% of patients had persistent functional abnormalities and 41% radiological abnormalities after 4 months. Embolic sequelae were rare but the main functional respiratory abnormality was reduced capillary volume. A respiratory check-up after severe COVID-19 pneumonia may be relevant to improve future management of these patients.

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With first cases noted towards the end of 2019 in China, COVID-19 infection was rapidly become a devastating pandemic. Even if most patients present with a mild to moderate form of the disease, the estimated prevalence of COVID-19-related severe acute respiratory failure (ARF) is 15-20% and 2-12% needed intubation and mechanical ventilation. In addition to mechanical ventilation some other techniques of respiratory support could be used in some forms of COVID-19 related ARF. This position paper of the Respiratory Support and Chronic Care Group of the French Society of Respiratory Diseases is intended to help respiratory clinicians involved in care of COVID-19 pandemic in the rational use of non-invasive techniques such as oxygen therapy, CPAP, non-invasive ventilation and high flow oxygen therapy in managing patients outside intensive care unit (ICU). The aims are: (1) to focus both on the place of each * Corresponding author.