Owennygaard5393

ated complement-activation in a small proportion of these patients highlights the relevance of recognising airway autoimmune phenomena and this requires further evaluation.Background The optimal non-invasive application of external positive end-expiratory pressure (EPAP) to abolish tidal-breathing expiratory flow limitation (EFLT) and minimise intrinsic PEEP (PEEPi) is challenging in COPD patients. We investigated whether auto-titrating EPAP, using the forced oscillation technique (FOT) to detect and abolish EFLT, would minimise PEEPi, work of breathing and neural respiratory drive (NRD) in patients with severe COPD. Methods Patients with COPD with chronic respiratory failure underwent auto-titration of EPAP using a FOT-based algorithm that detected EFLT. Once optimal EPAP was identified, manual titration was performed to assess NRD (using diaphragm and parasternal intercostal muscle electromyography, EMGdi and EMGpara, respectively), transdiaphragmatic inspiratory pressure swings (ΔPdi), transdiaphragmatic pressure-time product (PTPdi), and PEEPi, between EPAP levels 2 cmH2O below to 3 cmH2O above optimal EPAP. Results Of 10 patients enrolled (age 65±6 years; male 60%; body mass index 27.6±7.2 kg.m-2; %predicted FEV1 28.4±8.3), eight had EFLT, and optimal EPAP was 9 (range 4-13) cmH2O. SM-102 in vivo NRD was reduced from baseline EPAP at 1 cmH2O below optimal EPAP on EMGdi and at optimal EPAP on EMGpara. In addition, at optimal EPAP, PEEPi (0.80±1.27 cmH2O versus 1.95± 1.70 cmH2O; p less then 0.05) was reduced compared with baseline. PTPdi (10.3±7.8 cmH2O.s-1 versus 16.8±8.8 cmH2O.s-1; p less then 0.05) and ΔPdi (12.4±7.8 cmH2O versus 18.2±5.1 cmH2O; p less then 0.05) were reduced at optimal EPAP+1 cmH2O compared with baseline. Conclusion Auto-titration of EPAP, using a FOT-based algorithm to abolish EFLT, minimises transdiaphragmatic pressure swings and NRD in patients with COPD and chronic respiratory failure.A strategy of early extubation to non-invasive respiratory support in preterm infants could be boosted by the availability of a decision-support tool for clinicians. Using the Heart Rate Characteristics index (HRCi) with clinical parameters, we derived and validated predictive models for extubation readiness and success.Peri-extubation demographic, clinical and HRCi data for up to 96 h were collected from mechanically ventilated infants in the control arm of a randomised trial involving 8 neonatal centres, where clinicians were blinded to the HRCi scores. The data was used to produce a multivariable regression model for the probability of subsequent re-intubation. Additionally, a survival model was produced to estimate the probability of reintubation in the period after extubation.Of the 577 eligible infants, data from 397 infants (2/3rd) were used to derive the pre-extubation model and 180 infants for validation. The model was also fitted and validated using all combinations of training (5-centres) and test (3-centres) centres. The estimated probability for the validation episodes showed discrimination with high statistical significance, with the area under the curve of 0.72 (0.71, 0.74; p less then 0.001). Data from all infants were used to derive models of the predictive instantaneous hazard of re-intubation adjusted for clinical parameters.Predictive models of extubation readiness and success in real-time can be derived using physiological and clinical variables. The models from our analyses can be accessed using an online tool at www.heroscore.com/extubation/ and have the potential to inform and supplement the confidence of the clinician considering extubation in preterm infants.Background In mild asthma, as-needed budesonide-formoterol is superior or non-inferior to maintenance budesonide plus as-needed short-acting beta2-agonist in reducing severe exacerbations. In this pre-specified analysis, we investigated patterns of inhaled corticosteroid (ICS) and beta2-agonist use in PRACTICAL, a randomised controlled trial. Methods Participants were randomised 11 to as-needed budesonide-formoterol (200/6 mcg Turbuhaler, 1 prn) or maintenance budesonide (200 mcg Turbuhaler, 1 bd) with as-needed terbutaline (250 mcg, 2 prn) for 52 weeks; 110 participants had electronic monitors attached to their study inhalers which captured the time and date of every actuation. Key outcome measures were patterns of ICS and beta2-agonist use. One actuation of budesonide-formoterol was considered to be an equivalent bronchodilator dose as two actuations of terbutaline. Findings Participants randomised to as-needed budesonide-formoterol had more days with no ICS use compared with maintenance budesonide (median total days of no use 156 versus 22 days respectively), lower median daily budesonide dose (164 versus 328 mcg respectively), and a greater median number of days of ≥4 budesonide actuations (4 versus 1 days respectively). Participants randomised to as-needed budesonide-formoterol took higher equivalent doses of beta2-agonist both overall (median number of actuations 0.8 versus 0.3 per day respectively) and in response to worsening asthma (total number of "overuse days" of >8 or >16 actuations of budesonide-formoterol or terbutaline 33 versus 10 respectively). Interpretation The timing of ICS dose when self-titrated to beta2-agonist use is more important than total ICS dose in reducing severe exacerbation risk in mild asthma, when associated with greater overall use of as-needed beta2-agonist.We have read with great interest the paper by Leung et al. published in European Respiratory Journal [1], the correspondence by Russo et al. [2] and also the subsequent comment by the first group [3]. Both research teams are reporting increased ACE-2 expression in airways of current smokers and those with COPD with important implications for COVID-19 patients. Since ACE-2 has been shown to be the main receptor utilised by SARS-CoV-2 to enter the host cells [2], the authors conclude that nicotine is a risk factor for COVID-19 pandemic. Russo et al. [2] have shown that nicotine up-regulates ACE-2 through alpha7 nAChRs which are present in neuronal and non-neuronal cells. Leung et al. [3] provided further evidence in support of this hypothesis and propose the repurposing of alpha7-nAChR antagonists for the pandemic (e.g. methyllycaconitine, alpa-conotoxin), expecting that such treatment will alter ACE-2 expression and prevent SARS-CoV-2 entry.