Showing papers in "ERJ Open Research in 2021"

Benefits of pulmonary rehabilitation in COVID-19 – a prospective observational cohort study

Abstract: Background Coronavirus disease 2019 (COVID-19) can result in a large variety of chronic health issues such as impaired lung function, reduced exercise performance and diminished quality of life. Our study aimed to investigate the efficacy, feasibility and safety of pulmonary rehabilitation in COVID-19 patients and to compare outcomes between patients with a mild/moderate and a severe/critical course of the disease. Methods Patients in the post-acute phase of a mild to critical course of COVID-19 admitted to a comprehensive 3-week inpatient pulmonary rehabilitation programme were included in this prospective, observational cohort study. Several measures of exercise performance (6-min walk distance (6MWD)), lung function (forced vital capacity (FVC)) and quality of life (36-question short-form health survey (SF-36)) were assessed before and after pulmonary rehabilitation. Results 50 patients were included in the study (24 with mild/moderate and 26 with severe/critical COVID-19). On admission, patients had a reduced 6MWD (mild: median 509 m, interquartile range (IQR) 426–539 m; severe: 344 m, 244–392 m), an impaired FVC (mild: 80%, 59–91%; severe: 75%, 60–91%) and a low SF-36 mental health score (mild: 49 points, 37–54 points; severe: 39 points, 30–53 points). Patients attended a median (IQR) 100% (94–100%) of all provided pulmonary rehabilitation sessions. At discharge, patients in both subgroups improved in 6MWD (mild/moderate: +48 m, 35–113 m; severe/critical: +124 m, 75–145 m; both p Conclusion Our study shows that pulmonary rehabilitation is a feasible, safe and effective therapeutic option in COVID-19 patients independent of disease severity.

Chest radiography is a poor predictor of respiratory symptoms and functional impairment in survivors of severe COVID-19 pneumonia

Abstract: Background A standardised approach to assessing COVID-19 survivors has not been established, largely due to the paucity of data on medium- and long-term sequelae. Interval chest radiography is recommended following community-acquired pneumonia; however, its utility in monitoring recovery from COVID-19 pneumonia remains unclear. Methods This was a prospective single-centre observational cohort study. Patients hospitalised with severe COVID-19 pneumonia (admission duration ≥48 h and oxygen requirement ≥40% or critical care admission) underwent face-to-face assessment at 4–6 weeks post-discharge. The primary outcome was radiological resolution of COVID-19 pneumonitis (Radiographic Assessment of Lung Oedema score Results 119 patients were assessed between June 3, 2020 and July 2, 2020 at median (interquartile range (IQR)) 61 (51–67) days post-discharge: mean±sd age 58.7±14.4 years, median (IQR) body mass index 30.0 (25.9–35.2) kg·m−2, 62% male and 70% ethnic minority. Despite radiographic resolution of pulmonary infiltrates in 87%, modified Medical Research Council Dyspnoea (breathlessness) scale grades were above pre-COVID-19 baseline in 44%, and patients reported persistent fatigue (68%), sleep disturbance (57%) and breathlessness (32%). Screening thresholds were breached for post-traumatic stress disorder (25%), anxiety (22%) and depression (18%). 4MGS was slow ( Conclusions Persistent symptoms, adverse mental health outcomes and physiological impairment are common 2 months after severe COVID-19 pneumonia. Follow-up chest radiography is a poor marker of recovery; therefore, holistic face-to-face assessment is recommended to facilitate early recognition and management of post-COVID-19 sequelae.

Recovery from COVID-19: A sprint or marathon? 6-month follow-up data from online long COVID-19 support group members

Abstract: Background It remains unknown whether and to what extent members of online long COVID-19 peer support groups remain symptomatic and limited over time. Therefore, we aimed to evaluate symptoms in members of online long COVID-19 peer support groups up to 6 months after the onset of COVID-19-related symptoms. Methods Demographics, symptoms, health status, work productivity, functional status and health-related quality of life were assessed about 3 and 6 months after the onset of COVID-19-related symptoms in members of online long COVID-19 peer support groups. Results Data of 239 patients with a confirmed COVID-19 diagnosis (83% women; median (IQR) age: 50 (39–56) years) were analysed. During the infection, a median (IQR) of 15 (11–18) symptoms was reported, which was significantly lower 3 and 6 months later: 6 (4–9) and 6 (3–8), respectively (p Conclusion Although patients with confirmed COVID-19, who were all members of online long COVID-19 peer support groups, reported significant improvements in work productivity, functional status and quality of life between 3 and 6 months follow up, these data clearly highlight the long-term impact of COVID-19, as approximately 6 months after the onset of COVID-19-related symptoms a large proportion still experienced persistent symptoms, a moderate-to-poor health, moderate to severe functional limitations, considerable loss in work productivity, and/or an impaired quality of life. Action is needed to improve the management and healthcare of these patients.

Increased blood angiotensin converting enzyme 2 activity in critically ill COVID-19 patients

Abstract: Critically ill #COVID19 patients display markedly increased alternative angiotensin pathway activity compared to healthy controls, reflected by increased blood ACE2 levels as well as decreased angiotensin-II and enhanced angiotensin-1-7 formation https://bit.ly/2MU1z4z.

Diagnosis of COVID-19 by exhaled breath analysis using gas chromatography-mass spectrometry

Abstract: Background The ongoing coronavirus disease 2019 (COVID-19) pandemic has claimed over two and a half million lives worldwide so far. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is perceived to be seasonally recurrent, and a rapid noninvasive biomarker to accurately diagnose patients early on in their disease course will be necessary to meet the operational demands for COVID-19 control in the coming years. Objective The aim of this study was to evaluate the role of exhaled breath volatile biomarkers in identifying patients with suspected or confirmed COVID-19 infection, based on their underlying PCR status and clinical probability. Methods A prospective, real-world, observational study was carried out, recruiting adult patients with suspected or confirmed COVID-19 infection. Breath samples were collected using a standard breath collection bag, modified with appropriate filters to comply with local infection control recommendations, and samples were analysed using gas chromatography–mass spectrometry (TD-GC-MS). Results 81 patients were recruited between April 29 and July 10, 2020, of whom 52 out of 81 (64%) tested positive for COVID-19 by reverse transcription–polymerase chain reaction (RT-PCR). A regression analysis identified a set of seven exhaled breath features (benzaldehyde, 1-propanol, 3,6-methylundecane, camphene, beta-cubebene, iodobenzene and an unidentified compound) that separated PCR-positive patients with an area under the curve (AUC): 0.836, sensitivity: 68%, specificity: 85%. Conclusions GC-MS-detected exhaled breath biomarkers were able to identify PCR-positive COVID-19 patients. External replication of these compounds is warranted to validate these results.

Outcomes of COVID-19 patients treated with continuous positive airway pressure outside the intensive care unit

Abstract: Aim We aimed to characterise a large population of coronavirus disease 2019 (COVID-19) patients with moderate-to-severe hypoxaemic acute respiratory failure (ARF) receiving continuous positive airway pressure (CPAP) outside the intensive care unit (ICU), and to ascertain whether the duration of CPAP application increased the risk of mortality for patients requiring intubation. Methods In this retrospective, multicentre cohort study, we included adult COVID-19 patients, treated with CPAP outside ICU for hypoxaemic ARF from 1 March to 15 April, 2020. We collected demographic and clinical data, including CPAP therapeutic goal, hospital length of stay and 60-day in-hospital mortality. Results The study included 537 patients with a median (interquartile range (IQR) age of 69 (60–76) years. 391 (73%) were male. According to the pre-defined CPAP therapeutic goal, 397 (74%) patients were included in the full treatment subgroup, and 140 (26%) in the do not intubate (DNI) subgroup. Median (IQR) CPAP duration was 4 (1–8) days, while hospital length of stay was 16 (9–27) days. 60-day in-hospital mortality was 34% (95% CI 0.304–0.384%) overall, and 21% (95% CI 0.169–0.249%) and 73% (95% CI 0.648–0.787%) for full treatment and DNI subgroups, respectively. In the full treatment subgroup, in-hospital mortality was 42% (95% CI 0.345–0.488%) for 180 (45%) CPAP failures requiring intubation, and 2% (95% CI 0.008–0.035%) for the remaining 217 (55%) patients who succeeded. Delaying intubation was associated with increased mortality (hazard ratio 1.093, 95% CI 1.010–1.184). Conclusions We described a large population of COVID-19 patients treated with CPAP outside ICU. Intubation delay represents a risk factor for mortality. Further investigation is needed for early identification of CPAP failures.

Underestimation of COVID-19 mortality during the pandemic

Abstract: Background There has been considerable international variation in mortality during the COVID-19 pandemic. The objective of this study was to investigate the differences between mortality registered as due to COVID-19 and the excess all-cause mortality reported in countries worldwide during the COVID-19 pandemic. Methods Ecological analysis of 22 countries compared five-year historical all-cause mortality, reported all-cause mortality and expected all-cause mortality (calculated as the historical mortality plus the reported deaths attributed to COVID-19). Data available from the first week of January 2020 to that most recently available were analysed. Results Compared to the preceding five years, there was an excess of 716 616 deaths of which 64.3% were attributed to COVID-19. The proportion of deaths registered as COVID-19 related/excess deaths varied markedly between countries, ranging between 30% and 197% in those countries that had an excess of deaths during the period of observation. In most countries where a definite peak in COVID-19 related deaths occurred, the increase in reported all-cause mortality preceded the increase in COVID-19 reported mortality. During the latter period of observation, a few countries reported fewer all-cause deaths than the historical figures. Conclusion The increases in all-cause mortality preceded the increase in COVID-19 mortality in most countries that had definite spikes in COVID-19 mortality. The number of deaths attributed to COVID-19 was underestimated by at least 35%. Together these findings suggest that calculation of excess all-cause mortality is a better predictor of COVID-19 mortality than the reported rates, in those countries experiencing definite increases in mortality.

Current strategies for managing chronic thromboembolic pulmonary hypertension: results of the worldwide prospective CTEPH Registry

Abstract: Background Pulmonary endarterectomy (PEA), pulmonary arterial hypertension (PAH) therapy and balloon pulmonary angioplasty (BPA) are currently accepted therapies for chronic thromboembolic pulmonary hypertension (CTEPH). This international CTEPH Registry identifies clinical characteristics of patients, diagnostic algorithms and treatment decisions in a global context. Methods 1010 newly diagnosed consecutive patients were included in the registry between February 2015 and September 2016. Diagnosis was confirmed by right heart catheterisation, ventilation–perfusion lung scan, computerised pulmonary angiography and/or invasive pulmonary angiography after at least 3 months on anticoagulation. Results Overall, 649 patients (64.3%) were considered for PEA, 193 (19.1%) for BPA, 20 (2.0%) for both PEA and BPA, and 148 (14.7%) for PAH therapy only. Reasons for PEA inoperability were technical inaccessibility (n=235), comorbidities (n=63) and patient refusal (n=44). In Europe and America and other countries (AAO), 72% of patients were deemed suitable for PEA, whereas in Japan, 70% of patients were offered BPA as first choice. Sex was evenly balanced, except in Japan where 75% of patients were female. A history of acute pulmonary embolism was reported for 65.6% of patients. At least one PAH therapy was initiated in 35.8% of patients (26.2% of PEA candidates, 54.5% of BPA candidates and 54.1% of those not eligible for either PEA or BPA). At the time of analysis, 39 patients (3.9%) had died of pulmonary hypertension-related causes (3.5% after PEA and 1.8% after BPA). Conclusions The registry revealed noticeable differences in patient characteristics (rates of pulmonary embolism and sex) and therapeutic approaches in Japan compared with Europe and AAO.

COPD in the time of COVID-19: an analysis of acute exacerbations and reported behavioural changes in patients with COPD

Abstract: Introduction The impact of the SARS-CoV-2 pandemic, and lockdown measures, on acute exacerbations of COPD (AECOPD) is unknown. We aimed to evaluate the change in AECOPD treatment frequency during the first 6 weeks of lockdown in the UK compared with 2019 and assess changes in self-reported behaviour and well-being. Methods In this observational study in Leicestershire, UK, patients with COPD under a secondary care clinic were recruited. Exacerbation frequency in the first 6 weeks of COVID lockdown was compared with the same period in 2019 using electronic health records. A telephone survey was used to assess changes in anxiety, inhaler adherence, physical activity, and behaviour during the pre-lockdown and lockdown periods compared to normal. Results 160 participants were recruited (mean [sd] age 67.3 [8.1] years, 88 [55%] male, FEV1 34.3 [13] % predicted). 140 [88%] reported at least one AECOPD in the previous year. Significantly more community treated exacerbations were observed in 2020 compared with 2019 (126 versus 99, p=0.026). The increase was a result of multiple courses of treatment, with a similar proportion of patients receiving at least one course (34.4% versus 33.8%). During “lockdown” participants reported significantly increased anxiety, adherence to their preventative inhalers, and good adherence to shielding advice (all p Discussion Treatment for AECOPD events increased during the first 6 weeks of the SARS-CoV-2 pandemic in the UK compared to 2019. This was associated with increased symptoms of anxiety and significant behavioural change.

Descriptive analysis of long COVID sequelae identified in a multidisciplinary clinic serving hospitalised and non-hospitalised patients

Abstract: Background There are emerging data of long-term effects of coronavirus disease 2019 (COVID-19) comprising a diversity of symptoms. The aim of this study was to systematically describe and measure pulmonary and extra-pulmonary post-COVID-19 complications in relation to acute COVID-19 severity. Methods Patients attending a standard of care 3 months post-hospitalisation follow-up visit and those referred by their general practitioner because of persistent post-COVID-19 symptoms were included. Patients underwent symptomatic, quality of life, pulmonary (lung function and high-resolution computed tomography (HRCT)), cardiac (high-resolution ECG), physical (1-min sit and stand test (1-MSTST), handgrip strength, cardiopulmonary exercise testing (CPET)) and cognitive evaluations. Results All 34 hospitalised and 22 out of 23 non-hospitalised patients had >= 1 complaint or abnormal finding at follow-up. Overall, 67% of patients were symptomatic (Medical Research Council (MRC) >= 2 or COPD assessment test (CAT) >= 10), with no difference between hospitalised versus non-hospitalised patients. Pulmonary function ( forced expiratory volume in 1 s (FEV1) or diffusing capacity of the lung for carbon monoxide (D-LCO)) <80% of predicted) was impaired in 68% of patients. D-LCO was significantly lower in those hospitalised compared to non-hospitalised (70.1 +/- 18.0 versus 80.2 +/- 11.2% predicted, p=0.02). Overall, 53% had an abnormal HRCT (predominantly ground-glass opacities) with higher composite computed tomography (CT) scores in hospitalised versus non-hospitalised patients (2.3 (0.1-4.8) and 0.0 (0.0-0.3), p<0.001). 1-MSTST was below the 25th percentile in almost half of patients, but no signs of cardiac dysfunction were found. Cognitive impairments were present in 59-66% of hospitalised and 31-44% of non-hospitalised patients (p=0.08). Conclusion Three months after COVID-19 infection, patients were still symptomatic and demonstrated objective respiratory, functional, radiological and cognitive abnormalities, which were more prominent in hospitalised patients. Our study underlines the importance of multidimensional management strategies in these patients.

Identification and treatment of T2-low asthma in the era of biologics

Abstract: Currently, and based on the development of relevant biologic therapies, T2-high is the most well-defined endotype of asthma. Although much progress has been made in elucidating T2-high inflammation pathways, no specific clinically applicable biomarkers for T2-low asthma have been identified. The therapeutic approach of T2-low asthma is a problem urgently needing resolution, firstly because these patients have poor response to steroids, and secondly because they are not candidates for the newer targeted biologic agents. Thus, there is an unmet need for the identification of biomarkers that can help the diagnosis and endotyping of T2-low asthma. Ongoing investigation is focusing on neutrophilic airway inflammation mediators as therapeutic targets, including interleukin (IL)-8, IL-17, IL-1, IL-6, IL-23 and tumour necrosis factor-α; molecules that target restoration of corticosteroid sensitivity, mainly mitogen-activated protein kinase inhibitors, tyrosine kinase inhibitors and phosphatidylinositol 3-kinase inhibitors; phosphodiesterase (PDE)3 inhibitors that act as bronchodilators and PDE4 inhibitors that have an anti-inflammatory effect; and airway smooth muscle mass attenuation therapies, mainly for patients with paucigranulocytic inflammation. This article aims to review the evidence for noneosinophilic inflammation being a target for therapy in asthma; discuss current and potential future therapeutic approaches, such as novel molecules and biologic agents; and assess clinical trials of licensed drugs in the treatment of T2-low asthma.

Increased circulating levels of angiotensin-(1-7) in severely ill COVID-19 patients.

Abstract: This letter reports an unexpected increase of the ACE2 product angiotensin-(1-7) and a parallel decrease of its substrate angiotensin II, suggesting a dysregulation of the renin-angiotensin system towards angiotensin-(1-7) formation in #COVID19 patients https://bit.ly/3xFXuTU.

Prevalence, incidence and characteristics of chronic cough among adults from the Canadian Longitudinal Study on Aging

Abstract: The global prevalence of chronic cough is highly variable, ranging from 2% to 18% There is a lack of data on the prevalence and incidence of chronic cough in the general population The objective of this study was to investigate the prevalence and incidence of chronic cough in a sample of Canadian adults, and how these are influenced by age, sex, smoking, respiratory symptoms, medical comorbidities and lung function Participants with chronic cough were identified from the Canadian Longitudinal Study on Aging (CLSA) based on self-reported daily cough in the past 12 months This is a prospective, nationally generalisable, stratified random sample of adults aged 45–85 years at baseline recruited between 2011 and 2015, and followed-up 3 years later The prevalence and incidence per 100 person-years are described, with adjustments for age, sex and smoking Of the 30 097 participants, 29 972 completed the chronic cough question at baseline and 26 701 did so at follow-up The prevalence of chronic cough was 158% at baseline and 176% at follow-up with 104–171% variation across seven provinces included in the CLSA comprehensive sample Prevalence increased with age and current smoking, and was higher in males (152%), Caucasians (14%) and those born in North America, Europe or Oceania (14%) The incidence of chronic cough adjusted for age, sex and smoking was higher in males and in underweight and obese subjects Subjects with respiratory symptoms, airway diseases, lower forced expiratory volume in 1 s (% predicted), cardiovascular diseases, psychological disorders, diabetes and chronic pain had a higher incidence of chronic cough The prevalence and incidence of chronic cough is high in the CLSA sample with geographic, ethnic and gender differences, influenced by a number of medical comorbidities

Evaluation of a multicomponent grading system for obstructive sleep apnoea: the Baveno classification.

Abstract: New findings on pathophysiology, epidemiology, and outcome have raised concerns on the relevance of the apnoea-hypopnoea index (AHI) in the classification of obstructive sleep apnoea (OSA) severity. Recently, a multicomponent grading system decision integrating symptomatology and comorbidities (Baveno classification), was proposed to characterise OSA and to guide therapeutic decisions. We evaluated whether this system reflects the OSA population, whether it translates into differences in outcomes, and whether the addition of AHI improves the scheme. A total of 14 499 OSA patients from the European Sleep Apnoea Database cohort were analysed. The groups were homogeneously distributed and were found to clearly stratify the population with respect to baseline parameters. Differences in sleepiness and blood pressure between the groups were analysed in a subgroup of patients after 24-36 months of treatment. Group A (minor symptoms and comorbidities) did not demonstrate any effect of treatment on outcome. However, groups B (severe symptoms, minor comorbidities), C (minor symptoms, severe comorbidities) and D (severe symptoms and comorbidities) were associated with improvement in either or both parameters with treatment. The AHI is an essential prerequisite of the diagnosis; however, adding the AHI did not improve the classification. Rather, it was inferior with respect to guiding the treatment decision. Thus, the Baveno classification allows a better stratification of the OSA population and may provide a better guidance for therapeutic decisions in OSA.

Self-proning in COVID-19 patients on low-flow oxygen therapy: a cluster randomised controlled trial

Abstract: Rationale and objectives Prone positioning as a complement to oxygen therapy to treat hypoxemia in coronavirus disease (COVID-19) pneumonia in spontaneously breathing patients has been widely adopted, despite a lack of evidence for its benefit. To test the hypothesis that a simple incentive to self-prone for a maximum of 12 h per day would decrease oxygen needs in patients admitted to the ward for COVID-19 pneumonia on low-flow oxygen therapy. Methods Twenty-seven patients with confirmed COVID-19 pneumonia admitted to Geneva University Hospitals were included in the study. Ten patients were randomised to self-prone positioning and 17 to usual care. Measurements and Main Results Oxygen needs assessed by oxygen flow on nasal cannula at inclusion were similar between groups. Twenty-four hours after starting the intervention, the median oxygen flow was 1.0 L·min−1 (interquartile range, 0.1–2.9) in the prone position group and 2.0 L·min−1 (interquartile range, 0.5–3.0) in the control group (p=0.507). Median oxygen saturation/fraction of inspired oxygen ratio was 390 (interquartile range, 300–432) in the prone position group and 336 (interquartile range, 294–422) in the control group (p=0.633). One patient from the intervention group who did not self-prone was transferred to the high-dependency unit. Self-prone positioning was easy to implement. The intervention was well tolerated and only mild side-effects were reported. Conclusions Self-prone positioning in patients with COVID-19 pneumonia requiring low-flow oxygen therapy resulted in a clinically meaningful reduction of oxygen flow, but without reaching statistical significance.

INTREPID: single- versus multiple-inhaler triple therapy for COPD in usual clinical practice

Abstract: Introduction Real-world trial data comparing single- with multiple-inhaler triple therapy (MITT) in COPD patients are currently lacking. The effectiveness of once-daily single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) and MITT were compared in usual clinical care. Methods INTREPID was a multicentre, randomised, open-label, phase IV effectiveness study comparing FF/UMEC/VI 100/62.5/25 µg via the ELLIPTA inhaler with a clinician9s choice of any approved non-ELLIPTA MITT in usual COPD clinical practice in five European countries. Primary endpoint was proportion of COPD Assessment Test (CAT) responders (≥2-unit decrease in CAT score from baseline) at Week 24. Secondary endpoints in a subpopulation included change from baseline in forced expiratory volume in 1 s (FEV1) and percentage of patients making ≥1 critical error in inhalation technique at Week 24. Safety was also assessed. Results 3092 patients were included (FF/UMEC/VI N=1545; MITT N=1547). The proportion of CAT responders at Week 24 was significantly greater with FF/UMEC/VI versus non-ELLIPTA MITT (odds ratio: 1.31; 95% confidence interval [CI]: 1.13, 1.51; p Conclusions In a usual clinical care setting, treatment with once-daily single-inhaler FF/UMEC/VI resulted in significantly more patients gaining health status improvement and greater lung function improvement versus non-ELLIPTA MITT.

Impact of COVID-19 on COPD and asthma admissions, and the pandemic from a patient's perspective

Abstract: There has been a significant reduction in all-cause and exacerbation-related #asthma and #COPD admissions during the #COVID19 pandemic. Patients also report a subjective decline in disease control and describe a negative impact on their mental health. https://bit.ly/2Kv0O0H.

ICS-formoterol reliever versus ICS and short-acting β2-agonist reliever in asthma: a systematic review and meta-analysis.

Abstract: Background The Global Initiative for Asthma recommends as-needed inhaled corticosteroid (ICS)-formoterol as an alternative to maintenance ICS plus short-acting β2-agonist (SABA) reliever at step 2 of its stepwise treatment algorithm. Our aim was to assess the efficacy and safety of these two treatment regimens, with a focus on prevention of severe exacerbation. Methods We performed a systematic review and meta-analysis of all randomised controlled trials (RCTs) comparing as-needed ICS-formoterol with maintenance ICS plus SABA. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrials.gov were searched from database inception to 12 December 2019. The primary outcome was time to first severe exacerbation. RCTs were excluded if they used as-needed budesonide-formoterol as part of a maintenance and reliever regimen, or did not report on severe exacerbations. The review is registered with PROSPERO (identifier number CRD42020154680). Results Four RCTs (n=8065 participants) were included in the analysis. As-needed ICS-formoterol was associated with a prolonged time to first severe exacerbation (hazard ratio 0.85, 95% CI 0.73–1.00; p=0.048) and reduced daily ICS dose (mean difference −177.3 μg, 95% CI −182.2–−172.4 μg). Asthma symptom control was worse in the as-needed group (Asthma Control Questionnaire-5 mean difference 0.12, 95% CI 0.09–0.14), although this did not meet the minimal clinically important difference of 0.50 units. There was no significant difference in serious adverse events (OR 1.07, 95% CI 0.84–1.36). Conclusion As-needed ICS-formoterol offers a therapeutic alternative to maintenance low-dose ICS plus SABA in asthma and may be the preferred option when prevention of severe exacerbation is the primary aim of treatment.

Nicotine upregulates ACE2 expression and increases competence for SARS-CoV-2 in human pneumocytes

Abstract: The coronavirus disease 2019 (COVID-19) pandemic has a variable degree of severity according to underlying comorbidities and life-style. Several research groups have reported an association between cigarette smoking and increased severity of COVID-19. The exact mechanism of action is largely unclear. We exposed low angiotensin-converting enzyme 2 (ACE2)-expressing human pulmonary adenocarcinoma A549 epithelial cells to nicotine and assessed ACE2 expression at different times. We further used the nicotine-exposed cells in a virus neutralisation assay. Nicotine exposure induces rapid and long-lasting increases in gene and protein expression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor ACE2, which in turn translates into increased competence for SARS-CoV-2 replication and cytopathic effect. These findings show that nicotine worsens SARS-CoV-2 pulmonary infection and have implications for public health policies.

Radiological-pathological signatures of patients with COVID-19-related pneumomediastinum: is there a role for the Sonic hedgehog and Wnt5a pathways?

Abstract: Pneumomediastinum is a rare complication of ARDS but is more common during #COVID19. The fibrous hyaline degeneration of the tracheal rings seen in this autoptic series is an original observation that has not been previously described in COVID-19 patients. https://bit.ly/3vxTQde.

Placing a mask on COVID-19 patients during high-flow nasal cannula therapy reduces aerosol particle dispersion

Abstract: Wearing a surgical/procedure mask over high-flow nasal cannula (HFNC) reduces aerosol particle concentrations in the patients' vicinity. Wearing a mask over HFNC should be encouraged to reduce risks of aerosol transmission. #COVID19 https://bit.ly/2HLg5cE.

Increased myofibroblasts in the small airways, and relationship to remodelling and functional changes in smokers and COPD patients: potential role of epithelial-mesenchymal transition.

Abstract: Introduction: Previous reports have shown epithelial–mesenchymal transition (EMT) as an active process that contributes to small airway fibrotic pathology. Myofibroblasts are highly active pro-fibrotic cells that secrete excessive and altered extracellular matrix (ECM). Here we relate small airway myofibroblast presence with airway remodelling, physiology and EMT activity in smokers and COPD patients. Methods: Lung resections from nonsmoker controls, normal lung function smokers and COPD current and ex-smokers were stained with anti-human α-smooth muscle actin (SMA), collagen 1 and fibronectin. αSMA+ cells were computed in reticular basement membrane (Rbm), lamina propria and adventitia and presented per mm of Rbm and mm2 of lamina propria. Collagen-1 and fibronectin are presented as a percentage change from normal. All analyses including airway thickness were measured using Image-proplus 7.0. Results: We found an increase in subepithelial lamina propria (especially) and adventitia thickness in all pathological groups compared to nonsmoker controls. Increases in αSMA+ myofibroblasts were observed in subepithelial Rbm, lamina propria and adventitia in both the smoker and COPD groups compared to nonsmoker controls. Furthermore, the increase in the myofibroblast population in the lamina propria was strongly associated with decrease in lung function, lamina propria thickening, increase in ECM protein deposition, and finally EMT activity in epithelial cells. Conclusions: This is the first systematic characterisation of small airway myofibroblasts in COPD based on their localisation, with statistically significant correlations between them and other pan-airway structural, lung function and ECM protein changes. Finally, we suggest that EMT may be involved in such changes.

Donor-derived, cell-free DNA levels by next-generation targeted sequencing are elevated in allograft rejection after lung transplantation.

Abstract: Surveillance after lung transplantation is critical to the detection of acute cellular rejection (ACR) and prevention of chronic lung allograft dysfunction (CLAD). Therefore, we measured donor-derived cell-free DNA (dd-cfDNA) implementing a clinical-grade, next-generation targeted sequencing assay in 107 plasma samples from 38 unique lung transplantation recipients with diagnostic cohorts classified as: (1) biopsy-confirmed or treated ACR, (2) antibody-mediated rejection (AMR), (3) obstructive CLAD, (4) allograft infection (INFXN) and (5) Stable healthy allografts (STABLE). Our principal findings are as follows: (1) dd-cfDNA level was elevated in ACR (median 0.91%; interquartile range (IQR): 0.39-2.07%), CLAD (2.06%; IQR: 0.57-3.67%) and an aggregated cohort of rejection encompassing allograft injury (1.06%; IQR: 0.38-2.51%), compared with the STABLE cohort (0.38%; IQR: 0.23-0.87%) (p=0.02); (2) dd-cfDNA level with AMR was elevated (1.34%; IQR: 0.34-2.40%) compared to STABLE, although it did not reach statistical significance (p=0.07) due to limitations in sample size; (3) there was no difference in dd-cfDNA for allograft INFXN (0.39%; IQR: 0.18-0.67%) versus STABLE, which may relate to differences in "tissue injury" with the spectrum of bronchial colonisation versus invasive infection; (4) there was no difference for dd-cfDNA in unilateral versus bilateral lung transplantation; (5) "optimal threshold" for dd-cfDNA for aggregated rejection events representing allograft injury was determined as 0.85%, with sensitivity=55.6%, specificity=75.8%, positive predictive value (PPV)=43.3% and negative predictive value (NPV)=83.6%. Measurement of plasma dd-cfDNA may be a clinically useful tool for the assessment of lung allograft health and surveillance for "tissue injury" with a spectrum of rejection.

Alveolar macrophage transcriptomic profiling in COPD shows major lipid metabolism changes.

Abstract: Background Immune cells play a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Albeit established changes in distribution and cellular functions of major immune cells, such as alveolar macrophages (AMs) and neutrophils, their transcriptional reprogramming and contribution to the pathophysiology of COPD are still not fully understood. Aim and methods To determine changes in transcriptional reprogramming and lipid metabolism in the major immune cell type within the bronchoalveolar lavage fluid, we analysed whole transcriptomes and lipidomes of sorted CD45+Lin−HLA-DR+CD66b−Autofluorescencehi AMs from control and COPD patients. Results We observed global transcriptional reprogramming featuring a spectrum of activation states, including pro- and anti-inflammatory signatures. We further detected significant changes between COPD patients and controls in genes involved in lipid metabolism, such as fatty acid biosynthesis in GOLD2 patients. Based on these findings, assessment of a total of 202 lipid species in sorted AMs revealed changes of cholesteryl esters, monoacylglycerols and phospholipids in a disease grade-dependent manner. Conclusions Transcriptome and lipidome profiling of COPD AMs revealed GOLD grade-dependent changes, such as in cholesterol metabolism and interferon alpha and gamma responses.

The protective effect of SARS-CoV-2 antibodies in Scottish healthcare workers

Abstract: Background Healthcare workers (HCWs) are believed to be at increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It is not known to what extent the natural production of antibodies to SARS-CoV-2 is protective against re-infection. Methods A prospective observational study of HCWs in Scotland (UK) from May to September 2020 was performed. The Siemens SARS-CoV-2 total antibody assay was used to establish seroprevalence in this cohort. Controls, matched for age and sex to the general local population, were studied for comparison. New infections (up to 2 December 2020) post antibody testing were recorded to determine whether the presence of SARS-CoV-2 antibodies protects against re-infection. Results A total of 2063 health and social care workers were recruited for this study. At enrolment, 300 HCWs had a positive antibody test (14.5%). 11 out of 231 control sera tested positive (4.8%). HCWs therefore had an increased likelihood of a positive test (OR 3.4, 95% CI 1.85-6.16; p<0.0001). Dentists were most likely to test positive. 97.3% of patients who had previously tested positive for SARS-CoV-2 by reverse transcriptase (RT)-PCR had positive antibodies. 18.7% had an asymptomatic infection. There were 38 new infections with SARS-CoV-2 in HCWs who were previously antibody negative, and one symptomatic RT-PCR-positive re-infection. The presence of antibodies was therefore associated with an 85% reduced risk of re-infection with SARS-CoV-2 (hazard ratio 0.15, 95% CI 0.06-0.35; p=0.026). Conclusion HCWs were three times more likely to test positive for SARS-CoV-2 than the general population. Almost all infected individuals developed an antibody response, which was 85% effective in protecting against re-infection with SARS-CoV-2.

ROSE: radiology, obstruction, symptoms and exposure - a Delphi consensus definition of the association of COPD and bronchiectasis by the EMBARC Airways Working Group.

Abstract: Introduction The coexistence of chronic obstructive pulmonary disease (COPD) and bronchiectasis (BE) seems to be common and associated with a worse prognosis than for either disease individually. However, no definition of this association exists to guide researchers and clinicians. Methods We conducted a Delphi survey involving expert pulmonologists and radiologists from Europe, Turkey and Israel in order to define the “COPD-BE association”. A panel of 16 experts from EMBARC selected 35 statements for the survey after reviewing scientific literature. Invited participants, selected on the basis of expertise, geographical and gender distribution, were asked to express agreement on the statements. Consensus was defined as a score of ≥6 points (scale 0 to 9) in ≥70% of answers across two scoring rounds. Results A-hundred-and-two (72.3%) out of 141 invited experts participated the first round. Their response rate in the second round was 81%. The final consensus definition of “COPD-BE association” was: “The coexistence of (1) specific radiological findings (abnormal bronchial dilatation, airways visible within 1 cm of pleura and/or lack of tapering sign in ≥1 pulmonary segment and in >1 lobe) with (2) an obstructive pattern on spirometry (FEV1/FVC Conclusions The Delphi process formulated a European consensus definition of “COPD-BE association”. We hope this definition will have broad applicability across clinical practice and research in the future.

What matters to people with severe asthma? Exploring add-on asthma medication and outcomes of importance

Abstract: There is an increasing number of new therapies for severe asthma; however, what outcomes people with severe asthma would like improved and what aspects they prioritise in new medications remain unknown. This study aimed to understand what outcomes are important to patients when prescribed new treatments and to determine the characteristics of importance to patients in their choice of asthma treatments. Participants with severe asthma (n=50) completed a cross-sectional survey that ranked 17 potential hypothetical outcomes of treatment using a seven-point Likert scale, as well as selecting their top five overall outcomes. Participants also completed hypothetical scenarios trading off medication characteristics for four hypothetical add-on asthma treatments. Participants (58% male), had a mean±sd age of 62.2±13.5 years. Their top three prioritised outcomes were: to improve overall quality of life (selected by 83% of people), reduce number and severity of asthma attacks (72.3%), and being able to participate in physical activity (59.6%) When trading off medication characteristics, the majority of patients with severe asthma chose the hypothetical medication with the best treatment efficacy (68%). However, a subgroup of patients prioritised the medication's side-effect profile and mode of delivery to select their preferred medication. People with severe asthma value improved quality of life as an important outcome of treatment. Shared decision-making discussions between clinicians and patients that centre around medication efficacy and side-effect profile can incorporate patient preferences for add-on therapy in severe asthma.

Conservative management of COVID-19 associated hypoxaemia

Abstract: This correspondence argues that happy hypoxaemic patients should not be intubated as long as they remain happy https://bitly/3csrpWO

The impact of the first COVID-19 surge on severe asthma patients in the UK. Which is worse: the virus or the lockdown?

Abstract: Asthma therapy, including monoclonal antibodies, was not associated with #COVID19 infection or hospitalisation in a UK severe asthma population. Shielding led to a reported worsening of mental health in nearly half of patients contacted (47%). https://bit.ly/3jImUsG.

Sex Disparities in Cystic Fibrosis: Review on the Effect of Female Sex Hormones on Lung Pathophysiology and Outcomes

Abstract: Sex differences in morbidity and mortality have been reported in the cystic fibrosis (CF) population worldwide. However, it is unclear why CF women have worse clinical outcomes than men. In this review, we focus on the influence of female sex hormones on CF pulmonary outcomes and summarise data from in vitro and in vivo experiments on how oestrogen and progesterone might modify mucociliary clearance, immunity and infection in the CF airways. The potential for novel sex hormone-related therapeutic interventions is also discussed.