Genomic attributes of airway commensal bacteria and mucosa.

Microbial communities at the airway mucosal barrier are conserved and highly ordered, in likelihood reflecting co-evolution with human host factors. Freed of selection to digest nutrients, the airway microbiome underpins cognate management of mucosal immunity and pathogen resistance. We show here the initial results of systematic culture and whole-genome sequencing of the thoracic airway bacteria, identifying 52 novel species amongst 126 organisms that constitute 75% of commensals typically present in heathy individuals. Clinically relevant genes encode antimicrobial synthesis, adhesion and biofilm formation, immune modulation, iron utilisation, nitrous oxide (NO) metabolism and sphingolipid signalling. Using whole-genome content we identify dysbiotic features that may influence asthma and chronic obstructive pulmonary disease. We match isolate gene content to transcripts and metabolites expressed late in airway epithelial differentiation, identifying pathways to sustain host interactions with microbiota. Our results provide a systematic basis for decrypting interactions between commensals, pathogens, and mucosa in lung diseases of global significance.

Perceptions surrounding the possible interaction between physical activity, pollution and asthma in children and adolescents with and without asthma.

A cornerstone of asthma management is maintaining physical activity (PA), but this may lead to increased exposure to, and deeper inhalation of, pollutants. Furthermore, children and adolescents may be more susceptible to the deleterious impacts of such exposures. Despite the recent air quality campaigns and media coverage surrounding the dangers of air pollution to respiratory health, few target children and their understanding of such issues.Using semi structured interviews, understanding of PA, air pollution and their interaction was explored with 25 youth aged 7-17 years. Utilising NVIVO 12 software, an atheoretical, inductive thematic analysis was conducted to identify key themes which were subsequently presented as pen profiles with the number of common responses within a theme indicative of its strength.The majority (88%) of youth's indicated traffic-related air pollution and global manufacturing as key sources of air pollution. Whilst all youths were aware of outdoor pollution, only 52% were aware of indoor air pollutants, of which 62% had asthma. Despite some uncertainty, all youths described pollution in a negative fashion, with 52% linking air pollution to undesirable effects on health, specifically respiratory health. PA in a polluted area was thought to be more dangerous than beneficial by 44%, although 24% suggested the benefits of PA would outweigh any detriment from pollution.Youth are aware of, and potentially compensate for, the interaction between air pollution and PA. Strategies are needed to allow youth to make more informed decisions regarding how to promote PA whilst minimising exposure to air pollution.

Heterogeneous Treatment Effects after Inspiratory Muscle Training during Recovery from Postacute COVID-19 Syndrome.

PURPOSE: The objective of this study is to investigate whether heterogeneous treatment effects occur for changes in inspiratory muscle strength, perceived dyspnea, and health-related quality of life after 8 wk of unsupervised home-based inspiratory muscle training (IMT) in adults with postacute coronavirus disease 2019 (COVID-19) syndrome. METHODS: In total, 147 adults with self-reported prior COVID-19 either completed an 8-wk home-based IMT intervention ( n = 111, 92 females, 48 ± 11 yr, 9.3 ± 3.6 months postacute COVID-19 infection) or acted as "usual care" wait list controls ( n = 36, 34 females, 49 ± 12 yr, 9.4 ± 3.2 months postacute COVID-19 infection). RESULTS: Applying a Bayesian framework, we found clear evidence of heterogeneity of treatment response for inspiratory muscle strength: the estimated difference between standard deviations (SD) of the IMT and control groups was 22.8 cm H 2 O (75% credible interval (CrI), 4.7-37.7) for changes in maximal inspiratory pressure (MIP) and 86.8 pressure time units (75% CrI, 55.7-116.7) for sustained MIP (SMIP). Conversely, there were minimal differences in the SD between the IMT and the control group for changes in perceived dyspnea and health-related quality of life, providing no evidence of heterogeneous treatment effects. Higher cumulative power during the IMT intervention was related to changes in MIP ( ß = 10.9 cm H 2 O (95% CrI, 5.3-16.8) per 1 SD) and SMIP ( ß = 63.7 (32.2-95.3) pressure time units per 1 SD), clearly indicating an IMT dose response for changes in inspiratory muscle strength. Older age (>50 yr), a longer time postacute COVID-19 (>3 months), and greater severity of dyspnea at baseline were also associated with smaller improvements in inspiratory muscle strength. CONCLUSIONS: Heterogeneous individual responses occurred after an 8-wk home-based IMT program in people with postacute COVID-19 syndrome. Consistent with standard exercise theory, larger improvements in inspiratory muscle strength are strongly related to a greater cumulative dose of IMT.

Incidence determinants and serological correlates of reactive symptoms following SARS-CoV-2 vaccination.

Prospective population-based studies investigating associations between reactive symptoms following SARS-CoV-2 vaccination and serologic responses to vaccination are lacking. We therefore conducted a study in 9003 adults from the UK general population receiving SARS-CoV-2 vaccines as part of the national vaccination programme. Titres of combined IgG/IgA/IgM responses to SARS-CoV-2 spike (S) glycoprotein were determined in eluates of dried blood spots collected from all participants before and after vaccination. 4262 (47.3%) participants experienced systemic reactive symptoms after a first vaccine dose. Factors associating with lower risk of such symptoms included older age (aOR per additional 10 years of age 0.85, 95% CI: 0.81-0.90), male vs. female sex (0.59, 0.53-0.65) and receipt of an mRNA vaccine vs. ChAdOx1 nCoV-19 (0.29, 0.26-0.32 for BNT162b2; 0.06, 0.01-0.26 for mRNA-1273). Higher risk of such symptoms was associated with SARS-CoV-2 seropositivity and COVID-19 symptoms prior to vaccination (2.23, 1.78-2.81), but not with SARS-CoV-2 seropositivity in the absence of COVID-19 symptoms (0.94, 0.81-1.09). Presence vs. absence of self-reported anxiety or depression at enrolment associated with higher risk of such symptoms (1.24, 1.12-1.39). Post-vaccination anti-S titres were higher among participants who experienced reactive symptoms after vaccination vs. those who did not (P < 0.001). We conclude that factors influencing risk of systemic symptoms after SARS-CoV-2 vaccination include demographic characteristics, pre-vaccination SARS-CoV-2 serostatus and vaccine type. Participants experiencing reactive symptoms following SARS-CoV-2 vaccination had higher post-vaccination titres of IgG/A/M anti-S antibodies. Improved public understanding of the frequency of reactogenic symptoms and their positive association with vaccine immunogenicity could potentially increase vaccine uptake.

Estimating the contribution of respiratory pathogens to acute exacerbations of COPD using routine data.

OBJECTIVES: To characterise microbiology testing and results associated with emergency admissions for acute exacerbation of COPD (AECOPD), and determine the accuracy of ICD-10 codes in retrospectively identifying laboratory-confirmed respiratory pathogens in this setting. METHODS: Using person-level data from the Secure Anonymised Information Linkage Databank in Wales, we extracted emergency admissions for COPD from 1/12/2016 to 30/11/2018 and undertook linkage of admissions data to microbiology data to identify laboratory-confirmed infection. We further used these data to assess the accuracy of pathogen-specific ICD-10 codes. RESULTS: We analysed data from 15,950 people who had 25,715 emergency admissions for COPD over the two-year period. 99.5% of admissions could be linked to a laboratory test within 7 days of admission date. Sputum was collected in 5,013 (19.5%) of admissions, and respiratory virus testing in 1,219 (4.7%). Where respiratory virus testing was undertaken, 46.7% returned any positive result. Influenza was the virus most frequently detected, in 21.5% of admissions where testing was conducted. ICD-10 codes exhibited low sensitivity in detecting laboratory-confirmed respiratory pathogens. CONCLUSIONS: In people admitted to hospital with AECOPD, increased testing for respiratory viruses could enable more effective antibiotic stewardship and isolation of cases. Linkage with microbiology data achieves more accurate and reliable case definitions.

Defining clinical subtypes of adult asthma using electronic health records: Analysis of a large UK primary care database with external validation.

INTRODUCTION: Asthma is one of the commonest chronic conditions in the world. Subtypes of asthma have been defined, typically from clinical datasets on small, well-characterised subpopulations of asthma patients. We sought to define asthma subtypes from large longitudinal primary care electronic health records (EHRs) using cluster analysis. METHODS: In this retrospective cohort study, we extracted asthma subpopulations from the Optimum Patient Care Research Database (OPCRD) to robustly train and test algorithms, and externally validated findings in the Secure Anonymised Information Linkage (SAIL) Databank. In both databases, we identified adults with an asthma diagnosis code recorded in the three years prior to an index date. Train and test datasets were selected from OPCRD using an index date of Jan 1, 2016. Two internal validation datasets were selected from OPCRD using index dates of Jan 1, 2017 and 2018. Three external validation datasets were selected from SAIL using index dates of Jan 1, 2016, 2017 and 2018. Each dataset comprised 50,000 randomly selected non-overlapping patients. Subtypes were defined by applying multiple correspondence analysis and k-means cluster analysis to the train dataset, and were validated in the internal and external validation datasets. RESULTS: We defined six asthma subtypes with clear clinical interpretability: low inhaled corticosteroid (ICS) use and low healthcare utilisation (30% of patients); low-to-medium ICS use (36%); low-to-medium ICS use and comorbidities (12%); varied ICS use and comorbid chronic obstructive pulmonary disease (4%); high (10%) and very high ICS use (7%). The subtypes were replicated with high accuracy in internal (91-92%) and external (84-86%) datasets. CONCLUSION: Asthma subtypes derived and validated in large independent EHR databases were primarily defined by level of ICS use, level of healthcare use, and presence of comorbidities. This has important clinical implications towards defining asthma subtypes, facilitating patient stratification, and developing more personalised monitoring and treatment strategies.

Perceptions of inspiratory muscle training in adults recovering from COVID-19.

Post COVID-19 condition can occur following infection with SARS-CoV-2 and is characterised by persistent symptoms, including fatigue, breathlessness and cognitive dysfunction, impacting everyday functioning. This study explored how people living with post COVID-19 experienced an eight-week inspiratory muscle training (IMT) rehabilitation programme. Individualised semi-structured interviews with 33 adults (29 female; 49 ± 10 years; 6-11 months post-infection) explored expectations of IMT prior to the intervention, and post intervention interviews explored perceptions of IMT and its impact on recovery. Inductive thematic analysis was used to analyse the data. IMT helped many to feel proactive in managing their symptoms and was associated with perceived improvements in respiratory symptoms, exercise and work capacity, and daily functioning. IMT was well perceived and offers significant potential for use as part of a holistic recovery programme, although it is important to consider the complex, varied symptoms of post COVID-19, necessitating an individually tailored rehabilitation approach.

Determinants of Antibody Responses to SARS-CoV-2 Vaccines: Population-Based Longitudinal Study (COVIDENCE UK).

Antibody responses to SARS-CoV-2 vaccines vary for reasons that remain poorly understood. A range of sociodemographic, behavioural, clinical, pharmacologic and nutritional factors could explain these differences. To investigate this hypothesis, we tested for presence of combined IgG, IgA and IgM (IgGAM) anti-Spike antibodies before and after 2 doses of ChAdOx1 nCoV-19 (ChAdOx1, AstraZeneca) or BNT162b2 (Pfizer-BioNTech) in UK adults participating in a population-based longitudinal study who received their first dose of vaccine between December 2020 and July 2021. Information on sixty-six potential sociodemographic, behavioural, clinical, pharmacologic and nutritional determinants of serological response to vaccination was captured using serial online questionnaires. We used logistic regression to estimate multivariable-adjusted odds ratios (aORs) for associations between independent variables and risk of seronegativity following two vaccine doses. Additionally, percentage differences in antibody titres between groups were estimated in the sub-set of participants who were seropositive post-vaccination using linear regression. Anti-spike antibodies were undetectable in 378/9101 (4.2%) participants at a median of 8.6 weeks post second vaccine dose. Increased risk of post-vaccination seronegativity associated with administration of ChAdOx1 vs. BNT162b2 (adjusted odds ratio (aOR) 6.6, 95% CI 4.2−10.4), shorter interval between vaccine doses (aOR 1.6, 1.2−2.1, 6−10 vs. >10 weeks), poor vs. excellent general health (aOR 3.1, 1.4−7.0), immunodeficiency (aOR 6.5, 2.5−16.6) and immunosuppressant use (aOR 3.7, 2.4−5.7). Odds of seronegativity were lower for participants who were SARS-CoV-2 seropositive pre-vaccination (aOR 0.2, 0.0−0.6) and for those taking vitamin D supplements (aOR 0.7, 0.5−0.9). Serologic responses to vaccination did not associate with time of day of vaccine administration, lifestyle factors including tobacco smoking, alcohol intake and sleep, or use of anti-pyretics for management of reactive symptoms after vaccination. In a sub-set of 8727 individuals who were seropositive post-vaccination, lower antibody titres associated with administration of ChAdOx1 vs. BNT162b2 (43.4% lower, 41.8−44.8), longer duration between second vaccine dose and sampling (12.7% lower, 8.2−16.9, for 9−16 weeks vs. 2−4 weeks), shorter interval between vaccine doses (10.4% lower, 3.7−16.7, for <6 weeks vs. >10 weeks), receiving a second vaccine dose in October−December vs. April−June (47.7% lower, 11.4−69.1), older age (3.3% lower per 10-year increase in age, 2.1−4.6), and hypertension (4.1% lower, 1.1−6.9). Higher antibody titres associated with South Asian ethnicity (16.2% higher, 3.0−31.1, vs. White ethnicity) or Mixed/Multiple/Other ethnicity (11.8% higher, 2.9−21.6, vs. White ethnicity), higher body mass index (BMI; 2.9% higher, 0.2−5.7, for BMI 25−30 vs. <25 kg/m2) and pre-vaccination seropositivity for SARS-CoV-2 (105.1% higher, 94.1−116.6, for those seropositive and experienced COVID-19 symptoms vs. those who were seronegative pre-vaccination). In conclusion, we identify multiple determinants of antibody responses to SARS-CoV-2 vaccines, many of which are modifiable.

Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19: phase 3 randomised controlled trial (CORONAVIT).

OBJECTIVE: To determine the effect of population level implementation of a test-and-treat approach to correction of suboptimal vitamin D status (25-hydroxyvitamin D (25(OH)D) <75 nmol/L) on risk of all cause acute respiratory tract infection and covid 19. DESIGN: Phase 3 open label randomised controlled trial. SETTING: United Kingdom. PARTICIPANTS: 6200 people aged ≥16 years who were not taking vitamin D supplements at baseline. INTERVENTIONS: Offer of a postal finger prick test of blood 25(OH)D concentration with provision of a six month supply of lower dose vitamin D (800 IU/day, n=1550) or higher dose vitamin D (3200 IU/day, n=1550) to those with blood 25(OH)D concentration <75 nmol/L, compared with no offer of testing or supplementation (n=3100). Follow-up was for six months. MAIN OUTCOME MEASURES: The primary outcome was the proportion of participants with at least one swab test or doctor confirmed acute respiratory tract infection of any cause. A secondary outcome was the proportion of participants with swab test confirmed covid-19. Logistic regression was used to calculate odds ratios and associated 95% confidence intervals. The primary analysis was conducted by intention to treat. RESULTS: Of 3100 participants offered a vitamin D test, 2958 (95.4%) accepted and 2674 (86.3%) had 25(OH)D concentrations <75 nmol/L and received vitamin D supplements (n=1328 lower dose, n=1346 higher dose). Compared with 136/2949 (4.6%) participants in the no offer group, at least one acute respiratory tract infection of any cause occurred in 87/1515 (5.7%) in the lower dose group (odds ratio 1.26, 95% confidence interval 0.96 to 1.66) and 76/1515 (5.0%) in the higher dose group (1.09, 0.82 to 1.46). Compared with 78/2949 (2.6%) participants in the no offer group, 55/1515 (3.6%) developed covid-19 in the lower dose group (1.39, 0.98 to 1.97) and 45/1515 (3.0%) in the higher dose group (1.13, 0.78 to 1.63). CONCLUSIONS: Among people aged 16 years and older with a high baseline prevalence of suboptimal vitamin D status, implementation of a population level test-and-treat approach to vitamin D supplementation was not associated with a reduction in risk of all cause acute respiratory tract infection or covid-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04579640.

Risk factors for SARS-CoV-2 infection after primary vaccination with ChAdOx1 nCoV-19 or BNT162b2 and after booster vaccination with BNT162b2 or mRNA-1273: A population-based cohort study (COVIDENCE UK).

Background: Little is known about how demographic, behavioural, and vaccine-related factors affect risk of post-vaccination SARS-CoV-2 infection. We aimed to identify risk factors for SARS-CoV-2 infection after primary and booster vaccinations. Methods: This prospective, population-based, UK study in adults (≥16 years) vaccinated against SARS-CoV-2 assessed risk of breakthrough SARS-CoV-2 infection up to February, 2022, for participants who completed a primary vaccination course (ChAdOx1 nCoV-19 or BNT162b2) and those who received a booster dose (BNT162b2 or mRNA-1273). Cox regression models explored associations between sociodemographic, behavioural, clinical, pharmacological, and nutritional factors and test-positive breakthrough infection, adjusted for local weekly SARS-CoV-2 incidence. Findings: 1051 (7·1%) of 14 713 post-primary participants and 1009 (9·5%) of 10 665 post-booster participants reported breakthrough infection, over a median follow-up of 203 days (IQR 195-216) and 85 days (66-103), respectively. Primary vaccination with ChAdOx1 (vs BNT162b2) was associated with higher risk of infection in both post-primary analysis (adjusted hazard ratio 1·63, 95% CI 1·41-1·88) and after an mRNA-1273 booster (1·26 [1·00-1·57] vs BNT162b2 primary and booster). Lower risk of infection was associated with older age (post-primary: 0·97 [0·96-0·97] per year; post-booster: 0·97 [0·97-0·98]), whereas higher risk of infection was associated with lower educational attainment (post-primary: 1·78 [1·44-2·20] for primary/secondary vs postgraduate; post-booster: 1·46 [1·16-1·83]) and at least three weekly visits to indoor public places (post-primary: 1·36 [1·13-1·63] vs none; post-booster: 1·29 [1·07-1·56]). Interpretation: Vaccine type, socioeconomic status, age, and behaviours affect risk of breakthrough infection after primary and booster vaccinations. Funding: Barts Charity, UK Research and Innovation Industrial Strategy Challenge Fund.

SARS-CoV-2 infection risk among 77,587 healthcare workers: a national observational longitudinal cohort study in Wales, United Kingdom, April to November 2020.

OBJECTIVES: To better understand the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among healthcare workers, leading to recommendations for the prioritisation of personal protective equipment, testing, training and vaccination. DESIGN: Observational, longitudinal, national cohort study. SETTING: Our cohort were secondary care (hospital-based) healthcare workers employed by NHS Wales (United Kingdom) organisations from 1 April 2020 to 30 November 2020. PARTICIPANTS: We included 577,756 monthly observations among 77,587 healthcare workers. Using linked anonymised datasets, participants were grouped into 20 staff roles. Additionally, each role was deemed either patient-facing, non-patient-facing or undetermined. This was linked to individual demographic details and dates of positive SARS-CoV-2 PCR tests. MAIN OUTCOME MEASURES: We used univariable and multivariable logistic regression models to determine odds ratios (ORs) for the risk of a positive SARS-CoV-2 PCR test. RESULTS: Patient-facing healthcare workers were at the highest risk of SARS-CoV-2 infection with an adjusted OR (95% confidence interval [CI]) of 2.28 (95% CI 2.10-2.47). We found that after adjustment, foundation year doctors (OR 1.83 [95% CI 1.47-2.27]), healthcare support workers [OR 1.36 [95% CI 1.20-1.54]) and hospital nurses (OR 1.27 [95% CI 1.12-1.44]) were at the highest risk of infection among all staff groups. Younger healthcare workers and those living in more deprived areas were at a higher risk of infection. We also observed that infection rates varied over time and by organisation. CONCLUSIONS: These findings have important policy implications for the prioritisation of vaccination, testing, training and personal protective equipment provision for patient-facing roles and the higher risk staff groups.

Inspiratory muscle training enhances recovery post-COVID-19: a randomised controlled trial.

BACKGROUND: Many people recovering from coronavirus disease 2019 (COVID-19) experience prolonged symptoms, particularly breathlessness. We urgently need to identify safe and effective COVID-19 rehabilitative strategies. The aim of the current study was to investigate the potential rehabilitative role of inspiratory muscle training (IMT). METHODS: 281 adults (age 46.6±12.2 years; 88% female) recovering from self-reported COVID-19 (9.0±4.2 months post-acute infection) were randomised 4:1 to an 8-week IMT or a "usual care" waitlist control arm. Health-related quality-of-life and breathlessness questionnaires (King's Brief Interstitial Lung Disease (K-BILD) and Transition Dyspnoea Index (TDI)), respiratory muscle strength, and fitness (Chester Step Test) were assessed pre- and post-intervention. The primary end-point was K-BILD total score, with the K-BILD domains and TDI being key secondary outcomes. RESULTS: According to intention to treat, there was no difference between groups in K-BILD total score post-intervention (control: 59.5±12.4; IMT: 58.2±12.3; p<0.05) but IMT elicited clinically meaningful improvements in the K-BILD domains for breathlessness (control: 59.8±12.6; IMT: 62.2±16.2; p<0.05) and chest symptoms (control: 59.2±18.7; IMT: 64.5±18.2; p<0.05), along with clinically meaningful improvements in breathlessness according to TDI (control: 0.9±1.7 versus 2.0±2.0; p<0.05). IMT also improved respiratory muscle strength and estimated aerobic fitness. CONCLUSIONS: IMT may represent an important home-based rehabilitation strategy for wider implementation as part of COVID-19 rehabilitative strategies. Given the diverse nature of long COVID, further research is warranted on the individual responses to rehabilitation; the withdrawal rate herein highlights that no one strategy is likely to be appropriate for all.

Determinants of pre-vaccination antibody responses to SARS-CoV-2: a population-based longitudinal study (COVIDENCE UK).

BACKGROUND: Prospective population-based studies investigating multiple determinants of pre-vaccination antibody responses to SARS-CoV-2 are lacking. METHODS: We did a prospective population-based study in SARS-CoV-2 vaccine-naive UK adults recruited between May 1 and November 2, 2020, without a positive swab test result for SARS-CoV-2 prior to enrolment. Information on 88 potential sociodemographic, behavioural, nutritional, clinical and pharmacological risk factors was obtained through online questionnaires, and combined IgG/IgA/IgM responses to SARS-CoV-2 spike glycoprotein were determined in dried blood spots obtained between November 6, 2020, and April 18, 2021. We used logistic and linear regression to estimate adjusted odds ratios (aORs) and adjusted geometric mean ratios (aGMRs) for potential determinants of SARS-CoV-2 seropositivity (all participants) and antibody titres (seropositive participants only), respectively. RESULTS: Of 11,130 participants, 1696 (15.2%) were seropositive. Factors independently associated with  higher risk of SARS-CoV-2 seropositivity included frontline health/care occupation (aOR 1.86, 95% CI 1.48-2.33), international travel (1.20, 1.07-1.35), number of visits to shops and other indoor public places (≥ 5 vs. 0/week: 1.29, 1.06-1.57, P-trend = 0.01), body mass index (BMI) ≥ 25 vs. < 25 kg/m2 (1.24, 1.11-1.39), South Asian vs. White ethnicity (1.65, 1.10-2.49) and alcohol consumption ≥15 vs. 0 units/week (1.23, 1.04-1.46). Light physical exercise associated with  lower risk (0.80, 0.70-0.93, for ≥ 10 vs. 0-4 h/week). Among seropositive participants, higher titres of anti-Spike antibodies associated with factors including BMI ≥ 30 vs. < 25 kg/m2 (aGMR 1.10, 1.02-1.19), South Asian vs. White ethnicity (1.22, 1.04-1.44), frontline health/care occupation (1.24, 95% CI 1.11-1.39), international travel (1.11, 1.05-1.16) and number of visits to shops and other indoor public places (≥ 5 vs. 0/week: 1.12, 1.02-1.23, P-trend = 0.01); these associations were not substantially attenuated by adjustment for COVID-19 disease severity. CONCLUSIONS: Higher alcohol consumption and lower light physical exercise represent new modifiable risk factors for SARS-CoV-2 infection. Recognised associations between South Asian ethnic origin and obesity and higher risk of SARS-CoV-2 seropositivity were independent of other sociodemographic, behavioural, nutritional, clinical, and pharmacological factors investigated. Among seropositive participants, higher titres of anti-Spike antibodies in people of South Asian ancestry and in obese people were not explained by greater COVID-19 disease severity in these groups.

'I Live a Kind of Shadow Life': Individual Experiences of COVID-19 Recovery and the Impact on Physical Activity Levels.

Understanding of strategies to support individuals recovering from coronavirus disease 2019 (COVID-19) is limited. 'Long COVID' is a multisystem disease characterised by a range of respiratory, gastrointestinal, cardiovascular, neurological, and musculoskeletal symptoms extending beyond 12 weeks. The aim of this study was to explore individuals' experiences of recovering from COVID-19 to provide a better understanding of the acute and long-term impact of the disease on physical activity (PA). Individualised semi-structured interviews were conducted with 48 adults recovering from COVID-19 at 6-11 months post-infection. An inductive thematic analysis approach was used, reaching saturation at 14 interviews (10 female; 47 ± 7 years). Four overarching themes were identified: (i) Living with COVID-19, including managing activities of daily living; (ii) Dealing with the Unknown and self-management strategies; (iii) Re-introducing physical activity; and (iv) Challenges of returning to work. The return to PA, whether through activities of daily living, work or exercise, is often associated with the exacerbation of symptoms, presenting a range of challenges for individuals recovering from COVID-19. Individually tailored support is therefore required to address the unique challenges posed by COVID-19.

Identifying COPD in routinely collected electronic health records: a systematic scoping review.

Although routinely collected electronic health records (EHRs) are widely used to examine outcomes related to COPD, consensus regarding the identification of cases from electronic healthcare databases is lacking. We systematically examine and summarise approaches from the recent literature. MEDLINE via EBSCOhost was searched for COPD-related studies using EHRs published from January 1, 2018 to November 30, 2019. Data were extracted relating to the case definition of COPD and determination of COPD severity and phenotypes. From 185 eligible studies, we found widespread variation in the definitions used to identify people with COPD in terms of code sets used (with 20 different code sets in use based on the ICD-10 classification alone) and requirement of additional criteria (relating to age (n=139), medication (n=31), multiplicity of events (n=21), spirometry (n=19) and smoking status (n=9)). Only seven studies used a case definition which had been validated against a reference standard in the same dataset. Various proxies of disease severity were used since spirometry results and patient-reported outcomes were not often available. To enable the research community to draw reliable insights from EHRs and aid comparability between studies, clear reporting and greater consistency of the definitions used to identify COPD and related outcome measures is key.

Effect of high-intensity interval training in adolescents with asthma: The eXercise for Asthma with Commando Joe's® (X4ACJ) trial.

BACKGROUND: Higher levels of cardiorespiratory fitness are associated with reduced asthma severity and increased quality of life in those with asthma. Therefore, the purpose of this study was to evaluate the effectiveness of a 6-month high-intensity interval training (HIIT) intervention in adolescents with and without asthma. METHODS: A total of 616 adolescents (334 boys; 13.0 ± 1.1 years, 1.57 ± 0.10 m, 52.6 ± 12.9 kg, mean ± SD), including 155 with asthma (78 boys), were recruited as part of a randomized controlled trial from 5 schools (4 control and 1 intervention). The 221 intervention participants (116 boys; 47 asthma) completed 6 months of school-based HIIT (30 min, 3 times per week, 10-30 s bouts at >90% age-predicted maximum heart rate with equal rest). At baseline, mid-intervention, post-intervention, and 3-month follow-up, measurements for 20-m shuttle run, body mass index (BMI), lung function, Pediatric Quality of Life Inventory, Paediatric Asthma Quality of Life Questionnaire, and Asthma Control Questionnaire were collected. Additionally, 69 adolescents (39 boys (of the 36 with asthma there were 21 boys)) also completed an incremental ramp test. For analysis, each group's data (intervention and control) were divided into those with and without asthma. RESULTS: Participants with asthma did not differ from their peers in any parameter of aerobic fitness, at any time-point, but were characterized by a greater BMI. The intervention elicited a significant improvement in maximal aerobic fitness but no change in sub-maximal parameters of aerobic fitness, lung function, or quality of life irrespective of asthma status. Those in the intervention group maintained their BMI, whereas BMI significantly increased in the control group throughout the 6-month period. CONCLUSION: HIIT represents an effective tool for improving aerobic fitness and maintaining BMI in adolescents, irrespective of asthma status. HIIT was well-tolerated by those with asthma, who evidenced a similar aerobic fitness to their healthy peers and responded equally well to a HIIT program.

Predicting asthma-related crisis events using routine electronic healthcare data: a quantitative database analysis study.

BACKGROUND: There is no published algorithm predicting asthma crisis events (accident and emergency [A&E] attendance, hospitalisation, or death) using routinely available electronic health record (EHR) data. AIM: To develop an algorithm to identify individuals at high risk of an asthma crisis event. DESIGN AND SETTING: Database analysis from primary care EHRs of people with asthma across England and Scotland. METHOD: Multivariable logistic regression was applied to a dataset of 61 861 people with asthma from England and Scotland using the Clinical Practice Research Datalink. External validation was performed using the Secure Anonymised Information Linkage Databank of 174 240 patients from Wales. Outcomes were ≥1 hospitalisation (development dataset) and asthma-related hospitalisation, A&E attendance, or death (validation dataset) within a 12-month period. RESULTS: Risk factors for asthma-related crisis events included previous hospitalisation, older age, underweight, smoking, and blood eosinophilia. The prediction algorithm had acceptable predictive ability with a receiver operating characteristic of 0.71 (95% confidence interval [CI] = 0.70 to 0.72) in the validation dataset. Using a cut-point based on the 7% of the population at greatest risk results in a positive predictive value of 5.7% (95% CI = 5.3% to 6.1%) and a negative predictive value of 98.9% (95% CI = 98.9% to 99.0%), with sensitivity of 28.5% (95% CI = 26.7% to 30.3%) and specificity of 93.3% (95% CI = 93.2% to 93.4%); those individuals had an event risk of 6.0% compared with 1.1% for the remaining population. In total, 18 people would need to be followed to identify one admission. CONCLUSION: This externally validated algorithm has acceptable predictive ability for identifying patients at high risk of asthma-related crisis events and excluding those not at high risk.

Impact of COVID-19 lockdown on the incidence and mortality of acute exacerbations of chronic obstructive pulmonary disease: national interrupted time series analyses for Scotland and Wales.

BACKGROUND: The COVID-19 pandemic and ensuing national lockdowns have dramatically changed the healthcare landscape. The pandemic's impact on people with chronic obstructive pulmonary disease (COPD) remains poorly understood. We hypothesised that the UK-wide lockdown restrictions were associated with reductions in severe COPD exacerbations. We provide the first national level analyses of the impact of the COVID-19 pandemic and first lockdown on severe COPD exacerbations resulting in emergency hospital admissions and/or leading to death as well as those recorded in primary care or emergency departments. METHODS: Using data from Public Health Scotland and the Secure Anonymised Information Linkage Databank in Wales, we accessed weekly counts of emergency hospital admissions and deaths due to COPD over the first 30 weeks of 2020 and compared these to the national averages over the preceding 5 years. For both Scotland and Wales, we undertook interrupted time-series analyses to model the impact of instigating lockdown on these outcomes. Using fixed-effect meta-analysis, we derived pooled estimates of the overall changes in trends across the two nations. RESULTS: Lockdown was associated with 48% pooled reduction in emergency admissions for COPD in both countries (incidence rate ratio, IRR 0.52, 95% CI 0.46 to 0.58), relative to the 5-year averages. There was no statistically significant change in deaths due to COPD (pooled IRR 1.08, 95% CI 0.87 to 1.33). In Wales, lockdown was associated with 39% reduction in primary care consultations for acute exacerbation of COPD (IRR 0.61, 95% CI 0.52 to 0.71) and 46% reduction in COPD-related emergency department attendances (IRR 0.54, 95% CI 0.36 to 0.81). CONCLUSIONS: The UK-wide lockdown was associated with the most substantial reductions in COPD exacerbations ever seen across Scotland and Wales, with no corresponding increase in COPD deaths. This may have resulted from reduced transmission of respiratory infections, reduced exposure to outdoor air pollution and/or improved COPD self-management.

Impact of COVID-19 lockdown on emergency asthma admissions and deaths: national interrupted time series analyses for Scotland and Wales.

BACKGROUND: The COVID-19 pandemic's impact on people with asthma is poorly understood. We hypothesised that lockdown restrictions were associated with reductions in severe asthma exacerbations requiring emergency asthma admissions and/or leading to death. METHODS: Using data from Public Health Scotland and the Secure Anonymised Information Linkage Databank in Wales, we compared weekly counts of emergency admissions and deaths due to asthma over the first 18 weeks in 2020 with the national averages over 2015-2019. We modelled the impact of instigating lockdown on these outcomes using interrupted time-series analysis. Using fixed-effect meta-analysis, we derived pooled estimates of the overall changes in trends across the two nations. We also investigated trends in asthma-related primary care prescribing and emergency department (ED) attendances in Wales. RESULTS: Lockdown was associated with a 36% pooled reduction in emergency admissions for asthma (incidence rate ratio, IRR: 0.64, 95% CI: 0.49 to 0.83, p value 0.001) across both countries. There was no significant change in asthma deaths (pooled IRR: 0.57, 95% CI: 0.17 to 1.94, p value 0.37). ED asthma attendances in Wales declined during lockdown (IRR: 0.85, 95% CI: 0.73 to 0.99, p value 0.03). A large spike of 121% more inhaled corticosteroids and 133% more oral corticosteroid prescriptions was seen in Wales in the week before lockdown. CONCLUSIONS: National lockdowns were associated with substantial reductions in severe asthma exacerbations leading to hospital admission across both Scotland and Wales, with no corresponding increase in asthma deaths.