Respiratory
Recent Submissions
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Understanding the burden of interstitial lung disease post-COVID-19: the UK Interstitial Lung Disease-Long COVID Study (UKILD-Long COVID).Introduction: The COVID-19 pandemic has led to over 100 million cases worldwide. The UK has had over 4 million cases, 400 000 hospital admissions and 100 000 deaths. Many patients with COVID-19 suffer long-term symptoms, predominantly breathlessness and fatigue whether hospitalised or not. Early data suggest potentially severe long-term consequence of COVID-19 is development of long COVID-19-related interstitial lung disease (LC-ILD). Methods and analysis: The UK Interstitial Lung Disease Consortium (UKILD) will undertake longitudinal observational studies of patients with suspected ILD following COVID-19. The primary objective is to determine ILD prevalence at 12 months following infection and whether clinically severe infection correlates with severity of ILD. Secondary objectives will determine the clinical, genetic, epigenetic and biochemical factors that determine the trajectory of recovery or progression of ILD. Data will be obtained through linkage to the Post-Hospitalisation COVID platform study and community studies. Additional substudies will conduct deep phenotyping. The Xenon MRI investigation of Alveolar dysfunction Substudy will conduct longitudinal xenon alveolar gas transfer and proton perfusion MRI. The POST COVID-19 interstitial lung DiseasE substudy will conduct clinically indicated bronchoalveolar lavage with matched whole blood sampling. Assessments include exploratory single cell RNA and lung microbiomics analysis, gene expression and epigenetic assessment. Ethics and dissemination: All contributing studies have been granted appropriate ethical approvals. Results from this study will be disseminated through peer-reviewed journals. Conclusion: This study will ensure the extent and consequences of LC-ILD are established and enable strategies to mitigate progression of LC-ILD.
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Asthma control in severe asthma and occupational exposures to inhalable asthmagensIntroduction: Work-related asthma accounts for ≥25% of asthma in working-age populations, though the relationship between work exposures and symptoms is frequently missed, leading to poor health and employment outcomes. We hypothesised that inhalable exposures at work are associated with poor asthma control in severe asthma (SA). Methods: We searched the Birmingham (UK) Regional NHS SA Service clinical database (n=1453 records; 1 March 2004 to 1 March 2021) and undertook a cross-sectional study using baseline data collected at diagnosis. We included all employed patients aged 16-64 with documented current occupation (n=504), and collected socio-demographic, general health and asthma-specific data, including Asthma Control Questionnaire 7 (ACQ7) score. The Occupational Asthma Specific Job-Exposure Matrix (OAsJEM) was employed to determine the likelihood of exposure to respiratory sensitisers, irritants, cleaning agents and detergents; associations between exposures and ACQ7 were investigated using binary and multinomial regression. Results: Frequently reported occupations were care assistants (7%) and nurses (6%); 197/504 (39%) patients were exposed to an asthmagen, including respiratory sensitisers (30%), airway irritants (38%) and cleaning products/disinfectants (29%). ACQ7 score was available for 372/504 (74%) patients, of whom 14% had adequate control (ACQ7=0-1.5). After adjustment for major confounders there were no significant associations between inhaled asthmagens and ACQ7 score (either as binary or multinomial outcomes). Conclusion: JEM-determined workplace exposures to inhaled asthmagens are not associated with asthma control in SA; 29-39% of patients may have current exposure to workplace asthmagens. Routine collection of lifetime occupational data including current job role and level of exposure, in the national asthma registry, would give further insights into this relationship.
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1-year health outcomes associated with systemic corticosteroids for COVID-19: a longitudinal cohort studyBackground: In patients with coronavirus disease 2019 (COVID-19) requiring supplemental oxygen, dexamethasone reduces acute severity and improves survival, but longer-term effects are unknown. We hypothesised that systemic corticosteroid administration during acute COVID-19 would be associated with improved health-related quality of life (HRQoL) 1 year after discharge. Methods: Adults admitted to hospital between February 2020 and March 2021 for COVID-19 and meeting current guideline recommendations for dexamethasone treatment were included using two prospective UK cohort studies (Post-hospitalisation COVID-19 and the International Severe Acute Respiratory and emerging Infection Consortium). HRQoL, assessed by the EuroQol-Five Dimensions-Five Levels utility index (EQ-5D-5L UI), pre-hospital and 1 year after discharge were compared between those receiving corticosteroids or not after propensity weighting for treatment. Secondary outcomes included patient-reported recovery, physical and mental health status, and measures of organ impairment. Sensitivity analyses were undertaken to account for survival and selection bias. Findings: Of the 1888 participants included in the primary analysis, 1149 received corticosteroids. There was no between-group difference in EQ-5D-5L UI at 1 year (mean difference 0.004, 95% CI -0.026-0.034). A similar reduction in EQ-5D-5L UI was seen at 1 year between corticosteroid exposed and nonexposed groups (mean±sd change -0.12±0.22 versus -0.11±0.22). Overall, there were no differences in secondary outcome measures. After sensitivity analyses modelled using a cohort of 109 318 patients admitted to hospital with COVID-19, EQ-5D-5L UI at 1 year remained similar between the two groups. Interpretation: Systemic corticosteroids for acute COVID-19 have no impact on the large reduction in HRQoL 1 year after hospital discharge. Treatments to address the persistent reduction in HRQoL are urgently needed.
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Symptoms of COPD in the absence of airflow obstruction are more indicative of pre-COPD than overdiagnosisBackground: Dysfunction of the small airways is a precursor of COPD but is not detectable on standard spirometric testing until significant destruction has occurred. A proportion of COPD patients have a forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7 which is greater than the lower limit of normal (LLN), when adjusted for their age and sex. It is not understood whether this group of patients, known as "discordant COPD", are representative of "early COPD" or overdiagnosis. Methods: We sought to characterise discordant COPD (disCOPD) using radiology, lung function, serum biomarkers, activity monitoring and quality-of-life scores, comparing with COPD patients with an FEV1/FVC <0.7 and <LLN and healthy, age-matched controls. Results: Six out of eight serum biomarkers were significantly different in the disCOPD group versus healthy controls, as were the scores of all four quality-of-life questionnaires. Activity monitoring revealed similar levels of sedentary time between the disCOPD group and concordant COPD (conCOPD). Computed tomography analysis showed less involvement of small airway dysfunction and emphysema in the disCOPD group versus conCOPD. Conclusions: Collectively, our findings support the hypothesis that disCOPD is a clinically relevant phenomenon that represents a pre-COPD state. Identification of such patients is important for early intervention and management before progression to fully established COPD.
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Breaking barriers: holistic assessment of ability to work in patients with sarcoidosisNo abstract available
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Pulmonary function test and computed tomography features during follow-up after SARS, MERS and COVID-19: a systematic review and meta-analysisBackground: The COVID-19 pandemic follows severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus epidemics. Some survivors of COVID-19 infection experience persistent respiratory symptoms, yet their cause and natural history remain unclear. Follow-up after SARS and MERS may provide a model for predicting the long-term pulmonary consequences of COVID-19. Methods: This systematic review and meta-analysis aims to describe and compare the longitudinal pulmonary function test (PFT) and computed tomography (CT) features of patients recovering from SARS, MERS and COVID-19. Meta-analysis of PFT parameters (DerSimonian and Laird random-effects model) and proportion of CT features (Freeman-Tukey transformation random-effects model) were performed. Findings: Persistent reduction in the diffusing capacity for carbon monoxide following SARS and COVID-19 infection is seen at 6 months follow-up, and 12 months after MERS. Other PFT parameters recover in this time. 6 months after SARS and COVID-19, ground-glass opacity, linear opacities and reticulation persist in over 30% of patients; honeycombing and traction dilatation are reported less often. Severe/critical COVID-19 infection leads to greater CT and PFT abnormality compared to mild/moderate infection. Interpretation: Persistent diffusion defects suggestive of parenchymal lung injury occur after SARS, MERS and COVID-19 infection, but improve over time. After COVID-19 infection, CT features are suggestive of persistent parenchymal lung injury, in keeping with a post-COVID-19 interstitial lung syndrome. It is yet to be determined if this is a regressive or progressive disease.
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Prevalence, pattern, risks factors and consequences of antibiotic resistance in COPD: a systematic reviewA concern of antibiotic use in chronic obstructive pulmonary disease (COPD) is the emergence and propagation of antimicrobial resistance (AMR). A systematic review was conducted to determine prevalence, pattern, risk factors and consequences of AMR in COPD. Bibliographic databases were searched from inception to November 2020, with no language restrictions, including studies of any design that included patients with COPD and reported prevalence and pattern of AMR. 2748 unique titles and abstracts were identified, of which 63 articles, comprising 26,387 patients, met inclusion criteria. Forty-four (69.8%) studies were performed during acute exacerbation. The median prevalence of AMR ranged from 0-100% for Pseudomonas aeruginosa, Moraxella catarrhalis, Klebsiella pneumoniae and Acinetobacter baumannii. Median resistance rates of H influenzae and S pneumoniae were lower by comparison, with maximum rates ≤40% and ≤46%, respectively, and higher for Staphylococcus aureus. There was a trend towards higher rates of AMR in patients with poorer lung function and greater incidence of previous antibiotic exposure and hospitalisation. The impact of AMR on mortality was unclear. Data regarding antimicrobial susceptibility testing techniques and the impact of other risk factors or consequences of AMR were variable or not reported. This is the first review to systematically unify data regarding AMR in COPD. AMR is relatively common and strategies to optimise antibiotic use could be valuable to prevent the currently under-investigated potential adverse consequences of AMR.
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Predictors of mortality in COVID-19-positive patients on and off CPAP: a review from a tertiary care setting in the NHSIntroduction: Since the first description of a coronavirus-related pneumonia outbreak in December 2019, the virus SARS-CoV-2 that causes the infection/disease coronavirus disease 2019 (COVID-19) has evolved into a pandemic, and as of today, millions have been affected. Objectives: Our aim was to identify the predictors of mortality in COVID-19-positive patients on or off continuous positive airway pressure (CPAP). Methodology This was an observational study. Data were collected from February 2020 to April 2020 with patients admitted to the COVID-19 ward at The James Cook University Hospital, Middlesbrough, England. The inclusion criteria were COVID-19-positive patients confirmed through PCR tests on or off CPAP. Patients who had negative RT-PCR for COVID-19 and those who were intubated were excluded. Results A total of 56 patients diagnosed with COVID-19 (through RT-PCR) were included in the final analysis, among which 27 were on CPAP, while 29 did not require CPAP (NCPAP). The overall mean age of the patients was 66 ± 14 (range: 26-94) years. The mean age of CPAP and NCPAP patients was 63 ± 15 (range: 26-85) years and 68 ± 13 (range: 40-94) years, respectively. The ethnicity of 54 (96.4%) patients was White-Caucasian, while 2 (3.6%) were British-Asian. In the study sample, 16 (28.6%) patients expired, of which 11 (40.7%) were on CPAP, while 5 (16.7%) did not require CPAP during the disease course. Correlation analysis showed that overall higher age, Medical Research Council Dyspnoea (MRCD) score, performance status (PS), and consolidation affecting more than one quadrant of the lungs were significantly correlated with increased mortality. Among patients receiving CPAP, higher age, MRCD score, and PS were significant predictors of mortality. Among the NCPAP group, advancing age, respiratory rate, MRCD score, PS, increased creatinine levels, and consolidation affecting more than one quadrant of the lungs were the predictors of mortality. Conclusion: Even with a small sample size, we can see that there are definitive predictors that are directly proportional to increased mortality in COVID-19 patients on CPAP, such as higher age, performance status, MRCD score, and increased lung involvement of consolidation in more than one quadrant, which can help us rationalize management.
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Predicting the pulmonary effects of long-term e-cigarette use: are the clouds clearing?Commercially available since 2007, e-cigarettes are a popular electronic delivery device of ever-growing complexity. Given their increasing use by ex-smokers, smokers and never-smokers, it is important to evaluate evidence of their potential pulmonary effects and predict effects of long-term use, since there has been insufficient time to study a chronic user cohort. It is crucial to evaluate indicators of harm seen in cigarette use, and those potentially unique to e-cigarette exposure. Evaluation must also account for the vast variation in e-cigarette devices (now including at least five generations of devices) and exposure methods used in vivo and in vitroThus far, short-term use cohort studies, combined with in vivo and in vitro models, have been used to probe for the effects of e-cigarette exposure. The effects and mechanisms identified, including dysregulated inflammation and decreased pathogen resistance, show concerning overlaps with the established effects of cigarette smoke exposure. Additionally, research has identified a signature of dysregulated lipid processing, which is unique to e-cigarette exposure.This review will evaluate the evidence of pulmonary effects of, and driving mechanisms behind, e-cigarette exposure, which have been highlighted in emerging literature, and highlight the gaps in current knowledge. Such a summary allows understanding of the ongoing debate into e-cigarette regulation, as well as prediction and potential mitigation of future problems surrounding e-cigarette use.
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Technology-enabled multidisciplinary team in-reach for oral corticosteroid stewardship and optimizing care of suspected airways disease exacerbations.Overuse of corticosteroids is an important problem not only in asthma but also the management of other airways diseases including bronchiectasis and COPD and results in associated risks of serious side effects and irreversible harm. We report a pilot using an in-reach solution to review patients, optimise their care and facilitate early discharge. We discharged >20% of our patients immediately, which is potentially a significant reduction in hospital bed use and, most importantly, through this approach we were able to establish early diagnosis and reduce inappropriate oral corticosteroid use.
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Porphyromonas pasteri and Prevotella nanceiensis in the sputum microbiota are associated with increased decline in lung function in individuals with cystic fibrosisAlthough anaerobic bacteria exist in abundance in cystic fibrosis (CF) airways, their role in disease progression is poorly understood. We hypothesized that the presence and relative abundance of the most prevalent, live, anaerobic bacteria in sputum of adults with CF were associated with adverse clinical outcomes. This is the first study to prospectively investigate viable anaerobic bacteria present in the sputum microbiota and their relationship with long-term outcomes in adults with CF. We performed 16S rRNA analysis using a viability quantitative PCR technique on sputum samples obtained from a prospective cohort of 70 adults with CF and collected clinical data over an 8 year follow-up period. We examined the associations of the ten most abundant obligate anaerobic bacteria present in the sputum with annual rate of FEV1 change. The presence of Porphyromonas pasteri and Prevotella nanceiensis were associated with a greater annual rate of FEV1 change; -52.3 ml yr-1 (95 % CI-87.7;-16.9), -67.9 ml yr-1 (95 % CI-115.6;-20.1), respectively. Similarly, the relative abundance of these live organisms were associated with a greater annual rate of FEV1 decline of -3.7 ml yr-1 (95 % CI: -6.1 to -1.3, P=0.003) and -5.3 ml yr-1 (95 % CI: -8.7 to -1.9, P=0.002) for each log2 increment of abundance, respectively. The presence and relative abundance of certain anaerobes in the sputum of adults with CF are associated with a greater rate of long-term lung function decline. The pathogenicity of anaerobic bacteria in the CF airways should be confirmed with further longitudinal prospective studies with a larger cohort of participants.
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Pilot study investigating diagnostic utility of serum MMP-1 and TGF-β1 in asthma in 'real world' clinical practice in IndiaAims: At a tissue level, matrix metalloproteinase-1 (MMP-1) and transforming growth factor-beta 1 (TGF-β1) contribute to allergic airway inflammation, tissue remodelling and disease severity in asthma via different pathways. Their peripheral blood levels and role in diagnosis and therapeutic monitoring has not been adequately explored. We investigated the association between MMP-1 and TGF-β in moderate and severe persistent asthma and evaluated their performance characteristics by constructing receiver operating characteristic curves. Methods: Serum MMP-1 and TGF-β1 were measured using ELISA in 75 adults; moderate persistent asthma (n=25), severe persistent asthma (n=25) and healthy community controls (n=25). Severity of asthma was determined as per Global Initiative for Asthma guidelines. Subjects were followed up for 3 months and treatment responsiveness was assessed by spirometry and symptom response. Results: Serum MMP-1 and TGF-β1 were significantly elevated in asthmatics compared with controls (p<0.0001 and p<0.01). While serum MMP-1 was elevated in severe asthma compared with moderate asthma (p<0.05), TGF-β1 was lower in severe asthma compared with moderate asthma (p<0.05). The performance characteristics of serum MMP-1 and TGF-β1 were promising in this cohort with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 82%, 100%, 100% and 99% and 62%, 100%, 100% and 97.8%, respectively; sensitivity of MMP-1 being superior. Conclusion: This pilot study showed that serum MMP-1 and TGF-β1 levels are elevated in chronic asthma and may serve as a useful adjunct in differentiating moderate from severe asthma. A large multicentre study in well characterised cohort of asthmatics is warranted to investigate their role in diagnosis and therapeutic monitoring.
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Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort studyBackground: The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. Methods: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings: We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9-6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40-59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. Interpretation: We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care.
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Impact of comorbidities on EQ-5D quality-of-life index in severe asthma.Background: Severe asthma pathology encompasses a wide range of pulmonary and extrapulmonary treatable traits with a high prevalence of comorbidities. Although asthma-specific health-related quality-of-life measures are most sensitive to changes in asthma control, generic measures, such as EQ-5D-5L (EuroQol 5-Dimension 5-Level questionnaire), are potentially better for capturing the impact of comorbidities. Objective: We sought to examine the impact of pulmonary and extrapulmonary treatable traits on quality of life at initial severe asthma assessment, and to compare the characteristics of those patients whose quality of life does and does not improve during follow-up at severe asthma centers. Methods: Patients' characteristics at baseline assessment within the UK Severe Asthma Registry were compared by EQ-5D-5L utility index quartile. Patients with follow-up review data were stratified by change in EQ-5D-5L utility index from baseline to follow-up, and characteristics similarly examined. Results: Patients in the quartiles with worst dysutility at baseline were observed to exhibit more treatable traits and in particular extrapulmonary traits associated with cumulative systemic corticosteroids, including obesity, anxiety/depression, and osteoporosis. In those patients whose quality of life improved over follow-up, a reduction in exacerbations, uncontrolled symptoms, and requirement for maintenance oral corticosteroids were observed. Conclusions: Both pulmonary and extrapulmonary treatable traits are important determinants of quality of life in severe asthma. Comorbidities associated with cumulative systemic corticosteroid exposure are particularly associated with worse quality of life, emphasizing the importance of early identification and management of severe asthma before comorbidities develop.
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Use of the oral beta blocker bisoprolol to reduce the rate of exacerbation in people with chronic obstructive pulmonary disease (COPD): a randomised controlled trial (BICS).Background: Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity, mortality and healthcare costs. Beta blockers are well-established drugs widely used to treat cardiovascular conditions. Observational studies consistently report that beta blocker use in people with COPD is associated with a reduced risk of COPD exacerbations. The bisoprolol in COPD study (BICS) investigates whether adding bisoprolol to routine COPD treatment has clinical and cost-effective benefits. A sub-study will risk stratify participants for heart failure to investigate whether any beneficial effect of bisoprolol is restricted to those with unrecognised heart disease. Methods: BICS is a pragmatic randomised parallel group double-blind placebo-controlled trial conducted in UK primary and secondary care sites. The major inclusion criteria are an established predominant respiratory diagnosis of COPD (post-bronchodilator FEV1 < 80% predicted, FEV1/FVC < 0.7), a self-reported history of ≥ 2 exacerbations requiring treatment with antibiotics and/or oral corticosteroids in a 12-month period since March 2019, age ≥ 40 years and a smoking history ≥ 10 pack years. A computerised randomisation system will allocate 1574 participants with equal probability to intervention or control groups, stratified by centre and recruitment in primary/secondary care. The intervention is bisoprolol (1.25 mg tablets) or identical placebo. The dose of bisoprolol/placebo is titrated up to a maximum of 4 tablets a day (5 mg bisoprolol) over 4-7 weeks depending on tolerance to up-dosing of bisoprolol/placebo-these titration assessments are completed by telephone or video call. Participants complete the remainder of the 52-week treatment period on the final titrated dose (1, 2, 3, 4 tablets) and during that time are followed up at 26 and 52 weeks by telephone or video call. The primary outcome is the total number of participant reported COPD exacerbations requiring oral corticosteroids and/or antibiotics during the 52-week treatment period. A sub-study will risk stratify participants for heart failure by echocardiography and measurement of blood biomarkers. Discussion: The demonstration that bisoprolol reduces the incidence of exacerbations would be relevant not only to patients and clinicians but also to healthcare providers, in the UK and globally. Trial registration: Current controlled trials ISRCTN10497306 . Registered on 16 August 2018.
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The burden of progressive fibrotic interstitial lung disease across the UK.Almost 15% of new referrals with non-IPF fibrotic ILD go on to develop a progressive fibrotic phenotype and would benefit from antifibrotic therapy https://bit.ly/3uPhClN
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Venous or arterial samples for activated clotting time measurements: a systematic review.Objective: The systematic review aims to investigate the effect of sampling source on activated clotting time (ACT) measurement within cardiovascular surgery and cardiac catheterisation. It also examines the evidence surrounding novel clot assessment techniques and associated sampling variation. Methods: A comprehensive electronic search was conducted using PubMed, MEDLINE, Scopus, Cochrane database, and Google Scholar until 20th June 2020. All studies reporting sampling source variability of ACT in cardiac surgery, vascular surgery and cardiac catheterisation were included. Results: Fourteen studies were included in the systematic review. Inconsistent reports of variability were seen in cardiac surgery and cardiac catheterisation. There were no studies directly examining ACT variability in vascular surgery. Novel clot assessment techniques have been validated in cardiac surgery, but measurements vary depending on sampling source. Conclusion: Sampling source should be kept consistent to facilitate effective haemostatic strategies. More research is needed regarding variability in vascular surgery and novel clot assessment techniques.
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What good came out of the Covid-19 outbreak for workers with occupational asthma?No abstract available