RSS 1.0Respiratory
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Safety, tolerability, and efficacy of an in-class combination therapy switch from bosentan plus sildenafil to ambrisentan plus tadalafil in children with pulmonary arterial hypertension.The aim of this single-centre retrospective observational study was to evaluate the safety, tolerability, and efficacy of an in-class combination therapy switch from bosentan plus sildenafil to ambrisentan plus tadalafil in children with pulmonary arterial hypertension. Children aged over 5 years who were established on sildenafil plus bosentan were offered to undergo a therapy switch from May 2014 to May 2021 and, if remaining in the service, followed up to May 2024. Children with Eisenmenger syndrome, open intra or extra-cardiac shunt, or with pulmonary hypertension-associated lung disease were excluded. As part of a structured clinical program children were assessed via walk test, echocardiography, cardiac magnetic resonance imaging (CMRI), cardiopulmonary exercise testing, and serum biomarkers. Fifty-two children were included, 33 in the switch group and 19 in the control group. Clinical characteristics at diagnosis and baseline assessments did not differ between groups. All children tolerated the medication switch. Over a median 13.0 [12.0,13.7] week follow-up in the switch group there was a significant improvement in World Health Organization functional class (WHO FC, p < 0.001); reduction in estimated right ventricular systolic pressure by echocardiography of 7 mmHg (p = 0.03) and a 2% increase (p = 0.03) in right ventricular ejection fraction on CMRI. There was a sustained improvement in WHO FC (p < 0.01) in the switch group at medium-term follow-up of 40.9 [35.2,49.3] weeks. Long-term outcome of transplant- or Potts shunt-free survival was comparable between the two groups.
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Can symptoms of anosmia and dysgeusia be diagnostic for COVID-19?Objective: Olfactory and taste dysfunction (OTD) is a potential neurological manifestation of coronavirus-2019 (COVID-19). We aimed to investigate the diagnostic value of symptoms of anosmia and dysgeusia for COVID-19. Methods: A comprehensive electronic search was conducted using PubMed, MEDLINE, Scopus, Cochrane database, and Google Scholar from 1 June 2020 to 12 June 2020. All studies reporting symptoms of anosmia and dysgeusia in COVID-19-positive patients were included. A total of 23 studies were included in the systematic review. Results: Symptoms of anosmia and dysgeusia were frequently reported by COVID-19-positive patients. Symptoms were more common in females and in younger patients. There was no direct association between the severity of COVID-19 and the presence of symptoms. However, some evidence was found for a longer duration of these symptoms and increased severity of COVID-19 infection in young patients. Conclusion: OTD is commonly reported by COVID-19 patients. Due to limited literature on the association between OTD and COVID-19, it is currently not possible to conclude that these symptoms alone can be used to diagnose COVID-19. However, the presence of OTD can potentially be used as a screening tool for COVID-19 especially in young and female patients. Further research is required to establish the true diagnostic value of these symptoms and efficacy as screening tools for COVID-19 patients.
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BTS clinical statement on pulmonary sarcoidosisNo abstract available
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BronchUK: protocol for an observational cohort study and biobank in bronchiectasisBronchiectasis has been a largely overlooked disease area in respiratory medicine. This is reflected by a shortage of large-scale studies and lack of approved therapies, in turn leading to a variation of treatment across centres. BronchUK (Bronchiectasis Observational Cohort and Biobank UK) is a multicentre, prospective, observational cohort study working collaboratively with the European Multicentre Bronchiectasis Audit and Research Collaboration project. The inclusion criteria for patients entering the study are a clinical history consistent with bronchiectasis and computed tomography demonstrating bronchiectasis. Main exclusion criteria are 1) patients unable to provide informed consent, 2) bronchiectasis due to known cystic fibrosis or where bronchiectasis is not the main or co-dominant respiratory disease, 3) age <18 years, and 4) prior lung transplantation for bronchiectasis. The study is aligned to standard UK National Health Service (NHS) practice with an aim to recruit a minimum of 1500 patients from across at least nine secondary care centres. Patient data collected at baseline includes demographics, aetiology testing, comorbidities, lung function, radiology, treatments, microbiology and quality of life. Patients are followed up annually for a maximum of 5 years and, where able, blood and/or sputa samples are collected and stored in a central biobank. BronchUK aims to collect robust longitudinal data that can be used for analysis into current NHS practice and patient outcomes, and to become an integral resource to better inform future interventional studies in bronchiectasis.
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Bronchiectasis: a progressive phenotype of chronic obstructive pulmonary diseaseNo abstract available
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Integration of lung function data: turning snapshots into stories.Missing or inaccessible lung function measurements, gathered over time, have the potential to stagnate or impair clinical care decisions being made. This jeopardises patient safety and often contributes to excessive resource utilisation. Data integration is fundamental to clinical decision-making and entails amalgamating lung function data from multiple sources in a user-friendly format. Despite this, current systems for recording lung function data are suboptimal, with copious gaps in the clinical picture arising from missing or inaccessible lung function measurements. This article discusses the importance of data integration for lung function, with a call to action for key stakeholders involved in the performance, management and interpretation of such tests.
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Neutrophil dynamics in pulmonary fibrosis: pathophysiological and therapeutic perspectivesThe shared pathobiological mechanisms driving progressive fibrosis in interstitial lung diseases (ILDs) remain unclear. Neutrophils, the most common immune cells in the human body, contain an extensive array of proteinases that are important for cell function, including tissue repair and remodelling. Increasing observational studies have reported elevated neutrophil counts in the respiratory tract and circulation of patients with ILD and suggest a role as a biomarker of disease severity. Neutrophils and their contents (including the formation of neutrophil extracellular traps (NETs)) are present in fibrotic lung tissue. Proteinases and NETs may drive fibrogenesis in animal and in vitro models and may impact transforming growth factor-β1 activation. However, the effect of neutrophil action, whether reparative or pathologically destructive to the delicate lung architecture, has yet to be determined. This review aims to summarise the current literature surrounding the potential role of the neutrophil as a biomarker and contributor to the pathogenesis of ILD. There is currently a paucity of treatment options in ILD driven by the knowledge gap underlying the overall disease mechanisms. This review concludes that neutrophils warrant further evaluation as manipulation of recruitment and function could provide a novel and much needed therapeutic strategy.
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Biomarker-guided antibiotic stewardship in suspected ventilator-associated pneumonia (VAPrapid2): a randomised controlled trial and process evaluationBackground: Ventilator-associated pneumonia is the most common intensive care unit (ICU)-acquired infection, yet accurate diagnosis remains difficult, leading to overuse of antibiotics. Low concentrations of IL-1β and IL-8 in bronchoalveolar lavage fluid have been validated as effective markers for exclusion of ventilator-associated pneumonia. The VAPrapid2 trial aimed to determine whether measurement of bronchoalveolar lavage fluid IL-1β and IL-8 could effectively and safely improve antibiotic stewardship in patients with clinically suspected ventilator-associated pneumonia. Methods: VAPrapid2 was a multicentre, randomised controlled trial in patients admitted to 24 ICUs from 17 National Health Service hospital trusts across England, Scotland, and Northern Ireland. Patients were screened for eligibility and included if they were 18 years or older, intubated and mechanically ventilated for at least 48 h, and had suspected ventilator-associated pneumonia. Patients were randomly assigned (1:1) to biomarker-guided recommendation on antibiotics (intervention group) or routine use of antibiotics (control group) using a web-based randomisation service hosted by Newcastle Clinical Trials Unit. Patients were randomised using randomly permuted blocks of size four and six and stratified by site, with allocation concealment. Clinicians were masked to patient assignment for an initial period until biomarker results were reported. Bronchoalveolar lavage was done in all patients, with concentrations of IL-1β and IL-8 rapidly determined in bronchoalveolar lavage fluid from patients randomised to the biomarker-based antibiotic recommendation group. If concentrations were below a previously validated cutoff, clinicians were advised that ventilator-associated pneumonia was unlikely and to consider discontinuing antibiotics. Patients in the routine use of antibiotics group received antibiotics according to usual practice at sites. Microbiology was done on bronchoalveolar lavage fluid from all patients and ventilator-associated pneumonia was confirmed by at least 104 colony forming units per mL of bronchoalveolar lavage fluid. The primary outcome was the distribution of antibiotic-free days in the 7 days following bronchoalveolar lavage. Data were analysed on an intention-to-treat basis, with an additional per-protocol analysis that excluded patients randomly assigned to the intervention group who defaulted to routine use of antibiotics because of failure to return an adequate biomarker result. An embedded process evaluation assessed factors influencing trial adoption, recruitment, and decision making. This study is registered with ISRCTN, ISRCTN65937227, and ClinicalTrials.gov, NCT01972425. Findings: Between Nov 6, 2013, and Sept 13, 2016, 360 patients were screened for inclusion in the study. 146 patients were ineligible, leaving 214 who were recruited to the study. Four patients were excluded before randomisation, meaning that 210 patients were randomly assigned to biomarker-guided recommendation on antibiotics (n=104) or routine use of antibiotics (n=106). One patient in the biomarker-guided recommendation group was withdrawn by the clinical team before bronchoscopy and so was excluded from the intention-to-treat analysis. We found no significant difference in the primary outcome of the distribution of antibiotic-free days in the 7 days following bronchoalveolar lavage in the intention-to-treat analysis (p=0·58). Bronchoalveolar lavage was associated with a small and transient increase in oxygen requirements. Established prescribing practices, reluctance for bronchoalveolar lavage, and dependence on a chain of trial-related procedures emerged as factors that impaired trial processes. Interpretation: Antibiotic use remains high in patients with suspected ventilator-associated pneumonia. Antibiotic stewardship was not improved by a rapid, highly sensitive rule-out test. Prescribing culture, rather than poor test performance, might explain this absence of effect.
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Bilateral pulmonary embolism while receiving tranexamic acid: a case reportBackground: We present a case of a suspected tranexamic acid-related bilateral pulmonary embolism in a healthy and active middle-aged woman who was receiving tranexamic acid for menorrhagia with no other known significant risk factors for thromboembolism. Case presentation: A 46-year-old Asian woman who was usually fit and well with no remarkable past medical history except for menorrhagia of 1-year duration for which she was receiving tranexamic acid presented to our accident and emergency department with a 2-week history of intermittent pleuritic central chest pain. She was reviewed and discharged to home with a diagnosis of musculoskeletal pain on two hospital visits because she had no significant risk factors for thromboembolism and her workup investigation results for pulmonary embolism and other differential diagnoses were largely unremarkable. On her third visit to the emergency ambulatory clinic with recurring symptoms of pleuritic chest pain, a pulmonary computed tomographic angiogram confirmed bilateral subsegmental pulmonary embolism. Conclusion: This case report reinforces the possible increased risk of thromboembolism in patients receiving tranexamic acid.
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Risk of self-contamination among healthcare workers in the COVID-19 pandemicNo abstract available
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Reply to Thomson, to Neder ., and to Wouters.No abstract available
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Relationship between depression and anxiety, health status and lung function in patients with alpha-1 antitrypsin deficiencyAlpha-1 Antitrypsin deficiency (AATD) is a genetic condition that can lead to Chronic Obstructive Pulmonary Disease. The burden of psychological disease, its impact and contributing factors in patients with AATD are largely unknown. This study determined the prevalence of depression and anxiety in AATD and its clinical impact. All subjects with PiZZ/PiZnull (n = 635) and PiSZ (n = 111) genotypes within the AATD registry who had sufficient data to calculate pulmonary physiological and health status (HS) decline were grouped as those with or without a diagnosis of depression and/or anxiety. Univariate and multivariate analyses were performed on physiological, demographic and HS parameters. Depression and/or anxiety was present in 16.4% overall in both PiSZ and PiZZ/PiZnull cohorts and was associated with lower baseline pulmonary function and worse HS. In the multivariable analysis of the PiZZ/PiZnull cohort, a greater average decline in FEV1% predicted was observed in those with depression and/or anxiety than those without (-1.53 SD ± 2.26 per year, -0.99 ± 1.79, respectively; p = 0.03) but there was no difference in HS decline (p = 0.33). No differences were seen in the PiSZ cohort. Dyspnoea (mMRC score) was generally worse in those with depression and/or anxiety than those without. Comorbidity burden did not differ between those with or without depression and/or anxiety. Disease severity and progression may be contributing to the prevalence of psychological factors in PiZZ/PiZnull patients. Patients who are declining rapidly should be actively monitored for psychological co-morbidity and treated by cognitive or pharmacological means.
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Could a behaviour change intervention be used to address under-recognition of work-related asthma in primary care? A systematic reviewWe included 14 studies from n=768 retrieved citations, comprising 3 randomised control trials, 1 uncontrolled experimental study, and 10 studies employing recognized multi-step BC methodologies. None of the studies were concerned with identification of asthma. BCIs had been developed for facilitating screening programmes (5), implementing guidelines (3) and individual case finding (6). Five studies measured effectiveness, in terms of screening adherence rates, pre-/post-intervention competency, satisfaction and usability, for clinicians, though none measured diagnostic rates.
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Prevalence of invasive lung cancer in pure ground glass nodules less than 30 mm: A systematic reviewAll published studies were retrospective (n = 28) and the majority conducted in Asia (n = 25). Baseline patient cohorts were mainly from published surgical series (n = 22) or lung cancer screening programs (n = 6). The proportion of minimally invasive and invasive cancer ranged from 0.9 % to 100 % with a pooled prevalence of 42.4 % [95 % CI: 0.28, 0.57]. Considerable heterogeneity was observed (I2 =99 %) and patient selection was the most significant contribution, accounting for 73 % of the observed heterogeneity (p < 0.0001). Meta-regression based on size selection and country of investigation revealed no significant contribution to effect size effect or heterogeneity.
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Evaluating CRMS/CFSPID phenotypes and outcomes: A retrospective study from a large UK cystic fibrosis centreBackground: Cystic fibrosis transmembrane conductance regulator metabolic syndrome/cystic fibrosis screen-positive, inconclusive diagnosis (CRMS/CFSPID) is a designation given following a positive newborn screen for cystic fibrosis (CF) when CF is not excluded but cannot be confirmed. We describe the long-term clinical outcomes of a CRMS/CFSPID cohort. Methods: A retrospective, single centre study of children with a current or previous diagnosis of CRMS/CFSPID. Study period extended from February 1, 2007 to August 1, 2022. Baseline and longitudinal data were assessed. Results: 30 children were designated as CRMS/CFSPID between 2007 and 2021. At baseline, 13 CFTR variants were identified, of which F508del and R117H 7T/9T were most common (occurring in 25 and 20 children respectively). Initial mean immunoreactive trypsinogen and sweat chloride were 82.8 mmol/L and 34.3 mmol/L respectively. During longitudinal assessment (n = 27), occurring over a mean duration of 8.5 years, five children progressed to CF at a mean age of 9.5 years. All children were pancreatic sufficient except one who reclassified to CF. Four isolated Pseudomonas aeruginosa and 12 isolated Staphylococcus aureus, of which one and two progressed to CF respectively. All recent Z-scores for weight and spirometry were above -2. Initial mean sweat chloride was higher in those who progressed to CF versus those who did not, although this did not reach statistical significance (38.4 mmol/L versus 32.0 mmol/L respectively, p = 0.105). Conclusions: Most children with CRMS/CFSPID remained well with a low progression rate to CF. This supports a less intensive medical surveillance approach. Our results highlight the importance of assessment in a dedicated CRMS/CFSPID clinic during adolescence to detect progression to CF after 6 years of age.
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Physical, cognitive, and social triggers of symptom fluctuations in people living with long COVID: an intensive longitudinal cohort studyBackground: Symptom fluctuations within and between individuals with long COVID are widely reported, but the extent to which severity varies following different types of activity and levels of exertion, and the timing of symptoms and recovery, have not previously been quantified. We aimed to characterise timing, severity, and nature of symptom fluctuations in response to effortful physical, social and cognitive activities, using Ecological Momentary Assessments. Methods: We recorded activity, effort, and severity of 8 core symptoms every 3 h for up to 24 days, in cohorts from both clinic and community settings. Symptom severities were jointly modelled using autoregressive and moving average processes. Findings: Consent was received from 376 participants providing ≥1 week's measurements (273 clinic-based, 103 community-based). Severity of all symptoms was elevated 30 min after all categories of activity. Increased effort was associated with increased symptom severity. Fatigue severity scores increased by 1.8/10 (95% CI: 1.6-1.9) following the highest physical exertions and by 1.5 (1.4-1.7) following cognitive efforts. There was evidence of only mild delayed fatigue 3 h (0.3, 0.2-0.5) or one day later (0.2, 0.0- 0.5). Fatigue severity increased as the day progressed (1.4, 1.0-1.7), and cognitive dysfunction was 0.2 lower at weekends (0.1-0.3). Interpretation: Cognitive, social, self-care and physical activities all triggered increased severity across every symptom, consistent with associated common pathways as potential therapeutic targets. Clear patterns of symptom fluctuations emerged that support more targeted self-management.
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Opioids for the palliation of symptoms in people with serious respiratory illness: a systematic review and meta-analysis.Background: People living with serious respiratory illness experience a high burden of distressing symptoms. Although opioids are prescribed for symptom management, they generate adverse events, and their benefits are unclear. Methods: We examined the efficacy and safety of opioids for symptom management in people with serious respiratory illness. Embase, MEDLINE and the Cochrane Central Register of Controlled Trials were searched up to 11 July 2022. Reports of randomised controlled trials administering opioids to treat symptoms in people with serious respiratory illness were included. Key exclusion criteria included <80% of participants having a nonmalignant lung disease. Data were extracted regarding study characteristics, outcomes of breathlessness, cough, health-related quality of life (HRQoL) and adverse events. Treatment effects were pooled using a generic inverse variance model with random effects. Risk of bias was assessed using the Cochrane Risk of Bias tool version 1. Results: Out of 17 included trials, six were laboratory-based exercise trials (n=70), 10 were home studies measuring breathlessness in daily life (n=788) and one (n=18) was conducted in both settings. Overall certainty of evidence was "very low" to "low". Opioids reduced breathlessness intensity during laboratory exercise testing (standardised mean difference (SMD) -0.37, 95% CI -0.67- -0.07), but not breathlessness measured in daily life (SMD -0.10, 95% CI -0.64-0.44). No effects on HRQoL (SMD -0.42, 95% CI -0.98-0.13) or cough (SMD -1.42, 95% CI -3.99-1.16) were detected. In at-home studies, opioids led to increased frequency of nausea/vomiting (OR 3.32, 95% CI 1.70-6.51), constipation (OR 3.08, 95% CI 1.69-5.61) and drowsiness (OR 1.37, 95% CI 1.01-1.86), with serious adverse events including hospitalisation and death identified. Conclusions: Opioids improved exertional breathlessness in laboratory exercise studies, but did not improve breathlessness, cough or HRQoL measured in daily life at home. There were significant adverse events, which may outweigh any benefits.
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ARTP statement on pulmonary function testing.No abstract available
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The effect of telemonitoring (TM) on improving adherence with continuous positive airway pressure (CPAP) in obstructive sleep apnoea (OSA): a service improvement project (SIP).The benefits of CPAP demonstrated in clinical trials are difficult to deliver in real life due to the lack of adherence. We analysed the effect of a Telemonitoring (TM)-related intervention on adherence as part of a Service Improvement Project (SIP) analysed as a retrospective cohort study. The 'historical control' (HC) cohort (followed up in conventional clinics) included all patients who commenced on CPAP between 1 February and 30 April 2019 (n = 142). The 'telemonitoring' (TM) cohort included all patients who commenced on CPAP between 1 May and 31 July 2019 (n = 166). Adherence was checked at 30 days (baseline) and 73 days for both cohorts. Wilcoxon-Rank test was used for statistical analysis (results reported as mean ± SEM). Both cohorts had similar adherence at the 30-day baseline, compared to a significantly lower adherence in the HC-cohort at 73 days (55.7 ± 3.0 vs. 51.8 ± 3.2% of days ≥ 4 h: p = 0.0072, average usage 255 ± 12.8 vs. 236 ± 13.7 min: p = 0.0003). There was a significantly higher adherence in the TM-cohort at 73 days (50.8 ± 2.5 vs. 56.1 ± 2.9% of days ≥ 4 h: p = 0.0075; average usage 234 ± 10.4 vs. 252 ± 12.1 min: p = 0.0456). Telemonitoring-feedback is effective at improving adherence with CPAP, suggesting its potential beneficial role in the community setting, particularly in the post-COVID reality of increased remote consultations.