Respiratory

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The effect of sample site and collection procedure on identification of SARS-CoV-2 infection.
(Wiley, 2024-12-16) Davenport, Clare; Arevalo-Rodriguez, Ingrid; Mateos-Haro, Miriam; Berhane, Sarah; Dinnes, Jacqueline; Spijker, René; Buitrago-Garcia, Diana; Ciapponi, Agustín; Takwoingi, Yemisi; Deeks, Jonathan J; Emperador, Devy; Leeflang, Mariska M G; Van den Bruel, Ann
Background: Sample collection is a key driver of accuracy in the diagnosis of SARS-CoV-2 infection. Viral load may vary at different anatomical sampling sites and accuracy may be compromised by difficulties obtaining specimens and the expertise of the person taking the sample. It is important to optimise sampling accuracy within cost, safety and accessibility constraints. Objectives: To compare the sensitivity of different sampling collection sites and methods for the detection of current SARS-CoV-2 infection with any molecular or antigen-based test. Search methods: Electronic searches of the Cochrane COVID-19 Study Register and the COVID-19 Living Evidence Database from the University of Bern (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) were undertaken on 22 February 2022. We included independent evaluations from national reference laboratories, FIND and the Diagnostics Global Health website. We did not apply language restrictions. Selection criteria: We included studies of symptomatic or asymptomatic people with suspected SARS-CoV-2 infection undergoing testing. We included studies of any design that compared results from different sample types (anatomical location, operator, collection device) collected from the same participant within a 24-hour period. Data collection and analysis: Within a sample pair, we defined a reference sample and an index sample collected from the same participant within the same clinical encounter (within 24 hours). Where the sample comparison was different anatomical sites, the reference standard was defined as a nasopharyngeal or combined naso/oropharyngeal sample collected into the same sample container and the index sample as the alternative anatomical site. Where the sample comparison was concerned with differences in the sample collection method from the same site, we defined the reference sample as that closest to standard practice for that sample type. Where the sample pair comparison was concerned with differences in personnel collecting the sample, the more skilled or experienced operator was considered the reference sample. Two review authors independently assessed the risk of bias and applicability concerns using the QUADAS-2 and QUADAS-C checklists, tailored to this review. We present estimates of the difference in the sensitivity (reference sample (%) minus index sample sensitivity (%)) in a pair and as an average across studies for each index sampling method using forest plots and tables. We examined heterogeneity between studies according to population (age, symptom status) and index sample (time post-symptom onset, operator expertise, use of transport medium) characteristics. Main results: This review includes 106 studies reporting 154 evaluations and 60,523 sample pair comparisons, of which 11,045 had SARS-CoV-2 infection. Ninety evaluations were of saliva samples, 37 nasal, seven oropharyngeal, six gargle, six oral and four combined nasal/oropharyngeal samples. Four evaluations were of the effect of operator expertise on the accuracy of three different sample types. The majority of included evaluations (146) used molecular tests, of which 140 used RT-PCR (reverse transcription polymerase chain reaction). Eight evaluations were of nasal samples used with Ag-RDTs (rapid antigen tests). The majority of studies were conducted in Europe (35/106, 33%) or the USA (27%) and conducted in dedicated COVID-19 testing clinics or in ambulatory hospital settings (53%). Targeted screening or contact tracing accounted for only 4% of evaluations. Where reported, the majority of evaluations were of adults (91/154, 59%), 28 (18%) were in mixed populations with only seven (4%) in children. The median prevalence of confirmed SARS-CoV-2 was 23% (interquartile (IQR) 13%-40%). Risk of bias and applicability assessment were hampered by poor reporting in 77% and 65% of included studies, respectively. Risk of bias was low across all domains in only 3% of evaluations due to inappropriate inclusion or exclusion criteria, unclear recruitment, lack of blinding, nonrandomised sampling order or differences in testing kit within a sample pair. Sixty-eight percent of evaluation cohorts were judged as being at high or unclear applicability concern either due to inflation of the prevalence of SARS-CoV-2 infection in study populations by selectively including individuals with confirmed PCR-positive samples or because there was insufficient detail to allow replication of sample collection. When used with RT-PCR • There was no evidence of a difference in sensitivity between gargle and nasopharyngeal samples (on average -1 percentage points, 95% CI -5 to +2, based on 6 evaluations, 2138 sample pairs, of which 389 had SARS-CoV-2). • There was no evidence of a difference in sensitivity between saliva collection from the deep throat and nasopharyngeal samples (on average +10 percentage points, 95% CI -1 to +21, based on 2192 sample pairs, of which 730 had SARS-CoV-2). • There was evidence that saliva collection using spitting, drooling or salivating was on average -12 percentage points less sensitive (95% CI -16 to -8, based on 27,253 sample pairs, of which 4636 had SARS-CoV-2) compared to nasopharyngeal samples. We did not find any evidence of a difference in the sensitivity of saliva collected using spitting, drooling or salivating (sensitivity difference: range from -13 percentage points (spit) to -21 percentage points (salivate)). • Nasal samples (anterior and mid-turbinate collection combined) were, on average, 12 percentage points less sensitive compared to nasopharyngeal samples (95% CI -17 to -7), based on 9291 sample pairs, of which 1485 had SARS-CoV-2. We did not find any evidence of a difference in sensitivity between nasal samples collected from the mid-turbinates (3942 sample pairs) or from the anterior nares (8272 sample pairs). • There was evidence that oropharyngeal samples were, on average, 17 percentage points less sensitive than nasopharyngeal samples (95% CI -29 to -5), based on seven evaluations, 2522 sample pairs, of which 511 had SARS-CoV-2. A much smaller volume of evidence was available for combined nasal/oropharyngeal samples and oral samples. Age, symptom status and use of transport media do not appear to affect the sensitivity of saliva samples and nasal samples. When used with Ag-RDTs • There was no evidence of a difference in sensitivity between nasal samples compared to nasopharyngeal samples (sensitivity, on average, 0 percentage points -0.2 to +0.2, based on 3688 sample pairs, of which 535 had SARS-CoV-2). Authors' conclusions: When used with RT-PCR, there is no evidence for a difference in sensitivity of self-collected gargle or deep-throat saliva samples compared to nasopharyngeal samples collected by healthcare workers when used with RT-PCR. Use of these alternative, self-collected sample types has the potential to reduce cost and discomfort and improve the safety of sampling by reducing risk of transmission from aerosol spread which occurs as a result of coughing and gagging during the nasopharyngeal or oropharyngeal sample collection procedure. This may, in turn, improve access to and uptake of testing. Other types of saliva, nasal, oral and oropharyngeal samples are, on average, less sensitive compared to healthcare worker-collected nasopharyngeal samples, and it is unlikely that sensitivities of this magnitude would be acceptable for confirmation of SARS-CoV-2 infection with RT-PCR. When used with Ag-RDTs, there is no evidence of a difference in sensitivity between nasal samples and healthcare worker-collected nasopharyngeal samples for detecting SARS-CoV-2. The implications of this for self-testing are unclear as evaluations did not report whether nasal samples were self-collected or collected by healthcare workers. Further research is needed in asymptomatic individuals, children and in Ag-RDTs, and to investigate the effect of operator expertise on accuracy. Quality assessment of the evidence base underpinning these conclusions was restricted by poor reporting. There is a need for further high-quality studies, adhering to reporting standards for test accuracy studies.
Exacerbations of lung disease in Alpha-1 antitrypsin deficiency.
(COPD Foundation, 2021-01) Smith, Daniel J; Ellis, Paul R; Turner, Alice M; Respiratory Medicine; Medical and Dental; Turner, Alice
Alpha-1 antitrypsin deficiency (AATD) is an important risk factor for development of chronic obstructive pulmonary disease (COPD). Patients with AATD classically develop a different pattern of lung disease from those with usual COPD, decline faster and exhibit a range of differences in pathogenesis, all of which may be relevant to phenotype and/or impact of exacerbations. There are a number of definitions of exacerbation, with the main features being worsening of symptoms over at least 2 days, which may be associated with a change in treatment. In this article we review the literature surrounding exacerbations in AATD, focusing, in particular, on ways in which they may differ from such events in usual COPD, and the potential impact on clinical management.
A nebulised antitumour necrosis factor receptor-1 domain antibody in patients at risk of postoperative lung injury: A randomised, placebo-controlled pilot study.
(Lippincott Williams & Wilkins, 2020-11) Ryan, James; Bayliffe, Andrew I; McAuley, Daniel F; Yeung, Joyce; Thickett, David R; Howells, Phillip A; O'Donnell, Ciara; Vassallo, Arlette M; Wright, Tracey J; McKie, Elizabeth; Hardes, Kelly; Summers, Charlotte; Shields, Martin O; Powley, William; Wilson, Robert; Lazaar, Aili L; Fowler, Andrew; Perkins, Gavin D; Respiratory Medicine; Anaesthetics; Critical care; Medical and Dental; Thickett, David; Howells, Phillip; Perkins, Gavin D
Background: Tumour necrosis factor receptor 1 (TNFR1) signalling mediates the cell death and inflammatory effects of TNF-α. Objective: The current clinical trial investigated the effects of a nebulised TNFR1 antagonist (GSK2862277) on signs of lung injury in patients undergoing oesophagectomy. Design: Randomised double-blind (sponsor unblind), placebo-controlled, parallel group study. Setting: Eight secondary care centres, the United Kingdom between April 2015 and June 2017. Patients: Thirty-three patients undergoing elective transthoracic oesophagectomy. Interventions: Patients randomly received a single nebulised dose (26 mg) of GSK2862277 (n = 17) or placebo (n = 16), given 1 to 5 h before surgery; 14 and 16, respectively competed the study. Main outcome measurements: Physiological and biochemical markers of lung injury, pharmacokinetic and safety endpoints were measured. The primary endpoint was the change from baseline in pulmonary vascular permeability index (PVPI) at completion of surgery, measured using single-indicator transpulmonary thermodilution. Adjusted point estimates and 95% credible intervals (analogous to conventional confidence intervals) were constructed for each treatment using Bayesian statistical models. Results: The mean change (with 95% credible intervals) from baseline in PVPI on completion of surgery was 0.00 (-0.23, 0.39) in the placebo and 0.00 (-0.24, 0.37) in the GSK2862277 treatment groups. There were no significant treatment-related differences in PaO2/FiO2 or Sequential Organ Failure Assessment score. Levels of free soluble TNFR1, Macrophage Inflammatory Protein-1 alpha and total protein were significantly reduced in the bronchoalveolar lavage fluid of patients treated with GSK2862277 (posterior probability of decrease with GSK2862277 vs. placebo:≥0.977; equivalent to P < 0.05). The frequency of adverse events and serious adverse events were distributed evenly across the two treatment arms. Conclusion: Pre-operative treatment with a single 26 mg inhaled dose of GSK2862277 did not result in significantly lower postoperative alveolar capillary leak or extra vascular lung water. Unexpectedly small increases in transpulmonary thermodilution-measured PVPI and extra vascular lung water index at completion of surgery suggest less postoperative lung injury than historically reported, which may have also compromised a clear assessment of efficacy in this trial. GSK2862277 was well tolerated, resulted in expected lung exposure and reduced biomarkers of lung permeability and inflammation. Trial registration: clinicaltrials.gov: NCT02221037.
Development and relevance of hypercapnia in COPD.
(Wiley, 2021-02-22) Dave, Chirag; Wharton, Simon; Mukherjee, Rahul; Faqihi, Bandar M; Stockley, Robert A; Turner, Alice M; General Medicine; Respiratory Medicine; Medical and Dental; Dave, Chirag; Wharton, Simon; Mukherjee, Rahul; Turner, Alice M
Background: Identification of patients who may become hypercapnic, or develop acidotic hypercapnic respiratory failure (AHRF), is important in chronic obstructive pulmonary disease (COPD) to avoid hospital admission and select patients for use of home NIV. This study aimed to identify factors associated with presence and development of hypercapnia. Methods: 1224 patients, 637 with COPD and 587 with alpha 1 antitrypsin deficiency (AATD), from 4 previously established patient cohorts, were included in cross-sectional analyses of hypercapnia (PaCO2 ≥ 6.5 kPa or 48.8 mmHg), focusing on phenotypic features of COPD and mortality. Longitudinal associations of rising PaCO2 were also assessed. A second cohort of 160 COPD patients underwent sleep studies and 1-year follow-up, analysing in a similar way, incorporating additional information from their sleep studies if appropriate. Results: Hypercapnia was 15 times more common in usual COPD than AATD (p < 0.01) after adjustment for baseline differences by regression. Independent predictors of hypercapnia in COPD included FEV1 and current use of oxygen; these variables, together with lack of emphysema, explained 11% of variance in CO2. Increasing PaCO2 also associated with higher risk of death (p=0.03). 44/160 patients exhibited sleep disordered breathing. The sleep study cohort also showed an association of low FEV1 with hypercapnia. Prior hospital admission for AHRF was also clinically significant, being a feature of almost double the number of hypercapnic patients in both test and sleep study COPD cohorts. Conclusion: Lower FEV1 and prior AHRF are the main associations of hypercapnia in COPD, which carries a poor prognosis, particularly worsening over time.
'Attorneys of the poor': Ttraining physicians to tackle health inequalities.
(Elsevier, 2021-03) FitzPatrick, Michael Eb; Badu-Boateng, Charles; Huntley, Christopher; Morgan, Caitlin; Respiratory Medicine; Medical and Dental; Huntley, Christopher
he stellar gains in life expectancy and health over the past century have been accompanied by an increase in societal and health inequalities. This health gap between the most and least fortunate in our society is widening, driven by complex social determinants of health, as well as healthcare systems themselves. Physicians are not just well-qualified and well-placed to act as advocates for change, but have a moral duty to do so: to stand by silently is to be complicit. Following a workshop on health inequalities and medical training at the Royal College of Physicians Trainees Committee, we sought to examine how health inequalities could be addressed through changes to the medical education system. We discuss the arguments for reform in recruitment to medicine, and changes to undergraduate, postgraduate and continuing medical education in order to equip the profession to deliver meaningful improvements in health inequalities. We propose a population health credential as a mechanism by which specialists can gain additional skills to take on leadership roles addressing health inequalities, allowing them to support colleagues in public health and bring in specialty-specific knowledge and experience.
Authors' response to Young et al: re stage III non-small cell lung cancer management in England.
(W.B. Saunders, 2020-06-24) Harden, S V; Adizie, J B; Navani, N; Beckett, P; Acute Medicine; Medical and Dental; Adizie, Bhavani
No abstract available
Amikacin liposome inhalation suspension for chronic Pseudomonas aeruginosa infection in cystic fibrosis.
(Elsevier, 2019-08-23) Bilton, Diana; Pressler, Tacjana; Fajac, Isabelle; Clancy, John Paul; Sands, Dorota; Minic, Predrag; Cipolli, Marco; Galeva, Ivanka; Solé, Amparo; Quittner, Alexandra L; Liu, Keith; McGinnis, John P; Eagle, Gina; Gupta, Renu; Konstan, Michael W; Respiratory Medicine; Medical and Dental; Whitehouse, Joanna
Background: Shortcomings of inhaled antibiotic treatments for Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF) include poor drug penetration, inactivation by sputum, poor efficiency due to protective biofilm, and short residence in the lung. Methods: Eligible patients with forced expiratory volume in 1 s (FEV1) ≥25% of predicted value at screening and CF with chronic P. aeruginosa infection were randomly assigned to receive 3 treatment cycles (28 days on, 28 days off) of amikacin liposome inhalation suspension (ALIS, 590 mg QD) or tobramycin inhalation solution (TIS, 300 mg BID). The primary endpoint was noninferiority of ALIS vs TIS in change from baseline to day 168 in FEV1 (per-protocol population). Secondary endpoints included change in respiratory symptoms by Cystic Fibrosis Questionnaire-Revised (CFQ-R). Results: The study was conducted February 2012 to September 2013. ALIS was noninferior to TIS (95% CI, -4.95 to 2.34) for relative change in FEV1 (L) from baseline. The mean increases in CFQ-R score from baseline on the Respiratory Symptoms scale suggested clinically meaningful improvement in both arms at the end of treatment in cycle 1 and in the ALIS arm at the end of treatment in cycles 2 and 3; however, the changes were not statistically significant between the 2 treatment arms. Treatment-emergent adverse events (TEAEs) were reported in most patients (ALIS, 84.5%; TIS, 78.8%). Serious TEAEs occurred in 17.6% and 19.9% of patients, respectively; most were hospitalisations for infective pulmonary exacerbation of CF. Conclusions: Cyclical dosing of once-daily ALIS was noninferior to cyclical twice-daily TIS in improving lung function. ClinicalTrials.gov Identifier: NCT01315678.
A systematic review of the use of physiological tests assessing the acute response to treatment during exacerbations of COPD (with a focus on small airway function).
(Informa Healthcare, 2020-11-12) Alobaidi, Nowaf Y; Almeshari, Mohammed; Stockley, James A; Sapey, Elizabeth; Edgar, Ross G; Outpatient; Therapy; Allied Health Professional; Healthcare Scientists; Stockley, James A; Edgar, Ross G
Exacerbations are prevalent in Chronic Obstructive Pulmonary Disease (COPD) patients and associated with poor clinical outcomes. Currently, there is a lack of sensitive and specific tools that can objectively identify exacerbations and assess their progress or treatment response. FEV1 is often reported as a study outcome, but it has significant limitations. Studies have suggested that small airways measures might provide physiological biomarkers during exacerbations. Therefore, this study was done to assess which physiological tests of small airways function have been used in the acute setting during exacerbations of COPD and the evidence to support their use. An electronic databases search was conducted in April 2019. A standard systematic review methodology was used. Eligible studies were those of ≥10 participants that compared at least one small airway test with FEV1 to assess response to treatment with baseline and a follow-up measurement ≤2 months after. Analyses were narrative. Of 1436 screened studies, seven studies were eligible. There was heterogeneity in which tests of small airways were used and three different small airways measures were reported. Studies were small (including 20 to 87 subjects). Six articles reported improvements in small airway measurements during the recovery from exacerbation which correlated with FEV1. Included studies varied in their timing and duration of the assessment. There is some evidence to support the use of small airway tests in acute exacerbations of COPD. However, studies have been small with different tests being utilized. Further studies to determine the usefulness of each test may be of interest.
An exploration into experiences and attitudes regarding risky health behaviours in an adult cystic fibrosis population.
(Routledge, 2019-12-23) Keyte, Rebecca; Egan, Helen; Nash, Edward F; Regan, Anna; Jackson, Craig; Mantzios, Michail
Health risk behaviours (HRBs) are prevalent within the cystic fibrosis (CF) population, and there is a lack of research around what influences their engagement. This research explored beliefs associated with HRBs within an adult CF population using qualitative semi-structured interviews. Participants' beliefs towards their CF and its life impact were investigated to explore reasons for engaging in HRB. A desire for normalcy was evident, often accompanied by engagement in everyday HRB as a method of minimising the illness identity. Evidence of a life-orientated illness perspective was also prevalent, with participants engaging in some risky behaviours for fun. Overall, there was a lack of knowledge on the consequences of HRB, with many participants reporting not being informed of these by clinicians. This research highlights a dilemma between clinical recommendations and personal life strategies undertaken by individuals with CF to support their identity.
An overview of exacerbations of chronic obstructive pulmonary disease: can tests of small airways' function guide diagnosis and management?
(Medknow Publications, 2020-04-03) Alobaidi, Nowaf Y; Stockley, James A; Stockley, Robert A; Sapey, Elizabeth; Outpatient; Medicine; Additional Professional Scientific and Technical Field; Medical and Dental; Stockley, James A; Stockley, Robert
Chronic obstructive pulmonary disease (COPD) is common and debilitating. Most patients with COPD experience intermittent, acute deterioration in symptoms which require additional therapy, termed exacerbations. Exacerbations are prevalent in COPD and are associated with poor clinical outcomes including death, a faster decline in lung health, and a reduced quality of life. Current guidelines highlight the need to treat exacerbations promptly and then mitigate future risk. However, exacerbations are self-reported, difficult to diagnose and are treated with pharmacological therapies which have largely been unchanged over 30 years. Recent research has highlighted how exacerbations vary in their underlying cause, with specific bacteria, viruses, and cell types implicated. This variation offers the opportunity for new targeted therapies, but to develop these new therapies requires sensitive tools to reliably identify the cause, the start, and end of an exacerbation and assess the response to treatment. Currently, COPD is diagnosed and monitored using spirometric measures, principally the forced expiratory volume in 1 s and forced vital capacity, but these tests alone cannot reliably diagnose an exacerbation. Measures of small airways' function appear to be an early marker of COPD, and some studies have suggested that these tests might also provide physiological biomarkers for exacerbations. In this review, we will discuss how exacerbations of COPD are currently defined, stratified, monitored, and treated and review the current literature to determine if tests of small airways' function might improve diagnostic accuracy or the assessment of response to treatment.
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.
(Wiley, 2024-12-26) Morgan, Cara; Idris, Nikmah; Elterefi, Kathy; Di Ienno, Luca; Constantine, Andrew; Quyam, Sadia; Bini, Roberta; Moledina, Shahin; Cardiology; Medical and Dental; Constantine, Andrew
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.
Can symptoms of anosmia and dysgeusia be diagnostic for COVID-19?
(John Wiley & Sons, 2020-09-16) Zahra, Syeda Anum; Iddawela, Sashini; Pillai, Kiran; Choudhury, Rozina Yasmin; Harky, Amer; University of London; University Hospitals Birmingham NHS Foundation Trust; Liverpool Heart and Chest Hospital; University of Liverpool
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.
BTS clinical statement on pulmonary sarcoidosis
(British Medical Association, 2020-12-15) Thillai, Muhunthan; Atkins, Christopher P; Crawshaw, Anjali; Hart, Simon P; Ho, Ling-Pei; Kouranos, Vasileios; Patterson, Karen; Screaton, Nicholas J; Whight, Joanna; Wells, Athol U; Royal Papworth Hospitals NHS Foundation Trust; Norfolk and Norwich University Hospitals NHS Foundation Trust; University Hospitals Birmingham NHS Foundation Trust; University of Hull; Oxford University Hospitals NHS Foundation Trust; Guy's and St Thomas' NHS Foundation Trust; Brighton and Sussex Medical School; SarcoidosisUK; Respiratory Medicine; Medical and Dental; Crawshaw, Anjali
No abstract available
BronchUK: protocol for an observational cohort study and biobank in bronchiectasis
(European Respiratory Society, 2021-04-19) De Soyza, Anthony; Mawson, Philip; Hill, Adam T; Elborn, Stuart; Bradley, Judy M; Haworth, Charles S; Floto, R Andres; Wilson, Robert; Loebinger, Michael R; Carroll, Mary; Crichton, Megan; Chalmers, James D; Sullivan, Anita; Brown, Jeremy; Hurst, John R; Duckers, Jamie; Kelly, Martin; Steer, John; Gatheral, Tim; Walker, Paul P; Winstanley, Craig; McGuire, Alistair; Denning, David; McNally, Richard; Newcastle University; Royal Infirmary; University of Edinburgh; Queen's University; Royal Papworth Hospital; University of Cambridge; Imperial College London; University Hospital Southampton NHS Foundation Trust; University of Dundee; University Hospitals Birmingham NHS Foundation Trust; University College London; Cardiff and Vale University Health Board; Western Health and Social Care Trust; Northumbria Healthcare NHS Foundation Trust; University Hospitals of Morecambe Bay NHS Foundation Trust; Liverpool University Hospitals; University of Liverpool; London School of Economics; The University of Manchester; Respiratory Medicine; Medical and Dental; Sullivan, Anita
Bronchiectasis 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.
Bronchiectasis: a progressive phenotype of chronic obstructive pulmonary disease
(Oxford University Press, 2020-01-22) Stockley, R A; University Hospitals Birmingham NHS Foundation Trust; Lung Investigation Unit; Admin and Clerical; Stockley, Rob
No abstract available
Integration of lung function data: turning snapshots into stories.
(European Respiratory Society, 2024-11-12) Wallbanks, Samuel R; Apen, Calvin; Respiratory; Medical and Dental; Wallbanks, Samuel R
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.
External validation of potential breath biomarkers for asthma: a step forward toward the clinical implementation of breath analysis
(American Thoracic Society, 2024-11-21) Sola-Martínez, Rosa A; Turner, Alice M; de Diego Puente, Teresa; University of Murcia; University of Birmingham; University Hospitals Birmingham NHS Foundation Trust; Respiratory; Medical and Dental; Turner, Alice M
No abstract available
Neutrophil dynamics in pulmonary fibrosis: pathophysiological and therapeutic perspectives
(European Respiratory Society, 2024-11-27) Dosanjh, Davinder; Scott, Aaron; Parekh, Dhruv; Crowley, Louise E.; Stockley, Robert A.; Tickett, David R.; University Hospitals Birmingham NHS Foundation Trust; University of Birmingham; Respiratory; Critical Care; Medical and Dental; Crowley, Louise E.; Thickett, David R.; Parekh, Dhruv
The 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.
Biomarker-guided antibiotic stewardship in suspected ventilator-associated pneumonia (VAPrapid2): a randomised controlled trial and process evaluation
(Elsevier, 2019-12-03) Hellyer, Thomas P; McAuley, Daniel F; Walsh, Timothy S; Anderson, Niall; Conway Morris, Andrew; Singh, Suveer; Dark, Paul; Roy, Alistair I; Perkins, Gavin D; McMullan, Ronan; Emerson, Lydia M; Blackwood, Bronagh; Wright, Stephen E; Kefala, Kallirroi; O'Kane, Cecilia M; Baudouin, Simon V; Paterson, Ross L; Rostron, Anthony J; Agus, Ashley; Bannard-Smith, Jonathan; Robin, Nicole M; Welters, Ingeborg D; Bassford, Christopher; Yates, Bryan; Spencer, Craig; Laha, Shondipon K; Hulme, Jonathan; Bonner, Stephen; Linnett, Vanessa; Sonksen, Julian; Van Den Broeck, Tina; Boschman, Gert; Keenan, Dw James; Scott, Jonathan; Allen, A Joy; Phair, Glenn; Parker, Jennie; Bowett, Susan A; Simpson, A John; Newcastle University; Queen's University Belfast; The Royal Hospitals, Belfast; University of Edinburgh; Royal Infirmary of Edinburgh; University of Cambridge; Addenbrooke's Hospital; Imperial College London; University of Manchester; City Hospitals Sunderland NHS Foundation Trust; University of Warwick; University Hospitals Birmingham NHS Foundation Trust; Newcastle upon Tyne Hospitals NHS Foundation Trust; Western General Hospital; Manchester University NHS Foundation Trust; Countess of Chester NHS Foundation Trust; University of Liverpool; University Hospitals Coventry and Warwickshire NHS Trust; Northumbria Specialist Emergency Care Hospital; Lancashire Teaching Hospitals NHS Foundation Trust; Sandwell and West Birmingham Hospitals NHS Trust; South Tees Hospitals NHS Foundation Trust; Gateshead NHS Foundation Trust; Dudley Group NHS Foundation Trust; Becton Dickinson Biosciences Europe; Critical Care; Medical and Dental; Perkins, Gavin; Bassford, Christopher
Background: 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.
Bilateral pulmonary embolism while receiving tranexamic acid: a case report
(BioMed Central, 2020-11-06) Ijaopo, Ezekiel Oluwasayo; Ijaopo, Ruth Oluwasolape; Adjei, Sampson; East Kent Hospitals University NHS Foundation Trust; University Hospitals Birmingham NHS Foundation Trust
Background: 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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