BMJ Open Respiratory Research

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ISSN / EISSN : 2052-4439 / 2052-4439
Published by: BMJ (10.1136)
Total articles ≅ 528
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, James Stockley, , Brendan Cooper
Published: 12 October 2021
by BMJ
BMJ Open Respiratory Research, Volume 8; https://doi.org/10.1136/bmjresp-2021-001070

Abstract:
Introduction COVID-19 pandemic has had a huge impact on global health to date, with 5.6 million cases in the UK since its emergence. The respiratory symptoms largely mimic those of pneumonia’ with symptoms ranging from mild to severe. The effects on respiratory physiology are not yet fully understood, but evidence is emerging that there is much dysfunctional breathing reported but little information on tidal ventilation from the acute phase of the infection. Structured light plethysmography (SLP) is a contactless technique of respiratory function testing that measures tidal breathing parameters by assessing thoracoabdominal displacement. Methods In a postdischarge clinic, SLP was performed routinely on 110 hospitalised patients recovering from COVID-19 who had been screened for respiratory symptoms to confirm any respiratory changes occurring after the disease. Patients were categorised based on their hospital treatment in (1) the intensive therapy unit (ITU) (requiring intubation) (n=65) or (2) respiratory wards only (n=45). Data from these two patient cohorts were compared with preacquired data from healthy controls (n=30). Results We have found a significantly increased respiratory rate (p=0.006) in ITU patients compared with the healthy cohort and also a significant decrease in the inspiratory time (p=0.01), expiratory time (p=0.005) and the total breathing cycle (p=0.008). There were no significant differences between ITU and ward patients and no significant differences in healthy compared with ward patients. We examined the variability of breathing (‘entropy’) both in terms of the breath-to-breath interval and the volume-to-volume change. The breath-to-breath interval alone was significantly lower in ITU patients compared with healthy cohorts (p=0.02). Conclusion Our findings suggest that abnormalities in tidal breathing can be detected in COVID-19 recovery patients, and SLP may be a promising tool in assessing the aftermath of diseases such as COVID-19, particularly if more intensive management strategies such as mechanical ventilation are required.
Charlie McLeod, Richard Norman, Jamie Wood, Siobhain Mulrennan, Sue Morey, André Schultz, Mitch Messer, Kate Spaapen, Matthew Stoneham, Yue Wu, et al.
Published: 7 October 2021
by BMJ
BMJ Open Respiratory Research, Volume 8; https://doi.org/10.1136/bmjresp-2021-000877

Abstract:
Background A standardised framework for selecting outcomes for evaluation in trials has been proposed by the Core Outcome Measures in Effectiveness Trials working group. However, this method does not specify how to ensure that the outcomes that are selected are causally related to the disease and the health intervention being studied. Causal network diagrams may help researchers identify outcomes that are both clinically meaningful and likely to be causally dependent on the intervention, and endpoints that are, in turn, causally dependent on those outcomes. We aimed to (1) develop a generalisable method for selecting outcomes and endpoints in trials and (2) apply this method to select outcomes for evaluation in a trial investigating treatment strategies for pulmonary exacerbations of cystic fibrosis (CF). Methods We conducted a series of online surveys and workshops among people affected by CF. We used a modified Delphi approach to develop a consensus list of important outcomes. A workshop involving domain experts elicited how these outcomes were causally related to the underlying pathophysiological processes. Meaningful outcomes were prioritised based on the extent to which each outcome captured separate rather than common aspects of the underlying pathophysiological process. Results The 10 prioritised outcomes were: breathing difficulty/pain, sputum production/clearance, fatigue, appetite, pain (not related to breathing), motivation/demoralisation, fevers/night sweats, treatment burden, inability to meet personal goals and avoidance of gastrointestinal symptoms. Conclusions This proposed method for selecting meaningful outcomes for evaluation in clinical trials may improve the value of research as a basis for clinical decisions.
David J Jackson, Claire Butler, Rekha Chaudhuri, Katie Pink, Robert Niven, Samantha Prigmore, Charlotte Renwick, James Calvert
Published: 28 September 2021
by BMJ
BMJ Open Respiratory Research, Volume 8; https://doi.org/10.1136/bmjresp-2021-001057

Abstract:
Introduction Severe asthma affects an estimated 3%–5% of people with asthma and is associated with frequent exacerbations, poor symptom control and significant morbidity from the disease itself, as well as high dose of inhaled and systemic steroids used to treat it. The introduction of specialist asthma services across the UK has attempted to improve quality of care and ensure that patients undergo a full systematic assessment prior to initiation of advanced biological therapies. However, improvements are required in the patient pathway to minimise avoidable harm. Objectives To define standards of care in areas where the evidence base is lacking through patient and healthcare professional (HCP) consensus. Methods The precision UK National Working Group of asthma experts identified 42 statements formed from 7 key themes. An online four-point Likert scale questionnaire was sent to HCPs working in asthma throughout the UK to assess agreement (consensus) with these statements; a subset of the statements formed a patient questionnaire. Consensus was defined as high if ≥75% and very high if ≥90% of respondents agreed with a statement. Results A total of 117/197 responses (59.3% response rate) were received from severe asthma patients (n=15) and HCPs (n=102) including respiratory physicians, respiratory nurse specialists, respiratory pharmacists, specialist physiotherapists and general practitioners. Consensus was very high in 25 (60%) statements, high in 12 (29%) statements and was not achieved in 5 (12%) statements. Based on the consensus scores, the precision UK National Working Group derived 10 key recommendations. These focus on referrals from primary and secondary care, accessing specialist asthma services, homecare provision for severe asthma patients and outcome measures. Conclusions Implementation of these 10 recommendations across the severe asthma pathway in the UK has the potential to improve outcomes for patients by reducing delays to assessment and initiation of advanced phenotype-specific therapies.
Angelita Cabrera, Cesar Picado, ,
Published: 27 September 2021
by BMJ
BMJ Open Respiratory Research, Volume 8; https://doi.org/10.1136/bmjresp-2021-001004

Abstract:
Background In 2003, the International Study of Asthma and Allergies in Childhood (ISAAC) estimated the prevalence of asthma, rhinitis and eczema symptoms in Quito, Ecuador. Since then, no update of this study has been done in the last years. This study examined changes in the prevalence of asthma–rhinitis–eczema symptoms over a 16 years period in Quito and explored possible risk factors. Methods We conducted a comparative cross-sectional study in an adolescent population following the Global Asthma Network (GAN) methodology. A written questionnaire was used to explore symptoms of asthma–rhinitis–eczema. We calculated the prevalence and 95% CIs for each of the symptoms and compared them with the ISAAC results. We conducted bivariate and multivariate analysis using logistic regression to identify possible risk factors for recent wheeze, rhinitis and eczema. Results A total of 2380 adolescents aged between 13 and 14 years were evaluated. The prevalence of doctor diagnosis for asthma, rhinitis and eczema was 3.4%, 8.5% and 2.2%, respectively. Compared with ISAAC results, we found a lower prevalence of wheeze and eczema symptoms: wheeze ever (37.6% vs 12.7%), recent wheeze (17.8% vs 6.5%), asthma ever (6.9% vs 4.6%), recent rush (22.4% vs 13.9%) and eczema ever (11.7% vs 3.6%). The prevalence of rhinitis symptoms in the GAN study was higher than the ISAAC results: nose symptoms in the past 12 months (36.6% vs 45.8%) and nose and eye symptoms in the past 12 months (23.1% vs 27.9). Significant associations were observed between symptoms of asthma–rhinitis–eczema and sex, race/ethnicity, smoking habit, physical exercise and sedentary activities. Conclusions In the last two decades, the prevalence of asthma and eczema symptoms in adolescent population in the city of Quito has significantly declined; however, the prevalence of rhinitis symptoms has increased. The reduction in asthma symptoms could be related to better managing the disease and changes in local environmental risk factors in the last years. Further studies must be conducted in the country to evaluate the change in trends in asthma and other related allergic diseases.
Adrian M Shields, Sian E Faustini, Marisol Perez-Toledo, Sian Jossi, Joel D Allen, Saly Al-Taei, Claire Backhouse, Lynsey A Dunbar, Daniel Ebanks, Beena Emmanuel, et al.
Published: 24 September 2021
by BMJ
BMJ Open Respiratory Research, Volume 8; https://doi.org/10.1136/bmjresp-2020-000872

Abstract:
Objective To determine clinical and ethnodemographic correlates of serological responses against the SARS-CoV-2 spike glycoprotein following mild-to-moderate COVID-19. Design A retrospective cohort study of healthcare workers who had self-isolated due to COVID-19. Setting University Hospitals Birmingham NHS Foundation Trust, UK (UHBFT). Participants 956 healthcare workers were recruited by open invitation via UHBFT trust email and social media between 27 April 2020 and the 8 June 2020. Intervention Participants volunteered a venous blood sample that was tested for the presence of anti-SARS-CoV-2 spike glycoprotein antibodies. Results were interpreted in the context of the symptoms of their original illness and ethnodemographic variables. Results Using an assay that simultaneously measures the combined IgG, IgA and IgM response against the spike glycoprotein (IgGAM), the overall seroprevalence within this cohort was 46.2% (n=442/956). The seroprevalence of immunoglobulin isotypes was 36.3%, 18.7% and 8.1% for IgG, IgA and IgM, respectively. IgGAM identified serological responses in 40.6% (n=52/128) of symptomatic individuals who reported a negative SARS-CoV-2 PCR test. Increasing age, non-white ethnicity and obesity were independently associated with greater IgG antibody response against the spike glycoprotein. Self-reported fever and fatigue were associated with greater IgG and IgA responses against the spike glycoprotein. The combination of fever and/or cough and/or anosmia had a positive predictive value of 92.3% for seropositivity in self-isolating individuals a time when Wuhan strain SARS-CoV-2 was predominant. Conclusions and relevance Assays employing combined antibody detection demonstrate enhanced seroepidemiological sensitivity and can detect prior viral exposure even when PCR swabs have been negative. We demonstrate an association between known ethnodemographic risk factors associated with mortality from COVID-19 and the magnitude of serological responses in mild-to-moderate disease.
Entela Koco, Eleni Soilemezi, Panagiota Sotiriou, Savvoula Savvidou, Matthew Tsagourias, Ioannis Pnevmatikos, Dimitrios Matamis
Published: 23 September 2021
by BMJ
BMJ Open Respiratory Research, Volume 8; https://doi.org/10.1136/bmjresp-2021-001006

Abstract:
Transdiaphragmatic (Pdi) and oesophageal pressures (Pes) are useful in understanding the pathophysiology of the respiratory system. They provide insight into respiratory drive, intrinsic positive end-expiratory pressure, diaphragmatic fatigue and weaning failure. Background The use of Pdi and Pes in clinical practice is restricted due to the invasiveness of the technique and the cumbersome equipment needed. On the other hand, diaphragmatic displacement is non-invasively and easily assessed with M-mode ultrasound. Purpose We observed striking similarities in shape and magnitude between M-mode diaphragmatic displacement, Pes and Pdi pressures. The study aimed to evaluate if the information provided by these two pressures could be obtained non-invasively from the diaphragmatic displacement curve. Material and methods In 14 consecutive intubated patients undergoing a weaning trial, simultaneous recordings of Pes and Pdi pressures and the diaphragmatic displacement were assessed while breathing spontaneously and during a sniff-like manoeuvre. Moreover, the slope of the diaphragmatic displacement curve during relaxation was compared with the maximal relaxation rate (MRR) obtained from the Pdi curve. Results More than 200 breaths were analysed in pairs. Diaphragmatic displacement significantly correlated with Pdi (R2=0.33, p<0.001) and Pes (R2=0.44, p<0.001), and this correlation further improved during sniff (R2=0.47, p<0.001) and (R2=0.64, p<0.001), respectively. Additionally, a significant correlation was found between the relaxation slope derived from the diaphragmatic displacement curve and the MRR derived from the Pdi curve, both in normal breathing (R2=0.379, p<0.001) and during the sniff manoeuvre (R2=0.71, p<0.001). Conclusions M-mode diaphragmatic displacement parameters correlate well with the ones obtained from oesophageal pressure and Pdi, particularly during sniffing. Diaphragmatic displacement assessment possibly offers an alternative non-invasive solution for understanding and clinically monitoring the diaphragmatic contractile properties and weaning failure due to diaphragmatic fatigue.
Jim M Wild, Joanna C Porter, Philip L Molyneaux, Peter M George, , Richard James Allen, Raminder Aul, , Shaney L Barratt, Paul Beirne, et al.
Published: 23 September 2021
by BMJ
BMJ Open Respiratory Research, Volume 8; https://doi.org/10.1136/bmjresp-2021-001049

Abstract:
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.
Paul L Nguyen, Heba Osman, Donovan Watza, Suman Khicher, Aditi Sharma, Greg Dyson, Ghulam Saydain, Ayman Soubani
Published: 21 September 2021
by BMJ
BMJ Open Respiratory Research, Volume 8; https://doi.org/10.1136/bmjresp-2021-000875

Abstract:
Importance Use of non-invasive respiratory modalities in COVID-19 has the potential to reduce rates of intubation and mortality in severe disease however data regarding the use of high-flow nasal cannula (HFNC) in this population is limited. Objective To interrogate clinical and laboratory features of SARS-CoV-2 infection associated with high-flow failure. Design We conducted a retrospective cohort study to evaluate characteristics of high-flow therapy use early in the pandemic and interrogate factors associated with respiratory therapy failure. Setting Multisite single centre hospital system within the metropolitan Detroit region. Participants Patients from within the Detroit Medical Center (n=104, 89% African American) who received HFNC therapy during a COVID-19 admission between March and May of 2020. Primary outcome HFNC failure is defined as death or intubation while on therapy. Results Therapy failure occurred in 57% of the patient population, factors significantly associated with failure centred around markers of multiorgan failure including hepatic dysfunction/transaminitis (OR=6.1, 95% CI 1.9 to 19.4, p<0.01), kidney injury (OR=7.0, 95% CI 2.7 to 17.8, p<0.01) and coagulation dysfunction (OR=4.5, 95% CI 1.2 to 17.1, p=0.03). Conversely, comorbidities, admission characteristics, early oxygen requirements and evaluation just prior to HFNC therapy initiation were not significantly associated with success or failure of therapy. Conclusions In a population disproportionately affected by COVID-19, we present key indicators of likely HFNC failure and highlight a patient population in which aggressive monitoring and intervention are warranted.
Zhonghua Shi, Sylvia J P Bogaards, Stefan Conijn, Yeszamin Onderwater, Pedro Espinosa, Diewertje I Bink, Marloes Van Den Berg, Martijn van de Locht, Marianna Bugiani, Hans van der Hoeven, et al.
Published: 20 September 2021
by BMJ
BMJ Open Respiratory Research, Volume 8; https://doi.org/10.1136/bmjresp-2021-001052

Abstract:
Introduction The diaphragm is the main muscle of inspiration, and its dysfunction contributes to adverse clinical outcomes in critically ill patients. We recently reported the infiltration of SARS-CoV-2, and the development of fibrosis, in the diaphragm of critically ill patients with COVID-19. In the current study, we aimed to characterise myofiber structure in the diaphragm of critically ill patients with COVID-19. Methods Diaphragm muscle specimens were collected during autopsy from patients who died of COVID-19 in three academic medical centres in the Netherlands in April and May 2020 (n=27). We studied diaphragm myofiber gene expression and structure and compared the findings obtained to those of deceased critically ill patients without COVID-19 (n=10). Results Myofibers of critically ill patients with COVID-19 showed on average larger cross-sectional area (slow-twitch myofibers: 2441±229 vs 1571±309 µm2; fast-twitch myofibers: 1966±209 vs 1225±222 µm2). Four critically ill patients with COVID-19 showed extremely large myofibers, which were splitting and contained many centralised nuclei. RNA-sequencing data revealed differentially expressed genes involved in muscle regeneration. Conclusion Diaphragm of critically ill patients with COVID-19 has distinct myopathic features compared with critically ill patients without COVID-19, which may contribute to the ongoing dyspnoea and fatigue in the patients surviving COVID-19 infection.
, Florencia Boshier, Cristina Venturini, José Afonso Guerra-Assunção, Adela Alcolea-Medina, Angela Beckett, Themoula Charalampous, Ana Da Silva Filipe, Sharon Glaysher, Tabassum Khan, et al.
Published: 20 September 2021
by BMJ
BMJ Open Respiratory Research, Volume 8; https://doi.org/10.1136/bmjresp-2021-001029

Abstract:
Background SARS-CoV-2 lineage B.1.1.7 has been associated with an increased rate of transmission and disease severity among subjects testing positive in the community. Its impact on hospitalised patients is less well documented. Methods We collected viral sequences and clinical data of patients admitted with SARS-CoV-2 and hospital-onset COVID-19 infections (HOCIs), sampled 16 November 2020 to 10 January 2021, from eight hospitals participating in the COG-UK-HOCI study. Associations between the variant and the outcomes of all-cause mortality and intensive therapy unit (ITU) admission were evaluated using mixed effects Cox models adjusted by age, sex, comorbidities, care home residence, pregnancy and ethnicity. Findings Sequences were obtained from 2341 inpatients (HOCI cases=786) and analysis of clinical outcomes was carried out in 2147 inpatients with all data available. The HR for mortality of B.1.1.7 compared with other lineages was 1.01 (95% CI 0.79 to 1.28, p=0.94) and for ITU admission was 1.01 (95% CI 0.75 to 1.37, p=0.96). Analysis of sex-specific effects of B.1.1.7 identified increased risk of mortality (HR 1.30, 95% CI 0.95 to 1.78, p=0.096) and ITU admission (HR 1.82, 95% CI 1.15 to 2.90, p=0.011) in females infected with the variant but not males (mortality HR 0.82, 95% CI 0.61 to 1.10, p=0.177; ITU HR 0.74, 95% CI 0.52 to 1.04, p=0.086). Interpretation In common with smaller studies of patients hospitalised with SARS-CoV-2, we did not find an overall increase in mortality or ITU admission associated with B.1.1.7 compared with other lineages. However, women with B.1.1.7 may be at an increased risk of admission to intensive care and at modestly increased risk of mortality.
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