Real-world experience of nintedanib for progressive fibrosing interstitial lung disease in the UK.

Background: Nintedanib slows progression of lung function decline in patients with progressive fibrosing (PF) interstitial lung disease (ILD) and was recommended for this indication within the United Kingdom (UK) National Health Service in Scotland in June 2021 and in England, Wales and Northern Ireland in November 2021. To date, there has been no national evaluation of the use of nintedanib for PF-ILD in a real-world setting.

Methods: 26 UK centres were invited to take part in a national service evaluation between 17 November 2021 and 30 September 2022.

Nebulised interferon-β1a (SNG001) in hospitalised COVID-19: SPRINTER phase III study.

Background: Despite the availability of vaccines and therapies, patients are being hospitalised with coronavirus disease 2019 (COVID-19). Interferon (IFN)-β is a naturally occurring protein that stimulates host immune responses against most viruses, including severe acute respiratory syndrome coronavirus 2. SNG001 is a recombinant IFN-β1a formulation delivered to the lungs nebuliser.

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial.

Background: Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19.

Methods: In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days.

Utility of severity assessment tools in COVID-19 pneumonia: a multicentre observational study.

Background: Severity scores in pneumonia and sepsis are being applied to SARS-CoV-2 infection. We aimed to assess whether these severity scores are accurate predictors of early adverse outcomes in COVID-19.

Methods: We conducted a multicentre observational study of hospitalised SARS-CoV-2 infection.

Coronary artery thrombus resulting in ST-elevation myocardial infarction in a patient with COVID-19.

COVID-19 is a prothrombotic condition that is also associated with raised troponin levels and myocardial damage. We present a case of a 54-year-old man who was admitted with respiratory failure due to COVID-19 and developed a ST-elevation myocardial infarction (STEMI) during his admission. His coronary angiogram did not show any significant coronary artery disease other than a heavily thrombosed right coronary artery.

COVID-19 admission risk tools should include multiethnic age structures, multimorbidity and deprivation metrics for air pollution, household overcrowding, housing quality and adult skills.

Background: Ethnic minorities account for 34% of critically ill patients with COVID-19 despite constituting 14% of the UK population. Internationally, researchers have called for studies to understand deterioration risk factors to inform clinical risk tool development.

Methods: Multicentre cohort study of hospitalised patients with COVID-19 (n=3671) exploring determinants of health, including Index of Multiple Deprivation (IMD) subdomains, as risk factors for presentation, deterioration and mortality by ethnicity.

Increase in recruitment upon integration of trial into a clinical care pathway: an observational study.

Introduction: Many respiratory clinical trials fail to reach their recruitment target and this problem exacerbates existing funding issues. Integration of the clinical trial recruitment process into a clinical care pathway (CCP) may represent an effective way to significantly increase recruitment numbers.

Methods: A respiratory support unit and a CCP for escalation of patients with severe COVID-19 were established on 11 January 2021.

Real-world retrospective observational study exploring the effectiveness and safety of antifibrotics in idiopathic pulmonary fibrosis.

Background: Pirfenidone and nintedanib are the only disease-modifying treatments available for idiopathic pulmonary fibrosis (IPF). Our aim was to test their effectiveness and safety in clinical practice.

Methods: This is a single-centre retrospective observational study undertaken at a specialised interstitial lung disease centre in England.

Outcome of Hospitalization for COVID-19 in Patients with Interstitial Lung Disease. An International Multicenter Study.

The impact of coronavirus disease (COVID-19) on patients with interstitial lung disease (ILD) has not been established. To assess outcomes in patients with ILD hospitalized for COVID-19 versus those without ILD in a contemporaneous age-, sex-, and comorbidity-matched population. An international multicenter audit of patients with a prior diagnosis of ILD admitted to the hospital with COVID-19 between March 1 and May 1, 2020, was undertaken and compared with patients without ILD, obtained from the ISARIC4C (International Severe Acute Respiratory and Emerging Infection Consortium Coronavirus Clinical Characterisation Consortium) cohort, admitted with COVID-19 over the same period.

Early identification of severe community-acquired pneumonia: a retrospective observational study.

Background: Community-acquired pneumonia (CAP) is a leading cause of sepsis worldwide. Prompt identification of those at high risk of adverse outcomes improves survival by enabling early escalation of care. There are multiple severity assessment tools recommended for risk stratification; however, there is no consensus as to which tool should be used for those with CAP.

Pro-inflammatory effects of e-cigarette vapour condensate on human alveolar macrophages.

Objective: Vaping may increase the cytotoxic effects of e-cigarette liquid (ECL). We compared the effect of unvaped ECL to e-cigarette vapour condensate (ECVC) on alveolar macrophage (AM) function.

Methods: AMs were treated with ECVC and nicotine-free ECVC (nfECVC).

Oxygen prescription: improving compliance using methods from journal.

Oxygen is an important drug frequently used in the management of acutely unwell hospital patients. However, oxygen overuse can have fatal side effects particularly for those patients at risk of iatrogenic hypercapnia. British Thoracic Society Guidelines state that oxygen must be prescribed for all patients, with target saturations stipulated on the prescription for patient safety.

Sepsis Induces a Dysregulated Neutrophil Phenotype That Is Associated with Increased Mortality.

Background: Neutrophil dysfunction in sepsis has been implicated in the pathogenesis of multiorgan failure; however, the role of neutrophil extracellular traps (NETs) remains uncertain. We aimed to determine the sequential changes in ex vivo NETosis and its relationship with mortality in patients with sepsis and severe sepsis.

Methods: This was a prospective observational cohort study enrolling 21 healthy age-matched controls and 39 sepsis and 60 severe sepsis patients from acute admissions to two UK hospitals.

Statin therapy in patients with community-acquired pneumonia.

Community-acquired pneumonia (CAP) is the leading cause of death from infection in developed countries. There is evidence of an association between improved survival from infection and statin use. The possible beneficial effects of statins are complicated by the common use of macrolide antibiotics for pneumonia, with current guidance suggesting that concurrent macrolide and statin use is contraindicated.

Increased risk of Mycobacterium tuberculosis infection in household child contacts exposed to passive tobacco smoke.

Risk factors associated with Mycobacterium tuberculosis infection were investigated in a prospective cohort of household child tuberculosis contacts. A significantly increased risk of acquiring infection was associated with exposure to passive cigarette smoke, higher number of index cases, younger age and reduced household monthly income.

Novel M tuberculosis antigen-specific T-cells are early markers of infection and disease progression.

Background: Mycobacterium tuberculosis Region-of-Difference-1 gene products present opportunities for specific diagnosis of M. tuberculosis infection, yet immune responses to only two gene-products, Early Secretory Antigenic Target-6 (ESAT-6) and Culture Filtrate Protein-10 (CFP-10), have been comprehensively investigated.

Methods: T-cell responses to Rv3873, Rv3878 and Rv3879c were quantified by IFN-γ-enzyme-linked-immunospot (ELISpot) in 846 children with recent household tuberculosis exposure and correlated with kinetics of tuberculin skin test (TST) and ESAT-6/CFP-10-ELISpot conversion over six months and clinical outcome over two years.

Patient reported outcomes and their importance in the development of novel surgical techniques.

Introduction: Although traditional quality measures such as morbidity and mortality outcomes still pay an important role in the assessment of health care quality, greater emphasis is now being placed on patient-reported outcome measures such as patient satisfaction. This area is especially important for novel surgical technologies such as single-incision laparoscopic surgery (SILS) and natural orifice translumenal endoscopic surgery (NOTES). These new innovations are able to minimize or abolish surgical scarring and are likely to have most benefit in the area of patient satisfaction as opposed to traditional outcome measures.

Frequencies of region of difference 1 antigen-specific but not purified protein derivative-specific gamma interferon-secreting T cells correlate with the presence of tuberculosis disease but do not distinguish recent from remote latent infections.

The majority of individuals infected with Mycobacterium tuberculosis achieve lifelong immune containment of the bacillus. What constitutes this effective host immune response is poorly understood. We compared the frequencies of gamma interferon (IFN-gamma)-secreting T cells specific for five region of difference 1 (RD1)-encoded antigens and one DosR-encoded antigen in 205 individuals either with active disease (n = 167), whose immune responses had failed to contain the bacillus, or with remotely acquired latent infection (n = 38), who had successfully achieved immune control, and a further 149 individuals with recently acquired asymptomatic infection.

Use of T cell-based diagnosis of tuberculosis infection to optimize interpretation of tuberculin skin testing for child tuberculosis contacts.

Background: Treatment of recent tuberculosis infection in children aged <2 years is essential, because of high risk of progression to disease, but diagnosis is hindered by the inaccuracy of the tuberculin skin test (TST). More-accurate T cell-based tests of infection could enhance diagnosis by optimizing interpretation of the TST results.

Methods: A total of 979 child tuberculosis contacts in Istanbul underwent the TST and enzyme-linked immunospot assay.

Prognostic value of a T-cell-based, interferon-gamma biomarker in children with tuberculosis contact.

Background: Enzyme-linked immunospot (ELISpot) assay is an increasingly widely used, T-cell-based, interferon-gamma-release assay for diagnosing tuberculosis infection, but whether positive results are prognostic of active tuberculosis is not known.

Objective: To determine whether ELISpot results predict the development of active tuberculosis among persons with recent tuberculosis exposure.

Design: Longitudinal cohort study of children and adolescents with tuberculosis contact recruited from October 2002 to April 2004.