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Journal articleKnox-Brown B, Potts J, Franssen F, et al., 2025,
Concordance between FVC and FEV6 for identifying chronic airflow obstruction and spirometric restriction in the Burden of Obstructive Lung Disease (BOLD) study
, BMJ Open Respiratory Research, Vol: 12, ISSN: 2052-4439Introduction We investigated whether the forced expiratory volume in 6 s (FEV6) can be used as a surrogate for the forced vital capacity (FVC).Methods The Burden of Obstructive Lung Disease is a multinational cohort study. At baseline, data were collected from adults, aged 40 years or older, from 41 sites across 34 countries. Participants from 18 sites were followed-up after a median of 8.3 years. Participants who completed the study core questionnaire and had acceptable post-bronchodilator spirometry were included. We performed receiver operating characteristic analyses to measure the ability of FEV1/FEV6 less than the lower limit of normal (LLN) to correctly classify FEV1/FVC less than the LLN, and FEV6 less than the LLN to correctly classify FVC less than the LLN. We used multilevel regression analyses to assess the association of discordant measurements with respiratory symptoms, quality of life and lung function decline.Results At baseline, 28 604 participants were included. 53% were female (15 060). 10% (2876) had chronic airflow obstruction for FEV1/FVC, compared with 9% (2704) for FEV1/FEV6. 37% (10 637) had spirometric restriction for FVC, compared with 35% (9978) for FEV6. The FEV1/FEV6 had excellent accuracy in identifying FEV1/FVC less than the LLN (area under the curve (AUC): 0.90, 95% CI, 0.89 to 0.91, κ coefficient 0.82). The FEV6 also had excellent agreement in identifying FVC less than the LLN (AUC: 0.95, 95% CI, 0.94 to 0.95, κ coefficient 0.90). Discordant reductions in FEV1/FEV6 (1%, 345) and FEV6 (1%, 309) were associated with greater odds of having respiratory symptoms and a lower physical quality of life. 3870 participants were followed up. Those with discordant reductions in FEV1/FEV6 and FEV6 were more likely to have chronic airflow obstruction and spirometric restriction at follow-up.Conclusions There is strong agreement between the FVC and FEV6 in the identification of chronic airflow obstruction and spirometric r
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Journal articleHigham S, Wang Z, Murugaiah V, et al., 2025,
Intranasal delivery of mRNA expressing newly identified Acinetobacter baumannii antigens protects against bacterial lung disease
, npj Vaccines, Vol: 10, ISSN: 2059-0105Vaccines are central to the strategy to control antimicrobial resistant (AMR) bacterial infections; one multidrug resistant pathogen of particular concern is Acinetobacter baumannii. In this study we identified two novel A. baumannii antigens using mass spectrometry and phage expression: Oxa23 and PAL. These genes are highly conserved between different isolates of A. baumannii and recognised by convalescent human sera. We explored their protective immunity using two different vaccine platforms, recombinant outer membrane vesicles (rOMV) and mRNA. RNA vaccine immunised mice had significantly reduced bacterial load in their lower airways following challenge with carbapenem resistant A. baumannii, with Oxa23 providing better protection than PAL. We then compared routes of delivery and RNA vaccine platforms, demonstrating that intranasally delivery of mRNA encoding OXA-23 (formulated with GL67A) significantly reduced disease severity and enhanced bacterial clearance. These studies validate in silico identified antigens through challenge studies and novel mucosal vaccine delivery approaches.
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Journal articlePatrick T, Naidu SB, Bhamani A, et al., 2025,
Supporting clinical trial recruitment in COPD by leveraging lung cancer screening: an observational study
, ERJ OPEN RESEARCH, Vol: 11 -
Journal articleLee T, Hill K, Caudri D, et al., 2025,
Pulmonary endpoints in clinical trials for children with cystic fibrosis under two years of age
, Journal of Cystic Fibrosis, Vol: 24, Pages: 669-683, ISSN: 1569-1993Cystic fibrosis is a lifelong progressive disease in which lung disease is the main prognostic factor, where starting early treatment is crucial for improving long-term outcomes. Therefore, new treatment should be available as early as possible. However, choosing appropriate and feasible clinical trial endpoints in children under 2 years of age presents significant challenges. Most studies in this age group have extrapolated pulmonary efficacy from older age groups, focusing on safety, pharmacokinetics, and biomarker response. As lung health is near normal in infants, demonstrating absence of pulmonary decline requires large sample sizes and extended study duration, which may not be feasible for standard regulatory trials. To address this gap, the European Cystic Fibrosis Society Clinical Trials Network developed a consensus document evaluating direct pulmonary endpoints for therapeutic pulmonary studies in this young age group. The pulmonary endpoints evaluated include multiple-breath washout (MBW); chest computed tomography (CT); chest magnetic resonance imaging (MRI); airway infection and inflammation. Relevant literature, pitfalls, practice guidelines, and recommendations are presented. None of the pulmonary endpoints evaluated are currently suitable to serve as a primary efficacy endpoint in children below 2 years of age, as this will require large numbers and long follow-up. For clinical trials in infants with CF, pharmacokinetics, pharmacodynamics, safety and tolerability should remain the primary endpoints, with pulmonary endpoints as secondary or exploratory outcomes. Post authorization studies are essential to evaluate long-term pulmonary benefits, including MBW, structural lung assessment (e.g. CT and MRI), and markers of pulmonary inflammation to fully understand the impact of early therapy initiation in this young population.
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Journal articleFenn J, Koycheva A, Kundu R, et al., 2025,
Early de novo T cell expansion following SARS-CoV-2 infection predicts favourable clinical and virological outcomes
, eBioMedicine, Vol: 117, ISSN: 2352-3964BackgroundDe novo T cell expansion to a novel viral infection is assumed to confer protection, but empirical evidence in humans is limited. The SARS-CoV-2 pandemic provided a unique opportunity to investigate de novo T cell-mediated protection in antigen-naïve individuals without the confounding effects of preexisting immune memory.MethodsWe leveraged a prospective household contact study to recruit new COVID-19 cases a median of 4 days post-SARS-CoV-2 exposure. We longitudinally enumerated SARS-CoV-2 antigen-specific functional T cell subsets using dual IFN-γ/IL-2 fluorescence-linked immunospot (FLISpot) assays. We then correlated T cell dynamics with detailed clinical and virological outcomes derived from longitudinal measurement of symptom burden and viral load.FindingsEarly expansion (day 0–7) of SARS-CoV-2-specific IFN-γ-secreting T cells correlated with lower peak viral load and symptom burden. Conversely, late T cell expansion (day 7–28) correlated with higher symptom burden. Neither pre-existing cross-reactive T cells nor early antibody induction correlated with virological outcomes.InterpretationThese findings provide empiric evidence for early antigen-specific T cell expansion being protective against naturally acquired viral infection in humans.FundingThis work is supported by the NIHR Health Protection Research Unit in Respiratory Infections, Imperial College London in partnership with the UK Health Security Agency (Grant number: NIHR200927; AL) and the Medical Research Council (Grant number: MR/X004058/1).
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Journal articleHafidz F, Candrawati F, Hoyt J, et al., 2025,
Pilot implementation of intermittent preventive treatment with dihydroartemisinin-piperaquine to prevent adverse birth outcomes in Papua, Indonesia: a mixed-method evaluation.
, Lancet Prim Care, Vol: 1BACKGROUND: A previous trial showed that intermittent preventive treatment with dihydroartemisinin-piperaquine (IPTp-DP) was more effective than the current policy of single screening and treatment in preventing malaria during pregnancy in Papua, Indonesia. The STOPMiP-2 study evaluated the Ministry of Health pilot implementation of IPTp-DP through routine antenatal care in Papua. METHODS: A mixed-method evaluation was conducted in ten primary health-care facilities in the Mimika district in Papua, Indonesia from June 8, 2022, to Dec 27, 2023. Pregnant women aged 15-49 years who were HIV negative (when status known), in their second or third trimester of pregnancy, and provided written informed consent were eligible. IPTp-DP delivery effectiveness (3-day doses of three tablets [ie, nine tablets] with the first dose by directly observed therapy during antenatal care) and adherence (completion of all nine tablets, ascertained by pill count) were coprimary outcomes. Analyses were done in the modified intention-to-treat (mITT) population (defined for delivery effectiveness as all women who completed exit interviews, and for treatment adherence as all women who had a home visit). The mITT population excluded women with fever or malaria infection, those with a positive malaria test, or those who received IPTp-DP outside the designated timeframe (ie, less than 4 weeks between courses). We explored predictors of delivery effectiveness and adherence using multivariable logistic regression, and used qualitative data to provide explanatory insights. We used routine health information to assess monthly coverage by facility. This study was registered at ClinicalTrials.gov (NCT05294406) and is now complete. FINDINGS: From June 8, 2022, to Dec 27, 2023, we enrolled 1420 pregnant women in exit interviews, of whom 1366 had data available and were eligible for the effectiveness analysis. 490 women were visited at home, of whom 484 had data available and were eligible for the adherenc
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Journal articleMall MA, Wainwright CE, Legg J, et al., 2025,
Elexacaftor/tezacaftor/ivacaftor in children aged ≥6 years with cystic fibrosis heterozygous for<i> F508del</i> and a minimal function mutation: results from a 96-week open-label extension study
, EUROPEAN RESPIRATORY JOURNAL, Vol: 66, ISSN: 0903-1936- Cite
- Citations: 1
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Journal articleSingh D, Guller P, Reid F, et al., 2025,
A phase 2a trial of the IL-33 monoclonal antibody tozorakimab in patients with COPD: FRONTIER-4
, EUROPEAN RESPIRATORY JOURNAL, Vol: 66, ISSN: 0903-1936- Cite
- Citations: 7
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Journal articleBurney P, Amaral A, Shaheen S, 2025,
The importance of using appropriate reference ranges in spirometry
, The Lancet Respiratory Medicine, Vol: 13, Pages: e37-e37, ISSN: 2213-2600 -
Journal articleOgwang C, Samuels AM, Mcdermott DP, et al., 2025,
Attractive targeted sugar baits for malaria control in western Kenya (ATSB-Kenya) - Effect of ATSBs on epidemiologic and entomologic indicators: A Phase III, open-label, cluster-randomised, controlled trial
, PLOS GLOBAL PUBLIC HEALTH, Vol: 5- Cite
- Citations: 2
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Journal articleBurney P, Nguyen T, Agarwal D, et al., 2025,
Fibular length and vital capacity in the multinational Burden of Obstructive Lung Disease follow-up study
, European Respiratory Journal, ISSN: 0903-1936 -
Journal articleAbozid H, Wouters E, Cherkaski H, et al., 2025,
Quality of life associated with chronic cough in the multinational Burden of Obstructive Lung Disease (BOLD) study: a cross-sectional study
, ERJ Open Research, ISSN: 2312-0541Background. Chronic cough (CC) can impact daily life and persist for years. Its prevalence varies globally, but whether quality of life in CC also varies across regions is unknown. This study investigates the association of CC with mental and physical component scores of the 12-item Short Form Health Survey (SF-12) reflecting health-related quality of life in a multinational study. Methods. We analysed data from 19,642 adults (≥40 years), recruited between Jan 2, 2003 and Dec 26, 2016 in 31 sites (25 countries) from the Burden of Obstructive Lung Disease (BOLD) study, who provided information on quality of life and CC. We assessed associations using linear regression, adjusted for confounders, and used random-effects meta-analysis to examine differences by sex and gross national income.Findings. Overall, lower mental (-1.42, 95%CI -2.11 to -0.73; I2 = 32.7%) and physical (-2.59, 95%CI -3.22 to -1.96; I2 = 40.1%) health scores were associated with chronic cough. The association between physical health score and CC did not materially differ between sexes or gross national income. In males, physical health seems to be more affected by CC amongst those living in low- and middle-income countries (LMICs). In females, mental health also seems to be more affected by CC amongst those living in LMICs.Interpretation. CC impairs health-related quality of life globally. However, it appears that physical health in males and mental health in females living in LMICs may be particularly affected by CC. These findings support the need to consider CC as a target for specific interventions to attenuate its burden on health and the economy.Funding. Wellcome Trust (085790/Z/08/Z)
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Journal articleGreenland-Bews C, Shah S, Achieng M, et al., 2025,
Application of a high-resolution melt assay for monitoring SARS-CoV-2 variants in Burkina Faso and Kenya
, MSPHERE, Vol: 10 -
Journal articleZhou X-H, Prothon S, Liathdale E, et al., 2025,
A phase 1 study evaluating the safety, tolerability, and pharmacokinetics of the porcupine inhibitor, AZD5055
, ISCIENCE, Vol: 28 -
Journal articleHawkins A, Pantazi P, Yang L, et al., 2025,
Long-term culture and passaging of term trophoblast for the investigation of syncytiotrophoblast function
, PLACENTA, Vol: 166, Pages: 25-32, ISSN: 0143-4004- Cite
- Citations: 1
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Journal articleLeung CL, Jerene D, Meghji J, et al., 2025,
Post-TB sequelae and care: a systematic review and synthesis of qualitative research
, IJTLD OPEN, Vol: 2, Pages: 339-345, ISSN: 3005-7590TB has long-term health and social sequelae. The experiences of TB survivors are not well understood and there is limited evidence around gaps in care. This article aims to provide a comprehensive overview of qualitative research on post-TB sequelae and care, to identify knowledge gaps and inform future research and interventions to support person-centred care.A systematic search strategy, using two search strings incorporating post-TB and TB-related chronic respiratory disease. Searches were conducted on PubMed, Web of Science and CINAHL. Sources were screened systematically, data extracted independently and analyzed thematically.Sixty-six sources were identified. After applying exclusion/inclusion criteria, 16 articles were included in a qualitative synthesis. Key themes included the physical, psychological, economic and social impacts of TB. These included threats to TB survivors’ social role. People who suffer from long-term sequelae are stigmatised. Access to care is limited and tends to focus on acute respiratory disease. Policymakers indicate that the lack of data regarding the long-term impacts of TB contributed to insufficient resources being allocated.This systematic review underscores the post-TB physical and psychological impacts and the complexity of post-TB sequelae; it emphasizes the urgent need for evidence regarding the long-term impact of TB sequelae to improve care.
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Journal articleSayec ML, Davies G, Waller MD, et al., 2025,
A standard operating procedure for reducing risk from medications prohibited during clinical trials in cystic fibrosis
, Journal of Cystic Fibrosis, ISSN: 1569-1993 -
Journal articleFeary J, 2025,
Work-related asthma
, Ers Monograph, Vol: 2025-June, Pages: 448-459, ISSN: 2312-508XThis chapter provides a comprehensive overview of work-related asthma (WRA), encompassing occupational asthma (OA), irritant-induced asthma and work-aggravated asthma (WAA). It defines OA as asthma directly caused by workplace exposures, with >400 known causative agents divided into high and low molecular weight compounds. Diagnosis relies on occupational and clinical history, objective testing (spirometry, detailed peak flows, immunology) and, rarely, specific inhalation challenge. OA is frequently under-recognised and delayed diagnosis results in poorer outcomes. Management involves a balance between asthma control and employment factors, but complete avoidance of exposure confers the best clinical outcome. Over 50% are unemployed 3–5 years after diagnosis. Acute and chronic irritant-induced asthma are distinct entities triggered by high or prolonged irritant exposure, respectively, and not mediated by sensitisation. WAA reflects symptom worsening due to nonspecific work-related factors in individuals with pre-existing asthma. This chapter highlights the importance of asking all asthma patients about work-related symptoms and seeking expert advice for any possible cases of WRA.
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Journal articleBoivin W, Loeb M, Openshaw P, et al., 2025,
Seasonal influenza vaccination: overcoming immunosenescence with enhanced vaccines
, Vaccine: X, Vol: 24, ISSN: 2590-1362Influenza causes substantial morbidity and mortality worldwide. Risks are increased in older adults aged 50–64 and ≥ 65 years. They are further exacerbated in those with age-related comorbidities. Immunosenescence (strictly defined here as detrimental age-related decline in the function of some or all parts of the immune system) is associated with increased susceptibility to influenza infection and more severe disease, a process that begins at approximately 50 years of age. Age-associated chronic low-level inflammation (inflammaging) may also increase influenza risk and is associated with more serious disease but may also enhance responses to high-dose vaccines in older adults. The frequency of comorbidities also increases with age. Frail older adults are at highest risk of influenza complications, but adults with high-risk comorbidities also show improved immune responses to enhanced influenza vaccines (high-dose, adjuvanted, recombinant). Moreover, clinical studies with some enhanced influenza vaccines show improved immunogenicity and greater efficacy or effectiveness, not only for persons aged ≥65 years but also in those aged 50–64 years. Reduced immunogenicity in persons aged 50–64 years may be even greater in those with comorbidities who would specifically benefit from receiving enhanced vaccines. Thus, accelerated immunosenescence, inflammaging, and chronic disease may place some adults aged 50–64 years at high risk of influenza, justifying meeting an unmet need in vaccination with enhanced vaccines normally used in persons ≥65 years of age.
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Journal articleDobra R, Carroll S, Davies JC, et al., 2025,
Exploring the complexity of cystic fibrosis (CF) and psychosocial wellbeing in the 2020s: current and future challenges
, Paediatric Respiratory Reviews, Vol: 54, Pages: 35-42, ISSN: 1526-0542Cystic fibrosis (CF) is traditionally associated with considerable and progressive multisystem pathology, onerous treatment burden, complex psychosocial challenges, and reduced life-expectancy [1], [2], [3], [4], [5], [6], [7], [8], [9].This decade has seen transformative change in management for many, but not all, people with CF. The most notable change comes from Cystic Fibrosis Transmembrane Receptor (CFTR) modulators, which bring significant benefits for people who are eligible for, and able to access, them [10]. However alongside, or perhaps because of, this exciting progress, the past few years have also brought important novel challenges to the psychosocial wellbeing of people with CF.This article, written as a collaboration between CF psychologists, social workers, physicians and nurses aims to provide an accessible overview of the novel psychosocial challenges now faced by children, their families, and adults with CF, and to invite consideration of their changing psychosocial requirements to inform future holistic care. Themes include geopolitical stressors such as the pandemic and its wake, a growing divide between those able or unable to access CFTR modulators, potential rapid changes in life expectancy secondary to these drugs and the inevitable associated challenges this brings; evolving body image, mental health side effects of CFTR modulators, the challenges of adherence in apparently well children and young adults, as well as the diagnostic conundrum and associated anxiety of the cystic fibrosis screen positive inconclusive diagnosis (CFSPID) label. It also highlights some unmet research and service delivery needs in the area.
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