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Journal articleAlferes de Lima Headley D, Richardson H, Hennayake C, et al., 2026,
Sputum and oral microbiota profiles are associated with long COVID severity and phenotype post-hospitalisation: a UK multicentre, prospective cohort study.
, Eur Respir JBACKGROUND: Acute COVID-19 alters the airway microbiota. Whether these changes persist post-COVID-19 and contribute to long COVID is unknown. We aimed to describe the microbiota by long COVID severity and subtype, and identify links with inflammation. METHODS: Adults were prospectively recruited to the longitudinal UK Post-hospitalisation COVID-19 study (PHOSP-COVID). Patients were grouped by previously described "severity clusters" (of ongoing health impairments) and symptom subgroups. Oral and sputum microbiota (at 6 months post-discharge) were characterised through 16S ribosomal RNA gene amplicon sequencing, and microbiota diversity was assessed. Co-occurrence network analysis identified keystone taxa. Associations between keystone taxa and plasma inflammatory proteins were assessed through Spearman's rank correlations. RESULTS: 771 participants had their microbiota assessed. Of participants with oral rinses and "severity cluster" assignment (mean age 57.5 years), 278 out of 722 (38.5%) were women. The "very severe" cluster, in which disease was predominantly pulmonary in nature, was associated with a distinct microbiota profile post-COVID-19. Reduced lung function was associated with a distinct oral microbiota profile. Persistent neurocognitive symptoms were associated with a distinct oral microbiota profile, while gastrointestinal symptoms were associated with a distinct sputum microbiota profile. Microbiota keystone taxa shifted to a higher prevalence of lactic acid bacteria associated with worse health outcomes. Lactic acid bacteria abundance was associated with elevated blood inflammatory proteins. CONCLUSION: Distinct oral and sputum microbiota profiles were associated with pulmonary function and with neurocognitive and gastrointestinal symptoms in long COVID. Shifts in keystone microbiota taxa linked with inflammation, based on worse health outcomes, suggest a potential role change for lactic acid bacteria, which may be a
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Journal articleDiaz-Nicieza C, Sahyoun L, Michalaki C, et al., 2026,
Correction: Ageing results in an exacerbated inflammatory response to LPS by resident lung cells.
, Immun Ageing, Vol: 23, ISSN: 1742-4933 -
Journal articleLawton A, Hughes D, 2026,
Artificial intelligence in paediatric respiratory medicine.
, Paediatr Respir Rev, Vol: 59, Pages: 44-49Proponents of artificial intelligence (AI) believe that it will revolutionise the modern world, affecting how healthcare is delivered and improve both the clinical care we provide and the ease with which we perform our work. In this paper we explain what is meant by 'artificial intelligence' and explore how this technology has been implemented, or might be implemented, with respect to paediatric respiratory medicine. We review the current literature on how AI has been used to improve diagnostics - including examples in radiology, primary ciliary dyskinesia (PCD) diagnostics, sleep medicine, and pulmonary function tests. We also review how AI has been applied to therapeutics and drug discovery, how it will impact evidence-based medicine and literature review, and how clinician support tools will assist us in our work.
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Journal articleJackson R, Bentley S, Davies JC, et al., 2026,
Keeping up with CFTR modulator eligibility.
, Paediatr Respir Rev, Vol: 59, Pages: 12-19The availability of highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulators has transformed outcomes for people with cystic fibrosis (pwCF). Eligibility, conferred initially by clinical trial data, has evolved through advances in in vitro 'theratyping' and use of real‑world evidence. Since ivacaftor's approval for a single gating variant in 2012, eligibility has broadened to over 180 variants with the highly effective therapies elexacaftor/tezacaftor/ivacaftor and recently launched vanzacaftor/tezacaftor/deutivacaftor. Regulatory authorities have increasingly accepted non‑traditional evidence, notably the FDA's 2017 ivacaftor extension based on cell‑based assays and, in 2025, the EMA's decision to extend elexacaftor/tezacaftor/ivacaftor to people ≥2 years with at least one non class I variant. However, clinical response remains variable, influenced in part by baseline characteristics, pharmacokinetics, pharmacogenetics, and environmental exposures. We outline evolving approaches to determining eligibility and strategies to improve methods to predict, verify, and monitor clinical response in an era of personalised medicine.
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Journal articleBell RV, Faulkner NB, Sinadinos A, et al., 2026,
Assessment of F/HN-pseudotyped lentiviral vector following intravenous delivery to mice.
, Gene Ther, Vol: 33, Pages: 586-595In pursuit of a gene transfer agent with efficient pulmonary transduction, the UK Respiratory Gene Therapy Consortium has developed a lentiviral vector pseudotyped with the envelope proteins, F and HN from Sendai virus (rSIV.F/HN). In contrast to other viral vectors, pulmonary rSIV.F/HN delivery achieves sustained gene expression ( ~ 2 years in mice) in the lungs and systemic circulation following a single dose. Here, we investigate the application of the rSIV.F/HN vector-platform for wider indications, including systemic disorders that require serum expression of therapeutic proteins. To assess the potential for rSIV.F/HN to produce systemic proteins, intravenous vector delivery was characterised and compared against intrapulmonary administration, achieved via 'nasal sniffing'. Both delivery routes achieved sustained (at least 1 year) systemic expression of the secreted reporter protein Gaussia luciferase. Systemic rSIV.F/HN delivery resulted in widespread protein expression across multiple organs, accompanied by the generation of significant anti-vector neutralising antibodies limiting vector readministration. Conversely, localised airway transduction was observed following pulmonary administration, which we have previously shown is not an impediment to efficient vector readministration. These data support intrapulmonary rSIV.F/HN delivery for systemic protein production, with sustained high-level transgene expression and feasible readministration.
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Journal articleRosenheim J, Bender B, Gilmour J, et al., 2026,
Conference report: airway mucosal sampling and immune analysis.
, Vaccine, Vol: 88Respiratory pathogens cause substantial global morbidity, mortality, and pandemic risk. While parenteral vaccines can effectively reduce severe disease for some respiratory infections, they are often less effective at preventing infection and onward transmission. Vaccines delivered directly to the airways have the potential to induce protective mucosal immunity at the site of pathogen entry. However, progress in mucosal vaccine development has been constrained by limited understanding of airway immune mechanisms, the technical challenges of sampling respiratory tissues, and the lack of standardised, validated immunological assays capable of defining mucosal correlates of protection. To address these challenges, the Novo Nordisk Foundation and Wellcome Trust convened a workshop on airway mucosal sampling and immunological assays, bringing together researchers, clinicians, funders, and representatives from major research consortia. Participants reviewed approaches to sampling the upper and lower respiratory tract, assay technologies, and regulatory considerations for integrating mucosal endpoints into vaccine development. Discussions highlighted major barriers including variability in sampling techniques, low and inconsistent cell yields, limited assay standardisation, and insufficient cross-study comparability. The workshop produced a set of recommendations in four priority areas (i.e., Collaboration, Communication, Consistency and Conduct of research) to share knowledge, accelerate standardisation and validation, and generate evidence supporting mucosal vaccine development. Together, these advances will help strengthen the scientific and regulatory foundations needed to realize the full potential of airway-delivered vaccines for the prevention of respiratory diseases.
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Journal articleDvorscek AR, Kushnir AS, Dibben O, et al., 2026,
Mucosal immunity as a vaccine-induced correlate of protection against influenza.
, Mucosal Immunol, Vol: 19Licensure of influenza vaccines relies on serum hemagglutination inhibition (HAI) titers, a correlate of protection (CoP) that was developed more than 50 years ago and which is only poorly predictive of protection. This is especially true of immunity induced by intranasal live attenuated influenza vaccines (LAIVs). Unlike intramuscular inactivated influenza vaccines (IIVs), LAIV and natural infection selectively stimulate mucosal immunity. Developments in mucosal immunology now enable measurement of diverse aspects of mucosal immunity, including the frequencies and functions of nasal antibodies, T cells, and B cells. This review assesses the potential of new sampling and assay approaches that may overcome inconsistent findings from previous methodologies. Standardization of the collection and assessment of mucosal samples is essential in developing new CoPs for vaccine development and licensure of novel vaccines that induce nasal protection and are more effective in prevention of viral transmission.
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Journal articleDe Boeck K, Burgel P-R, Bierlaagh M, et al., 2026,
ECFS statement on theratyping and theranostics in the context of rare and ultrarare CFTR variants in people with CF.
, J Cyst Fibros, Vol: 25, Pages: 584-593Genotype-based drug development has yielded highly effective therapies, notably the triple combinations elexacaftor/tezacaftor/ivacaftor (ETI) and vanzacaftor/tezacaftor/deutivacaftor (VTD), now approved in Europe for people with CF having at least one non-class I variant. However not all these people with CF will respond to ETI or VTD, and a few not under the label may respond. Facilitating opportunities to access for patients with rare variants has required a shift in paradigm toward functional testing-based access. This approach assesses the potential benefit of modulator therapy using in vitro functional assays, either in engineered systems expressing defined CFTR variants (theratyping) or in patient-derived tissues (theranostics). We review theranostics as a critical tool for personalized medicine in CF, highlighting its validation in in vitro models derived from patients' own cells such as human intestinal organoids and human nasal epithelial cells. We discuss the current regulatory landscape regarding modulator approval and propose strategies for improving equitable access to effective treatments for all people with CF. Importantly, we advocate for functional assays to be accepted as standalone evidence of drug efficacy for patients with rare variants. Theranostic approaches remain critical when theratyping has not been achieved, and genetic data is not available or clearly interpretable. Indeed, theranostics has emerged as an essential pillar of CF drug access, complementing genotype-driven strategies. As the field advances, continued validation, standardization, and regulatory integration of in vitro functional assays will be key to ensuring that every person with CF-regardless of their genotype-has the opportunity to benefit from precision therapies.
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Journal articleDavies JC, Bakkeheim E, Chansard A, et al., 2026,
Perspective of the European Cystic Fibrosis Society on Improving Global Cystic Fibrosis Care.
, Pediatr Pulmonol, Vol: 61INTRODUCTION: Outcomes for people with the inherited disease, cystic fibrosis, have improved greatly over the last few decades, but one result of this is a widening gap between regions with high income and well-resourced healthcare systems and low/middle income countries. The gap stretches from newborn screening programs, provision of standard diagnostics and genetic testing through to access to standard of care therapies. METHODS AND RESULTS: This paper describes the various initiatives of the European Cystic Fibrosis Society: our Patient Registry, a Twinning Program linking centers from different regions and our Educational Program. CONCLUSIONS: The European Cystic Fibrosis Society recognizes this as a major issue and seeks through these programs to support colleagues, patients and families in low/middle income countries.
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Journal articleSinadinos A, Bell R, Juarez-Molina CI, et al., 2026,
Using the nose as a factory to secrete proteins into the lungs or circulation
, Molecular Therapy Advances, Vol: 34, ISSN: 3117-387XTargeting of the nasal epithelium for sustained therapeutic protein secretion represents a potential non-invasive lentiviral vector application strategy. Using reporter imaging, molecular, and radiopharmaceutical tracing methods in mice, we have developed an intranasal (nose-only) dosing strategy with a Sendai-virus envelope glycoprotein pseudotyped lentiviral vector (rSIV.F/HN). Using multiple (up to 10) small volume (5 μL) intranasal bolus applications, technetium radiotracer showed >90% liquid retention in the murine head and <1% in the lung. Following vector administration, transgene expression was dose-related in the nose with minimal lung expression. No acute nasal toxicity was associated with nose-only delivery. Next, we compared levels of a secreted protein, Gaussia luciferase (Gluc), in the airways and serum after nose-only and intravenous administration of rSIV.F/HN-Gluc (2e8 TU/mouse). Gluc expression in the nose and lungs was higher following nose-only versus intravenous administration. Serum levels were similar after either route of administration. Finally, nose-only delivery of rSIV.F/HN encoding GM-CSF, led to sufficient lung levels of this therapeutic protein to correct disease biomarkers in a mouse model of pulmonary alveolar proteinosis. We conclude that non-invasive administration of a lentiviral vector to the nasal epithelium provides a safe and convenient route for secreted protein production and is readily translatable into humans.
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