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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 articleChin D, Hernandez-Beeftink T, Donoghue L, et al., 2026,
Genome-wide association study of idiopathic pulmonary fibrosis susceptibility using clinically curated European ancestry datasets.
, Eur Respir J, Vol: 68New association signals suggest a potentially causal role for the gene encoding KL-6, a known biomarker of fibrosis, and implicate genes involved in angiogenesis in IPF development https://bit.ly/3Ocr01s
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Journal articleGandhi SA, Liu GY, Fazio JC, et al., 2026,
Silicosis in the Artificial Stone Countertop Industry: An Official American Thoracic Society Workshop Report.
, Ann Am Thorac SocArtificial stone-associated silicosis (AS silicosis) has emerged over the past decade as a severe, rapidly progressive, and preventable occupational lung disease affecting workers who manufacture, fabricate, and install artificial stone countertops. Characterized by short latency, accelerated progression, and high morbidity and mortality, AS silicosis disproportionately affects young workers employed in precarious conditions. In response to the growing global burden of disease, this American Thoracic Society workshop was convened in 2025 to review the current state of knowledge regarding AS silicosis, synthesize the current evidence, and identify priorities for research, clinical care, public health surveillance, and prevention. Workshop participants reviewed data spanning exposure science, epidemiology, clinical manifestations, health equity, and policy responses. Evidence demonstrates that artificial stone (AS) dust is highly toxic, containing high concentrations of respirable crystalline silica, resin-derived volatile compounds, and trace metals, resulting in exposures that routinely exceed occupational exposure limits. Despite widespread implementation of wet methods, ventilation, and respiratory protection, hazardous exposures persist across diverse settings globally, highlighting fundamental limitations of existing control strategies. Clinically, AS silicosis is associated with high rates of progressive massive fibrosis, autoimmune disease, infection, respiratory failure, and increasing need for lung transplantation. Treatment options remain limited, underscoring the importance of early detection and exposure cessation. The workshop identified critical gaps in medical screening and public health surveillance worldwide, with inconsistent regulatory frameworks, low compliance, underreporting, and delayed diagnoses. Case detection is often dependent on symptomatic presentation rather than proactive screening, exacerbating disease severity and inequities in care.
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Journal articleSibila O, Perea L, Burgel PR, et al., 2026,
The frequent exacerbator phenotype in bronchiectasis revisited: Data from EMBARC registry.
, Am J Respir Crit Care MedRATIONALE: The frequent exacerbator phenotype was previously defined using a threshold of ≥ 3 exacerbations per year in bronchiectasis. However, the contribution of each prior exacerbation to future risk, as well as the influence of severe exacerbations, different etiologies and regions, remain poorly understood. OBJECTIVES: To quantify the risk associated with each prior exacerbation in predicting future exacerbations and severe exacerbations, and to determine whether this association varies across different etiologies and geographic regions in bronchiectasis. METHODS: We analyzed data from the European Bronchiectasis Registry (EMBARC), including 30 countries across Europe and Asia. The association between baseline exacerbation history and future exacerbations was tested using negative binomial regression over up to 5 years of follow-up. Severe exacerbations were defined as those requiring hospitalization. MEASUREMENTS AND MAIN RESULTS: A total of 19,324 patients with bronchiectasis were included. Each prior exacerbation was associated with an increased risk of exacerbations and severe exacerbations. Incidence Rate Ratio (IRR) for future exacerbations was 1.45 (95%CI 1.34-1.58, p < 0.001) for one exacerbation, 1.84 (95%CI 1.69-1.99, p < 0.001) for two exacerbations, 2.50 (95%CI 2.29-2.73, p < 0.001) for three exacerbations and 3.56 (95%CI 3.32-3.82, p < 0.001) for patients with four or more prior exacerbations. Additionally, one prior severe exacerbation was associated with increased risk of exacerbation (IRR=1.52, 95%CI 1.45-1.60, p < 0.001) and strongly associated with future severe exacerbations (IRR=3.96, 95%CI 3.71-4.22, p < 0.001). The frequent exacerbator phenotype was consistent across different etiologies and geographic regions. CONCLUSIONS: The frequent exacerbator phenotype is highly consistent across patient subgroups and regions. Each
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Journal articleSenior P, Viegas P, Winterton J, et al., 2026,
Protracted bacterial bronchitis in adults and comparison to bronchiectasis
, ERJ Open Research, ISSN: 2312-0541 -
Journal articlePollock J, Huang JTJ, Shuttleworth M, et al., 2026,
Clinical, molecular and microbial characterisation of the eosinophilic endotype of bronchiectasis: data from the EMBARC-BRIDGE study.
, Thorax, Vol: 81, Pages: 642-653OBJECTIVES: Eosinophilic bronchiectasis is defined by a blood eosinophil count (BEC) ≥300 cells/µL, but blood eosinophils imperfectly reflect airway eosinophilic inflammation. Here, we investigated the relationship between eosinophilic airway inflammation, blood eosinophils and clinical severity in bronchiectasis and explored the phenotype associated with eosinophilic bronchiectasis. METHODS: Sputum from 180 patients with stable CT-confirmed bronchiectasis was utilised to investigate airway levels of eosinophil proteins (eosinophil peroxidase (EPX), eosinophil derived-neurotoxin (EDN), eosinophil cationic protein (ECP), major basic protein (MBP) and Galectin-10 (Gal-10)) using a novel stable isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. To profile eosinophilic bronchiectasis, a nested analysis of patients with BEC <150 cells/µL (n=52) and ≥300 cells/µL (n=49) was conducted. RESULTS: Sputum concentrations of Gal-10, ECP and EDN were weakly but significantly associated with radiological severity, FEV1 and sputum culture positivity for Pseudomonas aeruginosa. Airway eosinophil protein concentrations did not associate with exacerbation frequency. Total eosinophil protein concentration moderately correlated with BECs (r=0.33 95% CI 0.14 to 0.49, p=0.0007). Nested analysis revealed increased sputum PCR-positivity for P. aeruginosa (26.7% vs 7.7%, p=0.033) and an increased frequency of patients showing signs of Aspergillus sensitisation (defined as Aspergillus-specific IgE titres >0.35 kUA/L, 24.5% vs 3.8%) in eosinophilic bronchiectasis. Sputum inflammatory biomarkers and clinical parameters did not differ between groups. CONCLUSIONS: LC-MS/MS can detect eosinophilic inflammation within bronchiectasis sputum. Weak associations between elevated airway eosinophil proteins, bronchiectasis severity and P. aeruginosa infection were observed. Direct measurement of eosinophilic airway i
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Journal articleShah A, 2026,
Impact of allergic bronchopulmonary aspergillosis overlap in chronic pulmonary aspergillosis
, ERJ Open Research, ISSN: 2312-0541Background: Chronic pulmonary aspergillosis (CPA) is a destructive fungal infection caused by Aspergillus fumigatus, leading to significant morbidity in individuals with structural lung disease. Clinical and immunological overlap with allergic bronchopulmonary aspergillosis (ABPA) has been recognised, but its extent and prognostic relevance remain uncertain. This study assessed ABPA features in CPA and their relationship with immunological markers and long-term outcome.Methods: We conducted a retrospective cohort study including individuals with confirmed CPA at the Royal Brompton Hospital until December 2023. Diagnoses followed ERS/ESCMID and 2024 ISHAM criteria. Demographic, clinical, microbiological, and immunological data were analysed, and group comparisons performed using logistic regression and Cox proportional hazards models.Results: Among 166 individuals with CPA, 45 (27%) met ABPA diagnostic criteria. CPA–ABPA overlap was independently associated with asthma (OR-10.16) and pan-azole resistance (OR-19.37), and inversely with sarcoidosis (OR-0.22). Overall 5-year survival was 82% (84.6% in CPA alone vs 76.6% in overlap; p=0.44). Older age, lower BMI and albumin, elevated A. fumigatus-specific IgE and IgG were associated with higher mortality, while longitudinal increase in A. fumigatus-specific IgE was also linked to worse outcome. Low serum albumin independently predicted mortality (HR 0.72; p=0.001).Discussion: CPA–ABPA overlap represents a distinct clinical phenotype linked to airway disease, antifungal resistance, and Th2-driven inflammation. Nutritional status and immunological activity, particularly rising A. fumigatus-specific IgE, emerged as key prognostic markers, linking type 2 inflammation to disease progression. These findings highlight the need for phenotype-based risk stratification and exploration of targeted immunomodulatory strategies in CPA.
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Journal articleGnaim R, Kassim H, Neidhardt L, et al., 2026,
Navigating adoption barriers for microbial proteins in future food
, Nature Communications, Vol: 17, ISSN: 2041-1723Microbial biomass fermentation, in which microbes are cultivated to produce nutrient-dense biomass, offers a scalable route to sustainable protein production with low land, water, and greenhouse gas footprints. However, its shift from a speciality to a mainstream food continues to be difficult. Here, we move beyond technological overviews and propose a three-phase adoption framework: novelty barrier, early trust-building, and mainstream normalisation. This framework organises techno-economic, regulatory, and infrastructural barriers into a single trajectory. We trace single-cell proteins’ rise, decline and resurgence, map engineering and policy enablers by phase, and outline levers to move microbial proteins into resilient food systems.
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Journal articleVenkatesan T, Nagi N, Nwankwo L, et al., 2026,
Describing the burden and characteristics of Aspergillus- related chronic lung disease at Imperial College Healthcare Trust: a 10-year retrospective study
, BMJ Open Respiratory Research, Vol: 13, ISSN: 2052-4439Background The epidemiology of Aspergillus-related chronic lung disease remains poorly defined. We aimed to characterise the local burden at Imperial College Healthcare National Health Service Trust, London, across a 10-year period (2014–2024).Methods Electronic health records were reviewed to identify individuals tested for serological markers of Aspergillus species infection after which thoracic CT scans were reviewed for features of Aspergillus-related chronic lung disease. Patients were classified into diagnostic categories based on definitions provided in the recent British Thoracic Society Clinical Statement.Results In total, 334 individuals met criteria for serologic allergic bronchopulmonary aspergillosis (sABPA), 145 for ABPA, 74 for chronic pulmonary aspergillosis (CPA), 38 for simple aspergilloma and 11 with CPA-ABPA overlap. Serological responses varied: ABPA patients had higher median Aspergillus fumigatus-specific immunoglobulin (Ig)E titres (7.52 kUA/L, vs 1.94 kUA/L, p<0.05) and a greater proportion were positive for Aspergillus antibody (IgG) or precipitins (62.5% vs 32.9%, p<0.05) compared with sABPA. CPA patients had lower median total IgE (94 vs 1494 IU/mL, p<0.05) and A. fumigatus-specific IgE (2.24 vs 7.52 kUA/L, p<0.05) than ABPA patients. There was a wide spectrum of radiological presentations across diagnostic categories.Conclusions While case numbers are likely underestimated, our findings highlight a substantial and heterogeneous local burden. This improved understanding of local epidemiology will inform our local service development.
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Journal articleMadhuprakash J, Toghani A, Pai H, et al., 2026,
A potato late blight pathogen effector interacts with ENTH-domain protein TOL9a and an activated helper NLR to suppress immunity.
, Sci Adv, Vol: 12Pathogens counteract central nodes of NLR immune receptor networks to suppress immunity. However, the mechanisms by which pathogens hijack helper NLR pathways are poorly understood. We show that an effector from the late blight pathogen Phytophthora infestans interacts with the host protein NbTOL9a and a helper NLR to suppress immunity. We solved the crystal structure of the RXLR-LWY effector AVRcap1b in complex with the ENTH domain of NbTOL9a. The structure revealed that, unlike other RXLR-LWY effectors, AVRcap1b has a previously unidentified L-shaped fold that defines a distinct structural family of effectors in the genus Phytophthora. We defined the AVRcap1b/NbTOL9a binding interface and designed effector mutants that do not bind NbTOL9a, impairing immune suppression. This suggests that ENTH binding is required for full virulence activity. Last, we show that AVRcap1b associates specifically with activated NbNRC2 independently of NbTOL9a binding. We propose a model in which the effector interconnects NbNRC2 with the NbTOL9a pathway. Our results illustrate a previously uncharacterized pathogen mechanism to hijack NLR pathways and suppress immunity.
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