Publications
285 results found
Lloyd CM, Saglani S, 2023, Early-life respiratory infections and developmental immunity determine lifelong lung health., Nat Immunol, Vol: 24, Pages: 1234-1243
Respiratory infections are common in infants and young children. However, the immune system develops and matures as the child grows, thus the effects of infection during this time of dynamic change may have long-term consequences. The infant immune system develops in conjunction with the seeding of the microbiome at the respiratory mucosal surface, at a time that the lungs themselves are maturing. We are now recognizing that any disturbance of this developmental trajectory can have implications for lifelong lung health. Here, we outline our current understanding of the molecular mechanisms underlying relationships between immune and structural cells in the lung with the local microorganisms. We highlight the importance of gaining greater clarity as to what constitutes a healthy respiratory ecosystem and how environmental exposures influencing this network will aid efforts to mitigate harmful effects and restore lung immune health.
Scotney E, Fleming L, Saglani S, et al., 2023, Advances in the pathogenesis and personalised treatment of paediatric asthma, BMJ Medicine, Vol: 2, Pages: e000367-e000367
<jats:p>The diversity of pathology of severe paediatric asthma demonstrates that the one-size-fits-all approach characterising many guidelines is inappropriate. The term “asthma” is best used to describe a clinical syndrome of wheeze, chest tightness, breathlessness, and sometimes cough, making no assumptions about underlying pathology. Before personalising treatment, it is essential to make the diagnosis correctly and optimise basic management. Clinicians must determine exactly what type of asthma each child has. We are moving from describing symptom patterns in preschool wheeze to describing multiple underlying phenotypes with implications for targeting treatment. Many new treatment options are available for school age asthma, including biological medicines targeting type 2 inflammation, but a paucity of options are available for non-type 2 disease. The traditional reliever treatment, shortacting β2 agonists, is being replaced by combination inhalers containing inhaled corticosteroids and fast, longacting β2 agonists to treat the underlying inflammation in even mild asthma and reduce the risk of asthma attacks. However, much decision making is still based on adult data extrapolated to children. Better inclusion of children in future research studies is essential, if children are to benefit from these new advances in asthma treatment.</jats:p>
Saglani S, Yates L, Lloyd CM, 2023, Immunoregulation of asthma by type 2 cytokine therapies: Treatments for all ages?, EUROPEAN JOURNAL OF IMMUNOLOGY, ISSN: 0014-2980
Khaleva E, Rattu A, Brightling C, et al., 2023, Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA)., Eur Respir J, Vol: 61
BACKGROUND: Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) Working Group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies. METHODS: COMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult and paediatric clinicians, pharmaceutical representatives, and health regulators from across Europe. Evidence included a systematic review of development, validity and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients' and carers' views about outcome measures. It was discussed using a modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria. RESULTS: Both adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z-scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire and Asthma Control Test or Childhood Asthma Control Test, while the adult COM set includes the Severe Asthma Questionnaire and Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately). CONCLUSIONS: This patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.
Makrinioti H, Zhu Z, Camargo CA, et al., 2023, Application of Metabolomics in Obesity-Related Childhood Asthma Subtyping: A Narrative Scoping Review, METABOLITES, Vol: 13
Saglani S, Baraldo S, 2023, Remodeling phenotypes take center stage in the prediction of preschool wheeze attacks., American Journal of Respiratory and Critical Care Medicine, Vol: 207, Pages: 381-382, ISSN: 1073-449X
Bush A, Holguin F, Porsbjerg C, et al., 2023, Asthma: Closing in on the Biology of a Complex Life-course Disease, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 207, Pages: 375-376, ISSN: 1073-449X
Konstantinidi R, Yates LL, Saglani S, et al., 2022, Investigating the influence of mRNA encoded transcription factor delivery on human bronchial epithelial cell differentiation, 29th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy (ESCGT), Publisher: MARY ANN LIEBERT, INC, Pages: A194-A195, ISSN: 1043-0342
Khalaf Z, Saglani S, Bloom CI, 2022, CHARACTERISING SCHOOL-AGE CHILDREN WITH ASTHMA: ENGLISH POPULATION-COHORT STUDY, Publisher: BMJ PUBLISHING GROUP, Pages: A23-A23, ISSN: 0040-6376
Pavlou B, Scotney E, Makariou I, et al., 2022, ACCEPTABILITY AND FEASIBILITY OF MEASURING BLOOD EOSINOPHILS USING A POINT-OF-CARE DEVICE IN CHILDREN WITH ASTHMA, Publisher: BMJ PUBLISHING GROUP, Pages: A130-A131, ISSN: 0040-6376
Wells C, Wilkinson N, Makhecha S, et al., 2022, ACCEPTABILITY AND FEASIBILITY PILOT OF CODESIGNED TELEHEALTH PHYSIOTHERAPY INTERVENTIONS FOR CHILDREN WITH ASTHMA AND DYSFUNCTIONAL BREATHING, Publisher: BMJ PUBLISHING GROUP, Pages: A130-A130, ISSN: 0040-6376
Haider S, Fontanella S, Ullah A, et al., 2022, Evolution of eczema, wheeze and rhinitis from infancy to early adulthood: four birth cohort studies, American Journal of Respiratory and Critical Care Medicine, Vol: 206, Pages: 950-960, ISSN: 1073-449X
BACKGROUND: The relationship between eczema, wheeze/asthma and rhinitis is complex, and epidemiology and mechanisms of their comorbidities is unclear. OBJECTIVE: To investigate within-individual patterns of morbidity of eczema, wheeze and rhinitis from birth to adolescence/early adulthood. METHODS: We investigated onset/progression/resolution of eczema, wheeze and rhinitis using descriptive statistics, sequence mining and Latent Markov modelling (LMM) in four population-based birth cohorts. We used logistic regression to ascertain if early-life eczema or wheeze, or genetic factors (filaggrin mutations and 17q21 variants), increase the risk of multimorbidity. RESULTS: Single conditions, although the most prevalent, were observed significantly less frequently than by chance. There was considerable variation in the timing of onset/remission/persistence/intermittence. Multimorbidity of eczema+wheeze+rhinitis was rare, but significantly over-represented (3-6 times more often than by chance). Although infantile eczema was associated with subsequent multimorbidity, most children with eczema (75.4%) did not progress to any multimorbidity pattern. FLG mutations and rs7216389 were not associated with persistence of eczema/wheeze as single conditions, but both increased the risk of multimorbidity (FLG by 2-3-fold, rs7216389 risk variant by 1.4-1.7-fold). LMM revealed 5 latent states (No disease/low risk; Mainly eczema; Mainly Wheeze; Mainly rhinitis; Multimorbidity). The most likely transition to Multimorbidity was from Eczema state (0.21). However, although this was one of the highest transition probabilities, only 1/5 of those with eczema transitioned to multimorbidity. CONCLUSIONS: Atopic diseases fit a multimorbidity framework, with no evidence for sequential "atopic march" progression. The highest transition to multimorbidity was from eczema, but most children with eczema (>three quarters) had no comorbidities.
Liu C, Makrinioti H, Saglani S, et al., 2022, Microbial dysbiosis and childhood asthma development: Integrated role of the airway and gut microbiome, environmental exposures, and host metabolic and immune response, FRONTIERS IN IMMUNOLOGY, Vol: 13, ISSN: 1664-3224
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- Citations: 1
Makariou I, Rhamie S, Bush A, et al., 2022, Peak inspiratory flow in children with exercise induced laryngeal obstruction, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Makariou I, Bush A, Saglani S, et al., 2022, Ethnic differences in daily FeNO response after systemic steroids in children with severe asthma, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Scotney E, Jayarathna R, Gupta L, et al., 2022, The role of cardiopulmonary exercise testing to evaluate exercise induced dyspnoea in asthmatic children, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Tsu M, Genton C, Saglani S, et al., 2022, ERS scientific awards: striving for inclusivity, EUROPEAN RESPIRATORY JOURNAL, Vol: 60, ISSN: 0903-1936
Stolting H, Baillon L, Frise R, et al., 2022, Distinct airway epithelial immune responses after infection with SARS-CoV-2 compared to H1N1, Mucosal Immunology, Vol: 15, Pages: 952-963, ISSN: 1933-0219
Children are less likely than adults to suffer severe symptoms when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while influenza A H1N1 severity is comparable across ages except for the very young or elderly. Airway epithelial cells play a vital role in the early defence against viruses via their barrier and immune functions. We investigated viral replication and immune responses in SARS-CoV-2-infected bronchial epithelial cells from healthy paediatric (n = 6; 2.5–5.6 years old) and adult (n = 4; 47–63 years old) subjects and compared cellular responses following infection with SARS-CoV-2 or Influenza A H1N1. While infection with either virus triggered robust transcriptional interferon responses, including induction of type I (IFNB1) and type III (IFNL1) interferons, markedly lower levels of interferons and inflammatory proteins (IL-6, IL-8) were released following SARS-CoV-2 compared to H1N1 infection. Only H1N1 infection caused disruption of the epithelial layer. Interestingly, H1N1 infection resulted in sustained upregulation of SARS-CoV-2 entry factors FURIN and NRP1. We did not find any differences in the epithelial response to SARS-CoV-2 infection between paediatric and adult cells. Overall, SARS-CoV-2 had diminished potential to replicate, affect morphology and evoke immune responses in bronchial epithelial cells compared to H1N1.
Saglani S, 2022, Asthma Diagnosis: New European Respiratory Society (ERS) Guidelines, Publisher: WILEY, Pages: S28-S30, ISSN: 8755-6863
Saglani S, 2022, Update in Preschool Wheeze, Publisher: WILEY, Pages: S16-S18, ISSN: 8755-6863
Pijnenburg MW, Frey U, De Jongste JC, et al., 2022, Childhood asthma: pathogenesis and phenotypes, EUROPEAN RESPIRATORY JOURNAL, Vol: 59, ISSN: 0903-1936
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- Citations: 6
Saglani S, Cohen RT, Chiel LE, et al., 2022, WITHDRAWN: Update in Asthma 2021., Am J Respir Crit Care Med
Ahead of Print article withdrawn by publisher.
Ardura-Garcia C, Abellan A, Cuevas-Ocana S, et al., 2022, ERS International Congress 2021: highlights from the Paediatric Assembly, ERJ OPEN RESEARCH, Vol: 8
Wang KCW, Donovan GM, Saglani S, et al., 2022, Growth of the airway smooth muscle layer from late gestation to childhood is mediated initially by hypertrophy and subsequently hyperplasia, RESPIROLOGY, Vol: 27, Pages: 493-500, ISSN: 1323-7799
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- Citations: 2
Nichols A-L, Sonnappa-Naik M, Gardner L, et al., 2022, COVID-19 and delivery of difficult asthma services, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 107, ISSN: 0003-9888
Pattaroni C, Macowan M, Chatzis R, et al., 2022, Early life inter-kingdom interactions shape the immunological environment of the airways, Microbiome, Vol: 10, ISSN: 2049-2618
Background: There is increasing evidence that the airway microbiome plays a key role in the establishment of respiratory health by interacting with the developing immune system early in life. While it has become clear that bacteria are involved in this process, there is a knowledge gap concerning the role of fungi. Moreover, the inter-kingdom interactions that influence immune development remain unknown. In this prospective exploratory human study, we aimed to determine early post-natal microbial and immunological features of the upper airways in 121 healthy newborns.Results: We found that the oropharynx and nasal cavity represent distinct ecological niches for bacteria and fungi. Breastfeeding correlated with changes in microbiota composition of oropharyngeal samples with the greatest impact upon the relative abundance of Streptococcus species and Candida. Host transcriptome profiling revealed that genes with the highest expression variation were immunological in nature. Multi-omics factor analysis of host and microbial data revealed unique co-variation patterns. Conclusion: These data provide evidence of a diverse multi-kingdom microbiota linked with local immunological characteristics in the first week of life that could represent distinct trajectories for future respiratory health.
Bush A, Fitzpatrick AM, Saglani S, et al., 2022, Difficult-to-Treat Asthma Management in School-Age Children, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, Vol: 10, Pages: 359-375, ISSN: 2213-2198
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- Citations: 3
Custovic A, Siddiqui S, Saglani S, 2022, Considering biomarkers in asthma disease severity, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 149, Pages: 480-487, ISSN: 0091-6749
Byrne AJ, Saglani S, Snelgrove RJ, 2022, An Alarmin Role for P2Y(13) Receptor during Viral-driven Asthma Exacerbations, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 205, Pages: 263-265, ISSN: 1073-449X
Levina D, Leontjeva M, Abbasova N, et al., 2022, Changes in blood eosinophil levels in early childhood and asthma development: A case-control study, PEDIATRIC ALLERGY AND IMMUNOLOGY, Vol: 33, ISSN: 0905-6157
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