Imperial College London

ProfessorSejalSaglani

Faculty of MedicineNational Heart & Lung Institute

Professor of Paediatric Respiratory Medicine
 
 
 
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Contact

 

+44 (0)20 7594 3167s.saglani

 
 
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Location

 

112Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
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297 results found

Piggin M, Alvarado Cruz L, Hargreaves D, Barratt B, Saglani S, Ivie S, Asantewa-Sechereh N, Cunnington Aet al., 2024, Online public involvement session on early life respiratory infections and their impact on lung age

Report

Joulia RPG, Puttur F, Stölting H, Traves W, Entwistle L, Voitovich A, Garcia Martín M, Al-Sahaf M, Bonner K, Scotney E, Molyneaux P, Hewitt R, Walker S, Yates L, Saglani S, Lloyd Cet al., 2024, Mast cell activation disrupts interactions between endothelial cells and pericytes during early life allergic asthma, Journal of Clinical Investigation, ISSN: 0021-9738

Journal article

Khalaf Z, Bush A, Saglani S, Bloom Cet al., 2023, Influence of age on clinical characteristics, pharmacological management and exacerbations in children with asthma, THORAX, ISSN: 0040-6376

Journal article

Tian K, Dangarh P, Zhang H, Hines CL, Bush A, Pybus HJ, Harker JA, Lloyd CM, Tanaka RJ, Saglani Set al., 2023, Role of epithelial barrier function in inducing type 2 immunity following early-life viral infection., Clin Exp Allergy

BACKGROUND: Preschool wheeze attacks triggered by recurrent viral infections, including respiratory syncytial virus (RSV), are associated with an increased risk of childhood asthma. However, mechanisms that lead to asthma following early-life viral wheezing remain uncertain. METHODS: To investigate a causal relationship between early-life RSV infections and onset of type 2 immunity, we developed a neonatal murine model of recurrent RSV infection, in vivo and in silico, and evaluated the dynamical changes of altered airway barrier function and downstream immune responses, including eosinophilia, mucus secretion and type 2 immunity. RESULTS: RSV infection of neonatal BALB/c mice at 5 and 15 days of age induced robust airway eosinophilia, increased pulmonary CD4+ IL-13+ and CD4+ IL-5+ cells, elevated levels of IL-13 and IL-5 and increased airway mucus at 20 days of age. Increased bronchoalveolar lavage albumin levels, suggesting epithelial barrier damage, were present and persisted following the second RSV infection. Computational in silico simulations demonstrated that recurrent RSV infection resulted in severe damage of the airway barrier (epithelium), triggering the onset of type 2 immunity. The in silico results also demonstrated that recurrent infection is not always necessary for the development of type 2 immunity, which could also be triggered with single infection of high viral load or when the epithelial barrier repair is compromised. CONCLUSIONS: The neonatal murine model demonstrated that recurrent RSV infection in early life alters airway barrier function and promotes type 2 immunity. A causal relationship between airway barrier function and type 2 immunity was suggested using in silico model simulations.

Journal article

Khalaf Z, Bush A, Saglani S, Bloom Cet al., 2023, Effect of age on clinical characteristics, pharmacological management, and exacerbations in children with asthma, Thorax, ISSN: 0040-6376

Journal article

Wang KCW, Elliot JG, Saglani S, Donovan GM, James AL, Noble PBet al., 2023, The airway smooth muscle layer is structurally abnormal in low birth weight infants: implications for obstructive disease., Eur Respir J, Vol: 62

Journal article

Salehian S, Fleming L, Saglani S, Custovic Aet al., 2023, Phenotype and endotype based treatment of preschool wheeze, EXPERT REVIEW OF RESPIRATORY MEDICINE, ISSN: 1747-6348

Journal article

Lloyd CMM, Saglani S, 2023, Early-life respiratory infections and developmental immunity determine lifelong lung health, NATURE IMMUNOLOGY, ISSN: 1529-2908

Journal article

Saglani S, 2023, Which Wheezing Preschoolers Should Be Treated for Asthma?, Publisher: WILEY, Pages: S57-S59, ISSN: 8755-6863

Conference paper

Saglani S, 2023, Advances in the Etiology, Management and Prevention of Acute Asthma Attacks in Children, Publisher: WILEY, Pages: S76-S77, ISSN: 8755-6863

Conference paper

Lajunen KT, Mayoral K, Alabdulkareem F, Irving S, Fleming L, Sonnappa S, Bush A, Saglani Set al., 2023, Feasibility and Acceptability of Point-of-Care Blood Eosinophil Count Together With Lung Function in Wheezy Preschool Children, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

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

Journal article

Khaleva E, Rattu A, Brightling C, Bush A, Bossios A, Bourdin A, Chung KF, Chaudhuri R, Coleman C, Dahlen S-E, Djukanovic R, Deschildre A, Fleming L, Fowler SJ, Gupta A, Hamelmann E, Hashimoto S, Hedlin G, Koppelman GH, Melen E, Murray CS, Pilette C, Porsbjerg C, Pike KC, Rusconi F, Williams C, Ahrens B, Alter P, Anckers F, van den Berge M, Blumchen K, Brusselle G, Clarke GW, Cunoosamy D, Dahlen B, Dixey P, Exley A, Frey U, Gaillard EA, Giovannini-Chami L, Grigg J, Hartenstein D, Heaney LG, Karadag B, Kaul S, Kull I, Licari A, Maitland-van der Zee AH, Mahler V, Schoos A-MM, Nagakumar P, Negus J, Nielsen H, Paton J, Pijnenburg M, Ramiconi V, Vilarnau SR, Principe S, Rutjes N, Saglani S, Seddon P, Singer F, Staudinger H, Turner S, Vijverberg S, Winders T, Yasinska V, Roberts Get al., 2023, Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA), European Respiratory Journal, Vol: 61, ISSN: 0903-1936

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.

Journal article

Makrinioti H, Zhu Z, Camargo CA, Fainardi V, Hasegawa K, Bush A, Saglani Set al., 2023, Application of Metabolomics in Obesity-Related Childhood Asthma Subtyping: A Narrative Scoping Review, METABOLITES, Vol: 13

Journal article

Bush A, Holguin F, Porsbjerg C, Saglani Set 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

Journal article

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

Journal article

Smith FM, Saglani S, 2023, Demystifying controversies in preschool wheeze., Expert Rev Respir Med, Vol: 17, Pages: 1023-1031

INTRODUCTION: Wheezing disorders in preschool children are common. Current treatment approaches assume all preschool wheezers are the same and will respond to a short course of oral corticosteroids (OCS) during acute attacks and subsequent maintenance inhaled corticosteroids (ICS) to prevent future attacks. But we have increasing evidence showing preschool wheezing disorders are markedly heterogeneous and the response to corticosteroids either during acute attacks or as maintenance therapy can be variable between patients and is determined by disease severity and underlying pathological phenotype. AREAS COVERED: The aim of this review is to discuss recent evidence which will help to explain a few critical pathophysiological concepts that are often misunderstood, thus helping to demystify the controversies that often surround preschool wheezing disorders and can contribute to ineffective management. EXPERT OPINION: Preschool wheezing disorders are distinct from school-age allergic asthma. There is little evidence to support the use of oral corticosteroids for acute attacks. A staged approach to confirm the diagnosis, and objective tests to determine the pathological phenotype of preschool wheeze is essential prior to initiating maintenance therapy to control symptoms and prevent attacks in children with recurrent preschool wheeze.

Journal article

Scotney E, Fleming L, Saglani S, Sonnappa S, Bush Aet al., 2023, Advances in the pathogenesis and personalised treatment of paediatric asthma., BMJ Med, Vol: 2

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.

Journal article

Konstantinidi R, Yates LL, Saglani S, Lloyd CM, Patel AKet 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

Conference paper

Khalaf Z, Saglani S, Bloom CI, 2022, CHARACTERISING SCHOOL-AGE CHILDREN WITH ASTHMA: ENGLISH POPULATION-COHORT STUDY, Winter Meeting of the British-Thoracic-Society (BTS), Publisher: BMJ PUBLISHING GROUP, Pages: A23-A23, ISSN: 0040-6376

Conference paper

Pavlou B, Scotney E, Makariou I, Bingham Y, Jamalzadeh A, Hall P, Jackman C, Bush A, Sonnappa S, Fleming L, Saglani Set al., 2022, ACCEPTABILITY AND FEASIBILITY OF MEASURING BLOOD EOSINOPHILS USING A POINT-OF-CARE DEVICE IN CHILDREN WITH ASTHMA, Winter Meeting of the British-Thoracic-Society (BTS), Publisher: BMJ PUBLISHING GROUP, Pages: A130-A131, ISSN: 0040-6376

Conference paper

Wells C, Wilkinson N, Makhecha S, Hall P, Jamalzadeh A, Sonnappa S, Fleming L, Bush A, Saglani Set al., 2022, ACCEPTABILITY AND FEASIBILITY PILOT OF CODESIGNED TELEHEALTH PHYSIOTHERAPY INTERVENTIONS FOR CHILDREN WITH ASTHMA AND DYSFUNCTIONAL BREATHING, Winter Meeting of the British-Thoracic-Society (BTS), Publisher: BMJ PUBLISHING GROUP, Pages: A130-A130, ISSN: 0040-6376

Conference paper

Haider S, Fontanella S, Ullah A, Turner S, Simpson A, Roberts G, Murray CS, Holloway JW, Curtin JA, Cullinan P, Arshad SH, Hurault G, Granell R, Custovic A, STELARUNICORN11 investigatorset 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.

Journal article

Liu C, Makrinioti H, Saglani S, Bowman M, Lin L-L, Camargo Jr CA, Hasegawa K, Zhu Zet 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

Journal article

Makariou I, Rhamie S, Bush A, Saglani S, Fleming L, Sonnappa Set al., 2022, Peak inspiratory flow in children with exercise induced laryngeal obstruction, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Makariou I, Bush A, Saglani S, Fainardi V, Bossley CJ, Fleming Let 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

Conference paper

Scotney E, Jayarathna R, Gupta L, Bush A, Saglani S, Fleming L, Sonnappa Set 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

Conference paper

Creese H, Lai E, Mason K, Schlueter DK, Saglani S, Taylor-Robinson D, Saxena Set al., 2022, Disadvantage in early-life and persistent asthma in adolescents: a UK cohort study, THORAX, Vol: 77, Pages: 854-864, ISSN: 0040-6376

Journal article

Tsu M, Genton C, Saglani S, Humbert M, Simonds A, Roche N, Brightling CE, Ubags N, Donnelly LEet al., 2022, ERS scientific awards: striving for inclusivity, EUROPEAN RESPIRATORY JOURNAL, Vol: 60, ISSN: 0903-1936

Journal article

Stolting H, Baillon L, Frise R, Bonner K, Hewitt RJ, Molyneaux PL, Gore ML, Barclay WS, Saglani S, Lloyd CMet 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.

Journal article

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