Sejal Saglani

Imperial College London, Londinium, England, United Kingdom

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Publications (115)841.41 Total impact

  • No preview · Article · Feb 2016 · The Journal of allergy and clinical immunology
  • Sejal Saglani · Clare M Lloyd
    No preview · Article · Dec 2015 · American Journal of Respiratory and Critical Care Medicine
  • [Show abstract] [Hide abstract] ABSTRACT: Background: We hypothesized airway inflammation can be detected non-invasively by induced sputum (IS) or peripheral blood eosinophilia, and IS can detect bacterial and viral infection in preschool children with airway disease, with results comparable to broncho-alveolar lavage (BAL). Methods: Preschool children with cystic fibrosis, recurrent wheeze, or wet cough underwent IS with nebulized hypertonic saline, chest physiotherapy, and oropharyngeal suction. Samples were analyzed for inflammation by cytology and bacterial culture, viral detection by PCR. Results were compared to BAL and blood in a sub-group undergoing clinically indicated bronchoscopy. Results: 64 children (median age 33 [7-76] months) underwent IS without adverse events. IS was obtained from 61/64. Twenty out of sixty-four underwent BAL and IS, no IS was obtained in 2/23. Thirteen out of twenty-one (62%) had matching bacteria and viruses, 4/21 had positive BAL bacterial growth with negative IS, and 3/21 had negative BAL growth with positive IS. 67% of sputum samples were processed for cytology, 46% had <80% squamous cells; the proportion of squamous cells reduced with increasing age (r = -0.55, P < 0.01). IS was significantly more neutrophilic and less eosinophilic than BAL; 2/21 IS samples contained eosinophils compared to 17/23 BAL. There was a positive correlation between blood and BAL eosinophilia (r = 0.75, P < 0.01). Conclusion: IS from preschool children can be used to assess infection. BAL and IS culture concurred in approximately two-thirds. However, inflammation was measureable in only one-third of IS samples and the cell differential was predominantly neutrophilic compared to BAL. Blood eosinophils may provide a better reflection of lower airway eosinophilia in this age group. Pediatr Pulmonol. © 2015 WileyPeriodicals, Inc.
    No preview · Article · Dec 2015 · Pediatric Pulmonology
  • James Cook · Sejal Saglani
    [Show abstract] [Hide abstract] ABSTRACT: Purpose of review: Exacerbations of asthma in children are most frequently precipitated by respiratory infections with a seasonal pattern. However, management takes little account of the underlying infective or other precipitant abnormality. Recent findings: Interactions between environmental triggers, the airway microbiome and innate immune responses are key determinants of exacerbations. Elevated innate cytokines interleukin (IL)-33 and IL-25, and abnormal molecular responses in the interferon pathway are associated with rhinoviral infections. Exacerbations caused by fungal allergens also induce IL-33, highlighting this as an attractive therapeutic target. An equal contribution of bacterial and viral infection during exacerbations, particularly in preschool children, has become increasingly apparent, but some organisms may be protective. Investigation of mechanisms underlying infection-related exacerbations especially in preschool children is needed.Progressive loss of lung function from exacerbations is most pronounced in children aged 6-11 years, and low FEV1 is now recognized as a key predictor for the development of chronic obstructive pulmonary disease and premature death. Although prevention of exacerbations is critical, suboptimal patient education, prescription and adherence to maintenance therapy, and a lack of predictive biomarkers, remain key unaddressed issues in children. Summary: Precipitants and predictors of exacerbations, together with the child's age and clinical phenotype, need to be used to achieve individualized management in preference to the current uniform approach for all.
    No preview · Article · Nov 2015 · Current opinion in pulmonary medicine
  • Sejal Saglani · Clare M Lloyd
    [Show abstract] [Hide abstract] ABSTRACT: The hallmark pathological features of asthma include airway eosinophilic inflammation and structural changes (remodelling) which are associated with an irreversible loss in lung function that tracks from childhood to adulthood. In parallel with changes in function, pathological abnormalities occur early, during the pre-school years, are established by school age and subsequently remain (even though symptoms may remit for periods during adulthood). Given the equal importance of inflammation and remodelling in asthma pathogenesis, there is a significant disparity in studies undertaken to investigate the contribution of each. The majority focus on the role of inflammation, and although novel therapeutics such as those targeted against T-helper cell type 2 (Th2) mediators have arisen, it is apparent that targeting inflammation alone has not allowed disease modification. Therefore, unless airway remodelling is addressed for future therapeutic strategies, it is unlikely that we will progress towards a cure for asthma. Having acknowledged these limitations, the focus of this review is to highlight the gaps in our current knowledge about the mechanisms underlying airway remodelling, the relationships between remodelling, inflammation and function, remodelling and clinical phenotypes, and the importance of utilising innovative and realistic pre-clinical models to uncover effective, disease-modifying therapeutic strategies.
    No preview · Article · Nov 2015 · European Respiratory Journal
  • No preview · Article · Oct 2015 · European Respiratory Journal
  • [Show abstract] [Hide abstract] ABSTRACT: Background: Ethnicity may influence response to treatment of asthmatic patients, but this is controversial. This study's objective is to determine if ethnicity influences the response to intramuscular steroid (eliminating adherence as an issue). Methods: Children with severe therapy resistant asthma who had previously undergone a detailed assessment when potentially modifiable factors had been identified and addressed were admitted for further evaluation including assessment of steroid response. Children were classified as Caucasian, black, Asian or mixed Caucasian / black. Steroid responsiveness was defined according to symptoms (Asthma Control Test), inflammation (sputum eosinophils and exhaled nitric oxide), and spirometry (FEV1) which were measured before and 4 weeks after intramuscular triamcinolone. Data were collected regarding exacerbations. FeNO response was defined as a decrease to <24 ppb. Results: 79 subjects were identified (Caucasian = 54 (68%), Black = 16 (20%), Asian = 5 (6%), Mixed Caucasian/Black = 4 (5%)). After triamcinolone, there was a significant drop in median FeNO in Caucasians (46.8 to 23.1 ppb, p < 0.001) but not in black children (52.2 to 34.5 ppb, p = 0.58). More Black children than Caucasian (86.7%) were FeNO non-responders (86.7 vs. 45.3%, p<0.05). More Black children had exacerbations compared to Caucasian children (61 vs. 17%, p<0.05). Conclusions: Black asthmatic children were less likely to have a FeNO response and had more exacerbations 4 weeks after triamcinolone compared to Caucasians. Further research is needed to understand the mechanisms of these differences, but they cannot be due to differences in adherence or access to care.
    No preview · Article · Sep 2015 · Chest
  • No preview · Article · Sep 2015 · European Respiratory Journal
  • No preview · Article · Sep 2015 · European Respiratory Journal
  • No preview · Article · Sep 2015 · European Respiratory Journal
  • No preview · Article · Aug 2015 · The Journal of allergy and clinical immunology
  • Valentina Fainardi · Sejal Saglani
    [Show abstract] [Hide abstract] ABSTRACT: Severe asthma at all ages is heterogeneous incorporating several phenotypes that are distinct in children and adults, however, there are also numerous similar features including the limitation that they may not remain stable longitudinally. Severe asthma in both children and adults is characterized by eosinophilic airway inflammation and evidence of airway remodeling. In adults, targeting eosinophilia with anti-IL-5 antibody therapy is very successful, resulting in the recommendation that sputum eosinophils should be used to guide treatment. In contrast, data for the efficacy of blocking IL-5 remain unavailable in children. However, its effectiveness is uncertain since many children with severe asthma have normal blood eosinophils and the dominance of Th2-mediated inflammation is controversial. Approaches that have revealed gene signatures and biomarkers such as periostin that are specific to adult disease now need to be adopted in children to identify effective pediatric specific therapeutics and minimize the extrapolation of adult therapeutics to children.
    No preview · Article · Jul 2015 · Expert Review of Respiratory Medicine
  • Sejal Saglani · Andrew Bush
    No preview · Article · Jul 2015 · American Journal of Respiratory and Critical Care Medicine
  • Clare M Lloyd · Sejal Saglani
    [Show abstract] [Hide abstract] ABSTRACT: The triad of epithelial derived cytokines, IL-25, IL-33 and TSLP are important for the initiation and development of pulmonary immune responses to environmental stimuli. Data from experiments using mouse models provide compelling evidence for their involvement in both innate and adaptive immunity to drive type-2 responses, allergic inflammation and airway remodelling. These cytokines are known to be expressed in human lung tissue and immune cells, however their involvement in mediating allergic pulmonary responses in patients is less clear than in murine models of disease. This article focuses on evidence for the role of IL-25, IL-33 and TSLP in human allergic disease and discusses their potential as therapeutic targets for severe asthma. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · Jun 2015 · Current Opinion in Immunology
  • [Show abstract] [Hide abstract] ABSTRACT: This review focuses on the methods available for measuring reversible airways obstruction, bronchial hyperresponsiveness (BHR) and inflammation as hallmarks of asthma, and their role in monitoring children with asthma. Persistent bronchial obstruction may occur in asymptomatic children and is considered a risk factor for severe asthma episodes and is associated with poor asthma outcome. Annual measurement of forced expiratory volume in 1 s using office based spirometry is considered useful. Other lung function measurements including the assessment of BHR may be reserved for children with possible exercise limitations, poor symptom perception and those not responding to their current treatment or with atypical asthma symptoms, and performed on a higher specialty level. To date, for most methods of measuring lung function there are no proper randomised controlled or large longitudinal studies available to establish their role in asthma management in children. Noninvasive biomarkers for monitoring inflammation in children are available, for example the measurement of exhaled nitric oxide fraction, and the assessment of induced sputum cytology or inflammatory mediators in the exhaled breath condensate. However, their role and usefulness in routine clinical practice to monitor and guide therapy remains unclear, and therefore, their use should be reserved for selected cases. Copyright ©ERS 2015.
    No preview · Article · Jun 2015 · European Respiratory Review
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    Full-text · Dataset · Apr 2015
  • [Show abstract] [Hide abstract] ABSTRACT: Current data concerning maternal paracetamol intake during pregnancy, or intake during infancy and risk of wheezing or asthma in childhood is inconclusive based on epidemiological studies. We have investigated whether there is a causal link between maternal paracetamol intake during pregnancy and lactation and the development of house dust mite (HDM) induced allergic airways disease (AAD) in offspring using a neonatal mouse model. Pregnant mice were administered paracetamol or saline by oral gavage from the day of mating throughout pregnancy and/or lactation. Subsequently, their pups were exposed to intranasal HDM or saline from day 3 of life for up to 6 weeks. Assessments of airway hyper-responsiveness, inflammation and remodelling were made at weaning (3 weeks) and 6 weeks of age. Maternal paracetamol exposure either during pregnancy and/or lactation did not affect development of AAD in offspring at weaning or at 6 weeks. There were no effects of maternal paracetamol at any time point on airway remodelling or IgE levels. Maternal paracetamol did not enhance HDM induced AAD in offspring. Our mechanistic data do not support the hypothesis that prenatal paracetamol exposure increases the risk of childhood asthma. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    No preview · Article · Apr 2015 · Thorax
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    [Show abstract] [Hide abstract] ABSTRACT: The goal of asthma treatment is to obtain clinical control and reduce future risks to the patient. To reach this goal in children with asthma, ongoing monitoring is essential. While all components of asthma, such as symptoms, lung function, bronchial hyperresponsiveness and inflammation, may exist in various combinations in different individuals, to date there is limited evidence on how to integrate these for optimal monitoring of children with asthma. The aims of this ERS Task Force were to describe the current practise and give an overview of the best available evidence on how to monitor children with asthma. 22 clinical and research experts reviewed the literature. A modified Delphi method and four Task Force meetings were used to reach a consensus. This statement summarises the literature on monitoring children with asthma. Available tools for monitoring children with asthma, such as clinical tools, lung function, bronchial responsiveness and inflammatory markers, are described as are the ways in which they may be used in children with asthma. Management-related issues, comorbidities and environmental factors are summarised. Despite considerable interest in monitoring asthma in children, for many aspects of monitoring asthma in children there is a substantial lack of evidence. Copyright ©ERS 2015.
    Full-text · Article · Mar 2015 · European Respiratory Journal
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    [Show abstract] [Hide abstract] ABSTRACT: The mechanism underlying severe asthma with fungal sensitization (SAFS) is unknown. IL-33 is important in fungus-induced asthma exacerbations, but its role in fungal sensitization is unexplored. We sought to determine whether fungal sensitization in children with severe therapy-resistant asthma is mediated by IL-33. Eighty-two children (median age, 11.7 years; 63% male) with severe therapy-resistant asthma were included. SAFS (n = 38) was defined as specific IgE or skin prick test response positivity to Aspergillus fumigatus, Alternaria alternata, or Cladosporium herbarum. Clinical features and airway immunopathology were assessed. Chronic exposure to house dust mite and A alternata were compared in a neonatal mouse model. Children with SAFS had earlier symptom onset (0.5 vs 1.5 years, P = .006), higher total IgE levels (637 vs 177 IU/mL, P = .002), and nonfungal inhalant allergen-specific IgE. Significantly more children with SAFS were prescribed maintenance oral steroids (42% vs 14%, P = .02). SAFS was associated with higher airway IL-33 levels. In neonatal mice A alternata exposure induced higher serum IgE levels, pulmonary IL-33 levels, and IL-13(+) innate lymphoid cell (ILC) and TH2 cell numbers but similar airway hyperresponsiveness (AHR) compared with those after house dust mite exposure. Lung IL-33 levels, IL-13(+) ILC numbers, TH2 cell numbers, IL-13 levels, and AHR remained increased with inhaled budesonide during A alternata exposure, but all features were significantly reduced in ST2(-/-) mice lacking a functional receptor for IL-33. Pediatric SAFS was associated with more oral steroid therapy and higher IL-33 levels. A alternata exposure resulted in increased IL-33-mediated ILC2 numbers, TH2 cell numbers, and steroid-resistant AHR. IL-33 might be a novel therapeutic target for SAFS. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Full-text · Article · Mar 2015 · Journal of Allergy and Clinical Immunology
  • [Show abstract] [Hide abstract] ABSTRACT: Rhinovirus infections are the dominant cause of asthma exacerbations, and deficient virus induction of IFN-α/β/λ in asthmatic patients is important in asthma exacerbation pathogenesis. Mechanisms causing this interferon deficiency in asthmatic patients are unknown. We sought to investigate the expression of suppressor of cytokine signaling (SOCS) 1 in tissues from asthmatic patients and its possible role in impaired virus-induced interferon induction in these patients. We assessed SOCS1 mRNA and protein levels in vitro, bronchial biopsy specimens, and mice. The role of SOCS1 was inferred by proof-of-concept studies using overexpression with reporter genes and SOCS1-deficient mice. A nuclear role of SOCS1 was shown by using bronchial biopsy staining, overexpression of mutant SOCS1 constructs, and confocal microscopy. SOCS1 levels were also correlated with asthma-related clinical outcomes. We report induction of SOCS1 in bronchial epithelial cells (BECs) by asthma exacerbation-related cytokines and by rhinovirus infection in vitro. We found that SOCS1 was increased in vivo in bronchial epithelium and related to asthma severity. SOCS1 expression was also increased in primary BECs from asthmatic patients ex vivo and was related to interferon deficiency and increased viral replication. In primary human epithelium, mouse lung macrophages, and SOCS1-deficient mice, SOCS1 suppressed rhinovirus induction of interferons. Suppression of virus-induced interferon levels was dependent on SOCS1 nuclear translocation but independent of proteasomal degradation of transcription factors. Nuclear SOCS1 levels were also increased in BECs from asthmatic patients. We describe a novel mechanism explaining interferon deficiency in asthmatic patients through a novel nuclear function of SOCS1 and identify SOCS1 as an important therapeutic target for asthma exacerbations. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Jan 2015 · Journal of Allergy and Clinical Immunology