Sejal Saglani

Imperial College London, Londinium, England, United Kingdom

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Publications (95)752.54 Total impact

  • Sejal Saglani · Clare M Lloyd ·
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    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.
    European Respiratory Journal 11/2015; DOI:10.1183/13993003.01196-2014 · 7.64 Impact Factor

  • European Respiratory Journal 10/2015; DOI:10.1183/13993003.00791-2015 · 7.64 Impact Factor
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    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.
    Chest 09/2015; DOI:10.1378/chest.14-3241 · 7.48 Impact Factor

  • European Respiratory Journal 09/2015; 46(suppl 59):OA4466. DOI:10.1183/13993003.congress-2015.OA4466 · 7.64 Impact Factor

  • European Respiratory Journal 09/2015; 46(suppl 59):OA4775. DOI:10.1183/13993003.congress-2015.OA4775 · 7.64 Impact Factor

  • European Respiratory Journal 09/2015; 46(suppl 59):PA1316. DOI:10.1183/13993003.congress-2015.PA1316 · 7.64 Impact Factor

  • The Journal of allergy and clinical immunology 08/2015; DOI:10.1016/j.jaci.2015.06.038 · 11.48 Impact Factor
  • Valentina Fainardi · Sejal Saglani ·
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    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.
    Expert Review of Respiratory Medicine 07/2015; 9(4):1-10. DOI:10.1586/17476348.2015.1068693
  • Sejal Saglani · Andrew Bush ·

    American Journal of Respiratory and Critical Care Medicine 07/2015; 192(2):121-2. DOI:10.1164/rccm.201505-0989ED · 13.00 Impact Factor
  • Clare M Lloyd · Sejal Saglani ·
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    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.
    Current Opinion in Immunology 06/2015; 34. DOI:10.1016/j.coi.2015.02.001 · 7.48 Impact Factor
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    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.
    European Respiratory Review 06/2015; 24(136):204-215. DOI:10.1183/16000617.00003914
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    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
    Thorax 04/2015; 70(6). DOI:10.1136/thoraxjnl-2014-205280 · 8.29 Impact Factor
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    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.
    European Respiratory Journal 03/2015; 45(4). DOI:10.1183/09031936.00088814 · 7.64 Impact Factor
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    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.
    Journal of Allergy and Clinical Immunology 03/2015; 129(2). DOI:10.1016/j.jaci.2015.01.016 · 11.48 Impact Factor
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    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.
    Journal of Allergy and Clinical Immunology 01/2015; 179(1). DOI:10.1016/j.jaci.2014.11.039 · 11.48 Impact Factor
  • P. Hall · M. Bracken · D. Winch · P. Nagakumar · A. Bush · S. Saglani · L. Fleming ·
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    ABSTRACT: Introduction Poor adherence is one of the key determinants of sub-optimal asthma control in children. Correctly identifying children with poor adherence can avoid unnecessary escalation of treatment and enable a targeted adherence intervention. Objective To use electronic monitoring devices (Smartinhalers) to measure adherence to inhaled corticosteroids (ICS) in children with problematic severe asthma (PSA) and compare the data with prescription uptake and symptoms during the monitoring period. Methods Smartinhalers were issued to patients for a 6–8 week study period as part of an established nurse led assessment in a tertiary referral centre. Advice regarding adherence and the purpose of the Smartinhalers was explained to all children and their parents. Lung function, bronchodilator reversibility, exhaled nitric oxide (FENO), mini paediatric asthma quality of life questionnaire (mPAQLQ), and asthma control test (ACT) were recorded at baseline and follow up. Wilcoxon signed ranks was used to compare visit 1 and visit 2 data. GP prescription uptake for ICS and number of salbutamol canisters issued in past year were obtained. Results 33 children (21 male), median age 13 (5–17) years) were issued with Smartinhalers. 15 had adherence >80%, 14 between 50–80% and 4 < 50%. ACT and mPAQLQ improved significantly over the monitoring period (Figures 1 and 2). Children with a prescription uptake of <80% had a significant improvement in ACT compared to those with pick up of ≥80% (median change 3.5 (IQR 0.75–7.25) vs 0 (-4–3)) and a non-significant trend towards improvements in FEV1 and BDR. There was no relationship between prescription uptake and Smartinhaler adherence or salbutamol inhalers collected. Conclusion Even when children know they are being monitored over half used <80% of the prescribed dose. Improvements in objective markers of asthma control during the monitoring period can help to identify those who were previously poorly adherent. Smartinhalers are useful tools in the assessment of adherence in conjunction with GP prescriptions and clinical observations.
    Thorax 12/2014; 69(Suppl 2):A182-A182. DOI:10.1136/thoraxjnl-2014-206260.368 · 8.29 Impact Factor
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    ABSTRACT: Introduction Airway infection and inflammation in infancy and preschool years contribute to the pathogenesis of cystic fibrosis (CF), severe wheezing and recurrent cough. However, the use of sputum induction (SI) to guide management in preschool children with obstructive airways disease remains under-explored. We hypothesised that SI can be performed safely in preschool children with obstructive airways disease, and that samples of sufficient quality to assess infection and inflammation can be obtained. Methods SI was performed using nebulised hypertonic saline, 3.5% if there was a history of wheeze or 7% if the child had no wheeze or a diagnosis of CF. The procedure was undertaken for 15 min and safety was assessed using pulse-oximetry and auscultation. Physiotherapy, followed by a cough/oropharyngeal swab (CS), and oropharyngeal suction (OS) were undertaken to obtain samples. All samples were analysed for bacterial culture and viral PCR, a sub-set were processed for cytology. Results 35 children (16 males), median age 32 months (range 7–70 months) were included. 32/35 (91%) completed the procedure. The remaining three did not complete nebulisation as they became too upset, but underwent sample collection. None of the patients had any drop in oxygen saturation or increased respiratory symptoms. 16/35 (46%) patients had positive pathogen identification (22 separate bacterial or viral isolates) from SI samples obtained by OS. Only 3/35 (9%) positive isolates were identified from CS. 29/35 samples were able to be processed for cytology (see Table 1) Conclusions Performance of SI was safe, feasible and well tolerated by preschool children with a range of obstructive airways diseases. Pathogen identification was significantly higher in samples obtained by OS compared to CS. Samples were of sufficient quality for cytological analysis in approximately half the patients. Future work will determine the clinical utility of SI as a non-invasive sample to guide therapy in preschool obstructive airways disease.
    Thorax 12/2014; 69(Suppl 2):A123-A123. DOI:10.1136/thoraxjnl-2014-206260.246 · 8.29 Impact Factor
  • P. Nagakumar · P. Hall · M. Bracken · S. Saglani · A. Bush · L. Fleming ·
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    ABSTRACT: Introduction Sub-optimal adherence to medications results in poor asthma control, however objective measurement of adherence is challenging. Aim To assess adherence to inhaled corticosteroids (ICS) in children with problematic severe asthma (PSA) using prescription uptake and the Medicines Adherence Rating Scale (MARS) (self-reported adherence) and relate them to measures of asthma control. Methods 160 patients assessed as part of the established RBH difficult asthma protocol (2008–2013) were included [[Arch Dis Child 2009;94:780–4]. Adherence was assessed using prescription uptake data (GP and local hospital) and MARS. Sub-optimal adherence was defined as a prescription uptake of <80%. Spirometry (FEV1 pre bronchodilator), bronchodilator reversibility (BDR), and exhaled nitric oxide (FENO) were measured. The Asthma Control Test (ACT), Paediatric Asthma Quality of Life Questionnaire (PAQLQ) was used to evaluate control. Number of courses of oral steroids and hospital admissions in the previous 12 months were recorded. Results Median age was 11.6 yr (5–16). 66% were male. 52% had prescription uptake of <80%. MARS score showed only a weak correlation with prescription uptake (n = 48, r2 =0.03, p = 0.29), even in patients with prescription uptake of <50% (n = 23, r2=0.09, p = 0.32). No relationship was found between prescription uptake and ACT, MARS, FEV1, rescue courses of OCS, FeNO or BDR (Table 1). Conclusion Poor prescription uptake was not related to any measure of asthma control, meaning that we could not differentiate the genuine therapy resistant from the non-adherent. But it is not possible to assess how much ICS was actually inhaled. Patterns of ICS use may be a more important determinant of control. Self-reported adherence, as measured by MARS was high even in those with very poor <50%) prescription uptake highlighting the limitations of this questionnaire. More objective means of assessing adherence should be incorporated into protocols for assessing severe asthma.
    Thorax 12/2014; 69(Suppl 2):A98-A98. DOI:10.1136/thoraxjnl-2014-206260.196 · 8.29 Impact Factor
  • N. Collins · K. Robson · P. Nagakumar · S. Saglani · NWG Voase · JC Davies ·
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    ABSTRACT: Background Early detection of organisms such as Pseudomonas aeruginosa in CF is essential for successful eradication but is difficult in children, relying largely on non-invasive methods such as cough swabs (C/S) with sub-optimal sensitivity and specificity. Bronchoalvelolar lavage (BAL) remains the gold standard but disadvantages are its invasive nature, high cost and inability to be performed frequently. Sputum induction (SI) has previously been reported as a useful and safe technique in young children with CF, but it is not yet widely used. Hypothesis As part of a quality improvement initiative, we hypothesised that SI would reduce the need for BAL in school-aged CF children with deteriorating lung function and no significant bacterial growth on CS. Methods After CS and bronchodilator, 7% hypertonic saline was nebulised via an ultrasonic Ultraneb (DeVilbiss Healthcare) for 15 min. Spirometry was performed pre, post and at 5 min intervals throughout. Sputum was collected at 5 min intervals, and at the end of the procedure physiotherapy was performed to collect more sputum. If a child was unable to expectorate then a CS or oropharyngeal (OP) suction was performed. Results 39 children (41% male), median age 11 years (range 5–16 years), median FEV1 85% (range 39–112%) performed SI from June 2102 to July 2014. Significant bronchoconstriction occurred in 11%. 2 adverse events occurred (vomiting and dizziness). The procedure took a mean of 90 min including equipment set up and cleaning. 34/39 (87%) expectorated a sputum sample of which 15 (38.5%) had a positive bacterial culture; only 3 of these patients (20%) grew the same organism on the preceding CS. Five patients avoided planned BAL due to a positive SI result and 2 avoided an admission for intravenous antibiotics. Conclusion SI is well tolerated in the majority of school-aged children with CF. It has a higher rate of positive bacterial culture than same-day CS and, in this cohort, avoided the need for bronchoscopy in a significant proportion. It is a time-consuming procedure, but based on these data, we consider that establishing SI as a clinical procedure will be a priority for our service.
    Thorax 12/2014; 69(Suppl 2):A123-A124. DOI:10.1136/thoraxjnl-2014-206260.247 · 8.29 Impact Factor
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    Journal of Allergy and Clinical Immunology 11/2014; 135(3). DOI:10.1016/j.jaci.2014.09.044 · 11.48 Impact Factor

Publication Stats

2k Citations
752.54 Total Impact Points


  • 2006-2015
    • Imperial College London
      • Section of Leukocyte Biology
      Londinium, England, United Kingdom
  • 2004-2014
    • Royal Brompton and Harefield NHS Foundation Trust
      • Department of Paediatrics
      Harefield, England, United Kingdom
    • Royal Berkshire NHS Foundation Trust
      Reading, England, United Kingdom
  • 2010
    • National Heart, Lung, and Blood Institute
      Maryland, United States
  • 2001
    • The Queen Elizabeth Hospital
      Tarndarnya, South Australia, Australia