275 results found
Saglani S, Yates L, Lloyd CM, 2023, Immunoregulation of asthma by type2 cytokine therapies - treatments for all ages?, Eur J Immunol
Asthma is classically considered to be a disease of type 2 immune dysfunction, since many patients exhibit the consequences of excess secretion of cytokines such as IL-4, IL-5 and IL-13 concomitant with inflammation typified by eosinophils. Mouse and human disease models have determined that many of the canonical pathophysiologic features of asthma may be caused by these disordered type 2 immune pathways. As such considerable efforts have been made to develop specific drugs targeting key cytokines. There are currently available multiple biologic agents that successfully reduce the functions of IL-4, IL-5 and IL-13 in patients, and many improve the course of severe asthma. However, none are curative, and do not always minimise the key features of disease - such as airway hyperresponsiveness. Here, we review the current therapeutic landscape targeting type 2 immune cytokines and discuss evidence of efficacy and limitations of their use in adults and children with asthma. This article is protected by copyright. All rights reserved.
Saglani S, Baraldo S, 2023, Remodeling Phenotypes Take Center Stage in the Prediction of Preschool Wheeze Attacks., Am J Respir Crit Care Med, Vol: 207, Pages: 381-382
Bush A, Holguin F, Porsbjerg C, et al., 2023, Asthma: Closing in on the Biology of a Complex Life-course Disease., Am J Respir Crit Care Med, Vol: 207, Pages: 375-376
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
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
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
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.
Khaleva E, Rattu A, Brightling C, et al., 2022, Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA)., Eur Respir J
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 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 (ACT) or Childhood-ACT while the adult COM includes the Severe Asthma Questionnaire and the 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.
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
- Author Web Link
- 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
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
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
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, Update in Preschool Wheeze, Publisher: WILEY, Pages: S16-S18, ISSN: 8755-6863
Saglani S, 2022, Asthma Diagnosis: New European Respiratory Society (ERS) Guidelines, Publisher: WILEY, Pages: S28-S30, 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
- Author Web Link
- 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
- Author Web Link
- 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
- Author Web Link
- Citations: 3
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
Custovic A, Siddiqui S, Saglani S, et al., 2022, Considering biomarkers in asthma disease severity, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 149, Pages: 480-487, ISSN: 0091-6749
Saglani S, Bingham Y, Balfour-Lynn I, et al., 2022, Blood eosinophils in managing preschool wheeze: Lessons learnt from a proof-of-concept trial, Pediatric Allergy and Immunology, Vol: 33, Pages: 1-8, ISSN: 0905-6157
BackgroundManagement of preschool wheeze is based predominantly on symptom patterns.ObjectiveTo determine whether personalizing therapy using blood eosinophils or airway bacterial infection results in fewer attacks compared with standard care.MethodsA proof-of-concept, randomized trial to investigate whether the prescription of inhaled corticosteroids (ICS) guided by blood eosinophils, or targeted antibiotics for airway bacterial infection, results in fewer unscheduled healthcare visits (UHCVs) compared with standard care. Children aged 1–5 years with ≥2 wheeze attacks in the previous year were categorized as episodic viral wheeze (EVW) or multiple trigger wheeze (MTW). The intervention group was prescribed ICS if blood eosinophils ≥3%, or targeted antibiotics if there is positive culture on induced sputum/cough swab. The control group received standard care. The primary outcome was UHCV at 4 months.Results60 children, with a median age of 36.5 (range 14–61) months, were randomized. Median blood eosinophils were 5.2 (range 0–21)%, 27 of 60 (45%) children were atopic, and 8 of 60 (13%) had airway bacterial infection. There was no relationship between EVW, MTW and either blood eosinophils, atopic status or infection. 67% in each group were prescribed ICS. 15 of 30 control subjects and 16 of 30 patients in the intervention group had UHCV over 4 months (p = .8). The time to first UHCV was similar. 50% returned adherence monitors; in those, median ICS adherence was 67%. There were no differences in any parameter between those who did and did not have an UHCV.ConclusionClinical phenotype was unrelated to allergen sensitization or blood eosinophils. ICS treatment determined by blood eosinophils did not impact UHCV, but ICS adherence was poor.
Ko J, Jamalzadeh A, Makhecha S, et al., 2021, REAL LIFE EXPERIENCE WITH MEPOLIZUMAB AND COMPARISON WITH OMALIZUMAB IN CHILDREN WITH SEVERE ASTHMA, Publisher: BMJ PUBLISHING GROUP, Pages: A176-A177, ISSN: 0040-6376
Creese H, Lai E, Mason K, et al., 2021, Disadvantage in early-life and persistent asthma in adolescents: a UK cohort study, THORAX, Vol: 77, Pages: 854-864, ISSN: 0040-6376
- Author Web Link
- Citations: 1
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