258 results found
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
This article has been removed from the American Thoracic Society journals website, as it may be revised in the near future.
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
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.
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, 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
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
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
Golebski K, Dankelman LHM, Bjorkander S, et al., 2021, Expert meeting report: towards a joint European roadmap to address the unmet needs and priorities of paediatric asthma patients on biologic therapy, ERJ OPEN RESEARCH, Vol: 7
Porsbjerg C, Maitland-van der Zee AH, Brusselle G, et al., 2021, 3TR: a pan-European cross-disease research consortium aimed at improving personalised biological treatment of asthma and COPD, EUROPEAN RESPIRATORY JOURNAL, Vol: 58, ISSN: 0903-1936
Scotney E, Burchett S, Goddard T, et al., 2021, Pediatric problematic severe asthma: Recent advances in management, Pediatric Allergy and Immunology, Vol: 32, Pages: 1405-1415, ISSN: 0905-6157
Problematic severe asthma remains a significant challenge to manage, accounting for the majority of healthcare utilization among children with asthma. The heterogeneity is recognized and the clinical phenotypes of “difficult-to-treat” asthma (DA) and “severe therapy-resistant asthma” (STRA) help to guide management. Recent evidence supports molecular distinctions between these phenotypes and shows poor correlations between peripheral and airway markers of inflammation, especially in STRA. Airway neutrophils in the context of childhood severe asthma have been explored, but their role in disease causation, protection, or as bystanders remain unknown, and thus, treatment implications are unclear. Several novel management strategies, including once-daily maintenance therapy, single-device maintenance and reliever therapy, and novel biological treatments are being increasingly used for DA and STRA. However, pediatric data for efficacy of novel treatments is scarce, and when available, is restricted to adolescents. The aim of this review is to highlight recent advances in objective biomarkers that aid stratification and management of childhood severe asthma and to highlight gaps in pediatric evidence. Specifically, the urgent need for efficacy studies to improve the management of problematic severe asthma in children younger than 12 years.
Tanner N, Saglani S, Li AM, et al., 2021, Airway inflammation in severe asthmatics with acid gastro-oesophageal reflux, Thorax, Vol: 77, Pages: 398-399, ISSN: 0040-6376
The relationship between childhood asthma and gastro-oesophageal reflux (GOR) is contentious. Recent studies in adult asthmatics suggest that GOR is associated with worse control and differences in sputum proteomics related to epithelial integrity, systemic inflammation and host defence. We assessed 127 children with severe asthma undergoing bronchoscopy and pH study. There were no differences in asthma control or measures of airway inflammation or remodelling when those with acid GOR were compared with those without. These results suggest that acid GOR is not an important comorbidity in paediatric severe asthma.
Makhecha S, Jamalzadeh A, Irving S, et al., 2021, Paediatric severe asthma biologics service: from hospital to home, Archives of Disease in Childhood, Vol: 106, Pages: 900-902, ISSN: 0003-9888
Children with severe asthma may be treated with biologic agents normally requiring 2–4 weekly injections in hospital. In March 2020, due to COVID-19, we needed to minimise hospital visits. We assessed whether biologics could be given safely at home. The multidisciplinary team identified children to be considered for home administration. This was virtually observed using a video link, and home spirometry was also performed. Feedback was obtained from carers and young people. Of 23 patients receiving biologics, 16 (70%) families agreed to homecare administration, 14 administered by parents/patients and 2 by a local nursing team. Video calls for omalizumab were observed on 56 occasions, mepolizumab on 19 occasions over 4 months (April–July). Medication was administered inaccurately on 2/75 occasions without any adverse events. Virtually observed home biologic administration in severe asthmatic children, supported by video calls and home spirometry, is feasible, safe and is positively perceived by children and their families
Saglani S, 2021, Clinical Adaptations in Pediatric Pulmonology Post Covid-19 in High Income Countries., Publisher: WILEY, Pages: S27-S29, ISSN: 8755-6863
Saglani S, 2021, Personalized Treatments for Severe Asthma., Publisher: WILEY, Pages: S18-S20, ISSN: 8755-6863
Saglani S, 2021, Phenotype-based Management of Preschool Wheeze., Publisher: WILEY, Pages: S36-S37, ISSN: 8755-6863
Saglani S, Robinson P, Fontanella S, et al., 2021, Recurrent severe preschool wheeze: From pre-specified diagnostic labels to underlying endotypes, American Journal of Respiratory and Critical Care Medicine, Vol: 204, Pages: 523-535, ISSN: 1073-449X
Rationale: Preschool wheezing is heterogeneous, but the underlying mechanisms are poorly understood. Objectives: To investigate lower airway inflammation and infection in preschool children with different clinical diagnoses undergoing elective bronchoscopy/bronchoalveolar lavage-BAL. Methods: We recruited 136 children aged 1-5 years (105 recurrent severe wheeze-RSW; 31 non-wheeze respiratory disorders-NWRD). RSW were assigned as episodic viral-EVW or multiple trigger wheeze-MTW. We compared lower airway inflammation/infection in different clinical diagnoses and undertook data-driven analyses to determine clusters of pathophysiological features, and investigated their relationships with pre-specified diagnostic labels. Measurements and Main Results: Blood eosinophils and allergic sensitization were significantly higher in RSW than NWRD. Blood neutrophils, BAL eosinophils and neutrophils, and positive bacterial culture and virus detection rates were similar between groups. However, pathogen distribution differed significantly, with higher detection of rhinovirus in RSW and Moraxella in sensitized RSW. EVW and MTW did not differ in blood/BAL inflammation, or bacterial/virus detection. Partition Around Medoids algorithm revealed 4 clusters of pathophysiological features: (1) Atopic (17.9%); (2) Non-atopic, low infection rate, high inhaled corticosteroids-ICS (31.3%); (3) Non-atopic, high infection rate (23.1%); and (4) Non-atopic, low infection rate, no ICS (27.6%). Cluster allocation differed significantly between RSW and NWRD (RSW evenly distributed across clusters, 60% of NWRD assigned to cluster 4, p<0.001). There was no difference in cluster membership between EVW and MTW. Cluster 1 was dominated by Moraxella detection (p=0.04) and Cluster 3 by Haemophilus/Staphylococcus/ Streptococcus (p=0.02). Conclusions: We identified four clusters of severe preschool wheeze distinguished using sensitization, peripheral eosinophilia, lower airway neutrophilia and bacteriolog
Agerskov N, Coughlin S, Parrott H, et al., 2021, Quality of unsupervised home spirometry in children with asthma, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, Pages: 1-1, ISSN: 1073-449X
Rationale: Spirometry is a standard test that is used to support clinical decision making in patients with asthma.Laboratory spirometry is associated with high quality data but is performed only when patients attend thehospital. Hand-held spirometry can be performed regularly at home allowing clinical trends to be identified. It isunclear whether children perform these tests regularly and achieve adequate quality when unsupervised bytrained personnel. The goal of this study was to evaluate adherence to, and quality of, home spirometry inpaediatric asthma patients using NuvoAir Home. Methods: A retrospective analysis of data from 39 paediatricasthma patients (age, 13±3.3) using the NuvoAir Home platform, from the Royal Brompton Hospital (London,UK), was performed. The platform consists of a smartphone application, Bluetooth spirometer, and clinicianportal that allows patient data to be shared with their healthcare team. The built-in coaching system on the Appprovides feedback to patients on the quality of spirometry (2017 ATS) and tips on how to improve during futuretests. Patients were provided instructions on how to use the NuvoAir Home platform by a specialist respiratoryphysiologist using remote consultation. All sessions were performed in the home setting. Children were asked toperform tests prior to clinical review (1 to 3 monthly). Data were analysed for patients that had used the in-homesolution for at least 90 days. Assessment of session quality was completed over 30 day intervals, analyzing theoverall session grade, FEV1 and FVC percent predicted. All data were analysed anonymously, with informedconsent from the study participants. Results: A total of 517 sessions, performed over a period of 210 days wereanalysed. 288 (55.7%) of the sessions were of acceptable quality (grade A-C, at least 2 attempts <200 mL FEV1and FVC variability). A higher proportion (76.9%) of sessions performed in the last 30 days of the study were ofacceptable quality, compar
Coughlin S, Parrott H, Wells C, et al., 2021, Acceptability of Home Spirometry in Children with Asthma: The NuvoAir Platform, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Branchett WJ, Cook J, Oliver RA, et al., 2021, Airway macrophage-intrinsic TGF-β1 regulates pulmonary immunity during early life allergen exposure, Journal of Allergy and Clinical Immunology, Vol: 147, Pages: 1892-1906, ISSN: 0091-6749
BackgroundEarly life represents a major risk window for asthma development. However, the mechanisms controlling the threshold for establishment of allergic airway inflammation in early life are incompletely understood. Airway macrophages (AMs) regulate pulmonary allergic responses and undergo TGF-β–dependent postnatal development, but the role of AM maturation factors such as TGF-β in controlling the threshold for pathogenic immune responses to inhaled allergens remains unclear.ObjectiveOur aim was to test the hypothesis that AM-derived TGF-β1 regulates pathogenic immunity to inhaled allergen in early life.MethodsConditional knockout (Tgfb1ΔCD11c) mice, with TGF-β1 deficiency in AMs and other CD11c+ cells, were analyzed throughout early life and following neonatal house dust mite (HDM) inhalation. The roles of specific chemokine receptors were determined by using in vivo blocking antibodies.ResultsAM-intrinsic TGF-β1 was redundant for initial population of the neonatal lung with AMs, but AMs from Tgfb1ΔCD11c mice failed to adopt a mature homeostatic AM phenotype in the first weeks of life. Evidence of constitutive TGF-β1 signaling was also observed in pediatric human AMs. TGF-β1–deficient AMs expressed enhanced levels of monocyte-attractant chemokines, and accordingly, Tgfb1ΔCD11c mice exposed to HDM throughout early life accumulated CCR2-dependent inflammatory CD11c+ mononuclear phagocytes into the airway niche that expressed the proallergic chemokine CCL8. Tgfb1ΔCD11c mice displayed augmented TH2, group 2 innate lymphoid cell, and airway remodeling responses to HDM, which were ameliorated by blockade of the CCL8 receptor CCR8.ConclusionOur results highlight a causal relationship between AM maturity, chemokines, and pathogenic immunity to environmental stimuli in early life and identify TGF-β1 as a key regulator of this.
Bloom C, Franklin C, Bush A, et al., 2021, Burden of preschool wheeze and progression to asthma in the UK: population-based cohort 2007 to 2017, Journal of Allergy and Clinical Immunology, Vol: 147, Pages: 1949-1958, ISSN: 0091-6749
BackgroundWheeze is one of the most common symptoms of preschool children (age 1 to 5 years), yet we have little understanding of the burden in the UK.ObjectivesDetermine prevalence and pattern of physician-confirmed preschool wheeze, related healthcare utilisation, and factors associated with progression to school-age asthma.MethodsWe used nationally representative primary and secondary care electronic medical records between 2007-2017 to identify preschool children with wheeze. Factors associated with asthma progression were identified in a nested cohort of children with follow-up from 1-2 years of age, until at least 8 years of age.ResultsFrom 1,021,624 preschool children, 69,261 were identified with wheeze. Prevalence of preschool wheeze was 7.7% in 2017. Wheeze events were lowest in August and highest in late-autumn/early-winter. During median follow-up of 2.0 years (IQR 1.2-4.0), 15.8% attended an emergency department, and 13.9% had a hospital admission, for a respiratory disorder. The nested cohort with prolonged follow-up identified 15,085 children; 35.5% progressed to asthma between 5-8 years old. Of children with preschool wheeze, without an asthma diagnosis, 34.9% were prescribed inhaled corticosteroids, and 15.6% oral corticosteroids. The factors most strongly associated with progression to asthma were wheeze frequency and severity, atopy, prematurity, maternal asthma severity and first reported wheeze event occurring in September.ConclusionsPreschool wheeze causes considerable healthcare burden, a large number of children are prescribed asthma medication and have unplanned secondary care visits. Multiple factors influence progression to asthma, including first wheeze event occurring in September.
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