Publications
297 results found
Wang K, Elliot J, Saglani S, et al., 2021, INCREASED BUT SMALLER AIRWAY SMOOTH MUSCLE CELLS IN LOW-BIRTHWEIGHT INFANTS, Publisher: WILEY, Pages: 78-78, ISSN: 1323-7799
Bacharier LB, Guilbert TW, Jartti T, et al., 2021, Which wheezing preschoolers should be treated for asthma?, Journal of Allergy and Clinical Immunology: In Practice, Pages: 1-8, ISSN: 2213-2198
Wheezing disorders in children younger than 5 years are common, but lack of clarity remains about which children should be treated to prevent symptoms and acute episodes. The aim of this review was to discuss a practical approach to deciding which children younger than 5 years with asthma should be treated, and if so, with which strategy. The importance of having a clear definition of "asthma" for this age group, determined by a collection of presenting respiratory symptoms, without assumptions about underlying mechanisms is addressed. Subsequent consideration should be given to timing, severity, and frequency of symptoms, together with assessment of objective biomarkers, including aeroallergen sensitization and blood eosinophils, to inform whether or not a preschooler with recurrent wheezing requires treatment. Numerous unanswered questions remain about the optimal management of nonallergic preschool wheezing and asthma, and areas of specific unmet need and future directions for research are highlighted.
Jamalzadeh A, Makhecha S, Irving S, et al., 2021, FROM HOSPITAL TO HOME: VIRTUALLY OBSERVED ADMINISTRATION OF BIOLOGICS IN CHILDREN WITH SEVERE ASTHMA DURING COVID-19, Publisher: BMJ PUBLISHING GROUP, Pages: A138-A139, ISSN: 0040-6376
Roberts G, Almqvist C, Boyle R, et al., 2020, Developments allergy in 2019 through the eyes of clinical and experimental allergy, part I mechanisms, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 50, Pages: 1294-1301, ISSN: 0954-7894
Andersson CK, Iwasaki J, Cook J, et al., 2020, Impaired airway epithelial cell wound-healing capacity is associated with airway remodelling following RSV infection in severe preschool wheeze, ALLERGY, Vol: 75, Pages: 3195-3207, ISSN: 0105-4538
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- Citations: 12
Roberts G, Almqvist C, Boyle R, et al., 2020, Developments allergy in 2019 through the eyes of Clinical and Experimental Allergy, Part II clinical allergy, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 50, Pages: 1302-1312, ISSN: 0954-7894
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- Citations: 1
Creese H-M, Taylor-Robinson D, Saglani S, et al., 2020, Primary care of children and young people with asthma during the Covid-19 era, British Journal of General Practice, Vol: 70, Pages: 528-529, ISSN: 0960-1643
Around 1.1 million children and young people (CYP)currently receive treatment for asthma in the United Kingdom (UK)(1). The UK performs poorly compared with other European countries in children's outcomes of asthma management and has had amongst the highest number of reported asthma deaths in Europesince 1998 (2). We evaluate evidenceofthe impact of Covid-19 on CYP with asthma and consider what actionsgeneral practitioners can take to protect these children from serious harm.
Bush A, Saglani S, 2020, Medical algorithm: diagnosis and treatment of preschool asthma, Allergy, Vol: 75, Pages: 2711-2712, ISSN: 0105-4538
Bush A, Saglani S, 2020, Preschool wheeze: Challenges and research prospects reply to: Dr Jartti and Colleagues; in response to our manuscript entitled: Medical algorithm: Diagnosis and treatment of preschool asthma, ALLERGY, Vol: 75, Pages: 2718-2718, ISSN: 0105-4538
Fainardi V, Saglani S, 2020, An approach to the management of children with problematic severe asthma., Acta Biomed, Vol: 91
Children with poor asthma control despite high levels of prescribed treatment are described as having problematic severe asthma. Most of these children have steroid sensitive disease which improves with adherence to daily inhaled corticosteroids and after having removed modifiable factors like poor inhalation technique, persistent adverse environmental exposures and psychosocial factors. These children are described as having "difficult-to-treat asthma" while children with persistent symptoms despite above-mentioned factors having been addressed are described as having "severe therapy-resistant asthma". In this review, we will describe the 6-step approach to the diagnosis and management of a child with problematic severe asthma adopted by The Royal Brompton Hospital (London, UK). The role of a multidisciplinary team is crucial for identification and treatment of modifiable factors and comorbidities in order to avoid invasive examinations and useless pharmacological treatments. The current knowledge on add-on therapies will be discussed.
Davies B, Frost S, Rao S, et al., 2020, Accuracy of blood eosinophil count in predicting sputum eosinophils in children with problematic severe asthma (PSA), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Bingham Y, Fleming L, Sanghani N, et al., 2020, Electronic monitoring of adherence to inhaled corticosteroids in preschool children with wheeze, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Wells C, Cartwright M, Hirani S, et al., 2020, Identifying predictors for referral to a physiotherapy service for children with difficult asthma, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Scotney E, Saglani S, 2020, Diagnosis and Management of Problematic Severe Asthma., Acta Med Acad, Vol: 49, Pages: 117-129
This review will outline an evidence-based approach for diagnosing and managing children with problematic severe asthma (PSA). Children with PSA have uncontrolled asthma symptoms, despite maximal prescribed asthma treatment. These children have high morbidity and mortality and should be referred for specialist respiratory assessment and management. The first step in the assessment of a child with PSA is confirming the diagnosis of asthma using objective evidence. Following this, an assessment of inhaled corticosteroid adherence and a multi-disciplinary team approach is essential for separating difficult asthma (DA) from severe therapy resistant asthma (STRA). The majority of children have DA which entails uncontrolled asthma symptoms due to underlying modifiable factors including poor treatment adherence, poor inhaler technique, exposure to environmental allergens, co-morbid conditions and psycho-social factors. Approximately 20% of children with PSA have STRA, and have persistent asthma symptoms despite good treatment adherence and correction of modifiable factors. Children with STRA typically have multiple and severe aeroallergen sensitization, eosinophilic airway inflammation and high fraction exhaled nitric oxide (FeNO). Further investigation of children with STRA includes an assessment of systemic steroid responsiveness, this is important for confirming the diagnosis of STRA and guiding the choice of additional treatment. Biologics are an add on (immune targeted) therapy for STRA. The current biologics used in children target the T2 helper (Th2) pathway mediating eosinophilic, allergic asthma. CONCLUSION: Future clinical trials of biologics in children will be essential to help identify childhood specific biomarkers and to decide which biologic is best for which individual child.
Saglani S, Wisnivesky JP, Charokopos A, et al., 2020, Update in Asthma 2019, American Journal of Respiratory and Critical Care Medicine, Vol: 202, Pages: 184-192, ISSN: 1073-449X
In a recent review on childhood asthma, we proposed that knowledge gaps will only be addressed by integrating technological advances and human knowledge across diverse disciplines, with a patient at its center (1). So, how far have we come in turning “big data” into actionable information to address some of the most important questions in asthma today, including clinical and mechanistic insights about the architecture of asthma heterogeneity, to inform personalized treatments? In this Update focusing on publications in the American Thoracic Society journals, we review the progress made in 2019 on understanding asthma epidemiology and risk factors, mechanisms underpinning different disease subtypes, therapeutic options and prediction of treatment responses, and highlight areas for future research.
Bingham Y, Sanghani N, Cook J, et al., 2020, Electronic adherence monitoring identifies severe preschool wheezers who are steroid responsive., Pediatric Pulmonology, Vol: 55, Pages: 2254-2260, ISSN: 1099-0496
Little is known about adherence to inhaled corticosteroids (ICS) in preschool children with troublesome wheeze. Children with aeroallergen senitization, or those reporting multiple trigger wheeze (MTW), are more likely to respond to ICS. We hypothesized that adherence to ICS and symptom control are only positively related in atopic children, or those reporting MTW. Patients aged 1 to 5 years with recurrent wheeze prescribed ICS were recruited from a tertiary respiratory clinic. Clinical phenotype and aeroallergen senitization were determined, and adherence assessed using an electronic monitoring device (Smartinhaler). Symptom control (test for respiratory and asthma control in kids [TRACK]), quality of life (PACQLQ), airway inflammation (offline exhaled nitric oxide) were assessed at baseline and follow-up. Forty-eight children (mean age 3.7 years; SD, 1.2) were monitored for a median of 112 (interquartile range [IQR], 91-126) days. At baseline n = 29 reported episodic viral wheeze and n = 19 reported MTW. Twenty-four out of 48 (50%) wheezers had suboptimal ICS adherence (<80%). Median adherence was 64% (IQR, 38-84). There was a significant increase in TRACK and PACQLQ in the group as a whole, unrelated to adherence. In subgroup analysis only atopic wheezers with moderate or good adherence ≥ 60% had a significant increase in TRACK. There was no relationship between clinical phenotype, and adherence or TRACK. In this pilot study, overall adherence to ICS was suboptimal and was positively related to symptom control in atopic wheezers only. Assessments of adherence are important in preschool troublesome wheezers before therapy escalation to help identify those with an ICS responsive phenotype.
Wang K, Elliot J, Saglani S, et al., 2020, IN LOW BIRTH INFANTS, THE AIRWAY SMOOTH MUSCLE LAYER COMPRISES AN INCREASED NUMBER OF SMALLER CELLS AND PROPORTIONALLY GREATER EXTRACELLULAR MATRIX, Publisher: WILEY, Pages: 208-208, ISSN: 1323-7799
Foster W, Grime C, Tan H-L, et al., 2020, Enhanced frequency and function of follicular T cells in the tonsils of house dust mite sensitized children, Allergy, Vol: 75, Pages: 1240-1243, ISSN: 0105-4538
Irving S, Fleming L, Ahmad F, et al., 2020, Lung clearance index and steroid response in pediatric severe asthma, PEDIATRIC PULMONOLOGY, Vol: 55, Pages: 890-898, ISSN: 8755-6863
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- Citations: 8
Turner P, Fleming L, Saglani S, et al., 2020, Safety of live attenuated influenza vaccine in children with moderate-severe asthma, Journal of Allergy and Clinical Immunology, Vol: 145, Pages: 1157-1164.e6, ISSN: 0091-6749
Background:Live attenuated influenza vaccine (LAIV) is recommended for annual influenza vaccination in children from age 2 years. However, some guidelines recommend against its use in children with asthma or recurrent wheeze due to concerns over its potential to induce wheezing. Objective: To assess the safety of LAIV in children with moderate-severe asthma, and in preschool children with recurrent wheeze. Methods: Prospective, multi-center, open label, phase IV intervention studyin 14 specialist UK clinics.LAIV was administered under medical supervision, with follow-up of asthma symptoms 72 hours and 4 weeks late, using validated questionnaires.Clinical Trials.gov registration NCT02866942, EU Clinical Trials registration 2016-002352-24. Results: 478 young people (median 9.3, range 2–18 years) with physician-diagnosed asthma or recurrent wheeze were recruited, including 208 (44%) prescribed high-dose inhaled corticosteroids and 122 (31%) with severe asthma.There was no significant change in asthma symptoms in the 4 weeks following administration (median change 0, P=.26, McNemar’s test), with no impact of level of baseline asthma control/symptoms in predicting either a worsening of asthma or exacerbation following LAIV using a regression model. 47 subjects (14.7%, 95%CI 11% to 19.1%) reported a severe asthma exacerbation in the four weeks following immunization, requiring short course of systemic corticosteroids; in four cases, this occurred within 72 hours of vaccine. No association with asthma severity, baseline lung function or asthma control was identified.Conclusions: LAIV appears to be well-tolerated in the vast majority of children with asthma or recurrent wheeze, includingthosewhose asthma is categorized as severe or poorly controlled
Broadbent L, Manzoor S, Zarcone MC, et al., 2020, Comparative primary paediatric nasal epithelial cell culture differentiation and RSV-induced cytopathogenesis following culture in two commercial media, PLoS One, Vol: 15, Pages: 1-12, ISSN: 1932-6203
The culture of differentiated human airway epithelial cells allows the study of pathogen-host interactions and innate immune responses in a physiologically relevant in vitro model. As the use of primary cell culture has gained popularity the availability of the reagents needed to generate these cultures has increased. In this study we assessed two different media, Promocell and PneumaCult, during the differentiation and maintenance of well-differentiated primary nasal epithelial cell cultures (WD-PNECs). We compared and contrasted the consequences of these media on WD-PNEC morphological and physiological characteristics and their responses to respiratory syncytial virus (RSV) infection. We found that cultures generated using PneumaCult resulted in greater total numbers of smaller, tightly packed, pseudostratified cells. However, cultures from both media resulted in similar proportions of ciliated and goblet cells. There were no differences in RSV growth kinetics, although more ciliated cells were infected in the PneumaCult cultures. There was also significantly more IL-29/IFNλ1 secreted from PneumaCult compared to Promocell cultures following infection. In conclusion, the type of medium used for the differentiation of primary human airway epithelial cells may impact experimental results.
Byrne A, powell J, O'Sullivan B, et al., 2020, Dynamics of human monocytes and airway macrophages during healthy aging and post-transplant, Journal of Experimental Medicine, Vol: 217, Pages: 1-9, ISSN: 0022-1007
The ontogeny of airway macrophages (AMs) in human lung and their contribution to disease are poorly mapped out. In mice, aging is associated with an increasing proportion of peripherally, as opposed to perinatally derived AMs. We sought to understand AM ontogeny in human lung during healthy aging and after transplant. We characterized monocyte/macrophage populations from the peripheral blood and airways of healthy volunteers across infancy/childhood (2–12 yr), maturity (20–50 yr), and older adulthood (>50 yr). Single-cell RNA sequencing (scRNA-seq) was performed on airway inflammatory cells isolated from sex-mismatched lung transplant recipients. During healthy aging, the proportions of blood and bronchoalveolar lavage (BAL) classical monocytes peak in adulthood and decline in older adults. scRNA-seq of BAL cells from lung transplant recipients indicates that after transplant, the majority of AMs are recipient derived. These data show that during aging, the peripheral monocyte phenotype is consistent with that found in the airways and, furthermore, that the majority of human AMs after transplant are derived from circulating monocytes.
Forno E, Saglani S, 2020, Severe Asthma in Children and Adolescents Mechanisms and Management Preface, SEVERE ASTHMA IN CHILDREN AND ADOLESCENTS: MECHANISMS AND MANAGEMENT, Editors: Forno, Saglani, Publisher: SPRINGER INTERNATIONAL PUBLISHING AG, Pages: V-VI, ISBN: 978-3-030-27433-7
Saglani S, 2020, Basic Mechanisms Underpinning Severe Childhood Asthma, SEVERE ASTHMA IN CHILDREN AND ADOLESCENTS: MECHANISMS AND MANAGEMENT, Editors: Forno, Saglani, Publisher: SPRINGER INTERNATIONAL PUBLISHING AG, Pages: 251-269, ISBN: 978-3-030-27433-7
Forno E, Saglani S, 2020, Severe Asthma During Adolescence and the Transition to Adulthood, SEVERE ASTHMA IN CHILDREN AND ADOLESCENTS: MECHANISMS AND MANAGEMENT, Editors: Forno, Saglani, Publisher: SPRINGER INTERNATIONAL PUBLISHING AG, Pages: 237-247, ISBN: 978-3-030-27433-7
Wang KC, Elliot J, Saglani S, et al., 2020, In Low Birth Infants, the Airway Smooth Muscle Layer Comprises an Increased Number of Smaller Cells and Proportionally Greater Extracellular Matrix, Virtual International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Selby L, Saglani S, Bush A, et al., 2019, ADHERENCE, AIRWAY INFLAMMATION AND ADRENAL FUNCTION IN A COHORT OF PAEDIATRIC ASTHMA PATIENTS, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A43-A43, ISSN: 0040-6376
Roberts G, Almqvist C, Boyle R, et al., 2019, Developments in the mechanisms of allergy in 2018 through the eyes of Clinical and Experimental Allergy, Part I, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 49, Pages: 1541-1549, ISSN: 0954-7894
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- Citations: 2
Roberts G, Almqvist C, Boyle R, et al., 2019, Developments in the field of clinical allergy in 2018 through the eyes of Clinical and Experimental Allergy, Part II, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 49, Pages: 1550-1557, ISSN: 0954-7894
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- Citations: 1
Bingham Y, Moreiras J, Goldring S, et al., 2019, USE OF PATHOLOGICAL PHENOTYPE TO DETERMINE OPTIMAL MANAGEMENT FOR MODERATE TO SEVERE PRESCHOOL WHEEZE, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A44-A44, ISSN: 0040-6376
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