Publications
298 results found
Irving S, Fleming L, Saglani S, et al., 2016, Scond may better discriminate severe therapy resistant asthma (STRA) from mild-moderate asthma than lung clearance index (LCI), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Cook J, Bush A, Saglani S, et al., 2016, Higher doses of inhaled steroid are associated with bacterial bronchitis in children with severe therapy resistant asthma (STRA), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Pearce C, Jochmann A, Bush A, et al., 2016, Patterns of nonadherence in children with severe asthma, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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Jamalzadeh A, Jochmann A, Artusio L, et al., 2016, Improvements in asthma control following a period of electronic monitoring are sustained, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Saglani S, Fleming L, 2016, How to manage a child with difficult asthma?, Expert Review of Respiratory Medicine, Vol: 10, Pages: 873-879, ISSN: 1747-6348
Introduction: Children with difficult asthma have significant morbidity and fail to achieve asthma control despite being prescribed high dose maintenance treatment. If control remains poor after diagnostic confirmation, detailed assessments of the reasons for asthma being difficult-to-control are needed. Underlying modifiable factors including non-adherence to medication, persistent environmental exposures that trigger asthma symptoms and psychosocial factors contribute to poor control in these patients. Areas covered: The focus of this review is to provide a practical approach to the diagnosis and management of difficult asthma including an overview of long term assessments to identify potential progression to true, severe asthma. A multi-disciplinary team is critical to enable modifiable factors to be identified and addressed. Significant resources are required to manage paediatric difficult asthma optimally and only specialist centres should be tasked with the assessment of these patients. Although this may have an impact on healthcare resources, long term benefits for lung health are significant. Expert commentary: The management of paediatric difficult asthma is not simple and involves numerous professionals with varied expertise. However, if it is not undertaken with the appropriate skills, there is a significant risk of children receiving inappropriate invasive investigations and therapies that will have no impact on morbidity.
Bossley CJ, Fleming L, Ullmann N, et al., 2016, Assessment of corticosteroid response in pediatric patients with severe asthma by using a multidomain approach., Journal of Allergy and Clinical Immunology, Vol: 138, Pages: 413-420.e6, ISSN: 1097-6825
BACKGROUND: There is no agreed upon definition of systemic corticosteroid response in asthmatic children. Moreover, pediatric severe therapy-resistant asthma (STRA) is heterogeneous, and thus response to steroids is unlikely to be uniform in all patients. OBJECTIVE: We sought to evaluate the utility of a multidomain approach incorporating symptoms, lung function, and inflammation to determine steroid responsiveness in pediatric patients with STRA. METHODS: Eighty-two children (median age, 12 years) with STRA received a clinically indicated dose of intramuscular steroid. Changes in 4 separate domains were assessed 4 weeks after intramuscular triamcinolone acetonide: normalization of (1) symptoms (Asthma Control Test score, >19/25 or 50% increase), (2) spirometric results (FEV1 ≥80% of predicted value or ≥15% increase), (3) fraction of exhaled nitric oxide levels (<24 ppb), and (4) sputum eosinophil counts (<2.5%). Fifty-four of 82 children had complete data in all 4 domains. RESULTS: Twenty-three (43%) of 54 children had a symptom response, 29 (54%) of 54 had a lung function response, 28 (52%) of 54 had a fraction of exhaled nitric oxide response, and 29 (54%) of 54 had a sputum eosinophil response. Although a similar proportion of children responded to systemic corticosteroids in each domain, there were no reliable predictors of a response pattern. Seven (13%) of 54 were complete responders (response in all domains), 8 (15%) of 54 were nonresponders (no response in any domain), and 39 (72%) of 54 were partial responders (response in ≥1 domain). CONCLUSIONS: A multidomain evaluation of systemic steroid responsiveness using pragmatic clinical assessments confirms childhood STRA is heterogeneous and that a complete response in symptoms and inflammatory and physiologic parameters is rare. Individual response patterns to systemic steroids might be useful in guiding the choice of add-on therapies in each child as a step toward achieving pe
Bush A, Fleming L, 2016, Is asthma overdiagnosed?, Archives of Disease in Childhood, Vol: 101, Pages: 688-689, ISSN: 0003-9888
Fleming L, Koo M, Bossley CJ, et al., 2016, The utility of a multidomain assessment of steroid response for predicting clinical response to omalizumab, Journal of Allergy and Clinical Immunology, Vol: 138, Pages: 292-294, ISSN: 1097-6825
Kane B, Cramb S, Hudson V, et al., 2016, Specialised commissioning for severe asthma: oxymoron or opportunity?, THORAX, Vol: 71, Pages: 196-198, ISSN: 0040-6376
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- Citations: 12
Koo S, Gupta A, Fainardi V, et al., 2016, Ethnic variation in response to IM Triamcinolone in children with severe therapy-resistant asthma, Chest, Vol: 149, Pages: 98-105, ISSN: 0012-3692
BackgroundAlthough ethnicity may influence response to treatment of patients with asthma, this approach is controversial. The objective of this study was to determine if ethnicity influences the response to IM steroid use (eliminating adherence as an issue).MethodsChildren with severe therapy-resistant asthma who had previously undergone a detailed assessment (including a nurse-led hospital and home visit in which potentially modifiable factors had been identified and addressed) were admitted for further evaluation; this evaluation included assessment of steroid response. Children were classified as white, black, Asian, or mixed white/black. Steroid responsiveness was defined according to symptoms (Asthma Control Test), inflammation (sputum eosinophil count and exhaled nitric oxide), and spirometry (FEV1); these variables were measured before and 4 weeks after IM triamcinolone use. Data were collected regarding exacerbations. Fractional exhaled nitric oxide (Feno) response was defined as a decrease to < 24 parts per billion (ppb).ResultsSeventy-nine subjects were identified (white, n = 54 [68%]; black, n = 16 [20%]; Asian, n = 5 [6%]; and mixed white/black, n = 4 [5%]). After administration of triamcinolone, there was a significant drop in median Feno in white children (46.8 to 23.1 ppb; P < .001) but not in black children (52.2 to 34.5 ppb; P = .58). More black children than white children (86.7%) were Feno nonresponders (86.7% vs 45.3%; P < .05), and more black children had exacerbations compared with white children (61% vs 17%; P < .05).ConclusionsBlack children with asthma were less likely to report an Feno response and had more exacerbations 4 weeks after administration of triamcinolone than white children. Further research is needed to understand the mechanisms of these differences, but they cannot be due to differences in adherence or access to care.
Jochmann A, Artusio L, Robson K, et al., 2015, Infection and inflammation in induced sputum from preschool children with chronic airways diseases., Pediatric Pulmonology, Vol: 51, Pages: 778-786, ISSN: 8755-6863
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. 2016;51:778-786. © 2015 WileyPeriodicals, Inc.
Mckeon S, Saglani S, Bush A, et al., 2015, The relationship between invasive and non-invasive measures of inflammation in children with severe therapy-resistant asthma, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ Publishing Group, Pages: A124-A125, ISSN: 1468-3296
Background Children with severe therapy-resistant asthma (STRA) are refractory to treatment despite optimal management. Assessment of airway inflammation to phenotype these patients can enable targeted therapy. Samples obtained at bronchoscopy provide the most direct measure of lower airway inflammation; however, non-invasive measures (induced sputum and exhaled nitric oxide (FeNO)) are of greater clinical utility. We have previously demonstrated a poor relationship between blood and bronchoalveolar lavage (BAL) eosinophilic phenotype using clinical cut-offs for children (blood eosinophils 1.0 × 109/L).1 Recent studies of the anti-IL-5 antibody mepolizumab have used a lower cut point (0.3 × 109/L) for blood eosinophils.2 The aim of this study was to assess the concordance between BAL and non-invasive measures of inflammation.Methods 113 children (aged 4–17 years) with STRA underwent bronchoscopy at the Royal Brompton Hospital. They had all previously been assessed and potentially modifiable factors such as poor adherence had been addressed. Inflammation was measured invasively using BAL cytology and non-invasively by blood eosinophils, induced sputum cytology, and FeNO. The eosinophilic phenotype was defined as BAL eosinophils >1.19%; blood eosinophils ≥0.3 × 109/L; sputum eosinophils ≥2.5%; and FeNO >35ppb. The relationship between measures was assessed using Spearman rank correlation and Receiver Operator Characteristic (ROC) curves were constructed to determine which cut points best determined BAL eosinophilia and positive and negative predictive values (PPV and NPV) calculated.Results The predominant phenotype in all samples was eosinophilic. There was 75.6–77.8% concordance between the eosinophilic phenotype in BAL and each of the non-invasive measures.Blood and BAL eosinophils had the strongest correlation (r = 0.57, p < 0.001, n = 84). Weaker correlations were found between the other measures. The most promising pr
Downing B, Irving S, Bingham Y, et al., 2015, Feasibility of measuring lung clearance index (LCI) in a clinic setting in preschool children with a range of airway diseases, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ Publishing Group, Pages: A116-A116, ISSN: 1468-3296
Introduction and objectives LCI is a measurement of lung function (in particular distal airway disease) derived from the multiple breath washout (MBW) test (Eur Resp J 2013; 41:507–22). Although practical in a research setting, feasibility in a clinic setting (with limited time and without using sedation) in young children is not known. We looked at success rates of LCI, and LCI0.5 (a shortened washout which can be accomplished more quickly) in preschool children (aged 2–6 years) with recurrent wheeze (Eur Resp J 2008; 32:1096–110), cystic fibrosis (CF), recurrent cough/infections, and healthy controls. Our hypothesis (based on other research performed in this field (Thorax 2012; 68:586–587) was that shortened LCI0.5 would be more feasible than full LCI, and that the test would be more feasible in older preschool children than younger.
Tanou K, Irving S, Ahmad F, et al., 2015, Extrapolating lung clearance index (LCI) from shortened measurements, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ Publishing Group, Pages: A115-A115, ISSN: 0040-6376
Ahmad F, Irving S, Alton E, et al., 2015, Multiple breath washouts in children can be shortened without compromising quality, European Respiratory Journal, Vol: 46, Pages: 1814-1816, ISSN: 1399-3003
Fleming L, Murray C, Bansal AT, et al., 2015, The burden of severe asthma in childhood and adolescence: results from the paediatric U-BIOPRED cohorts, European Respiratory Journal, Vol: 46, Pages: 1322-1333, ISSN: 0903-1936
U-BIOPRED aims to characterise paediatric and adult severe asthma using conventional and innovative systems biology approaches.A total of 99 school-age children with severe asthma and 81 preschoolers with severe wheeze were compared with 49 school-age children with mild/moderate asthma and 53 preschoolers with mild/moderate wheeze in a cross-sectional study.Despite high-dose treatment, the severe cohorts had more severe exacerbations compared with the mild/moderate ones (annual medians: school-aged 3.0 versus 1.1, preschool 3.9 versus 1.8; p<0.001). Exhaled tobacco exposure was common in the severe wheeze cohort. Almost all participants in each cohort were atopic and had a normal body mass index. Asthma-related quality of life, as assessed by the Paediatric Asthma Quality of Life Questionnaire (PAQLQ) and the Paediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ), was worse in the severe cohorts (mean±se school-age PAQLQ: 4.77±0.15 versus 5.80±0.19; preschool PACQLQ: 4.27±0.18 versus 6.04±0.18; both p≤0.001); however, mild/moderate cohorts also had significant morbidity. Impaired quality of life was associated with poor control and airway obstruction. Otherwise, the severe and mild/moderate cohorts were clinically very similar.Children with severe preschool wheeze or severe asthma are usually atopic and have impaired quality of life that is associated with poor control and airflow limitation: a very different phenotype from adult severe asthma. In-depth phenotyping of these children, integrating clinical data with high-dimensional biomarkers, may help to improve and tailor their clinical management.
Shaw DE, Sousa AR, Fowler SJ, et al., 2015, Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort, European Respiratory Journal, Vol: 46, Pages: 1308-1321, ISSN: 1399-3003
U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach.This cross-sectional assessment of adults with severe asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements.Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations compared to patients with mild/moderate disease (n=88) (2.5 exacerbations versus 0.4 in the preceding 12 months; p<0.001), with worse quality of life, and higher levels of anxiety and depression. They also had a higher incidence of nasal polyps and gastro-oesophageal reflux with lower lung function. Sputum eosinophil count was higher in severe asthma compared to mild/moderate asthma (median count 2.99% versus 1.05%; p=0.004) despite treatment with higher doses of inhaled and/or oral corticosteroids.Consistent with other severe asthma cohorts, U-BIOPRED is characterised by poor symptom control, increased comorbidity and airway inflammation, despite high levels of treatment. It is well suited to identify asthma phenotypes using the array of “omic” datasets that are at the core of this systems medicine approach.
Pandis I, Guo Y, Guitton F, et al., 2015, eTRIKS IT platfroms for large-scale biomedical research, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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Jochmann A, Robson K, Fleming L, et al., 2015, Sputum induction for assessment of lower airway infection in preschool children, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Hoda U, Sousa A, Corfield J, et al., 2015, Characteristics of the frequent exacerbator in U-BIOPRED adult severe asthma cohort, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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Wang Y, Hashimoto S, Brinkman P, et al., 2015, Exhaled breath VOCs are associated with nocturnal wakening in asthmatic children, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Zimmels S, Kelly A, Fleming L, 2015, Swallow aspiration and respiratory symptoms in normally developing children, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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Jochmann A, Nagakumar P, Hall P, et al., 2015, Improvement in asthma control and airway inflammation during a period of electronic monitoring, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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- Citations: 2
Nagakumar P, Denney L, Fleming L, et al., 2015, Type 2 innate lymphoid cells in induced sputum from children with severe asthma, Journal of Allergy and Clinical Immunology, Vol: 137, Pages: 624-626.e6, ISSN: 1097-6825
Castanhinha S, Sherburn RT, Walker SA, et al., 2015, Pediatric severe asthma with fungal sensitization is mediated by steroid-resistant IL-33, Journal of Allergy and Clinical Immunology, Vol: 136, Pages: 312-322.e7, ISSN: 1097-6825
Background: 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. Objective: We sought to determine whether fungal sensitization in children with severe therapy-resistant asthma is mediated by IL-33. Methods: 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. Results: 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. Conclusion: 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.
Fleming L, 2015, Monitoring asthma in children: what does BATMAN tell us?, Thorax, Vol: 70, Pages: 517-518, ISSN: 1468-3296
Bush A, Fleming L, 2015, Diagnosis and management of asthma in children, BMJ-BRITISH MEDICAL JOURNAL, Vol: 350, ISSN: 0959-535X
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- Citations: 42
Fleming L, Bush A, 2015, Fraction of exhaled nitric oxide measurements and asthma control: Are the numbers starting to add up?, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 135, Pages: 689-U161, ISSN: 0091-6749
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Nagakumar P, Denney L, Fleming L, et al., 2015, Type 2 Innate Lymphoid Cells Are Increased In Bal And Induced Sputum But Not Blood In Children With Severe Therapy Resistant Asthma (stra), International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Tariq K, Nicholas BL, Lutter R, et al., 2015, Prevalence Of Gastro-Oesophageal Reflux (gord) And Associations With Clinical Phenotypic Markers In Adult Severe Asthmatics In The U-Biopred Cohort, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
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