Publications
1244 results found
Bush A, 2022, Transition to Adult Care: What adults should know about Pediatric Respiratory Diseases, Publisher: WILEY, Pages: S22-S24, ISSN: 8755-6863
Kotecha S, Doull I, Wild J, et al., 2022, Prematurity-associated lung disease: looking beyond bronchopulmonary dysplasia, LANCET RESPIRATORY MEDICINE, Vol: 10, Pages: E46-E46, ISSN: 2213-2600
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- Citations: 2
Hoda U, Pavlidis S, Bansal AT, et al., 2022, Clinical and transcriptomic features of persistent exacerbation-prone severe asthma in U-BIOPRED cohort, Clinical and Translational Medicine, Vol: 12, ISSN: 2001-1326
Background: Exacerbation-prone asthma is a feature of severe disease. Yet, the basis for its persistency remains unclear. Objectives: To determine the clinical and transcriptomic features of the frequent-exacerbator (FE) and of persistent FEs (PFE) in U-BIOPRED cohort. Methods: We compared features of FE (≥2 exacerbations in past year) to infrequent exacerbators (IE, <2 exacerbations) and of PFE with repeat ≥2 exacerbations during the following year to persistent IE (PIE). Transcriptomic data in blood, bronchial and nasal epithelial brushings, bronchial biopsies and sputum cells were analysed by gene set variation analysis for 103 gene signatures.Results: Of 317 patients, 62.4 % were FE of whom 63.6% were PFE, while 37.6% were IE of whom 61.3% were PIE. Using multivariate analysis, FE was associated with short-acting beta-agonist use, sinusitis and daily oral corticosteroid use, while PFE with eczema, short-acting beta-agonist use and asthma control index. CEA Cell Adhesion Molecule 5 (CEACAM5) was the only differentially-expressed transcript in bronchial biopsies between PE and IE. There were no differentially-expressed genes in the other 4 compartments. There were higher expression scores for Type 2 , T-helper type-17 and Type 1 pathway signatures together with those associated with viral infections in bronchial biopsies from FE compared to IE, while higher expression scores of Type 2, Type 1 and steroid insensitivity pathway signatures in bronchial biopsies of PFE compared to PIE.Conclusion: FE group and its PFE subgroup are associated with poor asthma control while expressing higher Type 1 and Type 2 activation pathways compared to IE and PIE, respectively.
Irving S, Bayfield K, Davies JC, et al., 2022, Curvilinearity provides additional information to lung clearance index only in a minority of children with early cystic fibrosis lung disease, ERJ Open Research, Vol: 8, ISSN: 2312-0541
Curvilinearity, as calculated from multiple-breath washout, is abnormal in a small number of children with cystic fibrosis when other tests are still normal https://bit.ly/3p9QAV4.
Pearce CJ, Chan AHY, Jackson T, et al., 2022, Features of successful interventions to improve adherence to inhaled corticosteroids in children with asthma: A narrative systematic review, PEDIATRIC PULMONOLOGY, Vol: 57, Pages: 822-847, ISSN: 8755-6863
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- Citations: 2
Bush A, Pabary R, 2022, Grappling with the granuloma: where is the ACE in the hole?, THORAX, Vol: 77, Pages: 320-321, ISSN: 0040-6376
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- Citations: 1
Pillai A, Semple T, Bush A, et al., 2022, Tracheomegaly following antenatal treatment for congenital diaphragmatic hernia, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 107, Pages: 288-288, ISSN: 0003-9888
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
Bush A, Pavord ID, 2022, Reply to: Challenging the paradigm, BREATHE, Vol: 18, ISSN: 1810-6838
Makrinioti H, Hasegawa K, Lakoumentas J, et al., 2022, The role of respiratory syncytial virus- and rhinovirus-induced bronchiolitis in recurrent wheeze and asthma-A systematic review and meta-analysis, PEDIATRIC ALLERGY AND IMMUNOLOGY, Vol: 33, ISSN: 0905-6157
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- Citations: 31
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.
Mikus MS, Kolmert J, Andersson L, et al., 2022, Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation, European Respiratory Journal, Vol: 59, Pages: 1-17, ISSN: 0903-1936
Rationale Asthma phenotyping requires novel biomarker discovery.Objectives To identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, COPD subjects and healthy controls (HCs).Methods An antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HCs in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a 2-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED.Results In U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HCs. 10 proteins were elevated in SA versus MMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, TNF receptor superfamily member 11a, transforming growth factor-β and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, high-sensitivity C-reactive protein and body mass index, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation.Conclusions The plasma proteomic panel revealed previously unexplored yet potentially useful Type-2-independent biomarkers and validated several proteins with established involvement in the pathophysiology of SA.
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
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- Citations: 8
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
Nagakumar P, Bush A, Gupta A, 2022, Childhood acute respiratory illnesses: will normal inadequate services be resumed?, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 107, Pages: 173-173, ISSN: 0003-9888
Bush A, 2022, Severe and Difficult Asthma: Diagnosis and Management-Challenges for a Low-Resource Environment, INDIAN JOURNAL OF PEDIATRICS, Vol: 89, Pages: 156-162, ISSN: 0019-5456
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- Citations: 2
Hopkinson NS, Vestbo J, Bush A, et al., 2022, Should e-cigarettes be licensed as medicines?, BMJ, Vol: 376, Pages: 1-3, ISSN: 1759-2151
Martinez FJ, Brochard L, Bush A, et al., 2022, Advancing Global Respiratory Health, Sleep, and Critical Care: Editorial from the New <i>American</i> <i>Journal of Respiratory and Critical Care Medicine Team</i>, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 205, Pages: I-II, ISSN: 1073-449X
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- Citations: 1
Badi Y, Pavel AB, Pavlidis S, et al., 2022, Mapping atopic dermatitis and anti–IL-22 response signatures to type 2–low severe neutrophilic asthma, Journal of Allergy and Clinical Immunology, Vol: 149, Pages: 89-101, ISSN: 0091-6749
Background:Transcriptomic changes in patients who respond clinically to biological therapies may identify responses in other tissues or diseases.Objective:We sought to determine whether a disease signature identified in atopic dermatitis (AD) is seen in adults with severe asthma and whether a transcriptomic signature for patients with AD who respond clinically to anti–IL-22 (fezakinumab [FZ]) is enriched in severe asthma.Methods:An AD disease signature was obtained from analysis of differentially expressed genes between AD lesional and nonlesional skin biopsies. Differentially expressed genes from lesional skin from therapeutic superresponders before and after 12 weeks of FZ treatment defined the FZ-response signature. Gene set variation analysis was used to produce enrichment scores of AD and FZ-response signatures in the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes asthma cohort.Results:The AD disease signature (112 upregulated genes) encompassing inflammatory, T-cell, TH2, and TH17/TH22 pathways was enriched in the blood and sputum of patients with asthma with increasing severity. Patients with asthma with sputum neutrophilia and mixed granulocyte phenotypes were the most enriched (P < .05). The FZ-response signature (296 downregulated genes) was enriched in asthmatic blood (P < .05) and particularly in neutrophilic and mixed granulocytic sputum (P < .05). These data were confirmed in sputum of the Airway Disease Endotyping for Personalized Therapeutics cohort. IL-22 mRNA across tissues did not correlate with FZ-response enrichment scores, but this response signature correlated with TH22/IL-22 pathways.Conclusions:The FZ-response signature in AD identifies severe neutrophilic asthmatic patients as potential responders to FZ therapy. This approach will help identify patients for future asthma clinical trials of drugs used successfully in other chronic diseases.
Edmondson C, Westrupp N, Seddon P, et al., 2022, The feasibility of home monitoring of young people with cystic fibrosis: results from CLIMB-CF, Journal of Cystic Fibrosis, Vol: 21, Pages: 70-77, ISSN: 1569-1993
BACKGROUND: CF is traditionally assessed in clinic. It is unclear if home monitoring of young people with CF is feasible or acceptable. The COVID-19 pandemic has made home monitoring more of a necessity. We report the results of CLIMB-CF, exploring home monitoring's feasibility and potential obstacles. METHODS: We designed a mobile app and enrolled participants with CF aged 2-17 years and their parents for six months. They were asked to complete a variety of measures either daily or twice a week. During the study, participants and their parents completed questionnaires exploring depression, anxiety and quality of life. At the end of the study parents and participants completed acceptability questionnaires. RESULTS: 148 participants were recruited, 4 withdrew prior to starting the study. 82 participants were female with median (IQR) age 7.9 (5.2-12 years). Median data completeness was 40.1% (13.6-69.9%) for the whole cohort; when assessed by age participants aged ≥ 12 years contributed significantly less (15.6% [9.8-30%]). Data completeness decreased over time. There was no significant difference between parental depression and anxiety scores at the start and the end of the study nor in CFQ-R respiratory domain scores for participants ≥ 14 years. The majority of participants did not feel the introduction of home monitoring impacted their daily lives. CONCLUSIONS: Most participants felt home monitoring did not negatively impact their lives and it did not increase depression, anxiety or decrease quality of life. However, uptake was variable, and not well sustained. The teenage years pose a particular challenge and further work is required.
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.
Ahmed B, Cox MJ, Cuthbertson L, et al., 2021, Comparison of the airway microbiota in children with chronic suppurative lung disease, BMJ Open Respiratory Research, Vol: 8, Pages: 1-10, ISSN: 2052-4439
Rationale:The airway microbiota is important in chronic suppurative lung diseases (CSLD), such as primary ciliary dyskinesia (PCD) and cystic fibrosis (CF). This comparison has not previously been described but is important because difference between the two diseases may relate to the differing prognoses and lead to pathological insights and potentially, new treatments. Objectives:To compare the longitudinal development of the airway microbiota in children with PCD to that of CF and relate this to age and clinical status. Methods:Sixty-two age-matched children (age range 0.5–17 years) with PCD or CF (n=31 in each group) were recruited prospectively and followed for 1.1 years. Throat swabs or sputum as well as clinical information were collected at routine clinical appointments. 16S rRNA gene sequencing was performed. Measurements and Main Results:The microbiota was highly individual and more diverse in PCD and differed in community composition when compared with CF. Whilst Streptococcus was the most abundant genus in both conditions, Pseudomonas was more abundant in CF with Haemophilus more abundant in PCD (Padj=0.0005). In PCD only, an inverse relationship was seen in the relative abundance of Streptococcus and Haemophilus with age. Conclusions:Bacterial community composition differs between children with PCD and those with CF. Pseudomonas is more prevalent in CF and Haemophilus in PCD, at least until infection with Pseudomonas supervenes. Interactions between organisms, particularly members of Haemophilus, Streptococcus, and Pseudomonas genera appear important. Study of the interactions between these organisms may lead to new therapies or risk stratification.
Mocelin HT, Fischer GB, Bush A, 2021, Adverse early-life environmental exposures and their repercussions on adult respiratory health, JORNAL DE PEDIATRIA, Vol: 98, Pages: S86-S95, ISSN: 0021-7557
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- Citations: 6
Makrinioti H, Bush A, Gern J, et al., 2021, The Role of Interferons in Driving Susceptibility to Asthma Following Bronchiolitis: Controversies and Research Gaps, FRONTIERS IN IMMUNOLOGY, Vol: 12, ISSN: 1664-3224
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- Citations: 5
Bush A, 2021, Impact of early life exposures on respiratory disease, PAEDIATRIC RESPIRATORY REVIEWS, Vol: 40, Pages: 24-32, ISSN: 1526-0542
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- Citations: 23
Bush A, Pavord ID, 2021, Forthcoming UK asthma guidelines: an opportunity to improve asthma outcomes, LANCET, Vol: 398, Pages: 1856-1858, ISSN: 0140-6736
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- Citations: 4
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
Baxter MS, Tibble H, Bush A, et al., 2021, Effectiveness of mobile health interventions to improve nasal corticosteroid adherence in allergic rhinitis: A systematic review, CLINICAL AND TRANSLATIONAL ALLERGY, Vol: 11
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- Citations: 4
De Simoni A, Fleming L, Holliday L, et al., 2021, Electronic reminders and rewards to improve adherence to inhaled asthma treatment in adolescents: a non-randomised feasibility study in tertiary care., BMJ Open, Vol: 11, Pages: 1-11, ISSN: 2044-6055
OBJECTIVE: To test the feasibility and acceptability of a short-term reminder and incentives intervention in adolescents with low adherence to asthma medications. METHODS: Mixed-methods feasibility study in a tertiary care clinic. Adolescents recruited to a 24-week programme with three 8-weekly visits, receiving electronic reminders to prompt inhaled corticosteroid (ICS) inhalation through a mobile app coupled with electronic monitoring devices (EMD). From the second visit, monetary incentives based on adherence of ICS inhalation: £1 per dose, maximum £2 /day, up to £112/study, collected as gift cards at the third visit. End of study interviews and questionnaires assessing perceptions of asthma and ICS, analysed using the Perceptions and Practicalities Framework. PARTICIPANTS: Adolescents (11-18 years) with documented low ICS adherence (<80% by EMD), and poor asthma control at the first clinic visit. RESULTS: 10 out of 12 adolescents approached were recruited (7 males, 3 females, 12-16 years). Eight participants provided adherence measures up to the fourth visits and received rewards. Mean study duration was 281 days, with 7/10 participants unable to attend their fourth visit due to COVID-19 lockdown. Only 3/10 participants managed to pair the app/EMD up to the fourth visit, which was associated with improved ICS adherence (from 0.51, SD 0.07 to 0.86, SD 0.05). Adherence did not change in adolescents unable to pair the app/EMD. The intervention was acceptable to participants and parents/guardians. Exit interviews showed that participants welcomed reminders and incentives, though expressed frustration with app/EMD technological difficulties. Participants stated the intervention helped through reminding ICS doses, promoting self-monitoring and increasing motivation to take inhalers. CONCLUSIONS: An intervention using electronic reminders and incentives through an app coupled with an EMD was feasible and acceptable to adolescents with asthma
Saglani S, Bingham Y, Balfour-Lynn I, et al., 2021, Blood eosinophils in managing preschool wheeze: lessons learnt from a proof-of-concept trial
<jats:p id="p1">Background: Management of preschool wheeze is based predominantly onsymptom pattern. Objective: To determine whether personalising therapyusing blood eosinophils or airway bacterial infection results in fewerattacks compared to standard care. Methods: A proof-of-concept,randomised trial to investigate whether prescription of inhaledcorticosteroids (ICS) guided by blood eosinophils, or targetedantibiotics for airway bacterial infection, results in fewer unscheduledhealthcare visits (UHCV) compared to standard care. Children aged 1-5years with >2 wheeze attacks in the previous year werecategorised as episodic viral wheeze (EVW), or multiple trigger wheeze(MTW). The intervention group were prescribed ICS if blood eosinophils>3%, or targeted antibiotics if positive culture oninduced sputum/cough swab. The control group received standard care.Primary outcome: UHCV at 4 months. Results: 60 children, median age 36.5(range 14-61) months were randomised. Median blood eosinophils were 5.2(range 0-21)%, 27/60 (45%) children were atopic and 8/60 (13%) hadairway bacterial infection. There was no relationship between EVW, MTWand either blood eosinophils, atopic status, or infection. 67% in eachgroup were prescribed ICS. 15/30 control subjects and 16/30 interventiongroup had UHCV over 4 months, p=0.8. Time to first UHCV was similar.50% returned adherence monitors, in those, median ICS adherence was67%. There were no differences in any parameter between those that didand did not have an UHCV. Conclusion: Clinical phenotype was unrelatedto allergen sensitisation or blood eosinophils. ICS treatment determinedby blood eosinophils did not impact UHCV, but ICS adherence was poor.</jats:p>
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