Imperial College London

ProfessorAndrewBush

Faculty of MedicineNational Heart & Lung Institute

Professor of Paediatric Respirology
 
 
 
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Contact

 

+44 (0)20 7352 8121 ext 2255a.bush

 
 
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Location

 

Chelsea WingRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
to

1048 results found

Dobra R, Bentley S, Edmondson C, Ovens M, Saunders C, Short C, Wilson G, Davies JC, Bush Aet al., 2022, Going the Extra Mile: Why Clinical Research in Cystic Fibrosis Must Include Children, Children, Vol: 9, Pages: 1080-1080

<jats:p>This is an exciting time for research and novel drug development in cystic fibrosis. However, rarely has the adage, “Children are not just little adults” been more relevant. This article is divided into two main sections. In the first, we explore why it is important to involve children in research. We discuss the potential benefits of understanding a disease and its treatment in children, and we highlight that children have the same legal and ethical right to evidence-based therapy as adults. Additionally, we discuss why extrapolation from adults may be inappropriate, for example, medication pharmacokinetics may be different in children, and there may be unpredictable adverse effects. In the second part, we discuss how to involve children and their families in research. We outline the importance and the complexities of selecting appropriate outcome measures, and we discuss the role co-design may have in improving the involvement of children. We highlight the importance of appropriate staffing and resourcing, and we outline some of the common challenges and possible solutions, including practical tips on obtaining consent/assent in children and adolescents. We conclude that it is unethical to simply rely on extrapolation from adult studies because research in young children is challenging and that research should be seen as a normal part of the paediatric therapeutic journey.</jats:p>

Journal article

Stolting H, Baillon L, Frise R, Bonner K, Hewitt RJ, Molyneaux PL, Gore ML, Barclay WS, Saglani S, Lloyd CMet al., 2022, Distinct airway epithelial immune responses after infection with SARS-CoV-2 compared to H1N1, Mucosal Immunology, 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.

Journal article

Fowler S, Bhatt J, Brown S, Fleming L, Mayell S, Sinha I, Bush Aet al., 2022, E-cigarette company tactics in sports advertising., Lancet Respir Med, Vol: 10, Pages: 634-636

Journal article

Carlens J, Johnson KT, Bush A, Renz D, Hehr U, Laenger F, Hogg C, Wetzke M, Schwerk N, Rayment JHet al., 2022, Heterogenous Disease Course and Long-term Outcome of Children's Interstitial Lung Disease Related to Filamin A Gene Variants., Ann Am Thorac Soc

RATIONALE: Variable disease course and outcomes have been reported in Children's interstitial lung disease (ChILD) associated with Filamin A gene (FLNA) variants. OBJECTIVES: To further delineate long term respiratory outcomes and identify potential contributing factors to severe disease course. METHODS: We retrospectively collected longitudinal data from 3 centres on 9 cases (1 male) with FLNA variants and early respiratory disease onset (within the first 24 months of life). Clinical, radiographic, and histopathologic data were analyzed, focusing on cardiorespiratory disease course. RESULTS: All required early respiratory support (3 invasive ventilation, 3 non-invasive ventilation, 3 supplemental oxygen) and all experienced frequent severe infective respiratory exacerbations. Three died in infancy from refractory respiratory failure and pulmonary hypertension (PH). The 6 surviving individuals were 3, 10, 11, 15, 18, and 33 years old at time of reporting. The extent of functional respiratory impairment decreased with age; at last follow-up there were no individuals on home invasive ventilation, 1 on nocturnal non-invasive ventilation, 4 on oxygen, and 1 on no respiratory support. Spirometry consistently demonstrated moderate to severe obstructive defects (forced expiratory volume over 1 second/ forced vital capacity (FEV1/FVC) Z score -3.76 to -1.77), percent predicted FVC 31.5 to 92.1 %. Seven required PH treatment in early childhood (7/9) and 3 of the survivors (3/6) still receive treatment. Radiologic and histopathologic findings were consistent between cases. CONCLUSION: Early mortality was common, but many survivors stabilized even after severe symptoms in infancy. All survivors had persistent obstructive defects on spirometry and half have persistent or recurrent PH. These typical findings are suggestive of this rare diagnosis and should prompt consideration of genetic testing.

Journal article

Barclay M, Buderi S, Bush A, Daniel M, Jordan S, Rice A, Ruggins N, Semple T, Smyth ARet al., 2022, Wheeze in the time of COVID-19: overcoming obstacles to an unusual diagnosis, THORAX, ISSN: 0040-6376

Journal article

Pifferi M, Boner AL, Gracci S, Fonnesu R, Maj D, Donzelli G, Michelucci A, Cangiotti A, Bertini V, Valetto A, Caligo MA, Miccoli M, Peroni D, Bush Aet al., 2022, Longitudinal nitric oxide levels and infections by ultrastructure and genotype in primary ciliary dyskinesia., Chest

BACKGROUND: We hypothesized that differences in nasal and fractional exhaled nitric oxide (nNO and FeNO respectively) relate to prognosis in primary ciliary dyskinesia (PCD). RESEARCH QUESTION: What is the relationship between baseline values and longitudinal evolution of nNO and FeNO and ultrastructure, genotype and respiratory infections in PCD? STUDY DESIGN AND METHODS: Prospective, longitudinal, single-center study in adults and children evaluated biannually for up to 10 years. We compared cross-sectional and longitudinal values of nNO and FeNO in ultrastructural (IDA/MTD) and genetic (CCDC39/CCDC40) groups, known to have worse pulmonary function with patients within the ultrastructural and genetic groups with a better prognosis. Linear mixed effects models were used to evaluate longitudinal associations. MEASUREMENTS AND MAIN RESULTS: 141 PCD patients had 1014 visits. At enrollment, in children there were no differences in nNO or FeNO between the IDA/MTD and the other ultrastructural groups. In adults nNO (p=0.038) and FeNO (p=0.032) were significantly lower in IDA/MTD than in all other combined ultrastructural groups. FeNO values were significantly lower in CCDC39/CCDC40 than DNAH5 and DNAH11 combined genotypes (p=0.033), and all other genotypes (p=0.032). IDA/MTD had a significant decline in nNO with age (p<0.01) compared with other ultrastructural groups who had stable levels. CCDC39/CCDC40 had the steepest decline in nNO over time (p<0.01) compared with all other genotypes. A higher nNO was associated with lower likelihood of any positive bacterial isolate from the lower respiratory tract (p=0.008). Changes in FeNO over time did not differ between structural groups or genotypes. INTERPRETATION: Lower nNO in PCD patients with genetic and ultrastructural changes associated with greater lung function decline may be related to worse prognosis, but whether a low nNO is causal needs further study. If lower nNO directly results in a poorer prognosis, strateg

Journal article

Chatziparasidis G, Bush A, 2022, Enigma variations: The multi-faceted problems of pre-school wheeze, PEDIATRIC PULMONOLOGY, ISSN: 8755-6863

Journal article

Bush A, 2022, How to Choose the Correct Drug in Severe Pediatric Asthma, FRONTIERS IN PEDIATRICS, Vol: 10, ISSN: 2296-2360

Journal article

Bush A, 2022, Transition to Adult Care: What adults should know about Pediatric Respiratory Diseases, Publisher: WILEY, Pages: S22-S24, ISSN: 8755-6863

Conference paper

Kotecha S, Doull I, Wild J, Bush Aet al., 2022, Prematurity-associated lung disease: looking beyond bronchopulmonary dysplasia., Lancet Respir Med, Vol: 10

Journal article

Aurora P, Duncan JA, Lum S, Davies G, Wade A, Stocks J, Viviani L, Raywood E, Pao C, Ruiz G, Bush A, London Cystic Fibrosis Collaboration LCFCet al., 2022, Early Pseudomonas aeruginosa predicts poorer pulmonary function in preschool children with cystic fibrosis., J Cyst Fibros

BACKGROUND: We previously reported relatively normal pulmonary function (2 years of age) and computed tomography (CT, 1 year of age) in cystic fibrosis (CF) newborn screened (NBS) infants. We now report follow up of these children to preschool age. METHODS: 67 NBS children with CF and 41 healthy controls underwent pulmonary function tests in infancy (∼3 months, 1 year and 2 years) and at preschool (3-6 years). Broncho-alveolar lavage (BAL) and CT were undertaken in those with CF at 1 year. Primary outcomes at preschool were lung clearance index (LCI) and forced expired volume (FEV0.75). Risk factors for lung function impairment were identified by regression modelling, emphasising factors that could be identified or measured in the first 2 years of life. RESULTS: At preschool age children with CF had poorer lung function than controls, mean(95% CI) difference in LCI z-score: 1.47(0.96;1.97) and FEV0.75 z-score -0.54(-0.98; -0.10). Isolation of Pseudomonas aeruginosa before 6 months was a highly significant predictor of raised (abnormal) preschool LCI, associated with a mean (95%CI) increase of 1.69(0.43, 2.95) z-scores, compared to those with no Pseudomonas aeruginosa during the first 2 years of life. Including 2 year LCI and 1 year CT data in the predictive model increased the r2 from 13% to 61%. CONCLUSIONS: Lung function deteriorates after 2 years in NBS children with CF. Isolation of Pseudomonas aeruginosa before 6 months and minor abnormalities of infant lung function tests and CT in infancy are associated with higher preschool LCI.

Journal article

Irving S, Bayfield K, Davies JC, Bush Aet 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.

Journal article

Bush A, Pabary R, 2022, Grappling with the granuloma: where is the ACE in the hole?, Thorax, Vol: 77, Pages: 320-321

Journal article

Bush A, Pavord ID, 2022, Reply to: Challenging the paradigm, BREATHE, Vol: 18, ISSN: 1810-6838

Journal article

Makrinioti H, Hasegawa K, Lakoumentas J, Xepapadaki P, Tsolia M, Castro-Rodriguez JA, Feleszko W, Jartti T, Johnston SL, Bush A, Papaevangelou V, Camargo CA, Papadopoulos NGet 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

Journal article

Mocelin HT, Fischer GB, Bush A, 2022, Adverse early-life environmental exposures and their repercussions on adult respiratory health, JORNAL DE PEDIATRIA, Vol: 98, Pages: S86-S95, ISSN: 0021-7557

Journal article

Nichols A-L, Sonnappa-Naik M, Gardner L, Richardson C, Orr N, Jamalzadeh A, Moore-Crouch R, Makhecha S, Wells C, Hall P, Bush A, Fleming L, Saglani S, Sonnappa Set al., 2022, COVID-19 and delivery of difficult asthma services, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 107, ISSN: 0003-9888

Journal article

Pearce CJ, Chan AHY, Jackson T, Fleming L, Foot H, Bush A, Horne Ret 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

Journal article

Pattaroni C, Macowan M, Chatzis R, Daunt C, Custovic A, Shields MD, Power UF, Grigg J, Roberts G, Ghazal P, Schwarze J, Gore M, Turner S, Bush A, Saglani S, Lloyd C, Marsland BJet 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.

Journal article

Levina D, Leontjeva M, Abbasova N, Petrova Y, Bitieva R, Erdes SI, Aminova AI, Nurtazina A, Blyuss B, Pikuza M, Avdeenko NV, Gadetskaya S, Ivanova YV, Saglani S, Bush A, Munblit Det 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

Journal article

Mikus MS, Kolmert J, Andersson L, Ostling J, Knowles RG, Gomez C, Ericsson M, Thorngren J-O, Khoonsari PE, Dahlen B, Kupczyk M, De Meulder B, Auffray C, Bakke PS, Beghe B, Bel EH, Caruso M, Chanez P, Chawes B, Fowler SJ, Gaga M, Geiser T, Gjomarkaj M, Horvath I, Howarth PH, Johnston SL, Joos G, Krug N, Montuschi P, Musial J, Nizankowska-Mogilnicka E, Olsson HK, Papi A, Rabe KF, Sandstrom T, Shaw DE, Siafakas NM, Uhlen M, Riley JH, Bates S, Middelveld RJM, Wheelock CE, Chung KF, Adcock IM, Sterk PJ, Djukanovic R, Nilsson P, Dahlen S-E, James Aet al., 2022, Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation, EUROPEAN RESPIRATORY JOURNAL, Vol: 59, ISSN: 0903-1936

Journal article

Bush A, Fitzpatrick AM, Saglani S, Anderson WC, Szefler SJet 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

Journal article

Bush A, 2022, Giving a voice to the voiceless: end of life second opinions, ARCHIVES OF DISEASE IN CHILDHOOD, ISSN: 0003-9888

Journal article

Paraskakis E, Sarikloglou E, Fouzas S, Steiropoulos P, Tsalkidis A, Bush Aet al., 2022, Improved prediction of asthma exacerbations by measuring distal airway inflammation., Eur Respir J

Journal article

Hopkinson NS, Vestbo J, Bush A, Grigg Jet al., 2022, Should e-cigarettes be licensed as medicines?, BMJ, Vol: 376, Pages: 1-3, ISSN: 1759-2151

Journal article

Martinez FJ, Brochard L, Bush A, Donaldson G, Han MKet al., 2022, Advancing Global Respiratory Health, Sleep, and Critical Care: Editorial from the New American Journal of Respiratory and Critical Care Medicine Team, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 205, Pages: I-II, ISSN: 1073-449X

Journal article

Edmondson C, Westrupp N, Seddon P, Olden C, Wallis C, Dawson C, Brodlie M, Baxter F, McCormick J, MacFarlane S, Rice D, Macleod A, Brooker R, Connon M, Ghayyda S, Blaikie L, Thursfield R, Brown L, Price A, Fleischer E, Itterman J, Hughes D, Barrett P, Surette M, Donnelly C, Mateos-Corral D, Padley G, Wallenburg J, Brownlee K, Alton EWFW, Bush A, Davies JCet 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.

Journal article

Saglani S, Bingham Y, Balfour-Lynn I, Goldring S, Gupta A, Banya W, Moreiras J, Fleming L, Bush A, Rosenthal Met 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.

Journal article

Ahmed B, Cox MJ, Cuthbertson L, James P, Gardner L, Cookson W, Davies J, Moffatt M, Bush Aet 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.

Journal article

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