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

822 results found

Ahmed B, Cox MJ, Cuthbertson L, James PL, Cookson WOC, Davies JC, Moffatt MF, Bush Aet al., 2018, Comparison of the upper and lower airway microbiota in children with chronic lung diseases., PLoS One, Vol: 13

RATIONALE: The lower airway microbiota is important in normal immunological development and chronic lung diseases (CLDs). Young children cannot expectorate and because of the uncertainty whether upper airway samples reflect the lower airway microbiota, there have been few longitudinal paediatric studies to date. OBJECTIVES: To assess whether throat swabs (TS) and cough swabs (CS) are representative of the lower airway microbiota. METHODS: TS, CS, bronchoalveolar lavage and bronchial brushings were prospectively collected from 49 children undergoing fibreoptic bronchoscopy for CLDs. Bacterial DNA was extracted and the 16S rRNA gene V4 region sequenced using the Illumina MiSeq. RESULTS: 5.97 million high quality reads were obtained from 168 samples (47 TS, 37 CS, 42 BALF and 42 bronchial brushings). CS sequenced poorly. At a community level, no difference in alpha diversity (richness, evenness or Shannon Diversity Index) was seen between lower airway samples and TS (P > 0.05). Less than 6.31% of beta diversity variation related to sampling method for TS (P = 0.001). Variation between pathologies and individual patients was greater (20%, 54% respectively P ≤ 0.001) than between TS and lower airway samples. There was strong correlation in the relative abundance of genera between samples (r = 0.78, P < 0.001). Similarity between upper and lower airway samples was observed to be less for individuals where one sample type was dominated by a single organism. CONCLUSIONS: At the community structure level, TS correlate with lower airway samples and distinguish between different CLDs. TS may be a useful sample for the study of the differences in longitudinal changes in the respiratory microbiota between different CLDs. Differences are too great however for TS to be used for clinical decision making.

JOURNAL ARTICLE

Bardin EE, Cameron SJS, Perdones-Montero A, Hardiman K, Bolt F, Alton EWFW, Bush A, Davies JC, Takats Zet al., 2018, Metabolic Phenotyping and Strain Characterisation of Pseudomonas aeruginosa Isolates from Cystic Fibrosis Patients Using Rapid Evaporative Ionisation Mass Spectrometry, SCIENTIFIC REPORTS, Vol: 8, ISSN: 2045-2322

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Buelo A, McLean S, Julious S, Flores-Kim J, Bush A, Henderson J, Paton JY, Sheikh A, Shields M, Pinnock H, ARC Groupet al., 2018, At-risk children with asthma (ARC): a systematic review., Thorax

INTRODUCTION: Asthma attacks are responsible for considerable morbidity and may be fatal. We aimed to identify and weight risk factors for asthma attacks in children (5-12 years) in order to inform and prioritise care. METHODS: We systematically searched six databases (May 2016; updated with forward citations January 2017) with no language/date restrictions. Two reviewers independently selected studies for inclusion, assessed study quality and extracted data. Heterogeneity precluded meta-analysis. Weighting was undertaken by an Expert Panel who independently assessed each variable for degree of risk and confidence in the assessment (based on study quality and size, effect sizes, biological plausibility and consistency of results) and then achieved consensus by discussion. Assessments were finally presented, discussed and agreed at a multidisciplinary workshop. RESULTS: From 16 109 records, we included 68 papers (28 cohort; 4 case-control; 36 cross-sectional studies). Previous asthma attacks were associated with greatly increased risk of attack (ORs between 2.0 and 4.1). Persistent symptoms (ORs between 1.4 and 7.8) and poor access to care (ORs between 1.2 and 2.3) were associated with moderately/greatly increased risk. A moderately increased risk was associated with suboptimal drug regimen, comorbid atopic/allergic disease, African-American ethnicity (USA), poverty and vitamin D deficiency. Environmental tobacco smoke exposure, younger age, obesity and low parental education were associated with slightly increased risk. DISCUSSION: Assessment of the clinical and demographic features identified in this review may help clinicians to focus risk reduction management on the high-risk child. Population level factors may be used by health service planners and policymakers to target healthcare initiatives. TRIAL REGISTRATION NUMBER: CRD42016037464.

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Bush A, 2018, Low Lung Function in Young Adult Life Is Associated with Early Mortality, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 197, Pages: 538-539, ISSN: 1073-449X

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Bush A, 2018, Translating Asthma: Dissecting the Role of Metabolomics, Genomics and Personalized Medicine, INDIAN JOURNAL OF PEDIATRICS, Vol: 85, Pages: 643-650, ISSN: 0019-5456

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Bush A, 2018, A scandal in South Africa: And not just there!, PEDIATRIC PULMONOLOGY, Vol: 53, Pages: 698-700, ISSN: 8755-6863

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Bush A, 2018, Management of "asthma" in children., Minerva Pediatr

This manuscript takes an a challenging look at the management of asthma in childhood, in particular in the light of the recent Lancet commission. One of the central pillars of the Commission is the need to deliver personalised medicine for airway disease by deconstructing the airway into components of fixed and variable airflow obstruction, inflammation and infection. Before any treatment for asthma, a diagnostic workup is essential to exclude other conditions. A diagnosis of asthma needs to be based on objective evidence of bronchodilator sensitive variable airflow obstruction, eosinophilic airway inflammation and atopy. Most children with atopic asthma respond to low dose inhaled corticosteroids, sometimes requiring a long acting β-agonist. If the response is unsatisfactory, then, rather than escalate treatment, an approach for which there is little evidence, a full review of the child should be undertaken, including extrapulmonary comorbidities, adherence and adverse environmental influences. If these cannot or will not be addressed by the family, then further treatment including biologicals may be indicated. Asthma attacks are a serious warning sign and should always be taken seriously, including a focussed re-assessment of all aspects of the management of the child. Finally, pre-school children with wheeze can also be evaluated for eosinophilic airway inflammation using peripheral blood eosinophil count as a surrogate. It is essential that we start to deliver personalised medicine to children with airway disease.

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Bush A, 2018, What Sort of Asthma Do I Have?, Publisher: WILEY, Pages: S9-S11, ISSN: 8755-6863

CONFERENCE PAPER

Bush A, Pavord ID, 2018, 'We can't diagnose asthma until < insert arbitrary age >', ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 103, Pages: 729-731, ISSN: 0003-9888

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Bush A, Saglani S, 2018, Structurally Unsound? Why Airways Become Asthmatic., Am J Respir Cell Mol Biol

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Castro-Rodriguez JA, Saglani S, Rodriguez-Martinez CE, Oyarzun MA, Fleming L, Bush Aet al., 2018, The relationship between inflammation and remodeling in childhood asthma: A systematic review, PEDIATRIC PULMONOLOGY, Vol: 53, Pages: 824-835, ISSN: 8755-6863

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Dehlink E, Richardson C, Marsh G, Lee K, Jamalzadeh A, Bush A, Hogg C, Carr SBet al., 2018, Are inhaled corticosteroids prescribed rationally in primary ciliary dyskinesia?, EUROPEAN RESPIRATORY JOURNAL, Vol: 51, ISSN: 0903-1936

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Demenais F, Margaritte-Jeannin P, Barnes KC, Cookson WOC, Altmueller J, Ang W, Barr RG, Beaty TH, Becker AB, Beilby J, Bisgaard H, Bjornsdottir US, Bleecker E, Bonnelykke K, Boomsma DI, Bouzigon E, Brightling CE, Brossard M, Brusselle GG, Burchard E, Burkart KM, Bush A, Chan-Yeung M, Chung KF, Alves AC, Curtin JA, Custovic A, Daley D, de Jongste JC, Del-Rio-Navarro BE, Donohue KM, Duijts L, Eng C, Eriksson JG, Farrall M, Fedorova Y, Feenstra B, Ferreira MA, Freidin MB, Gajdos Z, Gauderman J, Gehring U, Geller F, Genuneit J, Gharib SA, Gilliland F, Granell R, Graves PE, Gudbjartsson DF, Haahtela T, Heckbert SR, Heederik D, Heinrich J, Heliovaara M, Henderson J, Himes BE, Hirose H, Hirschhorn JN, Hofman A, Holt P, Hottenga J, Hudson TJ, Hui J, Imboden M, Ivanov V, Jaddoe VWV, James A, Janson C, Jarvelin M-R, Jarvis D, Jones G, Jonsdottir I, Jousilahti P, Kabesch M, Kahonen M, Kantor DB, Karunas AS, Khusnutdinova E, Koppelman GH, Kozyrskyj AL, Kreiner E, Kubo M, Kumar R, Kumar A, Kuokkanen M, Lahousse L, Laitinen T, Laprise C, Lathrop M, Lau S, Lee Y-A, Lehtimaki T, Letort S, Levin AM, Li G, Liang L, Loehr LR, London SJ, Loth DW, Manichaikul A, Marenholz I, Martinez FJ, Matheson MC, Mathias RA, Matsumoto K, Mbarek H, McArdle WL, Melbye M, Melen E, Meyers D, Michel S, Mohamdi H, Musk AW, Myers RA, Nieuwenhuis MAE, Noguchi E, O'Connor GT, Ogorodova LM, Palmer CD, Palotie A, Park JE, Pennell CE, Pershagen G, Polonikov A, Postma DS, Probst-Hensch N, Puzyrev VP, Raby BA, Raitakari OT, Ramasamy A, Rich SS, Robertson CF, Romieu I, Salam MT, Salomaa V, Schlunssen V, Scott R, Selivanova PA, Sigsgaard T, Simpson A, Siroux V, Smith LJ, Solodilova M, Standl M, Stefansson K, Strachan DP, Stricker BH, Takahashi A, Thompson PJ, Thorleifsson G, Thorsteinsdottir U, Tiesler CMT, Torgerson DG, Tsunoda T, Uitterlinden AG, van der Valk RJP, Vaysse A, Vedantam S, von Berg A, von Mutius E, Vonk JM, Waage J, Wareham NJ, Weiss ST, White WB, Wickman M, Widen E, Willemsen G, Williams LK, Wouterset al., 2018, Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks, NATURE GENETICS, Vol: 50, Pages: 42-+, ISSN: 1061-4036

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Griese M, Seidl E, Hengst M, Reu S, Rock H, Anthony G, Kiper N, Emiralioglu N, Snijders D, Goldbeck L, Leidl R, Ley-Zaporozhan J, Krueger-Stollfuss I, Kammer B, Wesselak T, Eismann C, Schams A, Neuner D, MacLean M, Nicholson AG, Lauren M, Clement A, Epaud R, de Blic J, Ashworth M, Aurora P, Calder A, Wetzke M, Kappler M, Cunningham S, Schwerk N, Bush Aet al., 2018, International management platform for children's interstitial lung disease (chILD-EU), THORAX, Vol: 73, Pages: 231-239, ISSN: 0040-6376

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Hekking P-P, Loza MJ, Pavlidis S, de Meulder B, Lefaudeux D, Baribaud F, Auffray C, Wagener AH, Brinkman P, Lutter R, Bansal AT, Sousa AR, Bates SA, Pandis Y, Fleming LJ, Shaw DE, Fowler SJ, Guo Y, Meiser A, Sun K, Corfield J, Howarth PH, Bel EH, Adcock IM, Chung KF, Djukanovic R, Sterk PJet al., 2018, Pathway discovery using transcriptomic profiles in adult-onset severe asthma, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 141, Pages: 1280-1290, ISSN: 0091-6749

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Irving S, Dixon M, Fassad MR, Frost E, Hayward J, Kilpin K, Ollosson S, Onoufriadis A, Patel MP, Scully J, Carr SB, Mitchison HM, Loebinger MR, Hogg C, Shoemark A, Bush Aet al., 2018, Primary Ciliary Dyskinesia Due to Microtubular Defects is Associated with Worse Lung Clearance Index, LUNG, Vol: 196, Pages: 231-238, ISSN: 0341-2040

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Jevnikar Z, Östling J, Ax E, Calvén J, Thörn K, Israelsson E, Öberg L, Singhania A, Lau LCK, Wilson SJ, Ward JA, Chauhan A, Sousa AR, De Meulder B, Loza MJ, Baribaud F, Sterk PJ, Chung KF, Sun K, Guo Y, Adcock IM, Payne D, Dahlen B, Chanez P, Shaw DE, Krug N, Hohlfeld JM, Sandström T, Djukanovic R, James A, Hinks TSC, Howarth PH, Vaarala O, van Geest M, Olsson H, Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes study groupet al., 2018, Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation., J Allergy Clin Immunol

BACKGROUND: Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) to asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthmatic patients is unclear. OBJECTIVE: We sought to explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthmatic patients. METHODS: An IL-6TS gene signature obtained from air-liquid interface cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R was used to stratify lung epithelial transcriptomic data (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes [U-BIOPRED] cohorts) by means of hierarchical clustering. IL-6TS-specific protein markers were used to stratify sputum biomarker data (Wessex cohort). Molecular phenotyping was based on transcriptional profiling of epithelial brushings, pathway analysis, and immunohistochemical analysis of bronchial biopsy specimens. RESULTS: Activation of IL-6TS in air-liquid interface cultures reduced epithelial integrity and induced a specific gene signature enriched in genes associated with airway remodeling. The IL-6TS signature identified a subset of patients with IL-6TS-high asthma with increased epithelial expression of IL-6TS-inducible genes in the absence of systemic inflammation. The IL-6TS-high subset had an overrepresentation of frequent exacerbators, blood eosinophilia, and submucosal infiltration of T cells and macrophages. In bronchial brushings Toll-like receptor pathway genes were upregulated, whereas expression of cell junction genes was reduced. Sputum sIL-6R and IL-6 levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, matrix metalloproteinase 3, macrophage inflammatory protein 1β, IL-8, and IL-1β. CONCLUSIONS: Local lung epithelial IL-6TS activation in the absence of type 2 airway inflammation defines a novel subset of asthmatic patients and might drive airway inflamma

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Lenney W, Bush A, Fitzgerald DA, Fletcher M, Ostrem A, Pedersen S, Szefler SJ, Zar HJet al., 2018, Improving the global diagnosis and management of asthma in children, THORAX, Vol: 73, Pages: 662-669, ISSN: 0040-6376

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McKibben S, Bush A, Thomas M, Griffiths Cet al., 2018, "Tossing a coin:" defining the excessive use of short-acting beta(2)-agonists in asthma-the views of general practitioners and asthma experts in primary and secondary care, NPJ PRIMARY CARE RESPIRATORY MEDICINE, Vol: 28, ISSN: 2055-1010

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McKibben S, De Simoni A, Bush A, Thomas M, Griffiths Cet al., 2018, The use of electronic alerts in primary care computer systems to identify the excessive prescription of short-acting beta(2)-agonists for people with asthma: a systematic review, NPJ PRIMARY CARE RESPIRATORY MEDICINE, Vol: 28, ISSN: 2055-1010

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Nagakumar P, Gambir N, Sanghani N, Hall P, Jamalzadeh A, Beresford F, Saglani S, Bush A, Fleming Let al., 2018, Role of a prolonged inpatient admission when evaluating children with problematic severe asthma, EUROPEAN RESPIRATORY JOURNAL, Vol: 51, ISSN: 0903-1936

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Pavord ID, Beasley R, Agusti A, Anderson GP, Bel E, Brusselle G, Cullinan P, Custovic A, Ducharme FM, Fahy JV, Frey U, Gibson P, Heaney LG, Holt PG, Humbert M, Lloyd CM, Marks G, Martinez FD, Sly PD, von Mutius E, Wenzel S, Zar HJ, Bush Aet al., 2018, After asthma: redefining airways diseases, LANCET, Vol: 391, Pages: 350-400, ISSN: 0140-6736

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Pifferi M, Bush A, Rizzo M, Tonacci A, Di Cicco M, Piras M, Maggi F, Paiola G, Michelucci A, Cangiotti A, Peroni D, Caramella D, Boner ALet al., 2018, Olfactory dysfunction is worse in primary ciliary dyskinesia compared with other causes of chronic sinusitis in children., Thorax

Cilia have multiple functions including olfaction. We hypothesised that olfactory function could be impaired in primary ciliary dyskinesia (PCD). Olfaction, nasal nitric oxide (nNO) and sinus CT were assessed in patients with PCD and non-PCD sinus disease, and healthy controls (no CT scan). PCD and non-PCD patients had similar severity of sinus disease. Despite this, defective olfaction was more common in patients with PCD (P<0.0001) and more severe in patients with PCD with major Transmission Electron Microscopy (TEM) abnormalities. Only in classical PCD did olfaction inversely correlate with sinusitis and nNO. We speculate that defective olfaction in PCD is primary in nature.

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Shoemark A, Moya E, Hirst RA, Patel MP, Robson EA, Hayward J, Scully J, Fassad MR, Lamb W, Schmidts M, Dixon M, Patel-King RS, Rogers AV, Rutman A, Jackson CL, Goggin P, Rubbo B, Ollosson S, Carr S, Walker W, Adler B, Loebinger MR, Wilson R, Bush A, Williams H, Boustred C, Jenkins L, Sheridan E, Chung EMK, Watson CM, Cullup T, Lucas JS, Kenia P, O'Callaghan C, King SM, Hogg C, Mitchison HMet al., 2018, High prevalence of CCDC103 p.His154Pro mutation causing primary ciliary dyskinesia disrupts protein oligomerisation and is associated with normal diagnostic investigations, THORAX, Vol: 73, Pages: 157-166, ISSN: 0040-6376

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Simmonds NJ, Bush A, 2018, The Man in the Paper Mask: One (Mask) for All and All for . . . Cystic Fibrosis?, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 197, Pages: 281-283, ISSN: 1073-449X

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Thursfield RM, Naderi K, Leaver N, Rosenthal M, Alton EWFW, Bush A, Davies JCet al., 2018, Children with cystic fibrosis demonstrate no respiratory immunological, infective or physiological, consequences of vitamin D deficiency., J Cyst Fibros

BACKGROUND: Vitamin D has health benefits in many respiratory diseases but the evidence in CF is unclear. Induction of the antimicrobial peptides cathelicidin (LL37) and human-beta-defensin-2 (HBD-2) may be the mechanism of any benefit. We hypothesised that antimicrobial peptide levels would be decreased, and airway infection and inflammation greater, in CF children with vitamin D deficiency. The objective of the study was to explore relationships between vitamin D, LL37 and HBD-2, and airway infection, inflammation and physiology in children with CF. METHODS: Bronchoalveolar lavage (BALF) and blood were obtained from children undergoing fibreoptic bronchoscopy. Serum vitamin D, BALF HBD-2 and LL37, cultured bacteria and inflammatory markers were measured. Clinical parameters were recorded. RESULTS: 113 patients with CF, 23 with non-CF chronic suppurative lung disease (CSLD) and 6 healthy controls were included. We found no relationship between serum vitamin D and BALF HBD-2 or LL-37. There were no differences in infective or inflammatory markers between vitamin D sufficient and deficient groups. Vitamin D deficient patients (<50 nmol/L) did not have a worse FEV1 (CF: 66 (58-71)% vs. 71.5 (61-76)%, ns; non-CF CSLD: 69 (36-88)% vs. 70 (62-95)%, ns). CONCLUSIONS: In the first bronchoscopic study exploring this question, we demonstrate that vitamin D deficiency is not associated with immunological, infective or clinical markers of disease severity in patients with CF or CSLD.

JOURNAL ARTICLE

Trucco F, Chatwin M, Semple T, Rosenthal M, Bush A, Tan H-Let al., 2018, Sleep disordered breathing and ventilatory support in children with Down syndrome., Pediatr Pulmonol

STUDY OBJECTIVES: Obstructive sleep apnoea (OSAS) in children with Down syndrome (DS) is now well recognized, but other forms of sleep disordered breathing (SDB) in this population are less well described. Anecdotally, respiratory support for SDB treatment in this population is not easily tolerated. We aimed to characterize the types of SDB in children with DS referred to a tertiary respiratory center and to assess the effectiveness and adherence to respiratory support. METHODS: Retrospective study of DS patients <18 years old under follow-up at a tertiary respiratory center. Anthropometrics, comorbidities, sleep study results, and details of respiratory support were collected. Satisfactory adherence to oxygen (O2 ), Continuous Positive Airway Pressure (CPAP), or bilevel noninvasive ventilation (NIV) was defined as use >4 h/night for >50% nights. RESULTS: Sixty patients were included, median age 1.5 (0.7-5.3) years; 49 (82%) had congenital heart disease, 16 (27%) pulmonary hypertension, 28 (47%) gastroesophageal reflux, 38 (63%) swallowing impairment; 16/17 who underwent CT scanning had evidence of aspiration. Forty-two had SDB: 27 (61%) OSAS (10 mild, 5 moderate, 12 severe), 11 (25%) central apnoeas, 19 (32%) nocturnal hypoventilation. Twenty-six had baseline saturations <95%. Lower SpO2 correlated with pulmonary hypertension (r2  = 0.1, P = 0.04). Thirty-nine (65%) patients started respiratory support (14 O2 , 18 CPAP, 7 NIV) and 22 (56%) have regularly used it. After a 1.9 years follow up 11/24 had satisfactory adherence to CPAP/NIV (average use 8 h/night). CONCLUSIONS: Our results confirm the high prevalence of OSAS in children with DS. A significant number also have low baseline saturations, central apnoeas, and nocturnal hypoventilation. Contrary to popular belief, more than half of children with DS had satisfactory adherence to respiratory support.

JOURNAL ARTICLE

Turnbull AR, Murphy R, Behrends V, Lund-Palau H, Simbo A, Mariveles M, Alton EWFW, Bush A, Shoemark A, Davies JCet al., 2018, Impact of T2R38 Receptor Polymorphisms on Pseudomonas aeruginosa Infection in Cystic Fibrosis, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 197, Pages: 1635-1638, ISSN: 1073-449X

JOURNAL ARTICLE

Wright MFA, Bush A, Carr SB, 2018, Hypersensitivity reactions to intravenous antibiotics in cystic fibrosis., Paediatr Respir Rev

Hypersensitivity reactions to intravenous antibiotics are common in cystic fibrosis (CF). As well as causing immediate morbidity, the need for future avoidance of the causative antibiotic can have a long-term negative impact on CF management. This paper reviews the epidemiology and clinical presentation of hypersensitivity reactions in CF patients, and using an illustrative case describes a rare but severe form of delayed drug reaction for which a high index of suspicion is required.

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