Imperial College London

ProfessorAdnanCustovic

Faculty of MedicineNational Heart & Lung Institute

Professor of Paediatric Allergy
 
 
 
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220Medical SchoolSt Mary's Campus

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Publications

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576 results found

Vogelezang S, Bradfield JP, Ahluwalia TS, Curtin JA, Lakka TA, Grarup N, Scholz M, van der Most PJ, Monnereau C, Stergiakouli E, Heiskala A, Horikoshi M, Fedko IO, Vilor-Tejedor N, Cousminer DL, Standl M, Wang CA, Viikari J, Geller F, Íñiguez C, Pitkänen N, Chesi A, Bacelis J, Yengo L, Torrent M, Ntalla I, Helgeland Ø, Selzam S, Vonk JM, Zafarmand MH, Heude B, Farooqi IS, Alyass A, Beaumont RN, Have CT, Rzehak P, Bilbao JR, Schnurr TM, Barroso I, Bønnelykke K, Beilin LJ, Carstensen L, Charles M-A, Chawes B, Clément K, Closa-Monasterolo R, Custovic A, Eriksson JG, Escribano J, Groen-Blokhuis M, Grote V, Gruszfeld D, Hakonarson H, Hansen T, Hattersley AT, Hollensted M, Hottenga J-J, Hyppönen E, Johansson S, Joro R, Kähönen M, Karhunen V, Kiess W, Knight BA, Koletzko B, Kühnapfel A, Landgraf K, Langhendries J-P, Lehtimäki T, Leinonen JT, Li A, Lindi V, Lowry E, Bustamante M, Medina-Gomez C, Melbye M, Michaelsen KF, Morgen CS, Mori TA, Nielsen TRH, Niinikoski H, Oldehinkel AJ, Pahkala K, Panoutsopoulou K, Pedersen O, Pennell CE, Power C, Reijneveld SA, Rivadeneira F, Simpson A, Sly PD, Stokholm J, Teo KK, Thiering E, Timpson NJ, Uitterlinden AG, van Beijsterveldt CEM, van Schaik BDC, Vaudel M, Verduci E, Vinding RK, Vogel M, Zeggini E, Sebert S, Lind MV, Brown CD, Santa-Marina L, Reischl E, Frithioff-Bøjsøe C, Meyre D, Wheeler E, Ong K, Nohr EA, Vrijkotte TGM, Koppelman GH, Plomin R, Njølstad PR, Dedoussis GD, Froguel P, Sørensen TIA, Jacobsson B, Freathy RM, Zemel BS, Raitakari O, Vrijheid M, Feenstra B, Lyytikäinen L-P, Snieder H, Kirsten H, Holt PG, Heinrich J, Widén E, Sunyer J, Boomsma DI, Järvelin M-R, Körner A, Davey Smith G, Holm J-C, Atalay M, Murray C, Bisgaard H, McCarthy MI, Early Growth Genetics Consortium, Jaddoe VWV, Grant SFA, Felix JFet al., 2020, Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits., PLoS Genet, Vol: 16

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.

Journal article

Jahić R, Porobić-Jahić H, Žepić D, Piljić D, Petrović J, Čustović Aet al., 2020, Knowledge, attitude and stigma towards HIV patients: a survey among medical students in Tuzla, Bosnia and Herzegovina., J Infect Dev Ctries, Vol: 14, Pages: 1019-1026

INTRODUCTION: This survey aims to assess knowledge, attitude and stigma towards HIV patients, among medical students in Tuzla, Bosnia and Herzegovina. We also aimed to assess potential risk factors for HIV infection among fourth year medical students. METHODOLOGY: Data were collected from specific questionnaire that was completed by 171 students of the Faculty of Medicine, University of Tuzla. A multivariable logistic regression was performed. RESULTS: Majority of students (79%) had a good knowledge of HIV, (median value of correct answers was 9 (95%) with at least 6 correct responses). Also, majority of students (73.6%) had a positive attitude towards HIV patients and the median positive value was 6 (95% CI: 6-7). More than a third of students considered that all hospitalized patients should be tested for HIV. Total of 81% of students considered that they should inform the sexual partner of HIV positive patient, although she/he disagrees. 61.4% of students had a discriminatory attitude towards HIV, with the median values of 3 (95% CI: 3-3). Multivariate regression analysis identified positive attitude towards HIV patients as an independent predictor for a non-discriminatory attitude. Moreover, an overall attitude towards HIV patients defines student`s determination to work with AIDS population. Male gender, and older age, were identified as predictors of risky behavior. CONCLUSIONS: Preventive measures, including better HIV education, are crucial. Knowledge can increase awareness of HIV infection, decrease the incidence and reduce stigma towards HIV patients.

Journal article

Custovic A, Custovic D, Kljaic Bukvic B, Fontanella S, Haider Set al., 2020, Atopic phenotypes and their implication in the atopic march, EXPERT REVIEW OF CLINICAL IMMUNOLOGY, ISSN: 1744-666X

Journal article

Incorvaia C, Al-Ahmad M, Ansotegui I, Arasi S, Bachert C, Bos C, Bousquet J, Bozek A, Caimmi D, Calderón M, Casale T, Custovic A, De Blay F, Demoly P, Devillier P, Didier A, Fiocchi A, Fox A, Gevaert P, Gomez M, Heffler E, Ilina N, Irani C, Jutel M, Karagiannis E, Klimek L, Kuna P, O'Hehir R, Kurbacheva O, Matricardi PM, Morais de Almeida M, Mosges R, Novak N, Okamoto Y, Panzner P, Papadopoulos N, Park H-S, Passalacqua G, Pawankar R, Pfaar O, Schmid-Grendelmeier P, Scurati S, Tortajada-Girbés M, Vidal C, Virchow C, Wahn U, Worm M, Zieglmayer P, Canonica GWet al., 2020, Personalized Medicine for allergy treatment: allergen immunotherapy still a unique and unmatched model., Allergy

The introduction of personalized medicine (PM) has been a milestone in the history of medical therapy, because it has revolutionized the previous approach of treating the disease with that of treating the patient. It is known today that diseases can occur in different genetic variants, making specific treatments of proven efficacy necessary for a given endotype. Allergic diseases are particularly suitable for PM, because they meet the therapeutic success requirements, including a known molecular mechanism of the disease, a diagnostic tool for such disease, and a treatment blocking the mechanism. The stakes of PM in allergic patients are molecular diagnostics, to detect specific IgE to single allergen molecules and to distinguish the causative molecules from those merely cross-reactive, pursuit of patient's treatable traits addressing genetic, phenotypic and psychosocial features, and omics, such as proteomics, epi-genomics, metabolomics and breathomics, to forecast patient's responsiveness to therapies, to detect biomarker and mediators, and verify the disease control. This new approach has already improved the precision of allergy diagnosis and is likely to significantly increase, through the higher performance achieved with the personalized treatment, the effectiveness of allergen immunotherapy by enhancing its already known and unique characteristics of treatment that acts on the causes.

Journal article

Custovic A, 2020, "Asthma" or "Asthma Spectrum Disorder"?, J Allergy Clin Immunol Pract, Vol: 8, Pages: 2628-2629

Journal article

Papadopoulos NG, Custovic A, Deschildre A, Mathioudakis AG, Phipatanakul W, Wong G, Xepapadaki P, Agache I, Bacharier L, Bonini M, Castro-Rodriguez JA, Chen Z, Craig T, Ducharme FM, El-Sayed ZA, Feleszko W, Fiocchi A, Garcia-Marcos L, Gern JE, Goh A, Gómez RM, Hamelmann EH, Hedlin G, Hossny EM, Jartti T, Kalayci O, Kaplan A, Konradsen J, Kuna P, Lau S, Le Souef P, Lemanske RF, Mäkelä MJ, Morais-Almeida M, Murray C, Nagaraju K, Namazova-Baranova L, Garcia AN, Yusuf OM, Pitrez PMC, Pohunek P, Pozo Beltrán CF, Roberts GC, Valiulis A, Zar HJ, Pediatric Asthma in Real Life Collaboratorset al., 2020, Impact of COVID-19 on pediatric asthma: practice adjustments and disease burden., Journal of Allergy and Clinical Immunology: In Practice, Vol: 8, Pages: 2592-2599.e3, ISSN: 2213-2198

BACKGROUND: It is unclear whether asthma may affect susceptibility or severity of coronavirus disease 2019 (COVID-19) in children and how pediatric asthma services worldwide have responded to the pandemic. OBJECTIVE: To describe the impact of the COVID-19 pandemic on pediatric asthma services and on disease burden in their patients. METHODS: An online survey was sent to members of the Pediatric Asthma in Real Life think tank and the World Allergy Organization Pediatric Asthma Committee. It included questions on service provision, disease burden, and the clinical course of confirmed cases of COVID-19 infection among children with asthma. RESULTS: Ninety-one respondents, caring for an estimated population of more than 133,000 children with asthma, completed the survey. COVID-19 significantly impacted pediatric asthma services: 39% ceased physical appointments, 47% stopped accepting new patients, and 75% limited patients' visits. Consultations were almost halved to a median of 20 (interquartile range, 10-25) patients per week. Virtual clinics and helplines were launched in most centers. Better than expected disease control was reported in 20% (10%-40%) of patients, whereas control was negatively affected in only 10% (7.5%-12.5%). Adherence also appeared to increase. Only 15 confirmed cases of COVID-19 were reported among the population; the estimated incidence is not apparently different from the reports of general pediatric cohorts. CONCLUSIONS: Children with asthma do not appear to be disproportionately affected by COVID-19. Outcomes may even have improved, possibly through increased adherence and/or reduced exposures. Clinical services have rapidly responded to the pandemic by limiting and replacing physical appointments with virtual encounters.

Journal article

Holt PG, Strickland DH, Custovic A, 2020, Targeting maternal immune function during pregnancy for asthma prevention in offspring: Harnessing the "farm effect"?, Journal of Allergy and Clinical Immunology, Vol: 146, Pages: 270-272, ISSN: 0091-6749

Journal article

Saglani S, Wisnivesky JP, Charokopos A, Pascoe CD, Halayko AJ, Custovic Aet 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.

Journal article

Bédard A, Antó JM, Fonseca JA, Arnavielhe S, Bachert C, Bedbrook A, Bindslev-Jensen C, Bosnic-Anticevich S, Cardona V, Cruz AA, Fokkens WJ, Garcia-Aymerich J, Hellings PW, Ivancevich JC, Klimek L, Kuna P, Kvedariene V, Larenas-Linnemann D, Melén E, Monti R, Mösges R, Mullol J, Papadopoulos NG, Pham-Thi N, Samolinski B, Tomazic PV, Toppila-Salmi S, Ventura MT, Yorgancioglu A, Bousquet J, Pfaar O, Basagaña X, MASK study groupet al., 2020, Correlation between work impairment, scores of rhinitis severity and asthma using the MASK-air® App, Allergy, Vol: 75, Pages: 1672-1688, ISSN: 0105-4538

BACKGROUND: In allergic rhinitis, a relevant outcome providing information on the effectiveness of interventions is needed. In MASK-air (Mobile Airways Sentinel Network), a visual analogue scale (VAS) for work is used as a relevant outcome. This study aimed to assess the performance of the work VAS work by comparing VAS work with other VAS measurements and symptom-medication scores obtained concurrently. METHODS: All consecutive MASK-air users in 23 countries from 1 June 2016 to 31 October 2018 were included (14 189 users; 205 904 days). Geolocalized users self-assessed daily symptom control using the touchscreen functionality on their smart phone to click on VAS scores (ranging from 0 to 100) for overall symptoms (global), nose, eyes, asthma and work. Two symptom-medication scores were used: the modified EAACI CSMS score and the MASK control score for rhinitis. To assess data quality, the intra-individual response variability (IRV) index was calculated. RESULTS: A strong correlation was observed between VAS work and other VAS. The highest levels for correlation with VAS work and variance explained in VAS work were found with VAS global, followed by VAS nose, eye and asthma. In comparison with VAS global, the mCSMS and MASK control score showed a lower correlation with VAS work. Results are unlikely to be explained by a low quality of data arising from repeated VAS measures. CONCLUSIONS: VAS work correlates with other outcomes (VAS global, nose, eye and asthma) but less well with a symptom-medication score. VAS work should be considered as a potentially useful AR outcome in intervention studies.

Journal article

Zuiani C, Custovic A, 2020, Update on house dust mite allergen avoidance measures for asthma, Current Allergy and Asthma Reports, Vol: 20, Pages: 1-8, ISSN: 1529-7322

Purpose of ReviewTo critically review the evidence in favor or against the use of house dust mite (HDM) allergen avoidance measures in patients with asthma.Recent FindingsSystematic reviews and meta-analyses suggested no positive effect of mite allergen avoidance strategies on asthma outcomes, resulting in a lack of consensus regarding the utility of these measures. However, such analyses have a number limitations and might not be the most adequate tool to evaluate current evidence and to derive clinical recommendations regarding mite allergen avoidance in asthmatic patients. We should not disproportionately rely on the results of meta-analyses and systematic reviews to inform clinical practice and asthma guidelines in this area. Recent high-quality evidence from randomized controlled trial in children confirmed that mite allergen–impermeable bed encasings reduce emergency hospital attendance with acute severe asthma exacerbations.SummaryUntil better evidence is available, we suggest that physicians should adopt a pragmatic approach to mite allergen avoidance and advise sensitized patients to implement a multifaceted set of measures to achieve as great a reduction in exposure as possible. Potential predictors of positive response (e.g., patient’s sensitization and exposure status) can pragmatically be evaluated using the size of skin test wheal or the titer of allergen-specific IgE. Finally, the intervention should be started as early as possible.

Journal article

Bousquet J, Anto JM, Bachert C, Haahtela T, Zuberbier T, Czarlewski W, Bedbrook A, Bosnic-Anticevich S, Walter Canonica G, Cardona V, ElisioCosta, Cruz AA, Erhola M, Fokkens WJ, Fonseca JA, Illario M, CarlosIvancevich J, Jutel M, Klimek L, PiotrKuna, Kvedariene V, Le L, Larenas-Linnemann D, Laune D, Lourenço OM, Melén E, Mullol J, Niedoszytko M, Odemyr M, Okamoto Y, Papadopoulos NG, Patella V, Pfaar O, Pham-Thi N, Rolland C, Samolinski B, Sheikh A, Sofiev M, SuppliUlrik C, Todo-Bom A, Tomazic PV, Toppila-Salmi S, Tsiligianni I, Valiulis A, Valovirta E, Ventura M-T, Walker S, Williams S, Yorgancioglu A, Agache I, Akdis CA, Almeida R, Ansotegui IJ, Annesi-Maesano I, Arnavielhe S, Basagaña X, Bateman E, Bédard A, Bedolla-Barajas M, Becker S, Bennoor KS, Benveniste S, Bergmann KC, Bewick M, Bialek S, Billo N, Bindslev-Jensen C, Bjermer L, Blain H, Bonini M, Bonniaud P, Bosse I, Bouchard J, Boulet LP, Bourret R, Boussery K, Braido F, Briedis V, Briggs A, Brightling CE, JanBrozek, Brusselle G, Brussino L, Buhl R, Buonaiuto R, Calderon MA, Camargos P, Camuzat T, Caraballo L, Carriazo AM, Carr W, Cartier C, Casale T, Cecchi L, Cepeda Sarabia AM, Chavannes N, Chkhartishvili E, Chu DK, Cingi C, Correia de Sousa J, Costa DJ, Courbis AL, Custovic A, Cvetkosvki B, D'Amato G, da Silva J, Dantas C, Dokic D, Dauvilliers Y, De Feo G, De Vries G, Devillier P, Di Capua S, Dray G, Dubakiene R, Durham SR, Dykewicz M, Ebisawa M, Gaga M, El-Gamal Y, Heffler E, Emuzyte R, Farrell J, Fauquert J-L, Fiocchi A, Fink-Wagner A, Fontaine J-F, Fuentes Perez JM, Gemicioğlu B, Gamkrelidze A, Garcia-Aymerich J, Gevaert P, Gomez M, González Diaz S, Gotua M, Guldemond NA, Guzmán M-A, Hajjam J, Huerta Villalobos YR, Humbert M, Iaccarino G, Ierodiakonou D, TomohisaIinuma, Jassem E, Joos G, Jung K-S, Kaidashev I, Kalayci O, Kardas P, Keil T, Khaitov M, Khaltaev N, Kleine-Tebbe J, Kouznetsov R, Kowalski ML, Kritikos V, Kull I, La Grutta S, Leonardini L, Ljungberg H, Lieberman P, Lipworth B, Lodrup Carlet al., 2020, ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice., Allergy, ISSN: 0105-4538

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis.It strengthens the ARIA change management strategy in the prevention and managementof airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.

Journal article

Thyssen JP, Ahluwalia TS, Paternoster L, Ballardini N, Bergstrom A, Melen E, Chawes BL, Stokholm J, Hourihane JO, O'Sullivan DM, Bager P, Melbye M, Bustamante M, Torrent M, Esplugues A, Duijts L, Hu C, Elbert NJ, Pasmans SGMA, Nijsten TEC, Von Berg A, Standl M, Schikowski T, Herberth G, Heinrich J, Lee Y-A, Marenholz I, Lau S, Curtin JA, Simpson A, Custovic A, Pennell CE, Wang CA, Holt PG, Bisgaard H, Bonnelykke Ket al., 2020, Interaction between filaggrin mutations and neonatal cat exposure in atopic dermatitis, Allergy, Vol: 75, Pages: 1481-1485, ISSN: 0105-4538

Journal article

Mathioudakis AG, Custovic A, Deschildre A, Ducharme FM, Kalayci O, Murray C, Garcia AN, Phipatanakul W, Price D, Sheikh A, Agache I, Bacharier L, Bonini M, Castro-Rodriguez JA, De Carlo G, Craig T, Diamant Z, Feleszko W, Ierodiakonou D, Gern JE, Grigg J, Hedlin G, Hossny EM, Jartti T, Kaplan A, Lemanske RF, Le Souef P, Makela MJ, Matricardi PM, Miligkos M, Morais-Almeida M, Pite H, Pitrez PMC, Pohunek P, Roberts G, Sanchez-Garcia S, Tsiligianni I, Turner S, Winders TA, Wong G, Xepapadaki P, Zar HJ, Papadopoulos NGet al., 2020, Research priorities in pediatric asthma: results of a global survey of multiple stakeholder groups by the Pediatric Asthma in Real Life (PeARL) Think Tank, Journal of Allergy and Clinical Immunology: In Practice, Vol: 8, Pages: 1953-1960.e9, ISSN: 2213-2198

BACKGROUND: Pediatric asthma remains a public health challenge with enormous impact worldwide. OBJECTIVE: The aim of this study was to identify and prioritize unmet clinical needs in pediatric asthma, which could be used to guide future research and policy activities. METHODS: We first identified unmet needs through an open-question survey administered to international experts in pediatric asthma who were members of the Pediatric Asthma in Real Life Think Tank. Prioritization of topics was then achieved through a second, extensive survey with global reach, of multiple stakeholders (leading experts, researchers, clinicians, patients, policy makers, and the pharmaceutical industry). Differences across responder groups were compared. RESULTS: A total of 57 unmet clinical need topics identified by international experts were prioritized by 412 participants from 5 continents and 60 countries. Prevention of disease progression and prediction of future risk, including persistence into adulthood, emerged as the most urgent research questions. Stratified care, based on biomarkers, clinical phenotypes, the children's age, and demographics were also highly rated. The identification of minimum diagnostic criteria in different age groups, cultural perceptions of asthma, and best treatment by age group were priorities for responders from low-middle-income countries. There was good agreement across different stakeholder groups in all domains with some notable exceptions that highlight the importance of involving the whole range of stakeholders in formulation of recommendations. CONCLUSIONS: Different stakeholders agree in the majority of research and strategic (eg, prevention, personalized approach) priorities for pediatric asthma. Stakeholder diversity is crucial for highlighting divergent issues that future guidelines should consider.

Journal article

Niespodziana K, Borochova K, Pazderova P, Schlederer T, Astafyeva N, Baranovskaya T, Barbouche M-R, Beltyukov E, Berger A, Borzova E, Bousquet J, Bumbacea RS, Bychkovskaya S, Caraballo L, Chung KF, Custovic A, Docena G, Eiwegger T, Evsegneeva I, Emelyanov A, Errhalt P, Fassakhov R, Fayzullina R, Fedenko E, Fomina D, Gao Z, Giavina-Bianchi P, Gotua M, Greber-Platzer S, Hedlin G, Ilina N, Ispayeva Z, Idzko M, Johnston SL, Kalayci O, Karaulov A, Karsonova A, Khaitov M, Kovzel E, Kowalski ML, Kudlay D, Levin M, Makarova S, Matricardi PM, Nadeau KC, Namazova-Baranova L, Naumova O, Nazarenko O, O'Byrne PM, Osier F, Pampura AN, Panaitescu C, Papadopoulos NG, Park H-S, Pawankar R, Pohl W, Renz H, Riabova K, Sampath V, Sekerel BE, Sibanda E, Siroux V, Sizyakina LP, Sun J-L, Szepfalusi Z, Umanets T, Van Bever HPS, van Hage M, Vasileva M, von Mutius E, Wang J-Y, Wong GWK, Zaikov S, Zidarn M, Valenta Ret al., 2020, Toward personalization of asthma treatment according to trigger factors, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 145, Pages: 1529-1534, ISSN: 0091-6749

Asthma is a severe and chronic disabling disease affecting more than 300 million people worldwide. Although in the past few drugs for the treatment of asthma were available, new treatment options are currently emerging, which appear to be highly effective in certain subgroups of patients. Accordingly, there is a need for biomarkers that allow selection of patients for refined and personalized treatment strategies. Recently, serological chip tests based on microarrayed allergen molecules and peptides derived from the most common rhinovirus strains have been developed, which may discriminate 2 of the most common forms of asthma, that is, allergen- and virus-triggered asthma. In this perspective, we argue that classification of patients with asthma according to these common trigger factors may open new possibilities for personalized management of asthma.

Journal article

Ober C, McKennan CG, Magnaye KM, Altman MC, Washington C, Stanhope C, Naughton KA, Rosasco MG, Bacharier LB, Billheimer D, Gold DR, Gress L, Hartert T, Havstad S, Khurana Hershey GK, Hallmark B, Hogarth DK, Jackson DJ, Johnson CC, Kattan M, Lemanske RF, Lynch SV, Mendonca EA, Miller RL, Naureckas ET, O'Connor GT, Seroogy CM, Wegienka G, White SR, Wood RA, Wright AL, Zoratti EM, Martinez FD, Ownby D, Nicolae DL, Levin AM, Gern JE, Environmental Influences on Child Health Outcomes-Children's Respiratory Research Workgroupet al., 2020, Expression quantitative trait locus fine mapping of the 17q12-21 asthma locus in African American children: a genetic association and gene expression study., Lancet Respir Med, Vol: 8, Pages: 482-492

BACKGROUND: African ancestry is associated with a higher prevalence and greater severity of asthma than European ancestries, yet genetic studies of the most common locus associated with childhood-onset asthma, 17q12-21, in African Americans have been inconclusive. The aim of this study was to leverage both the phenotyping of the Children's Respiratory and Environmental Workgroup (CREW) birth cohort consortium, and the reduced linkage disequilibrium in African Americans, to fine map the 17q12-21 locus. METHODS: We first did a genetic association study and meta-analysis using 17q12-21 tag single-nucleotide polymorphisms (SNPs) for childhood-onset asthma in 1613 European American and 870 African American children from the CREW consortium. Nine tag SNPs were selected based on linkage disequilibrium patterns at 17q12-21 and their association with asthma, considering the effect allele under an additive model (0, 1, or 2 effect alleles). Results were meta-analysed with publicly available summary data from the EVE consortium (on 4303 European American and 3034 African American individuals) for seven of the nine SNPs of interest. Subsequently, we tested for expression quantitative trait loci (eQTLs) among the SNPs associated with childhood-onset asthma and the expression of 17q12-21 genes in resting peripheral blood mononuclear cells (PBMCs) from 85 African American CREW children and in upper airway epithelial cells from 246 African American CREW children; and in lower airway epithelial cells from 44 European American and 72 African American adults from a case-control study of asthma genetic risk in Chicago (IL, USA). FINDINGS: 17q12-21 SNPs were broadly associated with asthma in European Americans. Only two SNPs (rs2305480 in gasdermin-B [GSDMB] and rs8076131 in ORMDL sphingolipid biosynthesis regulator 3 [ORMDL3]) were associated with asthma in African Americans, at a Bonferroni-corrected threshold of p<0·0055 (for rs2305480_G, odds ratio [OR] 1·36 [95% CI

Journal article

Turkalj M, Drkulec V, Haider S, Plavec D, Banic I, Malev O, Erceg D, Woodcock A, Nogalo B, Custovic Aet al., 2020, Association of bacterial load in drinking water and allergic diseases in childhood, Clinical and Experimental Allergy, Vol: 50, Pages: 733-740, ISSN: 0954-7894

BackgroundTreatment of drinking water may decrease microbial exposure.ObjectiveTo investigate whether bacterial load in drinking water is associated with altered risk of allergic diseases.MethodsWe recruited 1,110 schoolchildren aged 6‐16 years between 2011 and 2013 in Požega‐Slavonia County in Croatia, where we capitalized on a natural experiment whereby individuals receive drinking water through public mains supply or individual wells. We obtained data on microbial content of drinking water for all participants; 585 children were randomly selected for more detailed assessments, including skin prick testing. Since water supply was highly correlated with rural residence, we compared clinical outcomes across four groups (Rural/Individual, Rural/Public, Urban/Individual and Urban/Public). For each child, we derived quantitative index of microbial exposure (bacterial load in the drinking water measured during the child's first year of life).ResultsCumulative bacterial load in drinking water was higher (median [IQR]: 6390 [4190‐9550] vs 0 [0‐0]; P < .0001), and lifetime prevalence of allergic diseases was significantly lower among children with individual supply (5.5% vs 2.3%, P = .01; 14.4% vs 6.7%, P < .001; 25.2% vs 15.1%, P < .001; asthma, atopic dermatitis [AD] and rhinitis, respectively). Compared with the reference group (Urban/Public), there was a significant reduction in the risk of ever asthma, AD and rhinitis amongst rural children with individual supply: OR [95% CI]: 0.14 [0.03,0.67], P = .013; 0.20 [0.09,0.43], P < .001; 0.17 [0.10,0.32], P < .001. Protection was also observed in the Rural/Public group, but the effect was consistently highest among Rural/Individual children. In the quantitative analysis, the risk of allergic diseases decreased significantly with increasing bacterial load in drinking water in the first year of life (0.79 [0.70,0.88], P < .001; 0.90 [0.83,0.99], P = .025; 0.80 [0.74,0.86], P < .001; current whee

Journal article

Broadbent L, Manzoor S, Zarcone MC, Barabas J, Shields MD, Saglani S, Lloyd CM, Bush A, Custovic A, Ghazal P, Gore M, Marsland B, Roberts G, Schwarze J, Turner S, Power UFet 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.

Journal article

Roberts G, Fontanella S, Selby A, Howard R, Filippi S, Hedlin G, Nordlund B, Howarth P, Hashimoto S, Brinkman P, Fleming LJ, Murray C, Bush A, Frey U, Singer F, Schoos A-MM, van Aalderen W, Djukanovic R, Chung KF, Sterk PJ, Adnan C, U-BIOPRED Consortiumet al., 2020, Connectivity patterns between multiple allergen specific IgE antibodies and their association with severe asthma, Journal of Allergy and Clinical Immunology, ISSN: 0091-6749

BACKGROUND: Allergic sensitization is associated with severe asthma, but assessment of sensitization is not recommended by most guidelines. OBJECTIVE: We hypothesized that patterns of IgE responses to multiple allergenic proteins differ between sensitized participants with mild/moderate and severe asthma. METHODS: IgE to 112 allergenic molecules (components, c-sIgE) was measured using multiplex array among 509 adults and 140 school-age and 131 preschool children with asthma/wheeze from the Unbiased BIOmarkers for the PREDiction of respiratory diseases outcomes cohort, of whom 595 had severe disease. We applied clustering methods to identify co-occurrence patterns of components (component clusters) and patterns of sensitization among participants (sensitization clusters). Network analysis techniques explored the connectivity structure of c-sIgE, and differential network analysis looked for differences in c-sIgE interactions between severe and mild/moderate asthma. RESULTS: Four sensitization clusters were identified, but with no difference between disease severity groups. Similarly, component clusters were not associated with asthma severity. None of the c-sIgE were identified as associates of severe asthma. The key difference between school children and adults with mild/moderate compared with those with severe asthma was in the network of connections between c-sIgE. Participants with severe asthma had higher connectivity among components, but these connections were weaker. The mild/moderate network had fewer connections, but the connections were stronger. Connectivity between components with no structural homology tended to co-occur among participants with severe asthma. Results were independent from the different sample sizes of mild/moderate and severe groups. CONCLUSIONS: The patterns of interactions between IgE to multiple allergenic proteins are predictors of asthma severity among school children and adults with allergic asthma.

Journal article

Simpson A, Brough HA, Haider S, Belgrave D, Murray CS, Custovic Aet al., 2020, Early-life inhalant allergen exposure, filaggrin genotype and the development of sensitization from infancy to adolescence, Journal of Allergy and Clinical Immunology, Vol: 145, Pages: 993-1001, ISSN: 0091-6749

BackgroundWe hypothesized that filaggrin loss-of-function mutations modify the impact of allergen exposure on the development of allergic sensitization.ObjectiveTo determine whether early-life exposure to inhalant allergens increases the risk of specific sensitization, and whether filaggrin mutations modulate these odds.MethodsIn a population-based birth cohort, we measured mite, cat and dog allergen levels in dust samples collected from homes within the first year of life. Sensitization was assessed at 6 time-points between infancy and age 16 years. Genotyping was performed for six filaggrin mutations.ResultsIn the longitudinal multivariable model (age 1-16 years), we observed a significant interaction between filaggrin and Fel d 1 exposure on cat sensitization, with the effect of exposure being significantly greater among children with filaggrin mutations compared to those without (OR 1.36, 95% CI 1.02-1.80, p=0.035). The increase in risk of mite sensitization with increasing Der p 1 exposure was consistently higher among children with filaggrin mutations, but the interaction did not reach statistical significance. Different association were observed for dog: there was a significant interaction between filaggrin and dog ownership, but the risk of sensitization to any allergen was significantly lower among children with filaggrin mutations who were exposed to dog in infancy (OR 0.16, 95% CI 0.03–0.86, p=0.03).ConclusionsFilaggrin loss-of function mutations modify the relationship between allergen exposure and sensitization, but effects differ at different ages and between different allergens.

Journal article

Akar-Ghibril N, Casale T, Custovic A, Phipatanakul Wet al., 2020, Allergic endotypes and phenotypes of asthma, Journal of Allergy and Clinical Immunology: In Practice, Vol: 8, Pages: 429-440, ISSN: 2213-2198

Allergic asthma is defined as asthma associated with sensitization to aeroallergens, which leads to asthma symptoms and airway inflammation. Allergic asthma is the most common asthma phenotype. The onset of allergic asthma is most often in childhood and is usually accompanied by other comorbidities including atopic dermatitis and allergic rhinitis. It is often persistent although there is a wide variation in disease severity. It is a TH2-driven process. Biomarkers have been identified to distinguish patients with allergic asthma, particularly serum IgE levels, tests to indicate sensitization to aeroallergens such as specific IgE or skin prick test positivity, blood and sputum eosinophil levels, fraction of exhaled nitric oxide, and periostin. Treatments for allergic asthma include environmental control measures, allergen immunotherapy, and glucocorticoids. Biologics, targeting the TH2 pathway, have been shown to be effective in the treatment of allergic asthma.

Journal article

Deliu M, Fontanella S, Haider S, Sperrin M, Geifman N, Murray C, Simpson A, Custovic Aet al., 2020, Longitudinal trajectories of severe wheeze exacerbations from infancy to school age and their association with early-life risk factors and late asthma outcomes, Clinical and Experimental Allergy, Vol: 50, Pages: 315-324, ISSN: 0954-7894

IntroductionExacerbation‐prone asthma subtype has been reported in studies using data‐driven methodologies. However, patterns of severe exacerbations have not been studied.ObjectiveTo investigate longitudinal trajectories of severe wheeze exacerbations from infancy to school age.MethodsWe applied longitudinal k‐means clustering to derive exacerbation trajectories among 887 participants from a population‐based birth cohort with severe wheeze exacerbations confirmed in healthcare records. We examined early‐life risk factors of the derived trajectories, and their asthma‐related outcomes and lung function in adolescence.Results498/887 children (56%) had physician‐confirmed wheeze by age 8 years, of whom 160 had at least one severe exacerbation. A two‐cluster model provided the optimal solution for severe exacerbation trajectories among these 160 children: “Infrequent exacerbations (IE)” (n = 150, 93.7%) and “Early‐onset frequent exacerbations (FE)” (n = 10, 6.3%). Shorter duration of breastfeeding was the strongest early‐life risk factor for FE (weeks, median [IQR]: FE, 0 [0‐1.75] vs. IE, 6 [0‐20], P < .001). Specific airway resistance (sRaw) was significantly higher in FE compared with IE trajectory throughout childhood. We then compared children in the two exacerbation trajectories with those who have never wheezed (NW, n = 389) or have wheezed but had no severe exacerbations (WNE, n = 338). At age 8 years, FEV1/FVC was significantly lower and FeNO significantly higher among FE children compared with all other groups. By adolescence (age 16), subjects in FE trajectory were significantly more likely to have current asthma (67% FE vs. 30% IE vs. 13% WNE, P < .001) and use inhaled corticosteroids (77% FE vs. 15% IE vs. 18% WNE, P < .001). Lung function was significantly diminished in the FE trajectory (FEV1/FVC, mean [95%CI]: 89.9% [89.3‐90.5] vs. 88.1% [87.3‐88.8] vs. 85.1% [83.4‐86.7] vs. 74.7% [61.5‐87.8], NW, WNE, IE, FE respective

Journal article

Voraphani N, Stern DA, Spangenberg AL, Wright AL, Morgan WJ, Kraft M, Murray CS, Custovic A, Kull I, Bergstrom A, Ledford JG, Halonen MJ, Martinez FD, Simpson A, Melen E, Guerra Set al., 2020, Circulating CC16 Deficits and Frequent Asthma from Childhood Through Adult Life, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Voraphani N, Zhai J, Stern DA, Wright AL, Halonen MJ, Hallberg J, Kull I, Bergstrom A, Murray CS, Custovic A, Melen E, Simpson A, Morgan WJ, Martinez FD, Guerra Set al., 2020, Early-Life Nutritional Status and Spirometric Restriction in Adult Life, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Holguin F, Cardet JC, Chung KF, Diver S, Ferreira DS, Fitzpatrick A, Gaga M, Kellermeyer L, Khurana S, Knight S, McDonald VM, Morgan RL, Ortega VE, Rigau D, Subbarao P, Tonia T, Adcock IM, Bleecker ER, Brightling C, Boulet L-P, Cabana M, Castro M, Chanez P, Custovic A, Djukanovic R, Frey U, Frankemolle B, Gibson P, Hamerlijnck D, Jarjour N, Konno S, Shen H, Vitary C, Bush Aet al., 2020, Management of severe asthma: a European Respiratory Society/American Thoracic Society Guideline, European Respiratory Journal, Vol: 55, ISSN: 0903-1936

This document provides clinical recommendations for the management of severe asthma. Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence relevant to the Task Force's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of asthma experts, who made specific recommendations on 6 specific questions. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made the following recommendations: 1) Suggest using anti-IL5 and anti IL-5Rα for severe uncontrolled adult eosinophilic asthma phenotypes; 2) suggest using blood eosinophil cut-point of ≥150/μL to guide anti-IL5 initiation in adult patients with severe asthma; and 3) Suggest considering specific eosinophil (≥260/μL) and FeNO (≥19.5 ppb) cutoffs to identify adolescents or adults with the greatest likelihood or response to anti-IgE therapy; 4) Suggest using inhaled tiotropium for adolescents and adults with severe uncontrolled asthma despite GINA step 4-5 or NAEPP step 5 therapies; 5) Suggest a trial of chronic macrolide therapy to reduce asthma exacerbations in persistently symptomatic or uncontrolled patients on GINA step 5 or NAEPP step 5 therapies, irrespective of asthma phenotype; 6) Suggest using anti-IL4/13 for adult patients with severe eosinophilic asthma, and for those with severe corticosteroid-dependent asthma regardless of blood eosinophil levels. These recommendations should be reconsidered as new evidence becomes available.

Journal article

Haider S, Nakamura T, Colicino S, Murray C, Holloway J, Simpson A, Cullinan P, Custovic Aet al., 2019, Different definitions of atopic dermatitis: Impact on prevalence estimates and associated risk factors, British Journal of Dermatology, Vol: 181, Pages: 1272-1279, ISSN: 1365-2133

BackgroundThere is no objective test that can unequivocally confirm the diagnosis of atopic dermatitis (AD), and no uniform clinical definition.ObjectiveTo investigate to what extent operational definitions of AD cause fluctuation in the prevalence estimates and the associated risk factors.MethodsWe first reviewed operational definitions of AD used in the literature. We then tested the impact of the choice of the most common definitions of “Cases” and “Controls” on AD prevalence estimates and associated risk factors (including filaggrin‐FLG mutations) among children aged 5 years in two population‐based birth cohorts: Manchester Asthma and Allergy Study (MAAS) and Asthma in Ashford. Model performance was measured by the percentage of children within an area of clinical indecision (defined as having a posterior probability of AD between 25% and 60%).ResultsWe identified 59 different definitions of AD across 45 reviewed studies. Of those, we chose 4 common “Case” definitions, and 2 definitions of “Controls”. The prevalence estimates using different case definitions ranged between 22% and 33% in MAAS, and 12% and 22% in Ashford. The area of clinical indecision ranged from 32% to 44% in MAAS, and from 9% to 29% in Ashford. Depending on the case definition used, the associations with FLG mutations varied (ORs [95% CI]: 1.8 [1.1‐2.9] to 2.2 [1.3‐3.7] (MAAS) and 1.7 [0.8‐3.7] to 2.3 [1.2‐4.5] (Ashford)). Associations with FLG mutations also differed when using the same “Case” definition, but different definitions of “Controls”.ConclusionUse of different definitions of AD results in substantial difference in prevalence estimates, the performance of prediction models, and association with risk factors.

Journal article

Clark H, Granell R, Curtin JA, Belgrave D, Simpson A, Murray C, Henderson AJ, Custovic A, Paternoster Let al., 2019, Differential associations of allergic disease genetic variants with developmental profiles of eczema, wheeze and rhinitis, Clinical and Experimental Allergy, Vol: 49, Pages: 1475-1486, ISSN: 0954-7894

BACKGROUND: Allergic diseases (eczema, wheeze and rhinitis) in children often present as heterogeneous phenotypes. Understanding genetic associations of specific patterns of symptoms might facilitate understanding of the underlying biological mechanisms. OBJECTIVE: To examine associations between allergic disease-related variants identified in a recent genome-wide association study and latent classes of allergic diseases (LCADs) in two population-based birth cohorts. METHODS: Eight previously defined LCADs between 1 and 11 years: 'No disease', 'Atopic march', 'Persistent eczema and wheeze', 'Persistent eczema with later-onset rhinitis', 'Persistent wheeze with later-onset rhinitis', 'Transient wheeze', 'Eczema only' and 'Rhinitis only' were used as the study outcome. Weighted multinomial logistic regression was used to estimate associations between 135 SNPs (and a polygenic risk score, PRS) and LCADs among 6,345 individuals from The Avon Longitudinal Study of Parents and Children (ALSPAC). Heterogeneity across LCADs was assessed before and after Bonferroni correction. Results were replicated in Manchester Asthma and Allergy Study (MAAS) (n=896) and pooled in a meta-analysis. RESULTS: We found strong evidence for differential genetic associations across the LCADs; pooled PRS heterogeneity p-value=3.3x10-14 , excluding 'no disease' class. The associations between the PRS and LCADs in MAAS were remarkably similar to ALSPAC. Two SNPs (a protein truncating variant in FLG and a SNP within an intron of GSDMB) had evidence for differential association (pooled p-values≤ 0.006). The FLG locus was differentially associated across LCADs that included eczema, with stronger associations for LCADs with comorbid wheeze and rhinitis. The GSDMB locus in contrast was equally associated across LCADs that included wheeze. CONCLUSIONS & CLINICAL RELEVANCE: We have shown complex, but distinct patterns of genetic associations with LCADs, suggesting that heterogeneous mechanisms unde

Journal article

Bradfield JP, Vogelezang S, Felix JF, Chesi A, Helgeland Ø, Horikoshi M, Karhunen V, Lowry E, Cousminer DL, Ahluwalia TS, Thiering E, Boh ET-H, Zafarmand MH, Vilor-Tejedor N, Wang CA, Joro R, Chen Z, Gauderman WJ, Pitkänen N, Parra EJ, Fernandez-Rhodes L, Alyass A, Monnereau C, Curtin JA, Have CT, McCormack SE, Hollensted M, Frithioff-Bøjsøe C, Valladares-Salgado A, Peralta-Romero J, Teo Y-Y, Standl M, Leinonen JT, Holm J-C, Peters T, Vioque J, Vrijheid M, Simpson A, Custovic A, Vaudel M, Canouil M, Lindi V, Atalay M, Kähönen M, Raitakari OT, van Schaik BDC, Berkowitz RI, Cole SA, Voruganti VS, Wang Y, Highland HM, Comuzzie AG, Butte NF, Justice AE, Gahagan S, Blanco E, Lehtimäki T, Lakka TA, Hebebrand J, Bonnefond A, Grarup N, Froguel P, Lyytikäinen L-P, Cruz M, Kobes S, Hanson RL, Zemel BS, Hinney A, Teo KK, Meyre D, North KE, Gilliland FD, Bisgaard H, Bustamante M, Bonnelykke K, Pennell CE, Rivadeneira F, Uitterlinden AG, Baier LJ, Vrijkotte TGM, Heinrich J, Sørensen TIA, Saw S-M, Pedersen O, Hansen T, Eriksson J, Widén E, McCarthy MI, Njølstad PR, Power C, Hyppönen E, Sebert S, Brown CD, Järvelin M-R, Timpson NJ, Johansson S, Hakonarson H, Jaddoe VWV, Grant SFA, Early Growth Genetics Consortiumet al., 2019, A trans-ancestral meta-analysis of Genome-wide Association Studies reveals loci associated with childhood obesity, Human Molecular Genetics, Vol: 28, Pages: 3327-3338, ISSN: 0964-6906

Although hundreds of GWAS-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity, and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of thirty studies consisting of up to 13,005 cases (≥95th percentile of BMI achieved 2-18 years old) and 15,599 controls (consistently <50th percentile of BMI) of European, African, North/South American and East Asian ancestry. Suggestive loci were taken forward for replication in a sample of 1,888 cases and 4,689 controls from seven cohorts of European and North/South American ancestry. In addition to observing eighteen previously implicated BMI or obesity loci, for both early and late onset, we uncovered one completely novel locus in this trans-ancestral analysis (nearest gene: METTL15). The variant was nominally associated in only the European subgroup analysis but had a consistent direction of effect in other ethnicities. We then utilized trans-ancestral Bayesian analysis to narrow down the location of the probable causal variant at each genome-wide significant signal. Of all the fine-mapped loci, we were able to narrow down the causative variant at four known loci to fewer than ten SNPs (FAIM2, GNPDA2, MC4R and SEC16B loci). In conclusion, an ethnically diverse setting has enabled us to both identify an additional pediatric obesity locus and further fine-map existing loci.

Journal article

Diamant Z, Vijverberg S, Alving K, Bakirtas A, Bjermer L, Custovic A, Dahlen S-E, Gaga M, Gerth van Wijk R, Del Giacco S, Hamelmann E, Heaney L, Heffler E, Kalayci Ö, Kostikas K, Lutter R, Olin A-C, Sergejeva S, Simpson A, Sterk PJ, Tufvesson E, Agache I, Seys SFet al., 2019, Toward clinically applicable biomarkers for asthma: An EAACI position paper, Allergy, Vol: 74, Pages: 1835-1851, ISSN: 0105-4538

Inflammation, structural and functional abnormalities within the airways are key features of asthma. Although these processes are well-documented, their expression varies across the heterogeneous spectrum of asthma. Type 2 inflammatory responses are characterized by increased levels of eosinophils, FeNO and type 2 cytokines in blood and/or airways. Presently, type 2 asthma is the best-defined endotype, typically found in patients with allergic asthma, but surprisingly also in non-allergic patients with (severe) asthma. The etiology of asthma with non-type 2 inflammation is less clear. During the past decade, targeted therapies, including biologicals and small molecules, have been increasingly integrated into treatment strategies of severe asthma. These treatments block specific inflammatory pathways or single mediators. Single or composite biomarkers help to identify patients who will benefit from these treatments. So far, only a few inflammatory biomarkers have been validated for clinical application. The European Academy of Allergy & Clinical Immunology (EAACI) Task Force on Biomarkers in Asthma was initiated to review different biomarker sampling methods and to investigate clinical applicability of new and existing inflammatory biomarkers (point-of-care) to support diagnosis, targeted treatment and monitoring of severe asthma. Subsequently, we discuss existing and novel targeted therapies for asthma as well as applicable biomarkers.

Journal article

Bousquet JJ, Schünemann HJ, Togias A, Erhola M, Hellings PW, Zuberbier T, Agache I, Ansotegui IJ, Anto JM, Bachert C, Becker S, Bedolla-Barajas M, Bewick M, Bosnic-Anticevich S, Bosse I, Boulet LP, Bourrez JM, Brusselle G, Chavannes N, Costa E, Cruz AA, Czarlewski W, Fokkens WJ, Fonseca JA, Gaga M, Haahtela T, Illario M, Klimek L, Kuna P, Kvedariene V, Le LTT, Larenas-Linnemann D, Laune D, Lourenço OM, Menditto E, Mullol J, Okamoto Y, Papadopoulos N, Pham-Thi N, Picard R, Pinnock H, Roche N, Roller-Wirnsberger RE, Rolland C, Samolinski B, Sheikh A, Toppila-Salmi S, Tsiligianni I, Valiulis A, Valovirta E, Vasankari T, Ventura M-T, Walker S, Williams S, Akdis CA, Annesi-Maesano I, Arnavielhe S, Basagana X, Bateman E, Bedbrook A, Bennoor KS, Benveniste S, Bergmann KC, Bialek S, Billo N, Bindslev-Jensen C, Bjermer L, Blain H, Bonini M, Bonniaud P, Bouchard J, Briedis V, Brightling CE, Brozek J, Buhl R, Buonaiuto R, Canonica GW, Cardona V, Carriazo AM, Carr W, Cartier C, Casale T, Cecchi L, Cepeda Sarabia AM, Chkhartishvili E, Chu DK, Cingi C, Colgan E, de Sousa JC, Courbis AL, Custovic A, Cvetkosvki B, D'Amato G, da Silva J, Dantas C, Dokic D, Dauvilliers Y, Dedeu A, De Feo G, Devillier P, Di Capua S, Dykewickz M, Dubakiene R, Ebisawa M, El-Gamal Y, Eller E, Emuzyte R, Farrell J, Fink-Wagner A, Fiocchi A, Fontaine JF, Gemicioğlu B, Schmid-Grendelmeir P, Gamkrelidze A, Garcia-Aymerich J, Gomez M, González Diaz S, Gotua M, Guldemond NA, Guzmán M-A, Hajjam J, O'B Hourihane J, Humbert M, Iaccarino G, Ierodiakonou D, Illario M, Ivancevich JC, Joos G, Jung K-S, Jutel M, Kaidashev I, Kalayci O, Kardas P, Keil T, Khaitov M, Khaltaev N, Kleine-Tebbe J, Kowalski ML, Kritikos V, Kull I, Leonardini L, Lieberman P, Lipworth B, Lodrup Carlsen KC, Loureiro CC, Louis R, Mair A, Marien G, Mahboub B, Malva J, Manning P, De Manuel Keenoy E, Marshall GD, Masjedi MR, Maspero JF, Mathieu-Dupas E, Matricardi PM, Melén E, Melo-Gomes E, Meltzer EO, Menditto E, Mercier J, Miculinic N, Mihaltan Fet al., 2019, Next-generation ARIA care pathways for rhinitis and asthma: a model for multimorbid chronic diseases, Clinical and Translational Allergy, Vol: 9, ISSN: 2045-7022

Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy. Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Santé as a Good Practice in the field of digitally-enabled, integrated, person-centred care. Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.

Journal article

Bourdin A, Bjermer L, Brightling C, Brusselle GG, Chanez P, Chung KF, Custovic A, Diamant Z, Diver S, Djukanovic R, Hamerlijnck D, Horvath I, Johnston SL, Kanniess F, Papadopoulos N, Papi A, Russell RJ, Ryan D, Samitas K, Tonia T, Zervas E, Gaga Met al., 2019, ERS/EAACI statement on severe exacerbations in asthma in adults: facts, priorities and key research questions, European Respiratory Journal, Vol: 54, Pages: 1-25, ISSN: 0903-1936

Despite the use of effective medications to control asthma, severe exacerbations in asthma are still a major health risk and require urgent action on the part of the patient and physician to prevent serious outcomes such as hospitalisation or death. Moreover, severe exacerbations are associated with substantial healthcare costs and psychological burden, including anxiety and fear for patients and their families. The European Academy of Allergy and Clinical Immunology (EAACI) and the European Respiratory Society (ERS) set up a task force to search for a clear definition of severe exacerbations, and to also define research questions and priorities. The statement includes comments from patients who were members of the task force.

Journal article

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