Birth cohorts in asthma and allergic diseases: Report of a NIAID/NHLBI/MeDALL joint workshop
2014; Elsevier BV; Volume: 133; Issue: 6 Linguagem: Inglês
10.1016/j.jaci.2014.01.018
ISSN1097-6825
AutoresJean Bousquet, James E. Gern, Fernando D. Martínez, Josep M. Antó, Christine Cole Johnson, Patrick G. Holt, Robert F. Lemanske, Peter N. Le Souëf, Robert S. Tepper, Erika von Mutius, Syed Hasan Arshad, Leonard B. Bacharier, Allan B. Becker, Kathleen Belanger, Anna Bergström, David I. Bernstein, Michael D. Cabana, Kecia N. Carroll, Mario Castro, Philip J. Cooper, Matthew W. Gillman, Diane R. Gold, John Henderson, Joachim Heinrich, Soo‐Jong Hong, Daniel J. Jackson, Thomas Keil, Anita L. Kozyrskyj, Karin C. Lødrup Carlsen, Rachel L. Miller, Isabelle Momas, Wayne J. Morgan, Patricia Noël, Dennis R. Ownby, Mariona Pinart, Patrick Ryan, Julie M. Schwaninger, Malcolm R. Sears, Angela Simpson, Henriëtte A. Smit, Debra A. Stern, Padmaja Subbarao, Rudolf Valenta, Xiaobin Wang, Scott T. Weiss, Robert A. Wood, Anne L. Wright, Rosalind J. Wright, Alkis Togias, Peter J. Gergen,
Tópico(s)Delphi Technique in Research
ResumoPopulation-based birth cohorts on asthma and allergies increasingly provide new insights into the development and natural history of the diseases. More than 130 birth cohorts focusing on asthma and allergy have been initiated in the last 30 years. A National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; Mechanisms of the Development of Allergy (MeDALL; Framework Programme 7 of the European Commission) joint workshop was held in Bethesda, Maryland, on September 11-12, 2012, with 3 objectives: (1) documenting the knowledge that asthma/allergy birth cohorts have provided, (2) identifying the knowledge gaps and inconsistencies, and (3) developing strategies for moving forward, including potential new study designs and the harmonization of existing asthma birth cohort data. The meeting was organized around the presentations of 5 distinct workgroups: (1) clinical phenotypes, (2) risk factors, (3) immune development of asthma and allergy, (4) pulmonary development, and (5) harmonization of existing birth cohorts. This article presents the workgroup reports and provides Web links (AsthmaBirthCohorts.niaid.nih.gov or www.medall-fp7.eu), where the reader will find tables describing the characteristics of the birth cohorts included in this report, the type of data collected at differing ages, and a selected bibliography provided by the participating birth cohorts. Population-based birth cohorts on asthma and allergies increasingly provide new insights into the development and natural history of the diseases. More than 130 birth cohorts focusing on asthma and allergy have been initiated in the last 30 years. A National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; Mechanisms of the Development of Allergy (MeDALL; Framework Programme 7 of the European Commission) joint workshop was held in Bethesda, Maryland, on September 11-12, 2012, with 3 objectives: (1) documenting the knowledge that asthma/allergy birth cohorts have provided, (2) identifying the knowledge gaps and inconsistencies, and (3) developing strategies for moving forward, including potential new study designs and the harmonization of existing asthma birth cohort data. The meeting was organized around the presentations of 5 distinct workgroups: (1) clinical phenotypes, (2) risk factors, (3) immune development of asthma and allergy, (4) pulmonary development, and (5) harmonization of existing birth cohorts. This article presents the workgroup reports and provides Web links (AsthmaBirthCohorts.niaid.nih.gov or www.medall-fp7.eu), where the reader will find tables describing the characteristics of the birth cohorts included in this report, the type of data collected at differing ages, and a selected bibliography provided by the participating birth cohorts. Asthma and allergic diseases commonly appear during infancy and tend to persist until adult life, and thus birth cohort studies help in understanding their determinants and evolution. More than 130 birth cohorts focusing on asthma and allergy have been initiated in the last 30 years,1Tischer C.G. Hohmann C. Thiering E. Herbarth O. Müller A. Henderson J. et al.Meta-analysis of mould and dampness exposure on asthma and allergy in eight European birth cohorts: an ENRIECO initiative.Allergy. 2011; 66: 1570-1579Crossref PubMed Scopus (122) Google Scholar, 2Vrijheid M. Casas M. Bergström A. Carmichael A. Cordier S. Eggesbø M. et al.European birth cohorts for environmental health research.Environ Health Perspect. 2012; 120: 29-37Crossref PubMed Scopus (98) Google Scholar, 3Bousquet J. Anto J. Sunyer J. Nieuwenhuijsen M. Vrijheid M. Keil T. Pooling birth cohorts in allergy and asthma: European Union funded initiatives A MeDALL, CHICOS, ENRIECO, GA2LEN joint paper.Int Arch Allergy Immunol. 2013; 161: 1-10Crossref PubMed Scopus (50) Google Scholar and some have followed the participants for more than 30 years.4Phelan P.D. Robertson C.F. Olinsky A. The Melbourne Asthma Study: 1964-1999.J Allergy Clin Immunol. 2002; 109: 189-194Abstract Full Text Full Text PDF PubMed Scopus (415) Google Scholar, 5Taussig L.M. Wright A.L. Holberg C.J. Halonen M. Morgan W.J. Martinez F.D. Tucson Children's Respiratory Study: 1980 to present.J Allergy Clin Immunol. 2003; 111: 661-676Abstract Full Text Full Text PDF PubMed Scopus (520) Google ScholarWork has begun to pool information across birth cohorts.3Bousquet J. Anto J. Sunyer J. Nieuwenhuijsen M. Vrijheid M. Keil T. Pooling birth cohorts in allergy and asthma: European Union funded initiatives A MeDALL, CHICOS, ENRIECO, GA2LEN joint paper.Int Arch Allergy Immunol. 2013; 161: 1-10Crossref PubMed Scopus (50) Google Scholar An Asthma Birth Cohort Workshop was held in Bethesda, Maryland, on September 11-12, 2012, to further improve our understanding of existing asthma birth cohorts. The meeting was jointly sponsored by the National Institute of Allergy and Infectious Disease (NIAID) and the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health and Mechanisms of the Development of Allergy (MeDALL; Framework Program for Research and Technological Development 7 [FP7], European Commission). The workshop allowed epidemiologic, clinical, and laboratory researchers conducting research on asthma and other allergic diseases in birth cohorts to meet in order to address a wide research agenda. Representatives from major birth cohorts on asthma and allergies from North America, Europe, Asia, and Australasia attended.The workshop had the objectives of (1) documenting the knowledge that asthma/allergy birth cohorts have provided, (2) identifying the knowledge gaps and inconsistencies, and (3) developing strategies for moving forward, including potential new study designs and the harmonization of existing birth cohort data.The meeting was organized around the presentations of 5 distinct workgroups, 4 of which were charged with reviewing available birth cohort data and preparing a presentation of results and knowledge gaps in the preidentified topics of asthma phenotypes, risk factors, immune development, and pulmonary development. The fifth workgroup worked to identify approaches for data pooling and harmonization (Table I). Before the meeting, investigators from birth cohorts in North America, Europe, Asia, and Australasia were sent a questionnaire to report their findings to date relevant to the workgroups (Table II). The workgroups used this information along with extant literature and expertise as the basis for their reports. The draft reports were presented and discussed at the meeting.Table IParticipants in workgroupClinical PhenotypesAsthma Risk FactorsChair: Fernando D. Martinez, MDCo-Chair: Josep M. Anto, MD, PhDMembers:John Henderson, MDAllan Becker, MDJoachim Heinrich, PhD, MScRobert Wood, MDDavid I. Bernstein, MDDennis R. Ownby, MDChair: Erika R. M. von Mutius, MD, MScCo-Chair: Robert F. Lemanske, Jr, MDMembers:S. Hasan Arshad, DMDiane R. Gold, MD, MPHKathleen Belanger, PhDMalcolm R. Sears, MB, ChBAngela Simpson, MD, PhDXiaobin Wang, MD, MPH, ScDKecia N. Carroll, MD, MPHPhilip J. Cooper, PhDAnita Kozyrskyj, PhDImmune DevelopmentPulmonary DevelopmentChair: James E. Gern, MDCo-Chair: Patrick G. Holt, ScDMembers:Anne L. Wright, PhDRudolf Valenta, MDDaniel J. Jackson, MDMario Castro, MD, MPHRachel L. Miller, MDLeonard B. Bacharier, MDChair: Robert S. Tepper, MD, PhDCo-Chair: Peter N. Le Souëf, MDMembers:Rosalind J. Wright, MD, MPHScott T. Weiss, MD, MSPadmaja Subbarao, MD, MScKarin C. Lødrup Carlsen, MD, PhDWayne J. Morgan, MD, CMNetworking and HarmonizationOn paper but not on working groupChair: Jean Bousquet, MDCo-Chair: Christine C. Johnson, PhD, MPHMembers:Thomas Keil, MD, MScMatthew W. Gillman, MD, SMMichael D. Cabana, MD, MPHPatrick H. Ryan, PhDSoo-Jong Hong, MD, PhDDebra A. Stern, MSAnna Bergström, PhDIsabelle Momas, PhD (nonattendee)Henriette A. Smit, PhDMariona Pinart, PhD Open table in a new tab Table IIRequest for information sent to birth cohorts before the meetingClinical Phenotypes Workgroup 1. Which are the main asthma phenotypes you have identified in your birth cohort? Please provide a definition of these phenotypes. 2. Which are the more relevant new findings you have published so far about the asthma phenotypes in your cohort? Please mention up to 5 findings (each) about these phenotypes/risk factors. 3. Has your birth cohort contributed to any relevant methodological development in regard to phenotypes? Please specify. 4. Which are the main priority areas for future research in birth cohorts regarding asthma phenotypes?Asthma Risk Factors Workgroup 1. Which are the more relevant new findings you have published so far about the risk factors for asthma in your cohort? Please mention up to 5 findings (each) about these risk factors. 2. Has your birth cohort contributed to any relevant methodological development in regard to risk factors? Please specify. 3. Which are the main priority areas for future research in birth cohorts regarding asthma risk factors?Immune Development Workgroup 1. Which are the main immunologic outcomes you have measured in your birth cohort and at what ages? 2. Which are the more relevant new findings you have published so far about immune development in your cohort? Please mention relationships to wheezing, asthma, and allergic sensitization. 3. Has your birth cohort contributed to any relevant methodological development for immune assessments? Please specify. 4. Which are the main priority areas for future research in birth cohorts regarding immune development and asthma? Include suggestions related to technologic advances and study designs.Pulmonary Development Workgroup 1. What pulmonary outcomes have you included in your birth cohort and at what ages? 2. Which are the more relevant new findings you have published so far about the pulmonary development in your cohort? 3. Has your birth cohort contributed to any relevant methodological development in regard to pulmonary development? Please specify. 4. Which are the main priority areas for future research in birth cohorts regarding pulmonary development?Networking and Harmonization Workgroup 1. Harmonization efforts to date (current MeDALL focus on phenotypes) 2. Future harmonization efforts 3. Develop a harmonized questionnaire for the comparability of existing birth cohort studies Open table in a new tab This article contains the final reports incorporating input obtained from the meeting attendees. Additional information gathered as part of the workshop is available at the National Institute of Allergy and Infectious Disease (AsthmaBirthCohorts.niaid.nih.gov) and MeDALL (www.medall-fp7.eu) Web sites. At these sites, the reader will find the characteristics of the birth cohorts included in this report, the types of data collected at differing ages, and a selected bibliography provided by the participating birth cohorts. The database allows the user to search for data collected across cohorts. The database will be updated as more cohorts are identified.Workgroup 1: Clinical phenotypes (group membership: Table I)Current definition and classification of childhood wheezing/asthma and allergic diseasesBirth cohort studies have been a highly productive source of knowledge about the characteristics of asthma phenotypes in childhood because of their unique longitudinal nature.Studies in asthma have often used definitions developed by the International Study of Asthma and Allergies in Childhood (ISAAC)6Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee.Lancet. 1998; 351: 1225-1232Abstract Full Text Full Text PDF PubMed Scopus (3289) Google Scholar and partly adopted by the European birth cohort collaborations Global Allergy and Asthma European Network (GA2LEN)7Keil T. Kulig M. Simpson A. Custovic A. Wickman M. Kull I. et al.European birth cohort studies on asthma and atopic diseases: II. Comparison of outcomes and exposures—a GA2LEN initiative.Allergy. 2006; 61: 1104-1111Crossref PubMed Scopus (55) Google Scholar and MeDALL,8Antó J.M. Pinart M. Akdis M. Auffray C. Bachert C. Basagaña X. et al.Understanding the complexity of IgE-related phenotypes from childhood to young adulthood: a Mechanisms of the Development of Allergy (MeDALL) seminar.J Allergy Clin Immunol. 2012; 129: 943-954Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar, 9Bousquet J. Anto J. Auffray C. Akdis M. Cambon-Thomsen A. Keil T. et al.MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine.Allergy. 2011; 66: 596-604Crossref PubMed Scopus (144) Google Scholar particularly physician-diagnosed asthma. In some studies, definitions have combined symptoms and markers, such as lung function and airway hyperresponsiveness (AHR), to improve their validity.10Carlsten C. Dimich-Ward H. Ferguson A. Becker A. Dybuncio A. Chan-Yeung M. Airway hyperresponsiveness to methacholine in 7-year-old children: sensitivity and specificity for pediatric allergist-diagnosed asthma.Pediatr Pulmonol. 2011; 46: 175-178Crossref PubMed Scopus (11) Google Scholar Commonly, symptoms were combined with IgE measurement to stratify allergic and nonallergic subjects. Other approaches have included health care data using record linkage and with response to treatment (inhaled steroids) as a diagnostic criterion. Few cohorts have studied asthma severity or other specific phenotypes, such as exercise-induced asthma, cough, and difficulty in breathing. Most longitudinal studies in asthmatic patients have adopted the wheezing phenotype definitions described in the Tucson birth cohort (United States).11Martinez F.D. Wright A.L. Taussig L.M. Holberg C.J. Halonen M. Morgan W.J. Asthma and wheezing in the first six years of life. The Group Health Medical Associates.N Engl J Med. 1995; 332: 133-138Crossref PubMed Scopus (3252) Google Scholar The etiologic classification of wheezing (episodic viral wheeze and multitrigger wheeze12Brand P.L. Baraldi E. Bisgaard H. Boner A.L. Castro-Rodriguez J.A. Custovic A. et al.Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach.Eur Respir J. 2008; 32: 1096-1110Crossref PubMed Scopus (668) Google Scholar) has been used less often. An alternative approach has used scoring systems, such as the Asthma Predictive Index,13Castro-Rodriguez J.A. Holberg C.J. Wright A.L. Martinez F.D. A clinical index to define risk of asthma in young children with recurrent wheezing.Am J Respir Crit Care Med. 2000; 162: 1403-1406Crossref PubMed Scopus (935) Google Scholar or qualitative categories (eg, definite, probable, and possible asthma).For rhinitis, the term allergic is restricted to symptoms with demonstrable IgE sensitization (skin tests, serum-specific IgE measurements, or both). Either atopic dermatitis or atopic eczema is reported in the majority of birth cohorts, but definitions vary.Unsupervised statistical techniques, such as latent class or cluster analyses, were used to identify and define asthma phenotypes.8Antó J.M. Pinart M. Akdis M. Auffray C. Bachert C. Basagaña X. et al.Understanding the complexity of IgE-related phenotypes from childhood to young adulthood: a Mechanisms of the Development of Allergy (MeDALL) seminar.J Allergy Clin Immunol. 2012; 129: 943-954Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar, 9Bousquet J. Anto J. Auffray C. Akdis M. Cambon-Thomsen A. Keil T. et al.MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine.Allergy. 2011; 66: 596-604Crossref PubMed Scopus (144) Google Scholar, 14Ranciere F. Nikasinovic L. Bousquet J. Momas I. Onset and persistence of respiratory/allergic symptoms in preschoolers: new insights from the PARIS birth cohort.Allergy. 2013; 68: 1158-1167PubMed Google Scholar Using latent class analysis in the Avon Longitudinal Study of Parents and Children (ALSPAC; United Kingdom) and Prevention and Incidence of Asthma and Mite Allergy–Natural History Study (PIAMA; The Netherlands), wheezing patterns were in agreement with the Tucson classification.11Martinez F.D. Wright A.L. Taussig L.M. Holberg C.J. Halonen M. Morgan W.J. Asthma and wheezing in the first six years of life. The Group Health Medical Associates.N Engl J Med. 1995; 332: 133-138Crossref PubMed Scopus (3252) Google Scholar, 15Henderson J. Granell R. Heron J. Sherriff A. Simpson A. Woodcock A. et al.Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood.Thorax. 2008; 63: 974-980Crossref PubMed Scopus (387) Google Scholar, 16Savenije O.E. Granell R. Caudri D. Koppelman G.H. Smit H.A. Wijga A. et al.Comparison of childhood wheezing phenotypes in 2 birth cohorts: ALSPAC and PIAMA.J Allergy Clin Immunol. 2011; 127: 1505-1512Abstract Full Text Full Text PDF PubMed Scopus (260) Google Scholar The Manchester Asthma and Allergy Study (MAAS; United Kingdom) used another unsupervised approach to describe multiple longitudinal patterns of sensitization.17Simpson A. Tan V.Y. Winn J. Svensén M. Bishop C.M. Heckerman D.E. et al.Beyond atopy: multiple patterns of sensitization in relation to asthma in a birth cohort study.Am J Respir Crit Care Med. 2010; 181: 1200-1206Crossref PubMed Scopus (328) Google Scholar This is an area of growing interest, and many cohorts are part of MeDALL,8Antó J.M. Pinart M. Akdis M. Auffray C. Bachert C. Basagaña X. et al.Understanding the complexity of IgE-related phenotypes from childhood to young adulthood: a Mechanisms of the Development of Allergy (MeDALL) seminar.J Allergy Clin Immunol. 2012; 129: 943-954Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar, 9Bousquet J. Anto J. Auffray C. Akdis M. Cambon-Thomsen A. Keil T. et al.MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine.Allergy. 2011; 66: 596-604Crossref PubMed Scopus (144) Google Scholar which is applying both hypothesis-driven and data-driven (unsupervised) techniques to redefine asthma and allergic phenotypes.9Bousquet J. Anto J. Auffray C. Akdis M. Cambon-Thomsen A. Keil T. et al.MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine.Allergy. 2011; 66: 596-604Crossref PubMed Scopus (144) Google ScholarThe contribution of birth cohort studies to understanding asthma and allergy phenotypesIn the Tucson birth cohorts, late-onset and persistent wheezing, together with AHR and low airway function during childhood, are predictors of new asthma in young adulthood.18Stern D.A. Morgan W.J. Halonen M. Wright A.L. Martinez F.D. Wheezing and bronchial hyper-responsiveness in early childhood as predictors of newly diagnosed asthma in early adulthood: a longitudinal birth-cohort study.Lancet. 2008; 372: 1058-1064Abstract Full Text Full Text PDF PubMed Scopus (304) Google Scholar Reduced lung function at birth is associated with an increased risk of asthma by age 10 years and with a low respiratory function at the age of 22 years.19Håland G. Carlsen K.C. Sandvik L. Devulapalli C.S. Munthe-Kaas M.C. Pettersen M. et al.Reduced lung function at birth and the risk of asthma at 10 years of age.N Engl J Med. 2006; 355: 1682-1689Crossref PubMed Scopus (298) Google Scholar, 20Stern D.A. Morgan W.J. Wright A.L. Guerra S. Martinez F.D. Poor airway function in early infancy and lung function by age 22 years: a non-selective longitudinal cohort study.Lancet. 2007; 370: 758-764Abstract Full Text Full Text PDF PubMed Scopus (426) Google Scholar Lung function patterns have been studied in the Perth Infant Asthma Follow-up (PIAF) study (Australia), but the lung function impairment in children with transient wheeze was not replicated.21Turner S.W. Palmer L.J. Rye P.J. Gibson N.A. Judge P.K. Cox M. et al.The relationship between infant airway function, childhood airway responsiveness, and asthma.Am J Respir Crit Care Med. 2004; 169: 921-927Crossref PubMed Google ScholarThe Multi-centre Allergy Study (MAS; Germany) did not show that exposure to inhaled allergens was a causal determinant of asthma,22Lau S. Illi S. Sommerfeld C. Niggemann B. Bergmann R. von Mutius E. et al.Early exposure to house-dust mite and cat allergens and development of childhood asthma: a cohort study. Multicentre Allergy Study Group.Lancet. 2000; 356: 1392-1397Abstract Full Text Full Text PDF PubMed Scopus (606) Google Scholar a finding confirmed by other studies. However, in MAS, sensitization to inhaled allergens and persistence of sensitization during childhood were associated with persistence of wheezing at school age.23Illi S. von Mutius E. Lau S. Niggemann B. Gruber C. Wahn U. Perennial allergen sensitisation early in life and chronic asthma in children: a birth cohort study.Lancet. 2006; 368: 763-770Abstract Full Text Full Text PDF PubMed Scopus (591) Google Scholar MAS showed that children with nonallergic wheezing are more likely to lose their symptoms and have normal lung function at puberty.23Illi S. von Mutius E. Lau S. Niggemann B. Gruber C. Wahn U. Perennial allergen sensitisation early in life and chronic asthma in children: a birth cohort study.Lancet. 2006; 368: 763-770Abstract Full Text Full Text PDF PubMed Scopus (591) Google Scholar In MAS, allergic rhinitis in preschool children is a predictor for subsequent wheezing onset.24Rochat M.K. Illi S. Ege M.J. Lau S. Keil T. Wahn U. et al.Allergic rhinitis as a predictor for wheezing onset in school-aged children.J Allergy Clin Immunol. 2010; 126: 1170-1175Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar In the Childhood Asthma Prevention Study (CAPS; United States), children with atopic eczema were more likely to have a history of food allergies, allergic rhinitis, and current wheeze.25Kusel M.M. Holt P.G. de Klerk N. Sly P.D. Support for 2 variants of eczema.J Allergy Clin Immunol. 2005; 116: 1067-1072Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar A substantial degree of asthma, rhinitis, and eczema comorbidity was observed in the Environment and Childhood Asthma (ECA) study (Norway) and Barn (Children), Allergy, Milieu, Stockholm, Epidemiological Study (BAMSE; Sweden).26Ballardini N. Kull I. Lind T. Hallner E. Almqvist C. Ostblom E. et al.Development and comorbidity of eczema, asthma and rhinitis to age 12: data from the BAMSE birth cohort.Allergy. 2012; 67: 537-544Crossref PubMed Scopus (149) Google Scholar, 27Bertelsen R.J. Carlsen K.C. Carlsen K.H. Rhinitis in children: co-morbidities and phenotypes.Pediatr Allergy Immunol. 2010; 21: 612-622Crossref PubMed Scopus (43) Google ScholarPediatricians are frequently asked to predict the future course of wheezing and asthma in individual subjects. However, determining prognosis in an individual patient is difficult.28Smith A.K. White D.B. Arnold R.M. Uncertainty—the other side of prognosis.N Engl J Med. 2013; 368: 2448-2450Crossref PubMed Scopus (130) Google Scholar The Asthma Predictive Index13Castro-Rodriguez J.A. Holberg C.J. Wright A.L. Martinez F.D. A clinical index to define risk of asthma in young children with recurrent wheezing.Am J Respir Crit Care Med. 2000; 162: 1403-1406Crossref PubMed Scopus (935) Google Scholar is effective for groups of subjects and has been proposed for individual subjects.29Castro-Rodriguez J.A. Cifuentes L. Rodriguez-Martinez C.E. The asthma predictive index remains a useful tool to predict asthma in young children with recurrent wheeze in clinical practice.J Allergy Clin Immunol. 2011; 127: 1082-1083Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar In the ECA study, combining IgE levels to inhalant allergens and severity of airways obstruction at 2 years was superior in predicting asthma at 10 years than the use of either factor alone.30Lodrup Carlsen K.C. Soderstrom L. Mowinckel P. et al.Asthma prediction in school children; the value of combined IgE-antibodies and obstructive airways disease severity score.Allergy. 2010; 65: 1134-1140PubMed Google Scholar However, current prediction algorithms aiming to identify individual preschool children having asthma at school age are still of modest diagnostic value.31Savenije O.E. Kerkhof M. Koppelman G.H. Postma D.S. Predicting who will have asthma at school age among preschool children.J Allergy Clin Immunol. 2012; 130: 325-331Abstract Full Text Full Text PDF PubMed Scopus (104) Google ScholarUnmet needsThere is no consistent evidence that clinical phenotypes correspond to genuine biological entities that reflect specific interactions between genes and the environment. These phenotypes could eventually reflect a continuum of states rather than discrete entities. Exploration of new phenotypes could eventually result in a refined classification of phenotypes that more closely reflects the relevant pathogenic mechanisms. The interplay among asthma, rhinitis, and eczema is still poorly understood. Current asthma phenotypes are not amenable to primary prevention, and their natural history cannot be reliably predicted. There is a need to consider alternative research approaches, including the use of unsupervised statistical techniques with available data, as well as integrative systems biology. Some initiatives, such as MeDALL,8Antó J.M. Pinart M. Akdis M. Auffray C. Bachert C. Basagaña X. et al.Understanding the complexity of IgE-related phenotypes from childhood to young adulthood: a Mechanisms of the Development of Allergy (MeDALL) seminar.J Allergy Clin Immunol. 2012; 129: 943-954Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar, 9Bousquet J. Anto J. Auffray C. Akdis M. Cambon-Thomsen A. Keil T. et al.MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine.Allergy. 2011; 66: 596-604Crossref PubMed Scopus (144) Google Scholar combine both approaches.Research prioritiesBroadly, research priorities could be classified into 3 groups (Table III):1.Better characterization of phenotypes, including (1) a unique agreed-upon classification of asthma that can be applied to research, diagnosis, and treatment; (2) a better understanding of the interplay between asthma and allergy; (3) how allergic phenotypes interrelate across the life cycle; and (4) whether extreme phenotypes can be defined.8Antó J.M. Pinart M. Akdis M. Auffray C. Bachert C. Basagaña X. et al.Understanding the complexity of IgE-related phenotypes from childhood to young adulthood: a Mechanisms of the Development of Allergy (MeDALL) seminar.J Allergy Clin Immunol. 2012; 129: 943-954Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar, 9Bousquet J. Anto J. Auffray C. Akdis M. Cambon-Thomsen A. Keil T. et al.MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine.Allergy. 2011; 66: 596-604Crossref PubMed Scopus (144) Google Scholar2.Natural history and its determinants. There is a well-established relationship between lung function impairment and chronic wheezing and asthma. However, links to new-onset and chronic asthma in adults and to chronic obstructive pulmonary disease are of great interest but require more data.32Svanes C. Sunyer J. Plana E. Dharmage S. Heinrich J. Jarvis D. et al.Early life origins of chronic obstructive pulmonary disease.Thorax. 2010; 65: 14-20Crossref PubMed Scopus (310) Google Scholar Another relevant aspect concerns risk stratification and risk prediction because current models lack sufficient accuracy to be of clinical use at the individual level.3.Pathogenesis. Understanding the mechanisms of asthma and allergies from early life to old age (across the life cycle) is an important requirement for a better understanding of phenotypes and their natural history (ie, expression, progression, and remission). There is a close interaction between clinical and epidemiologic research.Table IIIResearch priorities of clinical phenotypes workgroupBetter characterization of clinical phenotypes Allergic vs nonallergic phenotypes Comorbidity of allergic phenotypes Unsupervised phenotyping (using cluster analysis, latent class analysis, and other methods) Environment-induced phenotypes (eg, air pollution and low chemical dose) Risk factors of severity and difficult-to-treat wheezing Stratified medicine approach in asthma Evolution and validation of new phenotypes Sex, race, and genetics as phenotypic determinants Computational models for complex data/multifactorial assessment of risk factorsNatural history and its determinants Long-term patterns of airflow limitation from early life to late adulthood and chronic obstructive pulmonary disease Role of lung function in assessing phenotypes Risk prediction and severity scores Natural history (eg, puberty, sex, race/ethnicity, and minorities) Influence of antenatal and in utero risk factors on phenotypesMechanisms of asthma and allergies Genomic (genes and epigenetics) determinants Overweight, obesity, growth, fat distribution, and related mechanisms Biomarkers Immunologic mechanisms and immunophenotyping Vitamin D Gut microbiome Stress and neurophenotyping Microbiome and its interactions with immunologic mechanisms Open table in a new tab Workgroup 2: Asthma risk factors (group membership: Table I)The contribution of birth cohort studies to understanding risk and protective factorsNumerous environmental determinants have been assessed in birth cohorts: exposure to environmental tobacco smoke, ambient air pollution, and indoor factors, such as household chemicals, molds, and water damage. Environment plays a role during preg
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