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      Profiling Persistent Asthma Phenotypes in Adolescents: A Longitudinal Diagnostic Evaluation from the INSPIRERS Studies

      research-article
      1 , 2 , 3 , 4 , * , 1 , 2 , 1 , 2 , 1 , 2 , 5 , 5 , 1 , 6 , 6 , 5 , 7 , 7 , 8 , 2 , 8 , 9 , 10 , 11 , 11 , 12 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 11 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 6 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 1 , 2 , 5
      International Journal of Environmental Research and Public Health
      MDPI
      asthma, adolescents, phenotypes, clustering, longitudinal studies, latent class analysis

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          Abstract

          We aimed to identify persistent asthma phenotypes among adolescents and to evaluate longitudinally asthma-related outcomes across phenotypes. Adolescents (13–17 years) from the prospective, observational, and multicenter INSPIRERS studies, conducted in Portugal and Spain, were included ( n = 162). Latent class analysis was applied to demographic, environmental, and clinical variables, collected at a baseline medical visit. Longitudinal differences in clinical variables were assessed at a 4-month follow-up telephone contact ( n = 128). Three classes/phenotypes of persistent asthma were identified. Adolescents in class 1 ( n = 87) were highly symptomatic at baseline and presented the highest number of unscheduled healthcare visits per month and exacerbations per month, both at baseline and follow-up. Class 2 ( n = 32) was characterized by female predominance, more frequent obesity, and uncontrolled upper/lower airways symptoms at baseline. At follow-up, there was a significant increase in the proportion of controlled lower airway symptoms ( p < 0.001). Class 3 ( n = 43) included mostly males with controlled lower airways symptoms; at follow-up, while keeping symptom control, there was a significant increase in exacerbations/month ( p = 0.015). We have identified distinct phenotypes of persistent asthma in adolescents with different patterns in longitudinal asthma-related outcomes, supporting the importance of profiling asthma phenotypes in predicting disease outcomes that might inform targeted interventions and reduce future risk.

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          Most cited references32

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          Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration.

          Much medical research is observational. The reporting of observational studies is often of insufficient quality. Poor reporting hampers the assessment of the strengths and weaknesses of a study and the generalizability of its results. Taking into account empirical evidence and theoretical considerations, a group of methodologists, researchers, and editors developed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations to improve the quality of reporting of observational studies. The STROBE Statement consists of a checklist of 22 items, which relate to the title, abstract, introduction, methods, results and discussion sections of articles. Eighteen items are common to cohort studies, case-control studies and cross-sectional studies and four are specific to each of the three study designs. The STROBE Statement provides guidance to authors about how to improve the reporting of observational studies and facilitates critical appraisal and interpretation of studies by reviewers, journal editors and readers.This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the STROBE Statement. The meaning and rationale for each checklist item are presented. For each item, one or several published examples and, where possible, references to relevant empirical studies and methodological literature are provided. Examples of useful flow diagrams are also included. The STROBE Statement, this document, and the associated web site (http://www.strobe-statement.org) should be helpful resources to improve reporting of observational research.
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            WHO Child Growth Standards based on length/height, weight and age

            To describe the methods used to construct the WHO Child Growth Standards based on length/height, weight and age, and to present resulting growth charts.
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              Global burden of asthma among children.

              About 334 million people worldwide suffer from asthma, and this figure may be an underestimation. It is the most common chronic disease in children. Asthma is among the top 20 chronic conditions for global ranking of disability-adjusted life years in children; in the mid-childhood ages 5-14 years it is among the top 10 causes. Death rates from asthma in children globally range from 0.0 to 0.7 per 100 000. There are striking global variations in the prevalence of asthma symptoms (wheeze in the past 12 months) in children, with up to 13-fold differences between countries. Although asthma symptoms are more common in many high-income countries (HICs), some low- and middle-income countries (LMICs) also have high levels of asthma symptom prevalence. The highest prevalence of symptoms of severe asthma among children with wheeze in the past 12 months is found in LMICs and not HICs. From the 1990s to the 2000s, asthma symptoms became more common in some high-prevalence centres in HICs; in many cases, the prevalence stayed the same or even decreased. At the same time, many LMICs with large populations showed increases in prevalence, suggesting that the overall world burden is increasing, and that therefore global disparities in asthma prevalence are decreasing. The costs of asthma, where they have been estimated, are relatively high. The global burden of asthma in children, including costs, needs ongoing monitoring using standardised methods.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Environ Res Public Health
                Int J Environ Res Public Health
                ijerph
                International Journal of Environmental Research and Public Health
                MDPI
                1661-7827
                1660-4601
                24 January 2021
                February 2021
                : 18
                : 3
                : 1015
                Affiliations
                [1 ]Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; cristinajacome.ft@ 123456gmail.com (C.J.); rutealmeida@ 123456med.up.pt (R.A.); ambrpereira@ 123456gmail.com (A.M.P.); sandra.mamendes@ 123456gmail.com (S.M.); fonseca.ja@ 123456gmail.com (J.A.F.)
                [2 ]Department of Community Medicine, Information and Health Decision Sciences (MEDCIDS), Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; ferreirademagalhaes@ 123456gmail.com
                [3 ]Department of Cardiovascular and Respiratory Sciences, Porto Health School, Polytechnic Institute of Porto, 4200-072 Porto, Portugal
                [4 ]Department of Women’s and Children’s Health, Paediatric Research, Uppsala University, SE-751 05 Uppsala, Sweden
                [5 ]Allergy Unit, CUF Porto Hospital and Institute, 4100-180 Porto, Portugal; magnacorreia1@ 123456gmail.com (M.A.-C.); luisaraujo78@ 123456gmail.com (L.A.)
                [6 ]Serviço de Pediatria, Hospital Pedro Hispano, Unidade Local de Saúde de Matosinhos, 4464-513 Matosinhos, Portugal; jccidraisrodrigues@ 123456hotmail.com (J.C.C.R.); joana.teixeiracarvalho@ 123456gmail.com (J.C.); cristina.lopes.abreu@ 123456gmail.com (C.L.)
                [7 ]Serviço de Pediatria, Hospital Senhora da Oliveira, 4835-044 Guimarães, Portugal; agcosta40@ 123456gmail.com (A.C.); armandinapf@ 123456gmail.com (A.S.)
                [8 ]Serviço de Pediatria, Centro Materno Infantil do Norte, Centro Hospitalar Universitário do Porto, 4099-001 Porto, Portugal; mfernandateixeira59@ 123456gmail.com
                [9 ]Serviço de Imunoalergologia, Hospital do Divino Espírito Santo, 9500-370 Ponta Delgada, Portugal; rodrigosralves@ 123456gmail.com
                [10 ]Unidade de Imunoalergologia, Hospital do Divino Espírito Santo, 9500-370 Ponta Delgada, Portugal; aninhasnet@ 123456gmail.com
                [11 ]Departamento de Pediatria, Hospital de Santa Maria, Centro Hospitalar de Lisboa Norte, 1649-035 Lisboa, Portugal; rmfernandes@ 123456campus.ul.pt (R.M.F.); rosariotferreira@ 123456sapo.pt (R.F.); amargaretemmendes@ 123456gmail.com (A.M.)
                [12 ]Serviço de Imunoalergologia, Hospital de Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, 1150-199 Lisboa, Portugal; pleiriapinto@ 123456gmail.com (P.L.P.); nuno.neuparth@ 123456nms.unl.pt (N.N.)
                [13 ]Pathophysiology, CHRC/CEDOC, High Burden and High Mortality Diseases Thematic Line Coordinator, Nova Medical School, 1150-190 Lisboa, Portugal
                [14 ]Serviço de Pediatria, Unidade Hospitalar de Famalicão, Centro Hospitalar do Médio Ave, 4780-371 Vila Nova de Famalicão, Portugal; diana.bordalo@ 123456gmail.com
                [15 ]Serviço de Imunoalergologia, Centro Hospitalar e Universitário de Coimbra, 3000-075 Coimbra, Portugal; flcosta@ 123456netcabo.pt
                [16 ]Serviço de Pediatria, Hospital de São Teotónio, Centro Hospitalar Tondela–Viseu, 3504-509 Viseu, Portugal; mariajosecalix@ 123456gmail.com
                [17 ]Unidade de Saúde Familiar Progresso e Saúde, ACeS Baixo Mondego, 3060-716 Tocha, Portugal; tani_ferreira@ 123456hotmail.com
                [18 ]Serviço de Imunoalergologia, Unidade I, Centro Hospitalar Vila Nova de Gaia/Espinho, 4434-502 Vila Nova de Gaia, Portugal; joanarqueirosg@ 123456gmail.com
                [19 ]Servicio de Alergia, Complejo Hospitalario Universitario de Santiago, 15706 Santiago De Compostela, Spain; carmen.vidal.pan@ 123456sergas.es
                [20 ]Serviço de Imunoalergologia, Centro Hospitalar Universitário de São João, 4200–319 Porto, Portugal; mariajoaosvasconcelos@ 123456gmail.com
                [21 ]Imunoalergologia, Grupo HPA Saúde, 8500-322 Portimão, Portugal; pedrotiagosilva@ 123456gmail.com
                [22 ]Imunoalergologia, Hospital Privado de Alfena, Trofa Saúde, 4445-243 Alfena, Portugal; zeferrazdeo@ 123456gmail.com
                [23 ]Serviço de Imunoalergologia, Hospital Infante D. Pedro, Centro Hospitalar Baixo Vouga, 3814-501 Aveiro, Portugal; anamorete@ 123456gmail.com
                [24 ]Serviço de Pneumologia, Hospital São Pedro de Vila Real, Centro Hospitalar De Trás-Os-Montes E Alto Douro, 5000-508 Vila Real, Portugal; csmnspinto@ 123456gmail.com
                [25 ]Serviço de Imunoalergologia, Centro Hospitalar Universitário do Algarve, 8000-386 Portimão, Portugal; nsantos.alergia@ 123456gmail.com
                [26 ]Serviço de Pneumologia, Hospitais da Universidade de Coimbra, 3000-076 Coimbra, Portugal; cl_loureiro@ 123456hotmail.com
                [27 ]Serviço de Pneumologia, Centro Hospitalar e Universitário de Coimbra, 3000-075 Coimbra, Portugal; ana.arrobas@ 123456gmail.com
                [28 ]Serviço de Imunoalergologia, Centro Hospitalar Universitário do Porto, 4099-001 Porto, Portugal; maluis234@ 123456gmail.com
                [29 ]Serviço de Imunoalergologia, Hospital Amato Lusitano, Unidade Local de Saúde de Castelo Branco, 6000-085 Castelo Branco, Portugal; clozoya@ 123456fcsaude.ubi.pt
                [30 ]Imunologia Básica e Clínica, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal
                [31 ]Unidade de Saúde Familiar Terras de Azurara, ACES Dão Lafões, 3530-113 Mangualde, Portugal; francisca.cardia@ 123456gmail.com
                [32 ]Departamento de Pediatria, Serviço de Pediatria Ambulatória, Centro Hospitalar e Universitário de Coimbra, 3000-075 Coimbra, Portugal; carlachavesloureiro@ 123456gmail.com
                [33 ]Serviço de Pneumologia, Hospital Nossa Senhora do Rosário, Centro Hospitalar Barreiro Montijo, 2834-003 Barreiro, Portugal; raquelpaulinetticamara@ 123456gmail.com
                [34 ]UCSP Dr. Arnaldo Sampaio, ACES Pinhal Litoral, 2419-014 Leiria, Portugal; ines_b_vieira@ 123456hotmail.com
                [35 ]USF Cuidarte, Unidade Local de Saúde do Alto Minho, 4925-083 Portuzelo, Portugal; sofia.carla.silva@ 123456gmail.com
                [36 ]Unidade de Saúde Familiar João Semana, ACeS Baixo Vouga, 3880-225 Ovar, Portugal; euriko7@ 123456gmail.com
                [37 ]Unidade de Saúde Familiar Mondego, ACES Baixo Mondego, 3045-059 Coimbra, Portugal; natalinarodrigues89@ 123456gmail.com
                Author notes
                [* ]Correspondence: rita.s.amaral@ 123456gmail.com ; Tel.: +351-917-006-669
                Author information
                https://orcid.org/0000-0002-0233-830X
                https://orcid.org/0000-0002-1151-8791
                https://orcid.org/0000-0001-7755-5002
                https://orcid.org/0000-0002-5468-0932
                https://orcid.org/0000-0003-2061-7844
                https://orcid.org/0000-0001-6561-2153
                https://orcid.org/0000-0002-7580-1166
                https://orcid.org/0000-0002-7253-6475
                https://orcid.org/0000-0003-1374-4327
                https://orcid.org/0000-0001-5149-7473
                https://orcid.org/0000-0002-0864-3612
                https://orcid.org/0000-0002-2844-2754
                https://orcid.org/0000-0003-2241-7889
                https://orcid.org/0000-0003-2925-2618
                https://orcid.org/0000-0002-0887-8796
                Article
                ijerph-18-01015
                10.3390/ijerph18031015
                7908090
                33498858
                cc1646a0-0374-4312-88e2-fad9a56b54e3
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 13 December 2020
                : 20 January 2021
                Categories
                Article

                Public health
                asthma,adolescents,phenotypes,clustering,longitudinal studies,latent class analysis
                Public health
                asthma, adolescents, phenotypes, clustering, longitudinal studies, latent class analysis

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