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BMJ Open Is Committed to Open Peer Review. As Part of This Commitment We Make the Peer Review History of Every Article We Publish Publicly Available BMJ Open: first published as 10.1136/bmjopen-2019-034192 on 22 April 2020. Downloaded from BMJ Open is committed to open peer review. As part of this commitment we make the peer review history of every article we publish publicly available. When an article is published we post the peer reviewers’ comments and the authors’ responses online. We also post the versions of the paper that were used during peer review. These are the versions that the peer review comments apply to. The versions of the paper that follow are the versions that were submitted during the peer review process. They are not the versions of record or the final published versions. They should not be cited or distributed as the published version of this manuscript. BMJ Open is an open access journal and the full, final, typeset and author-corrected version of record of the manuscript is available on our site with no access controls, subscription charges or pay-per-view fees (http://bmjopen.bmj.com). If you have any questions on BMJ Open’s open peer review process please email [email protected] http://bmjopen.bmj.com/ on September 30, 2021 by guest. Protected copyright. BMJ Open BMJ Open: first published as 10.1136/bmjopen-2019-034192 on 22 April 2020. Downloaded from Prevalence and risk factors for wheeze, decreased forced expiratory volume in one second and bronchoconstriction in young children living in Havana, Cuba: A prospective population-based study ForJournal: peerBMJ Open review only Manuscript ID bmjopen-2019-034192 Article Type: Original research Date Submitted by the 10-Sep-2019 Author: Complete List of Authors: Suarez-Medina, Ramon; INHEM Venero-Fernández, Silvia; INHEM Corona-Tamayo, Barbara; Dirección Municipal de Salud Pública municipios Cerro y Arroyo Naranjo Betancourt-López, Maria; INHEM Alvarez-Valdés, Vilma; Dirección Municipal de Salud Pública municipios Cerro y Arroyo Naranjo Sardiñas-Baez, Nieves; Dirección Municipal de Salud Pública municipios Cerro y Arroyo Naranjo Cristina, Carmona; Dirección Municipal de Salud Pública municipios Cerro y Arroyo Naranjo http://bmjopen.bmj.com/ Loinaz-Gonzalez, Maria; Dirección Municipal de Salud Pública municipios Cerro y Arroyo Naranjo Verdecia-Pérez, Zunilda; Dirección Municipal de Salud Pública municipios Cerro y Arroyo Naranjo Britton, John; UK Center for Tobacco and Alcohol Studies, Division of Epidemiology and Public Health Fogarty, Andrew; University of Nottingham, Keywords: PAEDIATRICS, Asthma < THORACIC MEDICINE, Cuba on September 30, 2021 by guest. 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Protected copyright. 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 2 of 26 Prevalence and risk factors for wheeze, decreased forced expiratory volume in one second 1 and bronchoconstriction in young children living in Havana, Cuba: A prospective 2 3 population-based study 4 BMJ Open: first published as 10.1136/bmjopen-2019-034192 on 22 April 2020. Downloaded from 5 * Ramon Suarez-Medina1 6 Silvia Josefina Venero-Fernández1 7 Vilma Alvarez-Valdés2 8 Nieves B Sardiñas-Baez2 9 Cristina Carmona2 10 2 11 María Luisa Loinaz-Gonzalez 12 Zunilda Verdecia-Pérez2 13 Barbara Corona-Tamayo2 14 María Antonia Betancourt-López1 15 John Britton3, 16 Andrew W Fogarty3 17 and the HINASIC (Historia Natural de la Sibilancia en Cuba/Natural History of Wheezing in Cuba) 18 For peer review only ++ 19 Study Group 20 21 1 Instituto Nacional de Higiene, Epidemiología y Microbiología, Infanta No 1158 e/ Llinás y Clavel, 22 Código Postal 10300, La Habana, Cuba. 23 2 Dirección Municipal de Salud Pública municipios Cerro y Arroyo Naranjo, La Habana, Cuba. 24 3 Nottingham Biomedical Research Unit, Division of Epidemiology and Public Health, University of 25 26 Nottingham, Clinical Sciences Building, City Hospital, Nottingham NG5 1PB, UK ++ 27 full list of collaborating researchers at the end of the manuscript 28 29 The corresponding author for the manuscript submission process is Dr Andrew Fogarty 30 ([email protected]) due to poor internet connections with Cuba. 31 32 (If accepted for publication) *Correspondence and requests for reprints to Dr. Ramón Suárez 33 34 Medina: 35 Address: Infanta No 1158 e/ Llinás y Clavel, Código Postal 10300, La Habana, Cuba. 36 Office phone: (537) 878 8479 http://bmjopen.bmj.com/ 37 Email: [email protected] 38 39 Key words: Cuba, asthma, children, wheeze 40 41 42 Word count: 3138 words 43 44 on September 30, 2021 by guest. Protected copyright. 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 1 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 3 of 26 BMJ Open Abstract (298 words) 1 2 3 4 Objectives; Asthma has not been extensively studied in low and middle-income countries, where BMJ Open: first published as 10.1136/bmjopen-2019-034192 on 22 April 2020. Downloaded from 5 risk factors and access to treatment may differ from more affluent countries. we aimed to identify 6 7 the prevalence of asthma and local risk factors in Havana, Cuba. 8 9 10 11 Setting: Four municipalities in Havana, Cuba. 12 13 14 Participants: A population-based cohort study design of young children living in Havana, Cuba. 15 16 Children were recruited from primary care centres at age 12-15 months. 17 18 For peer review only 19 Primary and secondary outcome measures: Data on wheeze in the past 12 months, asthma 20 21 treatment and environmental exposures collected regularly until the age of six years, when Forced 22 23 Expiratory Volume in one second (FEV1) and reversibility to aerosolised salbutamol were also 24 measured. 25 26 27 28 Results: 1106 children provided data at the age of six years old. The prevalence of wheeze in the 29 30 previous 12 months was 422 (38%), and 331 (37%) of the study population had bronchodilatation 31 of 10% or more in FEV after administration of inhaled salbutamol. In the previous 12 months, 182 32 1 33 (16%) of the children had received inhaled corticosteroids, 416 (38%) salbutamol inhalers, and 34 35 283 (26%) a course of systemic steroids. 36 http://bmjopen.bmj.com/ 37 38 Wheeze in the first year and a family history of asthma were both positively associated with 39 40 bronchodilatation to inhaled salbutamol (+1.94%; 95% confidence intervals CI: +0.81 to +3.08, and 41 42 +1.85%; CI: +0.14 to +3.57 respectively), while paracetamol use in the first year was associated 43 with wheeze at six years (OR 1.64, 95% CI: 1.14 to 2.35). There were large differences in FEV , 44 1 on September 30, 2021 by guest. Protected copyright. 45 bronchodilatation and risk of wheeze across different geographical areas. 46 47 48 49 Conclusions: Asthma is common in young children living in Havana, and the high prevalence of 50 systemic steroids administrated is likely to reflect the underuse of regular inhaled corticosteroids. If 51 52 replicated in other comparable low and middle-income countries, this represents an important 53 54 global public health issue. 55 56 57 Keywords: infection, asthma, children, Cuba, lung function 58 59 60 2 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 4 of 26 STRENGTHS AND LIMITATIONS OF THIS STUDY 1 2 There have been many epidemiological studies of asthma in children who live in developed 3 4 countries, but few population-based studies that have used objective measures of asthma BMJ Open: first published as 10.1136/bmjopen-2019-034192 on 22 April 2020.
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