Episodes de respiration sifflante chez le jeune enfant : prévalence et facteurs de risque en ville de São Paulo (Brésil)
Cuadros con sibilancias en la primera infancia: prevalencia y factores de riesgo en la ciudad de São Paulo, Brasil
Maria Helena D'A. BenícioI,1; Marcelo U. FerreiraII; Maria Regina A. CardosoIII; Sílvia C. KonnoIV; Carlos A. MonteiroV
IAssistant Professor, Department of Nutrition, School of Public Health, University of São Paulo, Avenue Dr. Arnaldo 715, 01246-904, São Paulo (SP), Brazil
IIAssistant Professor, Department of Parasitology, Institute for Biomedical Sciences, University of São Paulo, São Paulo, Brazil
IIIAssistant Professor, Department of Epidemiology, School of Public Health, University of São Paulo, Brazil
IVGraduate Student, Department of Nutrition, School of Public Health, University of São Paulo, Brazil
VProfessor, Department of Nutrition, School of Public Health, University of São Paulo, São Paulo, Brazil
OBJECTIVE: To investigate the prevalence and risk factors for wheezing disorders in early childhood in São Paulo, Brazil, the largest metropolitan area of South America.
METHODS: A population-based cross-sectional survey of 1132 children aged 659 months was carried out between 1995 and 1996 to obtain information on recent wheezing and on independent variables such as demographic, socioeconomic, environmental, maternal and nutritional variables and immunization status. Intestinal parasitic infections were diagnosed using standard techniques. Multiple unconditional logistic regression was used to describe associations between outcome and independent variables.
FINDINGS: The prevalence of recent wheezing (one or more reported episodes in the past 12 months) was 12.5%; 93% of children with wheezing were also reported to have a medical diagnosis of asthma. Recent wheezing was associated with low per capita income, poor quality of housing, day-care attendance, low birth weight and infection with intestinal helminths.
CONCLUSION: Wheezing in early childhood in São Paulo, although more common than in most developing countries, remains less prevalent than in urban areas of industrialized countries. Low income and conditions associated with poverty (poor housing, low birth weight and parasitic infections) are some of the main risk factors for wheezing disorders among young children in this city.
Keywords: Respiratory tract diseases/epidemiology; Asthma/epidemiology; Prevalence; Risk factors; Helminths; Giardiasis; Air pollution, Indoor; Socioeconomic factors; Housing; Vaccination; Child; Cross-sectional studies; Brazil (source: MeSH, NLM).
OBJECTIF: Etudier la prévalence et les facteurs de risque des épisodes de respiration sifflante chez le jeune enfant à São Paulo (Brésil), la plus grande métropole d'Amérique du Sud.
MÉTHODES: Une enquête transversale portant sur 1132 enfants de 6 à 59 mois a été réalisée dans la population entre septembre 1995 et septembre 1996 afin d'obtenir des informations sur les épisodes récents de respiration sifflante et sur des variables indépendantes telles que variables démographiques, socio-économiques, environnementales, maternelles et nutritionnelles et statut vaccinal. Les parasitoses intestinales ont été diagnostiquées selon les méthodes classiques. On a utilisé la régression logistique multiple non conditionnelle pour décrire les associations entre les observations et les variables indépendantes.
RÉSULTATS: La prévalence des épisodes récents de respiration sifflante (un ou plusieurs épisodes rapportés au cours des 12 derniers mois) était de 12,5 % ; chez 93 % des enfants atteints, un diagnostic d'asthme était également rapporté. Les épisodes récents de respiration sifflante étaient associés aux variables suivantes : faible revenu par habitant, qualité médiocre de l'habitat, fréquentation d'une crèche, faible poids de naissance et helminthiases intestinales.
CONCLUSION: Les épisodes de respiration sifflante chez le jeune enfant à São Paulo, bien que plus répandus que dans la plupart des pays en développement, ont une prévalence plus faible que dans les zones urbaines des pays industrialisés. Un faible revenu et des facteurs associés à la pauvreté (qualité médiocre de l'habitat, faible poids de naissance et parasitoses) figurent parmi les principaux facteurs de risque de respiration sifflante chez les jeunes enfants de cette ville.
Mots clés: Respiratoires, Maladies/épidémiologie; Asthme/épidémiologie; Prévalence; Facteur risque; Helminthe; Giardiase; Pollution air ambiant; Facteur socio-économique; Logement; Vaccination; Enfant; Etude section efficace; Brésil (source: MeSH, INSERM).
OBJETIVO: Investigar la prevalencia y los factores de riesgo de sufrir cuadros con sibilancias en la primera infancia en São Paulo, Brasil, el área metropolitana más extensa de América del Sur.
MÉTODOS: Entre 1995 y 1996 se llevó a cabo una encuesta transversal basada en la población entre 1132 niños de 6-59 meses con objeto de obtener información sobre los antecedentes recientes de sibilancias y sobre variables independientes relacionadas con características demográficas, socioeconómicas y ambientales, con el estado de la madre y la nutrición y con el estado de inmunización. Se diagnosticaron los casos de parasitosis intestinal mediante técnicas de uso común. Para describir las relaciones entre las variables dependientes y las independientes se utilizó el método de regresión múltiple incondicional.
RESULTADOS: La prevalencia de sibilancias recientes (notificación de uno o más episodios en los 12 últimos meses) fue del 12,5%; al 93% de los niños con sibilancias se les había diagnosticado también asma. Las sibilancias recientes se asociaron a unos ingresos per cápita bajos, una vivienda de calidad deficiente, la asistencia diurna, un bajo peso al nacer y la presencia de infección por helmintos intestinales.
CONCLUSIÓN: La prevalencia de sibilancias en la primera infancia en la ciudad de São Paulo, aunque superior a la de la mayoría de los países en desarrollo, sigue siendo menor que en las zonas urbanas de los países industrializados. Los ingresos bajos y los problemas asociados a la pobreza (vivienda deficiente, bajo peso al nacer e infecciones parasitarias) son algunos de los principales factores de riesgo de trastornos causantes de sibilancias entre los niños pequeños en esa ciudad.
Palabras clave: Enfermedades respiratorias/epidemiología; Asma/epidemiología; Prevalencia; Factores de riesgo; Helmintos; Giardiasis; Contaminación del aire interior; Factores socioeconómicos; Vivienda; Vacunación; Niño; Estudios transversales; Brasil (fuente: DeCS, BIREME).
The rising prevalence of asthma, one of the most common chronic disorders of childhood, has been associated with increased exposure to environmental allergens, air pollution and foods new to the children, and with reduced exposure to microbes as a result of more "hygienic" living conditions in developed countries (1, 2). Asthma and wheezing are less frequent in developing than in developed countries (3), but recent increases in prevalence have been reported in the tropics (4, 5). In São Paulo, Brazil, the largest metropolitan area in South America, the current prevalence of wheezing in children less than 5 years old has increased from 0.8% to 2.8% over the past decade (6).
Asthma in early childhood is difficult to distinguish from other wheezing disorders; transient wheeze due to viral infections, for example, differs in both pathogenesis and risk factors from atopy-related wheezing (7). Only 36% of the children less than 5 years old who had been diagnosed with wheezing of uncertain etiology during emergency consultations in São Paulo were diagnosed as asthmatic during the following 3 years (8). Moreover, some risk factors for transient wheeze, such as exposure to other children at home and at day-care centres, may protect them from atopy-related wheezing in later childhood (9, 10). This report presents the prevalence and risk factors for wheezing conditions obtained in a large population-based survey of children aged less than 5 years old living in São Paulo.
Subjects and methods
Study design and methodology
This cross-sectional survey, carried out between September 1995 and September 1996 in the city of São Paulo, was based on a random sample of 1073 households with at least one child aged 059 months. Participants were selected using a multiple-stage cluster sampling procedure, with deliberate over-representation of those in low-income areas (11). After informed consent had been obtained, a questionnaire with questions on demographic and socioeconomic factors was administered to the mothers or guardians of 1336 (96%) of the 1390 children less than 5 years old who lived in these 1073 homes. Housing quality was described using a four-level index based on wall and floor characteristics: 1. brick walls and floor covered with parquet or wall-to-wall carpet; 2. brick walls and floor paved with glazed paving tiles; 3. brick walls and floor paved with cement, brick or other kinds of flooring; and 4. walls made of construction scraps and floor paved with cement, brick or other kinds of flooring. Each mother or guardian was given a plastic container identified with the name of each of their children aged less than 5 years and asked to provide a stool sample from each child at the next visit.
At the second visit, 92% of the children from the original sample were clinically examined by a paediatrician and had their clinical history taken. Data on recent wheezing (defined as one or more episodes of wheeze in the past 12 months) were obtained as standardized for the International Study on Asthma and Allergies in Children (ISAAC) and validated in São Paulo (12). Information on any previous medical diagnosis of asthma was also obtained from the mothers or guardians, but no attempt was made to investigate family history of asthma or atopy. These analyses were restricted to the 1132 children aged 659 months at the time of the second visit. Of these children, 932 provided stool samples. The stool samples were examined for ova, cysts and larvae of intestinal parasites (13). No significant differences were found between the demographic and socioeconomic characteristics of children who provided a stool sample and those of the 200 children who did not provide such a sample (13).
Multiple unconditional logistic regression models were used to describe associations between potential risk factors (independent variables) and recent wheezing. Five-level hierarchical models were constructed to investigate independent associations between explanatory and outcome variables, while controlling for potential confounders in the same or more distal hierarchical levels (14). The variables included at each hierarchical level are shown in Table 1: the first (distal) level included socioeconomic variables, the next levels comprised environmental, maternal and nutritional variables and the last (proximate) level comprised data on exposure to infections. Variables associated with P values < 0.20 within each level were maintained in subsequent models including variables in more proximate levels. Models were adjusted for age and sex. Tests for linear trends in the logistic models were calculated by unfactoring the following variables: per capita family income, education (number of years of schooling) of mother, housing quality index and number of siblings. The software packages used were Epi Info 2000 (Centers for Disease Control and Prevention, Atlanta, GA, USA) and version 6.0 of the Stata software package (Stata, College Station, USA).
The weighted prevalence of recent wheezing, that took into account sampling weights, was 12.5%; similar figures were obtained for girls and boys (Table 1). Most children with recent wheezing (93%) were also reported, by their mothers or guardians, to have a medical diagnosis of asthma, but uncertainties in the clinical diagnosis of asthma in children in this age group limited further analysis of these results. The prevalence of recent wheezing varied according to income strata and housing conditions, with a clear doseresponse effect (Table 1).
The results of the adjusted analysis of data (Table 2) did not differ substantially from those of the unadjusted analysis shown in Table 1, with the exception of attendance at a day-care centre. The following variables were independently associated with an increased risk of recent wheezing: low family income, poor housing quality, day-care centre attendance, low birth weight, and infection with intestinal helminths. The predominant helminths in this population (prevalence, 5.8%) were Ascaris lumbricoides and Trichuris trichiura (13). To verify whether helminthic infection was merely a marker of increased exposure to other orofaecal microbes, we also examined the association between infection with Giardia duodenalis (the most prevalent intestinal protozoon in this population (13)) and recent wheezing, and found no significant relationship (Table 2).
This is one of the few population-based surveys of wheezing conditions in early childhood to be carried out in a tropical urban area. In this study recent wheezing was found to be nearly as prevalent (12.5%) as in southern Tanzania (14.0%) (15), but less frequent than in urban preschool children living in southern Brazil (21.1%) (16) and in most industrialized countries (17).
Analyses are complicated by the heterogeneity of wheezing conditions in early childhood (7), but wheezing and asthma may share common risk factors in schoolchildren (18). Most studies in industrialized countries, with few exceptions (1921), have found no relationship between asthma and socioeconomic status (2), whereas in tropical countries wheezing and asthma are more frequent in underprivileged children (16, 2224); other allergic conditions, such as hay fever and eczema, predominate in children from more affluent families in industrialized countries (25).
Day-care attendance, which was positively related to family income (frequencies of 11% and 30% in extreme strata), emerged as a significant risk factor only after controlling for socioeconomic variables (Table 2). Children attending day-care centres are at an increased risk of infections of the lower respiratory tract and transient wheeze (26), but may be protected from atopic conditions, including asthma, when they reach school age (9, 27). Low birth weight was associated with wheezing, both in our study and in surveys in the USA (28, 29), possibly due to the reduced lung function in premature infants (30). Nearly 70% of the low-birth-weight children born in São Paulo are preterm (31). It remains unclear whether the early occurrence of wheeze in low-birth-weight children (whether preterm or not) is associated with the development of asthma later in childhood.
Since the early report by Tullis (32), helminths have been suggested either to trigger or to inhibit wheezing conditions in children and adults (33). This hotly debated issue has huge public health implications, because intestinal helminths infect almost one-third of the world's population (34). Positive associations in areas of low prevalence of helminths may result from TH2-type T-cell responses elicited by acute infections, with increased levels of immunoglobulin E, eosinophilia, mastocytosis and allergic reactions (35). In addition, the pulmonary phase of larval migration of some intestinal nematodes, such as Ascaris lumbricoides and hookworm, may cause asthma-like symptoms (the so-called Loeffler's syndrome). Anthelminthic treatment resulted in clinical improvement of asthma in patients in Venezuela (36). The light burden of helminthic infections in our study population (13) fits well within this scenario of low prevalence, whereas in children in Africa who are heavily exposed, chronic helminthic infections may suppress inflammatory responses by mast cell saturation, blocking IgG4 antibodies, tolerance to aeroallergens and T-cell hyporesponsiveness (35, 37).
In contrast to previous studies, we found no significant association between wheezing and male sex (2, 16), parental smoking (2, 16, 38), low number of siblings (24, 39, 40), young maternal age (18), maternal marital status (41), bottle-feeding (42) or immunizations (43). Large surveys have similarly failed to detect associations between wheezing and risk factors such as bottle-feeding (44, 45), passive smoking (46) and immunizations (47). We did not investigate parental history of asthma and atopy, a powerful determinant of childhood asthma (2, 16) that can modify the effect of exclusive breastfeeding (42).
The recent rise in wheezing conditions in early childhood in São Paulo (6) did not result from increases in the proportion children of low-income families; living in poor-quality houses; or from exposure to intestinal helminths, because these risk factors have become less prevalent in the population of São Paulo over the past decade (13, 48, 49). The prevalences of low birth weight and preterm birth remained stable in São Paulo between 1993 and 1998 (31). The recent increase in attendance at day-care centres (6) and some variables not assessed here, such as exposure to air pollutants and indoor aeroallergens, and dietary factors (6, 17), may account for the rise in the prevalence of wheezing and represent additional targets for public health interventions.
Research supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (94/3493-5), the Ministry of Health of Brazil and National Research Council of Brazil (CNPq).
Conflicts of interest: none declared.
1. Magnus P, Jaakkola JJ. Secular trends in the occurrence of asthma among children and young adults: critical appraisal of repeated cross-sectional surveys. BMJ 1997;314:1795-9.
2. Sears MR. Epidemiology of childhood asthma. Lancet 1997;350:1015-20.
3. International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee. Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. Lancet 1998;35:1225-32.
4. Brabin BJ, Kelly Y. Prevalence of childhood asthma in the tropics. Annals of Tropical Paediatrics 1998;18 Suppl:S33-9.
5. Gracey M. Child health in an urbanizing world. Acta Paediatrica 2002;9:1-8.
6. Benício MHD'A, Cardoso MRA, Gouveia NC, Monteiro CA. Secular trends in child respiratory diseases in São Paulo city, Brazil (1984-1996). Revista de Saúde Pública 2000;34 Suppl:91-101.
7. Helms PJ. Issues in pediatric asthma. Pediatric Pulmonology 2001;21 Suppl:49-56.
8. Cardoso MRA, Cousens SN, Alves FM, Ribeiro MM, Abreu Neto BP. Diagnosis and prognosis of wheezing disorders in young children in the city of São Paulo, southeast Brazil. Acta Paediatrica 2000;89:1484-9.
9. Ball TM, Castro-Rodriguez JA, Griffith KA, Holberg CJ, Martinez F, Wright AL. Siblings, day-care attendance, and the risk of asthma and wheezing during childhood. New England Journal of Medicine 2000;343:538-43.
10. Wright AL. Epidemiology of asthma and recurrent wheeze in childhood. Clinical Reviews in Allergy and Immunology 2002;22:33-44.
11. Monteiro CA, Silva NN, Nazário CL. The field study. In: Monteiro CA, editor. How and why do the health and nutrition indicators in childhood improve (or worsen)? The case of the city of São Paulo in the second half of the 20th century. São Paulo: Center for Epidemiological Studies in Nutrition and Health, University of São Paulo; 1999. Technical report, p. 2-12.
12. Solé D, Vanna AT, Yamada E, Rizzo MC, Naspitz CK. International Study of Asthma and Allergies in Childhood (ISAAC) written questionnaire: validation of the asthma component among Brazilian children. Journal of Investigative Allergology and Clinical Immunology 1998;8:376-82.
13. Muniz PT, Ferreira MU, Ferreira CS, Conde WL, Monteiro CA. Intestinal parasitic infections in young children in São Paulo, Brazil: prevalences, temporal trends and associations with physical growth. Annals of Tropical Medicine and Parasitology 2002;96:503-12.
14. Victora CG, Huttly SR, Fuchs SC, Olinto MTA. The role of conceptual frameworks in epidemiological analysis: a hierarchical approach. International Journal of Epidemiology 1997;26:224-7.
15. Sunyer J, Menendez C, Ventura PJ, Aponte JJ, Schellenberg D, Kahigwa E, et al. Prenatal risk factors of wheezing at the age of four years in Tanzania. Thorax 2001;56:290-5.
16. Chatkin MN, Menezes AMB, Victora CG, Barros FC. High prevalence of asthma in preschool children in southern Brazil: a population-based study. Pediatric Pulmonology 2003;35:296-301.
17. Kuehni CE, Davis A, Brooke AM, Silverman M. Are all wheezing disorders in very young (preschool) children increasing in prevalence? Lancet 2001;357:1821-5.
18. Kurukulaaratchy RJ, Fenn M, Twiselton R, Matthews S, Arshad SH. The prevalence of asthma and wheezing illnesses amongst 10-year-old schoolchildren. Respiratory Medicine 2002;96:163-9.
19. Schwartz J, Gold D, Dockery DW, Weiss ST, Speizer FE. Predictors of asthma and persistent wheeze in a national sample of children in the United States. Association with social class, perinatal events, and race. American Review of Respiratory Diseases 1990;142:555-62.
20. Weitzman M, Gortmaker S, Sobol A. Racial, social, and environmental risks for childhood asthma. American Journal of Diseases of Childhood 1990;144:1189-94.
21. Crain EF, Weiss KB, Bijur PE, Hersh M, Westbrook L, Stein REK. An estimate of the prevalence of asthma and wheezing among inner-city children. Pediatrics 1994;94:356-62.
22. Britto MCA, Bezerra PGM, Ferreira OS, Maranhão ICV, Trigueiro GA. Asthma prevalence in schoolchildren in a city in north-east Brazil. Annals of Tropical Paediatrics 2000;20:95-100.
23. Kurunasekera KAW, Jayasinghe JACT, Alwis LWGR. Risk factors of childhood asthma: a Sri Lankan study. Journal of Tropical Pediatrics 2001;47:142-5.
24. Hassan MR, Kabir ARML, Mahmud AM, Rahman F, Houssain MA, Bennoor KS, et al. Self-reported asthma symptoms in children and adults of Bangladesh: findings of the National Asthma Prevalence Study. International Journal of Epidemiology 2002;31:483-8.
25. Strachan DP. Family size, infection and atopy: the first decade of the "hygiene hypothesis". Thorax 2000;55 Suppl 1:S2-S10.
26. Marbury MC, Maldonado G, Waller L. Lower respiratory illness, recurrent wheezing, and day care attendance. American Journal of Respiratory and Critical Care Medicine 1997;155:156-61.
27. Celedón JC, Litonjua AA, Ryan L, Weiss ST, Gold DR. Day care attendance, respiratory tract illnesses, wheezing, asthma, and total serum IgE level in early childhood. Archives of Pediatrics and Adolescent Medicine 2002;156:241-5.
28. Brooks A-M, Byrd RS, Weitzman M, Auinger P, McBride JT. Impact of low birth weight on early childhood asthma in the United States. Archives of Pediatrics and Adolescent Medicine 2002;155:401-6.
29. Palta M, Sadek-Badawi M, Sheehy M, Albanese A, Weinstein M, McGuinness G, et al. Respiratory symptoms at age 8 years in a cohort of very low birth weight children. American Journal of Epidemiology 2001;154:521-9.
30. Speer CP, Silverman M. Issues relating to children born prematurely. European Respiratory Journal 1998;27 Suppl:13S-16S.
31. Monteiro CA, Benício MHD'A, Ortiz LP. Secular trends in birth weight in São Paulo city, Brazil. Revista de Saúde Pública 2000;34 Suppl:26-40.
32. Tullis DCH. Bronchial asthma associated with intestinal parasites. New England Journal of Medicine 1970;282:370-2.
33. Weiss S. The relationship of parasites to asthma. Clinical and Experimental Allergy 1998;28 Suppl 1:38-9.
34. Albonico M, Crompton DWT, Savioli L. Control strategies for human intestinal nematode infections. Advances in Parasitology 1999;42:277-341.
35. Cooper PJ. Can intestinal helminth infections (geohelminths) affect the development and expression of asthma and allergic disease? Clinical and Experimental Immunology 2002;128:398-404.
36. Lynch NR, Palenque M, Hagel I, DiPrisco MC. Clinical improvement of asthma after anthelminthic treatment in a tropical situation. American Journal of Respiratory and Critical Care Medicine 1997;156:50-4.
37. Yazdanbakhsh M, Kremsner PG, van Ree R. Allergy, parasites, and the hygiene hypothesis. Science 2002;296:490-4.
38. Trager IB. Smoking and childhood asthma. Where do we stand? American Journal of Respiratory and Critical Care Medicine 1998;158:349-51.
39. Jarvis D, Chinn S, Luczynska C, Burney P. The association of family size to atopy and atopic disease. Clinical and Experimental Allergy 1997;27:240-5.
40. Bodner C, Godden D, Seaton A. Family size, childhood infections and atopic diseases. The Aberdeen WHEASE Group. Thorax 1998;53:28-32.
41. Sherriff A, Peters TJ, Henderson J, Strachan D and the ALSPAC Study Team. Risk factor associations with wheezing patterns in children followed longitudinally from birth to 3½ years. International Journal of Epidemiology 2001;30:1473-84.
42. Gdalevich M, Mimouni D, Mimouni M. Breast-feeding and the risk of bronchial asthma in childhood: A systematic review with meta-analysis of prospective studies. Journal of Pediatrics 2001;139:261-6.
43. Farooqi IS, Hopkin JM. Early childhood infection and atopic disorder. Thorax 1998;53:927-32.
44. Takemura Y, Sakurai Y, Honjo S, Kusakari A, Hara T, Gibo M, et al. Relation between breastfeeding and the prevalence of asthma. The Tokorozawa Childhood Asthma and Pollinosis Study. American Journal of Epidemiology 2001;154:115-9.
45. Sears MR, Greene JM, Willan AR, Taylor DR, Flannery EM, Cowan JO, et al. Long-term relation between breastfeeding and development of atopy and asthma in children and young adults: a longitudinal study. Lancet 2002;360:901-7.
46. Charpin D, Gouitaa M. Why is the prevalence of allergic diseases increasing? A critical assessment of some classical risk factors. Mediators of Inflammation 2001;10:292-4.
47. von Mutius E. Infection: friend or foe in the development of atopy and asthma? The epidemiological evidence. European Respiratory Journal 2001;18:872-81.
48. Monteiro CA, Freitas ICM. Secular trends in socioeconomic determinants of child health in São Paulo city, Brazil (1984-1996). Revista de Saúde Pública 2000;34 Suppl:8-12.
49. Monteiro CA, Nazário CL. Secular trends in environmental determinants of child health in São Paulo, Brazil (1984-1996). Revista de Saúde Pública 2000;34 Suppl:13-18.
(Submitted: 30 July 2003 Final revised version received: 3 November 2003 Accepted: 1 December 2003)