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Jornal de Pediatria

Print version ISSN 0021-7557On-line version ISSN 1678-4782

J. Pediatr. (Rio J.) vol.93 no.3 Porto Alegre May./June 2017 

Original articles

Acute viral bronchiolitis and risk of asthma in schoolchildren: analysis of a Brazilian newborn cohort,☆☆

Heli V. Brandãoa  * 

Graciete O. Vieiraa 

Tatiana O. Vieiraa 

Álvaro A. Cruzb 

Armênio C. Guimarãesc 

Carlos Telesa 

Paulo Camargosd 

Constança M.S. Cruzc 

aUniversidade Estadual de Feira de Santana (UEFS), Departamento de Saúde, Feira de Santana, BA, Brazil

bUniversidade Federal da Bahia (UFBA), Núcleo de Excelência em Asma, Departamento de Clínica Médica, Salvador, BA, Brazil

cEscola Bahiana de Medicina e Saúde Pública, Departamento de Clínica Médica, Salvador, BA, Brazil

dUniversidade Federal de Minas Gerais (UFMG), Departamento de Pediatria, Belo Horizonte, MG, Brazil



To verify whether the occurrence of acute viral bronchiolitis in the first year of life constitutes a risk factor for asthma at age 6 considering a parental history of asthma.


Cross-sectional study in a cohort of live births. A standardized questionnaire of the International Study of Asthma and Allergies in Childhood was applied to the mothers to identify asthma in children at the age of 6 years. Acute viral bronchiolitis diagnosis was performed by maternal report of a medical diagnosis and/or presence of symptoms of coryza accompanied by cough, tachypnea, and dyspnea when participants were 3, 6, 9, and 12 months. Socioeconomic, environmental data, parental history of asthma, and data related to pregnancy were collected in the first 72 h of life of the newborn and in prospective home visits by trained interviewers. The association between acute viral bronchiolitis and asthma was evaluated by logistic regression analysis and potential modifier effect of parental history was verified by introducing an interaction term into the adjusted logistic regression model.


Prevalence of acute viral bronchiolitis in the first year of life was 68.6% (461). The occurrence of acute viral bronchiolitis was a risk factor for asthma at 6 years of age in children with parental history of asthma OR: 2.66, 95% CI (1.10-6.40), modifier effect p = 0.002. Parental history of asthma OR: 2.07, 95% CI (1.29-3.30) and male gender OR: 1.69, 95% CI, (1.06-2.69) were other identified risk factors for asthma.


Acute viral bronchiolitis in the first year of life is a risk factor for asthma in children with parental history of asthma.

KEYWORDS Asthma; Risk factors; Bronchiolitis viral; Child


Asthma is the most prevalent chronic disease in children, resulting in high demand for care in emergency departments as well as hospitalizations,1,2 with a negative impact on quality of life of children and adults.3

Several studies have shown an association between bronchiolitis, recurrent wheezing, and asthma.4,5 Acute viral bronchiolitis (AVB) is the most common viral disease of the lower airways in infants, characterized by inflammation, edema, and necrosis of small airway epithelial cells, with increased mucus production and bronchospasm, whose diagnosis is mainly clinical.6

The pathogens involved in AVB include respiratory syncytial virus (RSV), rhinovirus, influenza A and B, parainfluenza, metapneumovirus, adenovirus, papillomavirus, and bocavirus.7 RSV is the most common pathogen, responsible for 70% of episodes of bronchiolitis in children younger than 2 years. Changes in the immune response of children with a parental history of asthma affected by AVB caused by RSV and rhinovirus are implicated in this virus/asthma association.8-10 Reinfection is common during the first two years of life.11 In Brazil, RSV is responsible for 31.9-64% of hospitalizations for AVB12,13 and co-infections occur in 40% of cases, with rhinovirus being the most common agent.14

Despite the evidence of the association between AVB and clinical manifestations of asthma, there have been few studies evaluating the action of genetic predisposition in this association. Thus, the role of the AVB as a marker of asthma in children with a parental history of the disease in the development of medium and long-term asthma is not exactly known.

The aim of this study was to investigate the association between AVB in the 1st year of life and asthma in children at 6 years of age, according to a parental history of asthma and other confounding variables in a cohort of live births in the Northeast of Brazil.


The cross-sectional study was carried out in a large northeastern city in Brazil with data obtained from a cohort of live births. The cohort was established between April 2004 and March 2005, with the consecutive inclusion of live births from all ten hospitals in the city of Feira de Santana, born to mothers living in the city. The data used in the study were related to those collected in the hospital and during four home visits in the first year of life (3, 6, 9, and 12 months) and at 6 years.

The inclusion criteria were: mothers and their children living in that city; infants born to mothers who had no perinatal complications; newborns who were not admitted to the nursery for a period longer than 24 h.

The exclusion criteria were: children born to mothers with health problems that contraindicated breastfeeding and mothers that were legally separated from their children.

Data collection tool

Children who were included in the cohort at birth were followed monthly by previously trained health care workers through monthly household interviews in the first 6 months of life and then were followed every three months up to the end of the first year, and at scheduled ages and at the sixth year of life.


Sample size calculation was performed in two stages, namely, sample calculation to estimate the prevalence of asthma in children, and then calculating the sample to identify independent asthma predictors.

The asthma prevalence sample calculation was carried out using the PEPI SAMPLE program (WINPEPI computer programs) using the following parameters: estimated prevalence of asthma in schoolchildren of 20%, confidence interval of 95%, and accuracy of 1.25% around the estimated prevalence of the population. The result showed the need to study 202 children, plus an expected loss of 10%, totaling 223 subjects.

To identify bronchiolitis as an asthma predictor, the sample calculation was carried out using the OpenEpi (Open Source Epidemiologic Statistics for Public Health, version 2.3.1) program, based on the following parameters: prevalence of AVB of 27%, confidence interval of 95%, statistical power of 80%, and relative-risk estimate of 2, considering the prevalence of asthma of 10% in non-exposed and 20% in those exposed to respiratory infections. According to the latter calculation, the minimum sample size consisted of 438 individuals.

Between the two calculations, the one with the highest number of participants was chosen (438 individuals). However, all 684 children aged 6 years who were followed in the cohort were included in the study.


The definition of active asthma at 6 years of age was obtained by applying the standardized ISAAC15 study questionnaire to mothers according to an affirmative answer to the question: Has your child had "wheezing" in the last 12 months?

The clinical diagnostic criterion of AVB followed the definition of the American Academy of Pediatrics,16 that is, rhinorrhea accompanied by tachypnea, cough, dyspnea, and intensification of respiratory symptoms such as nasal flaring and intercostal and/or subcostal retractions. Thus, this condition was considered when the child's mother affirmatively answered that her child had a respiratory illness and the physician reported AVB as the diagnosis or reported symptoms of rhinorrhea, accompanied by cough, tachypnea, or dyspnea in the last 15 days, during the interviews at 3, 6, 9, and 12 months of life.


The other co-variables were gestational age (<37 weeks, ≥37 weeks); parity (primiparous, multiparous); household income (<2 minimum wages, ≥2 minimum wages); maternal level of schooling (<8 years of schooling, ≥8 years of schooling); gender (male, female); birth weight (<2500 g, ≥2500 g); number of rooms in the household (<5 rooms, ≥5 rooms); number of individuals sleeping in the same room with the child (<4 individuals, ≥4 individuals); maternal smoking during pregnancy (yes, no); presence of dog or cat at home (yes, no); day care attendance up to 2 years (yes, no); truck traffic on the street where the household is located (yes, no); exclusive breastfeeding until the 3rd month (yes, no); exclusive breastfeeding until the 4th month (yes, no). Maternal clinical data were collected shortly after birth in the maternity wards and verified by checking their respective medical records.

Parental history of asthma was considered according to mother's answer to the question: "Does the child's father or mother have/still has asthma?" (Yes, no).

Statistical analysis

The frequency of the sociodemographic characteristics was calculated and the chi-squared test was used to compare proportions, with p-values <0.05 considered significant. Multivariate logistic regression models were used to assess factors associated with asthma at age 6 and AVB at 3, 6, 9, and 12 months, and in the 1st year of life, considering the main confounding variables and those with p-values ≤0.10 in the bivariate analysis.

The modifier effect of parental history of asthma in the association between AVB and asthma was verified by including the interaction term between parental history of asthma and AVB in the multivariate logistic regression analysis. Statistical analyses were performed using the SPSS (SPSS for Windows, version 14.0, Chicago, USA) program.

Ethical aspects

This study, as well as the free and informed consent form, were approved by the Research Ethics Committee of Universidade Estadual de Feira de Santana.


A total of 672 of 684 eligible children participated in the study (98.2%), as 12 children were not located due to change in home address. The assessed sample had 30 more participants than the previously estimated sample. The prevalence of active asthma was 13.8%.

The clinical and demographic characteristics of the sample are shown in Table 1. Most of the children slept in rooms with fewer than four individuals and were children of parents with no history of asthma.

Table 1 Sample characteristics and association of variables with asthma (n = 672). 

Variables n (%) OR (95 CI%) pa
Male 336 (50.0) 1.79 (1.14-2.81) 0.010
Female 336 (50.0)
Birth weight (grams)
<2500 30 (4.5) 1.25 (0.40-3.37) 0.646
≥2500 642 (95.5)
Gestational age (weeks)
<37 28 (4.2) 0.46 (0.10-2.00) 0.295
≥37 644 (95.8)
Family income (minimum wages)
Up to 2 477 (71.0) 1.28 (0.77-2.12) 0.326
≥2 195 (29.0)
Maternal level of schooling (years of study)
Up to 8 202 (30.1) 0.88 (0.54-1.44) 0.634
>8 470 (69.9)
Primiparous 336 (50.0) 0.88 (0.56-1.36) 0.576
Multiparous 336 (50.0)
Exclusive breastfeeding 3rd month
Yes 248 (36.8) 0.93 (0.59-1.47) 0.760
No 424 (63)
Exclusive breastfeeding 4th month
Yes 137 (20.4) 1.08 (0.63-1.84) 0.773
No 535 (79.6)
Maternal smoking during pregnancy
Yes 20 (3.0) 2.13 (0.75-6.02) 0.142
No 652 (97.0)
People sleeping in the child's bedroom (individuals)
<4 641 (95.4) 2.71 (1.20-6.09) 0.012
≥4 31 (4.6)
Rooms in household (rooms)
<5 541 (80.5) 0.74 (0.44-1.26) 0.275
≥5 131 (19.5)
Attended daycare at 24 months
Yes 104 (15.5) 0.69 (0.35-1.34) 0.277
No 568 (84.5)
Dog or cat in the household
Yes 297 (44.2) 0.99 (0.77-1.27) 0.982
No 375 (55.8)
Truck traffic on the household street
Yes 341 (50.7) 1.02 (0.85-1.22) 0.814
No 331 (49.3)
Parental history of asthma
Yes 180 (26.8) 2.01 (1.27-3.17) 0.002
No 492 (73.2)

aχ 2 test.

The risk factors for asthma in the logistic regression analysis were male gender, having a parental history of asthma, and AVB at 3 and 12 months, and in the 1st year of life (Table 2).

Table 2 Factors associated to asthma at the logistic regression analysis (n = 672). 

Variables OR (95% CI) pa Adjusted OR (95% CI) pb
Male gender 1.79 (1.14-2.81) 0.01 1.69 (1.06-2.69) 0.025
Bronchiolitis at 3 months 1.82 (1.00-3.38) 0.047 1.76 (0.95-3.27) 0.007
Bronchiolitis at 6 months 1.09 (0.63-1.86) 0.749 1.08 (0.62-1.86) 0.772
Bronchiolitis at 9 months 1.20 (0.68-2.10) 0.513 1.02 (0.57-1.82) 0.93
Bronchiolitis at 12 months 2.71 (1.49-4.91) 0.011 2.42 (1.31-4.46) 0.004
Bronchiolitis in the 1st year of life 1.31 (1.00-1.72) 0.028 1.59 (1.01-2.53) 0.04
Parental history of asthma 2.01 (1.27-3.17) 0.002 2.07 (1.29-3.30) 0.002
Number of people sleeping in the child's bedroom >4 2.71 (1.20-6.09) 0.012 2.31 (0.99-5.40) 0.051

aχ 2 test.

bMultivariate logistic regression test adjusted for gender, AVB, parental history of asthma, number of people sleeping in the room with the child, maternal smoking during pregnancy.

The number of children exposed to AVB in the 1st year of life was 50.7% (341) and the frequency of AVB was 461 episodes: 75 (11.5%) in the first, 136 (20.3%) in the second, 114 (16.9%) in the third, and 136 (20.3%) in the fourth trimester of life. The frequency of AVB/child in the first year of life was one episode, 234; two episodes, 83; and three or more episodes, 15. The frequency of AVB was not associated with increased risk of asthma at the age of 6 years (Table 3).

Table 3 Frequency of AVB episodes and association with asthma. 

AVB frequency % OR (95% CI) pa Adjusted OR (95% CI) pb
1 episode 34.8 1.15 (0.73-1.81) 0.540 1.19 (0.75-1.89) 0.454
2 episodes 12.3 1.73 (0.96-3.12) 0.610 1.58 (0.87-2.88) 0.132
3 or more episodes 2.2 1.57 (0.43-5.69) 0.485 1.27 (0.33-4.83) 0.717

aChi-squared test.

bMultivariate logistic regression test adjusted for gender, AVB, parental history of asthma, number of people sleeping in the room with the child, maternal smoking during pregnancy.

The prevalence of exclusive breastfeeding up to the 3rd month of life among the children was 36.4% (248), and was a protective factor for AVB, OR = 0.49, 95% CI (0.28-0.84); p = 0.009. Exclusive breastfeeding up to the 4th month did not result in protection against bronchiolitis at 6 months, OR: 0.76, 95% CI (0.42-1.16); 9 months OR: 1.19, 95% CI (0.74-1.93); 12 months, OR: 0.08, 95% CI (0.94-2.29), nor in the children's 1st year of life, OR: 0.60, 95% CI (0.29-1.24).

There was an modifier effect of the parental history of asthma for the association between bronchiolitis and asthma at 3, 6, 9, and 12 months, and in the 1st year; AVB at 12 months and in the 1st year of life was a risk factor for asthma in children with parental history of asthma, OR: 3.90 95% CI (1.36-11.1), and OR: 2.66, 95% CI (1.10-6.40), modifier effect p < 0.001 and p = 0.002, respectively (Table 4).

Table 4 Association between AVB and asthma according to parental history of asthma. 

Variables No parental history of asthma (n = 496) Parental history of asthma (n = 176) Modifier effect p-valueb
OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI)
Crude Adjusted Crude Adjusteda
Bronchiolitis at 3 months 1.35 (0.57-3.17) 1.37 (0.58-3.23) 2.30 (0.93-5.71) 2.48 (0.94-6.52) 0.003
Bronchiolitis at 6 months 1.07 (0.54-2.11) 1.05 (0.53-2.09) 1.14 (0.47-2.78) 1.30 (0.51-3.34) 0.001
Bronchiolitis at 9 months 1.31 (0.64-2.66) 1.23 (0.60-2.53) 0.96 (0.38-2.43) 0.76 (0.28-2.05) 0.004
Bronchiolitis at 12 months 2.28 (1.03-5.06) 2.00 (0.88-4.55) 3.11 (1.21-8.03) 3.90 (1.36-11.11) <0.001
Bronchiolitis in the 1st year 2.28 (1.03-5.06) 1.66 (1.10-6.40) 3.11 (1.21-8.00) 2.66 (1.10-6.40) 0.002

aAdjusted for gender, number of people sleeping in the room with the child, parental history of asthma, maternal smoking during pregnancy.

bModifier effect p-value - interaction test.


The present study shows that AVB in the 1st year of life was a risk factor for asthma in children and significantly increases when associated with a parental history of asthma. Exposure to AVB and other multiple environmental factors is important for the development of the disease, especially in predisposed children.17

Respiratory infections by viruses and AVB are more common in infants, and have been associated with risk of asthma, as they are related to its pathogenesis and the triggering of exacerbations.17,18 Although some infections caused by influenza and parainfluenza viruses can inhibit the development of asthma, despite repeated upper airway respiratory infections in the first two years of the child's life, other infections by RSV and rhinovirus may favor the onset of asthma and atopy.7,19,20

There are several hypotheses to explain the mechanisms involved in the association between viral infection, persistent dyspnea, and asthma: (i) induction of inflammation typical of allergic asthma by T lymphocyte differentiation into Th2; (ii) activation by the respiratory syncytial virus of Th17 cells and IL17 production, a neutrophilic inflammation-inducing cytokine. Th17 cells induce the regulation of other pro-inflammatory cytokines, such as IL6 and TNF-α, chemokines, and metalloproteinases, with a possible role in the pathogenesis of asthma21,22; (iii) increase in IL-4 and decrease in IFN-gamma levels, as demonstrated by the presence of positive allergy tests and specific IgE antibodies in children with AVB; (iv) bronchial hyperactivity mediated by inflammatory cells and sensory C-fiber neuropeptides caused by the increase in bronchial inflammation. Other risk factors for asthma in children may be related to the direct association between bronchiolitis and asthma, such as the presence of smaller-caliber airways in male children, which may lead to dyspnea during virus infections and the development of asthma.

The type of bacterial flora that comprises the nasopharynx microbiome of children in the early years of life has been associated to future risk of asthma. Nasopharyngeal colonization by Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae at the age of 1 month of life is associated with risk of asthma at age 5 years. RSV infection at an early age can change the nasopharyngeal microbiome, and the microflora imbalance can lead to lower respiratory tract infection by pathogenic bacteria and inflammation.21

There have been few studies considering the modifier effect of parental history of asthma in the association between AVB caused by RSV and rhinovirus and asthma development in children. Carroll et al. demonstrated that the presence of rhinovirus was associated with more severe infection in children of mothers with atopic asthma.23 Similarly, Jung et al. demonstrated through genotyping that an modifier effect of TLR4 (rs1927911), CD14 (rs2569190), and IL-13 (rs20541) occurred in the association between asthma and AVB in Korean children; the risk of developing asthma after AVB was significantly higher in children that had one of the three polymorphisms described above.24 It is well known that a parental history of asthma is the most important risk factor for asthma development.25 In the current study, it was an independent risk factor for asthma and played an important modifying effect on the association between AVB and asthma, increasing the risk of asthma in children with bronchiolitis.

A study carried out in the city of Salvador, state of Bahia, Brazil, to verify the association between viral infections and asthma among children aged 4-13 years showed no association between atopic and non-atopic asthma and the herpes simplex, varicella zoster, Epstein-Barr virus, and hepatitis A viruses,26 which are not associated to lower respiratory tract infections. Infections by herpes simplex and Epstein-Barr virus in children caused attenuation of the immediate hypersensitivity skin test verified by immediate aeroallergen hypersensitivity skin prick testing. The result of this study showed that viral infections commonly found in children have been associated with immediate hypersensitivity attenuation, but not the clinical disease.

The current study showed that the rate of exclusive breastfeeding rate in the 4th month of life was 20.4%, which is compatible with the national mean; this fact may have contributed to protect children from AVB and asthma at 3 months of life while in exclusive breastfeeding, due to the presence of immunological, anti-infectious factors, and immunomodulators present in human milk, according to the study by Kull et al.27

The prevalence of asthma in this study was lower when compared with the prevalence found in a previous study performed in the city of Feira de Santana.28 Possible reasons are the high rate of exclusive breastfeeding during the children's first four months of life and the asthma and allergic rhinitis control program actions implemented in the city in 2004, with the free distribution of asthma control drugs.1,2 Further studies planned for the future will add other criteria for disease identification, such as regular use of asthma medications, which can maintain patients asymptomatic.

Male gender and genetics also represented risk factors for asthma in this study. The 2.4-fold higher risk of asthma in male schoolchildren when compared to female ones was also found in the study by Casagrande et al. and can be justified by the smaller airway caliber of boys when compared to girls in this age group, which disappears in adolescence.29,30 Studies have shown that having parents with asthma is the main risk factor for having the disease.25

Some limitations inherent to cross-sectional studies, such as recall bias, have been minimized in the present study, as it was carried out in a prospective cohort of children. The diagnosis of asthma, using the ISAAC study questionnaire, was standardized and validated in Brazil, used to measure the overall prevalence of asthma and allergic disease symptoms in schoolchildren with questions limited to symptoms in the last year, thus reducing the recall bias. The diagnosis of AVB based on data provided by mothers on the medical diagnosis and the presence of respiratory tract symptoms can be faulty and may have overestimated the diagnosis of AVB. Febrile tachypnea and rhinorrhea are common in viral infections. The respiratory symptoms were not accompanied by fever in a significant percentage of the sample. Not performing serological tests for virus identification was also a limitation of the current study.

AVB in the 1st year of life was a risk factor for asthma in children in Northeast Brazil. Parental history of asthma further increases the risk of asthma in children exposed to bronchiolitis. The use of prevention and control measures for respiratory infections caused by RSV and rhinoviruses, such as vaccination for VSR, preventing contamination by washing hands, and avoiding crowded places, should be expanded and intensified by public health agencies, especially for children with a parental history of asthma, aiming to obtain a decrease in morbidity and mortality for bronchiolitis and asthma prevalence.

Please cite this article as: Brandão HV, Vieira GO, Vieira TO, Cruz ÁA, Guimarães AC, Teles C, et al. Acute viral bronchiolitis and risk of asthma in schoolchildren: analysis of a Brazilian newborn cohort. J Pediatr (Rio J). 2017;93:223-9.

☆☆Study conducted at Escola Bahiana de Medicina e Saúde Pública, Salvador, BA, Brazil.


Paulo Camargos received grants from CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, Grant #303396/2012-1) and FAPEMIG (Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Grant #PPM0065-14)


1 Brandão HV, Cruz CS, Pinheiro MC, Costa EA, Guimarães A, Souza-Machado A, et al. Risk factors for ER visits due to asthma exacerbations in patients enrolled in a program for the control of asthma and allergic rhinitis in Feira de Santana, Brazil. J Bras Pneumol. 2009;35:1168-73. [ Links ]

2 Brandão HV, Cruz CM, Santos Ida S, Ponte EV, Guimarães A, Augusto Filho A. Hospitalizations for asthma: impact of a program for the control of asthma and allergic rhinitis in Feira de Santana, Brazil. J Bras Pneumol. 2009;35:723-9. [ Links ]

3 Franco R, Nascimento HF, Cruz AA, Santos AC, Souza-Machado C, Ponte EV, et al. The economic impact of severe asthma to low-income families. Allergy. 2009;64:478-83. [ Links ]

4 Garcia-Garcia ML, Calvo Rey C, Del Rosal Rabes T. Pediatric asthma and viral infection. Arch Bronconeumol. 2016;52:269-73. [ Links ]

5 Sly PD, Kusel M, Holt PG. Do early-life viral infections cause asthma?. J Allergy Clin Immunol. 2010;125:1202-5. [ Links ]

6 Agency for Healthcare Research and Quality. Management of bronchiolitis in infants and children. Evidence Report/Technology Assessment No. 69. Rockville, MD: AHRQ; 2003, 03-E014. [ Links ]

7 Lee KK, Hegele RG, Manfreda J, Wooldrage K, Becker AB, Ferguson AC, et al. Relationship of early childhood viral exposures to respiratory symptoms, onset of possible asthma and atopy in high risk children: the Canadian Asthma Primary Prevention Study. Pediatr Pulmonol. 2007;42:290-7. [ Links ]

8 Illi S, von Mutius E, Lau S, Bergmann R, Niggemann B, Sommerfeld C, et al. Early childhood infectious diseases and the development of asthma up to school age: a birth cohort study. BMJ. 2001;322:390-5. [ Links ]

9 Martinez FD. Respiratory syncytial virus bronchiolitis and the pathogenesis of childhood asthma. Pediatr Infect Dis J. 2003;22:S76-82. [ Links ]

10 Sigurs N, Bjarnason R, Sigurbergsson F, Kjellman B. Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7. Am J Respir Crit Care Med. 2000;161:1501-7. [ Links ]

11 Shay DK, Holman RC, Roosevelt GE, Clarke MJ, Anderson LJ. Bronchiolitis-associated mortality and estimates of respiratory syncytial virus-associated deaths among US children, 1979-1997. J Infect Dis. 2001;183:16-22. [ Links ]

12 Riccetto AG, Ribeiro JD, Silva MT, Almeida RS, Arns CW, Baracat EC. Respiratory syncytial virus (RSV) in infants hospitalized for acute lower respiratory tract disease: incidence and associated risks. Braz J Infect Dis. 2006;10:357-61. [ Links ]

13 Salomão Junior JB, Gardinassi LG, Simas PV, Bittar CO, Souza FP, Rahal P, et al. Human respiratory syncytial virus in children hospitalized for acute lower respiratory infection. J Pediatr (Rio J). 2011;87:219-24. [ Links ]

14 Nascimento MS, Souza AV, Ferreira AV, Rodrigues JC, Abramovici S, Silva Filho LV. High rate of viral identification and coinfections in infants with acute bronchiolitis. Clinics (Sao Paulo). 2010;65:1133-7. [ Links ]

15 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. J Investig Allergol Clin Immunol. 1998;8:376-82. [ Links ]

16 American Academy of Pediatrics Subcommittee on Diagnosis and Management of Bronchiolitis. Diagnosis and management of bronchiolitis. Pediatrics. 2006;118:1774-93. [ Links ]

17 Jartti T, Korppi M. Rhinovirus-induced bronchiolitis and asthma development. Pediatr Allergy Immunol. 2011;22:350-5. [ Links ]

18 Connors T, Baird J, Farber DL. Viral bronchiolitis in children. N Engl J Med. 2016;374:1791-2. [ Links ]

19 Message SD, Johnston SL. Viruses in asthma. Br Med Bull. 2002;61:29-43. [ Links ]

20 Emuzyte R, Firantiene R, Petraityte R, Sasnauskas K. Human rhinoviruses, allergy, and asthma: a clinical approach. Medicina (Kaunas). 2009;45:839-47. [ Links ]

21 Teo SM, Mok D, Pham K, Kusel M, Serralha M, Troy N, et al. The infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development. Cell Host Microbe. 2015;17:704-15. [ Links ]

22 Lotz MT, Peebles RS. Mechanisms of respiratory syncytial virus modulation of airway immune responses. Curr Allergy Asthma Rep. 2012;12:380-7. [ Links ]

23 Carroll KN, Gebretsadik T, Minton P, Woodward K, Liu Z, Miller EK, et al. Influence of maternal asthma on the cause and severity of infant acute respiratory tract infections. J Allergy Clin Immunol. 2012;129:1236-42. [ Links ]

24 Jung YH, Seo JH, Kim HY, Kwon JW, Kim BJ, Kim HB, et al. The relationship between asthma and bronchiolitis is modified by TLR4, CD14, and IL-13 polymorphisms. Pediatr Pulmonol. 2015;50:8-16. [ Links ]

25 Sarafino EP, Goldfedder J. Genetic factors in the presence, severity, and triggers of asthma. Arch Dis Child. 1995;73:112-6. [ Links ]

26 Veiga RV, Cunha SS, Dattoli VC, Cruz ÁC, Cooper PJ, Rodrigues LC, et al. Chronic virus infections suppress atopy but not asthma in a set of children from a large Latin American city: a cross-section study. BMC Pulm Med. 2011;11:24-31. [ Links ]

27 Kull I, Almqvist C, Lilja G, Pershagen G, Wickman M. Breast-feeding reduces the risk of asthma during the first 4 years of life. J Allergy Clin Immunol. 2004;114:755-60. [ Links ]

28 Solé D, Wandalsen GF, Camelo-Nunes IC, Naspitz CK. Prevalence of symptoms of asthma, rhinitis, and atopic eczema among Brazilian children and adolescents identified by the International Study of Asthma and Allergies in Childhood (ISAAC) - Phase 3. J Pediatr (Rio J). 2006;82:341-6. [ Links ]

29 Casagrande RR, Pastorino AC, Souza RG, Leone C, Solé D, Jacob CM. Asthma prevalence and risk factors in schoolchildren of the city of São Paulo, Brazil. Rev Saude Publica. 2008;42:517-23. [ Links ]

30 Sánchez-Lerma B, Morales-Chirivella FJ, Peñuelas I, Blanco Guerra C, Mesa Lugo F, Aguinaga-Ontoso I, et al. High prevalence of asthma and allergic diseases in children aged 6 to [corrected] 7 years from the Canary Islands [corrected]. J Investig Allergol Clin Immunol. 2009;19:383-90. [ Links ]

Received: April 20, 2016; Accepted: August 03, 2016

* Corresponding author. (H.V. Brandão).

Conflicts of interest

The authors declare no conflicts of interest.

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