Adult asthma after non-respiratory syncytial virus bronchiolitis in infancy: Subgroup analysis of the 20-year prospective follow-up study

BACKGROUND: Recent studies have stressed the influence of other viruses than respiratory syncytial virus (RSV) in the development of asthma in later childhood after bronchiolitis in infancy. However, the virus-specific prognosis until adulthood has remained obscure, due to lack of sufficiently long follow-up studies. The aim of the present study was to evaluate adult respiratory morbidity after bronchiolitis in infancy, focused on cases not caused by RSV. METHODS: A total of 54 children hospitalized for bronchiolitis at age <2 years were re-studied at median age 19 years; 22 with RSV bronchiolitis and 22 with non-RSV bronchiolitis outside RSV epidemic were included. RSV etiology was studied by antigen and antibody assays on admission. Adult asthma was defined by two ways, based on written questionnaire, clinical examination and home peak expiratory flow monitoring. Lung function was evaluated by flow-volume spirometry (FVS), bronchial reactivity by methacholine inhalation challenge (MIC), and atopy by skin prick tests (SPT). RESULTS: In the non-RSV group, asthma by two definitions was present in 41-50% (vs 18-27% in RSV group). In logistic regression, adjusted for gender, age on admission, current atopy and smoking, non-RSV etiology of bronchiolitis, compared with RSV etiology, increased asthma risk by both strict (odds ratio [OR], 8.34; 95% confidence interval [CI], 1.18-58.69) and less strict (OR, 7.93; 95% CI, 1.14-55.41) criteria. An abnormal result in FVS was present in 32-41% and in MIC in 48-52% of cases in non-RSV and RSV groups, respectively. CONCLUSIONS: Infants with non-RSV bronchiolitis requiring treatment in hospital are at an increased risk for subsequent asthma in adulthood.     

Asthma and lung function 20 years after wheezing in infancy: results from a prospective follow-up study

OBJECTIVE: To determine the outcome until adulthood after wheezing in infancy, compared with pneumonia in infancy and with controls. DESIGN: An 18- to-20-year prospective cohort study. SETTING: Pediatric department at a university hospital, providing primary hospital care for a defined population.Patients Fifty-four children hospitalized for bronchiolitis and 34 for pneumonia at younger than 2 years, and 45 controls with no early-life wheezing or hospitalization, were studied at median age 19 years. MAIN OUTCOME MEASURES: A questionnaire on asthma symptoms and medication, physical examination, flow volume spirometry (FVS), methacholine inhalation challenge (MIC), home peak expiratory flow (PEF) monitoring, and skin prick testing (SPT) to common inhalant allergens. The 2 asthma definitions were physician-diagnosed asthma and previously diagnosed asthma with recent asthmatic symptoms (physician-diagnosed asthma included). RESULTS: By the 2 definitions, asthma was present in 30% (odds ratio [OR], 3.37; 95% confidence interval [CI], 1.12-10.10) and in 41% (OR 1.38; 95% CI, 0.37-5.21) in the bronchiolitis group, in 15% (OR, 5.50; 95% CI, 1.87-16.14) and in 24% (OR, 2.07; 95% CI, 0.59-7.22) in the pneumonia group, and in 11% in the control group. After bronchiolitis, the FVS values were forced vital capacity (FVC), 108% (SD, 13%) of predicted; forced expiratory volume in 1 second, 98% (SD, 12%); forced expiratory volume in 1 second divided by FVC, 91% (SD, 7.6%); midexpiratory flow at 50% of the FVC, 74% (SD, 19%); and midexpiratory flow at 25% of the FVC, 74% (SD, 22%). Bronchial reactivity by MIC was present in 25 (48%) of 52 subjects in the bronchiolitis group, in 13 (42%) of 31 in the pneumonia group, and in 14 (32%) of 44 in the control group. The prevalence of atopy (positive SPTs) was 48% to 63% in the 3 groups. In a logistic regression adjusted for atopy and smoking, infantile bronchiolitis was an independent risk factor for asthma by both definitions. CONCLUSION: The increased risk for asthma persists until adulthood after bronchiolitis in infancy.     

Hospitalization for RSV bronchiolitis before 12 months of age and subsequent asthma, atopy and wheeze: A longitudinal birth cohort study

Several epidemiological studies have reported recurrent wheezing and asthma in children after respiratory syncytial virus (RSV) bronchiolitis in infancy. The relationship with allergic sensitization is less clear and recent evidence suggests an interaction between atopy and RSV infection in the development of asthma. Data from a large, population-based, birth-cohort (Avon Longitudinal Study of Parents and Children) were used to compare outcomes of children according to whether or not they had been admitted to hospital in the first 12 months with RSV-proven bronchiolitis. Outcomes considered were 12-month prevalence of wheeze at two ages (between 30-42 and 69-81 months), cumulative prevalence of doctor-diagnosed asthma at 91 months and skin prick test defined atopy at 7 yr. Multivariable logistic regression models were used to calculate odds ratios for outcomes adjusted for potential confounders. A total of 150 infants (1.1% of the cohort) were admitted to hospital within 12 months of birth with RSV bronchiolitis. The prevalence of wheezing was 28.1% in the RSV group and 13.1% in controls at 30-42 months and 22.6% vs. 9.6% at 69-81 months. The cumulative prevalence of asthma was 38.4% in the RSV group and 20.1% in controls at 91 months. Atopy was found in 14.6% of the RSV group and in 20.7% of controls at 7 yr. RSV bronchiolitis was associated with subsequent wheezing between 30-42 (Odds ratio [95% CI] 2.3 [1.3, 3.9]) and 69-81 months (OR 3.5 [1.8, 6.6]) and with the cumulative prevalence of asthma at 91 months (OR 2.5 [1.4, 4.3]) but not with atopy (OR 0.7 [0.2, 1.7]). In a population-based birth cohort, RSV bronchiolitis was associated with subsequent wheezing and asthma but not with the development of atopy by age 7 yr.     

The outcome after severe bronchiolitis is related to gender and virus

The association between bronchiolitis in the first year of life and subsequent asthma, atopy, airway obstruction and bronchial hyper-responsiveness (BHR) is unsettled. Genetic predispositions, pre-morbid lung function, environmental interactions and altered immunological responses are risk factors that have been studied. The aim of this study was to assess lung function, BHR and the occurrence of asthma and atopy 11 yr after hospitalization for bronchiolitis in the first year of life, particularly focusing on the role of gender and virus involved. The study included 121 of 131 (92%) children hospitalized for bronchiolitis, 90 (74%) respiratory syncytial virus (RSV)-positive children and 141 children in an age-matched and unselected control group. At follow-up, current asthma was more common after RSV-negative bronchiolitis compared to controls (35.5% vs. 9.2%; p < 0.001), but not after RSV bronchiolitis (15.6%; p = 0.144). Higher BHR and an obstructive lung function pattern were observed after bronchiolitis, the latter most prominent after RSV-negative bronchiolitis. Higher BHR was confined to boys, but present in both the RSV-positive and RSV-negative groups (p = 0.007 and 0.003, respectively). Asthma after bronchiolitis was not associated with atopy. Atopy was similarly distributed between the RSV-positive and RSV-negative bronchiolitis groups and the control group. This study has shown that gender and type of virus are important factors to consider when addressing later development of asthma, BHR and lung function after hospitalization for bronchiolitis in early life.     

中国三城市儿童个人过敏原与喘息及气道高反应性的相关性研究

目的 了解个人过敏原阳性与喘息及气道高反应性的关系。方法 在北京、广州及香港三城市中采用整群抽样的方法,在9～11岁在校学龄儿童中,应用国际间儿童哮喘与过敏性疾病研究的第二阶段研究方案进行研究,内容包括(1)家长书面问卷(共收集问卷10902份),(2)儿童皮肤过敏原点刺试验(3478例),(3)乙酰甲胆碱支气管激发试验(608例)。结果 近期喘息(在12个月内有发作)发生率：北京3．8％、广州3．4％、香港5．8％。特应性(即≥1种过敏原阳性)阳性率北京23．9％、广州30．8％、香港41．2％。乙酰甲胆碱支气管激发试验阳性率：北京33．2％、广州45．8％、香港30．7％。多因素logistic回归分析显示,屋尘螨P[相对危险度(OR)=4．48;95％可信限(CI)：3．02—6．66]、猫毛(OR=2．59;95％CI：1．67～4．02)、粉尘螨F(OR=2．41;95％CI：1．65～3．51)及混合草花粉过敏(OR=2．85;95％CI：1．24～6．50)是近期喘息显著相关的危险因素;特应性(OR=1．29;95％CI：0．74～2．24)与近期喘息无显著相关性。特应性(OR=2．53;95％CI：1．07～5．97)、猫毛(OR：3．01;95％CI：1．39～6．52)及粉尘螨F(OR=3．67;95％CI：1．93～6．97)是气道高反应性显著相关的危险因素。结论 屋尘螨P、粉尘螨F、猫毛、混合草花粉是9-ll岁组儿童近期喘息的危险因素,而特应性不是近期喘息的独立危险因素。特应性、猫毛、粉尘螨F是气道高反应性的危险因素。     

RANTES启动子-28C/G基因多态性与呼吸道合胞病毒致细支气管炎易感性的关联

目的 探讨正常T淋巴细胞表达和分泌的活性调节蛋白RANTES的启动子-28C/G基因多态性与呼吸道合胞病毒(RSV)致细支气管炎(既往称毛细支气管炎)易感的关联性.方法 应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,检测238例RSV细支气管炎患儿及288例正常对照者的RANTES-28C/G多态性,ELISA法检测血清总IgE浓度,全自动血细胞计数仪计数嗜酸性粒细胞,并搜集受检者的特应性体质史、特应性家族史及临床相关资料.结果 RANTES-28C/G基因型分布在RSV细支气管炎组和对照组均符合Hardy-Weinberg平衡.与对照组比较,RANTES-28C/G基因型及等位基因频率在RSV细支气管炎组中的分布差异均有统计学意义(G=10.22,P＜0.01;x2=9.708,P＜0.01);与CC基因型个体相比,携带G等位基因的个体发生RSV细支气管炎的风险增加了2.09倍(OR:2.09,95% CI=1.32～3.30,P＜0.01).在RSV细支气管炎组,携带G等位基因个体具有特应性体质和特应性家族史的风险分别比CC基因型个体增加了1.85倍(OR=1.85,95% CI=1.01～3.38,P＜0.05)和1.91倍(OR=1.91,95% CI=1.03～3.54,P＜0.05),其嗜酸性粒细胞计数亦显著升高(Z=-2.303,P＜0.05).结论 RANTES启动子-28C/G基因多态性与RSV细支气管炎易感性相关联,并且-28G等位基因与RSV细支气管炎患儿的特应性体质及特应性家族史相关联.     

Prospective Multicenter Study of Children With Bronchiolitis Requiring Mechanical Ventilation

OBJECTIVE: To identify factors associated with continuous positive airway pressure (CPAP) and/or intubation for children with bronchiolitis. METHODS: We performed a 16-center, prospective cohort study of hospitalized children aged <2 years with bronchiolitis. For 3 consecutive years from November 1 until March 31, beginning in 2007, researchers collected clinical data and a nasopharyngeal aspirate from study participants. We oversampled children from the ICU. Samples of nasopharyngeal aspirate were tested by polymerase chain reaction for 18 pathogens. RESULTS: There were 161 children who required CPAP and/or intubation. The median age of the overall cohort was 4 months; 59% were male; 61% white, 24% black, and 36% Hispanic. In the multivariable model predicting CPAP/intubation, the significant factors were: age <2 months (odds ratio [OR] 4.3; 95% confidence interval [CI] 1.7-11.5), maternal smoking during pregnancy (OR 1.4; 95% CI 1.1-1.9), birth weight <5 pounds (OR 1.7; 95% CI 1.0-2.6), breathing difficulty began <1 day before admission (OR 1.6; 95% CI 1.2-2.1), presence of apnea (OR 4.8; 95% CI 2.5-8.5), inadequate oral intake (OR 2.5; 95% CI 1.3-4.3), severe retractions (OR 11.1; 95% CI 2.4-33.0), and room air oxygen saturation <85% (OR 3.3; 95% CI 2.0-4.8). The optimism-corrected c-statistic for the final model was 0.80. CONCLUSIONS: In this multicenter study of children hospitalized with bronchiolitis, we identified several demographic, historical, and clinical factors that predicted the use of CPAP and/or intubation, including children born to mothers who smoked during pregnancy. We also identified a novel subgroup of children who required mechanical respiratory support <1 day after respiratory symptoms began.     

Teenage asthma after severe infantile bronchiolitis or pneumonia

OBJECTIVE: The purpose of the study was to evaluate asthma at >13 y of age in children with infantile bronchiolitis or pneumonia. METHODS: In 1981-1982, 127 children at <2 y of age were hospitalized for bronchiolitis (n = 81) or pneumonia (n = 46). Respiratory syncytial virus (RSV) infection, eosinophilia and markers of atopy were assessed and recorded on admission. At a median age of 14.9 y, atopic and asthmatic symptoms were screened by a written questionnaire in 98/127 (77%) study subjects. RESULTS: Asthma was present, according to two definitions, in 14% to 23% in the original bronchiolitis and in 12% to 15% in the original pneumonia group. The figures were 8% to 17% in the RSV infection and 16% to 23% in the non-RSV infection group. Early asthma-predictive factors were repeated wheezing, atopic dermatitis and elevated blood eosinophils. All but one of the teenage asthmatics had allergic rhinitis. CONCLUSION: An increased risk for asthma persists until the teenage period after bronchiolitis and pneumonia in infancy. Both early and later atopy were significant risk factors. The present study was unable to demonstrate the association between early RSV infection and teenage asthma.     

Long-term effects of respiratory syncytial virus (RSV) bronchiolitis in infants and young children: a quantitative review

One of the major questions regarding long-term side effects of bronchiolitis by respiratory syncytial virus (RSV) is whether or not it induces asthma in later life. In this quantitative review, the data of 10 controlled studies are analysed. METHODS: Follow-up studies of RSV bronchiolitis published between January 1978 and December 1998 were identified through a MEDLINE search. Studies were selected if (i) postnatal age at the time of the initial illness was below 12 mo, (ii) all children were hospitalized for RSV bronchiolitis, (iii) the diagnosis RSV was virologically confirmed in all cases, and (iv) a control group was used. RESULTS: Six studies met all selection criteria. Up to 5 y of follow-up after RSV bronchiolitis in infancy, 40% of children reported wheezing as compared to only 11% in the control group (p <0.001). Between 5 and 10 y of follow-up 22% of the bronchiolitis group reported wheezing against 10% of the control group (p = 0.19). The incidence of recurrent wheezing as defined by three or more wheezing episodes also decreased with increasing years of follow-up: at 5 or more years of follow-up the difference between the RSV group and the control group was no longer significant. Furthermore, the presence of either a personal and/or a family history of either atopy and/or asthma did not differ between the two groups. CONCLUSIONS: Wheezing is common after RSV bronchiolitis in infancy. It may persist for > or = 5 y of follow-up. However, no significant difference between the RSV bronchiolitis and the control group was observed regarding recurrent wheezing by 5 y of follow-up. No significant difference between the RSV bronchiolitis and the control group were found regarding a personal history of atopy, a family history of atopy and/or asthma. Therefore it seems unlikely that RSV bronchiolitis is a cause of atopic asthma in later life.     

Asthma, lung function and sensitization in school children with a history of bronchiolitis.

BACKGROUND: The purpose of the present retrospective study was to investigate the association of school-age asthma with acute-bronchiolitis and examine the influence of potential risk factors. METHODS: One hundred and eighty-nine children aged 7.5 +/- 2.2 years consecutively hospitalized for respiratory syncytial virus (RSV)-positive acute bronchiolitis during infancy were evaluated by clinical examination and measurement of peak expiratory flow (PEFR), spirometry, IgE and skin-prick testing. Their pulmonary function was compared with that of 60 non-asthmatic matched controls. RESULTS: Of the entire cohort 57.1% were diagnosed as asthmatic. PEFR, the 1-second forced expiratory volume and forced expiratory flow of 50% vital capacity of children with a history of acute bronchiolitis were statistically significantly lower than in the control group (all P < 0.001). All the aforementioned measurements of children with/without asthma were also significantly lower than controls, while values of asthmatics were significantly lower than those of non-asthmatics. The incidence of asthma in childhood was independently associated with breast-feeding <3 months (adjusted odds ratio [aOR], 8.4; 95% confidence interval [CI]: 3.1-22.4), at least one positive skin prick test (aOR, 7.1; 95%CI: 2.8-18.1), male gender (aOR, 5.0; 95%CI: 2.2-11.5), evidence of moisture in the home environment (aOR, 2.9; 95%CI: 1.3-6.3) and presence of more than one house-resident smoking indoors (aOR, 4.9; 95%CI: 1.8-9.2). CONCLUSION: Children with a history of RSV-bronchiolitis during infancy have an increased risk for developing asthma in childhood, which was independently associated with male gender, breast-feeding <3 months, living in a home environment with moisture damage and/or tobacco smoke by two or more residents and sensitization to at least one aeroallergen. Children with a history of RSV bronchiolitis in infancy had lower spirometry in comparison to matched control group. The difference was more marked for asthmatic ones but remained significant even for non-asthmatic children.     

FLIP-2 Study: risk factors linked to respiratory syncytial virus infection requiring hospitalization in premature infants born in Spain at a gestational age of 32 to 35 weeks

BACKGROUND: Ex-premature infants are more predisposed to complicated primary respiratory syncytial virus (RSV) infection. The aim of the present study was to validate the risk factors found in a previous epidemiologic case-control study regarding hospitalization as a result of RSV infection in premature infants born at 32-35 weeks of gestational age (WGA) in Spain. METHODS: A prospective 2-cohort study was conducted during the 2005-2006 (October 2005 to April 2006) and 2006-2007 (October 2006 to April 2007) RSV seasons, respectively. Cases were premature infants hospitalized for RSV infection whereas controls were premature infants of the same age who did not require any hospitalization for respiratory causes. RESULTS: During the study period 5441 children from 37 Spanish hospitals were included in the risk factor analysis. Two hundred two (3.7%) were cases and the rest controls. Of the cases, 17.8% were admitted to the intensive care unit and 7.4% required mechanical ventilation. None of the patients died. Logistic regression analysis demonstrated that the risk of RSV-related respiratory infection requiring hospital admission in preterm infants (32-35 WGA) was associated with the following factors: absolute chronologic age of < or = 10 weeks at the onset of RSV season [odds ratio (OR): 2.99; 95% confidence interval (CI): 2.23-4.01]; presence of school-age siblings or day care attendance (OR: 2.04; 95% CI: 1.53-2.74); and smoking during pregnancy (OR: 1.61; 95% CI: 1.16-2.25). CONCLUSIONS: In premature infants (32-35 WGA), only 3 independent risk factors were found to significantly increase the risk of RSV-related respiratory infection and hospitalization.     

Pertussis vaccination and the risk of respiratory syncytial virus-associated hospitalization

BACKGROUND: Animal data suggest an association between recent vaccination with a pertussis-containing vaccine and increased severity of respiratory syncytial virus (RSV) infection. We sought to determine whether such an association exists in humans by studying a population-based cohort of young children. PATIENTS AND METHODS: We performed a nested case-control study of 280 children younger than 24 months of age hospitalized with RSV infection in Olmsted County, MN from January 1990 to December 1999. Controls (2 per case) consisted of nonhospitalized residents of Olmsted County matched to cases by date of birth and sex. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for the odds of hospitalization for RSV infection among subjects with a recent pertussis-containing vaccination in proximity to the cases' date of hospitalization relative to the odds among subjects with no vaccination. RESULTS: The OR for receipt of a pertussis-containing vaccine within 0 to 6 days of a case's hospitalization for RSV disease was 0.8 (95% CI 0.4-1.8). For the time intervals 7-13, 14-20 and > or =21 days, the OR were 1.3 (95% CI 0.5-3.0), 1.3 (95% CI 0.5-3.2) and 0.7 (95% CI 0.3-1.5), respectively. Adjusting for vaccine delay and for risk status did not alter the findings. The median interval between the most recent pertussis-containing vaccine and the case's date of hospitalization was 40 days for cases and 42.5 days for controls (P = 0.69). Among the RSV cases, pertussis vaccination in the month preceding hospitalization was not a risk factor for oxygen requirement (P = 0.82), intensive care unit admission (P = 0.46) or need for mechanical ventilation (P = 0.28). CONCLUSION: In our study, recent immunization with a pertussis-containing vaccine was not a risk factor for hospitalization for RSV infection. In addition, among children hospitalized with RSV infection, recent pertussis immunization was not associated with a more severe clinical course.     

Role of atopy in the natural history of wheeze and bronchial hyper-responsiveness in childhood

The role of atopy in the development of asthma has become increasingly recognised. We have been prospectively following a birth cohort of children of atopic parents to document the development of atopic disease. Our aim in this study was to document the natural history of BHR and wheeze at 10 years of age and to relate this to atopy. We reviewed 47 of our original cohort of 79 infants at 10 years of age and documented their clinical history of atopic disease and performed allergen skin prick tests and BHR to histamine. Thirty-three (70%) children wheezed at some time during their 10 years of life, with 13 commencing in infancy. Twenty-two children (47%) had current wheeze at 10 years of age. Wheeze in infancy was a poor predictor (RR 1.23, Cl₉₅ 0.66–2.23) of current wheeze while wheeze commencing after infancy was a good predictor (RR 2.89, Cl₉₅ 1.45–5.2). In contrast both atopy in infancy (RR 2.94, Cl₉₅ 1.92–4.53) and current atopy (RR 3.58, Cl₉₅ 1.43–9.03) were strong predictors of current wheeze. Analysis of BHR confirmed the importance of atopy in predicting its occurrence and severity. Sensitisation to D. pteronyssinus appeared to be the strongest predictor of both current wheeze and BHR. These observations confirm the importance of atopy in predicting outcome in children with asthma and suggest that wheezing in infancy and wheezing in later childhood may have different pathogenetic mechanisms.     

Case-control study of the risk factors linked to respiratory syncytial virus infection requiring hospitalization in premature infants born at a gestational age of 33-35 weeks in Spain

BACKGROUND AND OBJECTIVE: The aim of this study was to identify those risk factors most likely to lead to the development of RSV-related respiratory Infection and subsequent hospital admission among premature infants born at 33-35 WGA (FLIP study) METHODS: This was a prospective case-control study. Cases (186) hospitalized for respiratory syncytial virus (RSV) illness were recruited from 50 participating Spanish hospitals during the 2002-2003 RSV season (October 2002-April 2003). Controls (371) were selected in June 2003 but born at same time as cases. RESULTS: Of these cases, 20.5% were admitted to the intensive care unit intensive care unit, and 7.6% required mechanical ventilation. None of the patients died. Conditional logistic regression analysis adjusted for medical center demonstrated that the risk of RSV-related respiratory infection requiring hospital admission in preterm infants 33-35 weeks of gestation (WGA) in Spain was most often associated with absolute chronologic age at start of RSV season < or =10 weeks [ie, born between July 15 and December 15; odds ratio (OR), 3.95; 95% confidence interval (CI), 2.65-5.90], breast-feeding for < or =2 months total (OR 3.26; 95% CI 1.96-5.42), presence of > or =1 school age siblings (OR 2.85; 95% CI 1.88-4.33), > or =4 residents and visitors at home (discounting school age siblings and the case/control him/herself) (OR 1.91; 95% CI 1.19-3.07) and a family history of wheezing (OR 1.90; 95% CI 1.19-3.01). CONCLUSIONS: In premature infants born 33-35 WGA, certain underlying risk factors significantly increase the risk of RSV-related respiratory infection and hospitalization. Premature infants 33-35 WGA with additional risk factors should be considered for RSV prophylaxis with palivizumab.     

Risk factors of childhood asthma: a Sri Lankan study.

A case-control study was carried out to evaluate the genetic and environmental risk factors of childhood asthma in a group of Sri Lankan children. Three hundred cases (admitted with symptoms of asthma) and 300 age-matched controls were compared over a period of 23 months commencing in January 1996. Family history of atopy, feeding habits in infancy, bronchiolitis in infancy, passive smoking, exposure to dust and dampness, and exposure to pet animals were studied as risk factors for asthma. The risks associated with social factors were also studied. The risk associated with variables were calculated using the chi-squared test in the bivariate analysis and the forward logistic regression model in the multivariate analysis. Parental asthma, asthma in a sibling and in a relative, parental allergic rhinitis, discontinuation of breastfeeding after 6 months in infancy, bronchiolitis in infancy, living in a dusty environment, and a father with primary education compared to secondary education were independently associated with an increased risk of asthma (p < 0.05). This study reinforces the view that asthma has a multifactorial aetiology. Influence of paternal asthma is more than that of maternal asthma. As a preventive measure continuation of breastfeeding beyond 6 months is important.     

Factors associated with severe asthma

OBJECTIVE:To study the role of various factors associated with development and severity of bronchial asthma in children between 5-15 years of age. SETTING: Tertiary Care Medical College Hospital. METHODS: A case control study was carried out during May 96 to April 98. Sixty children each suffering from mild (chronic) and severe asthma (chronic) and 60 controls were enrolled to study the association of various risk factors with development of asthma and for severe disease. RESULTS: On univariate analysis factors associated with significant risk for development of asthma included family history of asthma (p = 0.003), lack of exclusive breastfeeding (p = 0.05), past history of bronchiolitis (p = 0.02), associated allergic rhinitis (p = 0.04) and atopic dermatitis (p = 0.01). For development of severe asthma, associated factors were early onset of symptoms (p = 0.01), family history of asthma in grandparents (p = 0.04) and more than 10 cigarettes per day smoked by any family member. No significant effect of air pollution, overcrowding, pets and passive smoking were found on either development of asthma or it's severity. On multivariate analysis only age of onset below 48 months was associated with severe asthma (OR 2.13, 95% CI 1.00-4.54). Exclusive breastfeeding for more than 4 months was the most protective factor for development of asthma (OR 0.25, 95% CI 0.08-0.70). A strong association between development of asthma and past history of bronchiolitis or tuberculosis (OR 5.26, 95% CI 1.7-16.20) and presence of associated atopic dermatitis or rhinitis (OR 7.5, 95% CI 1.64-34.48) was observed. CONCLUSION: History of associated allergic diseases and past history of bronchiolitis were significantly associated with development of asthma. Exclusive breastfeeding for first 4 months of life was protective. The most significant factor associated with severe asthma was onset of illness before 48 months of age. There was no significant effect of air pollution, over crowding, pets at home or passive smoking on severity of asthma     

Long-term consequences of respiratory syncytial virus acute lower respiratory tract infection in early childhood in Guinea-bissau

AIM: The study aimed to investigate long-term consequences of respiratory syncytial virus (RSV) positive acute lower respiratory tract infection (ALRI) in a low-income country according to severity of the initial infection. DESIGN: The study was a 1:1 matched case-control study of 335 RSV case children and 335 control children. The mean age of RSV ALRI was 0.9 year and at follow-up, 6.8 years. Case children were identified at the hospital and in the community with an antigen and an IgM test to diagnose RSV. Severe RSV infection was defined when a child was treated at the hospital, whereas disease was assumed less severe when a child was diagnosed at home and received no care in the hospital. RESULTS: At follow-up, forced expiratory volume in 1 second (FEV1) and peak flow were significantly lower in case children (odds ratio [OR] = 0.28; 95% confidence interval [CI] 0.10-0.79), the effect being particularly marked for children with severe RSV. Bronchitis at follow-up was reported more frequently among the case children with severe disease. Fewer case children had a positive skin-prick test for local allergens than control children (OR 0.64; 95% CI = 0.44-0.94). Specific IgE for dust mites and cockroach was elevated (52%) in both case and control children. However, specific IgE to peppertree was higher in the case children (OR 2.18; 95% CI = 1.17-4.07). All identified differences were particularly marked for children with severe RSV. CONCLUSION: Severe RSV infection in infancy was associated with decreased lung function in preschool age in Guinea-Bissau. Children with severe RSV disease had more long-term health problems than children with less severe disease.     

Wheezing due to rhinovirus infection in infancy: Bronchial hyperresponsiveness at school age

Background: Characteristics related to decreased lung function and increased bronchial responsiveness after early childhood wheezing requiring hospitalization are not fully established.
Methods: Seventy-nine children with wheezing requiring hospitalization at age <2 years were prospectively followed up and re-investigated at age 5.6–8.8 years when the measurements of baseline lung function and bronchial responsiveness to exercise were performed.
Results: At early school age, 23% of children had decreased lung function, and 13% had increased bronchial responsiveness to exercise. Predictors of decreased lung function were maternal history of smoking during pregnancy (odds ratio [OR], 12.8; 95% confidence interval [CI]: 1.2–139.6), parental history of asthma (OR, 4.3; 95%CI: 1.1–17.1), and female gender (OR, 4.0; 95%CI: 1.2–13.7). Increased bronchial responsiveness was associated with rhinovirus infection-induced wheezing in infancy (OR, 6.5; 95%CI: 1.2–36.3), and early cat or dog exposure leading to sensitization (OR, 26.6; 95%CI: 1.3–525.2). Inhaled anti-inflammatory therapy was common in children with rhinovirus infection-induced wheezing in infancy ( n  = 13/19; P  = 0.001 vs children with other/no confirmed virus infection etiology for wheezing in infancy, n  = 16/60), which may have improved lung function and attenuated bronchial responsiveness in them.
Conclusions: After early childhood wheezing requiring hospitalization, one-fourth of children will have decreased lung function and one-eighth of children will show increased bronchial responsiveness at school age. Gender, heredity of asthma, and antenatal exposure to tobacco smoke are predictors of decreased lung function, whereas rhinovirus infection etiology of wheeze and early animal exposure leading to sensitization are associated with increased bronchial responsiveness later in childhood.     

The role of breastfeeding and passive smoking on the development of severe bronchiolitis in infants

AIM: Bronchiolitis is an acute infectious disease of the lower respiratory tract which causes the obstruction of bronchioles in children younger than 2 years.The aim of this study was to investigate the effect of passive smoking alone and in conjunction with breastfeeding on the severity of acute bronchiolitis in infancy and the duration of hospitalisation. METHODS: We studied 240 consecutive infants aged from 6 to 24 months (137 boys and 103 girls) median age 14 months, who required hospital admission for acute bronchiolitis at the Paediatric Department of Democritus University Hospital, Alexandroupolis, Greece. The outcomes of interest were the severity of bronchiolitis and the duration of hospitalisation. RESULTS: Among the entire cohort, 122 (50.8%) children presented a severe attack of bronchiolitis. In multivariate regression analysis adjusting for confounding factors, breastfeeding for less than four months (aOR=6.1, 95% CI=3.4-10.7), exposure to environmental tobacco smoke (aOR=2.2, 95% CI=1.1-3.6) and their combination (aOR=16.2, 95% CI=6.0-34.3) showed significant association with severe bronchiolitis and prolonged hospitalisation. Passive smoking did not increase the risk of severe bronchiolitis, when infants breastfed for more than four months (aOR=1.9, 95% CI=0.8-5.1). CONCLUSION: In conclusion, exposure to environmental tobacco smoke worsens the symptoms and the prognosis of bronchiolitis, while breastfeeding seems to have a protective effect even in children exposed to environmental tobacco smoke.     

Lung function and bronchial hyper-reactivity from 11 to 18 years in children with bronchiolitis in infancy

Background

Various trajectories for lung function and bronchial hyper-reactivity (BHR) from early childhood to adulthood are described, including puberty as a period with excessive lung growth. Bronchiolitis in infancy may be associated with increased risk of developing chronic obstructive pulmonary disease, but the development of respiratory patterns during puberty is poorly characterized for these children. We aimed to study the development and trajectories of lung function and BHR from 11 to 18 years of age in children hospitalized for bronchiolitis in infancy.

Methods

Infants hospitalized for bronchiolitis at the University Hospitals in Stavanger and Bergen, Norway, during 1997-1998, and an age-matched control group, were included in a longitudinal follow-up study and examined at 11 and 18 years of age with spirometry and methacholine provocation test (MPT). The MPT data were managed as dose-response slope (DRS) in the statistical analyses. Changes in lung function and DRS from 11 to 18 years of age were analyzed by generalized estimating equations, including interaction terms.

Results

z-scores for forced vital capacity (FVC), forced expiratory volume in first second (FEV₁), FEV₁/FVC ratio, and DRS were not different from 11 to 18 years of age in both the post-bronchiolitis and the control group. The trajectories from 11 to 18 years did not differ between the two groups. BHR at age 11 was independently associated with asthma at age 18.

Conclusion

Children hospitalized for bronchiolitis had stable predicted lung function and BHR from 11 to 18 years of age. The lung function trajectories were not different from controls.