Does respiratory syncytial virus lower respiratory illness in early life cause recurrent wheeze of early childhood and asthma? Critical review of the evidence and guidance for future studies from a World Health Organization-sponsored meeting

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) and hospitalization in infants and children globally. Many observational studies have found an association between RSV LRTI in early life and subsequent respiratory morbidity, including recurrent wheeze of early childhood (RWEC) and asthma. Conversely, two randomized placebo-controlled trials of efficacious anti-RSV monoclonal antibodies (mAbs) in heterogenous infant populations found no difference in physician-diagnosed RWEC or asthma by treatment group. If a causal association exists and RSV vaccines and mAbs can prevent a substantial fraction of RWEC/asthma, the full public health value of these interventions would markedly increase. The primary alternative interpretation of the observational data is that RSV LRTI in early life is a marker of an underlying predisposition for the development of RWEC and asthma. If this is the case, RSV vaccines and mAbs would not necessarily be expected to impact these outcomes. To evaluate whether the available evidence supports a causal association between RSV LRTI and RWEC/asthma and to provide guidance for future studies, the World Health Organization convened a meeting of subject matter experts on February 12–13, 2019 in Geneva, Switzerland. After discussing relevant background information and reviewing the current epidemiologic evidence, the group determined that: (i) the evidence is inconclusive in establishing a causal association between RSV LRTI and RWEC/asthma, (ii) the evidence does not establish that RSV mAbs (and, by extension, future vaccines) will have a substantial effect on these outcomes and (iii) regardless of the association with long-term childhood respiratory morbidity, severe acute RSV disease in young children poses a substantial public health burden and should continue to be the primary consideration for policy-setting bodies deliberating on RSV vaccine and mAb recommendations. Nonetheless, the group recognized the public health importance of resolving this question and suggested good practice guidelines for future studies.     

Sex-specific trends in prevalence of childhood asthma over 30 years in Patras, Greece

Aim: According to four surveys conducted during 1978–2003, the prevalence of childhood asthma and wheezing has risen in the city of Patras, Greece, albeit at a decelerating rate. We examined sex‐specific wheeze and asthma prevalence in the same urban environment in 2008. Methods: A cross‐sectional parental questionnaire survey was performed in 2008 among third and fourth grade schoolchildren (8–9 year old), which was identical to previously conducted surveys in 1978 (n = 3003), 1991 (n = 2417), 1998 (n = 3076) and 2003 (n = 2725). Results: The prevalence of current wheeze and asthma in 1978, 1991, 1998, 2003 and 2008 (n = 2688) was 1.5%, 4.6%, 6.0%, 6.9% and 6.9%, respectively (p for trend <0.001). Respective values for lifetime (ever had) wheeze and asthma in the 1991–2008 surveys were 8.0%, 9.6%, 12.4% and 12.6% (p for trend <0.001). The male:female ratio of current and lifetime wheeze and asthma increased during the 30‐year surveillance period (p for trend <0.001). Irrespective of sex, diagnosed asthma declined among current wheezers by 17% (p < 0.001), but not among non‐current ones (6.7%, p = 0.16) during 2003–2008. Conclusions: Childhood wheeze and asthma have reached a plateau in an urban environment in Greece, while the male:female ratio increased. Asthma diagnosis declined among schoolage but not preschool wheezers during 2003–2008.     

An international comparison of risk factors between two regions with distinct differences in asthma prevalence

Background and purpose

Investigation of the geographic variation in asthma prevalence can improve our understanding of asthma etiology and management. The purpose of our investigation was to compare the prevalence of asthma and wheeze among adolescents living in two distinct international regions and to investigate reasons for observed differences.

Phthalate metabolites in urine and asthma,allergic rhinoconjunctivitis and atopic dermatitis in preschool children

Phthalate esters are among the most ubiquitous of indoor pollutants and have been associated with various adverse health effects. In the present study we assessed the cross-sectional association between eight different phthalate metabolites in urine and allergic disease in young children. As part of the Danish Indoor Environment and Children's Health study, urine samples were collected from 440 children aged 3–5 years, of whom 222 were healthy controls, 68 were clinically diagnosed with asthma, 76 with rhinoconjunctivitis and 81 with atopic dermatitis (disease subgroups are not mutually exclusive; some children had more than one disease). There were no statistically significant differences in the urine concentrations of phthalate metabolites between cases and healthy controls with the exception of MnBP and MECPP, which were higher in healthy controls compared with the asthma case group. In the crude analysis MnBP and MiBP were negatively associated with asthma. In the analysis adjusted for multiple factors, only a weak positive association between MEP in urine and atopic dermatitis was found; there were no positive associations between any phthalate metabolites in urine and either asthma or rhinoconjunctivitis. These findings appear to contradict earlier studies. Differences may be due to higher exposures to certain phthalates (e.g., BBzP) via non-dietary pathways in earlier studies, phthalates serving as surrogates for an agent associated with asthma (e.g., PVC flooring) in previous studies but not the present study or altered cleaning habits and the use of “allergy friendly” products by parents of children with allergic disease in the current study in contrast to studies conducted earlier.     

Interactions between traffic air pollution and glutathione S-transferase genes on childhood asthma

AIM: To evaluate the role of glutathione S-transferase P1 (GSTP1) genetic polymorphisms potentially modifying the association between NO₂ and asthma/wheeze in Taiwanese children. METHODS: We investigated 3714 schoolchildren in Taiwan Children Health Study from 14 communities. Children’s information was measured from questionnaire by parents. The traffic air pollutant was available from Environmental Protection Administration monitoring stations. RESULTS: A two-stage hierarchical model and a multiple logistic regression model were fitted to estimate the effects of NO₂ exposures and GSTs polymorphisms on the prevalence of asthma and wheeze. Among children with GSTP1 Ile/Val or Val/Val genotypes, those residing in high-NO₂ communities had significantly increased risks of asthma (OR = 1.76, 95%CI: 1.15-2.70), late-onset asthma (OR = 2.59, 95%CI: 1.24-5.41), active asthma (OR = 1.93, 95%CI: 1.05-3.57), asthma under medication (OR = 2.95, 95%CI: 1.37-6.32) and wheeze (OR = 1.54, 95%CI: 1.09-2.18) when compared with children in low-NO₂ communities. Significant interactions were noted between ambient NO₂ and GSTP1 on asthma, late-onset asthma, asthma under medication and wheeze (P for interaction < 0.05). However, we did not find any association with polymorphisms in GSTM1 and GSTT1. CONCLUSION: Children under high traffic air pollution exposure are more susceptible to asthma, especially among those with GSTP1 Val allele.     

Household Conditions, Eczema Symptoms and Rhinitis Symptoms: Relationship with Wheeze and Severe Wheeze in Children Living in the Polokwane Area, South Africa

Background This is the fifth study that applied the International Study of Asthma and Allergies in Childhood (ISAAC) methodology in the Southern African Development Community (SADC region). However, it is the first ISAAC study that focused on 6- to 7-year-old children living in South Africa and that also investigated the association between potential risk factors and asthma symptoms. Objective To assess the 12-month prevalence of wheeze and severe wheeze along with their potential risk factors. Setting Within a 60-km radius from the Polokwane city centre, Limpopo Province. Methods The survey was conducted during August 2004 and February 2005. Parents/guardians of 6- to 7-year-old children completed the questionnaires in English, Afrikaans or North-Sotho. However, the statistical analyses were restricted to the North-Sotho group (n = 2,437). Results The 12-month prevalence rates of wheeze and severe wheeze were 11.2% and 5.7%, respectively. The 12-month prevalence rates of eczema symptoms and rhinoconjunctivitis symptoms were 8.0% and 7.3%, respectively. Living in a rural area significantly decreased the likelihood of wheeze by 31%. Exposure to environmental tobacco smoke at home and the presence of eczema symptoms and rhinoconjunctivitis symptoms increased the likelihood of wheeze by 77%, 104% and 226%, respectively. Only the presence of rhinoconjunctivitis symptoms increased the likelihood of severe wheeze by 107%. Conclusion Wheeze appears to be an emerging public health problem in the Polokwane area. Hopefully, detailed analytical intervention studies will further explicate these results in the near future.

吸入糖皮激质素预防毛细支气管炎反复喘息发作

目的 探讨吸入糖皮质激素预防毛细支气管炎反复喘息发作的疗效。方法 将60例毛支患儿两组发作期治疗相同。治疗组30人在恢复期给予丙酸倍氯米松或氟替卡松吸入3～6个月，对照组30人恢复期不用药。结果 治疗组喘息发作的人数及次数明显低于对照组。结论 毛细支气管炎恢复期持续吸入糖皮质激素能有效地预防喘息的反复发作，大大减少了儿童哮喘的发生。