Supplementary Material for: INVITATION 20 - Association of outdoor allergens with respiratory allergic diseases: a systematic review

Introduction: The global burden of respiratory allergic diseases linked to outdoor allergens remains poorly quantified despite increasing evidence of the allergens’ impacts on respiratory allergic diseases. This systematic review synthesizes epidemiological evidence on the association between exposure to outdoor airborne allergens and respiratory disease incidence. Methods: Following PRISMA 2020 guidelines, we systematically searched three databases, PubMed, Embase, and the Cochrane Library, until December 2024. Observational studies reporting effect estimates for respiratory outcomes (asthma, allergic rhinitis, COPD exacerbations and cough) associated with quantified outdoor allergen exposure were eligible. Two reviewers independently conducted screening, data extraction, and quality assessment using an adapted Newcastle-Ottawa Scale. Random-effects models were employed to pool odds ratios (ORs), with subgroup analyses by sex. Publication bias were evaluated using Begg’s and Egger's tests, respectively. Results: From 6,551 identified records, 7 articles with 67 studies ( 46325 participants across 3 countries) met inclusion criteria. High-quality studies (NOS ≥7) constituted 86% of included articles. Pooled analyses revealed significant associations between outdoor allergen exposure and respiratory outcomes: OR=1.04 (95% CI: 1.02-1.06; P=0.008). Egger’s publication bias was non-significant (Egger's P=0.21), and Begg’s publication bias was also non-significant (Begg’s P=0.31). Trim-and-fill funnel plots suggested possible missing small-null studies, but the statistical analysis was non-significant. Sensitivity analyses confirmed robustness when excluding studies with potential residual confounding ( pooled OR range: 1.02-1.06). Subgroup analyses demonstrated female subgroup rather than male subgroup got stronger effects significantly: OR=1.04 (95% CI: 1.01-1.07), compared with male subgroup OR=1.02 (95% CI: 0.99-1.04). Conclusions: This comprehensive synthesis provides high-quality evidence that outdoor allergen exposure significantly increases risks of respiratory morbidity. The female is more likely to get respiratory morbidity compared with the male. Further research should prioritize harmonized exposure metrics and evaluate interactive effects with anthropogenic air pollutants.

背景：尽管越来越多证据表明室外变应原可对呼吸道变应性疾病产生影响，但与室外变应原相关的全球呼吸道变应性疾病负担仍未得到充分量化。本系统综述旨在综合有关室外空气变应原暴露与呼吸道疾病发病关联的流行病学证据。方法：遵循PRISMA 2020系统综述与荟萃分析报告规范，我们系统检索了PubMed、Embase及Cochrane Library三个数据库，检索时限截至2024年12月。纳入标准为报道了与量化室外变应原暴露相关的呼吸道结局（哮喘、变应性鼻炎、慢性阻塞性肺疾病急性加重及咳嗽）效应量的观察性研究。由2名评价者独立开展文献筛选、数据提取及质量评价，评价工具采用经过改良的纽卡斯尔-渥太华量表（Newcastle-Ottawa Scale, NOS）。本研究采用随机效应模型合并比值比（odds ratio, OR），并按性别进行亚组分析；分别采用Begg检验与Egger检验评估发表偏倚。结果：在初步检索得到的6551条记录中，最终有7篇文献包含67项研究（覆盖3个国家，共46325名研究对象）符合纳入标准。其中质量评分≥7分的高质量研究占纳入文献的86%。合并分析结果显示，室外变应原暴露与呼吸道结局存在显著关联：合并OR=1.04（95%置信区间[confidence interval, CI]：1.02~1.06；P=0.008）。Egger检验未发现显著发表偏倚（Egger's P=0.21），Begg检验同样未检出显著发表偏倚（Begg's P=0.31）。剪补漏斗图提示可能存在缺失的小型零效应研究，但相关统计学检验未达显著性水平。敏感性分析结果显示，在排除存在潜在残余混杂的研究后，合并效应量仍保持稳健（合并OR范围：1.02~1.06）。亚组分析结果表明，女性亚组的关联效应显著强于男性亚组：女性亚组OR=1.04（95%CI：1.01~1.07），男性亚组OR=1.02（95%CI：0.99~1.04）。结论：本综合综述提供了高质量证据，表明室外变应原暴露可显著升高呼吸道疾病的发病风险；与男性相比，女性发生呼吸道疾病的风险更高。未来研究应优先统一变应原暴露的量化指标，并评估其与人为源空气污染物的交互效应。