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Published on: August 7, 2017
Causal associations between pediatric asthma and united airways disease: a two-sample Mendelian randomization
Tongxun Gao1,2, Qiuhan Cai1,2, Siyuan Hu1,2
1Department of Clinical Trial Center, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Insights
Pediatric asthma may causally increase the risk of united airway diseases (UAD), including chronic rhinitis and COPD. This Mendelian randomization study highlights asthma as a potential risk factor for UAD development.
Area of Science:
- Respiratory Medicine
- Genetics
- Epidemiology
Background:
- Previous observational studies suggested a link between pediatric asthma and united airway diseases (UAD).
- Potential confounding factors and reverse causation in prior research necessitated further investigation.
- Mendelian randomization (MR) offers a robust method to explore causal relationships.
Purpose of the Study:
- To investigate the causal relationship between pediatric asthma and seven categories of UAD using a two-sample MR analysis.
- To determine if pediatric asthma is a risk factor for conditions such as chronic rhinitis, COPD, and others.
- To provide robust evidence supporting or refuting a causal link, addressing limitations of prior observational studies.
Main Methods:
- A comprehensive two-sample Mendelian randomization (MR) analysis was performed.
- Investigated associations between pediatric asthma and specific UADs including chronic rhinitis, chronic bronchitis, bronchiectasis, and COPD.
- Employed inverse variance weighted (IVW) as the primary method, supplemented by MR-Egger, Simple Mode, and weighted median models. Sensitivity analyses included heterogeneity, pleiotropy, MR-PRESSO, and leave-one-out tests.
Main Results:
- Significant causal effects of pediatric asthma were found for chronic rhinitis (OR=1.15), chronic diseases of tonsils and adenoids (OR=1.07), chronic bronchitis (OR=1.51), bronchiectasis (OR=1.51), and COPD (OR=1.43).
- No significant causal association was observed for chronic sinusitis or chronic laryngitis/laryngotracheitis.
- Results were validated through multiple sensitivity analyses ensuring robustness.
Conclusions:
- The study provides evidence supporting a potential causal relationship between pediatric asthma and several UADs.
- Pediatric asthma emerges as a significant potential risk factor for developing conditions like chronic rhinitis, chronic bronchitis, bronchiectasis, and COPD.
- Findings underscore the importance of managing pediatric asthma to potentially mitigate the risk of associated airway diseases.
Background:
Prior observational research has indicated a potential link between pediatric asthma and united airways disease (UAD). However, these findings could be subject to confounding factors and reverse causation. Therefore, our study utilizes Mendelian randomization (MR) method to further investigate the causal relationship between pediatric asthma and UAD.
Methods:
We conducted a comprehensive two-sample Mendelian randomization (MR) analysis to investigate the association between pediatric asthma and seven groups of UAD, including chronic sinusitis, chronic rhinitis, nasopharyngitis and pharyngitis, chronic diseases of tonsils and adenoids, chronic laryngitis and laryngotracheitis, chronic bronchitis, bronchiectasis, chronic obstructive pulmonary disease (COPD). The present study employed a range of methods for two-sample MR analysis, including inverse variance weighted (IVW), MR-Egger regression, Simple mode, weighted median, and weighted models. The conclusion of the MR analysis primarily relies on the IVW results, while other analytical methods are utilized as supplementary evidence to ensure result robustness in this MR analysis. And sensitivity analyses were conducted, including heterogeneity test, horizontal pleiotropy test, MR-PRESSO test, and leave-one-out analysis to validate the results.
Results:
The results of the MR analysis indicate significant causal effects of pediatric asthma on chronic rhinitis, nasopharyngitis and pharyngitis (IVW: OR = 1.15, 95%CI: 1.05-1.26, p-value = 0.003), chronic diseases of tonsils and adenoids (IVW: OR = 1.07, 95%CI: 1.00-1.15, p-value = 0.038), chronic bronchitis (IVW: OR = 1.51, 95%CI: 1.42-1.62, p-value <0.001), bronchiectasis (IVW: OR = 1.51, 95%CI: (1.30-1.75), p-value <0.001), and COPD (IVW: OR = 1.43, 95%CI: 1.34-1.51, p-value <0.001). However, no significant causal association was observed between pediatric asthma and chronic sinusitis (IVW: OR = 1.00, 95%CI: 1.00-1.00, p-value = 0.085), chronic laryngitis and laryngotracheitis (IVW: OR = 1.05, 95%CI: 0.90-1.21, p-value = 0.558).
Conclusion:
Our findings support a potential causal relationship between pediatric asthma and UAD, suggesting that pediatric asthma may be a potential risk factor for various UAD.
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