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Distinct phenotype and risk factor analysis of persistent airflow limitation among asthmatic children: a case-control
Shiqiu Xiong1,2,3, Xinyu Jia1, Wei Chen1
1Department of Allergy, Center for Asthma Prevention and Lung Function Laboratory, Children's Hospital of Capital Institute of Pediatrics, Beijing, 100020, China.
Insights
This study identified two distinct phenotypes of persistent airflow limitation (PAL) in children with asthma: non-eosinophilic and eosinophilic inflammation. Older age and pneumonia history are key risk factors for both, with specific factors like BMI and asthma duration linked to non-eosinophilic PAL.
Area of Science:
- Pediatric Pulmonology
- Asthma Research
- Inflammation Phenotyping
Background:
- Persistent airflow limitation (PAL) in childhood asthma is linked to poor prognosis.
- Understanding distinct PAL phenotypes is crucial for targeted treatment.
Purpose of the Study:
- To categorize asthmatic children with PAL into distinct phenotypes.
- To investigate risk factors associated with each identified PAL phenotype.
Main Methods:
- A case-control study involving 119 PAL patients and 120 non-PAL individuals.
- Unsupervised K-means clustering to identify PAL phenotypes.
- Logistic regression analysis to determine risk factors and odds ratios.
Main Results:
- K-means clustering revealed three groups: non-PAL, non-eosinophilic PAL (elevated neutrophils), and eosinophilic PAL (elevated eosinophils and FeNO).
- Older age and pneumonia history were independent risk factors for both PAL phenotypes.
- Non-eosinophilic PAL was associated with higher BMI, longer asthma duration, and specific neutrophil percentages.
- Eosinophilic PAL was linked to elevated blood eosinophil and FeNO levels.
Conclusions:
- Two distinct PAL phenotypes in childhood asthma were identified: non-eosinophilic and eosinophilic inflammation.
- Older age and pneumonia history are significant risk factors for both phenotypes.
- Specific clinical and biomarker profiles differentiate these phenotypes, guiding potential therapeutic strategies.
Background:
Persistent airflow limitation (PAL) in childhood asthma is associated with a poor prognosis. The aim of this study was to categorize asthmatic children with PAL into distinct phenotypes and investigate the risk factors associated with each phenotype.
Methods:
We conducted a case-control study with a total of 119 PAL patients and 120 non-PAL (NPAL) individuals. To classify the patients into appropriate clusters, unsupervised cluster analysis using K-means clustering was employed. The clusters were then compared to explore different PAL phenotypes. Univariate and multivariate logistic regression analyses were performed to identify risk factors for PAL and calculate odds ratios (ORs) with 95% confidence intervals (95%CIs).
Results:
K-means clustering divided patients into three clusters: Cluster 0 included 120 NPAL patients, Cluster 1 characterized by elevated blood neutrophils included 66 PAL patients, and Cluster 2 exhibited elevated blood eosinophils and FeNO levels, containing 53 PAL patients. Independent risk factors for PAL included older age in both Cluster 1 (9 11y: OR 12.67, 95%CI 3.30-55.74; 11y: OR 5.42, 95%CI 1.26-25.69) and Cluster 2 (9 11y: OR 7.25, 95%CI 1.70-33.35; 11y: OR 11.28, 95%CI 2.79-51.89), as well as pneumonia history, with an OR of 6.41(95%CI 1.34-33.41) in Cluster 1 and an OR of 7.92(95%CI 1.83-37.44) in Cluster 2. Furthermore, specific factors associated with Cluster 1 included BMI above 22 kg/ (OR 12.28, 95%CI 2.68-70.45), asthma duration exceeding three years (OR 4.77, 95%CI 1.60-15.94), and a blood neutrophil percentage between 0.4 and 0.5 (OR 4.13, 95%CI 1.17-16.6). In Cluster 2, independent risk factors included a blood eosinophil percentage greater than 0.07 (OR 4.36, 95%CI 1.16-19.73) and a high FeNO level (OR 3.94, 95%CI 1.35-11.97).
Conclusion:
Our study identified two phenotypes of PAL in asthmatic children: non-eosinophilic and eosinophilic inflammation. Older age and a history of pneumonia were independent risk factors for both phenotypes. For non-eosinophilic inflammation PAL, specific contributing factors included higher BMI, long duration of asthma, and a blood neutrophil percentage between 0.4 and 0.5. Elevated FeNO levels and blood eosinophilic percentage were independently associated with eosinophilic inflammation PAL.
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