Construction of models in predicting the result of bronchodilator reversibility test in mild to moderate asthmatics_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

 MA Ziwen ^1,2,3,4 ^# , ZHANG Li ^1,2,3,4 ^马 , DENG Ke ^1,2,4 , WANG Ji ^1,2,4 , LI Min ^1,4,5 ,  WANG Gang ^1,2,4

1. Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. State Key Laboratory of Respiratory Health and Multimobidity, Chengdu, Sichuan 610041, P. R. China;
3. Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
4. Laboratory of Pulmonary Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
5. Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P. R. China;

Corresponding author：

WANG Gang, Email: wong-gang@126.com

Keywords：

Asthma; bronchodilator reversibility test; prediction model; eosinophilic inflammation

DOI：

10.7507/1671-6205.202303080

Video：

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Objective To investigate factors influencing the results of bronchodilator reversibility tests (BDT) in mild to moderate asthma, and to develop a model predicting the result of BDT in this population. Methods A cross-sectional study was designed to recruit patients with forced expiratory volume in the first second (FEV₁) ≥ 70% predicted from the Australasian Severe Asthma Network during 2014 to 2021, whose asthma diagnosis was confirmed by a positive bronchial challenge test. Structural questionnaires, BDT, fractional exhaled nitric oxide (FeNO), induced sputum and peripheral blood sampling were conducted. Patients were further divided into positive group and negative group according to their BDT result. Then the comparative analysis between two groups, correlation analysis, and multivariate logistical regression were performed. Logistic models for predicting BDT result were developed using variables screened through LASSO regression. Results A total of 334 patients were included. Compared with the BDT negative group (n=240), the BDT positive group (n=94) was found to have worse airway obstruction in lung function, asthma control and quality of life, higher eosinophil counts in both peripheral blood and induced sputum, and higher FeNO. According to the multivariate regression, the positive BDT results significantly correlated with Asthma Control Questionnaire score, Asthma Questionnaire of Life Quality score, FEV₁%pred, MMEF%pred, FEV₁/FVC, blood and sputum eosinophil counts and FeNO. A total of 326 patients were included in the training set, and FEV₁%pred, MMEF%pred, FEV₁/FVC, smoking pack years, blood and sputum eosinophil counts and FeNO were then screened out by LASSO regression as stable predictors. The areas under the receiver operating characteristic curve of the 3 prediction models (P<0.001) constructed using the variables above ranged from 0.810 to 0.834. Internal validation was performed, and both the discrimination (0.810, 0.834 and 0.812, respectively) and the calibration (0.135, 0.133 and 0.192, respectively) of the models were acceptable. Conclusion The BDT results of patients with mild to moderate asthma were associated with asthma control, lung function, systemic or airway eosinophilia and FeNO, and models including lung function, eosinophils, and FeNO, etc. could predict the BDT results well.

Citation： MA Ziwen, ZHANG Li, DENG Ke, WANG Ji, LI Min, WANG Gang. Construction of models in predicting the result of bronchodilator reversibility test in mild to moderate asthmatics. Chinese Journal of Respiratory and Critical Care Medicine, 2023, 22(3): 189-196. doi: 10.7507/1671-6205.202303080 Copy

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13.	Han YY, Zhang X, Wang J, et al. Multidimensional Assessment of Asthma Identifies Clinically Relevant Phenotype Overlap: A Cross-Sectional Study. J Allergy Clin Immunol Pract, 2021, 9(1): 349-362. e18.
14.	Wang G, Wang F, Gibson PG, et al. Severe and uncontrolled asthma in China: a cross-sectional survey from the Australasian Severe Asthma Network. J Thorac Dis, 2017, 9(5): 1333-1344.
15.	Friedman J, Hastie T, Tibshirani R. Regularization paths for generalized linear models via coordinate descent. J Stat Softw, 2010, 33(1): 1-22.
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18.	Flood-Page P, Swenson C, Faiferman I, et al. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med, 2007, 176(11): 1062-1071.
19.	Haldar P, Brightling CE, Hargadon B, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma [published correction appears in N Engl J Med, 2011, 364(6): 588.]. N Engl J Med, 2009, 360(10): 973-984.
20.	Zhao B, Zheng HM, Li XP, et al. Evaluation of the peripheral blood eosinophil count as a predictor for fractional exhaled nitric oxide or bronchodilator reversibility test outcome. Allergy Asthma Proc, 2021, 42(3): 228-234.
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22.	Hao HJ, Bao WP, Xue YS, et al. Spirometric changes in bronchodilation tests as predictors of asthma diagnosis and treatment response in patients with FEV₁ ≥ 80% predicted. J Allergy Clin Immunol Pract, 2021, 9(8): 3098-3108. e4.

1. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2021 (GINA, 2021). https://ginasthma.org/.
2. 中华医学会呼吸病学分会哮喘学组. 支气管哮喘防治指南(2020年版). 中华结核和呼吸杂志, 2020, 43(12): 1023-1048.
3. 中华医学会呼吸病学分会肺功能专业组. 肺功能检查指南(第二部分)——肺量计检查. 中华结核和呼吸杂志, 2014, 37(7): 481-486.
4. 中华医学会呼吸病学分会肺功能专业组. 肺功能检查指南(第三部分)——组织胺和乙酰甲胆碱支气管激发试验. 中华结核和呼吸杂志, 2014, 37(8): 566-571.
5. 中华医学会呼吸病学分会肺功能专业组. 肺功能检查指南(第四部分)——支气管舒张试验. 中华结核和呼吸杂志, 2014, 37(9): 655-658.
6. Liu L, Zhang X, Zhang L, et al. Reduced bronchodilator reversibility correlates with non-type 2 high asthma and future exacerbations: a prospective cohort study. Respir Med, 2022, 200: 106924.
7. Castro M, Corren J, Pavord ID, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med, 2018, 378(26): 2486-2496.
8. Wenzel S, Castro M, Corren J, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β₂ agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet, 2016, 388(10039): 31-44.
9. Juniper EF, O'Byrne PM, Guyatt GH, et al. Development and validation of a questionnaire to measure asthma control. Eur Respir J, 1999, 14(4): 902-907.
10. Juniper EF, Buist AS, Cox FM, et al. Validation of a standardized version of the Asthma Quality of Life Questionnaire. Chest, 1999, 115(5): 1265-1270.
11. Dweik RA, Boggs PB, Erzurum SC, et al. An Official ATS Clinical Practice Guideline: Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical Applications. Am J Respir Crit Care Med, 2011, 184(5): 602-615.
12. Graham BL, Steenbruggen I, Miller MR, et al. Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement. Am J Respir Crit Care Med, 2019, 200(8): e70-e88.
13. Han YY, Zhang X, Wang J, et al. Multidimensional Assessment of Asthma Identifies Clinically Relevant Phenotype Overlap: A Cross-Sectional Study. J Allergy Clin Immunol Pract, 2021, 9(1): 349-362. e18.
14. Wang G, Wang F, Gibson PG, et al. Severe and uncontrolled asthma in China: a cross-sectional survey from the Australasian Severe Asthma Network. J Thorac Dis, 2017, 9(5): 1333-1344.
15. Friedman J, Hastie T, Tibshirani R. Regularization paths for generalized linear models via coordinate descent. J Stat Softw, 2010, 33(1): 1-22.
16. Hastie T, Tibshirani R, Tibshirani R. Best subset, forward stepwise or lasso? Analysis and recommendations based on extensive comparisons. Stat Sci, 2020, 35(4): 579-592.
17. Li M, Ma ZW, Deng SJ, et al. Development and validation of a noninvasive prediction model for identifying eosinophilic asthma. Respir Med, 2022, 201: 106935.
18. Flood-Page P, Swenson C, Faiferman I, et al. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med, 2007, 176(11): 1062-1071.
19. Haldar P, Brightling CE, Hargadon B, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma [published correction appears in N Engl J Med, 2011, 364(6): 588.]. N Engl J Med, 2009, 360(10): 973-984.
20. Zhao B, Zheng HM, Li XP, et al. Evaluation of the peripheral blood eosinophil count as a predictor for fractional exhaled nitric oxide or bronchodilator reversibility test outcome. Allergy Asthma Proc, 2021, 42(3): 228-234.
21. Milger K, Skowasch D, Hamelmann E, et al. Bronchodilator reversibility in the GAN severe asthma cohort[J/OL]. J Investig Allergol Clin Immunol, [2022-08-24].
22. Hao HJ, Bao WP, Xue YS, et al. Spirometric changes in bronchodilation tests as predictors of asthma diagnosis and treatment response in patients with FEV₁ ≥ 80% predicted. J Allergy Clin Immunol Pract, 2021, 9(8): 3098-3108. e4.

Chinese Journal of Respiratory and Critical Care Medicine

Construction of models in predicting the result of bronchodilator reversibility test in mild to moderate asthmatics

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