吸烟史对重度哮喘基线及生物制剂选择的影响
2025/03/04
摘要
背景：吸烟史超过10包年的哮喘患者常被排除在临床试验之外。目前关于吸烟如何影响此类患者临床特征及其对治疗选择潜在影响的研究仍有限。
目的：作者旨在评估累积吸烟史对重度哮喘患者临床特征的影响。
方法：本研究基于德国哮喘网络（GAN）重度哮喘登记数据，收集患者肺功能、哮喘控制水平、急性加重频率及生物标志物水平进行分析。根据吸烟情况，按当前吸烟、既往吸烟者（二者合称曾吸烟者）和从不吸烟者分为三组进行对比，并按吸烟史分层（<10包年、10-20包年、20包年）建立线性模型。
结果：本研究纳入了 2478 名患者：当前吸烟者65例（2.6%），既往吸烟者1005例（40.6%），从不吸烟者1408例（56.8%）。1070例曾吸烟者中，529例（21.3%）<10包年，304例（12.3%）10-20包年，237例（9.6%）>20包年。结果显示：累积吸烟史与较差的哮喘控制相关，尤其是吸烟史>20包年的患者（ACT评分降低1.76分，95% CI [-2.76, -0.77], p<0.001；mini-AQLQ评分降低0.31分，95% CI [-0.53, -0.10], p=0.004）；但与急性加重频率及维持性口服糖皮质激素剂量无显著差异（p=0.13 和 p=1.0）。累积吸烟史还与吸烟相关肺损伤显著相关，包括DLCO（10-20 包年降低 0.37 mmol/min/kPa （p=0.014），>20 包年降低0.92 （p<0.001）），但两组肺功能FEV1水平和 FEV1 可逆性相似。累积吸烟史导致FeNO降低至从不吸烟者组的0.84 [0.73;0.97] 倍（p=0.007），而血嗜酸性粒细胞计数（BEC）和 IgE 水平相似（BEC p=1.0，IgE p=0.49）。
结论：哮喘患者的累积吸烟史与疾病控制不佳、FeNO 水平更低和吸烟相关的肺损伤有关。尽管存在这些差异，但BEC、IgE、OCS 剂量和急性加重频率等关键哮喘特征相似。经过严格评估和筛选，吸烟史>10包年的患者仍可能符合接受靶向治疗。
关键词： 哮喘；FeNO;IgE；哮喘生物标志物；哮喘表型；生物疗法；血嗜酸性粒细胞计数；个性化治疗；吸烟
文献来源：（Biener L, Stoshikj S, Brugger J, et al. The impact of smoking history on baseline characteristic in patients with severe asthma in the German Asthma Net (GAN). J Allergy Clin Immunol Pract. Published online February 1, 2025. doi:10.1016/j.jaip.2025.01.024）
目的：作者旨在评估累积吸烟史对重度哮喘患者临床特征的影响。
方法：本研究基于德国哮喘网络（GAN）重度哮喘登记数据，收集患者肺功能、哮喘控制水平、急性加重频率及生物标志物水平进行分析。根据吸烟情况，按当前吸烟、既往吸烟者（二者合称曾吸烟者）和从不吸烟者分为三组进行对比，并按吸烟史分层（<10包年、10-20包年、20包年）建立线性模型。
结果：本研究纳入了 2478 名患者：当前吸烟者65例（2.6%），既往吸烟者1005例（40.6%），从不吸烟者1408例（56.8%）。1070例曾吸烟者中，529例（21.3%）<10包年，304例（12.3%）10-20包年，237例（9.6%）>20包年。结果显示：累积吸烟史与较差的哮喘控制相关，尤其是吸烟史>20包年的患者（ACT评分降低1.76分，95% CI [-2.76, -0.77], p<0.001；mini-AQLQ评分降低0.31分，95% CI [-0.53, -0.10], p=0.004）；但与急性加重频率及维持性口服糖皮质激素剂量无显著差异（p=0.13 和 p=1.0）。累积吸烟史还与吸烟相关肺损伤显著相关，包括DLCO（10-20 包年降低 0.37 mmol/min/kPa （p=0.014），>20 包年降低0.92 （p<0.001）），但两组肺功能FEV1水平和 FEV1 可逆性相似。累积吸烟史导致FeNO降低至从不吸烟者组的0.84 [0.73;0.97] 倍（p=0.007），而血嗜酸性粒细胞计数（BEC）和 IgE 水平相似（BEC p=1.0，IgE p=0.49）。
结论：哮喘患者的累积吸烟史与疾病控制不佳、FeNO 水平更低和吸烟相关的肺损伤有关。尽管存在这些差异，但BEC、IgE、OCS 剂量和急性加重频率等关键哮喘特征相似。经过严格评估和筛选，吸烟史>10包年的患者仍可能符合接受靶向治疗。
关键词： 哮喘；FeNO;IgE；哮喘生物标志物；哮喘表型；生物疗法；血嗜酸性粒细胞计数；个性化治疗；吸烟
文献来源：（Biener L, Stoshikj S, Brugger J, et al. The impact of smoking history on baseline characteristic in patients with severe asthma in the German Asthma Net (GAN). J Allergy Clin Immunol Pract. Published online February 1, 2025. doi:10.1016/j.jaip.2025.01.024）
（南方医科大学南方医院 胡玉玲 龚钊乾 赵文驱 赵海金）
Abstract
Background: Asthma patients with >10 pack-years are frequently excluded from asthma trials. Little is known about how smoking affects their characteristics, and therefore may impact treatment choices.
Objective: To evaluate the impact of cumulative smoking history on severe asthma patients' characteristics METHODS: We analysed pulmonary function tests, asthma control, exacerbation rate and biomarkers. We compared active and ex-smokers (=ever-smokers) vs. never-smokers and performed linear models for three groups stratified by smoking history (<10 pack-years (py), 10-20 py, >20 py). Data was obtained from the severe asthma registry German Asthma Net (GAN).
Results: We included 2.478 patients: 65 (2.6%) active smokers, 1.005 (40.6%) ex-smokers and 1.408 (56.8%) never-smokers. Of the 1070 ever-smokers, 529 patients (21.3%) had <10 py, 304 (12.3%) 10-20 py and 237 (9.6%) >20 py. Cumulative smoking history was associated with worse asthma control (>20 py: ACT -1.76 [-2.76; -0.77] points (p <.001); mini-AQLQ -0.31 [-0.53; -0.10] points (p=0.004)), while exacerbation rate and maintenance oral corticosteroid (OCS) doses were similar (p=.13 and p=1.0). Cumulative smoking history was associated with smoking-related lung injury e.g. DLCO (-0.37 mmol/min/kPa for 10-20 py (p=.014) respectively -0.92 for >20 py (p<.001)), but FEV1 and FEV1-reversibility were similar. Cumulative smoking history was furthermore associated 0.84- [0.73; 0.97] fold lower FeNO concentrations (p=.007) while blood eosinophil count and IgE-levels were comparable (BEC p=1.0, IgE p=.49)
CONCLUSION: Cumulative smoking history in asthma patients is associated with worse disease control, lower FeNO levels and smoking-related lung-injuries. Despite these differences, key asthma characteristics like BEC, IgE, OCS dose and exacerbation rates remain similar. If thoroughly examined and selected, patients with >10 py may also qualify for targeted treatments.
Keywords: Asthma; FeNO; IgE; asthma biomarkers; asthma phenotype; biologic therapy; blood eosinophil count; personalised therapy; smoking.
Background: Asthma patients with >10 pack-years are frequently excluded from asthma trials. Little is known about how smoking affects their characteristics, and therefore may impact treatment choices.
Objective: To evaluate the impact of cumulative smoking history on severe asthma patients' characteristics METHODS: We analysed pulmonary function tests, asthma control, exacerbation rate and biomarkers. We compared active and ex-smokers (=ever-smokers) vs. never-smokers and performed linear models for three groups stratified by smoking history (<10 pack-years (py), 10-20 py, >20 py). Data was obtained from the severe asthma registry German Asthma Net (GAN).
Results: We included 2.478 patients: 65 (2.6%) active smokers, 1.005 (40.6%) ex-smokers and 1.408 (56.8%) never-smokers. Of the 1070 ever-smokers, 529 patients (21.3%) had <10 py, 304 (12.3%) 10-20 py and 237 (9.6%) >20 py. Cumulative smoking history was associated with worse asthma control (>20 py: ACT -1.76 [-2.76; -0.77] points (p <.001); mini-AQLQ -0.31 [-0.53; -0.10] points (p=0.004)), while exacerbation rate and maintenance oral corticosteroid (OCS) doses were similar (p=.13 and p=1.0). Cumulative smoking history was associated with smoking-related lung injury e.g. DLCO (-0.37 mmol/min/kPa for 10-20 py (p=.014) respectively -0.92 for >20 py (p<.001)), but FEV1 and FEV1-reversibility were similar. Cumulative smoking history was furthermore associated 0.84- [0.73; 0.97] fold lower FeNO concentrations (p=.007) while blood eosinophil count and IgE-levels were comparable (BEC p=1.0, IgE p=.49)
CONCLUSION: Cumulative smoking history in asthma patients is associated with worse disease control, lower FeNO levels and smoking-related lung-injuries. Despite these differences, key asthma characteristics like BEC, IgE, OCS dose and exacerbation rates remain similar. If thoroughly examined and selected, patients with >10 py may also qualify for targeted treatments.
Keywords: Asthma; FeNO; IgE; asthma biomarkers; asthma phenotype; biologic therapy; blood eosinophil count; personalised therapy; smoking.
