女性哮喘患者中的肥胖：基线劣势加上更大的小气道反应性。

Obesity in women with asthma: Baseline disadvantage plus greater small-airway responsiveness.

机构信息

Department of Respiratory Diseases, Univ Montpellier, CHU Montpellier, Montpellier, France.

PhyMedExp, Univ Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France.

出版信息

Allergy. 2023 Mar;78(3):780-790. doi: 10.1111/all.15509. Epub 2022 Sep 15.

DOI:10.1111/all.15509

PMID:36070075

Abstract

BACKGROUND

Obesity is known to diminish lung volumes and worsen asthma. However, mechanistic understanding is lacking, especially as concerns small-airway responsiveness. The objective of this study was therefore to compare small-airway responsiveness, as represented by the change in expiratory:inspiratory mean lung density ratios (MLD , as determined by computed tomography [CT]) throughout methacholine testing in obese versus non-obese women with asthma.

METHODS

Thoracic CT was performed during methacholine bronchoconstriction challenges to produce standardized response curves (SRC: response parameter versus ln[1 + % PD20], where PD20 is the cumulative methacholine dose) for 31 asthma patients (n = 18 non-obese and n = 13 obese patients). Mixed models evaluated obesity effects and interactions on SRCs while adjusting for age and bronchial morphology. Small airway responsiveness as represented by SRC slope was calculated for each third of the MLD response and compared between groups.

RESULTS

Obesity-associated effects observed during experimental bronchoconstriction included: (i) a significant baseline effect for forced expiratory volume in 1 second with lower values for the obese (73.11 ± 13.44) versus non-obese (82.19 ± 8.78; p = 0.002) groups prior to methacholine testing and (ii) significantly higher responsiveness in small airways as estimated via differences in MLD slopes (group×ln(1 + % PD20 interaction; p = 0.023). The latter were pinpointed to higher slopes in the obese group at the beginning 2/3 of SRCs (p = 0.004 and p = 0.021). Significant obesity effects (p = 0.035 and p = 0.008) indicating lower forced vital capacity and greater % change in MLD (respectively) throughout methacholine testing, were also observed.

CONCLUSION

In addition to baseline differences, small-airway responsiveness (as represented by the change in MLD ) during methacholine challenge is greater in obese women with asthma as compared to the non-obese.

摘要

背景

肥胖已知会降低肺容量并使哮喘恶化。然而，缺乏对其机制的理解，特别是在涉及小气道反应性方面。因此，本研究的目的是比较肥胖和非肥胖哮喘女性在乙酰甲胆碱测试过程中，小气道反应性（由 CT 确定的呼气与吸气平均肺密度比[MLD]的变化来表示），以及小气道反应性随乙酰甲胆碱剂量递增而变化的特征（代表参数的标准反应曲线[SRC]：响应参数与 ln[1+%PD20]，其中 PD20 是累积乙酰甲胆碱剂量）。

方法

对 31 例哮喘患者（n=18 例非肥胖患者和 n=13 例肥胖患者）进行乙酰甲胆碱支气管收缩挑战，同时进行胸部 CT 检查，以产生标准化反应曲线（SRC：响应参数与 ln[1+%PD20]，其中 PD20 是累积乙酰甲胆碱剂量）。混合模型评估了肥胖对 SRC 的影响和相互作用，同时调整了年龄和支气管形态。通过比较每组之间的 MLD 响应的每三分之一的 SRC 斜率，来评估小气道反应性。

结果

在实验性支气管收缩过程中观察到与肥胖相关的影响包括：（i）在进行乙酰甲胆碱测试之前，用力呼气量在 1 秒内的基础值存在显著差异，肥胖组的数值较低（73.11±13.44），而非肥胖组的数值较高（82.19±8.78；p=0.002）；（ii）小气道的反应性显著增加，通过 MLD 斜率的差异来估计（组×ln(1+%PD20 相互作用；p=0.023）。后者是由于肥胖组在前 2/3 的 SRC 中斜率更高（p=0.004 和 p=0.021）。在整个乙酰甲胆碱测试过程中，还观察到肥胖的显著影响（p=0.035 和 p=0.008），这表明用力肺活量降低和 MLD 的变化百分比更大（分别）。