Izquierdo Manuel, Marion Chad R, Genese Frank, Newell John D, O'Neal Wanda K, Li Xingnan, Hawkins Gregory A, Barjaktarevic Igor, Barr R Graham, Christenson Stephanie, Cooper Christopher B, Couper David, Curtis Jeffrey, Han Meilan K, Hansel Nadia N, Kanner Richard E, Martinez Fernando J, Paine Robert, Tejwani Vickram, Woodruff Prescott G, Zein Joe G, Hoffman Eric A, Peters Stephen P, Meyers Deborah A, Bleecker Eugene R, Ortega Victor E
Section on Pulmonary, Critical Care, Allergy and Immunological Diseases, Wake Forest School of Medicine, Wake Forest, North Carolina, United States.
Department of Pulmonary Disease, Rochester General Hospital, Rochester, New York, United States.
Chronic Obstr Pulm Dis. 2023 Jul 26;10(3):199-210. doi: 10.15326/jcopdf.2023.0388.
Bronchiectasis is common among those with heavy smoking histories, but risk factors for bronchiectasis, including alpha-1 antitrypsin deficiency, and its implications for COPD severity are uncharacterized in such individuals.
To characterize the impact of bronchiectasis on COPD and explore alpha-1antitrypsin as a risk factor for bronchiectasis.
SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) participants (N=914; ages 40-80 years; ≥20-pack-year smoking) had high-resolution computed tomography (CT) scans interpreted visually for bronchiectasis, based on airway dilation without fibrosis or cicatrization. We performed regression-based models of bronchiectasis with clinical outcomes and quantitative CT measures. We deeply sequenced the gene encoding -alpha-1 antitrypsin, , in 835 participants to test for rare variants, focusing on the PiZ genotype (GluLys, rs28929474).
We identified bronchiectasis in 365 (40%) participants, more frequently in women (45% versus 36%, =0.0045), older participants (mean age=66[standard deviation (SD)=8.3] versus 64[SD=9.1] years, =0.0083), and those with lower lung function (forced expiratory volume in 1 second [FEV ] percentage predicted=66%[SD=27] versus 77%[SD=25], <0.0001; FEV to forced vital capacity [FVC] ratio=0.54[0.17] versus 0.63[SD=0.16], <0.0001). Participants with bronchiectasis had greater emphysema (%voxels ≤-950 Hounsfield units, 11%[SD=12] versus 6.3%[SD=9], <0.0001) and parametric response mapping functional small airways disease (26[SD=15] versus 19[SD=15], <0.0001). Bronchiectasis was more frequent in the combined PiZZ and PiMZ genotype groups compared to those without PiZ, PiS, or other rare pathogenic variants (N=21 of 40 [52%] versus N=283 of 707[40%], odds ratio [OR]=1.97; 95% confidence interval [CI]=1.002, 3.90, =0.049), an association attributed to White individuals (OR=1.98; 95%CI = 0.9956, 3.9; =0.051).
Bronchiectasis was common in those with heavy smoking histories and was associated with detrimental clinical and radiographic outcomes. Our findings support alpha-1antitrypsin guideline recommendations to screen for alpha-1 antitrypsin deficiency in an appropriate bronchiectasis subgroup with a significant smoking history.
支气管扩张在有重度吸烟史的人群中很常见，但支气管扩张的危险因素，包括α-1抗胰蛋白酶缺乏症，及其对慢性阻塞性肺疾病（COPD）严重程度的影响在这类人群中尚未明确。
明确支气管扩张对COPD的影响，并探究α-1抗胰蛋白酶作为支气管扩张危险因素的情况。
慢性阻塞性肺疾病亚组和中间结局指标研究（SPIROMICS）的参与者（N = 914；年龄40 - 80岁；吸烟史≥20包年）进行了高分辨率计算机断层扫描（CT），根据无纤维化或瘢痕形成的气道扩张情况，由专业人员对支气管扩张进行视觉解读。我们使用基于回归的模型分析支气管扩张与临床结局及定量CT测量值之间的关系。我们对835名参与者编码α-1抗胰蛋白酶的基因进行深度测序，以检测罕见变异，重点关注PiZ基因型（GluLys，rs28929474）。
我们在365名（40%）参与者中发现了支气管扩张，女性（45% 对36%，P = 0.0045）、年龄较大的参与者（平均年龄 = 66[标准差（SD）= 8.3]岁对64[SD = 9.1]岁，P = 0.0083）以及肺功能较低的参与者（第1秒用力呼气容积[FEV₁]预测百分比 = 66%[SD = 27]对77%[SD = 25]，P < 0.0001；FEV₁与用力肺活量[FVC]比值 = 0.54[0.17]对0.63[SD = 0.16]，P < 0.0001）中支气管扩张更为常见。患有支气管扩张的参与者肺气肿更严重（≤ - 950亨氏单位的体素百分比，11%[SD = 12]对6.3%[SD = 9]，P < 0.0001），且参数反应映射功能性小气道疾病更严重（26[SD = 15]对19[SD = 15]，P < 0.0001）。与没有PiZ、PiS或其他罕见致病变异的人群相比，PiZZ和PiMZ基因型组合组中支气管扩张更为常见（40人中21人[占52%]对707人中283人[占40%]，比值比[OR] = 1.97；95%置信区间[CI] = 1.002，3.90，P = 0.049），这种关联在白人个体中更为明显（OR = 1.98；95%CI = 0.9956，3.9；P = 0.051）。
支气管扩张在有重度吸烟史的人群中很常见，并且与不良的临床和影像学结局相关。我们的研究结果支持α-1抗胰蛋白酶指南中关于在有显著吸烟史的合适支气管扩张亚组中筛查α-1抗胰蛋白酶缺乏症的建议。
