Patel Bipen D, Coxson Harvey O, Pillai Sreekumar G, Agustí Alvar G N, Calverley Peter M A, Donner Claudio F, Make Barry J, Müller Nestor L, Rennard Stephen I, Vestbo Jørgen, Wouters Emiel F M, Hiorns Melanie P, Nakano Yasutaka, Camp Patricia G, Nasute Fauerbach Paola V, Screaton Nicholas J, Campbell Edward J, Anderson Wayne H, Paré Peter D, Levy Robert D, Lake Stephen L, Silverman Edwin K, Lomas David A
Department of Medicine, University of Cambridge, Cambridge, UK.
Am J Respir Crit Care Med. 2008 Sep 1;178(5):500-5. doi: 10.1164/rccm.200801-059OC. Epub 2008 Jun 19.
It is unclear whether airway wall thickening and emphysema make independent contributions to airflow limitation in chronic obstructive pulmonary disease (COPD) and whether these phenotypes cluster within families.
To determine whether airway wall thickening and emphysema (1) make independent contributions to the severity of COPD and (2) show independent aggregation in families of individuals with COPD.
Index cases with COPD and their smoking siblings underwent spirometry and were offered high-resolution computed tomography scans of the thorax to assess the severity of airway wall thickening and emphysema.
A total of 3,096 individuals were recruited to the study, of whom 1,159 (519 probands and 640 siblings) had technically adequate high-resolution computed tomography scans without significant non-COPD-related thoracic disease. Airway wall thickness correlated with pack-years smoked (P < or = 0.001) and symptoms of chronic bronchitis (P < 0.001). FEV(1) (expressed as % predicted) was independently associated with airway wall thickness at a lumen perimeter of 10 mm (P = 0.0001) and 20 mm (P = 0.0013) and emphysema at -950 Hounsfield units (P < 0.0001). There was independent familial aggregation of both the emphysema (adjusted odds ratio, 2.1; 95% confidence interval, 1.1-4.0; P < or = 0.02) and airway disease phenotypes (P < 0.0001) of COPD.
Airway wall thickening and emphysema make independent contributions to airflow obstruction in COPD. These phenotypes show independent aggregation within families of individuals with COPD, suggesting that different genetic factors influence these disease processes.
气道壁增厚和肺气肿是否对慢性阻塞性肺疾病（COPD）的气流受限有独立影响，以及这些表型是否在家族中聚集尚不清楚。
确定气道壁增厚和肺气肿（1）是否对COPD的严重程度有独立影响，以及（2）在COPD患者家族中是否表现出独立聚集。
COPD索引病例及其吸烟的兄弟姐妹接受了肺活量测定，并接受了胸部高分辨率计算机断层扫描以评估气道壁增厚和肺气肿的严重程度。
共招募了3096名个体参与研究，其中1159名（519名先证者和640名兄弟姐妹）进行了技术上足够的高分辨率计算机断层扫描，且无明显的非COPD相关胸部疾病。气道壁厚度与吸烟包年数（P≤0.001）和慢性支气管炎症状（P<0.001）相关。第1秒用力呼气容积（FEV₁，以预测值的百分比表示）与管腔周长为10mm（P = 0.0001）和20mm（P = 0.0013）时的气道壁厚度以及-950亨氏单位时的肺气肿独立相关（P<0.0001）。COPD的肺气肿（调整后的优势比，2.1；95%置信区间，1.1 - 4.0；P≤0.02）和气道疾病表型（P<0.0001）均存在独立的家族聚集。
气道壁增厚和肺气肿对COPD的气流阻塞有独立影响。这些表型在COPD患者家族中表现出独立聚集，提示不同的遗传因素影响这些疾病过程。
