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Am J Respir Crit Care Med. 2008 Sep 1;178(5):500-5. doi: 10.1164/rccm.200801-059OC. Epub 2008 Jun 19.

Airway wall thickening and emphysema show independent familial aggregation in chronic obstructive pulmonary disease.

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1
Department of Medicine, University of Cambridge, Cambridge, UK.

Abstract

RATIONALE:

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.

OBJECTIVES:

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.

METHODS:

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.

MEASUREMENTS AND MAIN RESULTS:

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.

CONCLUSIONS:

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.

PMID:
18565956
DOI:
10.1164/rccm.200801-059OC
[Indexed for MEDLINE]
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