Published ahead of print on June 19, 2008, doi:10.1164/rccm.200801-059OC
American Journal of Respiratory and Critical Care Medicine Vol 178. pp. 500-505, (2008)
© 2008 American Thoracic Society
doi: 10.1164/rccm.200801-059OC
Airway Wall Thickening and Emphysema Show Independent Familial Aggregation in Chronic Obstructive Pulmonary Disease
Bipen D. Patel1,2,*,
Harvey O. Coxson3,4,*,
Sreekumar G. Pillai5,
Alvar G. N. Agustí6,
Peter M. A. Calverley7,
Claudio F. Donner8,
Barry J. Make9,
Nestor L. Müller3,
Stephen I. Rennard10,
Jørgen Vestbo11,12,
Emiel F. M. Wouters13,
Melanie P. Hiorns3,
Yasutaka Nakano4,
Patricia G. Camp4,
Paola V. Nasute Fauerbach3,
Nicholas J. Screaton3,
Edward J. Campbell14,
Wayne H. Anderson5,
Peter D. Paré4,
Robert D. Levy4,
Stephen L. Lake15,
Edwin K. Silverman15, and
David A. Lomas1, on behalf of the the International COPD Genetics Network
1 Department of Medicine and 2 Institute of Public Health, University of Cambridge, Cambridge, United Kingdom; 3 Department of Radiology, University of British Columbia and Vancouver General Hospital, Vancouver, Canada; 4 Division of Respiratory Medicine and the James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, St. Paul's Hospital, Vancouver, Canada; 5 GlaxoSmithKline, Research Triangle Park, North Carolina; 6 Hospital Universitari Son Dureta, CIBER Enfermedades Respiratorias and Fundación Caubet-Cimera, Mallorca, Spain; 7 University of Liverpool, Liverpool, United Kingdom; 8 Division of Pulmonary Disease, S. Maugeri Foundation, Veruno, Novara, Italy; 9 National Jewish Medical and Research Center, Denver, Colorado; 10 University of Nebraska, Omaha, Nebraska; 11 Department of Cardiology and Respiratory Medicine, Hvidovre Hospital, Copenhagen, Denmark; 12 North West Lung Centre, Wythenshawe Hospital, Manchester, United Kingdom; 13 Department of Respiratory Medicine, University Hospital Maastricht, Maastricht, The Netherlands; 14 Department of Medicine, University of Utah, Salt Lake City, Utah; and 15 The Channing Laboratory and Pulmonary and Critical Care Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
Correspondence and requests for reprints should be addressed to Prof. David Lomas, Ph.D., F.R.C.P., Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 0XY, UK. E-mail: dal16{at}cam.ac.uk
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  0.001) and symptoms of chronic bronchitis (P < 0.001). FEV1 (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 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.
Key Words: high-resolution computed tomography • familial aggregation • genetics • epidemiology • chronic bronchitis
| AT A GLANCE COMMENTARY
Scientific Knowledge on the Subject
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.
What This Study Adds to the Field
Our data show that airway wall thickening and emphysema make independent contributions to airflow obstruction. These phenotypes also show independent aggregation within families of individuals with COPD.
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Copyright © 2008 American Thoracic Society
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