Published ahead of print on June 19, 2008, doi:10.1164/rccm.200801-059OC
Am. J. Respir. Crit. Care Med., Volume 178, Number 5, September 2008, 500-505
A more recent version of this article appeared on September 1, 2008
Submitted on January 10, 2008
Accepted on June 19, 2008
Airway Wall Thickening and Emphysema Show Independent Familial Aggregation in COPD
Bipen D Patel1, Harvey O Coxson2, Sreekumar G Pillai3, Alvar GN Agusti4, Peter MA Calverley5, Claudio F Donner6, Barry J Make7, Nestor L Muller8, Stephen I Rennard9, Jorgen Vestbo10, Emiel FM Wouters11, Melanie P Hiorns8, Yasutaka Nakano12, Patricia G Camp12, Paola V Nasute Fauerbach8, Nicholas J Screaton8, Edward J Campbell13, Wayne H Anderson3, Edwin K Silverman14, and David A Lomas15*
1 Department of Medicine, University of Cambridge, Cambridge, United Kingdom; Institute of Public Health, University of Cambridge, Cambridge, United Kingdom,
2 Department of Radiology, University of British Columbia, Vancouver General Hospital, Vancouver, British Columbia, Canada; Division of Respiratory Medicine and James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, St Paul's Hospital, Vancouver, British Columbia, Canada,
3 Research Triangle Park, GlaxoSmithKline, Raleigh Durham, NC, USA,
4 CIBER Enfermedades Respiratorias and Fundacion Caubet-Cimera, Hospital Universitari Son Durea, Mallorca, Spain,
5 University of Liverpool, Liverpool, United Kingdom,
6 Division of Pulmonary Disease, S. Maugeri Foundation, Veruno, Italy,
7 National Jewish Medical and Research Centre, Denver, CO, USA,
8 Department of Radiology, University of British Columbia, Vancouver General Hospital, Vancouver, British Columbia, Canada,
9 University of Nebraska, Omaha, NE, USA,
10 Department of Cardiology and Respiratory Medicine, Hvidovre Hospital, Copenhagen, Denmark; North West Lung Centre, Wythenshawe Hospital, Manchester, United Kingdom,
11 Department of Respiratory Medicine, University Hospital Maastricht, Maastricht, The Netherlands,
12 Division of Respiratory Medicine and James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, St Paul's Hospital, Vancouver, British Columbia, Canada,
13 Department of Medicine, University of Utah, Salt Lake City, UT, USA,
14 The Channing Laboratory and Pulmonary and Critical Care Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA,
15 Department of Medicine, University of Cambridge, Cambridge, United Kingdom
* To whom correspondence should be addressed. 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.
Objective: To determine whether airway wall thickening and emphysema: (i) make independent contributions to the severity of COPD and (ii) 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 (HRCT) scans of the thorax
to assess the severity of airway wall thickening and emphysema.
Results: 3096 individuals were recruited to the study of whom 1159 (519 probands and 640 siblings) had technically adequate HRCT 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 10mm (p=0.0001) and 20 mm (p=0.0013) and emphysema at -950 HU (p<0.0001). There was independent familial aggregation of both the emphysema (adjusted OR 2.1, C.I. 1.1 to 4.0, p0.02) 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: HRCT, familial aggregation, genetics, epidemiology, chronic bronchitis
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