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


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.
Department of Medicine, University of Cambridge, Cambridge, UK.
Bipen D
BD
Patel
Harvey O
HO
Coxson
Sreekumar G
SG
Pillai
Alvar G N
AG
Agustí
Peter M A
PM
Calverley
Claudio F
CF
Donner
Barry J
BJ
Make
Nestor L
NL
Müller
Stephen I
SI
Rennard
Jørgen
J
Vestbo
Emiel F M
EF
Wouters
Melanie P
MP
Hiorns
Yasutaka
Y
Nakano
Patricia G
PG
Camp
Paola V
PV
Nasute Fauerbach
Nicholas J
NJ
Screaton
Edward J
EJ
Campbell
Wayne H
WH
Anderson
Peter D
PD
Paré
Robert D
RD
Levy
Stephen L
SL
Lake
Edwin K
EK
Silverman
David A
DA
Lomas
D001987:Bronchiectasis / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D015331:Cohort Studies; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D011656:Pulmonary Emphysema / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D035781:Siblings; D012907:Smoking / Q000009:adverse effects; D014057:Tomography, X-Ray Computed