Bronchodilator responsiveness as a phenotypic characteristic of established chronic obstructive pulmonary disease.
BACKGROUND
Bronchodilator responsiveness is a potential phenotypic characteristic of chronic obstructive pulmonary disease (COPD). We studied whether change in lung function after a bronchodilator is abnormal in COPD, whether stable responder subgroups can be identified, and whether these subgroups experience different clinical outcomes.


METHODS
1831 patients with COPD, 285 smoking (SC) and 228 non-smoking (NSC) controls from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) cohort. Spirometric reversibility to 400 μg inhaled salbutamol was assessed on four occasions over 1 year.


RESULTS
Forced expiratory volume in 1 s (FEV(1)) increase after salbutamol was similar in SC (mean 0.14 litres (SD 0.15)) and COPD (0.12 litres (0.15)) and was significantly greater than NSC (0.08 litres (0.14)). Reversibility status varied with repeated testing in parallel with the day-to-day variation in pre-bronchodilator FEV(1), which was similar in control subjects and patients with COPD. Absolute FEV(1) change decreased by Global initiative for chronic Obstructive Lung Disease (GOLD) stage in patients with COPD (GOLD II, mean 0.16 litres (SD 0.17); III, 0.10 litres (0.13); IV, 0.05 litres (0.08) as did chances of being classified as reversible. CT-defined emphysema was weakly related to the absolute change in FEV(1) post salbutamol. Consistently reversible patients (n=227) did not differ in mortality, hospitalisation or exacerbation experience from irreversible patients when allowing for differences in baseline FEV(1).


CONCLUSIONS
Reversibility only assessed with salbutamol and defined by FEV(1) criteria. The COPD population was older than the control populations.


CONCLUSIONS
Post-salbutamol FEV(1) change is similar in patients with COPD and smoking controls but is influenced by baseline lung function and the presence of emphysema. Bronchodilator reversibility status varies temporally and does not distinguish clinically relevant outcomes, making it an unreliable phenotype.
School of Ageing and Chronic Disease, University Hospital Aintree, Lower Lane, Liverpool, UK.
Paul
P
Albert
Alvar
A
Agusti
Lisa
L
Edwards
Ruth
R
Tal-Singer
Julie
J
Yates
Per
P
Bakke
Bartolome R
BR
Celli
Harvey O
HO
Coxson
Courtney
C
Crim
David A
DA
Lomas
William
W
Macnee
Bruce
B
Miller
Stephen
S
Rennard
Edwin K
EK
Silverman
Jørgen
J
Vestbo
Emiel
E
Wouters
Peter
P
Calverley
D000328:Adult; D000368:Aged; D000420:Albuterol / Q000494:pharmacology / Q000627:therapeutic use; D001993:Bronchodilator Agents / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000503:physiopathology; D012907:Smoking / Q000009:adverse effects / Q000503:physiopathology; D013147:Spirometry / Q000379:methods; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
D001993:Bronchodilator Agents; D000420:Albuterol