Systemic inflammatory response to smoking in chronic obstructive pulmonary disease: evidence of a gender effect.
BACKGROUND
Tobacco smoking is the main risk factor of chronic obstructive pulmonary disease (COPD) but not all smokers develop the disease. An abnormal pulmonary and systemic inflammatory response to smoking is thought to play a major pathogenic role in COPD, but this has never been tested directly.


METHODS
We studied the systemic biomarker and leukocyte transcriptomic response (Affymetrix microarrays) to smoking exposure in 10 smokers with COPD and 10 smokers with normal spirometry. We also studied 10 healthy never smokers (not exposed to smoking) as controls. Because some aspects of COPD may differ in males and females, and the inflammatory response to other stressors (infection) might be different in man and women, we stratified participant recruitment by sex. Differentially expressed genes were validated by q-PCR. Ontology enrichment was evaluated and interaction networks inferred.


RESULTS
Principal component analysis identified sex differences in the leukocyte transcriptomic response to acute smoking. In both genders, we identified genes that were differentially expressed in response to smoking exclusively in COPD patients (COPD related signature) or smokers with normal spirometry (Smoking related signature), their ontologies and interaction networks.


CONCLUSIONS
The use of an experimental intervention (smoking exposure) to investigate the transcriptomic response of peripheral leukocytes in COPD is a step beyond the standard case-control transcriptomic profiling carried out so far, and has facilitated the identification of novel COPD and Smoking expression related signatures which differ in males and females.
Fundació Privada Clínic per a la Recerca Biomèdica, Barcelona, Spain; Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; CIBER Enfermedades Respiratorias (CIBERES), Barcelona, Spain.
Rosa
R
Faner
Fundació Privada Clínic per a la Recerca Biomèdica, Barcelona, Spain.
Nuria
N
Gonzalez
Fundació Privada Clínic per a la Recerca Biomèdica, Barcelona, Spain; Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Tamara
T
Cruz
Bioinformatics Core Facility, IDIBAPS, Barcelona, Spain.
Susana Graciela
SG
Kalko
Fundació Privada Clínic per a la Recerca Biomèdica, Barcelona, Spain; Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; CIBER Enfermedades Respiratorias (CIBERES), Barcelona, Spain; Thorax Institute, Hospital Clinic, University of Barcelona, Barcelona, Spain; Fundació de Investigació Sanitaria Illes Balears (FISIB), Mallorca, Spain.
Alvar
A
Agustí
D000368:Aged; D015415:Biomarkers; D016022:Case-Control Studies; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D007962:Leukocytes / Q000378:metabolism; D008168:Lung / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D025341:Principal Component Analysis; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology / Q000276:immunology / Q000503:physiopathology*; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects*; D013147:Spirometry; D014026:Nicotiana
D015415:Biomarkers