Chronic obstructive pulmonary disease beyond cigarette smoke.

lymphocytes and above all in lung epithelial cells [3] . The E1A gene, where the E stands for the fact that it is one of a group of genes transcribed early in the viral life cycle, is responsible for enhancing host infl ammatory mediator expression, because its products are transactivators that function by interacting with numerous cellular transcription factors, transcriptional coactivators and cell-cycleregulatory proteins. Furthermore, the E1A gene has been found to be integrated at a specifi c site on chromosome 19 in the lung cells of patients with COPD, and in patients with severe emphysema there is a fi vefold increase in the number of alveolar epithelial cells expressing E1A protein [2, 3] . These observations have led to a working hypothesis that the chronic expression of E1A might amplify the cigarette-smoke-induced infl ammatory process. Keicho et al. [4] demonstrated that E1A enhances the expression of IL-8 and intracellular adhesion molecules 1 after lipopolysaccharide stimulation through the modulation of nuclear factorB activity. In this issue of Respiration , Higashimoto et al. [5] add another important element to the understanding of the protean mechanism of adenoviral-E1A-enhancing airway infl ammation. The authors successfully demonstrate an E1A-mediated suppression of secretory leukoprotease inhibitor (SLPI) and elafi n/skin-derived antileukoproteinase (two protease inhibitors) produced by airway epitheAlthough cigarette smoking is the major risk factor for the development of chronic obstructive pulmonary disease (COPD), only 15–20% of all smokers develop airway obstruction, therefore not all smokers acquire COPD, and COPD can develop in non-smokers [1] . Unfortunately, in COPD, as in many other conditions, a complete description of the molecular components that encode a particular phenotype would not allow for a complete understanding of the disease without taking into account the infl uence of other factors such as environment. COPD, like asthma, seems to be a multigenic disease, and in the literature there are many essays pinpointing a specifi c genetic determinant of airway function as well as a predisposing factor that may confer susceptibility to COPD: 1 -antitrypsin defi ciency (PiMZ and PiMM genotype), and polymorphisms in matrix metalloproteinases 1 and 12 genes, the tumor necrosis factorgene promoter and in the antioxidant genes glutathione S-transferase (GSTM1, GSTT1, GSTP1), only to mention a few [2] . In recent years, epidemiological observations suggesting that childhood viral infections are an independent risk factor for the development of COPD in adulthood have increased the interest in virus infections, in particular group C adenovirus, which is endemic and could lead to latent infections that persist in tonsils, peripheral blood