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Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Smoking is considered the major cause of the disease. Relatively little is known about the molecular mechanisms underlying inflammatory response in smokers' lungs and how this relates to the susceptibility to the disease, particularly why only 10-15% of smokers develop COPD. Recent development in molecular biology techniques allowed the insight into the inner space of the cell, to the levels far beyond the reach of the traditional methods. We review recent hypotheses on cellular and molecular background of COPD with emphasis on the potential role of histone acetylation, as a key modulator of enhanced gene transcription responsible for proinflammatory cytokines production in COPD. Authors propose a role for modification of nucleosomal structure in inflammatory cytokine gene transcription in response to smoking. Cigarette smoke causes oxidative stress altering the balance between histone deacetylation and acetylation in favor of acetylation. This can contribute to the airflow obstruction in smokers susceptible to the development of COPD. Furthermore, histone acetylation seems to be a potential mechanism exclusive to smokers with susceptibility to COPD based on the transcription of specific pro- and anti-inflammatory cytokine combinations.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Smoking is considered the major cause of the disease. All smokers develop airway inflammation through oxidative stress with macrophages, neutrophiles, lymphocytes, eosinophils, NK-cells and mediators involved. Macrophages through the activation of Nuclear Factor kappa B (NF.-kappaB) release proinflammatory mediators, lymphocyte chemotactic agents and elastolytic enzymes, activate neutrophil driven serine proteases and GM-CSF. Neutrophiles release IL-8 which in turn recruits neutrophils to the airways. In response to cigarette smoke lung epithelium may release TNF-alpha, TGF-beta, IL-1beta, GM-CSF, IL-8 reactive oxygen species (ROS). Increased number of lymphocyte T CD8+ and CD4+ subpopulations may lead to lung epithelium cells apoptosis and necrosis through perphorines and granzyme-B and TNF-alpha activation. Moreover, increased expression of IL-6, IL-10, IL-12, IL-13, and INF-gamma is observed. Authors indicate the possibility of new treatment strategies such as: agents directed against adhesion molecules, chemokines, phosphodiesterase 4, p38 MAPK, NF.-kappaB phosphoinositide-3-kinase gamma, TGF-beta, NOS synthase, serine proteinases and matrix metalloproteinases.

Plasma Atrial Natriuretic Peptide (ANP) levels are elevated in patients wish chronic obstructive pulmonary disease (COPD) and can play a role in oedema formation. Plasma ANP levels measured in 60 patients with COPD were compared with results of pulmonary haemodynamics, with therapeutic response to treatment in the time of exacerbation of COPD and with physiologic status of patients with stable COPD. Plasma ANP levels did not correlate with right atrial and pulmonary artery pressure, but were significantly related with right ventricular end diastolic volume and with right ventricular wall volume measured by magnetic resonance imaging. Oxygen breathing (2 l/min by nasal prongs in 30 min.) did not change either mean pulmonary artery pressure or ANP levels. Among patients studied during an acute exacerbation of COPD, plasma ANP levels were higher in patients with oedema (302 +/- 185 pg/ml) than in patients without oedema (87 +/- 43 pg/ml). Oxygen therapy applied in one hour did not influence plasma ANP levels. Plasma ANP levels decreased during first three days of treatment in patients with oedema. This decrease was related to the body weight. In the group of patients with hypoxemia in stable COPD, plasma ANP levels (120 +/- 50 pg/ml) were higher in patients with the history of hypercapnia and oedema than in others (54 +/- 15 pg/ml).

It has been difficult to assess the progression of pulmonary emphysema since accurate quantification of the extent of this condition has only previously been possible on post mortem or resected lungs. Previously we have shown that measurements of CT lung density correlated with the degree of emphysema, measured morphometrically in resected lungs. We have therefore employed this technique to assess the progression of emphysema in 17 patients (12M, 5F) with wide range of chronic airflow limitation (FEV1 15-68% predicted). There was little change in the degree of airflow limitation, hyperinflation or arterial blood gas values over 30 +/- 4 months of follow up (p > 0.05). However during this period there was a significant decrease in the lowest 5th percentile of CT density, which fell from -920 +/- 32 to -940 +/- 36 Hounsfield units (p < 0.005) associated with significant fall in the diffusing capacity for carbon monoxide. We believe that these data show the ability of CT scanning to assess the progression of emphysema in patients with chronic obstructive pulmonary disease.