Airway epithelium represents the first line of defense against toxic inhalants. In some subjects, cigarette smoking causes airway inflammation, hypersecretion of mucus, and poorly reversible airflow limitation through mechanisms that are still largely unknown. Likewise, it is unclear why only some smokers develop chronic obstructive pulmonary disease (COPD). Two cell types consistently result in relation to chronic airflow limitation in COPD: neutrophils and CD8+ cells. Neutrophils are compartmentalized in the mucosal surface of the airways and air spaces, that is, the epithelium and lumen, whereas CD8+ cells exhibit a more extensive distribution along the subepithelial zone of the airways and lung parenchyma, including alveolar walls and arteries. This pattern of inflammatory cell distribution is observed in mild or moderate COPD, and in patients who have developed COPD, it is not modified by smoking cessation. The number of neutrophils further increases in the submucosa of patients with severe COPD, suggesting a role for these cells in the progression of the disease. Hypersecretion of mucus is a major manifestation in COPD. Mucus is produced by bronchial glands and goblet cells lining the airway epithelium. Unlike mucous gland enlargement, greater mucosal inflammation is associated with sputum production. Whereas neutrophil infiltration of submucosal glands occurs only in smokers with COPD, goblet cell hyperplasia in peripheral airways occurs both in smokers with or without COPD, suggesting that the major determinant of goblet cell hyperplasia is cigarette smoke itself.

Oxidant/antioxidant imbalance is implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD).The current study examined the expression of antioxidant and pro-oxidant enzymes, haem oxygenases (HO) and inducible nitric oxide synthase (iNOS) respectively, in patients with severe COPD and control smokers without lung function impairment. Immunoreactivity for HO-1, HO-2, iNOS and nitric oxide-derived oxidants expressed as nitrotyrosine (N-Tyr) was quantified in peripheral lung.HO-1+ alveolar macrophages were decreased in severe COPD compared to control smokers, whereas no difference was observed in iNOS+ macrophages. In contrast, severe patients had significantly higher numbers of iNOS+ cells in alveolar walls. These iNOS+ cells were identified as type 2 pneumocytes and their number was inversely related to HO-1+ macrophages. There were no significant differences in N-Tyr immunostaining between the two groups. However, the rate of protein nitration in lungtissue was directly related to iNOS expression and associated with lower valuesofforced expiratory volume in one second/forced vital capacity. HO-2 was constitutively expressed by type 2 pneumocytes and these cells were increased in severe COPD.In conclusion, the results suggest that the enzymes involved in the oxidative stressresponse may have a different role in the lung defence and that imbalance betweenhaemoxygenase-1 and inducible nitric oxide synthase may be associated withthe development of severe impairment in chronic obstructive pulmonary disease patients.

It has been suggested that oxidative stress protein heme oxygenase (HO)-1 plays a role in chronic airway diseases including chronic obstructive pulmonary disease (COPD). The inducible isoform HO-1 and the constitutive HO-2 catalyze the same reaction. Their distribution in situ was studied in lungs of 10 nonsmoking subjects, 6 healthy smokers, and 10 smokers with COPD. Paraffin-embedded sections of surgical lung specimens were immunostained with antibodies against HO-1 and HO-2. HO-1 immunoreactivity was observed mainly in alveolar macrophages. HO-1-positive macrophages were increased in smokers with COPD (median: 36%) as compared with nonsmoking subjects (13%; p < 0.02), whereas no differences were observed between patients with COPD and healthy smokers (34%). HO-2 had a more widespread distribution in cells of the alveolar wall, in adventitia of pulmonary arteries and bronchioles, and in vascular smooth muscle. Lower percentages of alveolar macrophages exhibited positive staining for HO-2 without significant differences between the three groups. HO-2+ cells in the alveolar wall were increased in smokers with (15/mm) and without COPD (12/mm) as compared with nonsmokers (8/mm, p < 0.01). In conclusion, inducible HO-1 and constitutive HO-2 are detectable in human lung tissue and their expression is increased in smokers, suggesting that oxidative stress due to cigarette smoke may increase lung cells expressing HO-1 and HO-2.

The outcome of occupational asthma after diagnosis is often poor. The identification of factors associated with a worse outcome may help in the management of the disease, determining its prognosis and assessing the permanent impairment attributable to occupational exposure.The aim of this systematic review was to provide the available evidence from the medical literature to answer the question: “What is the contribution of host factors and workplace exposure to the risk of a bad outcome of occupational asthma?”A systematic literature search was conducted in March 2010. We retrieved 177 abstracts. Of these, 67 were assessed as potentially relevant. After full text evaluation, 35 articles that were actually relevant for the question were included in the analysis.The information obtained was sufficient to establish that older age, high-molecular-weight agents, impaired lung function and longer duration of exposure to the offending agent at the time of diagnosis had a negative role on the outcome of occupational asthma. Atopy and smoking at diagnosis did not seem to influence the outcome of occupational asthma. A limited number of studies considered sex and the pattern of asthmatic reaction on specific inhalation challenge and their findings were contradictory.

Work-related asthma (WRA) includes heterogeneous conditions, which have in common (i) symptoms and signs compatible with asthma and (ii) a relationship with exposures in the workplace. The types of WRA described in this review are distinguished by their etiology, comprising of work-exacerbated asthma (WEA), irritant-induced asthma (IIA), and immunologic occupational asthma (OA). There have been significant advances in the definition and characterization of the different forms of WRA by international panels of experts. The present review provides a comprehensive and updated view of the current knowledge on causes and phenotypes of WRA. Health care practitioners should consider WRA in any case of adult asthma, given that one fifth of workers with asthma report symptoms of WEA and it has been estimated that OA represents 10% to 25% of asthma in adulthood. The information provided in this review will facilitate the physician in the recognition of the different forms of WRA, since it has been established that five categories of agents are responsible for at least 60% of WEA cases and seven groups of agents are the cause of 70% of immunologic OA. In addition, there is agreement that IIA can be elicited not only by a single massive irritant exposure, but also by low/moderate repeated irritant exposures.