Substantial epidemiologic and clinical evidence indicates that agents inhaled at work can induce asthma. In industrialized countries, occupational factors have been implicated in 9 to 15% of all cases of adult asthma. Work-related asthma includes (1) immunologic occupational asthma (OA), characterized by a latency period before the onset of symptoms; (2) nonimmunologic OA, which occurs after single or multiple exposures to high concentrations of irritant materials; (3) work-aggravated asthma, which is preexisting or concurrent asthma exacerbated by workplace exposures; and (4) variant syndromes. Assessment of the work environment has improved, making it possible to measure concentrations of several high- and low-molecular-weight agents in the workplace. The identification of host factors, polymorphisms, and candidate genes associated with OA is in progress and may improve our understanding of mechanisms involved in OA. A reliable diagnosis of OA should be confirmed by objective testing early after its onset. Removal of the worker from exposure to the causal agent and treatment with inhaled glucocorticoids lead to a better outcome. Finally, strategies for preventing OA should be implemented and their cost-effectiveness examined.

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Background: The predominant emphysema phenotype is associated with more severe airflow limitation in patients with chronic obstructive pulmonary disease (COPD). A study was undertaken to investigate whether COPD patients, with or without emphysema quantitatively confirmed by high resolution computed tomography (HRCT), have different COPD severity as assessed by the BODE index (body mass index, airflow obstruction, dyspnoea, exercise performance) and inspiratory capacity to total lung capacity ratio (IC/TLC), and by different biological markers of lung parenchymal destruction. Methods: Twenty six outpatients with COPD and eight healthy non-smokers were examined. Each subject underwent HRCT scanning, pulmonary function tests, cell counts, and measurements of neutrophil elastase, matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in induced sputum, as well as measurement of desmosine, a marker of elastin degradation in urine, plasma and sputum. Results: Patients with HRCT confirmed emphysema had a higher BODE index and lower IC/TLC ratio than subjects without HRCT confirmed emphysema and controls. Forced expiratory volume in 1 second (FEV 1 ), FEV 1 /forced vital capacity ratio, and carbon monoxide transfer coefficient were lower, whereas the number of eosinophils, MMP-9, and the MMP-9/TIMP-1 ratio in sputum were higher in patients with emphysema. In COPD patients the number of sputum eosinophils was the biological variable that correlated positively with the HRCT score of emphysema (p = 0.04). Conclusions: These results suggest that COPD associated with HRCT confirmed emphysema is characterised by more severe lung function impairment, more intense airway inflammation and, possibly, more serious systemic dysfunction than COPD not associated with HRCT confirmed emphysema.

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To investigate whether the airway inflammatory process is different in patients with chronic bronchitis with airflow limitation and those with chronic bronchitis without airflow limitation, we obtained bronchial biopsies from 14 subjects with chronic sputum production and fixed airway obstruction, and from 10 subjects with chronic sputum production and normal FEV1, all with a history of cigarette smoking. Paraffin-embedded and frozen bronchial biopsies were examined by immunohistochemistry to identify the number of neutrophils (neutrophil-elastase), eosinophils (antieosinophil cationic protein [EG-2]), mast cells (tryptase), T-lymphocytes (CD3), T-lymphocyte subpopulations (CD4 and CD8), B-lymphocytes, and macrophages (CD68) in the submucosa. Subjects with chronic bronchitis with airflow limitation had a greater number of T-lymphocytes (p < 0.01) and macrophages (p < 0.05) than subjects with chronic bronchitis without airflow limitation, whereas the T-lymphocyte subpopulations and the numbers of B-lymphocytes, neutrophils, eosinophils, and mast cells were similar in the two groups. When all the subjects were considered together, the number of T-lymphocytes correlated inversely with the values of FEV1 (r = 0.46, p < 0.02). In conclusion, airflow limitation in subjects with chronic bronchitis is associated with an increased number of T-lymphocytes and macrophages in the bronchial mucosa.

Background: Exacerbations represent an important feature of the clinical manifestation and natural history of chronic obstructive pulmonary disease (COPD). Nuclear localisation of p65 is a signal of nuclear factor-κB (NF-κB) activation. A study was undertaken to evaluate whether NF-κB activation is modified in sputum cells during COPD exacerbations. Methods: Total and nuclear p65 immunoreactivity was measured by immunocytochemistry in the sputum cells of 11 smokers with moderate COPD during an exacerbation and after 6-8 weeks of clinical stability. Results: Total sputum cell count was significantly increased during exacerbations from a median (IQR) of 880 (510-1865) to 1914.5 (1065-3205) × 10

The mechanism by which late asthmatic reactions are induced by toluene diisocyanate (TDI), a low molecular weight chemical that causes occupational asthma in exposed subjects, is unknown. We investigated whether early and late asthmatic reactions induced by TDI are associated with changes in airway responsiveness to methacholine and airway inflammation as determined by bronchoalveolar lavage. We measured FEV1 before and at regular intervals after exposure to TDI, and performed dose-response curves to methacholine and bronchoalveolar lavage at 8 h after TDI in a group of 6 subjects with late asthmatic reactions and in 6 subjects with only early asthmatic reactions. The same procedure was followed 2 h after TDI in a group of 6 subjects with previously documented late asthmatic reactions and in a group of 6 subjects without any previously documented asthmatic reaction after TDI. In subjects with late asthmatic reactions, neutrophils were increased at both 2 and 8 h, and eosinophils and airway responsiveness were increased only at 8 h. By contrast, neutrophils, eosinophils and airway responsiveness were not increased at 8 h after TDI in subjects with an early asthmatic reaction or at 2 h after TDI in normal control subjects. These results suggest that late asthmatic reactions to TDI, and the associated increase in airway responsiveness, may be caused by airway inflammation.

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