Chronic obstructive pulmonary disease (COPD) and occupational exposures

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality in both industrialized and developing countries. Cigarette smoking is the major risk factor for COPD. However, relevant information from the literature published within the last years, either on general population samples or on workplaces, indicate that about 15% of all cases of COPD is work-related. Specific settings and agents are quoted which have been indicated or confirmed as linked to COPD. Coal miners, hard-rock miners, tunnel workers, concrete-manufacturing workers, nonmining industrial workers have been shown to be at highest risk for developing COPD. Further evidence that occupational agents are capable of inducing COPD comes from experimental studies, particularly in animal models. In conclusion, occupational exposure to dusts, chemicals, gases should be considered an established, or supported by good evidence, risk factor for developing COPD. The implications of this substantial occupational contribution to COPD must be considered in research planning, in public policy decision-making, and in clinical practice

Recettori accoppiati alle proteine G nella bronchite cronica e nella BPCO

Dottorato di ricerca in fisiopatologia respiratoria sperimentale. 11. ciclo. Coordinatore Dario Olivieri. Relatore Leonardo M. Fabbri. Correlatore Cristina E. MappConsiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7, Rome; Biblioteca Nazionale Centrale - P.za Cavalleggeri, 1, Florence / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

Occupational asthma

Early cessation of exposure is importan

Asthma induced by isocyanates: a model of IgE-independent asthma

Developments in the understanding of causes and natural history of asthma induced by isocyanates may allow improved preventive strategies for occupational asthma (OA), and may also lead to improved understanding of mechanisms involved in IgE-independent nonoccupational asthma. Studies of genetic markers in OA induced by isocyanates suggest that HLA class II genes, glutathione S-transferase and NAT1 genotypes may predispose to development of this type of OA. Specific IgE antibodies against isocyanates are not always found in subjects with OA caused by isocyanates, leading most researchers to consider this type of OA, as a model of IgE-independent asthma. Evidence for cell-mediated immunity in OA induced by isocyanates has been provided by bronchoalveolar lavage, bronchial biopsy and induced sputum studies. The pathology of this type of asthma is similar to that of nonoccupational asthma, with cells such as eosinophils and T lymphocytes that exhibit signs of activation, and with thickening of the reticular layer of the basement membrane. Animal studies have shown that isocyanate asthma is driven primarily by CD4+ T cells and is dependent upon the expression of Th2 cytokines. However, animal models are not always reflective of human responses. OA induced by isocyanates similarly to nonoccupational asthma, is a multifactorial condition, and it is likely that complex gene-environment interactions play a role. Better understanding of these interactions is important for affected workers, and also has potential relevance for nonoccupational asthma

Mechanisms of occupational asthma

Background: The pathogenesis and the pathologic alterations of occupational asthma are similar to those of nonoccupational asthma. Occupational asthma may therefore represent a useful model of "human asthma" to investigate mechanisms and pathophysiology of asthma in general. In an occupational setting the cause and onset of asthma may be easily identified, and the natural history may be examined in follow-up studies. The mechanisms involved in occupational asthma include genetic predisposition, immunologically mediated responses, as well as nonspecific airway inflammation. In particular, high molecular weight (eg, grain dust, flour) and some low molecular weight sensitizers (eg, acid anhydrides and platinum halide salts) have been shown to induce occupational asthma through an immunoglobulin E (IgE)-dependent mechanism, while cell-dependent immunologic mechanisms are likely to be more relevant for occupational asthma induced by other low molecular weight sensitizers (eg, toluene diisocyanate and plicatic acid contained in western red cedar). The pathology of the airway mucosa of occupational asthma is remarkably similar to the pathology of nonoccupational asthma, ie, characterized by infiltration and accumulation of eosinophils, mast cells, and activated lymphocytes along with subepithelial fibrosis. In this article, the most relevant mechanisms are discussed with particular reference to the similarities and discrepancies between occupational and nonoccupational asthma

Interleukin-13 and-4 expression in the central airways of smokers with chronic bronchitis

The aim of this study was to determine whether the T-helper 2-type cytokines interleukin (IL)-13 and -4 are involved in mucus hypersecretion, the hallmark of chronic bronchitis (CB). Surgical specimens were examined from 33 subjects undergoing lung resection for localised peripheral malignant pulmonary lesions: 21 smokers with symptoms of CB, 10 asymptomatic smokers (AS) and two nonsmokers with normal lung function. The number of IL-4 and -13 positive (+) cells in the central airways was quantified. To better assess the cytokine profile, a count was also made of IL-5+ and interferon (IFN)-gamma+ cells. Compared to AS, the CB group had an increased number of IL-13+ and -4+ cells in the bronchial submucosa, while the number of IL-5+ and IFN-gamma+ cells were similar in all the groups. No significant associations were found between the number of cells expressing IL-13 or -4 and the number of inflammatory cells. Double labelling showed that 13.2 and 12.9% of IL-13+ cells were also CD8+ and CD4+, whereas 7.5 and 5% of IL-4+ cells were CD8+ and CD4+, respectively. In conclusion, T-helper-2 and -1 protein expression is present in the central airways of smokers and interleukin-4 and -13 could contribute to mucus hypersecretion in chronic bronchitis

CC Ligand 2 levels are increased in LPS-stimulated peripheral monocytes of patients with Non Small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) shows a particular aggressive behaviour. Tumour associated macrophages (TAMs) play an important role in tumour growth and progression and CC ligand 2 (CCL2)/CCR2 axis is markedly involved in their recruitment in the tumour mass from the circulation. The aim of this study was to determine the plasma levels of CCL2 and the expression of CCR2 in the peripheral blood mononuclear cells (PBMCs) of 18 smokers with NSCLC, eight healthy smokers and nine non-smokers. Then, we investigated CCL2 levels in the supernatants of unstimulated and LPS-stimulated PBMC cultures of the same groups of patients. CCL2 levels in plasma and supernatants of PBMC cultures were determined by ELISA. CCR2 expression in PBMC cytospins was assessed by immunocytochemistry. CCL2 plasma levels and CCR2 expression by PBMCs were similar in patients with NSCLC, healthy smokers and non-smokers. In the supernatants of unstimulated PBMC cultures, CCL2 content was not different between the three groups of subjects. Supernatants of LPS-stimulated PBMCs of NSCLC patients showed a higher content of CCL2 as compared to supernatants of non-smokers (p<0.005). CCL2 content increased 28.5-fold vs baseline production in the group of NSCLC patients, 15-fold in healthy smokers and 13-fold in the group of non-smokers. In conclusion, after LPS stimulation, PBMCs of patients with NSCLC release higher levels of CCL2 as compared to those of non-smokers, supporting the hypothesis of a CCL2 involvement in NSCLC biology

Occupational exposure and chronic heart failure severity

Lo scompenso cardiaco cronico (SCC) è una patologia caratterizzata dall’incapacità del muscolo cardiaco di apportare all’organismo una quantità di sangue adeguata ai bisogni metabolici e circolatori. I principali fattori di rischio per l’insorgenza dello SCC sono: ipertensione arteriosa, diabete, ipercolesterolemia, obesità, fumo, malattie renali croniche. È noto che alcune esposizioni lavorative, quali temperature estremamente elevate o troppo basse, prolungata esposizione a rumore, vibrazioni,\ud pesticidi, ecc, possono contribuire all’eziologia di questa patologia. Lo scopo del nostro studio è stato quello di valutare se l’esposizione professionale può influire sulla gravità dello SCC. Abbiamo condotto un’analisi retrospettiva sui primi 76 soggetti fumatori di età superiore ai 65 anni, che si sono presentati al Centro dello Scompenso che sono risultati affetti da SCC. I pazienti sono stati divisi in quattro gruppi in base alle mansioni lavorative svolte: impiegati, agricoltori, metalmeccanici e soggetti con esposizioni professionali diverse (parrucchiera, fuochista, muratore, ecc.). I nostri risultati hanno evidenziato che gli agricoltori hanno una frazione di eiezione del ventricolo sinistro minore rispetto agli impiegati (p=0.0045) pur non essendoci differenza di classe NYHA e/o di presenza/ assenza dei fattori di rischio dello SCC. Questi dati suggeriscono pertanto che la mansione di agricoltore si associa ad una maggiore gravità dello SCC

Substance P in sputum of patients with chronic obstructive pulmonry disease and occupational exposure to respiratory irritants

The role of tachykininis in airway inflammation has been extensively demonstrated in experimental animal models, but evidence in humans is very sparse. The aim of this study was first to quantify the content of substance P (SP) in sputum of a group of patients, with chronic obstructive pulmonary disease and with exposure to occupational irritants. Secondly, to compare them with sputum SP content of a group of control subjects