Elena Zeni

Association between markers of emphysema and more severe chronic obstructive pulmonary disease

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 (FEV1), FEV1/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.

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.

Macrophage expression of interleukin-10 is a prognostic factor in nonsmall cell lung cancer.

Interleukin (IL)-10 is expressed in many solid tumours and plays an ambiguous role in controlling cancer growth and metastasis. In order to determine whether IL-10 is involved in tumour progression and prognosis in nonsmall cell lung cancer (NSCLC), IL-10 expression in tumour cells and tumour-associated macrophages (TAMs) and its associations, if any, with clinicopathological features were investigated. Paraffin-embedded sections of surgical specimens obtained from 50 patients who had undergone surgery for NSCLC were immunostained with an antibody directed against IL-10. TAMs and tumour cells positive for IL-10 were subsequently quantified. IL-10-positive TAM percentage was higher in patients with stage II, III and IV NSCLC, and in those with lymph node metastases compared with patients with stage I NSCLC. High IL-10 expression by TAMs was a significant independent predictor of advanced tumour stage, and thus was associated with worse overall survival. Conversely, IL-10 expression by tumour cells did not differ between stages II, III and IV and stage I NSCLC. In conclusion, interleukin-10 expression by tumour-associated macrophages, but not by tumour cells, may play a role in the progression and prognosis of nonsmall cell lung cancer. These results may be useful in the development of novel approaches for anticancer treatments.

Vasoactive intestinal peptide receptors in the airways of smokers with chronic bronchitis

Vasoactive intestinal peptide (VIP) is a neuropeptide involved in the regulation of airway mucus secretion. The biological functions of VIP are mediated through two receptors, the vasoactive intestinal peptide receptor type 1 (VPAC1R) and type 2 (VPAC2R). The aim of this study was to quantify the expression of both VPAC1R and VPAC2R in the central airways of smokers with chronic bronchitis. Surgical specimens were obtained from 33 smokers undergoing thoracotomy for localised pulmonary lesions: 23 smokers with symptoms of chronic bronchitis and 10 asymptomatic smokers with normal lung function. By using immunohistochemical and microscopic analysis, an increased expression of VPAC1R, but not VPAC2R, was found in bronchial epithelium, bronchial glands and vessels of smokers with symptoms of chronic bronchitis compared with asymptomatic smokers. Smokers with symptoms of chronic bronchitis also had an increased number of mononuclear cells positive for both VPAC1R and VPAC2R in the bronchial submucosa. In conclusion, the expression of type 1 and type 2 vasoactive intestinal peptide receptors is increased in the central airways of smokers with chronic bronchitis, suggesting their possible involvement in the pathogenesis of chronic bronchitis.

Increased neurokinin-2 receptor expression in alveolar macrophages of smokers with COPD.

A Maciejczyk V Materna M Drag-Zalesińska A Wojnar M Pudelko W Kędzia M Spaczyński M Dietel M Zabel H Lage Institute of Pathology, Charité Campus Mitte, Berlin, Germany, Department of Histology and Embryology, University School of Medicine and Lower Silesian Centre of Oncology, Wrocław, Department of Obstetrics and Gynaecology and Department of Histology and Embryology, University School of Medicine, Poznań, Poland

A possible role of food intolerance in the pathogenesis of gastroesophageal reflux disease.

To the Editor: Gastroesophageal re ux disease (GERD) is an extremely common condition characterized by symptoms of heartburn and acid regurgitation. ˜ e etiopathogenetic steps of GERD remain largely unknown even though up to 20 % of the adult population in Western coun-tries is thought to be a( ected by re ux symptoms on a weekly basis (1) , natural-history studies indicate that patients with GERD symptoms su er from a chronic relapsing course of disease, with at least 50 % remaining on continuous medical therapy (2) , and the condition is known to predispose to an increased cancer risk. We know that GERD is caused by an abnormal contact of gastrointestinal contents with esophageal mucosa, and insu cient clearance of the esophageal body, lower esophageal sphinter incom-petence, and delayed gastric emptying have been identi- ed as putative patho-physiological mechanisms of disease, but the exact etiology of this backward displacement of gastrointestinal contents has yet to be elucidated. Because a possible role for food intol-erance in the etiology of GERD has not, to our knowledge, been investigated, and the so-called typical symptoms are con-sidered speci c, although not sensitive, for the diagnosis (3) , we decided to retro-spectively evaluate the results of a leuko-cytotoxic test for food intolerance using a panel of 60 foods (Allergoline Biotech & Research, Modena, Italy). ˜ e test was performed at the local center of a food ple that has come into direct contact with speci c food substances. On the basis of observation of the leukocytes, degrees of reaction to the food extracts are rated according to the following scale: level 0 = n egative ,level 1 = s lightly positive, level 2 = m oderately positive ,and level 3 = highly positive .˜ ese levels corre-spond to (i) the state of the leukocytes, which react by swelling, then developing research group, ACSIAN (Associazione Centro Studie Ricerche delle Intolleranze Alimentari e della Nutrizione) , from the date of the opening of the center in April 2007 to April 2008, in 16 patients su ering from typical GERD symp-toms (heartburn and regurgitation, in the absence of dysphagia) and 7 healthy subjects. ˜ is test is based on the optical evaluation of leukocytes in a blood sam-