Adalberto Ciaccia

COPD increases the risk of squamous histological subtype in smokers who develop non-small cell lung carcinoma

Background: Squamous cell carcinoma has a stronger association with tobacco smoking than other non-small cell lung cancers (NSCLC). A study was undertaken to determine whether chronic obstructive pulmonary disease (COPD) is a risk factor for the squamous cell carcinoma histological subtype in smokers with surgically resectable NSCLC. Methods: Using a case-control design, subjects with a surgically confirmed diagnosis of squamous cell carcinoma were enrolled from smokers undergoing lung resection for NSCLC in the District Hospital of Ferrara, Italy. Control subjects were smokers who underwent lung resection for NSCLC in the same hospital and had a surgically confirmed diagnosis of NSCLC of any histological type other than squamous cell. Results: Eighty six cases and 54 controls (mainly adenocarcinoma, n = 50) were enrolled. The presence of COPD was found to increase the risk for the squamous cell histological subtype by more than four times. Conversely, the presence of chronic bronchitis was found to decrease the risk for this histological subtype by more than four times. Among patients with chronic bronchitis (n = 77), those with COPD had a 3.5 times higher risk of having the squamous cell histological subtype. Conclusions: These data suggest that, among smokers with surgically resectable NSCLC, COPD is a risk factor for the squamous cell histological subtype and chronic bronchitis, particularly when not associated with COPD, is a risk factor for the adenocarcinoma histological subtype.

Mucin expression in peripheral airways of patients with chronic obstructive pulmonary disease.

Aims:  To study the expression of mucins in peripheral airways in patients with chronic obstructive pulmonary disease (COPD).

Mechanisms and pathology of occupational asthma

Since the pathogenesis and the pathological features of occupational asthma are similar to those of nonoccupational asthma, the former represents a very useful model for the investigation of the pathogenesis of asthma in general. More than one mechanism may be operative in occupational asthma. Among the mechanisms proposed, immunological mechanisms and airway inflammation play an important role. There is evidence to confirm that T-lymphocyte activation and local accumulation in the bronchial wall of activated eosinophils occurs in asthma of diverse aetiology, i.e. immunoglobulin E (IgE)-mediated, occupational and intrinsic. Neurogenic pathways should be further investigated as a potential mechanism of modulation and amplification of airway inflammation in occupational asthma.

Xanthine oxidase activity in bronchoalveolar lavage fluid from patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a serious respiratory pathology characterized by irreversible limitation of expiratory flow and includes chronic obstructive bronchitis, chronic airflow limitation, and emphysema. To determine whether xanthine oxidase activity increased in the airspaces of COPD patients, we examined bronchoalveolar lavage fluid (BAL) from COPD patients recruited during a 2-year clinical study. Filtered BAL supernatant from COPD patients and healthy nonsmoking controls was examined by fluorometric analysis of DNA unwinding (FADU) and spectrophotometric assays (cytochrome c reduction kinetics and uric acid kinetics). Compared to controls, filtered BAL supernatant of subjects with COPD exhibited a detectable clastogenic activity probably related to superoxide production. The method of BAL preparation as an acellular system strongly suggests that superoxide production may be due to xanthine oxidase activity.

Association between toluene diisocyanate-induced asthma and DQB1 markers: a possible role for aspartic acid at position 57

Toluene diisocyanate (TDI) is the most common cause of occupational asthma in western countries. The aim of this study was to investigate whether genetic factors are involved in toluene diisocyanate-induced asthma. We studied the frequency of human leucocyte antigen (HLA) class II genetic markers in three groups of subjects: 1) subjects with TDI-induced asthma (n = 30); 2) exposed subjects with no history of TDI-induced asthma (n = 12); and 3) normal subjects not exposed to TDI (n = 126). Venous blood samples were collected from the three groups and the polymorphic second exon of DQA and DQB genes was amplified by the polymerase chain reaction (PCR) method. Evaluation of HLA class II gene products in TDI-induced asthma cases showed a positive association with HLA-DQB1 * 0503 and a negative association with HLA-DQB1 * 0501 alleles, which differed at residue 57 for a single amino acid, i.e. aspartic acid in DQB1 * 0503 and valine in DQB1 * 0501. No significant difference was found in the distribution of DQA1 alleles between asthmatics and controls. Our results confirm the hypothesis that HLA-DQB1 * 0503 has a role in conferring susceptibility to TDI-induced asthma and that residue 57 of HLA-DQB1 is a potentially critical location.

Detection of xanthine oxidase activity products by EPR and HPLC in bronchoalveolar lavage fluid from patients with chronic obstructive pulmonary disease

Xanthine oxidase (xanthine: oxygen oxidoreductase, EC 1.1.3.22), a molybdenum-containing hydroxylase that produces superoxide and uric acid from purine substrates and molecular oxygen, is involved in the oxidative stress underlying several human pathologies including lung diseases. An enzymatic activity similar to xanthine oxidase was previously reported in bronchoalveolar lavage fluid of patients with chronic obstructive pulmonary disease (COPD-BAL), by fluorometric analysis of DNA unwinding and cytochrome c reduction kinetics. Here we report the detection of xanthine oxidase activity products by electron paramagnetic resonance (EPR) in presence of the spin-trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and reversed-phase high-performance liquid chromatography (RP-HPLC) in COPD-BAL (n = 14, average age of patients 65 years, range 38-81) and BAL from healthy nonsmoker controls (n = 6, average age 64 years, range 44-73). Superoxide DMPO adducts were detected in COPD-BAL and in an in vitro system containing xanthine and xanthine oxidase (XA/XO), but not in BAL controls and when superoxide dismutase (SOD, 1000 I.U./ml) was added to COPD-BAL. The HPLC analyses after addition of xanthine showed production of uric acid in COPD-BAL and in the XA/XO system but not in BAL controls. These results support the involvement of xanthine oxidase in the mechanisms of superoxide production by BAL supernatant, which increases oxidative stress in chronic obstructive pulmonary disease.

Helicobacter pylori and chronic bronchitis.

BACKGROUND Chronic infections such as those caused by Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus have been epidemiologically related to coronary heart disease (CHD). Other studies place H. pylori in relation to other extradigestive diseases. We carried out an epidemiologic pilot study to evaluate the prevalence of H. pylori in patients with chronic bronchitis, a respiratory disease characterized by persistent chronic inflammation, in comparison with a matched control group. METHODS An enzyme-linked immunosorbent assay IgG test for H. pylori diagnosis was performed in 60 consecutive patients with chronic bronchitis (15 women and 45 men; age range, 50-89 years; mean age, 70.38 years) and in 69 control subjects, well matched for age and social status (19 women and 50 men: age range, 52-90 years; mean age, 71.3 years). RESULTS Foty-nine of 60 patients with chronic bronchitis (81.6%) and 40 of 69 subjects in the control group (57.9%) were H. pylori-positive (P = 0.0079). The odds ratio, calculated by simple analysis (3.2) and confirmed by logistic regression analysis (3.399), indicated that H. pylori infection greatly increases the risk of chronic bronchitis. CONCLUSIONS To date, CHD is the only convincing association between H. pylori infection and an extradigestive disease. The main conclusion of this pilot study is that H. pylori infection seems to increase the risk of developing of chronic bronchitis. An important step in this field will be to evaluate the possible change in the clinical conditions after successful eradication therapy in H. pylori-positive patients with chronic bronchitis.

Role of Xanthine Oxidase Activation and Reduced Glutathione Depletion in Rhinovirus Induction of Inflammation in Respiratory Epithelial Cells

Rhinoviruses are the major cause of the common cold and acute exacerbations of asthma and chronic obstructive pulmonary disease. We previously reported rapid rhinovirus induction of intracellular superoxide anion, resulting in NF-κB activation and pro-inflammatory molecule production. The mechanisms of rhinovirus superoxide induction are poorly understood. Here we found that the proteolytic activation of the xanthine dehydrogenase/xanthine oxidase (XD/XO) system was required because pretreatment with serine protease inhibitors abolished rhinovirus-induced superoxide generation in primary bronchial and A549 respiratory epithelial cells. These findings were confirmed by Western blotting analysis and by silencing experiments. Rhinovirus infection induced intracellular depletion of reduced glutathione (GSH) that was abolished by pretreatment with either XO inhibitor oxypurinol or serine protease inhibitors. Increasing intracellular GSH with exogenous H2S or GSH prevented both rhinovirus-mediated intracellular GSH depletion and rhinovirus-induced superoxide production. We propose that rhinovirus infection proteolytically activates XO initiating a pro-inflammatory vicious circle driven by virus-induced depletion of intracellular reducing power. Inhibition of these pathways has therapeutic potential.

Slower rise of exhaled breath temperature in chronic obstructive pulmonary disease

In chronic obstructive pulmonary disease (COPD) there is decreased vascularity of the bronchi and inflammation of the airways that may have opposite effects on the regulation of heat loss. Exhaled air temperature increase (Δe°T) was measured in 23 patients with moderate COPD (18 male, mean age±sem 70±1 yrs; forced expiratory volume in one second (FEV1) 45±3%, FEV1/forced vital capacity 54±4%) and 16 normal volunteers (64±4 yr) and compared to exhaled nitric oxide (eNO) and inflammatory cells in induced sputum as a marker of airway inflammation. Δe°T was measured during a flow- and pressure-controlled single exhalation with a fast-response thermometer. Δe°T was reduced in patients with COPD (1.86±0.15 Δ°C·s−1) compared to normal subjects (4.00±0.26 Δ°C·s−1). There was no difference in Δe°T between patients treated with inhaled steroids and those who were steroid naïve. Δe°T was correlated with eNO (r=0.60) but not with sputum neutrophilia. In COPD patients, Δe°T was increased (2.26±0.16 Δ°C·s−1) after the inhalation of 200 µg of albuterol, which is a known vasodilator, indicating that Δe°T and bronchial blood flow may be correlated. Exhaled temperature increase is reduced in chronic obstructive pulmonary disease patients and is increased by the inhalation of vasodilators and therefore may be related to changes of bronchial blood flow and tissue remodelling.

Chronic obstructive pulmonary disease international guidelines

Although chronic obstructive pulmonary disease (COPD) has a public health importance similar to asthma, it has received less attention. The first guideline on the management of COPD was released in 1987 by the American Thoracic Society. In 1992 the Canadian Thoracic Society released its guidelines. In 1995 the European Respiratory Society and the Thoracic Society of Australia and New Zealand released their guidelines and the American Thoracic Society updated and expand its COPD guidelines. All these documents were followed in 1997 by the guidelines developed by the British Thoracic Society. These COPD guidelines show many similarities but also have some interesting differences. The aim of this paper is to review these similarities and discrepancies. Like all guidelines, COPD guidelines suffer from the limited amount of evidence-based medicine supporting them, a limitation that, however, provides a strong stimulus for further research.