M. Del Donno

Eotaxin and CCR3 are up-regulated in exacerbations of chronic bronchitis

Background: Eosinophils and T lymphocytes represent constant features in the airways of subjects with exacerbated chronic bronchitis. Eotaxin is the most potent and selective eosinophil chemoattractant which can also attracts lymphocytes. The aim of the study was to evaluate the expression of eotaxin and its receptor, CCR3, in bronchial airways during exacerbation of chronic bronchitis.

Ambroxol for the Prevention of Chronic Bronchitis Exacerbations: Long-Term Multicenter Trial

In a 6-month, double-blind multicenter trial conducted over the winter, the effects of daily administration of ambroxol retard (75 mg) were compared with those of placebo in preventing exacerbations and improving symptoms and clinical signs in chronic bronchitis patients. The trial was completed by 110 patients in the ambroxol group and by 104 in the placebo group. Initially, there were no significant differences between the groups. By the end of the 2nd month of treatment, 67.2% of the ambroxol group had had no exacerbations compared to 50.4% in the placebo group. At the end of the 6-month trial, 45.5% of the treatment group had had no exacerbations, compared to only 14.4% of the control group. These differences were statistically significant. Patients in the treatment group lost significantly fewer days through illness (442) and had fewer days when they needed antibiotic therapy (371) compared to the placebo group patients (837 and 781). Ambroxol also produced statistically significant symptomatic improvement, measured as difficulty in expectoration, coughing, presence of dyspnea and the auscultatory signs as compared to controls. Since ambroxol was well tolerated and compliance was good, it appears like a drug of choice for pharmacological prophylaxis of chronic bronchitis.

Activity of Erdosteine on Mucociliary Transport in Patients Affected by Chronic Bronchitis

The influence of erdosteine (a mucomodulator endowed with mucolytic and antioxidant properties) on human mucociliary transport (MCT) was investigated in a double-blind placebo controlled study. Sixteen former smokers affected by chronic bronchitis, preselected for their mucociliary responsiveness to an inhaled beta 2-agonist, were divided into two groups (matched by number, sex, age and FEV1%) and orally treated with placebo or erdosteine (300 mg t.i.d.) for 8 days. Their MCT was assessed by the bronchofiberscopy technique just before starting the treatment and at the end of the treatment. The pretreatment mucus transport velocity in these patients was significantly decreased with respect to healthy subjects. The erdosteine treatment induced a significant improvement of MCT while placebo was inactive (mean % variation +/- SE against their baseline values being +60.4 +/- 18.4 and -3.0 +/- 5.9, respectively). This peculiar activity of erdosteine on mucus transport may be of clinical usefulness in chronic bronchitic patients and it can be added to beta 2-agonist to restore the decreased MCT.

MICROSATELLITE ANALYSIS OF INDUCED SPUTUM DNA IN PATIENTS WITH LUNG CANCER IN HEAVY SMOKERS AND IN HEALTHY SUBJECTS

Abnormality in the fragile histidine triade (FHIT), a candidate tumor suppressor gene located in chromosome region 3 (3p14.2), has been frequently found in multiple tumor types, including lung cancer. In this study, the authors assessed the consistency of DNA microsatellite analysis of induced sputum (IS), as compared to that of blood and plasma. They also evaluated the loss of heterozigosity (LOH) and microsatellite instability (MSI) in 3 different loci, D3S1300, D3S1313, and D3S1234, all internal to the FHIT gene, in IS, blood, and plasma from patients with lung cancer, smokers, and healthy subjects. Eighteen patients with lung cancer (3 females, age mean ± SD: 63 ± 7 years), 39 smokers (23 females, age mean ± SD: 57 ± 6 years and cigarette pack-years mean ± SD: 34 ± 12), and 22 healthy nonsmoking subjects (13 females, age mean ± SD: 63 ± 5 years) were studied. DNA was extracted from blood, plasma, and IS, by means of a standard method. Analysis of LOH and MSI were performed using a fluorescent polymerase chain reaction (PCR)-based approach, followed by capillary electrophoresis. The ratios between the peak heights (phs), expressed as random fluorescence units, from plasma/blood (p/b) and induced sputum/blood (is/b) in all three loci were considered. The biases (agreement limits) between the mean ph ratio from p/b and is/b of D3S1300, D3S1313, and D3S1234 were respectively 0.07 (− 0.39 to 0.53), 0.016 (− 0.32 to 0.35), − 0.10 (− 0.51 to 0.30) in the patients; − 0.04 (− 0.52 to 0.43), − 0.06 (− 0.31 to 0.18), − 0.08 (− 0.48 to 0.30) in smokers; and − 0.11 (− 0.40 to 0.17), − 0.05 (− 0.53 to 0.43), − 0.09 (− 0.51 to 0.33) in healthy subjects. LOH and MSI in at least one locus were observed in 55% of patients, in 18% of smokers, and in 4.5% of healthy subjects (P < 0.001). These results showed that IS DNA provided data that were consistent with those from blood and plasma. These findings highlight new prospects for early tumor detection by a noninvasive technique based on the analysis of genetic alterations in induced sputum.

Efficacy and Safety of Moguisteine in Comparison with Dextromethorphan in Patients with Persistent Cough

SummaryCough is a protective mechanism and an important symptom of many respiratory diseases. When coughing is only an annoying reflex and produces no mucus clearance, inducing fatigue or exhaustion for patients and worsening their pathological condition, antitussive drugs may be indicated.In this study we evaluated the efficacy and safety of moguisteine, a new antitussive drug with a peripheral mechanism of action, in a population of 124 adult patients with persistent cough associated with various respiratory disorders. Obstructive chronic bronchitis, reported in about 50% of the study population, was the most frequent underlying diagnosis. We conducted a randomised single-blind short term treatment trial in 7 centres, comparing moguisteine (3 doses of 200mg, over 2 days) to dextromethorphan (3 doses of 30mg, over 2 days). The primary efficacy variable was the percentage reduction in the audio tape-recorded number of coughs during a 6-hour period in the morning after the last dose of the study drug versus a 6-hour recording at baseline.Patients’ subjectively assessed visual analogue scale (VAS) scores of cough frequency and cough troublesomeness at night and during the morning were considered as secondary efficacy variables.Safety was assessed by means of routine clinical laboratory tests and adverse event monitoring.The postdrug percentage reduction in the number of coughs approached 30% on either drug. VAS scores of cough frequency and cough troublesomeness showed remarkable reductions in both groups, without any noteworthy difference between treatments. Possible or probable drug-related adverse events were reported in 3 of 61 patients on moguisteine (1 heartburn, 1 gastric pain, 1 diarrhoea) and in 4 of 63 patients on dextromethorphan (1 rhinitis and slight decrease of white blood cell count, 1 syncope, 1 gastric discomfort, 1 diarrhoea). Treatment discontinuation was necessary only for 1 patient, who had a syncope after the first dose of dextromethorphan.Our results indicate that treatment with moguisteine rapidly induces substantial cough relief and that it is well tolerated and as effective as dextromethorphan.