Carlo Grassi

Influence of Aging on Some Specific and Nonspecific Mechanisms of the Host Defense System in 146 Healthy Subjects

The influence of aging on some parameters of systemic host defense mechanisms, i.e. white cell counts, lymphocyte subpopulations, delayed-type hypersensitivity (DTH), polymorphonuclear and mononuclear leukocyte functions, was evaluated. One hundred and forty-six healthy volunteers (60 men and 86 women), aged 25-100 years, were enrolled. None of the subjects had taken any drug in the month before the study. Subjects were divided into three age groups: 25-45, 46-65 and 66-100 years. Groups were comparable in size, and sex distribution was similar throughout all age groups. Elderly people were 51 healthy volunteers between the ages of 66 and 100 years (mean age 79.2). Younger people were 41 subjects between the ages of 46 and 65 years (mean age 54.3) and 53 between the ages of 25 and 45 years (mean age 32.7). As for the comparison between sexes, no significant differences in the values of the studied parameters were found between males and females (p > 0.05). Only quantitative DTH data, i.e. the number of antigens producing positive reactions and the score (sum of positive reaction diameters), were significantly (p < 0.05) reduced in responsive females when compared to males. Aging did not affect white cell counts, lymphocyte subsets and many phagocytic functions, i.e. phagocytosis frequency and index, nitroblue tetrazolium reduction, superoxide production, microbicidal activity against bacteria and yeasts. A significant decrease (p < 0.05) in the chemotactic response to serum-derived chemotactic factors was observed in aged people in comparison to younger subjects. Anergy was more frequent in older (about 29%) than in younger (5-9.4%) healthy volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Evaluation of Systemic Host Defense Mechanisms in Chronic Bronchitis

Seventy-six chronic bronchitis patients were studied in order to determine the possible presence of disorders in their systemic defense mechanisms. No significant difference in lymphocyte subsets, in serum immunoglobulin and complement component (C3 and C4) levels was found in chronic bronchitis patients compared to normal adult controls. Skin tests for delayed hypersensitivity revealed a high frequency (39%) of hypoergic patients (with 1-2 positive reactions) in comparison to normal subjects. Altered values of many functional properties of both neutrophils and monocytes were demonstrated. The percentage of patients with intermediate (between 1 and 2 SD below the mean of controls) and defective (lower than 1.96 SD) values of chemotaxis, phagocytosis index and Candida killing was about 50%. Phagocytosis frequency and nitroblue tetrazolium reduction frequency were less frequently impaired.

Clinical Efficacy of Ofloxacin in Lower Respiratory Tract Infections A Multicentre Study

SummaryA multicentre clinical trial was carried out to determine the activity and tolerability of ofloxacin in the treatment of lower respiratory tract infections. 667 patients were randomly allocated to 1 of 3 different twice daily dosage regimens: 400mg (245 patients), 600mg (211) or 800mg (211). The mean duration of treatment was 8.77 ± 2.62 days. Satisfactory overall clinical results (i.e. cured or improved) were obtained in 612 of 667 patients (91.8%). Eradication of pathogens was achieved for 279 of 354 isolated strains (78.8%). Side effects were observed in 31 patients and consisted of gastrointestinal disturbance (22), skin rash (1), neurological disturbance (3) and others (5). No significant alteration of haematological parameters was reported.

Randomized, Double-Blind Study of Prulifloxacin versus Ciprofloxacin in Patients with Acute Exacerbations of Chronic Bronchitis

Background: Recently the role of bacteria in acute exacerbations of chronic bronchitis (AECB) as well as antibiotic treatment with selected drugs, especially fluoroquinolones, have been better defined. Objective:To assess the efficacy and safety in patients with AECB of prulifloxacin in comparison with ciprofloxacin. Methods: AECB was defined according to the guidelines for the evaluation of new anti-infective drugs for the treatment of respiratory tract infections (1992). 235 patients took part in the trial; 117 (88 males and 29 females, mean age 64.8 years) received 600 mg prulifloxacin once daily and 118 (91 males and 27 females, mean age 64.5 years) 500 mg ciprofloxacin twice a day, for a duration of 10 days. The study design was randomized, multicenter, double-blind, double-dummy. Efficacy evaluations were performed by comparing pretreatment and posttreatment assessments. The clinical response was determined by 4-point rating scores on cough, dyspnea, and expectoration (volume and appearance). The microbiological response was assessed on sputum specimen. Results: Clinical success was observed in 84.7 and 85% of patients in the prulifloxacin and ciprofloxacin groups, respectively. The 95% confidence interval proved the equivalence of treatments. Both drugs successfully eradicated the most commonly isolated strains, including Haemophilus influenzae, Streptococcus pneumoniae, Klebsiella pneumoniae and Pseudomonas aeruginosa. Both treatments were well tolerated. Adverse drug reactions were always of mild or moderate intensity. Conclusion: The study showed that a 10-day course of prulifloxacin is as effective and safe as ciprofloxacin in the treatment of patients with AECB.

Pattern of Lung Cancer in Turkey, 1994–1998

Background: Lung cancer is the most common neoplasm in Turkey, but there is not enough data on the characteristics of this mortal illness in our country. Objectives and Methods: The Turkish Thoracic Society, Lung and Pleural Malignancies Study Group (TTS-LPMSG) conducted a national retrospective hospital-based study to determine the pattern of lung cancer in Turkey. Results: A total of 11,849 lung cancer patients were studied between 1994 and 1998, 90.4% were male and 9.6% were female. The majority of patients were smokers (77.9%) or ex-smokers (10.8%). The mean age at the time of diagnosis was 58.4 years (20–84) and 56.7% of the patients were aged between 46 and 65 years. The most common histological types were squamous cell (45.4%), small cell (SCLC; 20.5%) and adenocarcinoma (20.2%). The majority of patients with non-small-cell lung cancer were diagnosed with metastatic disease (40.4%). Of the patients with SCLC patients, 37.9% had limited stage disease and 62.7% extensive stage disease at diagnosis. Conclusion: The results of the largest data so far collected in Turkey show that the vast majority of patients with lung cancer are male, squamous cell is the most common histological type, and only a small proportion of patients are diagnosed at an early stage.

Feasibility and validation of telespirometry in general practice: The Italian “Alliance” study

INTRODUCTION At variance from office spirometry, telespirometry has not been tested as a tool for improving the ability of general practitioners (GPs) to manage chronic airway diseases. METHODS After adequate training, 937 Italian GPs agreed to perform telespirometry in subjects attending their clinics who had risk factors, persistent respiratory symptoms, or a previous diagnosis of asthma or COPD. Each subject performed at least three forced expiratory manoeuvres using a turbine spirometer. Traces were sent by telephone to a Telespirometry Central Office, where they were interpreted by a pulmonary specialist, according to defined criteria. The result was sent in real time to the GP to assist the management of the patient. RESULTS During 2 years, 20,757 telespirometries were performed, with a mean of 22.2+/-25.2 examinations for each GP. 70% of the tests met the criteria for good or partial co-operation, allowing spirometric abnormalities to be detected in more than 40% of the tracings. The rate of telespirometries that could not be evaluated at all was reasonably low (9.2%). For a subset of the telespirometries, a comparison between acceptability criteria for telespirometry and those recommended for laboratory (ATS) or office spirometry showed that the majority of telespirometries with good co-operation satisfied completely, or with minor deviations, the ATS and Office criteria. CONCLUSIONS Telespirometry was well accepted by Italian GPs, who obtained acceptable screening traces in a large percentage of subjects. Therefore it might be considered a useful alternative to office spirometry in improving the management of chronic airway diseases by GPs.

Studies of MR 889, a new synthetic proteinase inhibitor.

We investigated the proteinase inhibitory activity of MR 889, a thiolactic acid derivative. It is able to in vitro inhibit at low concentration (10(-5),10(-6)M) the activity of porcine pancreatic elastase, human neutrophil elastase and bovine chymotrypsin. In addition, MR 889 is able to inhibit the residual activity of alpha 2-macroglobulin-trapped human neutrophil elastase, paralleling the efficacy of phenylmethylsufonylfluoride. Finally, MR 889 has been shown to in vitro reduce the burden of elastase- and chymotrypsin-like activity found in sputum sol-phases of patients admitted for chronic bronchitis exacerbation.

Normal and Pathological Respiratory Sounds Analyzed by Means of a New Phonopneumographic Apparatus

A technique and an original apparatus for recording and displaying the sound levels emitted by human lungs during respiratory movements are described. By means of it a graphic recording of chest acoustics can be obtained. An analysis of the phonopneumographic findings shows clear differences between normal pathological readings, both in the level of the sounds and in their frequency content. Evidence is given of cases in which the physician can directly recognize the presence of special diseases. Beside this, FPGraphic representations are also useful for retaining evidence of findings which cannot be recorded by other methods, and for checking the natural evolution of a disease or its response to clinical treatments.

Immunological and Clinical Effect of Long-Term Oral Treatment with RU 41740 in Patients with Chronic Bronchitis: Double-Blind Trial Long-Term versus Standard Dose Regimen

The immunological and clinical effects of two oral treatment schedules of RU 41740 (standard for 3 months vs. long-term for 6 months) were assessed in 40 patients with chronic bronchitis by a controlled, double-blind, randomized trial. Both treatments significantly improved phagocytosis index of both neutrophils and monocytes, and the phagocytosis frequency and the candidacidal activity of neutrophils, showing the maximum stimulation at the end of the third course of treatment. Both treatment schedules reduced the number and the duration of infectious exacerbations of chronic bronchitis with respect to those observed in the corresponding period of the previous year. However, no significant difference between standard and long-term treatment with RU 41740 was found with respect to the immunological and clinical effect and tolerability.