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This study was performed in a randomized double-blind manner on 6 separate days in 10 asthmatic patients to investigate the effect of a sustained theophylline on baseline bronchial hyperreactivity to histamine in relation to the theophylline serum levels and the degree of bronchodilatation produced. No significant bronchodilatation was seen after theophylline administration at every time of evaluation. An improvement of PD20 values of histamine was observed after 4 h (p less than 0.05), 8 h (p less than 0.01) and 12 h (p less than 0.05) from theophylline administration versus respective PD20 values obtained with placebo at the same times. No significant correlation was found between serum theophylline levels and percentage change of PD20 values after drug administration (r = 0.250). We observed an improvement of PD20 mean values in relation to the maximal serum theophylline concentration but our study failed to correlate the degree of protection with serum concentration.

There is evidence suggesting the involvement of the surfactant system in the development of lung diseases in cigarette smokers. The aim of the present study was to evaluate the effect of Ambroxol on lung epithelial permeability (LEP) in healthy smokers. Ambroxol is known to stimulate surfactant production. Twenty male patients aged between 20 and 60 years participated in the study. They all smoked at least 15 cigarettes daily for 10 years. We carried out a random double-blind study versus placebo: the drug (Ambroxol 75 mg) or the placebo were given once a day after breakfast for 30 days. Lung permeability was evaluated through scanning pulmonary scintigraphy by inhalation of the polydispersed liquid aerosol diethylenetriaminepentaacetic acid (DTPA), labelled with 99Tc, and delivered by a 'Venticis' system. LEP was expressed as the half-time clearance from the lung of 99Tc-DTPA (T50). The significance of the differences between the two treatments was determined by the Student's test for unpaired data. LEP was not different from the baseline value (T50 = 18.49 min) after placebo administration (T50 = 19.57 min). The patients receiving Ambroxol showed an increased LEP mean value (T50 = 18.36 min) in comparison with the baseline mean value (T50 = 16.41 min). Our results demonstrate that the treatment with Ambroxol was able to decrease LEP in 6 subjects, though not significantly.

Inhaled adenosine causes bronchoconstriction in asthmatic patients. In 7 symptom-free asthmatics a study was performed to investigate the effect of sodium cromoglycate and nifedipine on adenosine-induced bronchoconstriction. All patients were challenged with increasing doses (from 0.03 to 2 mg) of nebulized adenosine to assess airway reactivity. The same procedure was repeated on different days at the same time each morning after administration of placebo and drugs in a randomized double-blind study. Airway response was measured as the forced expiratory volume in 1 s (FEV1). The PD20 value and the fall of FEV1 at the provocative dose were calculated. The PD20 data were modified in log values and the statistical analysis was performed by two-way analysis of variance. Mean decrease of FEV1 after adenosine challenge was 26.02 and 28.87% with placebo sodium cromoglycate and placebo nifedipine, respectively. Sodium cromoglycate and nifedipine gave a mean decrease of FEV1 of 6.44% (p less than 0.05) and 22.22%, respectively. PD20 values (geometric mean) after adenosine inhalation were 0.72 and 0.74 mg for placebo sodium cromoglycate and placebo nifedipine and 0.86 mg for nifedipine. Sodium cromoglycate gave a significant protection against adenosine in all subjects and in no case did the maximum dose used (2 mg) result in a fall in FEV1 value greater than 20%. Adenosine antagonism could be considered as a possible factor contributing to the pharmacologic efficacy of sodium cromoglycate in asthmatic patients. No protective effect was noticed with nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of this study was to evaluate in vivo the effect of inhaled substance P (SP) and to determine the effect of sodium cromoglycate (SCG) on bronchospasm induced by its inhalation in 6 asthmatic patients. At the beginning of the study, all patients were asymptomatic, with an FEV1 value not less than 20%. SP was administered as aerosol, prepared in 0.9% saline to produce a dose range of 0.03-1 mg. Airway response was measured as FEV1 using a pulmonary system 47120A Hewlett-Packard instrument. The dose of SP producing a 20% change in FEV1 was calculated from the individual semi-logarithmic dose-response curve (PD20). After administration of the placebo, SP produced a dose-related bronchoconstriction with a geometric mean PD20 of 0.15 mg. After SCG, the mean PD20 value was of 0.64 mg (p less than 0.01). These results confirmed the bronchospasm induced by inhalation of SP and demonstrated that SCG is able to prevent this effect although it is impossible to define the exact mechanism of the drug.