Skin prick-test reactivity to aeroallergens and allergic symptoms in an urban population of central Italy: a longitudinal study.

BACKGROUND: Cross-sectional studies report an increasing prevalence of allergic diseases, such as rhinitis and asthma. Not thoroughly known, instead, is the natural history of allergic sensitization and the progress of the allergic disease-related symptoms. AIM: The purpose of this study was to evaluate longitudinally the skin reactivity for the most common aeroallergens and the allergic symptoms in an urban population living in Perugia, a town of central Italy with a low-level of air pollution exposure. METHODS: In the 1998-1999 period 788 subjects were tested for skin reactivity to a panel of aeroallergens and underwent the administration of a questionnaire. These same subjects were part of a cohort of 1200 subjects who participated in a previous epidemiological study performed in 1984-1985 using the same tools. Subjects were aged between 14 and 64 years at the time of the first survey. RESULTS: In the present survey 196 subjects (24.9%) had skin reactivity to at least one aeroallergen, while in the previous survey 143 subjects (18.1%) had skin prick-test reactivity. The increase of the skin reactivity between the two observations was highly significant (P<0.001) and was mainly observed in subjects <40-years old. The greatest increment in skin reactivity was seen to Dermatophagoides pteronyssinus (house dust mite) allergen. Data obtained from questionnaires showed that subjects who declared allergic symptoms increased from 341 (43.3%) to 380 (48.2%). However, the increase was significant (P<0.01) only in subjects who had a positive association between allergic symptoms and prick-test reactivity and was greater for rhino-conjunctivitis than for asthma-related symptoms. CONCLUSIONS: In a cohort of urban population of the centre of Italy, exposed to a low and stable level of air pollution, the sensitization to common aeroallergens increased with time, mostly in people <40-years of age. The greatest increment was found for indoor allergens such as Dermatophagoides pteronysimus. A significant increase in allergic symptoms, mainly related to rhino-conjunctivitis, was observed only in the presence of positive prick test.

Ineffectiveness of a four week treatment with the thromboxane synthetase inhibitor, imidazole salycilate, in reducing airway hyperresponsiveness to methacholine in asthmatics.

In a randomized, double-blind, placebo-controlled study, the acute and long-term effects of the reduction of thromboxane A2 (TxA2) synthesis on airway sensitivity and maximal airway narrowing in response to methacholine was evaluated in 12 subjects with mild-to-moderate stable asthma, using imidazole salycilate (IS), an anti-inflammatory drug which selectively inhibits the TxA2 synthetase. Dose-response curves with methacholine (MCh) were performed in basal conditions (baseline); 1-1.5 h after administration of 1,500 mg of IS or placebo (acute); at 15 and 30 days of treatment with 750 mg t.i.d. of IS or placebo; and after a 2 week period of run-off (45 days). The serum levels of thromboxane B2 (TxB2) were measured at the same time points, except after acute administration, in five patients from each group. Baseline forced expiratory volume in one second (FEV1) was 78 +/- 7 and 85 +/- 8% of predicted in the IS and control group, respectively (NS). Throughout the study FEV1 remained unchanged in both groups, indicating that IS did not caused substantial modification of resting bronchial calibre. The initial provocative dose of methacholine causing a 20% fall in FEV1 (PD20) amounted to 27.0 +/- 1.5 micrograms in the IS group and 41.7 +/- 1.5 micrograms in the control group (geometric mean +/- GSEM) (NS). Despite a reduction of TxB2 serum levels with IS vs placebo at 15 days (24.9 +/- 8.5 vs 45.5 +/- 3.4 pg.mL-1; p < 0.05) and 30 days (27.0 +/- 6.3 vs 45.0 + 3.2 pg.mL-1; p < 0.05), MCh-induced bronchoconstriction, evaluated either as PD20 or maximal airway narrowing, did not change significantly during active treatment compared to placebo. These results show that prolonged reduction of thromboxane A2 synthesis does not improve airway sensitivity and limit maximal bronchoconstriction in asthmatic subjects, suggesting that thromboxane A2 per se does not play a substantial role in the pathogenesis of the airway hyperresponsiveness in human asthma.

Diurnal change of bronchial caliber and airway responsiveness in asthmatics during long-term treatment with long-acting beta 2-agonist salmeterol.

Measurements of bronchial caliber and airway sensitivity were performed 4 times during the day (at 9, 11, 16, and 22 hr) at basal conditions (baseline), following the first inhalation of 50 micrograms salmeterol (acute) and at the 21st, 90th and 150th day after the initiation of an uninterrupted long-term treatment with inhaled salmeterol (50 micrograms b.i.d., at 10 and 22 hr). In each period of the protective effect was assessed by computing the increase of the methacholine dose able to induce a 20% fall of the forced expiratory volume in the first second (PD20FEV1) in terms of doubling dose (DD), either against the respective 9-hour PD20FEV1 value (DD9hr) or against the corresponding baseline PD20FEV1 value (DDbaseline). After the first dose of salmeterol the forced expiratory volume in the first second (FEV1) increased significantly as compared with the 9-hour FEV1 and the corresponding baseline FEV1 at each observation time (p < 0.01). During regular treatment FEV1 was higher than baseline at the 21st and 90th day at each observation time (p < 0.05), whereas at the 150th day no significant FEV1 increments were observed at 9 hr and 22 hr. The acute protective effect exerted by salmeterol amounted to about 2 DD9hr (p < 0.05) and 2 DDbaseline (p < 0.05) at each observation time. At the 21st, 90th, and 150th day, however, no significant increase of DD9hr was found, although a mild decrease of airway sensitivity of 1 DDbaseline of magnitude was observed for all periods at each observation time. We conclude that in mild to moderate asthma salmeterol appears to rapidly lose its ability to improve bronchial responsiveness while it is effective in maintaining a well-sustained bronchodilation despite a small degree of tachyphylaxis.

Acute respiratory effects of sublingual buprenorphine: comparison with intramuscular morphine.

In this randomized, double-blind, placebo study, the respiratory effects of a single dose of sublingual buprenorphine (0.4 mg) were examined and compared with those induced by one dose of intramuscular morphine (10 mg) in a population of women, aged 25-65 years, admitted at the Hospital for Elective Surgery because of uterine fibromyomatosis. Some indices of control of breathing (P0.1, VT/TI, VE, VA, TI, TE, TI/TTot, RR), gas exchange parameters (D[A-a]O2, VD/VT, PAO2) and blood gases (PaO2, PaCO2) were measured in basal condition and at 30, 60, 90, 180 and 360 min after the administration of the drugs. No significant changes of the respiratory function were observed in patients who have received sublingual buprenorphine. In the morphine-group, however, mild PaO2 decrease and PaCO2 increase were found at 60 and 90 min (p less than 0.05), without any reduction of the respiratory drive activity, as shown by P0.1, VT/TI and VE. The significant FRC reduction, observed in the morphine-group (p less than 0.05), could have induced both TE shortening and RR increase with larger dead space ventilation and consequent fall of VA (p less than 0.05). These results suggest that the administration of one dose of sublingual buprenorphine (0.4 mg) does not cause any detrimental respiratory effect; on the other hand, an appreciable, although clinically trivial, worsening of the respiratory function results from intramuscular morphine (10 mg), in the absence of any obvious respiratory depression.

Comparative evaluation of cardioselectivity of metoprolol OROS and atenolol: a double-blind, placebo-controlled crossover study.

Cardioselectivity of a single oral dose of metoprolol oral osmotic (OROS) (14/190 mg) and atenolol (100 mg) was compared in 12 patients with reversible obstructive airway disease by assessing the dose-response curve to increasing doses of inhaled salbutamol. The beta-blocking activity of the two drugs, which was determined by measuring heart rate, blood pressure, and derived indexes at peak plasma drug levels, was similar. Both metoprolol and atenolol significantly reduced forced vital capacity and peak expiratory flow, with no difference between drugs. Atenolol but not metoprolol also significantly reduced forced expiratory volume in 1 second and specific airway conductance. Both metoprolol and atenolol shifted the dose-response curve of specific airway conductance to the right. The results indicate that the new OROS delivery system for metoprolol, which produces a relatively constant plasma drug level, provides a cardioselectivity comparable to or greater than that of atenolol at maximum plasma levels.

Acute ventilatory and gas-exchange effects of a new beta-2 agonist, broxaterol, in asthmatics.

The ventilatory and gas-exchange effects of broxaterol, a new selective beta 2-adrenoceptor agonist, were investigated in ten asthmatics following intravenous administration of a single dose of 200 mcg. Broxaterol elicited a prompt and marked bronchodilating effect (increase in forced expiratory volume in one second and specific conductance), maintained at least up to the sixtieth minute. Minute ventilation and the mean expiratory flow did not increase significantly, the pattern of breathing showing a reduction of expiratory time, without modification of inspiratory time. On the other hand, occlusion pressure did not show any significant rise at all times of observation. Furthermore, the partial arterial oxygen and carbon dioxide pressures and alveolar-arterial difference in oxygen and physiological dead space remained unchanged, when measured at 20 min. The results demonstrated that broxaterol was an effective bronchodilating agent, also when rapidly injected, causing a prompt relief of bronchospasm. With respect to other beta 2-adrenoceptor agonists, this compound did not appear to increase minute ventilation or to induce an impairment of ventilation/perfusion ratio, at least after 20 min, when the bronchodilation was still evident. Finally, no side-effects or alterations of heart rate or blood pressure were reported.

Acute on chronic comparative effects of a combination of fenoterol-ipratropium bromide and terbutaline in patients with chronic obstructive lung disease.

Twenty patients suffering from chronic obstructive lung disease (COLD) were examined in a randomized intra-individual single-blind study in order to compare the ventilatory response, tolerance and side-effects of a combination of 40 micrograms ipratropium bromide and 100 micrograms fenoterol (Duovent) with 250 micrograms terbutaline, both given by inhalation (2 puffs) three times a day. The ventilatory parameters FVC, FEV1, sGaw, RV and PaO2, tested on the 7th and 14th days at 0, 30, and 240 min after the morning administration of the two drugs, showed significant differences between treatments, revealing a greater persistence of bronchodilator effect and a more prolonged duration of action with Duovent than with terbutaline. We believe that the results obtained suggest the usefulness of a combination of anti-cholinergic and beta 2-agonist drugs in the treatment of reversible bronchial obstruction in COLD, where even the parasympathetic nervous system seems to play an important role. The observed clinico-functional effects (intensity and duration of bronchodilatation) together with the lack of side-effects permit us to affirm that Duovent is a rational pharmacologic combination which represents real progress in the difficult treatment of COLD patients.