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Biomedical subjects

A Foresi

Publications and source records attributed to A Foresi.

62 records · Page 4Linked to original sources

Provocative dose and dose-response curve to inhaled propranolol in asthmatic patients with bronchial hyperresponsiveness to methacholine.

This study was carried out to compare bronchial responses to inhaled propranolol (P) and methacholine (M) in a group of asthmatic subjects with mild to moderate bronchial hyperresponsiveness to M; to determine the short term reproducibility of bronchial response to propranolol; and to examine the shape of dose-response curve to P relative to that of M. Doses of M and P were given in mumoles and bronchial responses to both agents were expressed as the provocative dose that induced a 20 percent fall in FEV1 (PD20 FEV1). In 16 asthmatic patients, there was no correlation between the PD20 of the two agents. Mean PD20 M (+/- SD in log scale) was approximately nine times lower than mean PD20 P (0.64 +/- 0.96 and 5.80 +/- 1.65, respectively). This difference was statistically significant (t = 4.58, p less than 0.001). In six asthmatic patients, the reproducibility of PD20 P was similar to that of M (intraclass correlation coefficient 0.969 and 0.957, respectively). The shape of the dose-response curves to P was different from that of M in five of nine asthmatic patients when all experimental points were analyzed by double-reciprocal plot. We noticed that even small doses of inhaled P may cause a severe bronchoconstriction. Therefore, special caution should be taken to increase P doses very gradually, when studying the dose-response curve. We demonstrated that P inhalation induced a measurable bronchoconstriction in subjects with mild to moderate hyperresponsiveness and it was reproducible. However, the bronchial sensitivity to P was lower than to M. Our findings suggest that P and M have different mechanisms of action.

Asthma↗

Refractory period to ultrasonic mist of distilled water: relationship to methacholine responsiveness, atopic status, and clinical characteristics.

Twenty asthmatic subjects had two successive methacholine challenges, two successive challenges with ultrasonically nebulized distilled water (UNDW) and an UNDW followed by methacholine on three separate days. Only ten subjects showed a refractory period to repeated UNDW stimulation. Prior stimulation with UNDW provoked increased methacholine responsiveness in the non-refractory group and a more rapid recovery from methacholine-induced bronchoconstriction in the refractory subset.

Adult↗

Late bronchial response and increase in methacholine hyperresponsiveness after exercise and distilled water challenge in atopic subjects with asthma with dual asthmatic response to allergen inhalation.

We investigated the occurrence of late asthmatic response and increased methacholine responsiveness after exercise and ultrasonically nebulized distilled water (UNDW) inhalation in 12 subjects with asthma with dual asthmatic response and increased responsiveness after allergen challenge. On 3 separate days, allergen, exercise, and UNDW challenges were performed 2 hours after methacholine. FEV1 was measured for 8 hours to detect any delayed change in airway caliber. If there were a further significant reduction in FEV1 after the recovery from the immediate bronchoconstriction, methacholine challenge was performed again when FEV1 had returned to baseline. Reproducibility of any observed late response to exercise and UNDW was also investigated by repeating these challenges on 2 subsequent days. After allergen inhalation only nine subjects had an early asthmatic response, whereas all the tested subjects demonstrated a late reaction and increased methacholine responsiveness. Ten subjects had an immediate response to exercise, and this was followed by a late response in only four patients. Nine subjects demonstrated early response to UNDW inhalation, and five subjects also had a late reaction. These late responses were associated with an increase in methacholine responsiveness in a subset of the tested subjects. Late-phase reactions to exercise and UNDW were not reproducible.

Administration, Inhalation↗

Increase in bronchial responsiveness to methacholine and late asthmatic response after the inhalation of ultrasonically nebulized distilled water.

We studied ten subjects who had an asthmatic response after the inhalation of ultrasonically nebulized distilled water and did not show any refractory period to repeated challenge with such water. The change in responsiveness to methacholine after inhalation of distilled water and the occurrence of any water-induced late asthmatic response were investigated on separate days. All of the tested subjects showed a significant increase in bronchial responsiveness to methacholine after prior stimulation with ultrasonically nebulized distilled water, which waned within two hours in eight of them. The other two subjects showed a progressive increase in responsiveness to methacholine, and they also had a further reduction in the caliber of the airways three to four hours after inhalation of distilled water. The late responses were less severe than the initial responses and lasted four to five hours. After the spontaneous recovery, no significant increase in responsiveness to methacholine was detected. Our results confirm previous observations on hyperresponsiveness induced by ultrasonically nebulized distilled water and demonstrate the occurrence of late reactions after inhalation of such water.

Aerosols↗

Comparison of bronchial responses to ultrasonically nebulized distilled water, exercise, and methacholine in asthma.

We compared the responses to inhaled methacholine, ultrasonically nebulized distilled water, and exercise in 25 subjects with atopic asthma. The methacholine inhalation test and challenges with distilled water and exercise were performed on three separate days 48 hours apart. Bronchial responsiveness to methacholine and ultrasonically nebulized distilled water was measured as the concentration of methacholine (PC20M) and the volume output of the ultrasonic nebulizer (PO20 UNDW) producing a 20 percent fall in the forced expiratory volume in one second (FEV1). The response to exercise was expressed as the percentage of fall in FEV1 from the value before exercise. Seventeen subjects showed a fall in FEV1 of more than 20 percent after exercise. Eight subjects had a stimulus-response curve to distilled water that was flat up to the maximal volume output from the nebulizer, but only four of them also showed no significant response to exercise. The response to exercise correlated better with PO20 UNDW (r = -0.66; p less than 0.01) than with PC20M (r = -0.19; p greater than 0.5) in those responding to distilled water. In all of the tested subjects, exercise-induced bronchoconstriction correlated with PC20M (r = -0.61; p less than 0.01). The mean PC20M was significantly lower in the subjects with a significant response to distilled water and exercise (p less than 0.001 and p less than 0.0001, respectively). We concluded that ultrasonically nebulized distilled water and exercise provoke significant bronchoconstriction in the subjects with more severe nonspecific bronchial hyperresponsiveness. The correlation found between the two stimuli supports the hypothesis that they act by similar mechanisms.

Adolescent↗

Protective effect of disodium cromoglycate on allergen-induced bronchoconstriction and increased hyperresponsiveness: a double-blind placebo-controlled study.

The protective effect of 40 mg cromolyn on allergen-induced late response and increased hyperresponsiveness were studied in five asthmatic children to whom this drug and saline placebo were administered 20 minutes before allergen inhalation, at random, double-blind. Cromolyn reduced the magnitude of early and late responses and abolished the increase in methacholine responsiveness.

Adolescent↗

Short-term treatment with a low dose of inhaled fluticasone propionate decreases the number of CD1a+ dendritic cells in asthmatic airways.

The activation of T-lymphocytes through the recognition of specific allergens is a crucial event in the development of allergic inflammation. Dendritic cells (DC) are potent accessory cells that play an important role in initiating bronchial immune responses by activation of T-lymphocytes. We investigated the distribution of CD1a+ DC in the bronchial biopsies from asthmatic patients, and evaluated the effects of a short course of low dose inhaled fluticasone propionate treatment. Twenty-three mild to moderate stable asthmatic patients and eight normal subjects were included in the study. Bronchoscopy with bronchial biopsies were performed in each subject. Eighteen of the 23 asthmatics underwent a second bronchoscopy after 6 weeks of low dose inhaled fluticasone propionate treatment (250 mcg bd) in a placebo-controlled double-blind study. Biopsies were embedded into glycolmethacrylate resin and analysed by immunohistochemistry methods using specific monoclonal antibodies against CD1a, which is a widely recognized marker for DC. In asthmatics, CD1a+ DC number was significantly higher in bronchial epithelium (P < 0.001) and in lamina propria (P < 0.001) when compared with normal controls. In addition, we observed that a short course of low dose inhaled fluticasone propionate treatment decreased the number of CD1a+ DC in both the bronchial epithelium (P < 0.05) and lamina propria (P < 0.01). The increased number of CD1a+ DC support the hypothesis that DC play an important role in the modulation of the immune response in chronic asthma. Short-term low dose fluticasone propionate treatment induces down-regulation of the CD1a+ DC number.

Administration, Inhalation↗

Lung function and diffusing capacity for carbon monoxide in patients with juvenile chronic arthritis: effect of disease activity and low dose methotrexate therapy.

OBJECTIVE: We measured lung function, in terms of lung volumes, forced expiratory flow-volume curves and diffusing capacity of carbon monoxide (DLCO), in a group of 61 patients with juvenile chronic arthritis (42 female; age range 5 to 33 years) to ascertain whether disease activity and treatment with low dose methotrexate (MTX) influenced these parameters. The whole population was divided into subgroups based on onset type (systemic, n = 27; pauciarticular, n = 12; polyarticular, n = 22), disease activity (active, n = 42; inactive, n = 19), and MTX treatment (treated, n = 27; not treated, n = 34). RESULTS: We found that maximal-mid expiratory flow (MMEF) was significantly reduced in patients with active disease (p < 0.025). The mean DLCO value, expressed as a percentage of the predicted value, and DLCO corrected for the hemoglobin value were lower than expected (67% and 80%, respectively). Multiple regression analysis showed that the forced vital capacity (FVC), forced expiratory flow in one second (FEV1) and DLCO were all correlated to the clinical subtype of the disease (p < 0.05, p < 0.02, p < 0.02, respectively), and MMEF was related to disease activity (p < 0.025). There was no evidence of any effect of MTX treatment on the pulmonary parameters. CONCLUSION: This study confirms that JCA is characterized by an impairment of lung function, mainly involving the small airways, and by interstitial damage. These changes are related to the clinical subtypes of the disease and to disease activity.

Adolescent↗