Biomedical subjects

S Mattoli

Publications and source records attributed to S Mattoli.

50 records · Page 3Linked to original sources

PubMed1990

Specific binding of endothelin on human bronchial smooth muscle cells in culture and secretion of endothelin-like material from bronchial epithelial cells.

Endothelin, synthesized by endothelial cells, is the most potent vasoconstrictor and bronchoconstrictor agent known. We investigated endothelin release from human bronchial epithelial cells and the binding of the peptide to autologous bronchial smooth muscle cells in culture. Epithelial and smooth muscle cells were isolated by enzymatic digestion of bronchial tissue obtained on surgery, and cultured to confluency by standard methods. Epithelial cells stained positively for cytokeratin filaments. Smooth muscle cells stained uniformly for alpha-smooth muscle actin. Immunoreactive endothelin contents in the supernatants of epithelial cells extracted on C8 Amprep columns were evaluated by radioimmunoassay. Epithelial cells released appreciable amounts of immunoreactive endothelin into the culture medium (from 0.65 to 2.1 pmol/ml). A single specific binding site for [125I]endothelin 1 was identified on bronchial smooth muscle cells with an apparent Kd of 113 pM and a maximal binding capacity of 22.1 fmol/10(6) cells. At room temperature the binding was saturable, reached equilibrium at 120 min (25 pM endothelin 1), and was slowly and incompletely reversed by unlabeled endothelin over a period of 8 h. Conditioned medium from epithelial cells inhibited the [125I]endothelin 1 binding, dose dependently, and the effect was antagonized by monospecific antiserum. Thus, human bronchial smooth muscle cells possess specific binding sites for endothelin 1 and human bronchial epithelial cells secrete an endothelin-like material. This may have a role in the pathogenesis of asthma.

Binding Sites↗

PubMed1989

Cellular characteristics of sputum from patients with asthma and chronic bronchitis.

The reproducibility of sputum cell counts was examined and the cell counts in patients with asthma were compared with those in patients with chronic bronchitis. Three groups of subjects were studied. Sputum from eight patients with chronic asthma and with sputum production were studied to determine the reproducibility of sputum cell counts. The findings in 10 non-smokers with asthma uncomplicated by other airway disease examined at the time of an exacerbation with sputum (group 2) were compared with those from eight smokers with chronic cough and sputum but no features of asthma (group 3). Sputum plugs were selected by microscopy to ensure their origin from the lower respiratory tract. A total cell count was performed on a trypsinised suspension, and differential and metachromatic cell counts were performed on undiluted plugs. The within specimen and test-retest reproducibility of these measurements was high (reliability coefficient, R, = 0.99 and 0.89). The sputum of the asthmatic patients was characterised by eosinophilia (69%, range 46-92%) and the presence of formaldehyde blockable metachromatic cells (1.5%, range 0.6-2.8%). In comparison, the sputum of the patients with chronic bronchitis had few eosinophils (0.5%) or metachromatic cells (0.14%); the dominant cell type was the macrophage (83%). It is concluded that sputum cell counts are reproducible in the short term, the inflammation of asthma is characterised by eosinophilia and metachromatic cells in sputum, and sputum may provide a useful source of cells for investigating the cellular characteristics of airway inflammation.

Adult↗

PubMed1989

[Non-allergic factors of bronchial asthma].

The functional characteristic of all forms of asthma is the airway hyperresponsiveness to several stimuli. Airway hyperresponsiveness is always present in current asthmatics and can be also documented in some subjects during the symptom-free periods. The mechanisms of the spontaneous or induced increases of airway hyperresponsiveness are probably different from those responsible for stable airway hyperresponsiveness. The transitory increases in airway hyperresponsiveness are associated with an acute inflammatory response of the bronchial mucosa, whereas airway inflammation is not a constant finding in subjects with stable airway hyperresponsiveness. The mechanisms involved in the latter condition might be a functional and/or structural derangement of bronchial epithelium, a functional or structural alteration of airway smooth muscle or alteration in the function of the autonomic nervous system.

Asthma↗

PubMed1989

Bronchial epithelium and asthma.

The bronchial epithelium has a number of mechanical functions, including mucociliary clearance and protection against noxious agents. It may also modulate the function of the underlying smooth muscle by metabolism and regulation of mediators and the production of relaxant or constrictor substances, and regulate the activation and differentiation of lymphocytes and mast cells by releasing chemotactic factors and cytokines. It is possible that epithelial structural and functional abnormalities may lead via several mechanisms to increased bronchial responsiveness in asthmatic subjects.

Asthma↗

PubMed1988

Probit analysis applied to the allergen dose-response curve: a method for epidemiologic surveys.

The degree of skin sensitivity to five common allergens (grass, Dermatophagoides pteronyssinus, mugwort, birch, and Parietaria) was determined by the threshold dilution technique in all the skin test reactors of a random sample of 295 schoolchildren (142 male and 153 female subjects, age range 11 to 14 years), and the frequency distribution of responders at each concentration was analyzed by probit analysis. The potency of each allergen was presented in terms of median effective dose (ED50), and comparison between different allergens and between symptomatic and asymptomatic subjects was made by computing the relative potency. The ED50 of the allergens was found to be nearly identical (grass, 13.5; D. pteronyssinus, 12.3; mugwort, 9.6 activity units by RAST (AUR)/ml) with the exception of birch (22 AUR/ml). Grass and D. pteronyssinus demonstrated a lower ED50 in symptomatic subjects (3.3 and 2.8 AUR/ml, respectively) than in asymptomatic subjects (85 and 27 AUR/ml, respectively). The lower fiducial limits of ED50 in symptomatic subjects demonstrated to be a cutoff point, since they included only 5% and 12% of asymptomatic reactors to grass and D. pteronyssinus, respectively. We conclude that probit analysis applied to the distribution of threshold doses of allergen extracts is a useful method to evaluate skin sensitivity in epidemiologic surveys. We believe that the ED50 is a practical and reliable allergy index.

Allergens↗

PubMed1987

Effects of two doses of cromolyn on allergen-induced late asthmatic response and increased responsiveness.

We selected five atopic children with asthma with previously documented late asthmatic response (LAR) associated with increased hyperresponsiveness to methacholine after the inhalation of Dermatophagoides pteronyssinus. The children had four allergen inhalation tests on 4 different days, at least 14 days apart. On days 1 and 4, saline placebo was inhaled 1 hour before the expected onset of LAR, and FEV1 was measured hourly until FEV1 returned within 10% of baseline value; then methacholine challenge was performed. On days 2 and 3, 20 and 40 mg of cromolyn was inhaled double blind 1 hour before the expected onset of LAR. FEV1 and methacholine responsiveness were measured as on days 1 and 4. The two doses of cromolyn significantly delayed the LAR onset without altering the overall LAR magnitude and prevented the allergen-induced increase in methacholine responsiveness. Both these effects were greater at the maximal dose used. We conclude that cromolyn can prevent the allergen-induced increase in methacholine responsiveness and that this effect is not due to alteration in the magnitude of LAR. Our findings reveal a possible explanation of the effectiveness of this drug in the treatment of allergic asthma.

Adolescent↗

PubMed1987

The effect of indomethacin on the refractory period occurring after the inhalation of ultrasonically nebulized distilled water.

We examined the involvement of inhibitory prostaglandins in refractoriness induced by repeated ultrasonically nebulized distilled water (UNDW) challenge. Six male subjects with asthma who developed both UNDW-induced bronchoconstriction and refractoriness after UNDW were studied on 3 separate days, 1 week apart. On each study day, subjects had an initial UNDW challenge. UNDW responsiveness was assessed with dose-response curves of UNDW volume output versus the percent fall in FEV1. The output provoking a 20% fall in FEV1 (PO20 UNDW) was calculated. FEV1 was measured again at 5-minute intervals until it returned to within 5% of baseline value. UNDW challenge was then repeated. On day 1, the two successive UNDW challenges were performed in absence of any treatment (control day). Before days 2 and 3, subjects received placebo capsules or indomethacin, 100 mg per day, in a double-blind, randomized fashion for 3 days. On both the control and placebo days, repeated UNDW inhalation provoked a significant increase in PO20 UNDW (p less than 0.01), indicating refractoriness. On the indomethacin day, the mean PO20 UNDW during the second UNDW challenge was not significantly different from that obtained during the initial test on that day (p greater than 0.05), indicating that refractoriness did not occur. We suggest that inhibitory prostaglandins are involved in the development of refractoriness after UNDW inhalation.

Adolescent↗

PubMed1987

Allergy indices based on allergen dose-response curve in a randomly selected sample of schoolchildren.

Skin-test sensitivity was computed in 61 schoolchildren drawn from a stratified random sample in order to generate two allergy indices based on a quantitative skin-test assay: Individual Allergy Index (IAI) and Population Allergy Index (PAI). The former to quantitate IgE-mediated skin test sensitivity of each subject, the latter to describe the degree of skin reactivity of our sample to a single allergen. Five allergen extracts were tested at 4-fold dilutions. Sensitivity endpoint data were used to generate IAI. Frequency distribution of IAI seemed to be bimodal as asymptomatic subjects gathered at the lower part while symptomatic children showed a peak in the middle. By means of criteria based on the relation between IAI and the prevalence of symptoms we were able to classify atopy in five classes from normal (all asymptomatic subjects) to severe atopy (all symptomatic subjects). Each positive reaction was plotted as a function of the allergen concentration eliciting the weal, and linear regression with confidence limits was calculated for grass and Dermatophagoides pteronyssinus only. PAI was represented by the slope, which depends on the reactivity of the sample, and the intercept, which involves the potency of the allergen as well. Grass and D. pteronyssinus showed the same slope while the intercepts differed. The slope increased if we considered symptomatic subjects only. We propose both these indices for clinical and epidemiological studies.

Adolescent↗

PubMed1987

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↗

PubMed1986

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↗

PubMed1986

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↗

PubMed1986

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↗

PubMed1986

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↗

PubMed1985

The immediate and short-term effects of corticosteroids on cholinergic hyperreactivity and pulmonary function in subjects with well-controlled asthma.

We investigated the immediate effect of corticosteroids on pulmonary function (FEV1 and forced expiratory flow measured between 25% and 75% of vital capacity) and methacholine airway reactivity during a period of 8 hours after an intravenous bolus of 6-methyl-prednisolone (1 mg/kg) or saline placebo administered in a double-blind, crossover schedule in 12 patients with well-controlled asthma. The short-term effect of corticosteroids was also studied with bronchial reactivity to methacholine and pulmonary function measured before and at the end of 8 days of 6-methyl-prednisolone therapy (32 mg once a day, orally) in a group of six treated subjects as well as in a control group. There were no immediate or short-term effects from 6-methyl-prednisolone on bronchial response to inhaled methacholine. After 8 days of corticosteroid administration, forced expiratory flow measured between 25% and 75% of vital capacity significantly increased in the treated group (p less than 0.025). We concluded that "primary hyperreactivity" appears to be insensitive to an intravenous bolus or 8 days of treatment with oral corticosteroids and that the improvement in respiratory function is slight and slowly evolving in subjects with well-controlled asthma.

Adolescent↗