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Biomedical subjects

V Brusasco

Publications and source records attributed to V Brusasco.

At least 55 records · Page 3Linked to original sources
PubMed1997

Allergen challenge of passively sensitized human bronchi alters M2 and beta2 receptor function.

We investigated whether antigen challenge may alter M2 and beta2 receptor function in isolated passively sensitized human bronchi. Bronchial rings (2-4 mm internal diameter) were obtained from 12 patients. Passive sensitization was induced by serum containing high IgE levels to Dermatophagoides pteronyssinus and Dermatophagoides farinae. Rings from six patients were used to study M2 receptor function by incubating with cumulatively increasing concentrations (10(-8) M to 10(-4) M) of pilocarpine and applying electric field stimulation (EFS) at 24 Hz. The rings from the other six patients were used to study beta2 receptor function by precontracting with carbachol 10(-6) M and adding cumulatively salbutamol (10(-9) M to 10(-4) M). Additional rings from these patients were used to determine whether dysfunction occurred distal to cAMP production by precontracting with carbachol 10(-6) M and adding cumulatively theophylline (10(-9) M to 10(-4) M). The attenuation of EFS-induced force by pilocarpine and the relaxation of carbachol-precontracted rings by salbutamol were less in challenged than in control and sensitized rings. No difference between challenged, sensitized, and control rings was observed with theophylline. We conclude that allergen challenge in passively sensitized isolated human bronchial rings may result in M2 and beta2 receptor dysfunction without involving mechanisms distal to cAMP formation. It appears that products from inflammatory cells recruited from blood are not necessary for this receptor dysfunction.

Adrenergic beta-Agonists↗
PubMed1997

On the causes of lung hyperinflation during bronchoconstriction.

Airway obstruction in asthma and chronic obstructive pulmonary disease (COPD) is often associated with lung hyperinflation. In this review, we examine the mechanisms that may cause functional residual capacity (FRC), residual volume (RV) and total lung capacity (TLC) to increase during acute and chronic airway obstruction. Normally, FRC at rest is determined by the static characteristics of the lung and chest wall. When airways narrow, FRC may be also be determined by dynamic factors. There are data suggesting that expiratory flow limitation during tidal breathing represents the starting trigger for FRC to increase, in order to allow breathing at higher flows. Indeed, the increase in FRC during induced bronchoconstriction in asthma is closely associated with the occurrence of flow limitation, i.e. the achievement of maximum flow during tidal breathing. Conversely, the decrease in FRC following bronchodilatation in COPD is closely associated with flow limitation disappearing or occurring at lower lung volumes. In normal young people, RV is determined by the static characteristics of the chest wall. During bronchoconstriction RV may also be determined by dynamic factors; therefore, changes in flow or airway calibre at low lung volumes may modulate RV during bronchoconstriction. During acutely induced bronchoconstriction, RV achieved with an expiration from TLC is less than with an expiration from tidal breathing, and this effect appears to be linked to the bronchodilator effect of the deep inhalation. The reasons for the increase in TLC during airway narrowing are not clear, but the duration of the bronchoconstriction by itself may play a role.

Bronchoconstriction↗
PubMed1997

Vital capacities in acute and chronic airway obstruction: dependence on flow and volume histories.

The aim of this study was to investigate whether measurements of vital capacity (VC) are affected by the direction of the manoeuvre (inspiratory vs expiratory) and by the rate of expiratory flow. The study was performed on 25 individuals with chronic airway obstruction (CAO) and a forced expiratory volume in one second (FEV1) (expressed in standardized residuals (SR)) of -2.0+/-1.4 SD (CAO group), and 10 asthmatic subjects with methacholine (MCh)-induced bronchoconstriction (FEV1 -23+/-1.02 SR) (MCh group). VCs were measured during fast inspiration following both slow (FIVCse) and forced (FIVCfe) expiration from end-tidal inspiration to residual volume (RV), and during slow (EVC) or forced (FVC) expiration from total lung capacity (TLC). In the CAO group, FVC was the smallest volume (3.75+/-1.03 L) and significantly different from the other three estimates of VC; FIVCse (4.03+/-0.91 L) was the largest volume and significantly different from FVC and FIVCfe (3.83+/-0.98 L). In the MCh group, FVC (4.16+/-0.94 L) and EVC (4.19+/-0.89 L) were the largest volumes, although only the difference between FVC and FIVCfe (3.76+/-0.81 L) reached statistical significance. These data suggest that both flow and volume histories contribute to decreased vital capacities during bronchoconstriction. However, whereas increasing expiratory flow always tends to decrease vital capacity, the volume history of full inflation has different effects in chronic and acute bronchoconstriction, probably due to different effects on airway calibre. These results stress the importance of using standardized manoeuvres in order to obtain comparable values of vital capacity.

Acute Disease↗
PubMed1997

Lung hyperinflation and flow limitation in chronic airway obstruction.

We reasoned that if flow limitation plays an important role in lung hyperinflation, then bronchodilatation should be associated with a decrease of functional residual capacity (FRC) only in subjects breathing under conditions of flow limitation. This hypothesis was tested in 33 subjects with chronic airway narrowing due to asthma or chronic obstructive pulmonary disease (COPD). Flow limitation during tidal breathing was inferred from the impingement of the tidal flow-volume loop on the flow recorded during submaximally forced expiratory manoeuvres initiated from end-tidal inspiration. At baseline, flow limitation during tidal breathing was present in seven asthmatic (Group 1) and eight COPD subjects (Group 2), but absent in 11 asthmatic (Group 3) and seven COPD subjects (Group 4). FRC (mean+/-SEM) was similar in the four groups (range 117+/-7 to 134+/-6% of predicted). Inhalation of salbutamol (200 microg) caused significant increments of the forced expiratory volume in one second (FEVI) (range 6+/-1 to 21+/-8% of baseline) and forced expiratory flows at 30% of baseline forced vital capacity (V'30) (range 58+/-13 to 235+/-93% of baseline) in all groups. In groups with flow limitation during tidal breathing at baseline the FRC measured by plethysmography decreased significantly (12+/-2% in Group 1, and 9+/-2% in Group 2), and the inspiratory capacity (IC) measured by spirometry increased significantly (17+/-3% in Group 1 and 7+/-3% in Group 2). This was associated with flow limitation disappearing at the volume of baseline end-tidal expiration. In Groups 3 and 4 neither FRC nor IC changed significantly. The breathing pattern was not modified in any group after salbutamol. These findings suggest that flow limitation may contribute to generation of lung hyperinflation both in asthma and chronic obstructive pulmonary disease. We speculate that the increment of functional residual capacity could be triggered by dynamic airway compression downstream from the flow-limiting segment.

Adult↗
PubMed1996

Cutaneous antihistaminic action of cetirizine and dose-related EEG concomitants of sedation in man.

The cutaneous antihistaminic action (prick test; 1:100, 1:200 and 1:1000) and neuropsychological and electroencephalographic (EEG) concomitants of sedation following the histamine H1 receptor antagonist cetirizine (10- and 20-mg acute oral doses) and chlorpheniramine, 4 mg, were investigated in a cross-over, placebo-controlled study in healthy male volunteers (age 23-29 years). With an average Cmax of cetirizine of 697.0 ng/ml (10 mg) and 1000.2 ng/ml (20 mg), the diameter of histamine-induced skin weals was reduced by 24.0-74.9% depending on histamine concentration and with no dose dependence for cetirizine. Placebo and chlorpheniramine were ineffective. Behavioral or neuropsychological signs of sedation were never observed. An increase of the 6.5-14.5 Hz EEG power, with anterior scalp preponderance, was observed after chlorpheniramine or cetirizine 20 mg. This effect of cetirizine was accounted for by a substantial increase of power in the 6.5-8.0 Hz frequency subsegment and is regarded, for these experimental conditions, as an established early EEG indication of mild sedation (vigilance 'state A'). No EEG effects were observed after placebo or cetirizine at the 10 mg dose. The existence of some histaminergic (H1) specificity of the mechanisms modulating vigilance and of a threshold dose of cetirizine for sedative action is suggested.

Administration, Oral↗
PubMed1996

Maximal bronchoconstriction in humans. Relationship to deep inhalation and airway sensitivity.

We hypothesized that maximal bronchoconstriction can be predicted from the bronchomoter effect of deep inhalation (DI) and the degree of airway sensitivity to methacholine (MCh). We studied 26 healthy or mildly asthmatic subjects with limited response to MCh (maximal FEV1 decrease, 23 +/- 9 SD%; Group 1) and 26 subjects with moderate to severe asthma with exaggerated response (maximal FEV1 decrease > 40%, Group 2). The effect of DI was quantified as the linear regression coefficient of the percent decrements of maximal (Vm50) versus partial (Vp50) forced expiratory flow at 50% of FVC over the initial steps of challenge (MP slope). Airway sensitivity was inferred from the MCh doses (PDs) causing Vm50 or Vp50 to decrease by 40% or FEV1 by 15%. The absence of limit to bronchonstriction was predicted by either MP slope or any PD with accuracies between 71 and 81%, but with an accuracy of 87% by a discriminant function including MP slope and PD40Vp50. Within Group 1, the maximal FEV1 decrease correlated linearly with MP slope (r2 = 0.41); but it was better predicted by a multiple regression including MP slope and PD40Vp50 (In mg) (r2 = 0.54). We conclude that the magnitude of the bronchodilator effect of DI during induced bronchoconstriction and airway sensitivity predict the level of maximal bronchoconstriction in vivo. We speculate that these parameters reflect some of the mechanisms modulating the response to bronchoconstrictor stimuli such as airway wall structure, airway-to-parenchymal interdependence, and contractile properties of airway smooth muscle.

Adult↗
PubMed1996

Comparison of early and late asthmatic responses between patients with allergic rhinitis and mild asthma.

Allergic rhinitic subjects without symptoms of asthma show airway hyperresponsiveness, but to a lesser degree than asthmatics. As airway responsiveness is a determinant of the bronchial response to allergen, rhinitic subjects should also respond to allergen challenge, but to a lesser extent than asthmatics. However, studies have so far failed to show quantitative differences in allergen responses between patients with rhinitis and patients with asthma. We studied 123 allergic subjects classified, on the basis of a scored symptom questionnaire, as follows: pure rhinitics without any symptom of asthma (Group 1, n = 39), true asthmatics with or without rhinitis (Group 2, n = 41), and subjects with borderline symptoms of asthma (Group 3, n = 43). All subjects underwent both methacholine and allergen inhalation challenges, with pollen challenges performed out of season. When the three groups were pooled, the asthma symptom score was directly correlated with the sensitivities both to methacholine and allergen, whilst both the sensitivity to allergen and the severity of late-phase response were correlated with the sensitivity to methacholine. The percentage of subjects with a positive early-phase asthmatic response to allergen was similar in Groups 1 and 2. Group 2 had higher sensitivities both to methacholine and to allergen than Group 1. A late-phase asthmatic response occurred more frequently in Group 2 than in Group 1, and this difference was due to a higher occurrence of late-phase response in subjects allergic to house dust mite in Group 2. This study confirms that the bronchial response to allergen can be predicted, in rhinitic as well as in asthmatic allergic subjects, on the basis of airway responsiveness to methacholine. We conclude that the presence or the absence of asthma symptoms in allergic subjects may be related to a quantitatively different airway responsiveness to allergen.

Adolescent↗
PubMed1996

Postjunctional effect of pinacidil on contractility of isolated bovine trachealis.

Potassium channel openers hyperpolarize the smooth muscle cell membrane and relax airway smooth muscle. In this study, pre- and postjunctional effects of pinacidil ((+/-) N-cyano-N'-(4-pyridil)-N"-(1,2,2-trimethylpropyl)-guanidine monohydrated), an adenosine triphosphate (ATP)-sensitive K(+)-channel opener, were determined in isolated bovine trachealis. The effects of pinacidil on the frequency-response to electrical field stimulation (EFS), 0.1-32 Hz, and on the concentration response to acetylcholine (ACh), 10(9)-10(-4) M, were compared in muscle strips from six animals. In addition, the effect of pinacidil on the inhibitory nonadrenergic noncholinergic (iNANC) system was evaluated in histamine-contracted muscle strips from another eight animals. Pinacidil (10(-6) or 10(-5) M) shifted both the EFS frequency-response and the ACh concentration-response curves significantly (p < 0.01) to the right. Glibenclamide (10(-7)-10(-5) M) antagonized these responses in a concentration-dependent manner. The inhibitory effects of pinacidil on contractions of the same magnitude induced by EFS or exogenous ACh were not significantly different (p = 0.11), suggesting that pinacidil had only a postjunctional effect. Pinacidil had no effect on iNANC-mediated muscle relaxation. We conclude that pinacidil attenuates the contraction of isolated bovine tracheal smooth muscle by postjunctional mechanisms.

Acetylcholine↗
PubMed1996

Effects of lung volume and thoracic gas compression on maximal and partial flow-volume curves.

Comparing isovolume flows, measured at the mouth during forced expiratory manoeuvres as started from maximal or partial lung inflation, is a means of assessing the effects of deep inhalation on airway calibre. The aim of this study was to investigate whether the assessment of the effect of deep inhalation during induced bronchoconstriction is influenced by the lung volume at which it is determined and by volume differences due to thoracic gas compression that occur during forced expiratory manoeuvres. Four healthy subjects and six subjects with mild-to-moderate asthma subjects performed partial and maximal forced expiratory manoeuvres in a flow-type body plethysmograph at control and during a methacholine (MCh) inhalation challenge. Mouth flow (V1) was plotted against both the expired volume (Vmo) and the simultaneous thoracic volume measured by plethysmography (Vpl) changes (V1-Vmo loop and V1-Vpl loop, respectively). The effects of deep inhalation were quantified by determining 1) the ration of maximal to partial expiratory flows (M/P) at 30, 40 and 50% of control forced vital capacity (FVC) both on V1-Vmo loops (M/Pmo) and V1-Vpl loops (M/Ppl) at control and at MCh end-point; and 2) the slope of the linear regression of maximal vs partial expiratory flows at 30, 40 and 50% of control FVC both on V1-Vmo loops (MPst,mo) and V1-Vpl loops (MPsl,pl) over the entire challenge. At control, M/Pmo and M/Ppl were similar. At MCh end-point, M/Pmo and M/Ppl increased more than twofold (p < 0.002), with M/Pmo consistently exceeding M/Ppl (p < 0.001). In addition, both M/Pmo and M/Ppl varied inversely with lung volume (p < 0.001). By contrast, MPsl,mo and MPsl,pl were not significantly different from each other (p = 0.8), and were also similar at the different lung volumes (p = 0.6). We conclude that during induced bronchoconstriction, the bronchodilation following a deep inhalation, expressed as maximal to partial flow ratio is dependent both on lung volume and volume differences due to thoracic gas compression. The use of expired flow and volume measurements may lead to a small but systematic overestimation of the bronchodilator effect of a deep inhalation. On the contrary, maximal to partial flow slope is insensitive either to lung volume or volume differences due to thoracic gas compression and can, therefore, be fairly determined from expired flow-volume loops.

Adult↗
PubMed1995

Nedocromil sodium versus theophylline in the treatment of reversible obstructive airway disease.

BACKGROUND: Previous clinical therapeutic research has shown that inhaled nedocromil sodium can replace maintenance oral sustained release theophylline in the management of asthma patients. OBJECTIVE: To compare directly the efficacy and safety of nedocromil sodium and sustained release theophylline. METHODS: Using a randomized, double-blind, double-dummy, parallel-group design, 105 patients with reversible obstructive airways disease (77 asthmatic patients) recruited from four referred-care clinics received, in addition to their existing therapy, 4 mg nedocromil sodium four times daily or sustained release theophylline (maximum daily dose 13 mg/kg) for 6 weeks. Patients with serum theophylline levels within the therapeutic range of 10 to 20 micrograms/mL were retained for efficacy analysis. All were included in a tolerability analysis. Day and nighttime symptoms, inhaled bronchodilator use, morning tightness, cough, and twice daily peak flows were recorded on diary cards. Disease severity, lung function and unusual events were evaluated bi-weekly, and opinion of treatment after 6 weeks. RESULTS: Both treatments improved symptoms, inhaled bronchodilator use and lung function to the same extent. Both treatments were very to moderately effective in > 70% patients. The occurrence of gastrointestinal (P < .05) and central nervous system (P < .01) unusual events was significantly lower for nedocromil sodium compared with theophylline treated patients. CONCLUSIONS: Nedocromil sodium and theophylline were equally effective in this group of patients but nedocromil sodium treatment was associated with significantly fewer side effects, and therefore may be the treatment of choice.

Adolescent↗
PubMed1994

Allergy and sports: exercise-induced asthma.

In some asthmatic subjects exercise is followed by a bronchospastic response that generally lasts 30-60 minutes and regresses spontaneously. The initiating stimulus is thought to be the cooling and/or dehydration of airways caused by hyperpnea. The mechanisms leading from thermodynamic changes to airway narrowing are object of controversy. Two hypotheses have been proposed, one suggesting that an increase in the osmolarity of airway lining fluid following water loss causes mediator release, and the other suggesting that an excessive vasodilation during airway rewarming causes vascular engorgement, thus reducing airway caliber. Other controversial issues in exercise-induced asthma are the role of airway inflammation and the question whether a late-phase response may occur. That inflammatory cells and mediators play a role is suggested by increased numbers of eosinophil and epithelial cells in bronchoalveolar lavage and by the efficacy of cromolyn and leukotriene antagonists in preventing EIA. The existence of late-phase response to exercise is questionable because exercise does not cause an increase in airway responsiveness, which usually accompanies late-phase responses to allergens. Furthermore, data of bronchoalveolar lavage and bronchial biopsy suggest that the delayed broncho-constriction that may be observed after exercise reflects airway instability in subjects with more prominent eosinophilic inflammation of airways and is not specific to exercise.

Adult↗
PubMed1994

Quantitative analysis of peripheral allergen-specific B lymphocytes in asthma.

We have recently shown that the number of peripheral allergen-specific T cells can, in part, predict, together with methacholine hyperresponsiveness, the bronchial response to inhaled allergen in asthmatic patients. This study was designed to explore the role of blood B cells committed to produce allergen-specific IgE in asthma. Twenty-three asthmatic patients sensitized to Dermatophagoides pteronyssinus and 11 control subjects were studied. Peripheral blood B cells, committed to produce allergen-specific IgE, were enumerated by limiting dilution microcultures of Epstein-Barr virus (EBV)-transformed B cells. An allergen inhalation challenge was performed in all asthmatic subjects. No difference was found in the frequency of B cells committed to produce allergen-specific IgE either between asthmatic patients and controls or between asthmatic patients with or without late-phase bronchial response to allergen. No correlation was found between the frequency of B cells committed to produce allergen-specific IgE and the bronchial response to the allergen inhalation challenge. We conclude that, in quantitative terms, peripheral allergen-specific B cells are not as relevant as T cells to the development of the asthmatic response in the model of provoked asthma.

Administration, Inhalation↗
PubMed1994

Changes in residual volume during induced bronchoconstriction in healthy and asthmatic subjects.

The increase of residual volume (RV) was investigated during acute bronchoconstriction induced in healthy subjects by methacholine (MCh) (Group 1, n = 13) and in asthmatics by MCh (Group 2, n = 21), or housemite dust (Group 3, n = 11) during early and late airway responses (EAR and LAR), or a series of deep breaths (Group 4, n = 7). In all subjects the difference between residual volume after partial (RVp) and maximal maneuver (RV), expressed as a percentage of control FVC, increased during bronchoconstriction and was correlated with the percent increase of maximal to partial flow ratio at 50% of control FVC (M/P50) (r = 0.854, p < 0.0001). At comparable reduction of partial expiratory flow at 50% of control FVC (VP50), the decreases of FEV1 and FVC were less in healthy than asthmatic subjects, whereas the change of FEV1/FVC was similar in all groups, reflecting similar change in slope of flow-volume curves. The increase of RVp was similar in all groups (range: 15 to 19%), but the increase of RV was 6 +/- 1% (SEM) in healthy subjects and significantly greater (range: 11.1 to 13.3%) in all groups of asthmatics (p < 0.02, analysis of variance [ANOVA]). The effect of deep inhalation (DI) on the airway caliber as assessed by the increase of M/P50 was higher in normal subjects than in all groups of asthmatics (p < 0.0001). A negative correlation was found between the increases of RV and M/P50 in all groups (r = -0.358, p < 0.01), suggesting that healthy subjects had a limited increase of RV because of a marked bronchodilator effect of DI.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Lung volumes and expiratory flow during bronchoconstriction in asthma.

Bronchial asthma is characterized by excessive airway narrowing and hyperinflation. In this review, the mechanisms linking the increases of functional residual capacity (FRC) and residual volume (RV) to reduced airway calibre are analysed. The authors have shown that the increase in FRC is closely associated with the occurrence of flow limitation, i.e. the achievement of maximum flow during tidal volume; whereas, the increase in RV can be modulated by the magnitude of the bronchodilator effect of the deep inhalation during induced bronchoconstriction. It can be speculated that flow limitation contributes to the increase in FRC through a reflex mechanism; whereas, the increase in RV depends on the site of airway narrowing, which in turn determines the relationship between airway and parenchymal properties.

Asthma↗