Biomedical subjects

R Polosa

Publications and source records attributed to R Polosa.

At least 109 records · Page 6Linked to original sources

PubMed1990

Tachyphylaxis to repeated challenges with inhaled adenosine in asthmatic subjects.

Adenosine, when administered as an aerosol to asthmatic subjects, provokes a prompt dose-dependent bronchoconstriction. The aim of this study was to establish whether tachyphylaxis in response to repeated inhalations with adenosine occurs in asthmatic subjects. Eight asthmatic patients were studied on three separate days (days A, B, and C) at the same time of day for each subject. Three inhalation tests were performed, separated by one hour, on each study day. The study was conducted in a double-blind fashion and performed in random order. On day A, three adenosine inhalation tests were performed to assess adenosine tachyphylaxis. On day B, a saline inhalation test was carried out between two adenosine challenges to assess the time course of the adenosine tachyphylaxis. On day C, three methacholine inhalation tests were performed to confirm that tachyphylaxis does not occur to methacholine. Repeated inhalation with adenosine, but not methacholine, produced a progressive loss of responsiveness to the nucleoside, which was particularly manifest with the third challenge.

Adenosine↗

PubMed1989

Effect of indomethacin on adenosine-induced bronchoconstriction.

The exact mechanism of adenosine-induced bronchoconstriction in patients with asthma is unknown. Adenosine contraction of guinea pig trachea was antagonized by inhibitors of cyclooxygenase. The aim of this study was to investigate the effect of indomethacin (100 mg/day) on adenosine-induced bronchoconstriction in 14 asymptomatic patients with asthma. Airway response was evaluated as FEV1, and adenosine was administered as an aerosol diluted in 0.9% saline to produce a concentration range of 0.125 to 4 mg/ml. The dose of adenosine producing a 20% change in FEV1 (PD20) was calculated from the individual semilogarithmic dose-response curve; the results of PD20 were converted to log values for statistical analysis (Student's paired t test). The study was performed on 3 separate days. On the first day, the adenosine challenge was performed, and on subsequent days patients were pretreated with either placebo or indomethacin in a randomized, double-blind manner. Inhaled adenosine caused bronchoconstriction with a geometric mean PD20 of 0.71 mg (95% confidence limits, 0.44 to 1.16). After placebo, a geometric mean PD20 of 0.91 mg (95% confidence limits, 0.53 to 1.58) was obtained. Indomethacin pretreatment decreased adenosine hyperresponsiveness and shifted the dose-response curves of adenosine challenge to the right with a geometric mean PD20 of 1.28 mg (95% confidence limits, 0.64 to 2.56). The effect of indomethacin on adenosine bronchoconstriction (p less than 0.01 versus baseline; p less than 0.05 versus placebo) suggests an indirect mechanism of adenosine on inducing release of arachidonic acid derivatives. Inflammatory mediators inhibited by indomethacin may be involved in adenosine bronchoconstriction, even if this mechanism is not relevant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1989

Adenosine as a pro-inflammatory mediator in asthma.

Adenosine, which may be formed by all cells during relative energy or oxygen deficit, may act as an autocoid by modifying the function of other cells in the local environment. In asthmatic, but not normal, subjects, inhalation of adenosine causes a marked bronchoconstriction which may be reduced by the purinoceptor antagonist theophylline, sodium cromoglycate, nedocromil sodium, histamine, H1-antagonists and cyclo-oxygenase inhibitors. Repeated exposure to adenosine induces a state of tachyphylaxis and cross-tachyphylaxis with exercise-induced bronchoconstriction but not with that provoked by allergen. Although the mechanisms by which adenosine induces changes in airways function are not clear, it is suggested that it has an indirect effect, possibly by up-regulating bronchoconstrictor factors already present in asthma such as mast cell mediator release or neuronal reflexes.

Adenosine↗

PubMed1989

The effect of histamine-H1 receptor antagonism with terfenadine on concentration-related AMP-induced bronchoconstriction in asthma.

Selective histamine-H1 receptor antagonists inhibit adenosine 5'-monophosphate (AMP)-induced bronchoconstriction by greater than 80% when expressed as a percentage inhibition of the FEV1 time-response curve following inhalation of the provocation concentration of AMP required to produce a 20% decrease in FEV1 from baseline (PC20). To investigate this further we have determined that, in eight mild atopic asthmatic subjects, terfenadine (180 mg), administered 3 hr pre-challenge, increases the geometric mean PC20 for histamine from 0.4 (range 0.03-3) mg/ml after placebo, to 20.2 (range 0.6-64) mg/ml following active treatment (P less than 0.0001). For AMP, the PC20 increased from 9.3 (range 1.0-113.3) mg/ml after placebo, to 150.2 (range 32.1-1177.7) mg/ml with terfenadine (P less than 0.0001). This 16.2-fold (range, 5.5-47.9) displacement to the right of the AMP concentration-response curve by a selective histamine-H1 receptor antagonist emphasizes the central role of histamine in the airways response to this nucleotide.

Adult↗

PubMed1989

Effect of an aerosol delivery system on bronchodilator activity.

Metered dose inhalers (MDIs) are often used incorrectly by patients who find difficulty using MDI for drug inhalation. The study was performed in 11 asthmatic patients in four days in order to evaluate the efficiency of a new Drug Delivery System (DDS-InspirEase) for metered dose inhalers. Clenbuterol was administered via DDS and via conventional MDI in a randomized manner. On the first two days, DDS and MDI were used by patients without any physician's help. On the subsequent days, clenbuterol was administered via DDS and via conventional MDI directly by the physician. FEV1 and MEF75 values were measured 15', 30', one hour, and two hours post-drug inhalation. Statistical analysis (ANOVA) showed that clenbuterol delivered by DDS, administered by patients or by physician, produced a greater increase in FEV1 values (P less than .05) and MEF75 values (P less than .01) in comparison to the conventional MDI on each test day. No significant differences existed between physician or patient administration of clenbuterol with DDS and MDI. The results showed a greater bronchodilator effect obtained by clenbuterol delivered by DDS.

Adult↗

PubMed1988

Effect of vasoactive intestinal peptide (VIP) on propranolol-induced bronchoconstriction.

There is now considerable evidence in favor of vasoactive intestinal peptide (VIP) as a neurotransmitter of nonadrenergic noncholinergic nerves in the airways. The purpose of our study was to evaluate the influence of inhaled VIP on bronchomotor tone after a beta-adrenergic- and cholinergic-receptor blockage. The study was performed in six patients with asthma in 4 days. On the first day, a propranolol provocative dose producing a 20% change in FEV1 (PD20) was determined from the individual semilogarithmic dose-response curve. On the other days, the propranolol challenge was performed after inhalation of ipratropium bromide (40 micrograms), VIP (70 micrograms), and both drugs in randomized double-blind order. Statistical analysis was performed by two-way analysis of variance. The results demonstrated that mean propranolol PD20 was 0.14 mg (geometric mean + SD = 1.22). Ipratropium bromide administration, like VIP administration, significantly raised the PD20 value. The administration of both drugs elicited a further remarkable increase of mean propranolol PD20. The results demonstrated that inhaled VIP influences bronchomotor tone and that this effect is independent of the cholinergic blockage.

Adult↗

PubMed1988

Comparative study of the effects of nedocromil sodium (4 mg) and sodium cromoglycate (10 mg) on adenosine-induced bronchoconstriction in asthmatic subjects.

The effect of nedocromil sodium (4 mg; 7.8 X 10(-6) M) on adenosine-induced bronchoconstriction was compared with that of a higher dose of sodium cromoglycate (10 mg; 24.1 X 10(-6) M). Eleven allergic asthmatic patients (mean age 26.28 +/- 12.21 years) were studied. Adenosine (0.03-4.00 mg) was administered as nebulized aerosol. The dose of adenosine producing a 20% change in FEV1(PD20) was calculated from the individual semi-logarithmic dose-response curves. Patients were studied on 4 separate days. On the first day the adenosine challenge was performed; on subsequent days patients were pretreated (20 min before challenge) with either placebo or test drug (nedocromil sodium 2 x 2 mg or sodium cromoglycate 2 x 5 mg) administered by pressurized aerosol in a randomized, double-blind manner. Statistical analysis was performed by two-way analysis of variance. Neither sodium cromoglycate nor nedocromil sodium showed a significant bronchodilator effect. In patients treated with placebo, inhalation of adenosine produced a dose-related bronchoconstriction with a geometric mean PD20 of 0.42 mg. After drug administration the mean PD20 values were 1.29 mg with sodium cromoglycate and 2.30 mg with nedocromil sodium. Both drugs produced a significant increase in mean PD20 value in comparison with placebo and baseline (P less than 0.01). These results demonstrate that nedocromil sodium (4 mg) is significantly more potent than a larger dose of sodium cromoglycate (10 mg) in inhibiting adenosine-induced bronchoconstriction (P less than 0.05).

Adenosine↗

PubMed1988

Effect of nedocromil on bronchospasm induced by inhalation of substance P in asthmatic subjects.

Several studies have demonstrated that neuropeptides are present in peptidergic fibres of bronchial tissue. The aim of the present study was to evaluate in vivo the effect of nedocromil sodium (2 x 2 mg) on bronchospasm induced by inhalation of substance P. Six moderate asthmatic patients, mean age 25.17 years, were studied. Airway response was measured as FEV1 and the dose of substance P (using a dose range of 23-736 nmol) producing a 20% decrease in FEV1 (PD20) was calculated from the individual semilogarithmic dose-response curves. Patients were studied on 3 separate days in a randomized, double-blind manner. On the first day a baseline PD20 value was determined. On subsequent days substance P challenge was performed after pretreatment (20 min before challenge) with either placebo or nedocromil sodium. Student's paired t-test and Wilcoxon's test were used for statistical analysis. The results of this study demonstrated that inhalation of substance P causes a dose-dependent bronchoconstriction and that the bronchoconstriction induced by substance P can be prevented by pre-treatment with nedocromil sodium.

Adolescent↗

PubMed1988

Enhancing effect of dipyridamole inhalation on adenosine-induced bronchospasm in asthmatic patients.

The study was performed on 13 asthmatic patients to determine whether inhaled dipyridamole would act directly by inducing bronchoconstriction or indirectly by potentiating the adenosine-induced bronchoconstriction. The study was performed in 3 consecutive days. On the first day adenosine challenge was performed and the PD20 value calculated. On the other days the adenosine challenge was done 5 min after randomized inhalations of dipyridamole or a control solution. The mean percent change in FEV1 after dipyridamole (delta % = 2.0) and control solution (delta % = 1.0) was not significant. Inhaled adenosine caused bronchoconstriction with a geometric mean PD20 of 1.09 mg. After control solution inhalation, a mean PD20 value of 1.31 mg was observed. Dipyridamole inhalation increased adenosine hyperresponsiveness and in all subjects shifted the dose-response curves of adenosine challenge to the left with a mean PD20 value of 0.40 mg. This enhancing effect of dipyridamole was significant when compared with the baseline value (P less than 0.01) and control solution (P less than 0.01). The study demonstrated that dipyridamole inhalation increased airway responsiveness to adenosine in all subjects. This effect is due to indirect activity of dipyridamole on airways without changes in baseline airway caliber.

Adenosine↗

PubMed1988

Effect of sodium cromoglycate and nifedipine on adenosine-induced bronchoconstriction.

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)

Adenosine↗

PubMed1988

Bronchospasm induced by inhalation of substance P: effect of sodium cromoglycate.

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.

Administration, Inhalation↗

PubMed1987

Influence of asthmatic and rhinitic symptomatology duration on bronchial responsiveness to histamine.

Our Study aimed to investigate the influence of the time in years elapsed from the onset of symptoms on bronchial nonspecific responsiveness in rhinitic and asthmatic patients. The study was performed on 83 asthmatic patients and on 46 patients with allergic rhinopathy. The beginning of the symptoms and years of asthmatic or rhinitic history were particularly investigated. A histamine challenge was performed. The dose of histamine producing at 20% change in FEV1 (forced expiratory volume in one second) was calculated from the individual semilogarithmic dose-response curve (PD20). Bronchial responsiveness to histamine showed wide variability in subjects of two groups, and an overlap of the distribution curves was observed between asthmatic and rhinitic patients. A significant relationship (p less than 0.01) between the years elapsed from the onset of symptoms and bronchial responsiveness to histamine was observed in each group of patients. We noticed that the number of the years passed heightened the bronchial responsiveness to histamine in both groups of patients.

Adolescent↗

PubMedDate not supplied

Particulate air pollution from motor vehicles: a putative proallergic hazard?

Air pollution generated from motor vehicle exhaust has become a major cause for scientific and public concern worldwide over recent years. The rapid and marked increase in the motor vehicle traffic and its associated emissions in urban areas have paralleled a sharp increase in the prevalence of allergic diseases such as asthma and rhinitis. Epidemiological studies have demonstrated a strong association between people living in close proximity to roads with high traffic density and increased allergic symptoms, reduced lung function and increased sensitization to common aeroallergens. Several laboratory-based studies have demonstrated that pollutants emitted from motor vehicles can induce allergic inflammation and increase airway hyperresponsiveness, which may provide an underlying mechanism for the increasing prevalence of allergic diseases. Although the detrimental effects of air pollution on human health have been brought to public attention, it appears that less attention has been given to the potential role of road traffic fumes in the induction of the allergic state. Legislators should consider pollutants emitted from motor vehicle exhausts as a potential pro-allergic hazard, before making important changes in environmental policy.

Humans↗

PubMedDate not supplied

Histamine releasability after adenosine challenge in subjects with allergic and non-allergic rhinitis: possible implications for mast cell priming.

Nasal provocation with adenosine 5'-monophosphate elicits nasal symptoms in subjects with rhinitis. Histamine released from airway mast cells may play a role in adenosine-induced nasal responses. To investigate the possible role of histamine in mediating adenosine-induced nasal responses, we measured its release in the fluid obtained by nasal lavage after adenosine 5'-monophosphate, guanosine 5'-monophosphate, and placebo instillations. Nasal lavages were performed before and 3, 5, 10, 15, 30 and 45 min after challenge with adenosine 5'-monophosphate, guanosine 5'-monophosphate, and normal saline in 11 patients with rhinitis and 7 normal subjects in a double-blind randomized placebo-controlled cross-over study to evaluate symptoms and to monitor changes in histamine levels. No symptoms or significant increases in histamine were observed after guanosine 5'-monophosphate and placebo challenge. Symptom scores increased in response to adenosine 5'-monophosphate challenge in the rhinitic subjects but not in the normal controls. Nasal provocation with adenosine elicited a significant release of histamine in the nasal lavage fluids with an immediate peak response: its median (range) concentration increased from the baseline value of 1.33 (0.16-14.54) ng/mL to 2.68 (0.31-61.11) ng/mL at 3 min. However, increased histamine levels were not associated with nasal symptom scores. When compared to non-atopic subjects, significantly higher levels of histamine were seen in the nasal lavage fluids of the atopic subjects following adenosine challenge. In the atopic subjects, the median (range) histamine concentration increased from the baseline value of 1.54 (0.16-14.54) ng/mL to that of 4.21 (0.70-61.11) ng/mL at 3 min, whereas no increment was seen in the non-atopic subjects, their histamine concentration being 0.81 (0.29-5.56) ng/mL and 0.74 (0.31-14.25) ng/mL at baseline and 3 min after adenosine challenge respectively. These findings indicate that adenosine elicits nasal responses in patients with rhinitis but not in normal controls. Moreover, adenosine elicits an immediate rise in histamine levels in the nasal lavage fluid, with the highest rise in atopic compared to non-atopic volunteers, suggesting that the nasal responses to adenosine may be an index of mast cell priming.

Adenosine Monophosphate↗

PubMedDate not supplied

[The modulator effect of bradykinin with respect to tracheobronchial clearance in healthy subjects].

Bradykinin (Bk), a vasoactive nonapeptide which has been proposed as mediator in the pathogenesis of bronchial asthma, is a potent secretagogue in canine airways and in human nasal mucosa in vivo. A study was carried out in order to evaluate the effect of inhaled Bk on tracheobronchial clearance (TBC), measured by a radioaerosol technique in 10 healthy volunteers. Subjects inhaled Bk (8 mg/mL) or vehicle placebo on two occasions, at least 2 weeks apart, in a double blind and randomized fashion 30 min after radioaerosol inhalation. TBC, expressed as the area under the tracheobronchial radioaerosol retention curve calculated for the first 6 hours (AUC 0-6h), was enhanced in 9 of 10 subjects following inhaled Bk when compared to placebo. The mean values for AUC 0-6h were significantly reduced from 132%.h to 92%.h (p < 0.001) with placebo and Bk respectively. We conclude that Bk has a marked effect on tracheobronchial clearance in normal human airways.

Adult↗

PubMedDate not supplied

[The response of the airways in asthmatic patients to kinin inhalations define a type-B2 receptor profile].

Kinins (i.e. bradykinin, kallidin and [desArg9]-bradykinin) are vasoactive oligopeptides which may contribute as mediators in the pathogenesis of asthma by interacting with specific receptors designated as B1 and B2. The aim of the present study was to investigate the airway response to inhaled histamine, bradykinin, kallidin and [desArg9]-bradykinin in normal and asthmatic subjects. Changes in airway caliber were followed as FEV1 (forced expiratory volume in 1 sec) and as Vp30 (maximum expiratory flow at 30% of the vital capacity). Neither histamine, bradykinin, kallidin nor [desArg9]-bradykinin had any measurable bronchoconstrictor effect in the normal subjects. However, in the asthmatic subjects, histamine, bradykinin and kallidin, but not [desArg9]-bradykinin, produced prompt concentration-related bronchoconstriction. The geometric mean PC20FEV1 (provocation-concentration of inhaled agonist reducing the FEV1 by 20% from baseline) values were 0.027, 0.082 and 0.44 mg/mL for bradykinin, kallidin and histamine respectively. Because bradykinin and kallidin are agonists of B2 receptors and [desArg9]-bradykinin is an agonist for B1 receptors, our data suggest that asthmatic, but not normal, airways are hyperresponsive to kinins and that this potent bronchoconstrictor response is due to a specific pharmacologic effect compatible with the stimulation of B2 receptors.

Administration, Inhalation↗

PubMedDate not supplied

The effect of inhaled furosemide and acetazolamide on bronchoconstriction induced by deep inspiration in asthma.

In some asthmatics deep inspiration causes a sustained bronchoconstration, which is dependent on Ca2+ uptake. Inhaled diuretics protect against bronchoconstriction induced by a variety of indirect stimuli, by inhibiting the ionic fluxes involving Ca2+ uptake across the cell membrane of airway epithelium. The aim of this study was therefore to investigate the protective effect of inhaled furosemide on the bronchoconstriction induced by deep inspiration in asthma and to compare it with the effect of acetazolamide, an inhibitor of carbonic anhydrase devoid of effect on ion cotransport but possessing inhibitory effects on chloride ion influx and Na+/K+ exchange. The study was carried out on three different study days according to a randomized, double-blind, placebo-controlled, crossover design. Nine non smoking asthmatic subjects first performed a series of 9 controlled deep inspirations to TLC followed by forced expirations to RV within 20 min, which caused a decrease of FEV1 > 20% from baseline. Two hours later, the subjects inhaled either furosemide (40 mg), or acetazolamide (500 mg), or saline (placebo) in random order, and then two more deep-inspiration challenges were performed after 30 and 140 mins. The progressive percent decrement of FEV1 caused by deep-inspiration challenge was taken as an index of bronchoconstriction. Bronchoconstriction was significantly blunted at 30 mins, but not 140 mins, after inhaling furosemide (p < 0.01) or acetazolamide (p < 0.05) compared to control. We interpret these results as due to a modulation of ionic fluxes across the smooth muscle cell membrane afforded by inhaled furosemide and acetazolamide.

Acetazolamide↗

PubMedDate not supplied

[Adverse reaction following suspected inhalation of nickel tetracarbonyl: case report].

BACKGROUND: Nickel tetracarbonyl (Ni(CO)4) is a highly toxic chemical that is produced as an intermediate compound in the Mond process of nickel refining. Occupational poisoning due to Ni(CO)4 is not frequent, and up to now about 300 cases have been reported in the medical literature worldwide. OBJECT: A clinical case is reported of an industrial worker who developed clinical symptoms of respiratory distress probably due to accidental exposure to Ni(CO), METHODS: Clinical examination, chest X-ray data, history of exposure to nickel in the presence of carbon monoxide (CO) from a production plant that was located close to the reactor containing nickel, led to diagnosis of respiratory distress due occupational poisoning. RESULTS: Patient history, clinical symptoms that were characteristic of Ni(CO)4 poisoning: mild transient initial symptoms followed within 24 hours by more severe life-threatening events environmental data, history of exposure to nickel near a carbon monoxide (CO) production plant that was located close to the nickel containing reactor, indicated a putative causal relationship between diagnosis and exposure to nickel tetracarbonyl. CONCLUSIONS: The accident that without adequate respiratory therapy might have had fatal consequences, could have been avoided if the rules of technical and procedural prevention had been carefully observed.

Accidents, Occupational↗