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Biomedical subjects

R Polosa

Publications and source records attributed to R Polosa.

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

The effect of treatment with oral corticosteroids on asthma symptoms and airway inflammation.

To improve understanding of the mechanisms of action of oral corticosteroids in asthma, we have conducted a double-blind, placebo-controlled study with prednisolone (20 mg for 2 wk followed by 10 mg for 4 wk) or placebo in 14 and 13 atopic corticosteroid-naive asthmatic subjects, respectively. Before and after treatment subjects underwent bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsy. Treatment with prednisolone, but not placebo, significantly reduced asthma symptoms (from mean +/- SEM total weekly score of 34 +/- 6.2 to 15.7 +/- 3.2, p = 0.02) and albuterol usage (from mean +/- SEM number of puffs/wk of 29.7 +/- 6.2 to 18.2 +/- 3.7, p = 0.01) and significantly increased FEV1 (from 89.8 +/- 4.4% to 99.3 +/- 4.1% of predicted, p = 0.03). There were no significant changes in inflammatory or epithelial cell counts, levels of T-cell activation or albumin concentration in BAL. However, immunohistochemistry of bronchial biopsies showed that in the submucosa prednisolone significantly decreased numbers of mast cells by 62% (from median 45 to 17/mm2, p = 0.01), eosinophils by 81% (from median 30.1 to 5.7/mm2, p = 0.004), and CD4+ T-cells by 68% (from median 64.6 to 18.5/mm2, p = 0.02). In the epithelium only the reduction in the numbers of eosinophils was significant (from median 1.1 to 0/mm of epithelium, p = 0.02). There were no significant changes in any cell counts in the subjects receiving placebo, and comparison of the changes between the treatment groups identified a significant prednisolone-related reduction in submucosal eosinophil and mast cell counts (p = 0.003 and 0.03, respectively). The temporal association between the clinical and physiologic improvement, and the correlation between the magnitude of change in CD4+ T-cell counts in the submucosa and increase in PC20 methacholine (rs = 0.60, p = 0.049) suggests that the reduction in airways inflammatory cell numbers underlies the clinical efficacy of oral corticosteroids.

Administration, Oral↗
PubMed1997

Neutral endopeptidase inhibition with inhaled phosphoramidon: no effect on bronchial responsiveness to adenosine 5'-monophosphate (AMP) in asthma.

Part of the contractile response of adenosine in the asthmatic airways may be due to the activation of peptidergic pathways with subsequent local release of spasmogenic neuropeptides. At present, little is known about the potential role of lung peptidases in modulating adenosine-induced airway dysfunction in humans in vivo. We have, therefore, investigated the change in bronchial reactivity to adenosine 5'-monophosphate (AMP), after treatment with inhaled phosphoramidon, a potent neutral endopeptidase (NEP) inhibitor, in a double-blind, placebo-controlled, randomized study of 12 asthmatic subjects. Subjects attended on six separate occasions, during which concentration response studies with inhaled AMP and methacholine were carried out, initially in the absence of treatment and then after nebulized phosphoramidon sodium salt (10[-5] M) or matched placebo 5 min prior to a bronchoprovocation test with AMP or methacholine. Agonist responsiveness was expressed as the provocative concentration of AMP or methacholine producing a 20% fall in FEV1 from baseline (PC[20,AMP] or PC[20,meth], respectively). When compared to placebo, phosphoramidon failed to potentiate the airway response to AMP. The geometric mean (range) PC20 AMP value of 23.4 (4.4-190.6) mg x mL(-1) after placebo was not significantly different from that of 20.7 (45-100.9) mg x mL(-1) obtained after phosphoramidon. The lack of change in bronchial reactivity to adenosine 5'-monophosphate after phosphoramidon indicates that endogenous airway neutral endopeptidase may not be of physiological importance in modulating the contractile response of adenosine in the airways. Thus, the present data do not support the view that activation of peptidergic pathways with subsequent local release of spasmogenic neuropeptides is important in the airway response to adenosine

Adenosine Monophosphate↗
PubMed1997

Activity of inhaled lysine acetylsalicylate (L-ASA) on bradykinin-induced bronchoconstriction in asthmatics: evidence of contribution of prostaglandins.

When administered by inhalation, bradykinin provokes dose-related bronchoconstriction in asthmatic subjects by a mechanism believed to involve activation of sensory nerve endings. However, little is known of the change in airway responsiveness to bradykinin after cyclo-oxygenase blockade. The aim of the present study was to investigate the effect of the potent cyclo-oxygenase inhibitor, lysine acetylsalicylate (L-ASA), administered by inhalation, on bradykinin-induced bronchoconstriction in a group of 12 asthmatic subjects. The subjects attended the laboratory on four separate occasions to receive nebulized L-ASA (solution of 90 mg x mL(-1)) or matched placebo (glycine, solution of 30 mg x mL(-1)) 15 min prior to bronchoprovocation tests with bradykinin and methacholine in a randomized, double-blind order with at least a 5 day interval. Changes in airway calibre were followed as forced expiratory volume in one second (FEV1), and responsiveness to agonists was expressed as the provocative concentration causing a 20% fall in FEV1 from baseline (PC20). Administration both of L-ASA and glycine solution caused a small but significant acute fall in FEV1 from baseline, with gradual recovery within 20 min. When compared to placebo, inhaled L-ASA reduced the airway responsiveness to bradykinin in 11 of the 12 subjects studied, the geometric mean (range) values for PC20 bradykinin increasing significantly (p<0.001) by 1.7 doubling dose from 0.55 (0.11-5.05) to 1.72 (0.26-6.05) mg x mL(-1) after placebo and L-ASA, respectively. No significant change in airway responsiveness to methacholine was recorded after L-ASA. It is concluded that administration of lysine acetylsalicylate by inhalation protects the asthmatic airways against bradykinin-induced bronchoconstriction, thus suggesting that endogenous prostaglandins may play a contributory role in the bronchoconstriction to kinins in human asthma.

Administration, Inhalation↗
PubMed1997

[Guidelines for the treatment of acute asthma. A critical retrospective analysis].

Acute asthma attacks are frequently observed in common medical practice. However a unified and scientifically proven directive which advises objectively on the best management strategy for patients with acute asthma attacks is still lacking. In the present review we have accurately assessed various important points addressed in the recent international guidelines for acute asthma. This work has enabled us to derive precise and documented suggestions of practical importance which may be useful to the physician for a correct and judicious approach to the management of those patients with acute asthma attacks.

Acute Disease↗
PubMed1996

Inhaled lysine acetylsalicylate (L-ASA) attenuates histamine-induced bronchoconstriction in asthma.

When administered by inhalation, histamine provokes dose-related bronchoconstriction in asthmatic subjects mainly by a direct activation of histamine H1-receptors on airway smooth muscle. However, little is known of the change in airway responsiveness to histamine after cyclooxygenase blockade. The aim of the study was to investigate the effect of the potent cyclooxygenase inhibitor, lysine acetylsalicylate (L-ASA), administered by inhalation on histamine-induced bronchoconstriction in a group of 16 asthmatic subjects. The subjects studied attended the laboratory on four separate occasions to receive nebulized L-ASA (solution of 90 mg/ml) or matched placebo (glycine solution of 30 mg/ml) 15 min before bronchoprovocation tests with histamine and methacholine in a randomized, double-blind order. Changes in airway caliber were followed as forced expiratory volume in 1 s (FEV1), and agonist responsiveness was expressed as the provocative concentration causing a 20% fall in FEV1 from baseline (PC20). Administration of both L-ASA and glycine solution caused a small but significant acute fall in FEV1 from baseline, which returned to normal within 15 min. When compared to placebo, inhaled L-ASA reduced the airway responsiveness to histamine in 13 of the 16 subjects studied, the geometric mean (range) values fro PC20 histamine increasing significantly (P < 0.001) from 1.72 (0.13-5.49) mg/ml to 3.31 (0.36-12.00) mg/ml after placebo and L-ASA, respectively. No significant change in airway responsiveness to methacholine was recorded after L-ASA. Acute administration of L-ASA by inhalation protects the asthmatic airways against histamine-induced bronchoconstriction, thus suggesting that endogenous prostaglandins may play a contributory role in the airways response to histamine in human asthma.

Administration, Inhalation↗
PubMed1996

Safety aspects of local endobronchial allergen challenge in asthmatic patients.

Local endobronchial allergen challenge is being increasingly used to investigate the role of allergic inflammation in asthma. However, little information is available about the safety of this procedure and the changes induced in airway physiology. BAL and biopsy were performed at 10 min and at 4 to 6 h, or 24 h after segmental allergen challenge in 49 patients with atopic asthma. Two hours after challenge, FEV1 was reduced from 97.6 +/- 13.9 (mean +/- SD) to 83.4 +/- 21.7% predicted. FEV1 remained reduced at 4 to 6 h (87.7 +/- 20.4%), but it had nearly returned to baseline by 24 h (93.2 +/- 14.0%). When endobronchial challenge was combined with BAL and biopsy, the initial fall in FEV1 was slightly greater (from 101.8 +/- 14.2 to 78.5 +/- 13.6%). Bronchial responsiveness to methacholine was measured in 10 subjects, and it showed a twofold increase 24 h after local challenge and lavage. Significant changes in FEV1 and methacholine PC20 were still detectable 72 h after challenge. Widespread wheezing occurred in 29% of the subjects, but none of the them had to be admitted to hospital. We conclude that local endobronchial allergen challenge, although producing measurable changes in airway physiology, is in general well tolerated and is an acceptable method to investigate airway pathophysiologic processes in patients with mild to moderate asthma.

Adult↗
PubMed1996

Changes in neurokinin A airway responsiveness with inhaled lysine-acetylsalicylate in asthma.

Endogenously released cyclooxygenase products modulate the bronchoconstrictor response to various stimuli in asthma. Little is known of the change in airway responsiveness to neurokinin A (NKA) after cyclooxygenase blockade. In this randomized, double-blind, placebo-controlled study, we have investigated the effect of the potent cyclooxygenase inhibitor, lysine acetylsalicylate (L-ASA) administered by inhalation, on the bronchoconstrictor response both to neurokinin A (NKA) and methacholine in nine asthmatic subjects. Subjects attended the laboratory on four separate occasions to receive nebulized L-ASA (solution of 90 mg.mL-1) or matched placebo (glycine, solution of 30 mg.mL-1) 15 min prior to bronchial challenge with NKA or methacholine, in a randomized, double-blind order. Changes in airway calibre were followed as forced expiratory volume in one second (FEV1) and agonist responsiveness, expressed as the provocative concentration causing a 20% fall in FEV1 from baseline (PC20). L-ASA elicited a significant fall in FEV1 from baseline. When compared with placebo, inhaled L-ASA reduced the airway responsiveness to NKA in 8 of the 9 subjects studied, the geometric mean (range) values for PC20 NKA increasing significantly from 153.2 (52.0-258.9) to 303.1 (83.4-668.5) micrograms.mL-1 after placebo and L-ASA, respectively. However, no significant change in airway responsiveness to methacholine was recorded after L-ASA, their geometric mean (range) PC20 values being 1.60 (0.17-9.59) and 1.53 (0.09-14.01) mg.mL-1 after placebo and L-ASA, respectively. The small decrease in airway responsiveness to neurokinin A after administration of lysine acetylsalicylate by inhalation suggests that endogenous prostaglandins may play a contributory protective role in the airway response to neurokinin A in human asthma.

Administration, Inhalation↗
PubMed1996

Opposite effects of inhaled bradykinin and [desArg9]-bradykinin on tracheobronchial clearance in normal humans.

Kinins may affect lung mucociliary clearance in man by interacting with specific surface receptors designated B1 and B2. To evaluate this possibility, we have compared the effect of inhaled bradykinin and [desArg9]-bradykinin on mucociliary clearance in healthy volunteers. Four subjects attended the laboratory on three separate occasions to undertake tracheobronchial clearance studies, by a noninvasive radioisotopic technique, followed by inhalation with either bradykinin (8 mg.mL-1), [desArg9]-bradykinin (8 mg.mL-1), or vehicle placebo 30 min after radioaerosol inhalation. Half-hourly whole lung counts were measured for 6 h with two collimated scintillation counters and a tracheobronchial clearance curve was plotted for each subject on each occasion. In all the subjects studied, mucociliary clearance, expressed as the area under the tracheobronchial radioaerosol retention curve calculated for the first 6 h (AUCo-6h) was enhanced after inhaling bradykinin and prolonged following exposure with [desArg9]-bradykinin when compared to placebo. The median values (range) for AUCo-6h were significantly reduced from 123 (83-152)%.h to 92 (51-133)%.h with placebo and bradykinin, respectively, and significantly augmented to 269 (144-331)%.h after exposure with [desArg9]-bradykinin. This small study suggests that acute exposure with inhaled bradykinin accelerates, whilst [desArg9]-bradykinin delays, tracheobronchial clearance in normal human airways.

Administration, Inhalation↗
PubMed1995

Measurements of hormonal peptides in the bronchoalveolar fluid as tumor markers of lung cancer.

A large number of lung cancers contains and releases a variety of neuropeptides such as adrenocorticotropic hormone (ACTH) and beta-endorphin (beta-EP). Although the plasma levels of these peptides have been extensively investigated as possible markers that may help in the early diagnosis of the disease, the data collected have shown their limited clinical usefulness. The present study was undertaken to evaluate whether corticotropin-releasing hormone (CRH), ACTH or beta-EP levels in the bronchoalveolar lavage (BAL) fluid of patients with lung cancer might have been more helpful. To accomplish this, bronchial lavages were carried out in 25 patients affected by lung cancer (17 squamous carcinomas, 4 adenocarcinomas, 2 small cell carcinomas, and 2 not classified) and 18 controls. After centrifugation, BAL fluid was extracted using cartridges of SepPak C-18 and CRH, ACTH and beta-EP levels were measured by radioimmunoassay. CRH and ACTH BAL levels in patients with lung cancer were not significantly different from those of controls. beta-EP concentrations in the BAL fluid were about 200-fold higher than those of ACTH and showed a downward trend (p = 0.08, Mann-Whitney test) in patients with cancer. No histologic tumor type was associated with particularly elevated levels of any of the peptides measured, not even the two patients with small cell carcinoma, a tumor type which tends to release higher peptide levels. Therefore we conclude that measurements of CRH, ACTH and/or beta-EP in the BAL fluid are not useful diagnostic tumor markers of lung cancer.

Adrenocorticotropic Hormone↗
PubMed1995

Pulmonary tuberous sclerosis in a woman of child-bearing age with no mental retardation.

Tuberous sclerosis is a rare disease characterized by epilepsy, mental retardation and adenoma sebaceum. We describe the case of a 29-year-old woman with a clinical history of tuberous sclerosis who also had severe hypoxaemia, multifocal hamartoma-like lesions of various extrapulmonary organs, massive hypersplenism and coagulation defects. This case emphasizes the value of high resolution computed tomography (HRCT) in patients with pulmonary tuberous sclerosis.

Adult↗
PubMed1995

Effect of an inhaled neutral endopeptidase inhibitor, phosphoramidon, on baseline airway calibre and bronchial responsiveness to bradykinin in asthma.

BACKGROUND: Bradykinin is a potent vasoactive peptide which has been proposed as an important inflammatory mediator in asthma since it provokes potent bronchoconstriction in asthmatic subjects. Little is known at present about the potential role of lung peptidases in modulating bradykinin-induced airway dysfunction in vivo in man. The change in bronchial reactivity to bradykinin was therefore investigated after treatment with inhaled phosphoramidon, a potent neutral endopeptidase (NEP) inhibitor, in a double blind, placebo controlled, randomised study of 10 asthmatic subjects. METHODS: Subjects attended on six separate occasions at the same time of day during which concentration-response studies with inhaled bradykinin and histamine were carried out, without treatment and after each test drug. Subjects received nebulised phosphoramidon sodium salt (10(-5) M, 3 ml) or matched placebo for 5-7 minutes using an Inspiron Mini-neb nebuliser 5 minutes before the bronchoprovocation test with bradykinin or histamine. Agonists were administered in increasing concentrations as an aerosol generated from a starting volume of 3 ml in a nebuliser driven by compressed air at 8 1/min. Changes in airway calibre were measured as forced expiratory volume in one second (FEV1) and responsiveness as the provocative concentration causing a 20% fall in FEV1 (PC20). RESULTS: Phosphoramidon administration caused a transient fall in FEV1 from baseline, FEV1 values decreasing 6.3% and 5.3% on the bradykinin and histamine study days, respectively. When compared with placebo, phosphoramidon elicited a small enhancement of the airways response to bradykinin, the geometric mean PC20 value (range) decreasing from 0.281 (0.015-5.575) to 0.136 (0.006-2.061) mg/ml. In contrast, NEP blockade failed to alter the airways response to a subsequent inhalation with histamine, the geometric mean (range) PC20 histamine value of 1.65 (0.17-10.52) mg/ml after placebo being no different from that of 1.58 (0.09-15.21) mg/ml obtained after phosphoramidon. CONCLUSIONS: The small increase in bronchial reactivity to bradykinin after phosphoramidon exposure suggests that endogenous airway NEP may play a modulatory role in the airways response to inflammatory peptides in human asthma.

Administration, Inhalation↗
PubMed1995

Release of mast-cell-derived mediators after endobronchial adenosine challenge in asthma.

Preformed and newly generated mediators released from airway mast cells may play a role in adenosine-induced bronchoconstriction. To investigate the possible role of mast-cell-derived mediator release in mediating bronchoconstriction induced by adenosine 5'-monophosphate (AMP), we have examined the fluid obtained by bronchoalveolar lavage for inflammatory mediators and markers of airway permeability immediately after instillation of AMP directly into an airway segment of 10 asthmatic subjects. Eight subjects completed the protocol. When compared with the saline-challenged segment, the response to endobronchial stimulation with AMP was characterized by a prompt reduction in airway caliber paralleled by a significant rise in PGD2, histamine, and tryptase levels in the lavage fluid. After AMP challenge, the median (range) concentration for PGD2 increased from 36 to 205 pg/ml (p = 0.006), for histamine from 184 to 433 pg/ml (p = 0.018), and for tryptase from 0.30 to 0.54 ng/ml (p = 0.013). In addition, a small but significant rise in albumin levels (from 27.8 to 36.1 micrograms/ml; p = 0.031) was detected after endobronchial challenge with AMP. These findings indicate that adenosine-induced responses may be initiated by the acute release of mast-cell-derived mediators, including PGD2, histamine, and tryptase.

Adenosine Monophosphate↗
PubMed1995

Inhaled lysine acetylsalicylate (L-ASA) attenuates the bronchoconstrictor response to adenosine 5'-monophosphate (AMP) in asthmatic subjects.

When administered by inhalation, adenosine 5'-monophosphate (AMP) provokes dose-related bronchoconstriction in asthmatic subjects by a mechanism believed to involve mast cell mediator release. However, little is known of the change in airway responsiveness to AMP after cyclo-oxygenase blockade. The aim of this study was to investigate the effect of the potent cyclo-oxygenase inhibitor, lysine acetylsalicylate (L-ASA) administered by inhalation, on AMP-induced bronchoconstriction in a group of nine asthmatic subjects. The subjects studied attended the laboratory on six separate occasions to receive nebulized L-ASA (solution of 90 mg.ml-1) or matched placebo (glycine solution, 30 mg.ml-1) 15 min prior to bronchoprovocation tests with AMP, histamine and methacholine in a randomized, double-blind order. Changes in airway calibre were followed as forced expiratory volume in one second (FEV1) and agonist responsiveness was expressed as the provocative concentration causing a 20% fall in FEV1 from baseline (PC20). Administration of both L-ASA and glycine solution caused a small but significant acute fall in FEV1 from baseline, which returned to normal within 15 min. When compared to placebo, inhaled L-ASA reduced the airway responsiveness to AMP in all the subjects studied, the geometric mean (range) values for PC20 AMP increasing significantly from 36.3 (7.9-250.5) to 101.8 (27.2-1300) mg.ml-1 after placebo and L-ASA, respectively. Moreover, nebulized L-ASA induced a small but significant reduction in airway responsiveness to histamine, the geometric mean (range) PC20 values for histamine increasing from 2.77 (1.05-5.49) to 4.36 (1.69-11.24) mg.ml-1 after placebo and L-ASA, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Monophosphate↗
PubMed1995

Inhaled loop diuretics and basal airway responsiveness in man: evidence of a role for cyclo-oxygenase products.

Inhaled frusemide protects asthmatic airways against a wide variety of bronchoconstrictor stimuli by unknown mechanisms. To investigate whether inhaled loop diuretics modulate baseline bronchial responsiveness, a randomized, double-blind, placebo-controlled study was conducted to test the ability of frusemide (40 mg) and bumetanide (2 mg) to displace concentration-response curves with methacholine in 14 healthy volunteers. In addition, separate randomized, double-blind studies were carried out to evaluate the effects of oral flurbiprofen, a potent cyclo-oxygenase inhibitor, on the protective action of frusemide against methacholine-induced bronchoconstriction. Inhaled loop diuretics significantly increased the provocative concentration of methacholine causing a 15% decrease in forced expiratory volume in one second (PC15FEV1) from the geometric mean (range) value of 58.6 (9.2-233) mg.ml-1 after placebo administration, to 129 (13.8-505) and to 106 (6.6-510) mg.ml-1 after administration of frusemide and bumetanide, respectively. Similar results were obtained when data from partial flow-volume curves were used for analysis. In the eight subjects studied, pretreatment with oral placebo and inhaled frusemide reduced airway responsiveness to methacholine, with a geometric mean (range) PC15FEV1 value of 116 (25.4-405) mg.ml-1, and premedication with oral flurbiprofen abolished this protective effect, the geometric mean (range) PC15FEV1 methacholine being reduced to a value of 50.3 (16.6-189) mg.ml-1. In addition, oral flurbiprofen alone failed to alter airway responsiveness to methacholine. In view of these findings, it is suggested that bronchoprotective prostaglandins may mediate the effects of loop diuretics against methacholine-induced bronchoconstriction in man.

Administration, Inhalation↗
PubMed1994

Inhibition of neutral endopeptidase potentiates bronchoconstriction induced by neurokinin A in asthmatic patients.

The endogenous tachykinins exhibit a range of properties which may be relevant in the pathophysiology of asthma. Their effects on the airways seem to be modulated by a variety of lung peptidases, including neutral endopeptidase (NEP). In order to evaluate the potential role of endogenous NEP activity in modulating tachykinins-induced bronchoconstriction in man in vivo, six atopic asthmatic patients, with a mean FEV1 value of 3.38 +/- 0.76 l, and a histamine PD20 mean value of 0.024 mg, were studied. The influence of inhaled phosphoramidon (a potent NEP inhibitor) was examined against the NKA-induced bronchospasm in a double-blind, placebo-controlled randomized study. Changes in airway calibre were followed as FEV1 and agonists responsiveness expressed as PD20 and PD15 for histamine and NKA respectively. Patients received nebulized phosphoramidon sodium salt (10(-5) M) or a control solution 10 min prior to the bronchoprovocation test with NKA. No significant difference was noticed between any of the study days and after inhaled phosphoramidon on baseline FEV1 values (3.29 +/- 0.90 l) in comparison with the control solution (3.31 +/- 0.79 l). Inhaled NKA produced a dose-dependent fall in FEV1 values in all the subjects studied with a mean PD15 value of 20.91 x 10(-9) mol. Phosphoramidon administered by inhalation elicited a significant (P < 0.01 vs baseline and control solution) potentiation in the airway responsiveness to inhaled NKA, the NKA PD15 value decreasing to 9.45 x 10(-9) mol. The present study confirms that inhaled NKA induces a dose-related bronchoconstriction in asthmatic patients and demonstrates that inhaled phosphoramidon potentiates NKA-induced bronchoconstriction.

Adolescent↗