Biomedical subjects

N Frossard

Publications and source records attributed to N Frossard.

At least 55 records · Page 3Linked to original sources

PubMed1998

Serum eosinophil cationic protein measurements in the management of perennial and periodic asthma: a prospective study.

We performed a prospective study in order: 1) to determine whether a correlation could be found between serum eosinophil cationic protein (ECP) levels and clinical and functional status in perennial asthmatics during a 5 month prospective study; and 2) to evaluate the relationship between allergic exposure and ECP levels in periodic asthmatics. Two groups of asthmatic patients were selected: a group of acutely ill perennial asthmatics and a group of periodic asthmatics. The acutely ill perennial asthmatics (n=22, mean age=39.4 yrs) were included on the basis of hospitalization for acute asthma. At the end of the hospitalization, there was a 5 month follow-up of clinical, functional and medication scores, as well as eosinophil counts and ECP levels. The periodic asthmatic group was composed of asthmatics sensitized to birch and tree pollens (n=10, mean age=33.8 yrs). The same measurement were performed on this group, before, during and after the pollen season. Under corticosteroid treatment in the acutely ill patients, there was a significant decrease in serum ECP levels between the first day of hospitalization and the day of discharge (mean: 23.2 microg x L(-1) and 9.5 microg x L(-1), respectively; p=0.006). No correlation was found between the clinical status, functional status and serum ECP levels during the 5 month follow-up. A significant increase in ECP levels was found in periodic asthmatics during the pollen season. Our results suggest that serum eosinophil cationic protein is a useful marker of allergen exposure and of acute asthma treatment. This could be of importance in the prevention and follow-up of allergic asthma; the value of serum eosinophil cationic protein measurements in the day-to-day management of adult asthmatics needs to be further clarified.

Acute Disease↗

PubMed1997

Onset of action in the nasal antihistaminic effect of cetirizine and loratadine in patients with allergic rhinitis.

Several studies have compared the cutaneous efficacy of cetirizine and loratadine and their onset of action. We assessed the nasal effect of these two antihistamines in a randomized, double-blind, crossover, placebo-controlled trial in order to compare objectively their efficacy and onset of action in the noses of patients with allergic rhinitis. Nasal challenge was performed by nebulization of increasing doubling doses of histamine (0, 0.04-1.28 mg/nostril) in 12 patients (eight men, four women, aged 22-39 years). Nasal airway resistance (NAR) was measured by posterior rhinomanometry either 1.5 h or 4 h after intake of cetirizine (10 mg), loratadine (10 mg), or placebo. Baseline NAR was identical between all study days (2.60-2.88 cmH2O.l-1.s). One and a half hours after intake, the increase in NAR induced by histamine was significantly reduced by both cetirizine and loratadine in contrast to placebo. However, with cetirizine the nasal obstruction was significantly lower than with loratadine (P < 0.05). Four hours after intake, a similar inhibition of the nasal obstruction caused by histamine was observed with both cetirizine and loratadine (P < 0.05). In conclusion, this study found cetirizine and loratadine to have similar nasal efficacy at therapeutic dosage 4 h after intake, whereas cetirizine was more effective than loratadine 1.5 h after intake. In agreement with the results observed in the skin, our study suggests a more rapid onset of action of cetirizine in the nose in allergic rhinitis.

Adult↗

PubMed1997

Adenosine reduces airway excitatory non-cholinergic (e-NC) contraction through both A1 and A2 adenosine receptor activation in the guinea pig.

The influence of adenosine and selective A1 and A2 agonists and antagonists was investigated on the cholinergic and the excitatory non-cholinergic (e-NC) contractions induced by electrical field stimulation in the guinea-pig bronchi. Adenosine (10 nM-1 mM) induced a concentration-dependent inhibition of the e-NC contraction (EC50 = 90 +/- 14 microM), whereas the cholinergic peak was only slightly affected. Preincubation of the tissue with the adenosine uptake blocker dipyridamole (10 microM) significantly shifted the concentration-inhibition curve to adenosine to the left (EC50 = 10 +/- 1 microM), suggesting an interaction with extracellular adenosine receptors of A1 and/or A2 subtype. To characterize the receptor type involved in this effect, selective adenosine derivatives were studied. The agonist to both A1 and A2 adenosine receptors, 5'-N-ethylcarboxamidoadenosine (NECA) was more potent than the selective A1 agonist, (-)-R-6-phenylisopropyladenosine (R-PIA), in inhibiting the e-NC contraction (EC50 = 0.10 +/- 0.04 and 0.60 +/- 0.12 microM, respectively, with a maximal inhibition of 70 and 45%, respectively). The concentration-response curve to NECA was shifted to the right by the A2 receptor selective antagonist 3,7-dimethyl-1-propargylxanthine (DMPX) (10 microM) (EC50 = 1.4 +/- 0.5 microM) as well as by the specific A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) (10 microM) (EC50 = 0.7 +/- 0.3 microM). The inhibitory effect induced by the association of both antagonists, DPCPX and DMPX, was considerably potentiated (EC50 > 22 +/- 2.5 microM). The effect of R-PIA was also shifted to the right by DPCPX (EC50 = 8.2 +/- 1.6 microM) but was not modified by DMPX. The contractile response to exogenous substance P was unaffected by NECA pretreatment (0.3 microM). Altogether, these results suggest that adenosine-induced inhibition of e-NC contraction of guinea-pig bronchi is mediated through activation of both A1 and A2 adenosine receptors linked to inhibition of the release of neuropeptides from C-fibre nerve endings.

Adenosine↗

PubMed1996

Phenotypic and quantitative changes in mast cells after syngeneic unilateral lung transplantation in the rat.

1. Lung transplantation causes a total interruption of the inneration and vascularization within the transplanted organ, followed by repair processes. This is frequently associated with bronchial hyper-responsiveness. A common feature of tissue repair is an increase in the number of mast cells. Three phenotypically distinct mast cell subsets, with respect to their protease content, have been identified in rat lung, and it is probable that mast cells of differing protease phenotype fulfil different functions. 2. We have compared the number, protease phenotype and distribution of mast cells in left lung from transplanted and control Lewis rats 1 month after syngeneic unilateral left lung transplantation, without interference of inflammation, graft rejection or of any treatment. Connective and mucosal-type mast cell phenotypes were characterized using antibodies directed against their specific rat mast cell proteases, RMCPI and RMCPII, respectively. 3. After transplantation, RMCPI and RMCPII tissue concentrations increased by 172% and 239%, respectively, compared with controls (13.1 +/- 1.2 and 5.6 +/- 1.0 micrograms/g). 4. Localization of mast cell phenotypes was studied by immunohistochemistry after double immunostaining. The number of mast cells increased after transplantation: the increase in the number of RMCPI-immunoreactive mast cells (RMCPI+) was significant around bronchioles and arterioles, around large vessels and in the pleura. The number of RMCPII+ mast cells also significantly increased around bronchioles and arterioles, as well as in the smooth muscle layer of large airways. Some mast cells stained for the presence of both RMCPI and RMCPII, supporting the existence of co-expressing phenotype in rat lung. The number of mast cells of the RMCPI+/II+ phenotype significantly increased around bronchioles and arterioles and in the pleura. Moreover, the distribution of the mast cell phenotypes was modified in the different areas after transplantation. 5. This indicates a local differentiation/maturation of mast cells after transplantation.

Animals↗

PubMed1996

Activation of the TNF alpha-p55 receptor induces myocyte proliferation and modulates agonist-evoked calcium transients in cultured human tracheal smooth muscle cells.

Evidence suggests that cytokines may modulate smooth muscle cell function in a variety of inflammatory diseases. In the present study, we characterized the specific receptor subtypes that mediate tumor necrosis factor alpha (TNF alpha) effects on myocyte proliferation and on agonist-induced calcium transients in cultured human tracheal smooth muscle cells (TSMC). Pretreatment of human TSMC with TNF alpha potentiated cytosolic calcium [(Ca2+)i] transients evoked by carbachol. In a similar manner, selective TNF alpha-p55 receptor agonists such as htr-9, an activating monoclonal antibody, or a recombinant TNF-p55 (rTNF-p55), which specifically activates the TNF alpha-p55 receptor but not the TNF alpha-p75 receptor, also augmented [Ca2+]i transients evoked by carbachol. In parallel experiments, TNF alpha, rTNF alpha-p55, and htr-9 induced human TSMC proliferation as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Interestingly, activation of the TNF alpha-p75 receptor with a selective agonist, recombinant TNF alpha-p75 (rTNF alpha-p75), or inhibition of the TNF alpha-p75 receptor with utr-1, an inhibitory anti-TNF alpha-p75 receptor antibody, had no effect on TNF alpha-augmented calcium transients or on myocyte growth. To further confirm the receptor specificity of these findings, immunocytochemical studies were performed using receptor-specific antibodies. These studies demonstrated marked cell-surface expression of the TNF alpha-p55 receptor compared with expression of the TNF alpha-p75 receptor on human TSMC. Taken together, our results suggest that TNF alpha modulates agonist-induced calcium transients and induces human TSMC proliferation by specific activation of the TNF alpha-p55 receptor. Further studies addressing the cellular and molecular mechanisms regulating cytokine modulation of airway smooth muscle function may provide new insight into mechanisms that induce airway hyperresponsiveness in asthma.

Antibody Specificity↗

PubMed1996

[New hypotheses in asthma: the mastocytes].

Increasing progress has been made in the understanding of the biology of mast cells. The precursors of mast cells leave the bone marrow in a non-differentiated form as CD34+ cells. The presence of mast cells growth and differentiation factors controls in tissues maturation of different mast cells phenotypes. The main factors are the mast cell growth factor SCF (stem cell factor), NGF (Nerve Growth Factor), and IL-3 (Interleukin-3). The potential role of each of these factors in the airways is discussed. An altered production of these growth factors in the airways of asthmatic patients might be the cause of the presence of an increased number of mast cells and of phenotypic modifications in the bronchi of these patients.

Asthma↗

PubMed1995

Selective recruitment of eosinophils by substance P after repeated allergen exposure in allergic rhinitis.

We have investigated the nasal response to substance P after pollen exposure in seasonal allergic rhinitic patients. Seven patients with strictly seasonal allergic rhinitis were studied during the pollen season, 24 h after nasal challenge with pollen. They received increasing doses of nebulized substance P (0 to 80 nmol) in each nostril. Responses were assessed by measurement of nasal airway resistance by posterior rhinomanometry and quantification of albumin, histamine, and inflammatory cells in the nasal lavage fluid. Nasal airway resistance increased in a dose-dependent manner after substance P challenge. Protein and albumin in nasal lavage fluids increased after administration of substance P: from 2.6 +/- 0.3 to 6.8 +/- 1.1 mg for protein (P < 0.01) and from 0.2 +/- 0.1 to 3.1 +/- 0.6 mg for albumin (P < 0.02). Expressed as a percentage of total protein, albumin increased from 10.5 +/- 3.6% to 39.9 +/- 3.5% (P < 0.02), suggesting occurrence of plasma leakage. No histamine release was observed after challenge with substance P. Total cell counts significantly increased from 11.4 +/- 2.4 to 41.8 +/- 17.3 x 10(3) cells/ml after substance P (P < 0.05). Eosinophils were already numerous before substance P challenge (2.1 +/- 0.7 x 10(3) cells/ml), and the number of eosinophils markedly increased in all patients after substance P (for the whole group, 25.8 +/- 13.3 cells/ml, P < 0.05). In contrast, the number of neutrophils only slightly increased in five patients, and changes did not reach significance for the group as a whole. Our results show that substance P induces nasal obstruction and albumin extrusion in allergic rhinitic patients after repeated pollen exposure. These vascular phenomena are associated with recruitment of eosinophils. Since substance P is known to be released after nasal allergen challenge, our data suggest a role for substance P in the chronic eosinophilic inflammation of the nasal mucosa observed in symptomatic allergic rhinitis.

Administration, Intranasal↗

PubMed1995

5-HT2-mediated bronchial responses after syngeneic lung transplantation in the rat.

1. The effect of lung transplantation was assessed on the subsequent bronchial responses to 5-hydroxytryptamine (5-HT) in the rat in vitro. 2. Bronchial ring segments from syngeneic lung transplant recipients, from sham-operated and from non-operated control animals were studied in organ baths one month after unilateral left lung transplantation. 3. Responses of the bronchial smooth muscle to 5-HT (10(-8) to 10(-4) M) significantly increased after lung transplantation (80.6 +/- 7.6% of the maximal contractile response to acetylcholine) compared with the responses of all other controls (ca. 40% of the maximal contractile response to acetylcholine, P < 0.01). pD2 values were similar for the left transplanted (5.70 +/- 0.11) and all other control bronchi (ranging from 5.53 to 5.82). 4. Contraction to 5-HT was blocked by the selective 5-HT2 antagonist, ketanserin. Responses to the selective 5-HT2 agonist, alpha-methyl-5-HT, were similar to those to 5-HT; pD2 values were similar in all groups (ranging from 5.41 to 5.74). 5. The selective 5-HT3 agonist, 1-m-chlorophenyl biguanide, had no contractile effect on rat bronchus, whether transplanted or not. 6. Atropine, a muscarinic cholinoceptor blocking agent, had no effect on 5-HT-induced bronchial contraction. Hence, acetylcholine released from nerve terminals does not play any role in the observed bronchial hyperresponsiveness to 5-HT. 7. These results show bronchial hyperresponsiveness to 5-HT in vitro one month after lung transplantation in the rat, mediated through 5-HT2 receptor activation. This might be caused by upregulation of 5-HT2 receptors in the lung after transplantation.

Animals↗

PubMed1995

[Airway neuropeptides--what is their role in physiopathology?].

Research work over the last ten years has identified a nonadrenergic, non cholinergic innervation in the upper and lower airways, in man and other animals. This innervation has two components: An excitatory bronchoconstrictor component, of which the neurotransmitters are peptides, substance P, neurokinin A, CGRP and gastrin-releasing peptide. A bronchodilating component known as inhibitor, of which the neurotransmitters are the vasoactive intestinal peptide and nitric oxide. Those neurotransmitters effect all the systems that are involved in allergic respiratory diseases, asthma and allergic rhinitis. They may therefore have a role to play in the physiopathology of these diseases.

Adrenergic Fibers↗

PubMed1994

Do nasal mast cells release histamine on stimulation with substance P in allergic rhinitis?

The effects of nasal administration of increasing doses of exogenous substance P have been studied in patients with allergic rhinitis treated with placebo or with the H1 antagonist cetirizine (10 mg twice daily for 3 days). Responses to substance P were assessed by posterior rhinomanometry (measuring nasal airway resistance) and by measure of histamine, protein and albumin production and cell recovery in nasal lavage fluids before and after challenge. Substance P induced a dose-dependent increase in nasal airway resistance which was similar after treatment with either cetirizine or placebo (maximal increase in nasal airway resistance was 4.2-fold greater than the baseline with the placebo and 4.7-fold greater than the baseline with cetirizine). No histamine release was observed. Similar increases in protein and albumin production were observed after stimulation with substance P along with the placebo (protein: from 0.35 +/- 0.11 to 3.31 +/- 0.62 mg and albumin: from 0.09 +/- 0.04 to 2.08 +/- 0.39 mg) and when combined with cetirizine treatment (proteins: from 0.42 +/- 0.09 to 3.62 +/- 0.77 and albumin: from 0.17 +/- 0.04 to 2.19 +/- 0.51 mg). After stimulation with substance P, percentages of neutrophils recovered in nasal fluids increased from 26.2 +/- 11.5 to 54.5 +/- 9.5 with the placebo and from 35.5 +/- 11.0 to 53.6 +/- 9.5 with cetirizine. Eosinophils were inconsistently found after substance P stimulation during both treatments. In conclusion, nasal response to substance P is not modified by cetirizine which suggests that the effect of substance P is not secondary to histamine release in the nose in man.

Adult↗

PubMed1994

Inhibition of substance P-induced microvascular leakage by inhaled methoxamine in rat airways.

1. The effect of the inhaled alpha-adrenoceptor agonist, methoxamine (MTX), was studied on experimental airway oedema induced by injection of substance P (SP) in the rat. Sprague-Dawley rats (300-350 g) were anaesthetized with sodium thiopentone, tracheotomized and artificially ventilated. 2. MTX or its vehicle was administered by inhalation. Airway resistance and blood pressure were monitored continuously. Evans Blue dye (EB, 20 mg kg-1) was injected through a jugular catheter 1 min before SP (14.8 nmol kg-1). Airways were dissected out, weighed and placed in formamide for EB extraction and determination by spectrophotometry. 3. EB extravasation induced by SP was significantly reduced in distal intraparenchymal bronchi by inhaled MTX at doses of 50 micrograms kg-1 (58 +/- 9 vs 96 +/- 9 ng EB mg-1 tissue after vehicle, P < 0.001) and 100 micrograms kg-1 (69 +/- 11 vs 137 +/- 26 ng EB mg-1 tissue after vehicle, P < 0.01). Inhaled MTX by itself (100 micrograms kg-1) increased blood pressure: 172 +/- 6 vs 132 +/- 10 mmHg baseline (P < 0.02), but neither induced extravasation nor increased airway resistance. 4. In another set of experiments without SP, MTX was administered intravenously 1 min after EB. At 100 micrograms kg-1, i.v. MTX increased blood pressure to a similar extent as inhaled MTX (180 vs 147 mmHg baseline, P < 0.01), increased airway resistance and caused leakage of plasma proteins in distal intraparenchymal bronchi (79 +/- 7 vs 47 +/- 1 ng EB mg-1 tissue, P < 0.02). 5 Similarly, after sequential i.v. injections of doubling doses of MTX (50-800 microg kg-1), a marked EB extravasation was found in the airways. This was abrogated by pretreatment with prazosin (100 microg kg-1)but not with propranolol (2 mg kg-1).6 These results suggest that microvascular leakage and airway oedema induced by i.v. MTX may be linked to an increase in pressure in the pulmonary circulation, resulting from vasoconstriction of the pulmonary vasculature and acute cardiac dysfunction due to systemic hypertension.7 Our results with inhaled MTX show that direct deposition of MTX at the bronchial vasculature induces a reduction in SP-induced microvascular leakage in rat airways and that inhaled MTX does not share the untoward effect of i.v. MTX inducing airway oedema.

Administration, Inhalation↗

PubMed1994

[Neuropeptides of the nasal innervation and allergic rhinitis].

In the last decade, several neuropeptides have been localized in sensory, sympathetic and parasympathetic neurons of the upper and lower airways in animals and man. Tachykinins are sensory neuropeptides: after nasal allergen challenge in patients with allergic rhinitis, substance P is locally released and induces nasal obstruction. Like neurokinin A, another tachykinin of sensory C fibers, substance P induces an increase in vascular permeability and a recruitment of inflammatory cells. Thus, tachykinins partially mimic nasal response to antigen. Calcitonin gene-related peptide (CGRP) is another sensory neuropeptide and vasoactive intestinal peptide (VIP) is a neuropeptide localized to parasympathetic fibers. The distributions of CGRP and VIP fibers and of their binding sites, as well as their physiological effects described in other tissues, are consistent with a vasodilator effect. On the other hand, neuropeptide Y (NPY), a sympathetic neuropeptide, would seem to be a potent vasoconstrictor. Thus, nasal neuropeptides, and above all sensory neuropeptides, could play a role in the pathophysiology of allergic rhinitis.

Allergens↗

PubMed1994

[Bronchial hyperreactivity: neurogenic factors].

Over the last fifty years, the role of neurogenic factors in asthma and bronchial hyperreactivity has been intensively investigated. The roles of the cholinergic and adrenergic nervous systems have been clarified and several sub-types of muscarinic receptors identified. The localisation and functions of both muscarinic and adrenergic receptors have been further specified. It has also been shown that afferent nerve fibers as well as sympathetic and parasympathetic nerve fibers secrete various neuropeptides. The physiological role of these peptides is not yet known but it appears that they have a powerful effect on bronchial smooth muscle tone, microvascular permeability, mucus secretion and secretion of mediators by inflammatory cells. The results of numerous studies suggest that there are several abnormalities in the adrenergic and cholinergic nervous systems of asthmatic patients, but that these abnormalities are not themselves the cause of bronchial hyperreactivity. They may however contribute to enhance it. The role of the various newly identified neuropeptides in the genesis and maintenance of bronchial hyperreactivity remains to be determined.

Adrenergic Fibers↗

PubMed1993

Muscarinic receptors after syngeneic unilateral lung transplantation.

We have characterized the muscarinic cholinergic receptor population by binding assay in left and right lung membranes from syngeneic Lewis rats one month after unilateral left lung transplantation and from controls. The density of muscarinic receptors measured by [3H](-)QNB binding was similar in left and right lung membranes one month after unilateral left lung transplantation (Bmax = 28.2 +/- 2.2 and 29.0 +/- 1.4 fmol/mg protein, respectively) and was similar between transplanted and control rats. Binding affinity also was similar on both sides (Kd = 28.5 +/- 9.5 and 32.3 +/- 2.7 pM, respectively). Binding parameters (Ki) of four selective muscarinic antagonists determined from competitive binding experiments of 0.5 nM [3H](-)QNB showed an order of potency: atropine > 4-DAMP > AF-DX 116 BS > pirenzepine both in transplanted and in control lungs. There was no significant difference in Ki values between left transplanted and right non transplanted lungs (1.8 +/- 0.1 and 1.9 +/- 0.1 nM; 4.3 +/- 0.5 and 3.5 +/- 0.5 nM; 80.9 +/- 13.8 and 78.9 +/- 18.8 nM; 480.4 +/- 40.9 and 481.7 +/- 78.2 nM, respectively for atropine, 4-DAMP, AF-DX 116 BS and pirenzepine). Values were also similar between transplanted and control lungs. These observations suggest a similar population of muscarinic receptors in the transplanted and the non transplanted lung in the Lewis rat. This result is in accordance with the similar physiological effect of exogenous acetylcholine that we previously observed in transplanted and non transplanted bronchi.

Animals↗

PubMed1993

Inhaled substance P induces activation of alveolar macrophages and increases airway responses in the guinea-pig.

Guinea-pigs pretreated with phosphoramidon or saline were treated with an aerosol of substance P (SP) or saline. 24 h later, the pulmonary inflation pressure (PIP) to substance P or to cumulative doses of acetylcholine or of histamine was recorded. The PIP response to SP itself was significantly enhanced in animals treated with phosphoramidon+SP as compared with phosphoramidon+saline (2.5-fold increase 1 min after the end of the inhalation, P < 0.001). The response to acetylcholine and to histamine was also significantly enhanced in phosphoramidon+substance P-treated as compared with phosphoramidon+saline-treated guinea-pigs (PC200 = 38.9 and 1.6 as compared with 77.6 and 3.9 micrograms/ml, P < 0.01 and P < 0.05 respectively). The production of superoxide anions by alveolar macrophages in response to f-MLP was also enhanced after treatment with phosphoramidon+SP as compared with phosphoramidon+saline (6.4 +/- 0.7 and 3.8 +/- 0.3 cpm, P < 0.001 respectively). In animals treated with saline+SP or saline+saline, the PIP responses and the production of superoxide anion were similar. Altogether these results suggest that SP contributes to the bronchial hyper-responsiveness in asthma and this probably through activation of alveolar macrophages.

Acetylcholine↗

PubMed1993

Effect of 5-lipoxygenase inhibitors on the anti-IgE-induced contraction of passively sensitized human bronchus in vitro.

We assessed the effect of 5-lipoxygenase inhibitors on the contraction of human bronchial ring segments passively sensitized with IgE in vitro. Contraction was induced by increasing doses of anti-IgE (0.01-0.5 micrograms/ml) in the presence of the antihistamine mepyramine. Zileuton and MK-886 (10 microM) significantly inhibited the dose-related contraction to anti-IgE as compared with solvent (DMSO). At the highest dose of anti-IgE used, contraction reached 10.3 and 9.6% of the maximal carbachol contraction, respectively, as compared with 30.3% for solvent. Maximal carbachol contraction was unaffected. These results suggest a potential beneficial effect of 5-lipoxygenase inhibitors in anaphylactic reactions in man.

Antibodies, Anti-Idiotypic↗

PubMed1992

Inhibition of histamine-induced nasal obstruction by cetirizine in allergic rhinitis.

This double-blind randomized crossover placebo-controlled study was designed to assess objectively the nasal antihistamine effect of cetirizine in patients with allergic rhinitis and control subjects. Nasal challenge was performed by nebulization of increasing doubling doses of histamine (0; 0.04 to 1.28 mg/nostril) in six patients with allergic rhinitis and six control subjects on cetirizine (2 x 10 mg daily for 3 days) or placebo. Sneezings were counted and nasal obstruction was assessed by subjective scoring and by objective measurement of nasal airway resistance by posterior rhinomanometry. Histamine induced sneezing and a dose-dependent increase in nasal airway resistance and in perceived sensation of obstruction. Responses were greater in patients with allergic rhinitis compared with controls, although of borderline significance for nasal obstruction. Cetirizine totally abolished sneezing and significantly reduced increase in nasal airway resistance and perceived sensation of nasal obstruction both in normal and rhinitic subjects. Our results demonstrate by an objective measurement the nasal antihistamine effect of cetirizine. We propose this simple provocation test to assess the time-course of the effect of antihistamines and to compare the relative potency of related compounds.

Adult↗

PubMed1992

In vitro bronchial hyperresponsiveness after lung transplantation in the rat.

In this study, we examined the effect of unilateral lung transplantation on in vitro responses of bronchial smooth muscle to electrical field stimulation (EFS) and exogenous acetylcholine (ACh). In syngeneic Lewis rats, we compared the contractile responses of the left hilar transplanted bronchus with that of the nontransplanted right bronchus and the left and right bronchi from control and sham-operated animals. Atropine-sensitive bronchial contraction to EFS was greater on left transplanted than on right nontransplanted bronchi at all frequencies and voltages used. In control and sham-operated animals, contractile responses to EFS were identical on left and right sides and similar to the responses of the right nontransplanted bronchus of the lung transplant recipient. Concentration-response curves to exogenous ACh were similar on transplanted and all control bronchi. Intramural cholinergic nerve cell bodies reactive for acetylcholinesterase were present in the transplanted bronchus. We conclude that EFS-induced cholinergic contraction of rat bronchial smooth muscle is enhanced after lung transplantation. Enhancement is not a result of medication, inflammation, or rejection, absent from our syngeneic transplant, or of upregulation of muscarinic post-junctional receptors because the response to exogenous ACh was normal. Hence, an increased release of ACh from cholinergic nerve terminals may occur, due either to hyperexcitability of postganglionic parasympathetic nerves or to loss of inhibitory mechanism resulting from interruption of neural connections with the central nervous system.

Acetylcholine↗