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P Chanez

Publications and source records attributed to P Chanez.

At least 181 records · Page 10Linked to original sources
PubMed1991

[Bronchial asthma: hypodense macrophages of the airway].

Alveolar macrophages (AM), together with other cells such as eosinophils, have been implicated in the bronchial inflammation associated with asthma. Examination of bronchoalveolar lavage (BAL) fluid has shown that these cells are activated and that the degree of activation is correlated with both the clinical severity of asthma and with the level of bronchial hyperreactivity. The cell population recovered by BAL is normally heterogeneous with regard to AM and this study was designed to investigate whether the proportion of hypodense AM is greater in asthmatics (n = 12) compared to normal subjects (n = 10). Our results show that AM from asthmatic donors are mainly found in the fractions corresponding to low densities (1.03 to 1.04 g/ml) whilst those from normal donors are found at higher densities (1.07 g/ml). Examination of the cells by electron microscopy showed that the hypodense AM displayed the morphological characteristics of activated cells in contrast to the normodense AM which had the characteristics of quiescent cells. In order to determine whether this increased activation was a result of an expansion in the AM population following recruitment of monocytes from the medulla, we studied the functional characteristics of cells recovered from each of five fractions as assessed by their ability to release oxygen-derived free radicals. No differences were observed between AM recovered from the five different density fractions in either asthmatics or in normal subjects. In conclusion, if there is a difference in the density of AM from asthmatics as compared to normal subjects, it is unliked to be due to the recruitment of new cells, but rather a result of an accelerated progression from a mature but resting state to an hyperactivated state.

Adolescent↗
PubMed1990

Eosinophilic inflammation in asthma.

BACKGROUND AND METHODS: The importance of eosinophils in the pathogenesis of bronchial asthma is not established. In an attempt to evaluate the role of eosinophilic inflammation in asthma, we compared 10 normal subjects with 43 patients with chronic asthma, 19 of whom had severe disease as assessed by a clinical scoring method described by Aas and by pulmonary-function tests. Eosinophils were counted in peripheral blood and bronchoalveolar-lavage fluid, and in biopsy specimens obtained from the patients and post mortem from 8 subjects without asthma, but not from the 10 normal controls. Eosinophil cationic protein was titrated by radioimmunoassay in the bronchoalveolar-lavage fluid from all subjects and studied by immunohistochemistry in the biopsy specimens. RESULTS: There was a significant increase in the number of peripheral-blood eosinophils in the patients that was correlated with the clinical severity of asthma (P less than 0.001) and pulmonary function (P less than 0.03). Levels of eosinophils and eosinophil cationic protein were increased in the bronchoalveolar-lavage fluid from the patients and were also correlated with the severity of asthma (P less than 0.001 and P less than 0.002, respectively). Hematoxylin-eosin staining of bronchial-biopsy specimens showed that intraepithelial eosinophils were present only in patients with asthma. Immunohistochemical analysis of eosinophil cationic protein revealed that normal subjects had only a few nondegranulated eosinophils deep in the submucosa, whereas all the patients had degranulated eosinophils beneath the basement membrane and among epithelial cells. In some patients there was a relation between the presence of degranulated eosinophils and epithelial damage. CONCLUSIONS: Eosinophilic inflammation of the airways is correlated with the severity of asthma. These cells are likely to play a part in the epithelial damage seen in this disease.

Adult↗
PubMed1990

Comparison between RAST and Pharmacia CAP system: a new automated specific IgE assay.

RAST represents the standard technique to titrate serum-specific IgE and was found to have a higher efficiency in the diagnosis of IgE-mediated allergy than other in vitro tests. Pharmacia CAP system (CAP) is a new solid-phase immunoassay, fully automated, used for the titration of specific IgE antibodies. Results are listed in kilounits per liter, equilibrated against the World Health Organization standard for IgE. RAST and CAP were compared in 106 unselected patients (6 to 59 years) characterized by a detailed clinical history and skin prick tests with standardized allergen extracts. IgE to cat, Dermatophagoides pteronyssinus, Alternaria, orchard grass, olive, and Parietaria pollen were tested; 470 tests were run. The specificity, sensitivity, and efficiency of both in vitro tests ranged from 85.5% to 100% except for olive pollen, in which the sensitivity of both in vitro tests was low (68.2% for the new test and 63.6% for RAST). Except for orchard-grass pollen, the sensitivity and specificity of CAP were better than that of RAST. There was a highly significant correlation between both tests (r range, between 0.864 to 0.987). CAP competes favorably with RAST and has the advantage of being automated and eliciting results in kilounits per liter.

Adolescent↗
PubMed1990

Atrial natriuretic factor (ANF) is a potent bronchodilator in asthma.

The bronchodilating effects of atrial natriuretic factor (ANF) were compared to effects of salbutamol in a double-blind, placebo-controlled, crossover study in eight subjects with asthma and with airflow limitation. ANF was infused intravenously (0.1 microgram/kg/min during 30 minutes) and caused a short-lasting significant (p less than 0.012) bronchodilation in all patients similar in intensity to intravenous salbutamol (0.13 microgram/kg/min). The duration of the effect of the beta 2-agonist, however, was longer. No severe side effects were noted with ANF infusion. ANF may play a role in the modulation of the bronchial tone in humans, but its usefulness in the treatment of asthma remains to be determined.

Asthma↗
PubMed1990

Pathophysiology and treatment of seasonal allergic rhinitis.

Therapeutic approaches to seasonal allergic rhinitis are reviewed in this paper. Pharmacotherapeutic approaches include nonsedative antihistamines, anti-allergic drugs, vasoconstrictors, anticholinergic agents and topical corticosteroids. The choice of treatment depends upon its relative efficacy and safety. Although effective, immunotherapy has been seriously questioned in recent years owing to the occurrence of possibly serious side-effects. Antihistamines are safe and effective for treatment of histamine-mediated symptoms of itching, sneezing and rhinorrhoea. The newer compounds do not cause sedation. For nasal symptoms, topical anti-allergic drugs are not as effective as other treatments. Topical vasoconstrictors are often used, though they cause side-effects when the treatment is prolonged. Anticholinergic drugs are safe and effective for rhinorrhea. Corticosteroids are highly effective for most symptoms, but their administration by oral or parenteral routes cannot be recommended because of side-effects. Topical corticosteroids inactivated by hepatic first pass metabolism are favoured as they are highly effective and safe. Their mechanism of action is not completely understood, but they act through both an anti-inflammatory effect and an anti-allergic activity decreasing mediator release. These drugs are the most effective in the treatment of nasal obstruction because of their anti-inflammatory effect. They are usually administered in response to symptoms, but in the future, it is likely that they will be used prophylactically before the pollen season in order to decrease the priming effect.

Humans↗
PubMed1990

Beta 2-adrenergic receptors on eosinophils. Binding and functional studies.

We have studied the binding characteristics and functional effects of beta-adrenoceptors on human and guinea pig eosinophils. We determined the binding of the beta-antagonist radioligand [125I]pindolol (IPIN) to intact eosinophils obtained from the peritoneal cavity of guinea pigs and from blood of patients with eosinophilia. Specific binding was saturable, and Scatchard analysis showed a single binding site with a dissociation constant (Kd) of 24.6 pM and maximal number of binding sites (Bmax) of 7,166 per cell. ICI 118,551, a beta 2-selective antagonist, inhibited IPIN binding with a Ki value of 0.28 nM and was approximately 5,000-fold more effective than the beta 1-selective antagonist, atenolol. Isoproterenol increased cAMP levels about 5.5-fold above basal levels (EC50 = 25 microM); albuterol, a beta 2-agonist, behaved as a partial agonist with a maximal stimulation of 80%. Binding to human eosinophils gave similar results with a Kd of 25.3 pM and a Bmax corresponding to 4,333 sites per cell. Incubation of both human and guinea pig eosinophils with opsonized zymosan (2 mg/ml) or with phorbol myristate acetate (PMA) (10(-8) and 10(-6) M) resulted in superoxide anion generation and the release of eosinophil peroxidase; albuterol (10(-7) to 10(-5) M) had no inhibitory effect on the release of these products. Thus, eosinophils from patients with eosinophilia and from the peritoneal cavity of guinea pigs possess beta-receptors of the beta 2-subtype that are coupled to adenylate cyclase; however, these receptors do not modulate oxidative metabolism or degranulation. The possible therapeutic consequences of these observations to asthma are discussed.

Adenylyl Cyclases↗
PubMed1990

[Characterization of platelet-activating factor (PAF)-receptors in neutrophilic and eosinophilic granulocytes].

It has recently been shown that the triazolodiazepine WEB 2086 inhibits the platelet-activating factor (PAF)-induced platelet aggregation, bronchoconstriction (J. Pharmacol. Exp. Therap. 1987; 241:974) and microvascular leakage (Br. J. Pharm. 1987; in press) in guinea pigs. In the present study we have determined the PAF antagonistic properties of WEB 2086 in human neutrophil and eosinophil leukocytes. In addition, we have characterized [3H] WEB 2086 as a radioligand in direct binding experiments with these cell types. PAF increased the beta-glucuronidase release from neutrophils with an EC50 of 138 nM. WEB 2086 caused a concentration-dependent inhibition of this PAF effect with an inhibition constant (Ki) of 11.9 nM. Binding of [3H] WEB 2086 to neutrophils was specific, reversible and saturable with a dissociation constant (KD) of 18.9 nM and a maximal number of binding sites of 40000 sites per cell. The characteristics of the binding sites were identical to those of PAF receptors. In human eosinophils PAF induced an increase in lucigenin-enhanced chemiluminescence with an EC50 of 2.5 nM. WEB 2086 competitively inhibited this response with a Ki of 16.4 nM. [3H] WEB 2086 bound to eosinophils with a KD of 18.5 nM, which is in good agreement with the Ki from the functional studies. Our results show that WEB 2086 is a potent and specific antagonist of PAF in human neutrophils and eosinophils. Also, [3H] WEB 2086 appears to be a suitable antagonist radioligand for labelling of PAF receptors in these inflammatory cells. WEB 2086 should be of value in further elucidation of the role of endogenous PAF in asthma through activation of inflammatory cells recruited to the lung.

Azepines↗
PubMed1990

[Role of modern imaging (CT-MRI) in the preoperative evaluation of bronchial cancers. Results in 202 cases].

The authors present the results of a comparative prospective study of the staging 202 bronchogenic carcinomas (T and N) before surgery. The results of CT (202 cases) and MRI (64 cases) were compared with surgical evaluation and pathologic findings. CT and MRI were part of the decisive criteria for therapeutic-surgery choice and were interpreted before surgery. The results showed poor sensitivity for the T and N but better specificity. MRI is superior to CT with the 3 dimensional demonstration and T1 T2 weighted sequences, but its utility remains limited. The authors give their preferred indications for MRI investigation after CT staging. Staging by CT (and MRI) is of great value to avoid impossible thoracotomy and to confirm the findings of mediastinoscopy (suspected N2 and even more N3).

Adult↗
PubMed1990

Generation of oxygen free radicals from blood eosinophils from asthma patients after stimulation with PAF or phorbol ester.

Eosinophils (EOS) may play an important role in the pathophysiology of bronchial asthma because they can release oxygen free radicals and several basic proteins which are cytotoxic to bronchial epithelium. We have studied the response of EOS isolated from the blood of atopic subjects with symptoms of asthma (AS, n = 7) or rhinitis (AR, n = 4) or without symptoms (AA, n = 5) and of subjects with the hypereosinophilic syndrome (HES, n = 5). EOS were separated using metrizamide density gradients and activated in vitro with platelet-activating factor (PAF, 100 nM) or phorbol 12-myristate-13-acetate (PMA, 100 nM). Oxygen free radical generation was assessed by a lucigenin-enhanced chemiluminescence (CL) assay. EOS purity was 83 +/- 1.7% (mean +/- SEM) with greater than 95% viability. Background CL responses of EOS from HES were significantly higher than those from AA (p less than 0.01) and AR (p less than 0.05). Normodense EOS from AS (PAF-induced CL = 90 +/- 27 mV) were more responsive to PAF than were those from AR (17 +/- 13 mV, p less than 0.01) and from AA (23 +/- 14 mV, p less than 0.01). Similar results were obtained with PMA. Hypodense EOS from HES subjects were as responsive as normodense EOS from AS to PMA and PFA. Thus, EOS from AS have an enhanced potential for activation, particularly by PAF; this may represent an important mechanism for the perpetuation of the inflammatory response in asthma, since EOS can also release PAF.

Adult↗
PubMed1990

[Contribution of high resolution x-ray computed tomography to the diagnosis of pulmonary histiocytosis X. Apropos of 12 cases].

The authors studied the value of high resolution computed tomography in twelve patients with pulmonary histiocytosis X. The aim of this study was to define the CT signs. More or less thin-walled air-filled cysts were observed in all but one case, although the subsequent follow-up of this case revealed the development of such cysts 6 months later. Nodules were also present in all but two cases. They sometimes consisted of excavated nodules. Reticulations, "frosted glass" appearance and irregularities of interface--all signs of a classical interstitial syndrome--were observed less frequently. The lesions were always diffuse, cortical and medullary. The predominance for the upper lobes was only observed in 50% of cases. The case examined on 2 occasions during the course of the disease at an interval of 6 months suggested the progression of small solid nodules towards larger, excavated nodules, finally resulting in thin-walled cysts which may eventually coalesce to force a "lacework" appearance. The pathophysiology of this progression of the lesions and therefore of the pulmonary eosinophilic granuloma is discussed by the authors.

Adult↗
PubMed1989

Characterization of PAF receptors on human neutrophils using the specific antagonist, WEB 2086. Correlation between receptor binding and function.

The antagonism of PAF effects by WEB 2086 and the receptor binding of [3H]WEB 2086 were investigated in isolated human neutrophils. WEB 2086 inhibited PAF-induced beta-glucuronidase release and [3H]WEB 2086 bound specifically to high-affinity sites on the cells. Close concordance between affinity constants for WEB 2086 from functional and radioligand-binding studies suggests that WEB 2086 interacts with the neutrophil PAF receptors and that [3H]WEB 2086 may be a useful ligand in investigation of these receptors.

Azepines↗
PubMed1989

Phagocytosis induction of chemiluminescence and chemoattractant increased superoxide anion release from activated human alveolar macrophages in asthma.

Human alveolar macrophages (AM) were demonstrated to generate reactive toxic derivatives of oxygen in many pulmonary disorders. These cells are involved in local inflammation which characterizes bronchial asthma. In the present work, we studied the ability of stimulated macrophages from healthy volunteers, and asthmatic patients to generate oxygen species in vitro. AM obtained by bronchoalveolar lavage were purified by adherence. The production of oxygen species was measured by luminol-enhanced chemiluminescence (CL) after challenge with opsonized zymosan. The maximal values were significantly (p less than 0.03 and p less than 0.01) higher in AM from asthmatics than in AM from healthy subjects. A significant correlation (p less than 0.01) was observed between maximal value of CL and the severity of asthma as assessed by the clinical score. But, no difference was observed between AM from asthmatics in a stable state and healthy subjects. On the other hand, assays for superoxide anion generation emphasized the activation state of these macrophages stimulated by formyl-peptides.

Adult↗
PubMed1989

Substance P activation of bronchoalveolar macrophages from asthmatic patients and normal subjects.

The role of substance P in the pathogenesis of asthma is unclear. Animal studies suggest that it may be important, whereas human studies do not confirm this. Alveolar macrophages can be recovered easily by bronchoalveolar lavage (BAL) and stimulated in vitro. To assess the role of substance P in humans, we tested its ability to stimulate alveolar macrophages from six normal subjects and seven asthmatic patients. BAL cells were separated by adherence and alveolar macrophages constituted 95% of the adherent cell population. Four concentrations of substance P were used (10(-7), 10(-6), 10(-5), 10(-4) M). To assess the non-specific activation of alveolar macrophages we used three concentrations of lipopolysaccharides (LPS) (5, 10, 20 micrograms/ml). The stimulation of alveolar macrophages was assessed by the release of thromboxane B2 by radioimmunoassay. This study indicates that alveolar macrophages are stimulated by LPS but are poorly activated or not at all by substance P.

Adolescent↗
PubMed1989

Inhibition by histamine of platelet-activating-factor-induced neutrophil chemotaxis in bronchial asthma.

Circulating human polymorphonuclear neutrophils are involved in asthma after their migration into the lung by local chemotactic factors. Investigation of the locomotion of neutrophils in Boyden chambers, showed that the chemotactic intensity of the platelet-activating factor (PAF) was similar in cells from healthy subjects and allergic asthmatics, although the optimal effect of the mediator was observed at 10(-6) M and 10(-8) M, respectively. Histamine had no direct chemoattractant effect on neutrophils but inhibited PAF-induced chemotaxis of neutrophils from healthy subjects and allergic asthmatics. This study provides additional evidence that neutrophils are involved in asthma, and points out the interaction between PAF and histamine in the migration of neutrophils to the lung.

Asthma↗
PubMed1989

Effect of theophylline and adenosine on eosinophil function.

Eosinophils may play a critical role in asthma and bronchial hyperresponsiveness, yet the effect of theophylline on their function is not certain. We have examined the effects of theophylline on opsonized zymosan-induced superoxide anion (O2-) release from guinea pig eosinophils harvested from the peritoneal cavity and from human eosinophils obtained by differential centrifugation of blood from patients with peripheral eosinophilia. Theophylline at high concentration (10(-3) M) inhibited O2- release by 27.6 +/- 9.4% (mean +/- SEM, p less than 0.05), whereas at clinically relevant concentrations (10(-6) and 10(-5) M), it significantly potentiated this by 26.8 +/- 9.9% (p less than 0.05) and 36.9 +/- 6.3% (p less than 0.01), respectively. 8-phenyltheophylline (10(-7) to 10(-3) M), which like theophylline inhibits adenosine receptors but does not inhibit phosphodiesterase activity, produced potentiation at all concentrations. Preincubation of eosinophils with adenosine deaminase (0.1 U/ml) enhanced O2- release by 72.4 +/- 15.2% (p less than 0.01), whereas addition of adenosine (3 x 10(-8) to 10(-6) M) reversed the potentiation induced by theophylline (10(-5) M) in a concentration-dependent manner. Inhibition was greater with the A2-selective analog N-ethylcarboxamide adenosine than the A1-selective analog phenylisopropyladenosine, suggesting that A2-receptors are involved. In human eosinophils we have demonstrated a similar effect of theophylline and adenosine on O2- release. Our results indicate that therapeutic concentrations of theophylline may potentiate eosinophil activation in vivo by competing with circulating adenosine for eosinophil A2-receptors. This would be consistent with the lack of effect of theophylline on bronchial hyperresponsiveness, which may be related to eosinophilic inflammation.

Adenosine↗
PubMed1989

[Physiopathology of asthma].

Bronchial asthma is a unique disease; knowledge of the pathophysiology increases rapidly and underlines that is more a syndrome than a disease. Indeed a new definition has been recently proposed: desquamative eosinophilic chronic bronchitis. The airway obstruction, which is responsible for the wheezing breathlessness, is the consequence of a spasm but also an inflammation. After activation of the resident cells in the airways (mast cells, epithelial cells and alveolar macrophages), mediators are released and - in cooperation with the nervous system-recruit inflammatory cells from blood and bone marrow (mainly eosinophils). A kind of vicious circle seems to amplify the initial (allergic or not) event. Desquamation of the epithelium and disposition of collagen on the basement membrane take a quite long time to be cleared after an asthma attack. Mechanisms of repair must be studied in order to improve treatment. Bronchial asthma is not really a disease; indeed a lot of precipitating agents are able to induce and increase bronchial hyperreactivity. Allergy is the most important factor; but environment, hormones and other infectious agents could be quite important in many patients.

Allergens↗