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Biomedical subjects

J Bousquet

Publications and source records attributed to J Bousquet.

At least 19 recordsLinked to original sources
PubMed1992

[Treatment of bronchial inflammation].

Inflammation is a general defence mechanism. It is constant in asthma where it is characterized by the presence of eosinophils in sputum and blood. Treatment of bronchial inflammation is one of the master pieces of therapeutic strategy and relies on inhaled corticosteroids in most cases. These drugs are remarkably effective and can be used for long periods with little or no side-effects, but compliance with treatment must be checked regularly. In all cases, even when corticosteroids are the mainstay of maintenance treatment, bronchodilators must be used simultaneously. The triggering factors must be taken into account and re-evaluated according to the course of the disease. In the short-term all efforts must concentrate on educating the patients and making sure that they comply with their treatment. In the mid-term new, more effective steroids with even less side-effects than the others can be tried. In the long-term anti-inflammatory agents might multiply and be prescribed in combinations for successful cure of a multifactorial syndrome.

Asthma↗
PubMed1992

Extensive variation in evolutionary rate of rbcL gene sequences among seed plants.

Extensive variation in synonymous and nonsynonymous rates of substitution was observed among 50 sequences of the gene coding for the large subunit of ribulose-1,5-bisphosphate carboxylase (rbcL) representing bryophyte, conifer, dicot, and monocot taxa. Relative rate tests revealed rate differences of up to 138% for nonsynonymous substitutions and up to 85% for synonymous ones. Within angiosperms, the annual forms evolved more rapidly, on average, than perennial forms. This rate heterogeneity was more extensive at nonsynonymous sites than synonymous ones, and it resulted primarily from a recent acceleration of substitution rate in many groups of angiosperms.

Biological Evolution↗
PubMed1992

[Mediators and neuromediators in asthma].

The physiopathological mechanisms underlying the multifactorial syndrome that is asthma are very complex and protean. Most probably, they are genetically determined, but they are largely modulated by the environment and by the inflammation of bronchi in which allergy occupies a special place. Chemical mediators of cellular origin interact with each other and with the cells that live or are recruited in the airways. Among these mediators histamine and arachidonic acid metabolites seem to play a predominant role, but the clinical use of antagonists has not confirmed the data obtained in vitro and in vivo in animals and even man. Cytotoxic mediators (cationic proteins, free oxygen radicals) are though to exert their noxious effect directly on the bronchial epithelium. No single neuromediator of the adrenergic and cholinergic system can explain the dysfunctions observed in asthma. Mediators of the non-adrenergic non-cholinergic system seem to be more interesting owing to their potential interaction with cells and with chemical mediators which contribute to the development of a true neurogenic inflammation.

Asthma↗
PubMed1992

Systemic reactions occurring during immunotherapy with standardized pollen extracts.

Specific immunotherapy with standardized extracts administered by a rush protocol can induce systemic reactions (SRs). A prospective study was conducted in 454 pollen-allergic patients (aged 5 to 62 years) (1) to compare the incidence of SRs during a 3-day rush or step protocol, (2) to determine if patients presenting pollen asthma or those allergic to multiple pollen species would have an increased incidence of SRs, and (3) to attempt to decrease SRs. According to their sensitivity, patients received standardized extracts of orchard grass, and/or Parietaria, and/or olive, and/or plane-tree pollen with the same allergenically bioequivalent maintenance dose. Patients 10 years of age and older received 2000 BU; patients younger than 10 years, 1000 BU. The occurrence of SRs was carefully monitored. The incidence of SRs per patient ranged from 2.6% to 31.1%. With the rush protocol, there was a significant decrease in SRs after premedication (p less than 0.015). Severe SRs decreased further when the increase in doses was stopped because large local reactions occurred. Step protocol was only slightly better tolerated than rush protocol. Bronchial adverse reactions occurred more often in patients presenting asthma during previous pollen seasons. No reaction started 45 minutes or later after the last injection.

Adolescent↗
PubMed1992

Indirect evidence of nasal inflammation assessed by titration of inflammatory mediators and enumeration of cells in nasal secretions of patients with chronic rhinitis.

Pathophysiologic mechanisms of perennial rhinitis are poorly understood. The characterization of inflammation was studied in nasal lavage of patients with perennial rhinitis by the enumeration of cells involved in the allergic inflammation and the measurement of six mediators released in nasal secretions to determine whether some mediators were relevant for the etiologic diagnosis and the occurrence of symptoms. Ten healthy subjects and 57 patients with perennial rhinitis were placed into four groups according to the symptoms they presented at the time of the study and the origin of the allergy. Allergy was characterized by the history, skin prick tests to standardized allergens, and RAST. Eosinophil protein X (EPX), tryptase, histamine, myeloperoxidase, prostaglandin D2, and leukotriene C4/D4 (LTC4/D4) were measured in nasal lavage by enzyme assay or radioimmunoassay. Eosinophils and neutrophils were enumerated after cytocentrifugation of the lavage fluid and May Grunwald Giemsa staining. Tryptase, myeloperoxidase and EPX but not histamine levels were increased in all four patient groups. Eosinophils, LTC4/D4, and prostaglandin D2 were significantly (p < 0.001, p < 0.03, and p < 0.01) increased in allergic and symptomatic patients. EPX was significantly increased in symptomatic allergic and nonallergic patients. This study suggests the involvement of mast cells, neutrophils, and eosinophils, but the latter cells appear to have a more prominent role. The importance of EPX and LTC4/D4 in the characterization of chronic symptomatic rhinitis was also observed.

Adolescent↗
PubMed1992

Complete congruence between morphological and rbcL-based molecular phylogenies in birches and related species (Betulaceae).

Estimations of phylogenies from morphological and molecular data often show contrasting results. We compared morphological and molecular phylogenies in an ancient family of woody dicots, the Betulaceae (birch family). The phylogeny of the family was estimated from parsimony analysis of morphological characters in the genera Alnus, Betula, Carpinus, Corylus, Ostrya, and Ostryopsis and from parsimony and distance-matrix analyses of DNA sequences of the chloroplast gene encoding the large subunit of ribulose-1,5-biphosphate carboxylase (rbcL) in the genera Alnus, Betula, Carpinus, Corylus, and Ostrya and in two outgroups, Quercus and Liquidambar. The topologies obtained by the different methods were completely congruent, and bootstrapping strongly supported the division of the family Betulaceae into two major clades, Betuleae (Alnus and Betula) and Coryleae (other members). Only slightly more homoplasy was present in the rbcL sequence data set than in the morphological set. Relative-rate tests indicated that the Coryleae clade had a faster rate of rbcL evolution than did the Betuleae clade. Heterogeneity of rates of morphological evolution also paralleled those for rbcL.

Base Sequence↗
PubMed1992

Immunohistochemical characterization of the cellular infiltration in asthmatic bronchi.

Bronchial biopsies obtained from 16 asthmatic patients and six normal subjects were analyzed by immunohistochemistry. In the asthmatic patients, the total numbers of macrophages infiltrating the airway mucosa were increased. Many of the macrophages had the phenotypic characteristics of blood monocytes. HLA Class II antigen was expressed on infiltrating cells and airway epithelial cells. In biopsies from the asthmatics there was a significant increase in activated eosinophils, but not in neutrophils. There was also a significant increase in the numbers of T-lymphocytes in the asthmatics, but very few B-lymphocytes were detected. These results suggest that lung macrophages may have a central role to play in the mechanisms of the chronic immune-mediated inflammatory response seen in the airway mucosa of asthmatic patients.

Adult↗
PubMed1992

Safety of bronchoalveolar lavage and bronchial biopsies in patients with asthma of variable severity.

The safety of fiberoptic bronchoscopy, bronchoalveolar lavage (BAL), and bronchial biopsies has been questioned in asthma, and current recommendations indicate that bronchoscopies should only be performed in mild to moderate asthma. Moreover, in most studies patients receive premedication with nebulized bronchodilators that may enhance the safety of the procedures. The purpose of this study was to determine (1) whether the overall safety of fiberoptic bronchoscopy, BAL, and bronchial biopsies in mild to moderate asthma could be extended to patients with more severe asthma and (2) whether these procedures are safe without premedication with nebulized bronchodilators. A group of 50 patients with asthma of variable severity (FEV1 ranging from 37 to 107% of predicted values) and 25 healthy volunteers were studied. Bronchoscopy, BAL (250 ml), and four bronchial biopsies were performed in a standardized manner, without premedication with a nebulized bronchodilator, by the same investigator. Safety was assessed by clinical follow-up, continuous recording of arterial oxygen saturation during the procedure with a digital oximeter, and measuring FEV1, FEF25-75, and FVC just before and 5 min after bronchoscopy. Arterial oxygen saturation decreased in asthmatic patients from 97% (range 91 to 99%) (T1) to 92% (range 79 to 98%) (T8) (ANOVA, Fisher's PLSD) and in control subjects from 97% (range 94 to 99%) (T1) to 93% (range 88 to 98%) (T8) (ANOVA, Fisher's PLSD). The fall in arterial oxygen saturation was not significantly different between asthmatic and normal subjects, and there was no correlation between arterial oxygen desaturation and the severity of asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Chest radiography and high resolution computed tomography of the lungs in asthma.

CT scans have been studied only in asthmatics who were smokers, and no such study has been performed in patients with chronic uncomplicated asthma where a permanent bronchial destruction is likely to occur after a long course of the disease. The object of the study was to characterize CT-scan abnormalities and determine whether bronchial destructive lesions may be observed. Fifty-seven adults with chronic asthma of variable severity and etiology and 10 normal subjects were studied. None of the subjects smoked. Chest radiographs and HR-CT scans were performed in all patients. To discriminate between reversible and irreversible CT-scan abnormalities, two examinations were made in 10 patients with acute asthma both before and 2 wk after parenteral high dose corticosteroid treatment. The chest radiographs showed the expected abnormalities of asthma in 37.8% of the asthmatics. CT scans were abnormal in 71.9% of the asthmatics. Reversible abnormalities included mucoid impactions, acinar pattern, and lobar collapse. Irreversible abnormalities included bronchiectasis, bronchial wall-thickening, sequellar line shadows, and emphysema. Most of these abnormalities are likely to be related to bronchial destruction.

Adult↗
PubMed1992

c-fos proto-oncogene expression in bronchial biopsies of asthmatics.

c-fos, a proto-oncogene regulating the transcription of many genes, plays a critical role in the cell cycle and differentiation and may be involved in the regulation of inflammation in asthma. Very low levels of c-fos are detectable in most human cells, and its expression is rapidly and transiently increased by multiple factors, some of which are involved in the airways inflammation of asthma (histamine, eicosanoids, and cytokines). The presence of c-fos protein, as detected by immunofluorescence, and the immunoreactivity of PCNA, a cell proliferation marker, were examined in bronchial biopsies obtained from 12 asthmatics and 10 normal subjects. Biopsies of eight of 12 asthmatics expressed c-fos versus none of 10 normal subjects. The expression was heterogeneous and localized to cells positive for anti-cytokeratin monoclonal antibody, indicating their epithelial origin. On the other hand, PCNA immunoreactivity was only observed in one asthmatic and one control subject but it was not related with c-fos expression. This study demonstrates the induction of c-fos in epithelial cells of asthmatics, suggesting a role for this proto-oncogene in activation rather than in proliferation.

Adult↗
PubMed1992

Comparison between bronchial and alveolar samples of bronchoalveolar lavage fluid in asthma.

BACKGROUND: Cell content of BALF may vary according to the segment of the lung washed. It was proposed to separate BALF into several aliquots, the first sample being more related to bronchi. The present study compared bronchial and alveolar samples by fractionating aliquots of BALF in normal and asthmatic subjects. METHODS: One hundred asthmatic subjects (mean +/- SEM: 37 +/- 1.5 yr in age) were compared with 31 normal subjects (mean +/- SEM: 32 +/- 2.2 yr in age). None of the subjects was a smoker and none was taking drugs that might interfere with the results. The severity of asthma was defined by the clinical score of Aas examining the chronic severity of asthma and ranging from 1 to 5 (range: 1 to 4; mean +/- SEM: 2.2 +/- 0.1) and FEV1 (range: 45 to 130 percent; mean +/- SEM: 82 +/- 1.8 percent of predicted values). Bronchoscopy was done in a standardized manner. A first aliquot of 50 ml of saline each were instilled and the BALF recovered was pooled (alveolar sample). After centrifugation, total and differential cell counts (May Grünwald-Giemsa) were carried out on bronchial and alveolar samples. RESULTS: The alveolar sample contained significantly more cells per milliliter of BALF than the bronchial sample in normal (p less than 0.0077, Wilcoxon test) and in asthmatic subjects (p = 0.0001, Wilcoxon test). Both in normal and asthmatic subjects, bronchial samples contained significantly more neutrophils and epithelial cells and fewer macrophages and lymphocytes than alveolar samples. In asthmatic subjects, the bronchial sample contained a significantly greater percentage of eosinophils than the alveolar sample. Eosinophils were significantly increased in asthmatic subjects for both the bronchial and alveolar samples. Bronchial and alveolar eosinophilia both were correlated with the Aas score (r = 0.25, p = 0.024 and r = 0.38, p = 0.0006, respectively, by Spearman Rank test). CONCLUSIONS: This study shows in a large number of subjects that the cell content of bronchial and more distal segments of the lung is not comparable, indicating that studies should not give pooled data in asthmatic subjects. Moreover, it confirms the presence of BALF eosinophilia in asthmatic subjects.

Adolescent↗
PubMed1992

[Pharmacological properties of salmeterol].

Salmeterol is an original molecule characterized by its long duration of action (greater than 12 hrs in humans). Salmeterol is a highly selective beta-2 agonist that is from 2 to 15 times more potent than salbutamol on beta-2 receptors of bronchial smooth muscle and 10,000 times more potent than isoprenaline on beta-1 receptors. The duration of action of salmeterol on bronchial smooth muscle has been shown to be much superior than all other beta-2 sympathomimetics that have been studied, including formoterol. Salmeterol has two side chains that are linked by a long hydroxycarbon chain. Its long duration of action could be explained by the link to the cell membrane through an exo-site which is distinct from the beta-2 receptor. In vitro and in the animal model, salmeterol has a triple effect: inhibition of the liberation of inflammatory mediators (histamine, prostaglandins, leukotrienes), inhibition of cell influx and of protein extravasation. The relevance of this effect remains to be establish in humans.

Adrenergic beta-Agonists↗