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Biomedical subjects

P Godard

Publications and source records attributed to P Godard.

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

[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

Enhanced esterification process of 5-hydroxyeicosatetraenoic acid (5-HETE) in PMN from asthmatic patients.

Polymorphonuclear neutrophils (PMN) generate 5-HETE which can be retained within cells as free metabolites or esterified into cellular lipids. Since this metabolite has been shown to have certain inflammatory properties, we compared the generation and distribution profile of 5-HETE in A 23187-stimulated PMN from asthmatic patients (AP) and normal subjects (NS). 5-HETE was analyzed using RP-HPLC. After 5 min, total 5 HETE generation was similar in the two populations. However, esterified 5-HETE was significantly enhanced in AP (72 +/- 3% versus 47 +/- 2% of the total synthesis, p less than 0.005), whereas intracellular free 5-HETE was decreased (13 +/- 3% versus 37 +/- 4%, p less than 0.005) and similar low release was observed. Kinetic studies showed that PMN from AP esterified 5-HETE more rapidly and to a greater extent than PMN from NS. By contrast, more intracellular free 5-HETE was recovered in PMN from NS. Esterification seems to be the major pathway of 5-HETE metabolism in PMN from AP. Moreover, we showed that most of the 5-HETE added exogenously was esterified into cellular lipids. In these experimental conditions, PAF-induced migration of PMN was increased. The enhanced ability of PMN to migrate could be due to the increase of 5-HETE esterification process.

Adult↗
PubMed1992

Inhibitory effect of cetirizine on the bronchial eosinophil recruitment induced by allergen inhalation challenge in allergic patients with asthma.

In patients with asthma there is a recruitment of eosinophils in bronchoalveolar lavage fluid (BALF) after the late asthmatic reaction (LAR). Cetirizine is a selective H1 antagonist that inhibits the eosinophil recruitment induced by allergen in the skin. The aim of this study was to evaluate whether cetirizine was able to inhibit the LAR-induced inflammatory reaction. Twelve allergic asymptomatic subjects with asthma (aged 18 to 58 years) without any treatment were enrolled in the study; FEV1 was greater than 83% predicted in each case. An allergen inhalation-challenge test was performed to assess the presence of an LAR. In a double-blind, randomized, placebo-controlled study, the patients were treated for 8 days with either cetirizine, 15 mg twice a day (six patients, group 1), or placebo (six patients, group 2). On day 8, a second allergen inhalation-challenge test with the same allergen was performed, and BAL was realized 24 hours later; as usual 250 ml of saline was instilled by 50 ml aliquots, and the first recovery was analyzed separately. In each case, the LAR observed after treatment was similar to the first one. In placebo-treated patients, an increased number of cells, mainly eosinophils, was observed in the first recovery of BALF compared with the number in subsequent recoveries. These numbers were significantly higher than numbers observed in cetirizine-treated patients. Cetirizine did not modify significantly the allergen inhalation-challenge test, but it inhibited the recruitment of inflammatory cells, mainly eosinophils.

Administration, Inhalation↗
PubMed1992

Chest tumor response measurement during lung cancer chemotherapy. Comparison between computed tomography and standard roentgenography.

Chemotherapy of lung cancer has, until now, been an experimental approach that requires careful evaluation of tumor response. The growing number of lung cancer patients now undergoing chemotherapy has led to a rapid increase in the number of computed tomography (CT) scans performed. Eighty consecutive lung cancer patients (55 non-small cell and 25 small cell lung cancers) were included in a prospective study to analyze whether the standard chest roentgenography is as effective as computed tomography in evaluating tumor response. Both standard chest roentgenography and CT scanning were performed before the chemotherapy began and were repeated after 10 to 12 wk of treatment. Response evaluations were performed according to the World Health Organization recommendations. When two-dimensional measurements were possible, the indicator lesions were defined as measurable tumors. Both roentgenography methods were used, independently, to classify the response into the following categories: complete response, partial response, minor response, stable disease, and progressive disease. A comparison of CT scans versus standard chest roentgenography as a measurement of indicator lesion showed a concordance of borderline significance (kappa = 0.146, p less than 0.05); a significant asymmetry was demonstrated (McNemar = 35.6, p less than 0.001), indicating that CT scanning may be a more appropriate method for measuring tumors than standard chest roentgenography. Moreover, no concordance was observed comparing CT scan and standard chest roentgenography measurability in the subgroups of patients with T3 or T4 tumor, hilar tumor, and patients with pleural effusion or atelectasis in which the McNemar test of symmetry constantly showed a better measurability using CT scan.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
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

Increased oxygen species generation in blood monocytes of asthmatic patients.

Besides eosinophils, inflammatory processes in asthma are characterized by an infiltration of inflammatory cells, including mononuclear phagocytes, such as alveolar macrophages (AM) and blood monocytes, in the airways. Monocyte activation has been observed in the blood after exercise or allergen-induced asthma. Stimulated AM in chronic and stable asthmatic patients have been shown to release oxygen species. We thus investigated the intensity of the activation of monocytes from 18 asthmatic patients compared with 18 healthy subjects. Oxygen species release was analyzed for monocytes in suspension by chemiluminescence using a luminometer and for monocytes maintained in adherence using conventional assay and video imaging camera. Circulating blood monocytes in suspension from asthmatic patients and control subjects showed the same baseline free radical release. Monocytes in suspension from asthmatic patients were more stimulatable by PMA: specifically, monocytes release more H2O and peaks of O2-. are sooner; moreover, peaks of total free radical release are higher, and this plateau is sustained. Compared with monocytes from control subjects, those from asthmatic patients evaluated after adherence show a higher baseline for O2-. and higher total free radical release. Monocytes from asthmatic patients spontaneously release more O2-. over time in nonstimulated cells and release more O2-. with PMA stimulation; they show the same peak level total free radical release as those from control subjects after stimulation. SOD activity analysis on adherent monocytes was lower in asthmatic compared with control subjects. These data show that monocytes from asthmatic patients were activated compared with control monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acridines↗
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

[Effects of Tilade in asthma].

When administered in a single dose, nedocromil can inhibit the effect of various stimuli: adenosine, SO2, cold air, smog, tachykinins, metabisulfite, exercise and antigen. When administered in a chronic way, this preparation diminishes bronchial hyperresponsiveness. In a clinical study done in England, nedocromil has improved asthma symptoms, PEFR and the need for inhaled beta-2-sympathomimetics. In a study carried out in Israel, nedocromil given for 6 weeks has resulted in an improvement in FEV1 of 0.5 l. In an international study, nedocromil has been preferred to placebo by asthmatic subjects and physicians. Nedocromil can therefore be proposed in: 1) mild asthma, as a long term treatment, with or without allergic causes; 2) in moderate asthma to improve symptoms; 3) in severe asthma to reduce the need for oral steroids (?) There is a need for widening the delivery system of nedocromil, which is only available in a metered-dose inhaler and to find more powerful formulations.

Adrenal Cortex Hormones↗
PubMed1992

Formation of lipoxins and leukotrienes by human alveolar macrophages incubated with 15(S)-HETE: a model for cellular cooperation between macrophages and airway epithelial cells.

Human alveolar macrophages (AM) from bronchoalveolar lavage of asthmatic patients (AP) and healthy volunteers (HS) were compared for their respective capacities to produce lipoxins and leukotrienes when stimulated by calcium ionophore A23187 with or without 15(S)-HETE. The metabolites were analyzed using an isocratic RP-HPLC system and their formation profiles evaluated on the basis of chromatographic behaviour, UV spectral characteristics and co-elution with synthetic standards. Without 15-HETE, AM from AP produced more LTB4 and 5-HETE than those from HS. In the presence of 15-HETE, human AM were able to produce 5,15-diHETE and lipoxins. Moreover, the total amount of lipoxins synthesized by AM from AP was 2 fold higher than that synthesized by AM from HS, thus showing an enhanced cell activation via the 5-lipoxygenase (5-LO) pathway. These results presented AM as in vitro 15-HETE metabolizing cells and suggested some hypothesis about human AM 5-LO regulation mechanism. The enhanced 5-LO activity in AM from AP suggested that in vivo they could participate in cell to cell interaction mechanisms involved in inflammatory lung diseases and might also take up and transform 15-HETE predominantly released by airway epithelial cells.

Adult↗
PubMed1992

[Prolonged effect against exercise-induced bronchospasm: salmeterol versus sodium cromoglycate].

Nineteen subjects with isolated exercise-induced asthma (FEV1, FEF25-75%, PEFR, FVC greater than 95% predicted values, fall in FEV1 of at least 15% after exercise, typical recent symptoms of exercise-induced asthma, no other treatment) were entered in a multicenter trial carried out in a double blind, double placebo, cross-over manner. After a one-month baseline period, subjects underwent an exercise after inhaling 100 micrograms of salmeterol (n = 12) or 40 mg of sodium cromoglycate (n = 7). Treatments were alternated before the second exercise which took place at least 2 days after the first. Efficacy was assessed by examining changes in FEV1, FEF25-75% after exercise carried out 30 minutes and 7 hours after administering the treatment by comparison with baseline values (assessments done 1, 10 and 30 minutes after exercise, lowest of three values kept for the analysis of each parameter). FEV1 and FEF25-75% were significantly higher 30 minutes after taking salmeterol. Salmeterol was found to be superior to sodium cromoglycate for all parameters 7 hours after administering the drug. Both treatments were well tolerated. This study confirms that the longer duration of effect of salmeterol and its superiority by comparison with the standard treatments of exercise-induced asthma.

Adrenergic beta-Agonists↗
PubMed1992

Antihistamines in the treatment of asthma.

Histamine is an important mediator of asthma. The new anti-histamines which block histamine at the H1-receptor level also possess some anti-allergic properties. At current dosages they appear to be safe. These drugs are effective in the treatment of rhinitis and conjunctivitis but their role in asthma is still under investigation. At a dose higher than usually recommended, they were shown to block exercise-induced asthma and, inconstantly, the early phase reaction after allergen challenge. Their effect on the late phase allergic reaction as well as their clinical efficacy during trials is, however, less consistent. The indication of H1-blockers in the treatment of asthma is therefore limited, especially since doses higher than recommended may lead to adverse reactions.

Asthma↗
PubMed1992

In vitro activation of bronchoalveolar lavage cells by house dust mite allergens.

Mast cells represent a small but important proportion of bronchoalveolar lavage cells and are directly exposed to environmental triggers including allergens. Histamine and PGD2 are mediators released during the activation of mast cells. Fourteen patients allergic to Dermatophagoides pteronyssinus were studied. After bronchoalveolar lavage the unfractionated cell pellet containing metachromatic cells was submitted to allergen challenge using three concentrations of a standardized Dermatophagoides pteronyssinus extract and one concentration of A23187 (2.5 microM). The release of histamine was measured by radioimmunoassay using a monoclonal antibody against acylated histamine and PGD2 was measured by enzyme immunoassay using a polyclonal antibody against methoxamine-PGD2. Histamine was released in 13/14 patients following stimulation of the cells with A23187 and 12/14 patients after stimulation with Dermatophagoides pteronyssinus extract. The release of histamine was 3.5-fold greater when cells were stimulated by the Dermatophagoides pteronyssinus extract than with A23187. PGD2 was released in 10/12 patients when cells were stimulated with A23187 and 6/14 patients in the case of Dermatophagoides pteronyssinus extract stimulation. In the latter case, the mean release was not significantly greater than baseline. For histamine, the maximum release usually occurred with the more concentrated extract whereas in the experiments where PGD2 was released, maximal generation usually occurred with the lowest concentration used. There was no correlation between the severity of asthma and the release of mediators. This study confirms the activation of metachromatic cells by allergen and shows some heterogeneity in the release of granule and membrane-derived mediators.

Adult↗
PubMed1992

Airway macrophages releasability in bronchial asthma.

Asthma is a multifactorial disease on genetic basis. Its development is influenced by maternal and environmental factors, i.e. allergens and adjuvants. Early identification of candidates at high risk for development of asthma will enable giving recommendations on preventive measures focussing on exposure to tobacco smoke and other pollutants, indoor and outdoor allergens and possibly viral infections during infancy.

Asthma↗
PubMed1992

[Bronchial epithelium and asthma].

Asthma is a type of chronic desquamative bronchitis and, so far, the role of the bronchial epithelium in this disease has not been fully assessed. There are at least 3 ways by which bronchial epithelial cells may modulate the pathophysiology of asthma: 1. They are resident cells, capable of liberating pro-inflammatory mediators, which may be chemotactic for other cells such as neutrophils and eosinophils. 2. An asthmatic attack results in desquamation of the bronchial epithelium which may have multiple consequences. 3. A repair phase must follow the desquamation although the precise mechanisms underlying this phase are incompletely understood. The level of reparation is likely to play an important role in the prognosis of the disease.

Asthma↗