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Biomedical subjects

N Meslier

Publications and source records attributed to N Meslier.

At least 19 recordsLinked to original sources

[Profiles of 939 patients with obstructive sleep apnea syndrome treated with continuous positive pressure].

The aim of this study was to analyze the characteristics of patients on long-term continuous positive pressure therapy for obstructive sleep apnea in order to determine the efficacy, observance, tolerance, degree of patient satisfaction and patient quality of life using the Nottingham scale. A questionnaire was sent to 939 patients treated for at least six months in 11 centers. Factorial analysis of multiple correspondences and two classification analyses were used to establish patient profiles. Factorial analysis evidenced a relationship between patient satisfaction, reduced symptoms, observance and tolerance. The classification analyses distinguished three groups. Group A (n = 596) included primarily men (93%) who were satisfied with the treatment (99%) and showed good observance. Group B (n = 284) was characterized by patient satisfaction, observance, improved symptoms and lower quality of life than group A. Group C was composed of older patients who were satisfied with their treatment and showed good observance but who had no notable improvement in their symptoms. In conclusion, this study pointed out the difficulty in defining which patients with obstructive sleep apnea would benefit most from continuous positive pressure therapy. Good observance is not a sufficient criterion for therapeutic efficacy.

Adult↗

A French survey of 3,225 patients treated with CPAP for obstructive sleep apnoea: benefits, tolerance, compliance and quality of life.

The aim of this study was to investigate in a large population of patients with obstructive sleep apnoea and on long-term treatment with continuous positive airway pressure (CPAP) the patients' perception of symptomatic improvement, side-effects and quality of life. Questionnaires were mailed via local respiratory homecare associations to 5,339 French patients who had been treated at home for at least 6 months with CPAP machines and who continued their treatment. In total, 3,225 questionnaires were analysable. More than 80% of the responding patients reported that CPAP treatment had greatly improved their symptoms. Despite discomfort related to nasal problems and excess noise from the blower, the mean rate of use for the whole population was 6 h 36 min+/-2 h 15 min. The perceived health evaluated by the Nottingham Health Profile was good (mean score <50) for at least 75% of the patients in each dimension explored. The perceived health was significantly related to the improvement in symptoms, the overall satisfaction and the objective compliance. This retrospective study indicates that patients who continued continuous positive airway pressure treatment for more than 6 months felt a great improvement in their symptoms, were satisfied with the treatment and had a relatively good perception of their health.

Adult↗

Simultaneous laboratory-based comparison of ResMed Autoset with polysomnography in the diagnosis of sleep apnoea/hypopnoea syndrome.

ResMed Autoset (AS) is a simplified diagnosis system for obstructive sleep apnoea/hypopnoea syndrome (OSAS) based on the respiratory flow/time relationship by pressure variation measured through simple nasal prongs. A multicentre prospective trial was used to compare AS and polysomnography (PSG) for diagnosing 95 patients, with suspected OSAS. Physicians gave a pretest probability of the patient having OSAS. The apnoea/hypopnoea index (AHI) was compared between the two methods of diagnosis for the whole population and for subgroups according to the pretest probability. Twenty-four patients had AHI < 15 events x h(-1) on PSG and 19 AHI 15-30, and 52 patients had AHI > or = 30. Correlation between AHI assessed by AS and PSG was r=0.87 for total sleep time (TST), p<0.0001. A Bland and Altman plot gave an agreement between the two methods of +/-40%. For a threshold of AHI > or = 15 events x h(-1) to diagnose OSAS, AS has a sensitivity of 92%, specificity of 79%, positive predictive value of 93% and negative predictive value of 76%. With a pretest probability > or = 80%, sensitivity and positive predictive value were 98 and 100% respectively. Of six false negative, four had a high pretest probability (> 80%) or Epworth score > or = 10. Using these parameters as a criterion for proceeding to PSG after a negative AS study would mean that two apnoeic patients (AHI 20 and 17 events x h(-1) by PSG) would escape detection. The Autoset is useful for the detection of obstructive sleep apnoea but with high pretest probability and a negative Autoset result polysomnography should be performed.

Adult↗

Accidents in obstructive sleep apnea patients treated with nasal continuous positive airway pressure: a prospective study. The Working Group ANTADIR, Paris and CRESGE, Lille, France. Association Nationale de Traitement à Domicile des Insuffisants Respiratoires.

Many studies have shown a relationship between obstructive sleep apnea (OSA) and accidents, but to our knowledge, none have investigated prospectively the effects of treatment with nasal continuous positive airway pressure (CPAP). CPAP was proposed to 973 patients, of whom 893 patients actually underwent CPAP. These patients were consecutively invited to enter a prospective follow-up study including a questionnaire before treatment and after 6 and 12 months of treatment; 547 patients completed the study (153 left the study, and only partial data were available for 193). The baseline questionnaire included questions concerning accidents in the previous 12 months, asking whether patients had had an accident and, if so, whether they felt that the accident(s) were related to sleepiness, and whether the patients felt that they had had near-miss accidents due to sleepiness. The questionnaires at 6 and 12 months included the same questions referring to the previous 6 months; the accidents reported on each follow-up questionnaire were cumulated and compared with the accidents during the 1-year period before treatment. The number of patients having an accident decreased with treatment for real accidents (from 60 to 36; p<0.01), as well as for near-miss accidents (from 151 to 32; p<0.01). The average number of accidents per patient also decreased, for real accidents (from 1.6+/-1.3 to 1.1+/-0.3; p<0.01) and for near-miss accidents (from 4.5+/-6.5 to 1.8+/-1.4; p<0.01). The cost, in terms of days in hospital related to accidents, decreased from 885 to 84 days. With caution due to the absence of a control group, it is suggested that treatment with CPAP decreases the number of accidents occurring in OSA patients. This result may have important implications in the evaluation of the cost/benefit ratio when treating OSA patients.

Accidents↗

Wheezes.

Wheezes are continuous adventitious lung sounds. The American Thoracic Society Committee on pulmonary nomenclature define wheezes as high-pitched continuous sounds with a dominant frequency of 400 Hz or more. Rhonchi are characterized as low-pitched continuous sounds with a dominant frequency of about 200 Hz or less. The large variability in the predominant frequency of wheezes is one of the difficulties encountered with automated analysis and quantification of wheezes. The large variations observed in automated wheeze characterization emphasize the need for standardization of breath sound analysis. This standardization would help determine diagnostic criteria for wheeze identification. The mechanism of wheeze production was first compared to a toy trumpet whose sound is produced by a vibrating reed. The pitch of the wheeze is dependent on the mass and elasticity of the airway walls and on the flow velocity. More recently, a model of wheeze production based on the mathematical analysis of the stability of airflow through a collapsible tube has been proposed. According to this model, wheezes are produced by the fluttering of the airways walls and fluid together, induced by a critical airflow velocity. Many circumstances are suitable for the production of continuous adventitious lung sounds. Thus, wheezes can be heard in several diseases, not only asthma. Wheezes are usual clinical signs in patients with obstructive airway diseases and particularly during acute episodes of asthma. A relationship between the degree of bronchial obstruction and the presence and characteristics of wheezes has been demonstrated in several studies. The best result is observed when the degree of bronchial obstruction is compared to the proportion of the respiratory cycle occupied by wheeze (tw/ttot). However, the relationship is too scattered to predict forced expiratory volume in one second (FEV1) from wheeze duration. There is no relationship between the intensity or the pitch of wheezes and the pulmonary function. The presence or quantification of wheezes have also been evaluated for the assessment of bronchial hyperresponsiveness. Wheeze detection cannot fully replace spirometry during bronchial provocation testing but may add some interesting information. Continuous monitoring of wheezes might be a useful tool for evaluation of nocturnal asthma and its treatment.

Asthma↗

[Chronic respiratory diseases from tobacco use].

Cigarette smoke exerts significant deleterious effects on both lung structures and function. Tobacco alone is the most important risk factor for the development of chronic obstructive lung disease (COLD). The responsibility of smoking for the occurrence of COLD has been demonstrated by epidemiological studies and anatomicopathological findings. Smoking-related lesions initially involve the small airways and remain silent for a long time. There are still uncertainties concerning the mechanisms through which some smokers develop clinical COLD. The clinical diagnosis of COLD rests on the demonstration of dyspnoea by meticulous questioning. Only respiratory function tests can assert the presence of bronchial obstruction. These tests also are necessary to evaluate the severity of the disease, determine its prognosis and follow up its course. In clinical practice the early diagnosis of COLD rests on repeated measurements of FEV1 in smokers.

Forced Expiratory Volume↗

Effect of interferon-gamma on the 5-lipoxygenase pathway of rat lung macrophages.

In view of conflicting reports concerning the effect of macrophage activation on arachidonic acid metabolism, we examined the effect of the macrophage activator, interferon-gamma (IFN-gamma), on the 5-lipoxygenase pathway in rat lung macrophages. Rat lung macrophages were conditioned in the presence or absence of 10(2) U/ml IFN-gamma for 4 h before stimulation with 1 microM A23187 for 15 min or 100 micrograms/ml opsonized zymosan for 60 min at 37 degrees C as well as other stimuli. Lipoxygenase products in extracted cell supernatants were identified and analyzed by high-pressure liquid chromatography and ultraviolet spectroscopy. The predominant lipoxygenase products included leukotriene (LT) B4, LTC4, and 5-hydroxyeicosatetraenoic acid (5-HETE). These products were not qualitatively altered by conditioning with IFN-gamma. However, 5-lipoxygenase pathway activity, as measured by LTB4 release, was maximally increased 2-fold after conditioning with IFN-gamma and stimulating with either A23187 or opsonized zymosan. IFN-gamma-conditioned macrophages, stimulated with A23187, released greater quantities of lipoxygenase products in comparison with control cells (307.6 +/- 13.3 versus 167.6 +/- 3.9 pmol LTB4/10(6) cells) (mean +/- SEM) (P less than 0.05). Similar results were obtained with the less potent stimulus, opsonized zymosan. IFN-gamma had no direct stimulatory effect on the 5-lipoxygenase pathway. No effect was observed with a variety of other stimuli with or without IFN-gamma conditioning.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Leukotriene A4 hydrolase activity of human airway epithelial cells.

Human tracheal epithelial cells were incubated with LTA4 and metabolic products were identified in extracted supernatants by high pressure liquid chromatography, ultraviolet spectroscopy, and gas chromatography-mass spectrometry. In the presence of epithelial cells, LTA4 was converted to LTB4, but not to LTC4 or LTD4. Maximum LTB4 was released at an LTA4 concentration of 3 microM and had occurred by 30 min. LTB4 release was increased in the presence of albumin, but was not affected by extracellular calcium or A23187. This LTA4 hydrolase activity had a slower time course and could not be clearly inactivated by repeated exposure to substrate as is the case for previously described LTA4 hydrolase enzymes. This hydrolase appears to have novel biochemical characteristics.

Chromatography, High Pressure Liquid↗

Biosynthesis of paf-acether. Paf-acether but not leukotriene C4 production is impaired in cultured macrophages.

After adherence for 24 or 48 h mouse peritoneal macrophages, upon a zymosan challenge, synthesized 114 +/- 55 and 82 +/- 31 pmol of paf-acether (paf)/mg of protein respectively, as compared with 513 +/- 195 pmol of paf/mg of protein in 2 h-adherent macrophages (means +/- S.D., n = 10). By contrast, 24 h- and 48 h-adherent macrophages exposed to zymosan produced more leukotriene C4 (2.7 +/- 1.1 and 1.4 +/- 0.2 nmol/mg of protein respectively, n = 5) than did 2 h-adherent macrophages (0.5 +/- 0.2 nmol/mg of protein, n = 5). Paf production was not altered when 2 h- and 24 h-adherent cells were cultured and/or stimulated in the presence of 5 microM-indomethacin, 10 microM-nordihydroguaiaretic acid or 100 microM-BW755C as compared with untreated cells. These results indirectly exclude the regulation of paf production by arachidonic acid metabolites. We investigated the efficiency of the enzymic steps which govern paf synthesis. We showed that the anabolic process was not impaired since (1) the amounts of alkylacylglycerophosphocholine and lyso-paf were similar in 2 h-, 24 h- and 48 h-adherent macrophages; (2) adding synthetic lyso-paf or acetyl-CoA to intact cells did not increase paf production in zymosan-stimulated 24 h- and 48 h-adherent macrophages; (3) the basal level of acetyltransferase was comparable in 2 h-, 24 h- and 48 h-adherent macrophages and in all cases was increased by 2-3 times upon zymosan challenge. We also showed that impaired paf production in 24 h- and 48 h-cultured macrophages was not due to the nature of the stimulus used to induce its synthesis.

Acetyltransferases↗

Transcellular lipoxygenase metabolism between monocytes and platelets.

We have examined the effects of co-culture and in vitro co-stimulation on lipoxygenase metabolism in monocytes and platelets. Monocytes were obtained from the peripheral blood of normal volunteers by discontinuous gradient centrifugation and adherence to tissue culture plastic. Platelets were obtained from the platelet-rich plasma of the same donor. When 10(9) platelets and 2.5 x 10(6) monocytes were co-stimulated with 1 microM A23187, these preparations released greater quantities of 12(S)-hydroxy-10-trans-5,8,14-cis-eicosatetraenoic acid, 5(S),12-(S)dihydroxy-6,10-trans-8,14-cis-eicosatetraenoic acid, and leukotriene C4, 5(S)-hydroxy-6(R)-S-glutathionyl-7,9-trans-11,14-cis-eicosatetraenoic (LTC4) when compared with monocytes alone. Release of arachidonic acid, 5-HETE, delta 6-trans-LTB4, and delta 6-trans-12-epi-LTB4 from monocytes was decreased in the presence of platelets. A dose-response curve was constructed and revealed that the above changes became evident when the platelet number exceeded 10(7). Dual radiolabeling experiments with 3H- and 14C-arachidonic acid revealed that monocytes provided arachidonic acid, 5-HETE, and LTA4 for further metabolism by the platelet. Monocytes did not metabolize platelet intermediates detectably. In addition, as much as 1.2 microM 12(S)-hydroxy-10-trans-5,8,14-cis-eicosatetraenoic acid and 12(S)-hydroperoxy-10-trans-5,8,14-cis-eicosatetraenoic acid had no effect on monocyte lipoxygenase metabolism. Platelets were capable of converting LTA4 to LTC4, but conversion of LTA4 to LTB4 was not detected. We conclude that the monocyte and platelet lipoxygenase pathways undergo a transcellular lipoxygenase interaction that differs from the interaction of the neutrophil and platelet lipoxygenase pathways. In this interaction monocytes provide intermediate substrates for further metabolic conversion by platelets in an unidirectional manner.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Diagnostic value of reversibility of chronic airway obstruction to separate asthma from chronic bronchitis: a statistical approach.

Our aim was to assess the usefulness of tests of reversibility of airways obstruction (AO) in the differential diagnosis of asthma (A) and chronic bronchitis (CB). We selected on strict clinical criteria 20 CB and 32 A patients with stable AO and measured maximal forced expiratory flows before and after increasing doses of inhaled salbutamol. The highest sensitivity (Se), specificity (Sp) and likelihood ratio (L) were obtained when the improvement in forced expiratory volume in one second (FEV1) was expressed as a percentage of predicted FEV1. Se, Sp and L were 0.97, 0.95 and 19.3 (highest possible L: 20) for an increase of 10% of predicted FEV1 on 0.2 mg of salbutamol, and 1.0, 1.0 and 20, respectively, for an increase of 15% on 1 mg of salbutamol. Conversely, L was only 2.8 when the widely used increase in FEV1 of 20% over baseline was tested. In a second group of 42 unselected patients, who were referred to the laboratory for routine lung function testing with a presenting diagnosis of A or CB, L was only 5.5 when the 10% increase in predicted FEV1 was used and even lower for the classical 20% increase over baseline FEV1. We submit that routine tests of reversibility of AO have little diagnostic usefulness in unselected patients with AO and that the commonly used criteria of 15 or 20% increase in FEV1 over baseline are of no value in separating A from CB.

Albuterol↗

Local cellular and humoral responses to antigenic and distilled water challenge in subjects with allergic rhinitis.

We studied nasal responses to allergen, saline, and distilled water aerosol in 7 subjects with allergic rhinitis to determine whether they caused a similar release of mediators and influx of inflammatory cells into the nasal lumen. The subjects were challenged first with allergen and then with aerosols of distilled water and of normal saline in random order on separate days. We measured nasal airway resistance (Rn) by posterior rhinomanometry, measured the concentrations of protein, histamine, leukotrienes (LT) B4, C4, and D4, and platelet-activating factor (PAF-acether) and performed total and differential cell counts in nasal lavage fluid obtained before and after each challenge. Allergen challenge provoked a 2-fold or greater increase in nasal airway resistance in all subjects (mean increase = 12.2-fold). This response was associated with significant increases in protein, histamine, LTB4, and sulfidopeptide leukotrienes. 2-lyso-PAF-acether increased significantly, indicating activation of phospholipase A2, but PAF-acether was detected in only one subject. The total cell count increased from 55 +/- 44 x 10(3)/ml to 200 +/- 168 x 10(3)/ml; polymorphonuclear neutrophils increased from 11 +/- 22 x 10(3)/ml to 108 +/- 96 x 10(3)/ml, and eosinophils increased from 1.3 +/- 1.8 x 10(3)/ml to 10.6 +/- 15.3 x 10(3)/ml (p less than 0.05). Saline insufflation provoked insignificant changes in mean Rn, in the levels of protein and all inflammatory mediators, and in the number and types of cells in nasal lavage fluid. Distilled water insufflation also provoked an insignificant increase in mean Rn, but there was a 14-fold increase in one subject.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Frequency and severity of hypoxemia during sleep in COPD. Clinical and therapeutic impact].

The occurrence of episodes of desaturation during sleep in patients suffering from chronic airflow obstruction is well known. The severity of nocturnal hypoxaemia depends, in part, on the level of the diurnal PaO2. Hypoventilation linked to sleep is the principle mechanism responsible for the decrease in PaO2 and the desaturation which results and depends on the level of oxyhaemoglobin saturation (SaO2) during wakefulness. However, it is not possible to predict the severity of nocturnal desaturation solely on the basis of diurnal oxyhaemoglobin saturation. Numerous factors may contribute to a worsening of nocturnal desaturation. In some patients it may be associated with hypoventilation and a worsening of the ventilation perfusion inequalities. A fall in the ventilatory response to hypoxaemia and hypercapnea contributes equally to the severity of desaturation. The awake response to hypoxia is variable according to the stage of their respiratory failure but may play a role in worsening nocturnal hypoxia. Snoring and obstructive apnoea are responsible for severe desaturation in chronic airflow obstruction presenting as hypoxaemia which may be moderated during the day. At present the value of systematic nocturnal polygraphic recordings in the "work-up" of chronic airflow obstruction has not been demonstrated. Its principle practical interest is in research into the associated sleep apnoea syndrome. It should be recognised in a patient with chronic airflow obstruction who snores and is somnolent with hypoxaemia and/or poorly explained hypercapnea. The therapeutic approach in respiratory failure should take account of nocturnal desaturation and the oxygen flow at night should be superior to the one to two litres which are required to correct the diurnal hypoxaemia.

Humans↗

Forced expirations in normal subjects. Is the shape of the flow rate curve related to existence of a wheeze?

The flow rate curve takes different shapes during forced expirations performed by normal subjects. In some cases a wheeze may exist. In this study, we examine the conditions for appearance of a wheeze, before and after the peak flow, and the relationship between the wheeze and the shape of the flow rate curve. We analyzed ten parameters in 83 forced expirations produced by 32 normal subjects (16 men and 16 women) using multidimensional scaling techniques. Among these expirations, 53 presented a wheeze. The first two axes of the analysis define a plane on which forced expirations are divided into four quadrants. Two opposite quadrants (upper right and bottom left) contain the wheezing expirations, while the two others only have the ones with no wheezing. This distribution corresponds to specific shapes of the flow rate curve. We found that wheezes are associated with two main shapes. One of them consists of a short onset until a sharp peak, followed by a fast exponential decay. The other is about triangular, with a late appearance of the wheeze, and is only produced by women.

Adult↗