[Measurement of nasal potential difference].
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Biomedical subjects
Publications and source records attributed to T Chinet.
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Metered-dose inhalers are the most widely-used mode of administration of bronchodilators and anti-inflammatory agents in the treatment of asthma. However, their use is complex and about 50% of the patients do not use their metered-dose inhaler(s) properly. The most frequent errors include inadequate coordination between actuation and inspiration, rapid inspiration, absence of breathhold, and actuation of the aerosol on more than one occasion during the same inspiration. The misuse of metered-dose inhalers results in a loss of efficacy of the drug. It is, therefore, recommended that the patient be carefully trained in the proper use of metered-dose inhalers at the time of prescription. If a patient is unable to use a metered-dose inhaler properly, despite education, it may be advisable to employ a different inhalation system.
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To investigate bronchial permeability in asthma, we measured the bronchial clearance of 113mIn-DTPA in seven asthmatics during and after an acute attack of asthma, seven asthmatics with chronic airflow limitation, and seven asthmatics without airflow limitation but with bronchial hyperresponsiveness to methacholine. We compared these results with those from seven normal subjects, seven patients with chronic bronchitis and bronchial infection, and seven patients with emphysema. An aerosol of 113mIn-DTPA was produced with a spinning disc to ensure a predominantly bronchial deposition of inhaled particles (6.3 microns MMAD). Radioactivity over the chest was recorded with a gamma-camera for 10 min after the subject inhaled the aerosol. Central regions of interest were selected, and the logarithm of the radioactivity was plotted against time; bronchial clearance of 113mIn-DTPA was calculated as the negative slope of the regression line. Clearance was substantially higher in asthmatics during their acute attacks than in all other groups (p less than 0.0001), and it decreased toward normal levels after recovery from the acute episode. The bronchial clearance of 113mIn-DTPA in all other groups did not differ from normal. We conclude that the bronchial clearance of 113mIn-DTPA is increased in asthmatics during attacks of asthma but in the stable state is not related either to bronchial hyperresponsiveness or to airflow limitation. Our findings are best explained by an increase in permeability of the bronchial mucosa of asthmatics during acute attacks.
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The most important of ion transport abnormalities is a reduced permeability to chlorine of certain epithelial cells, notably those of the sweat glands and bronchi. This abnormality is due to a defective regulation of the chlorine channels located in the apical membrane of these cells, and more precisely to the lack of activation of these channels by protein kinases A and C. Other epithelial ion transports are affected, but the mechanism of these disturbances is imperfectly known. In the airways, for instance, a decrease of chlorine secretion and an increase of sodium absorption concur to dehydrate the bronchial secretions and thus produce the respiratory manifestations of cystic fibrosis.
To investigate the relation between lung function and inflammation and fibrosis in patients with diffuse lung fibrosis, a study was made of untreated patients without appreciable airway obstruction (14 patients with cryptogenic fibrosing alveolitis and seven with pneumoconiosis). Quantitative assessment of inflammatory infiltration and fibrosis was carried out on open lung biopsy specimens and compared with lung volumes, carbon monoxide transfer factor (TLCO), TLCO corrected for alveolar volume (TLCO/VA), and arterial blood gases at rest and during exercise. The degree of fibrosis and the degree of cellular infiltration were positively correlated. Lung volumes and TLCO were correlated with the grades of fibrosis and cellular infiltration of alveoli; arterial blood gases during exercise tended to correlate with both fibrosis and infiltration (p less than 0.06). In contrast, morphological data were not correlated with gas exchange at rest or with TLCO/VA. It is concluded that, in untreated patients with diffuse lung fibrosis, lung volumes, TLCO, and arterial blood gases during exercise reflect the lung lesions, and that the pulmonary function tests used cannot discriminate between fibrosis and infiltration of the lung by inflammatory cells.
Respiratory epithelial clearance of 99mTc-DTPA (RC-Tc-DTPA) and pulmonary function tests (PFT) were determined at intervals of 6 or 12 months in 37 untreated, nonsmoking patients with sarcoidosis over a period of 6 to 36 months. PFT included the measurements of total lung capacity (TLC), vital capacity (VC), FEV1, and diffusing capacity for carbon monoxide. No difference was found between the respiratory clearance of 113mIn-DTPA (2.25 +/- 1.00%/min) and RC-Tc-DTPA (2.29 +/- 1.11%/min) in eight patients with pulmonary sarcoidosis. Pulmonary function decreased 15% or more in at least 2 function tests during 11 follow-up periods, but it remained stable during 47 follow-up periods. In patients whose lung function deteriorated, RC-Tc-DTPA increased to 3.51 +/- 1.55%/min; in contrast, in patients whose lung function remained stable, regardless of the initial values, RC-Tc-DTPA was normal (1.00 +/- 0.50%/min; p less than 0.001). In eight patients who were treated with corticosteroids, RC-Tc-DTPA decreased from 3.48 +/- 1.31%/min to 1.56 +/- 0.64%/min (p less than 0.001), and PFT improved. We conclude that in nonsmokers with pulmonary sarcoidosis, increased RC-Tc-DTPA is not related to dissociation of 99mTc from DTPA, RC-Tc-DTPA is increased when pulmonary function decreases, and, when increased, RC-Tc-DTPA decreases with corticosteroid therapy.
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We compared the cumulative dose-response curves obtained during carbachol inhalation by simultaneous measurements of airway specific conductance (sGaw) and respiratory conductance, in 23 subjects with or without bronchial hyperresponsiveness. The sGaw was measured by a body plethysmograph, whilst the random noise forced oscillation technique (FOT) was used to determine respiratory conductance. The sGaw was compared to respiratory conductance extrapolated to zero frequency (Grs0). Bronchial sensitivity was assessed by the threshold dose of carbachol (TD) that induced a decrease in sGaw and Grs0 of twice the baseline coefficient of variation. Bronchial responsiveness was assessed by the slopes (S) of the individual dose-response curves. The TD and S values obtained by FOT and by plethysmography were closely correlated (p less than 0.001). The carbachol doses inducing a 50% reduction in sGaw were equivalent to those causing a 42% reduction in Grs0 (r = 0.90; p less than 0.001). During bronchial challenge testing, FOT provides comparable information in terms of bronchial sensitivity and responsiveness to that supplied by plethysmography.
We assessed the effectiveness of various aerosol-generating systems. Taplin's settling method and Venticis generators had a lower efficiency (37.3 +/- 3.8% and 51.8 +/- 9.6%, respectively) than the Syntevent (88.8 +/- 6.9%, p less than 0.001), Cadema (89.8 +/- 9.9%, p less than 0.001) and Mefar (85.3 +/- 19.4%, p less than 0.001) generators. The Mass Median Aerodynamic Diameter of the particles produced by the Mefar nebulizer (2.05 +/- 0.27 micron) was larger than that of any other generators (p less than 0.001). The Syntevent (0.54 +/- 0.09 micron) generator produced smaller particles than the Mefar, Taplin (0.89 +/- 0.10 micron, p less than 0.01) and Venticis (0.79 +/- 0.06 micron, p less than 0.02) generators. Particles produced by the Cadema system (0.69 +/- 0.06 micron) were smaller than those generated by the Taplin system (p less than 0.05). We conclude: that the Syntevent, Mefar and Cadema aerosol generators are more efficient than the others, and that all the generators tested except the Mefar may be used for studies that depend on the peripheral deposition of small particles within the lungs.
As asthma is nearly always associated with non-specific bronchial hyperreactivity, this factor has been considered to be an essential requirement for the development of symptomatic asthma. Some factors appear to be inducers of bronchial hyperreactivity and others promotors of asthmatic symptoms. In clinical practice, it is very difficult to classify aetiological factors as inducers or promotors: there is evidence to support the fact that the same factors may cause both bronchial hyperreactivity and asthmatic symptoms; conversely, the evidence for hereditary non-specific bronchial hyperreactivity is hardly convincing. These observations suggest that non- specific bronchial hyperreactivity is more a marker of bronchial asthma than a true aetiological factor.
The severity and type of clinical manifestations are variable in patients with cystic fibrosis (CF). The respiratory syndromes in these patients consist of lung infections associated with disseminated bronchiectasis (DB), asthma, and chronic obstructive pulmonary disease. To investigate the possible involvement of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in chronic pulmonary disease in adults, we studied 32 DB patients with a clinically isolated respiratory syndrome. Careful analysis of all the CFTR gene exons and their flanking regions revealed a significantly increased frequency of CFTR gene mutations in these patients. Thirteen CFTR gene mutations were identified in sixteen different alleles. Six of these mutations, which have previously been reported as CF defects, were found on nine alleles. A further four, two of which had not previously been described (D192N and 406-2 AdeltaC), are potentially disease-causing mutations. We also identified three rare substitutions (R31C, L997F, T1220I), which could be involved in mild CFTR gene disease. Four patients were compound heterozygotes, one carried two CFTR gene mutations (possibly allelic) and six were heterozygous for a mutation. These results indicate that CFTR gene mutations may play a role in bronchiectatic lung disease, possibly in a multifactorial context. These findings have implications for genetic counselling of DB patients and their families.