The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology
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Comparative Study
Effects of lung volume and thoracic gas compression on maximal and partial flow-volume curves.
Comparing isovolume flows, measured at the mouth during forced expiratory manoeuvres as started from maximal or partial lung inflation, is a means of assessing the effects of deep inhalation on airway calibre. The aim of this study was to investigate whether the assessment of the effect of deep inhalation during induced bronchoconstriction is influenced by the lung volume at which it is determined and by volume differences due to thoracic gas compression that occur during forced expiratory manoeuvres. Four healthy subjects and six subjects with mild-to-moderate asthma subjects performed partial and maximal forced expiratory manoeuvres in a flow-type body plethysmograph at control and during a methacholine (MCh) inhalation challenge. ⋯ We conclude that during induced bronchoconstriction, the bronchodilation following a deep inhalation, expressed as maximal to partial flow ratio is dependent both on lung volume and volume differences due to thoracic gas compression. The use of expired flow and volume measurements may lead to a small but systematic overestimation of the bronchodilator effect of a deep inhalation. On the contrary, maximal to partial flow slope is insensitive either to lung volume or volume differences due to thoracic gas compression and can, therefore, be fairly determined from expired flow-volume loops.
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Comparative Study
Glucocorticoid resistant asthma: T-lymphocyte steroid metabolism and sensitivity to glucocorticoids and immunosuppressive agents.
We have previously shown that T-lymphocytes from clinically glucocorticoid (GC) resistant asthmatics are more refractory to dexamethasone suppression in vitro than those of GC sensitive asthmatics. We wished to extend these observations to compare three GCs used topically for asthma therapy (budesonide, beclomethasone dipropionate and fluticasone 17 alpha-propionate) and three immunosuppressive drugs (cyclosporin A, FK506 (tacrolimus) and mycophenolate mofetil) with dexamethasone for their antiproliferative effects on T-lymphocytes from GC sensitive and resistant asthmatics, and also to compare the rates of steroid metabolism by T-lymphocytes from these patients. Antiproliferative activity of the drugs was measured on peripheral blood T-lymphocytes activated with phytohaemagglutinin (PHA) and anti-CD3 antibody in vitro. ⋯ The rates of total metabolism and 20 alpha-hydroxylation of steroid by homogenates of T-lymphocytes from GC sensitive and resistant asthmatics were equivalent. Thus, relative GC resistance in T-lymphocytes from GC resistant as compared with sensitive asthmatics is: 1) manifest with GC molecules of variable molecular structure; 2) not accompanied by elevated intracellular metabolism of steroids; and 3) overcome by immunosuppressive drugs which inhibit T-lymphocytes by non-GC-mediated mechanisms. We conclude that current anti-asthma glucocorticoids at therapeutic concentrations are unlikely to be of benefit for the therapy of glucocorticoid resistant asthma, and that other immunosuppressive drugs may have potential as therapeutic agents in these patients.
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The aim of this study was to determine the current incidence of side-effects severe enough to cause intolerance of standard antituberculosis therapy with isoniazid, rifampin and pyrazinamide in patients hospitalized as a result of pulmonary tuberculosis. Five hundred and nineteen patients with proven pulmonary tuberculosis, who initially received standard antituberculosis therapy, were retrospectively studied in the department of infectious diseases in a teaching chest hospital. The incidence of severe side-effects related to the therapy, which led to the definitive termination of one of the three standard drugs, was measured and the risk factors for intolerance were analysed. ⋯ Significant risk factors for intolerance of the standard therapy following a multivariate analysis were a history of hepatitis (odds ratio (OR) 3.4; 95% confidence interval (95% CI) 1.6-7.6; p = 0.0026) and an age > or = 60 yrs (OR 1.9; 95% CI 1.2-3.2; p = 0.017). Both of these risk factors were also significantly associated with the intolerance of pyrazinamide (history of hepatitis: OR 2.5; 95% CI 1.4-4.3; p = 0.0045; age > or = 60 yrs: OR 2.1, 95% CI 1.3-3.5; p = 0.0029) but not of isoniazid and rifampin. The side-effects of standard antituberculosis therapy are frequent in hospitalized patients aged > or = 60 yrs or with a history of previous hepatitis, and are probably due to pyrazinamide rather than to isoniazid or rifampin.
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In a prospective study, we investigated the effect of single-lung transplantation (SLT) on pulmonary haemodynamics and the relationship between pulmonary hypertension (PH) and the fraction of perfusion to the transplant in patients with end-stage pulmonary parenchymal disease. Twenty four SLT recipients were included in the study, 19 with chronic obstructive pulmonary disease (COPD), two with sarcoidosis and three with fibrosing alveolitis. Spirometry, determination of arterial blood gas values, perfusion scintigraphy and right heart catheterization were performed before and 1, 6, 12 and 24 months after transplantation. ⋯ In conclusion, patients with pulmonary hypertension obtain pulmonary haemodynamics within the normal range after single-lung transplantation. Presence or absence of pulmonary hypertension before transplantation does not influence perfusion to the graft. These findings persist up to 2 yrs, despite the coexistence of an "end-stage" native lung and a lung transplant.
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Weaning from mechanical ventilation is a period of transition from total ventilatory support to spontaneous breathing. It represents a relevant clinical problem because as many as 25% of intubated and mechanically-ventilated critically ill patients will need a progressive withdrawal from artificial ventilatory support. From a clinical standpoint, it is very important to recognize as soon as possible when a patient is ready to be weaned. ⋯ Different ventilatory techniques can be used to wean these patients from mechanical ventilation. Up to now, the most efficient techniques seem to be pressure support ventilation and once daily trials of T-piece interspersed with conventional volume assist-control ventilation. Finally, knowledge-based system applied to modern microprocessor mechanical ventilators can help in the process of weaning by automatically reducing the ventilatory assistance and indicating the optimal time to perform extubation.