Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0729233 (Thoracic)
 6,478 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Short-term trials of bronchodilator drugs are widely used to assess patients with stable chronic obstructive pulmonary disease (COPD), but there is an uncertainty about the equivalence of the FEV1 response to beta-agonists and anticholinergic drugs, their relative ability to identify patients likely to improve with corticosteroids, the most appropriate way to express the results of these tests, and whether age or allergic status affects the beta-agonist and anticholinergic response differently. We studied 100 consecutive patients with stable COPD (mean FEV1, 0.96 +/- 0.48 L; mean age, 62 +/- 8 yr). Spirometry was measured before and after either 5 mg of nebulized salbutamol or 500 micrograms of nebulized ipratropium bromide and repeated after 2 wk of 30 mg of oral prednisolone daily. Total IgE, specific RAST, and skin prick testing values were recorded. Using modified American Thoracic Society response criteria, 33 patients failed to bronchodilate after the acute trials, 16 responded only to nebulized salbutamol, 17 to nebulized ipratropium, and 34 to both drugs. Twenty-two patients improved after corticosteroids. This was usually detected by a positive acute trial response (salbutamol 90% specific; ipratropium 84% specific). Baseline FEV1 differed between days, and in those who responded on only 1 day, this variation correlating with the response to ipratropium (r = 0.66). Expressing the response criterion as a percentage change in the available bronchodilatation increased the numbers responding with a high baseline FEV1, and vice versa. Neither age nor allergic status was related to the change in FEV1 after either drug in these patients. In COPD patients, testing with high-dose nebulized bronchodilators identifies a substantial number of partially reversible patients whatever age it is employed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute bronchodilator trials in chronic obstructive pulmonary disease. 138 72

Lung function measurements were performed before and after bronchodilator, nebulized ipratropium bromide (10 micrograms kg-1), in 20 pre-term infants [median gestational age 28 weeks (range 23-32 weeks) at a median postnatal age of 10 months (range 6-16 months)]. Eight of the infants had recurrent respiratory symptoms. Thoracic gas volume (TGV) and airways resistance (Raw) were measured by a plethysmographic technique and functional residual capacity (FRC) by a helium gas dilution technique. There was no significant change in either TGV or FRC following bronchodilator in the symptomatic and asymptomatic infants. Nebulized bronchodilator resulted in a significant improvement in Raw amongst the symptomatic infants (P less than 0.05), but a paradoxical response, that is, a deterioration (P less than 0.05) in Raw amongst the asymptomatic infants. In three asymptomatic infants, lung function measurements were repeated before and after nebulized saline and a similar deterioration in Raw was noted. We conclude the demonstration of respiratory symptoms at follow-up is useful in predicting infants who would have a beneficial response to nebulized ipratropium bromide.
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PMID:Paradoxical response to nebulized ipratropium bromide in pre-term infants asymptomatic at follow-up. 183 16

A detailed morphological study was performed to localize the probable sites of connections between two identified populations of interneurons (ventral giant interneurons and type-A thoracic interneurons) in the cockroach. Type-A thoracic interneurons (TIAS) appear to play an important role in orienting the cockroach during wind-mediated escape. However, their large number, approximately 100 neurons, precludes analyzing each cell's role electrophysiologically. The TIAS are characterized by a prominent branch located on one or both sides of the ventral median (VM) region of the thoracic ganglion in which their soma resides. The presence of this ventral median branch can be used to predict connectivity with left or right ventral giant interneurons (vGIs) (Ritzmann and Pollack, 1988) and is correlated with the TIA's directional response to wind (Westin, Ritzmann, and Goddard, 1988), suggesting that this is the locus of synaptic connection. Two approaches were employed to address this hypothesis. Morphological overlap of differentially labelled cells (ethidium bromide, Lucifer Yellow) was examined at the light microscopic level to locate areas of possible synaptic contact. Experiments were also performed in which one-half of the vGI input to the TIAs was surgically removed early in postembryonic development. Although no changes in the overall branching pattern were observed, the VM branches on the operated side were significantly shorter than were those on the unoperated side. Thoracic interneurons that do not receive inputs from vGIs were unaffected by this surgery. The data reported here thereby confirm previous observations by localizing the vGI inputs specifically to the VM branch, and provide a morphological cue for predicting connectivity and function.
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PMID:Localization of ventral giant interneuron connections to the ventral median branch of thoracic interneurons in the cockroach. 191 68

To evaluate the effects of salbutamol and ipratropium bromide on the isolated hyperinflation, without central airways obstruction, during asymptomatic periods in asthmatic children, 31 children, out of ca. 500, were selected for a double-blind therapy trial, according to the following criteria: Thoracic gas volume greater than 140% predicted (mean +/- 1SD: 162 +/- 16%) and/or trapped-gas greater than 15% (21 +/- 5%); airways resistance less than 140% (105 +/- 25%) and forced expiratory volume in one second greater than 75% (91 +/- 11%). On 4 consecutive mornings spirometry, bodyplethesmography and measurement of functional residual capacity by helium-dilution were performed before and 20' after inhalation of 2 ml of each of 4 solutions respectively. The children received the solution which produced the largest fall of thoracic gas volume and/or trapped-gas, 4 times/day for 4-5 weeks: 1. five children received saline; 2. 13 salbutamol, 2.5 mg; 3. 6 ipratropium, 0.250 mg; 4. 7 both drugs. Clinical aspects and lung function differed not significantly between the 4 groups. Lung function values showed no correlations with duration, clinical severity and typ of asthma. At the beginning and after 4-5 weeks of treatment lung function improved significantly in the groups 2-4, compared with pretreatment values. At study end, the improvements of thoracic gas volume, trapped-gas and airways resistance differed significantly between the groups, salbutamol + ipratropium produced altogether the best effect. With time, the effect of salbutamol + ipratropium on thoracic gas volume and trapped-gas increased and that of salbutamol on airways resistance and forced expiratory volume in one second decreased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of ipratropium bromide and salbutamol on isolated lung hyperinflation in symptom-free intervals in asthmatic children]. 214 Nov 4

The effect of nebulized ipratropium bromide in 14 infants (mean age: 20 weeks, range: 4-41) with acute respiratory syncytial virus bronchiolitis was examined. A modified rapid chest compression technique was used to obtain partial expiratory flow-volume curves and maximum flow at functional residual capacity. Passive respiratory mechanics were assessed by brief occlusion at end inspiration. Thoracic gas volume was measured in a body plethysmograph. No significant difference was found in forced and passive respiratory mechanics pre- and post-ipratropium bromide. No subgroups could be identified. These results do not support the use of ipratropium bromide in acute viral bronchiolitis.
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PMID:Effect of ipratropium bromide on respiratory mechanics in infants with acute bronchiolitis. 295 49

We have previously been shown that the phospholipase inhibitor p-bromophenacyl bromide (BPB) modifies neurite morphology and growth rate in rat dorsal root ganglion explants. Neurite extension is stimulated by 2.5 X 10(-7) M BPB but it is prevented by concentrations higher than 10(-5) M. Under our experimental conditions, no neurites appeared in the absence of added nerve growth factor (NGF). Therefore, we have tested the effect of a low BPB concentration at different levels of exogenous NGF. Thoracic and lumbar ganglia were obtained from 19.5-day-old fetal rats and were cultured for 24 h on a polyornithine substrate. Neurite growth and development of a dense halo were NGF-dependent in both ganglionic populations; however, each of them showed a characteristic dose-response curve. Incubation with BPB induced neurites in the absence of added NGF and stimulated their growth when low levels of this factor were added. In lumbar ganglia incubated with higher levels of NGF, BPB had no detectable effects. On the contrary, similarly treated thoracic ganglia showed an inhibition of neurite extension. Our findings suggest a relationship between the effects of BPB and the initial, membrane-activating actions of NGF.
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PMID:Effects of p-bromophenacyl bromide on neurite growth at different levels of nerve growth factor. 338 Mar 27

Perfluorocarbon (PFC) compounds induce pulmonary hyperinflation and respiratory distress in some animals following intravenous administration. This study was designed to quantify the effects of two PFC emulsions on lung volumes and compliance and to identify the mechanism of pulmonary hyperinflation. New Zealand White rabbits received isotonic saline (3 ml/kg), Fluosol (15 ml/kg) or Oxygent (90% perfluorooctyl-bromide emulsion, 3 ml/kg). After seven days we measured functional residual capacity, vital capacity, lung compliance and thoracic gas volume. Gross and microscopic histologic examination of the lungs was performed. Functional residual capacity after Fluosol administration was 16.0 +/- 4.0 ml/kg, significantly greater than after saline (3.4 +/- 1.0 ml/kg) or Oxygent (4.0 +/- 1.4 ml/kg). Vital capacity was lower with Fluosol (30 +/- 5.0 ml/kg) than after saline (37 +/- 3.0 ml/kg) or Oxygent (37 +/- 2.0 ml/kg). Thoracic gas volume increased from 9 +/- 1.0 ml/kg (saline) to 16 +/- 13 ml/kg (Oxygent) and 33 +/- 7.0 ml/kg (Fluosol). Lung compliance was the same after saline (1.6 +/- 0.5 ml.cm H2O-1.kg-1) and Oxygent (1.5 +/- 0.3 ml.cm H2O-1.kg-1) but lower after Fluosol (0.9 +/- 0.1 ml.cm H2O-1.kg-1). Gross pathology demonstrated foam exudation from airways of animals receiving PFCs and intra-alveolar foam was identified by light microscopy. These results show intra-airway foam formation causes gas trapping and shifts tidal breathing to a less compliant region of the pressure-volume curve.
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PMID:Perfluorocarbon induced alterations in pulmonary mechanics. 963 19

Chronic obstructive pulmonary disease (COPD) is a common disability, largely encountered in the elderly population, in whom it causes significant morbidity and mortality. The general perception of health professionals is that COPD is often a self-inflicted disorder affecting the more socio-economically disadvantaged segment of the population with significant comorbidity. COPD is the least funded in terms of research in relation to illness burden compared with other chronic diseases. However, recently published guidelines of both the British Thoracic Society and the Global Initiative for Chronic Obstructive Lung Disease have highlighted best management strategies both of chronic symptoms and acute exacerbations in this patient group. The chronic management of COPD should, like asthma, involve a stepwise approach with smoking cessation being pivotal for all severities of COPD, regardless of patient age. The mainstay of therapeutic treatment remains regular bronchodilators, both beta(2)-adrenoreceptor agonists and anticholinergic agents. Current evidence suggests that long-acting beta(2)-adrenoreceptor agonists such as salmeterol and the new long-acting anticholinergic agent tiotropium bromide are more efficacious than their shorter acting equivalents such as salbutamol and ipratropium bromide in terms of bronchodilation, improved well-being and a reduction in acute exacerbation rates. Additionally since they are taken once or twice daily compliance should be improved. The role of long-term inhaled corticosteroids in the chronic management of COPD is contentious. Only those patients with COPD who have been shown to respond to a formal corticosteroid trial, preferably with a 2-week course of oral corticosteroid, should receive long-term inhaled corticosteroids. In the management of acute exacerbations in acidotic patients nasal ventilation is the treatment of choice in addition to conventional treatment with bronchodilators and oral corticosteroids. Antibacterials need not be prescribed universally in all exacerbations of COPD. Pulmonary rehabilitation classes either individually or in groups have been shown to be beneficial in the management of patients with COPD and their use in secondary care is to be encouraged. Most treatment modalities do not improve pulmonary function in patients with severe COPD. Therefore, pulmonary function including spirometry should be used to make the diagnosis of COPD but not as a monitor of efficacy of treatment. Assessment of severity of COPD and improvement with treatment modalities is best done with dynamic exercise testing such as 6-minute walk tests and incremental shuttle walk tests or with the administration of disease-specific physical disability and quality-of-life questionnaires. Most COPD research does not specifically target the older COPD patients and these patients may merit special consideration for their optimum assessment and management.
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PMID:Treatment of chronic obstructive pulmonary disease in older patients: a practical guide. 1257 1

Tiotropium bromide (Spiriva) is a long-acting anticholinergic bronchodilator that maintains bronchodilation for at least 24 hours, allowing once-daily administration. The active moiety is the tiotropium cation (tiotropium); tiotropium bromide 22.5 micrograms is equivalent to 18 micrograms of tiotropium cation. Greater improvements in lung function from baseline (primary endpoint mean trough FEV(1)) were observed with inhaled tiotropium 18 micrograms once daily than with placebo in 6-month and 1-year randomized, double-blind trials in patients with COPD. Tiotropium improved lung function (trough FEV(1) response) more effectively than ipratropium bromide (ipratropium) 40 micrograms four times daily in 1-year clinical trials, and was at least as effective as salmeterol 50 micrograms 12-hourly in 6-month trials. Preliminary data suggest that tiotropium alone or in combination with once-daily formoterol has a greater bronchodilator effect than twice-daily formoterol in patients with COPD. Improvements in patients' perception of health-related quality of life (HR-QOL) or dyspnea were greater with tiotropium than with placebo or ipratropium, and were similar to those with salmeterol. Reductions in the frequency and severity of acute exacerbations and in the use of rescue medication were also greater with tiotropium than with ipratropium or placebo. There was no evidence of tachyphylaxis with tiotropium during 1-year clinical trials. Inhaled tiotropium was generally well tolerated in clinical trials. Apart from dry mouth, the type and incidence of adverse events with tiotropium were similar to those with ipratropium, salmeterol or placebo in patients with COPD. In conclusion, inhaled tiotropium 18 micrograms once daily improved lung function, dyspnea, and HR-QOL, and decreased the incidence of acute COPD exacerbations and the use of rescue medication relative to placebo or ipratropium in clinical trials in patients with COPD. Tiotropium was at least as effective as salmeterol in terms of bronchodilator efficacy and improvements in dyspnea or HR-QOL. With the exception of dry mouth, the tolerability profile of tiotropium was similar to that with placebo, ipratropium, or salmeterol. Consequently, inhaled tiotropium is likely to be a valuable option for first-line, long-term maintenance therapy in the management of bronchoconstriction in patients with symptomatic COPD. Tiotropium bromide has a quaternary ammonium structure and acts as an anticholinergic bronchodilator; the active moiety is the tiotropium cation (tiotropium). A 22.5 micrograms dose of tiotropium bromide provides 18 micrograms of tiotropium. Orally inhaled tiotropium bromide antagonizes the muscarinic M(1), M(2), and M(3) receptors located in airway smooth muscle, reversing vagally mediated bronchoconstriction. Receptor binding assays and in vitro tests indicate that tiotropium bromide is kinetically selective for M(1) and M(3) receptors over the M(2) receptor, unlike ipratropium bromide, which is nonselective. Animal and in vitro studies showed that tiotropium bromide was more potent ( approximate, equals 20-fold) than ipratropium bromide in displacing [(3)H]N-methylscopolamine (NMS) from muscarinic receptors, and had a more sustained protective effect (>70% inhibition) against NMS binding. Tiotropium bromide was a more potent inhibitor of bronchial contraction than atropine ( approximate, equals 23-fold), and had a slower onset and markedly longer duration of action than atropine or an equipotent dose of ipratropium bromide. Aerosol particle penetration is improved with tiotropium, without delaying mucus clearance from the lungs. Tiotropium 4.5-36 micrograms once daily for 4 weeks increased mean trough and average FEV(1) and FVC and mean PEFR values from baseline compared with placebo, with no evidence of tachyphylaxis. Improvements in trough FEV(1) from baseline with tiotropium 4.5-36 micrograms were not dose dependent. Based on a lack of dose response, the optimal once-daily tiotropium dosage is 18 micrograms. Steady-state trough FEV(1) values are achieved within 48 hours of commencing tiotrochodilation (for >/=24 hours) and an attenuation of the nocturnal decline in FEV(1) that were unaffected by timing of the daily tiotropium dose were seen in randomized, double-blind, placebo-controlled studies in patients with stable COPD. The drug improved static and dynamic lung hyperinflation (evidenced by reduced trapped air volume and increased tidal volume and end-of-exercise inspiratory capacity), and improved exertional dyspnea (during activities of daily living and exertion) and exercise tolerance compared with placebo in randomized, double-blind studies. In patients with stable COPD, improved sleep-related oxygen desaturation that was unaffected by the timing of the daily dose was seen with tiotropium but not with placebo. Clinically significant treatment-related disorders of conduction or rhythm, or changes in heart rate were not observed with tiotropium in this patient group. Mean maximal plasma concentrations (C(max)) were observed within 5 minutes of inhalation of a single dose of tiotropium 18 micrograms in patients with COPD. Plasma drug levels declined to minimum concentrations (C(min)) within 1 hour of treatment in healthy volunteers. Mean steady-state C(max) concentrations (16 ng/L) were achieved after 2-3 weeks of once-daily inhaled tiotropium 18 micrograms in elderly patients with COPD; tiotropium does not appear to accumulate once steady-state has been achieved.The estimated absolute bioavailability of tiotropium at steady state in healthy volunteers was approximately 20-25%, and approximately 72% of the drug is bound to plasma proteins. Excretion of tiotropium is predominantly renal (through active secretion by the kidneys), although in vitro studies suggest that cytochrome P450 (CYP) oxidation (possibly involving CYP2D6 and CYP3A4 enzymes) may have a minor role. In patients with COPD, renal excretion of the unchanged drug at 24 hours (Ae(24)) was approximately 7%. The mean plasma elimination half-life after single or multiple doses in healthy volunteers and elderly patients with COPD was approximately 5-6 days. The renal clearance and urinary excretion of tiotropium decrease with increasing age; however, these changes are not considered to be clinically significant. Because of altered steady-state C(max), C(min), area under the concentration-time curve, and Ae(24) values, caution is required with tiotropium administration in patients with moderate-to-severe renal impairment. The pharmacokinetics of tiotropium in patients with severe renal or hepatic impairment have not been studied. Tiotropium does not interact with drugs such as cimetidine or ranitidine, which are also eliminated by active renal secretion. Orally inhaled tiotropium bromide has been evaluated as a bronchodilator for the management of patients with COPD in randomized, double-blind 6-month and 1-year trials, and in several shorter studies. In clinical trials, COPD was diagnosed according to the American Thoracic Society guidelines. The bronchodilator effect was expressed as the trough FEV(1) response (the mean change in FEV(1) from baseline measured 1 hour prior to and immediately before a scheduled dose), and was the primary endpoint in all but two clinical trials. The bronchodilator effect with tiotropium 18 micrograms once daily was superior to that with placebo in several well designed trials in patients with COPD. Moreover, greater improvements in mean peak and average FEV(1) responses occurred with tiotropium but not with placebo. Mean trough, peak, and average FVC responses, and weekly mean morning and evening PEFR values were also improved to a greater extent with tiotropium than with placebo. Tiotropium demonstrated a greater bronchodilator effect than ipratropium bromide (hereafter referred to as ipratropium when used at approved dosages) 40 micrograms four times daily in two 1-year trials in patients with COPD. Mean peak and average FEV(1), mean trough FVC responses, and weekly mean morning and evening PEFR values were also increased to a greater extent with tiotropium than with ipratropium. In one of the two 6-month trials that compared the efficacy of tiotropium with that of inhaled salmeterol 50 micrograms twice daily, greater improvements from baseline in mean trough, peak, and average FEV(1) and FVC responses were seen with tiotropium than with salmeterol. Increases in weekly mean evening, but not morning, PEFR values were generally greater with tiotropium than salmeterol. In the second trial, improvement in the primary endpoint (mean trough FEV(1) response from baseline) with tiotropium or salmeterol was similar, although peak and average responses were superior with tiotropium. Preliminary results from a 6-week crossover study in patients with COPD suggested that tiotropium alone or in combination with once-daily formoterol improved mean trough and average FEV(1) and trough FVC values from baseline to a greater extent than twice-daily formoterol. More patients achieved a clinically important improvement (increase of >/=1 unit) in the transitional dyspnea index focal score (a measure of dyspnea-related impairment) with tiotropium than with placebo in the 1-year trials. Tiotropium was superior to ipratropium in 1-year trials, and was at least as effective as salmeterol in 6-month trials, in achieving a clinically important improvement in focal scores. Tiotropium recipients experienced fewer COPD exacerbations than placebo or ipratropium recipients and had fewer and shorter COPD-related hospitalizations compared with placebo recipients. Unlike salmeterol, tiotropium lengthened the time to onset of the first exacerbation and decreased the number of exacerbations compared with placebo in two 6-month trials. Similar proportions of tiotropium, salmeterol, and placebo recipients required COPD-related hospitalizations. (ABSTRACT TRUNCATED)
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PMID:Tiotropium bromide. A review of its use as maintenance therapy in patients with COPD. 1535 Jan 63