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BACKGROUND The metered dose inhaler is difficult to use correctly, synchronising actuation with inhalation being the most important problem. A breath actuated pressurised inhaler, designed to help patients with poor inhaler technique, was compared with a conventional metered dose inhaler in terms of aerosol deposition and bronchodilator response. METHODS Radioaerosol deposition and bronchodilator response to 100 micrograms salbutamol were measured in 18 asthmatic patients, who inhaled from a conventional metered dose inhaler by their own chosen metered dose inhaler technique, from a conventional metered dose inhaler by a taught metered dose inhaler technique, and from a breath actuated pressured inhaler (Autohaler). RESULTS In the 10 patients who could coordinate actuation and inhalation of the inhaler on their own deposition of aerosol in the lungs and bronchodilator response were equivalent on the three study days. By contrast, in the eight patients who could not coordinate the mean (SEM) percentage of the dose deposited in the lungs with their own inhaler technique (7.2% (3.4%] was substantial lower than those attained by the taught metered dose inhaler technique (22.8% (2.5%] and by Autohaler (20.8% (1.7%]. CONCLUSION Although of little additional benefit to asthmatic patients with good coordination, the Autohaler is potentially a valuable aid to those with poor coordination, and should be considered in preference to a conventional metered dose inhaler in any patient whose inhaler technique is not known to be satisfactory.
Thorax 1991 Oct
PMID:Improvement of drug delivery with a breath actuated pressurised aerosol for patients with poor inhaler technique. 175 17

The effect of positive expiratory pressure breathing, alone and in combination with coughing, was investigated in eight patients with cystic fibrosis. Functional residual capacity and total lung capacity was measured with a body plethysmograph before, during, and immediately after breathing with expiratory pressure of 5 and 15 cm H2O, and after a coughing period. The positive expiratory pressure breathing was carried out five times for two minutes with a two minute interval between each period. Mucus transport was measured in a peripheral lung region and over the whole lung by a radioactive aerosol tracer technique. Clearance measurements were carried out continuously during positive expiratory pressure breathing and during a control period. Two minutes' breathing with an expiratory pressure of 5 and 15 cm H2O caused an increase in mean (SEM) functional residual capacity from 2.6 (0.1) to 3.6 (0.3) and 4.4 (0.5) 1 and an increase in total lung capacity from 5.1 (0.2) to 5.9 (0.3) and 6.9 (0.4) 1. Lung volumes were higher during breathing with an expiratory pressure of 15 cm H2O than with 5 cm H2O; both returned to baseline values immediately after positive expiratory pressure breathing. Spontaneous mucus clearance and mucus clearance by coughing were not influenced by positive expiratory pressure breathing at either expiratory pressure. Thus in patients with cystic fibrosis positive expiratory pressure breathing increases lung volumes in relation to the expiratory pressure imposed; these changes in lung volume did not, however, lead to an improvement of mucus transport.
Thorax 1991 Apr
PMID:Effect of positive expiratory pressure breathing in patients with cystic fibrosis. 153 53

Blood carboxyhaemoglobin levels were estimated by double wavelength spectrophotometry in non-smoking women living in Chandigarh and its environs and related to the cooking fuel they used. Twenty nine used kerosene, 28 biomass fuel, and 30 liquified petroleum gas; the 27 control subjects had not done any cooking for seven days. The carboxyhaemoglobin concentrations were significantly higher in the women using the three types of fuel (mean (SEM) concentration 7.49% [corrected] (0.67%) for kerosene, 15.74% (0.83%) for biomass fuel, and 17.16% (0.62%) for liquified petroleum gas, compared with 3.52% (0.33%) in the control subjects. It is concluded that cooking with any of the three fuels causes indoor air pollution. It is important to have better designed houses with adequate ventilation and stove vents that are cleaned regularly if pollution is to be reduced.
Thorax 1991 May
PMID:Carboxyhaemoglobin in women exposed to different cooking fuels. 206 90

A study was carried out to investigate whether an imbalance in the autonomic nervous system or release of histamine, or both, is responsible for the nocturnal increase in airflow obstruction in asthmatic children. The study comprised 18 children with allergic asthma, nine with (group 1) and nine without (group 2) nocturnal airflow obstruction, and an age matched control group. All drugs were withheld for three days before and during the study. On day 4 each child was admitted to hospital and a series of measurements was made every four hours for 24 hours. These included measurements of the forced expiratory volume in one second (FEV1), heart rate and sinus arrhythmia gap from an electrocardiogram (an indirect measure of parasympathetic activity) and urine sampling for determination of catecholamine and N'-methylhistamine concentrations (measures of sympathetic activity and histamine release respectively). Urinary N'-methylhistamine excretion was significantly higher over the 24 hours in children in group 1 than in children in group 2, and overnight values were also significantly higher in children in group 1 than those in group 2. Mean (SEM) values (mumol/mol creatinine) were 154.6 (11.2) in group 1 and 110 (11.2) in group 2 for 2400-0400 hours samples and 139.2 (13.1) and 101.2 (10.6) 0400-0800 hours samples. There was no evidence of decreased sympathetic or increased parasympathetic activity in association with the nocturnal airflow obstruction; noradrenaline concentrations were increased in group 1. These observations indicate that nocturnal airflow obstruction is associated with increased release of histamine overnight.
Thorax 1991 May
PMID:Nocturnal airflow obstruction, histamine, and the autonomic central nervous system in children with allergic asthma. 206 94

Preoperative nutritional assessment was carried out on 39 consecutive patients with bronchial carcinoma who underwent thoracotomy. For 18 patients the body mass index and triceps and subscapular skinfold thickness fell below the 25th centile. In 23 patients the creatinine height index was less than 80% of the predicted value. The mean (SEM) serum albumin concentration was 40.3 (0.57) g/l (reference range 35-50 g/l) and mean (SEM) serum transferrin 1.77 (0.1) g/l (reference range 2.0-3.0 g/l). Although only three patients were hypoalbuminaemic, transferrin concentrations were depressed in 26 patients. There was a significant fall in the serum concentrations of both prealbumin and transferrin in the first postoperative week. Nutritional insufficiency was particularly severe in the four patients who developed an early bronchopleural fistula. It is concluded that protein-energy malnutrition is common in patients with operable bronchial carcinoma and that routine postoperative feeding does not prevent further depletion of circulating proteins. A larger prospective study is needed to examine the relation between preoperative nutritional state and outcome.
Thorax 1990 Mar
PMID:Nutritional state of patients with lung cancer undergoing thoracotomy. 210

Induced bronchoconstriction in normal subjects can be transiently reversed by a deep breath (airway hysteresis). The mechanisms of airway hysteresis are not fully understood. The aim of these studies was to determine whether the nature of the deep breath (slow or fast inspiration, five or 10 second breath hold) affects the resultant bronchodilatation. Bronchoconstriction was induced in 10 normal subjects by inhalation of histamine until specific airway conductance (sGaw) was halved (mean (SEM) post-histamine sGaw 0.099* (0.009) s-1 cm H2O-1). A subsequent deep breath to total lung capacity (TLC) increased sGaw by 57% (13%) and neither the rate of inspiration to TLC nor periods of breath holding at TLC produced a significantly different degree of bronchodilation. Reducing the volume of the deep breath produced progressively less bronchodilatation and this was no longer significant after a breath to 68% (2%) TLC. To determine whether the volume of the deep breath or the accompanying increase in transpulmonary pressure (PstL) was responsible for the effect on sGaw, subjects were studied with an oesophageal balloon in place with and without their chest strapped. Subjects took a deep breath to a PstL of 20 cm H2O after bronchoconstriction had been induced by histamine. The degree of bronchodilatation (mean (SEM) %) was not significantly different (strap on 25 (6), strap off 36 (5)) even though significantly larger lung volumes (as % TLC) were reached with the strap off (strap on 57 (2), strap off 78 (3)). These results suggest that PstL rather than lung volume during a deep breath determines airway hysteresis.
Thorax 1990 Dec
PMID:Bronchodilatation induced by deep breaths in relation to transpulmonary pressure and lung volume. 228 25

An estimate of the absolute pulmonary deposition of nebulised pentamidine isethionate was obtained in nine patients with AIDS. Two nebuliser systems were compared, System 22 Mizer (Medic-Aid) and Respirgard II (Marquest), with 50 and 150 mg doses of pentamidine in a 3 ml solution driven by an air flow of 6 l/min with the patient in the sitting position. The 50 mg pentamidine dose was repeated with a 6 ml fill with both devices. The nebuliser cloud was labelled with technetium-99m human serum albumin (Ventocol) and lung deposition was measured with a gamma camera. Of the two nebulisers studied, System 22 Mizer delivered more drug to the lungs as a whole and to each individual lung region, including the peripheral and upper zones. For the 50 mg dose the mean (SEM) total pulmonary deposition with the 3 and the 6 ml fill respectively was 2.63 (0.34) and 3.71 (0.41) mg for the System 22 Mizer and 1.37 (0.26) and 1.45 (0.18) mg for the Respirgard II. For the 150 mg dose the System 22 Mizer delivered 7.16 (1.02) mg and the Respirgard II 4.34 (0.57) mg. Increasing the volume of fill from 3 to 6 ml increased pulmonary deposition with System 22 Mizer, and this was related to an increase in nebuliser output. Neither pulmonary deposition nor nebuliser output was increased by using a 6 ml solution in the Respirgard II. Increasing the volume of fill prolonged the time required for nebulisation with both nebulisers. The System 22 Mizer produced more nonpulmonary (gastric and oropharyngeal) deposition of drug, more frequent local adverse effects (cough, burning in the throat, and a metallic taste), and small reductions in lung function, particularly with the 150 mg pentamidine dose. Thus nebuliser type, volume of fill, and nebuliser dose affect the pulmonary deposition of pentamidine. A 300 mg dose of pentamidine via a Respirgard II is generally recommended as providing effective prophylaxis; our results suggest that similar pulmonary deposition can be produced with System 22 Mizer and 150 mg pentamidine. A clinical trial would be needed to show whether this regimen provides similar prophylactic benefit.
Thorax 1990 Jun
PMID:Pulmonary deposition of nebulised pentamidine isethionate: effect of nebuliser type, dose, and volume of fill. 239 91

The lung dose and deposition patterns of drug delivered by dry powder inhaler are not known. The effects of inhaling 400 micrograms salbutamol delivered by dry powder inhaler (two 200 micrograms salbutamol Rotacaps), by pressurised metered dose inhaler, and by Acorn nebuliser were studied in nine subjects with chronic stable asthma. Technetium-99m labelled Teflon particles were mixed with micronised salbutamol in the pressurised metered dose inhaler and in the capsules; technetium-99m labelled human serum albumin was mixed with the salbutamol solution for the nebuliser study. The pressurised metered dose inhaler deposited 11.2% (SEM 0.8%) of the dose within the lungs; this was significantly more than the dose deposited by the dry powder inhaler (9.1% (0.6%], but did not differ significantly from the dose delivered by the nebuliser (9.9% (0.7%]. Distribution within the peripheral third of the lung was significantly greater with the nebuliser than with the other two systems; FEV1 improved to a significantly greater extent after inhalation of 400 micrograms salbutamol from the pressurised metered dose inhaler (35.6% from baseline) than from the nebuliser (25.8%) or dry powder inhaler (25.2%). Thus after inhalation of similar doses of salbutamol a larger proportion of drug was deposited within the lungs when it was inhaled from a metered dose inhaler than from a dry powder system; the nebuliser achieved the greatest peripheral deposition. The bronchodilator response seems to depend on the amount of drug within the lungs rather than its pattern of distribution.
Thorax 1990 Jun
PMID:Comparison of bronchodilator responses and deposition patterns of salbutamol inhaled from a pressurised metered dose inhaler, as a dry powder, and as a nebulised solution. 239 93

The neuropeptides substance P and neurokinin A are present in sensory airway nerves. Their effect on airway calibre was compared in six healthy non-smoking subjects and six asthmatic subjects. On separate days increasing concentrations (from 10(-9) to 10(-6) mol/ml) of each neuropeptide were administered by nebuliser and the airway response measured as change in specific airway conductance (sGaw). Substance P and neurokinin A caused no change in sGaw in the healthy subjects. Inhalation of substance P up to the highest concentration of 10(-6) mol/ml caused no change in sGaw in the asthmatic subjects. Neurokinin A, however, caused bronchoconstriction with a mean fall in sGaw of 48% (SEM 12%) after 5 x 10(-7) mol/ml. The onset of bronchoconstriction was rapid, but sGaw had returned to baseline values within one hour in all but one patient.
Thorax 1987 Oct
PMID:Effect of inhaled substance P and neurokinin A on the airways of normal and asthmatic subjects. 244 63

Inhalation of sodium metabisulphite is thought to induce bronchoconstriction by release of sulphur dioxide. We sought to establish the reproducibility of the airway response to inhaled sodium metabisulphite given in increasing doubling concentrations (0.3 to 160 mg/ml) to 13 asthmatic and five atopic non-asthmatic subjects and the contribution of cholinergic mechanisms to this response. In 15 of the 18 subjects bronchoconstriction was sufficient to allow calculation of the dose of metabisulphite causing a 20% reduction in the forced expiratory volume in one second (FEV1) from baseline values (PD20 metabisulphite). The 95% confidence limit for the difference between this and a second PD20 metabisulphite determined 2-14 days later was 2.5 doubling doses. The difference between repeat PD20 metabisulphite measurements was unrelated to the number of days between challenges or change in baseline FEV1. Ten subjects returned for a third study 3-120 days after the second challenge; variability in PD20 metabisulphite did not differ from that seen between the first and second challenges. PD20 methacholine was determined between the two metabisulphite challenges and found to correlate with PD20 metabisulphite (r = 0.71). Inhaled ipratropium bromide 200 micrograms given in a randomised, placebo controlled, crossover study to 10 subjects increased PD20 methacholine 42 fold but had no significant effect on the response to metabisulphite. A single inhalation of the PD20 metabisulphite in five subjects induced maximal bronchoconstriction 2-3 minutes after inhalation, with a plateau in FEV1 lasting a further four minutes before recovery. A further single inhalation of the same PD20 dose 43 minutes later produced a 27% (SEM 4%) smaller fall in FEV1 than the first inhalation. These results show that metabisulphite PD20 values measured over days and weeks show similar reproducibility to those reported for histamine inhalation and that PD20 metabisulphite correlates with methacholine responsiveness. Most of the bronchoconstriction is not inhibited by antimuscarinic agents; the underlying mechanisms require further investigation.
Thorax 1989 Dec
PMID:Characterisation of bronchoconstrictor responses to sodium metabisulphite aerosol in atopic subjects with and without asthma. 253 10


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