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Biomedical subjects

N C Thomson

Publications and source records attributed to N C Thomson.

At least 73 records · Page 4Linked to original sources
PubMed1994

Activity of the renin-angiotensin system in acute severe asthma and the effect of angiotensin II on lung function.

BACKGROUND: The activity of the renin-angiotensin system in asthma has not been studied previously and the effect of angiotensin II (AII) on bronchomotor tone in vivo is unknown. METHODS: Plasma levels of renin and AII levels were measured in 20 patients with acute severe asthma, nine with mild asthma, 10 with severe chronic asthma, and 16 normal volunteers. The effect of AII, given as an intravenous infusion, on bronchomotor tone was also investigated in eight mild asthmatic patients. RESULTS: In acute severe asthma plasma levels of renin [median (interquartile range)] were elevated on days 1, 2, and 5 after admission [48.7 (24-79), 44.2 (15-75), and 45.5 (21-70) microU/ml, respectively]. Plasma AII levels were significantly elevated at day 5 [56 (12-109) pg/ml]. In the second study a bronchoconstrictor response to intravenous AII was seen with a mean (SE) maximal fall in FEV1 of 0.34 (0.13) litres or 12.4 (3.3)% from baseline following the high dose infusion of AII (8 ng/kg/min) with a corresponding plasma AII concentration of 121.3 pg/ml. CONCLUSIONS: The renin-angiotensin system is activated in acute asthma and AII causes bronchoconstriction in vivo in man. These observations suggest that in some patients AII may contribute to bronchoconstriction during acute severe asthma.

Acute Disease↗
PubMed1994

Ultrasound assessment of normal hemidiaphragmatic movement: relation to inspiratory volume.

BACKGROUND: Traditionally the radiological assessment of diaphragmatic movement has relied on fluoroscopy. Ultrasound scanning has recently been shown to be a sensitive and reproducible method of assessing hemidiaphragmatic movement in normal subjects. A study was undertaken to examine how movement of the diaphragm measured by ultrasound scanning relates to inspired lung volumes measured by spirometric testing. METHODS: Ultrasound examinations were performed on 14 normal volunteers using a 3.5 MHz sector transducer (Acuson 128). A fixed skin position on each lateral chest wall between the anterior clavicular and midaxillary line was selected symmetrically to obtain a longitudinal plane of each hemidiaphragm including the maximal renal bipolar length, allowing identification of the adjacent posterior aspect of the diaphragm. Craniocaudal excursions of the posterior part of each hemidiaphragm on successive respiratory cycles were recorded on videotape and compared with spirometric measurements recorded simultaneously on a water bath spirometer. Measurements were made in the sitting and supine position and were repeated on a separate occasion (at least two weeks apart) in 10 subjects by the same operator to assess reproducibility. RESULTS: The relation between inspired volume and hemidiaphragmatic movement was found to be linear. The gradient of these observed linear relations (hemidiaphragmatic excursion (mm)/inspired volume (1)) was calculated and their distribution for each hemidiaphragm followed a normal distribution irrespective of position. The 95% confidence limits of the right to left ratio of these gradients in the supine position were 0.53 and 1.7. Change of posture from the supine to the sitting position reduced the gradient. The technique had acceptable reproducibility with coefficients of variation for the supine position of 7.5% and 11.7% for right and left hemidiaphragm respectively. CONCLUSION: Ultrasound scanning is a simple, non-invasive and reproducible means of assessing hemidiaphragmatic movement, yielding quantitative information which relates to inspired lung volumes.

Adult↗
PubMed1994

Computed tomographic scanning of the lung in patients with allergic bronchopulmonary aspergillosis and in asthmatic patients with a positive skin test to Aspergillus fumigatus.

BACKGROUND: Allergic bronchopulmonary aspergillosis is a disease of asthmatic patients which may follow a protracted course and result in chronic lung damage such as central bronchiectasis. In asthma uncomplicated by allergic bronchopulmonary aspergillosis, in particular in asthmatic patients with immediate hypersensitivity type skin reactions to Aspergillus fumigatus, the incidence of bronchiectasis is uncertain. METHODS: Computed tomographic (CT) scans were performed in 17 asthmatic patients of mean (SE) age 60.1 (2.5) years, FEV1 49.4 (5.8)% predicted with allergic bronchopulmonary aspergillosis (all with current or previous positive precipitins to A fumigatus) and in 11 asthmatic patients of mean (SE) age 49.5 (5.8) years, FEV1 75.5 (6.5)% predicted, skin test positive for A fumigatus, but without the clinical or serological features of allergic bronchopulmonary aspergillosis (non-allergic bronchopulmonary aspergillosis group). RESULTS: Bronchial dilatation was more common in the group with allergic bronchopulmonary aspergillosis, affecting 14 patients compared with two in the non-allergic bronchopulmonary aspergillosis group. Evidence of bronchiectasis was found in 43 of a possible 102 lobes of patients with allergic bronchopulmonary aspergillosis, compared with three of a possible 66 in the non-allergic bronchopulmonary aspergillosis group. Bronchial wall thickening was common to both, affecting 16 and nine patients respectively. Pleural thickening on CT scanning was common in the group with allergic bronchopulmonary aspergillosis, being noted in 14 patients compared with only three in the non-allergic bronchopulmonary aspergillosis group. CONCLUSIONS: Bronchiectasis is common in allergic bronchopulmonary aspergillosis but occurs only occasionally in asthmatic patients with a positive skin test to A fumigatus but without other features of the disease.

Aspergillosis, Allergic Bronchopulmonary↗
PubMed1994

High dose inhaled atrial natriuretic peptide is a bronchodilator in asthmatic subjects.

Atrial natriuretic peptide (ANP) has been shown to be an effective bronchodilator when given intravenously, but its efficacy by inhalation has not been assessed. In the first part of the current study, six asthmatic subjects, mean (SEM) forced expiratory volume in one second (FEV1) 2.09 (0.30) l, received 0.1 and 1 mg atrial natriuretic peptide by inhalation, and in the second study five subjects, FEV1 1.92 (0.40) l, received 5 mg ANP by inhalation. ANP was given in a placebo-controlled, double blind, randomized manner, with measurement of FEV1 over the following 60 min. Nebulized salbutamol was given at 60 min as a measure of the maximal bronchodilator response attainable by conventional therapy. No significant bronchodilator effect was seen following the 0.1 or 1 mg inhalation, although the latter produced a minimal transient elevation in peripheral atrial natriuretic peptide plasma levels. A bronchodilator effect was seen with the 5 mg dose, which produced delta FEV1 0.42 (0.09) l compared to 0.93 (0.13) l subsequently produced by salbutamol. This effect peaked at 5 min and was no different from placebo from 10 min onwards. We conclude that atrial natriuretic peptide may produce significant bronchodilation when given by inhalation in high doses, and speculate that substances which generate cyclic guanosine monophosphate (cGMP) in airway smooth muscle warrant further investigation as potential bronchodilatory agents.

Administration, Inhalation↗
PubMed1994

No effect of the oral neutral endopeptidase inhibitor candoxatril, on bronchomotor tone and histamine reactivity in asthma.

Neutral endopeptidase (NEP) is found in many tissues in man, including the lung. Metabolism by NEP is one of the main mechanisms for the clearance of atrial natriuretic peptide (ANP), a hormone that causes bronchodilation and reduces nonspecific bronchial reactivity in man. Candoxatril, an oral NEP inhibitor has been shown to elevate circulating ANP levels. We have sought to determine whether the administration of candoxatril will alter bronchomotor tone (forced expiratory volume in one second (FEV1)) and histamine reactivity. Ten male asthmatic patients with stable asthma were enrolled (mean (SD) age 32 (10) yrs; FEV1 92 (11)% predicted) in a randomized, double-blind, placebo-controlled study. On each study day, after baseline spirometry, patients received 200 mg of candoxatril or placebo. Spirometry was repeated at half hourly intervals. After 2 h a histamine inhalation test was performed. There was no significant difference in FEV1 values at baseline or at 2 h post-dosing between active and placebo study days, with mean (SEM) FEV1 at baseline and 2 h of 3.71 (0.29) l and 3.85 (0.29) l on the placebo day, and 3.89 (0.27) l and 4.05 (0.82) l on the active day, respectively. The geometric mean (range) provocative concentration of histamine producing a 20% fall in FEV1 (PC20) on the placebo day and active day did not differ significantly, being 1.17 (0.25-25.8) and 0.93 (0.13-32) mg.ml-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Bronchodilator, cardiovascular, and cyclic guanylyl monophosphate response to high-dose infused atrial natriuretic peptide in asthma.

Atrial natriuretic peptide (ANP) has bronchodilator and vasodilator properties thought to be mediated through the generation of cyclic guanylyl monophosphate (cGMP). The current study was designed to examine the effects of infused ANP on respiratory (FEV1), cardiovascular (blood pressure and pulse), and metabolic (plasma cGMP) function in asthmatic patients. Eight patients with a mean +/- SD age of 45.6 +/- 8.2 yr and mean FEV1 of 56.4 +/- 15.4% of predicted were studied using a randomized double-blind crossover design. On one study day after baseline measurements (FEV1, blood pressure, pulse, and plasma cGMP), ANP was infused for 20-min periods at 5 pmol/kg/min and at 25 pmol/kg/min; a placebo (saline) inhalation was then administered. On the other day the placebo infusion was followed by inhalation of 5 mg albuterol. Measurements were repeated at the end of each 20-min period. The highest rate of ANP infusion increased the FEV1 by 0.50 +/- 0.09 L compared with 0.09 +/- 0.05 after the placebo infusion (p < 0.001). The increase in FEV1 produced by ANP plus placebo inhalation (0.50 +/- 0.28 L) was similar to that produced by placebo infusion plus albuterol inhalation (0.61 +/- 0.30 L). There was no clinically significant fall in systolic or diastolic blood pressure (torr) at the 25 pmol/kg/min infusion rate. The mean basal cGMP was 602 +/- 242 fmol/ml and increased to 5,883 +/- 1,460 and 21,182 +/- 2,509 with the two rates of ANP infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Asthma. Anti-inflammatory therapies.

It is likely that airway inflammation has an central role in the development and maintenance of the structural and functional abnormalities that characterise asthma. The recognition that asthma is a chronic inflammatory disorder of the airways has resulted in an increased emphasis on the use of anti-inflammatory drugs. The principal anti-inflammatory drugs are corticosteroids and to a lesser extent sodium cromoglycate and nedocromil sodium. Several other drugs and therapies may also have anti-inflammatory effects in asthma. The early use of prophylactic anti-inflammatory agents is advocated in the treatment of chronic asthma. It is hoped that this treatment scheme will result in a reduction in the morbidity and mortality from this common chronic condition.

Adult↗
PubMed1992

Effect of atrial natriuretic peptide given by intravenous infusion on bronchoconstriction induced by ultrasonically nebulized distilled water (fog).

Atrial natriuretic peptide (ANP) is secreted by cardiac atria and lung tissue; it has a bronchodilator action in normal subjects and patients with asthma and has been shown to protect against histamine-induced bronchoconstriction in patients with asthma. Bronchoconstriction caused by inhalation of ultrasonically nebulized distilled water (fog), in contrast to histamine-induced bronchoconstriction, has features in common with exercise-induced asthma but can be given more easily in a dose-response fashion. The present study aimed to determine the effect of elevated plasma ANP concentrations on the bronchoconstrictor response to inhalation of fog. Eight patients with atopic asthma were studied, mean baseline FEV1 3.00 1, equivalent to 89% (range 76-103%) predicted. The provocation dose of fog producing a 25% fall in FEV1 (PD25) was determined for each subject. On 4 study days, subjects received an intravenous infusion of placebo or ANP at a rate of 1.25, 3.0, or 10.0 pmol/kg/min in randomized, double-blind manner for 30 min to allow steady-state plasma concentrations to be achieved; the PD25 fog was then administered and FEV1 recorded over 30 min. Mean (SEM) baseline plasma ANP concentration was 19.3 (4.1) pg/ml and increased to 39.4 (6.6), 106.4 (11.1), and 445.9 (105.4) with the three rates of ANP infusion. The highest rate of infusion increased prechallenge FEV1 by 8.7 (2.4)% (p less than 0.01), but the lower rates of infusion had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Effect of controlled-release salbutamol in predominantly non-reversible chronic airflow obstruction.

We conducted a multicentre, randomized, double-blind, placebo-controlled, parallel group study to determine the efficacy of controlled release salbutamol (SCR) tablets in clinically stable patients with predominantly non-reversible chronic airflow obstruction (CAO). Patients received either 8 mg SCR or matching placebo tablets twice daily for 6 weeks. Fifty-eight patients (30 on SCR and 28 on placebo) completed the study. Outcome measurements included FEV1, FVC, 6-min walking distance, and patient assessment of efficacy recorded at the clinic visits and twice daily PEFR measurements plus daytime symptom score recorded in diary cards. The absolute change between baseline and 6-week measurements with SCR was compared to that with placebo. Favourable trends were observed with SCR for all variables tested except FVC. The only significant difference between SCR and placebo was in FEV1 where there was a small net change of 95 ml in favour of SCR. We conclude, therefore, that the effects of lung function of long-term bronchodilator therapy with SCR in patients with stable non-reversible CAO are slight, and are likely to be of limited clinical benefit.

Albuterol↗
PubMed1991

Circulating plasma concentrations of atrial natriuretic peptide and catecholamines in response to maximal exercise in normal and asthmatic subjects.

BACKGROUND: Intravenous infusion of atrial natriuretic peptide has been shown to cause bronchodilatation in patients with asthma and endogenous atrial natriuretic peptide is known to rise with exercise. Whether an aberration in release of atrial natriuretic peptide is concerned in the pathogenesis of exercise induced bronchoconstriction has not been studied. METHODS: The atrial natriuretic peptide response to exercise was studied in eight men with exercise induced asthma and eight age matched non-asthmatic men. Subjects exercised to exhaustion on a treadmill, using the Bruce protocol. Atrial natriuretic peptide and catecholamines were measured at the end of each stage of exercise and oxygen consumption and heart rate were monitored throughout. RESULTS: Both groups showed a 3.5 fold increase in plasma atrial natriuretic peptide during exercise (mean (SE): normal subjects 25 (4) pmol/l; asthmatic subjects 24 (5) pmol/l), with no difference between the two groups. There was a close correlation between plasma atrial natriuretic peptide concentrations and oxygen uptake, catecholamine release, and heart rate in both groups. The catecholamine response was similar in the asthmatic and normal subjects, both groups showing a four fold rise in plasma adrenaline and a 4-5 fold rise in plasma noradrenaline. CONCLUSION: A defect in the release of circulating atrial natriuretic peptide does not account for exercise induced asthma; the concentrations of the circulating peptide that were achieved may effect a small reduction in airway reactivity. Our data do not support the idea that asthmatic patients have abnormal sympathoadrenal activity.

Adult↗
PubMed1991

Influence of elevated plasma levels of atrial natriuretic factor on bronchial reactivity in asthma.

Recent studies have demonstrated that elevation of plasma atrial natriuretic factor (ANF) levels may produce significant bronchodilation in the constricted asthmatic airway. The current study was designed to examine the effect of both physiologic and pharmacologic plasma levels of ANF on bronchial reactivity to histamine in asthmatic subjects. A total of eight atopic men with well-controlled asthma were studied, mean (SD) FEV1 3.50 (0.73) L, equivalent to 87 (11)% of predicted; bronchial reactivity as measured by histamine PC20 was 0.77 mg/ml (geometric mean). On four separate study days infusions of 1, 3, or 10 pmol/kg/min of ANF or placebo were administered in a double-blind, randomized manner. Once steady-state plasma levels had been achieved, measurement of bronchial reactivity was repeated. Mean (SEM) basal ANF level was 18.5 (3.5) pg/ml and rose to 41 (4.3), 157 (15), and 500 (30) pg/ml with increasing doses of ANF. With placebo infusion geometric mean histamine PC20 was 0.77 mg/ml and rose to 1.15 mg/ml (p less than 0.05), 1.90 mg/ml (p less than 0.001), and 3.38 mg/ml (p less than 0.001), corresponding to a 1.5-, 2.5-, and 4.4-fold protection with respective ANF infusions. There was no significant change in plasma epinephrine. These results show that at both physiologic and pathophysiologic plasma levels ANF may significantly decrease bronchial reactivity to histamine in asthma.

Adult↗
PubMed1990

Airway responses to deep inspiration in diabetic autonomic neuropathy.

The role of vagal mechanisms in the reversal of pharmacologically-induced bronchoconstriction by deep inspiration is unclear. We examined the effect of lung inflation on methacholine-induced bronchoconstriction in six patients with severe diabetic autonomic neuropathy compared with five patients with diabetes mellitus and normal tests of autonomic function. The effect of deep inspiration on bronchomotor tone was expressed as the ratio of maximal flow rates at 70% of expiratory vital capacity (V30) calculated from complete (V30(c)) and partial (V30(p)) flow-volume curves (V30(c)/V30(p)). In patients with autonomic neuropathy the mean (range) of this ratio was 1.31 (1.19-1.47) and was not significantly different from the control patients with a mean ratio of 1.69 (1.28-2.13). These results suggest that the reversal of methacholine-induced bronchoconstriction by a deep inspiration is not mediated via vagal nerves.

Adult↗
PubMed1990

Prophylaxis of exercise-induced asthma with inhaled formoterol, a long-acting beta 2-adrenergic agonist.

The prophylaxis of exercise-induced asthma with inhaled formoterol (12 micrograms) was compared with inhaled salbutamol (200 micrograms) and placebo in 12 patients with atopic asthma. Both drugs produced equal bronchodilation 2 and 4 h after administration. Both drugs protected equally against exercise-induced bronchoconstriction 2 h after administration; at 4 h, formoterol gave undiminished protection from that seen at 2 h while salbutamol was no more effective than placebo.

Adult↗
PubMed1990

Effect of atrial natriuretic factor on bronchomotor tone in the normal human airway.

1. Asthmatic patients bronchodilate in response to infused atrial natriuretic factor. We wished to determine whether the airways of normal subjects responded in a similar way. 2. Changes in airway resistance, as determined by specific airway conductance, were measured in eight normal subjects in response to intravenous infusion of atrial natriuretic factor at doses of 0.5, 2 and 10 pmol min-1 kg-1. 3. No significant effect was observed on specific airway conductance at any rate of infusion despite maximum mean (SEM) plasma levels of 597 (62) pg of atrial natriuretic factor/ml in peripheral venous blood. 4. A second study was performed using six of the eight original subjects and employing a pharmacological dose of 50 pmol of atrial natriuretic factor min-1 kg-1. This produced mean plasma levels of 2056 pg/ml and a mean increase of 31% in specific airway conductance. 5. It is concluded that pharmacological, but not pathophysiological, elevations of plasma atrial natriuretic factor may significantly alter bronchomotor tone in normal subjects.

Adult↗
PubMed1990

Management of recurrent malignant pleural effusion in the United Kingdom: survey of clinical practice.

Malignant pleural effusions are often symptomatic and tend to recur after simple aspiration. Pleurodesis may prevent recurrence of the effusion; many agents and techniques have been described. A questionnaire was sent to 448 clinicians in the United Kingdom to determine how pleurodesis is performed in practice. There was a 56% overall response, with replies from 101 respiratory physicians, 88 general physicians, 29 thoracic surgeons, and 35 general surgeons. General surgeons saw few cases of malignant pleural effusion and rarely performed pleurodesis. A patient with recurrent malignant pleural effusion would usually be managed with pleurodesis by 76 (76%) respiratory physicians, 26 (30%) general physicians, and 23 (81%) thoracic surgeons; a further 29 (33%) general physicians would refer such patients to another specialist. Most medical pleurodesis were performed by junior staff, whereas consultant thoracic surgeons were more likely to be concerned with the procedure. All the thoracic surgeons used an intercostal tube drain, usually with suction. An intercostal tube drain was used routinely by only 54 (54%) of the respiratory physicians and 28 (32%) general physicians. Thoracic surgeons preferred talc for pleurodesis whereas physicians most commonly used tetracycline. The variety of methods in use supports the need for randomised, controlled studies to determine the most effective technique of pleurodesis.

Bleomycin↗