Search PubMed⌕ Search

Biomedical subjects

E H Ramsdale

Publications and source records attributed to E H Ramsdale.

At least 19 recordsLinked to original sources
PubMed2000

Induced sputum examination: diagnosis of pulmonary involvement in Fabry's disease.

Fabry's disease is a rare inherited metabolic disorder caused by a deficiency in the enzyme alpha-galactosidase A. It can affect almost every organ, including the lungs. Confirmation of lung involvement has depended on invasive bronchial biopsy specimens or brushings to confirm the presence of typical lamellar inclusion bodies within bronchial epithelial cells. We report a patient with known Fabry's disease in whom these inclusion bodies were identified by examination of induced sputum.

Adult↗
PubMed1992

A research method to induce and examine a mild exacerbation of asthma by withdrawal of inhaled corticosteroid.

This study evaluated a research method to examine an exacerbation of asthma induced by corticosteroid withdrawal. Ten non-smoking adult asthmatics who were stable on treatment with inhaled steroid underwent a graded reduction of the daily dose by 200 micrograms at weekly intervals until an exacerbation of symptoms occurred. A daily symptom, peak expiratory flow rate (PEF) and medication diary was kept. Weekly clinic visits were used to assess symptoms, spirometry, methacholine airway responsiveness (expressed as the provocative concentration to cause a fall in FEV1 of 20%, PC20), circulating eosinophils, basophils and their progenitors (Eo/B-CFU), and sputum inflammatory cells. The laboratory tests were performed blind to the clinical details. Each subject developed an exacerbation of symptoms, on average at 16 (7-26) days after the onset of steroid reduction. This was accompanied by a deterioration in each of the objective measures. There was a fall in FEV1 by 320 ml (s.e.m. 9.5) and in PC20 from 0.8 to 0.43 mg/ml. Circulating eosinophils rose from 114 (24) x 10(3)/ml to 227 (50) x 10(3)/ml and Eo/B-CFU rose from 31 (5.6) to 44 (11.3)/10(6) cells. Sputum developed in five subjects and contained 36 (5.2)% eosinophils and 1.98 (0.21)% metachromatic cells (mast cells or basophils). The symptom diary and weekly questionnaire were demonstrated to be valid and responsive to change. A deterioration indicated by the daily symptom score preceded changes in PEF. Treatment by an increase in steroid was followed by reversal of each of the changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1992

Formoterol compared with beclomethasone and placebo on allergen-induced asthmatic responses.

Formoterol is a new long-acting beta 2-agonist. We compared the protective effect of 24 micrograms formoterol with 200 micrograms beclomethasone and placebo on inhaled allergen-induced asthmatic responses in mild stable asthmatic subjects. We measured airflow rates, histamine airway responsiveness, cell counts from sputum and peripheral blood, and markers of lymphocyte and eosinophil activation. Adjustments were made for the confounding effect of bronchodilatation produced by formoterol in comparisons using a control inhalation of normal saline. Formoterol caused bronchodilation and inhibition of histamine airway responsiveness for at least 24 h. It completely inhibited the early asthmatic responses when beclomethasone had no effect. Control comparisons of the effect of formoterol and beclomethasone on the allergen-induced late asthmatic response and increase in histamine responsiveness showed each to be equally effective but not to inhibit the responses completely. Formoterol caused bronchodilation in addition to preventing bronchoconstriction. Both drugs inhibited the rise in serum eosinophil cationic protein 24 h after allergen, but neither inhibited the allergen-induced increases in sputum or blood eosinophils or CD25+ lymphocytes. These results suggest that formoterol modifies allergen-induced airway responses through functional antagonism rather than the inhibition of inflammatory cell infiltration.

Adult↗
PubMed1991

Prolonged protection against methacholine-induced bronchoconstriction by the inhaled beta 2-agonist formoterol.

Formoterol fumarate is a new, high-affinity, beta 2-adrenergic receptor agonist that causes bronchodilation for at least 12 h. The purpose of this study was to compare the magnitude and duration of the effect of inhalation of formoterol (12 and 24 micrograms), albuterol (200 micrograms), and placebo in terms of protection against methacholine-induced bronchoconstriction. The 16 stable adult asthmatic subjects were studied on four separate study days. On each study day the subjects inhaled 2 puffs of the study medication, and methacholine tests were performed at 30 min and 4, 8, and 12 h later. Results were expressed as the provocative concentration of methacholine required to cause a 20% fall in FEV1 (PC20). At 30 min, 12 and 24 micrograms formoterol caused a mean 14- to 20-fold decrease in responsiveness, and albuterol a 12-fold decrease. However, albuterol had no significant protective effect at 4 h or thereafter, whereas there was still an 8-fold decrease in responsiveness for 24 micrograms formoterol and a 6-fold decrease for 12 micrograms formoterol at 12 h. This study has shown that both doses of formoterol were still actively protective against induced bronchoconstriction 12 h after inhalation, with minimal side effects. This suggests that formoterol may prove to be a very useful bronchodilator for the treatment of patients with asthma who have significant airway hyperresponsiveness or nocturnal symptoms and who require inhaled beta 2-agonists at least twice daily.

Administration, Inhalation↗
PubMed1990

The role of measurements of airway responsiveness.

In smokers with chronic airflow limitation (CAL), airway hyperresponsiveness (AHR) to stimuli like methacholine, which act directly on airway smooth muscle, are not specific for the pathogenesis which is responsible for AHR to methacholine in subjects with normal spirometry, nor predictive for a beneficial effect of glucocorticosteroid (GCS) treatment. In contrast, AHR to stimuli like hyperventilation, which act indirectly through mediator release, may be specific for the pathogenesis of asthma and predictive for a beneficial effect of GCS. The validation of this possibility requires the demonstration that patients with CAL and AHR to hyper-ventilation demonstrate improvement after treatment with GCS (and have an increase in eosinophils and metachromatic cells in the sputum or bronchoalveolar lavage (BAL), like that seen in asthmatics uncomplicated by CAL).

Asthma↗
PubMed1990

Comparison of the efficacy and side effects of aqueous steroid nasal spray (budesonide) and allergen-injection therapy (Pollinex-R) in the treatment of seasonal allergic rhinoconjunctivitis.

The efficacy and side effects of two approaches to the treatment of ragweed pollen-induced rhinoconjunctivitis were compared in a double-blind, parallel-group trial. Sixty ragweed-sensitive adults were randomized either to a course of four Pollinex-R hyposensitization injections during the 6 weeks before the ragweed-pollen season, or to budesonide aqueous nasal steroid spray, 400 micrograms daily, throughout the season. A double-dummy technique was used to achieve blinding. During the ragweed-pollen season, troublesome nasal symptoms were treated with terfenadine, 60 mg, when treatment was needed, up to 240 mg daily, and eye symptoms were treated with naphazoline eye drops, when treatment was needed, up to four times daily. Every day, subjects recorded the severity of nasal and eye symptoms and medication use in a diary. Fourteen of the subjects receiving Pollinex-R were unable to complete the course of injections because of systemic or large local reactions. Eight subjects withdrew during the pollen season because of severe rhinitis; all subjects had received Pollinex-R. Subjects in the budesonide-treated group had minimal nasal symptoms and used very little terfenadine, compared with subjects in the Pollinex-R-treated group (p less than 0.0001). Eye symptoms and eye drop use were similar in the two treatment groups. No clinically important side effects were reported by the subjects receiving budesonide. The results of this study suggest that aqueous budesonide nasal spray is markedly more effective than Pollinex-R in controlling symptoms of seasonal rhinitis while the side effects and inconvenience of immunotherapy are avoided.

Aldehydes↗
PubMed1990

Differences in airway responsiveness in asthma and chronic airflow obstruction.

In patients with chronic obstructive lung disease, it is difficult to distinguish clinically between asthma, chronic bronchitis, and emphysema. This is due in part to the fact that the original definitions were not mutually exclusive. Diagnosis has not been helped by the measurement of airway responsiveness to methacholine or histamine, since responsiveness seems to be increased as often in those with chronic airflow obstruction as in asthmatic patients.

Asthma↗
PubMed1990

Effect of long-term treatment with an inhaled corticosteroid (budesonide) on airway hyperresponsiveness and clinical asthma in nonsteroid-dependent asthmatics.

Several short-term studies have shown that inhaled steroids can reduce airway hyper-responsiveness in asthma. To evaluate whether prolonged treatment can bring about full recovery, this double-blind, randomized, controlled trial examined the effect of budesonide, 400 micrograms daily for 1 yr, on airway hyperresponsiveness. The time course and characteristics of improvements and associated changes in clinical asthma severity were also evaluated. Thirty-two stable adult asthmatics, requiring bronchodilators alone, were selected. Before and monthly throughout the study, airway responsiveness to methacholine was measured and clinical asthma severity assessed by questionnaire, daily bronchodilator use, and number of asthma exacerbations. Patients receiving budesonide showed a fourfold mean improvement in airway responsiveness compared with those receiving placebo (p less than 0.0005), whose responsiveness remained very stable. Fifteen of the 16 budesonide subjects improved and 5 returned to the normal range. Largest improvements occurred during the first 3 months but, in some, were still progressing slowly at 1 yr. Improvements in responsiveness were accompanied by significant improvements in asthma symptoms, bronchodilator use, and number of asthma exacerbations. The results show that regular, prolonged use of inhaled steroid can produce marked improvements in airway hyperresponsiveness, sometimes with full resolution, and these improvements are accompanied by clinically significant improvements in clinical asthma.

Administration, Inhalation↗
PubMed1990

Long-term effects of budesonide on airway responsiveness and clinical asthma severity in inhaled steroid-dependent asthmatics.

Budesonide 400 micrograms daily, in nonsteroid-dependent asthma, can produce improvements in airway responsiveness and clinical asthma severity, with some patients returning to normal responsiveness and becoming asymptomatic. This study examined whether similar improvements occur when asthmatics, who are dependent upon inhaled steroids, take either a regular maintenance dose of inhaled steroid or twice that amount for a year. Thirty two asthmatics were each stabilized on the minimum amount of inhaled steroid that would keep symptoms non-troublesome. In a double-blind, randomized manner, half were assigned to remain on a maintenance dose (MD) and the rest received twice that dose (MDx2) for one year. Before and monthly throughout the study, airway responsiveness to methacholine was measured and clinical asthma severity assessed by questionnaire, inhaled bronchodilator use and number of asthma exacerbations. There was a significant improvement in airway responsiveness and clinical asthma severity in both treatment groups. Those on MDx2 showed the greatest improvement but the difference between the two groups did not reach significance. This study provides strong evidence that prolonged use of inhaled steroids is associated with improvement in airway responsiveness and clinical asthma severity in inhaled steroid-dependent asthma with a suggestion that the improvements are dose related.

Administration, Inhalation↗
PubMed1989

Chronic cough: eosinophilic bronchitis without asthma.

Sputum cell-counts were studied in 7 non-smokers with corticosteroid-responsive chronic cough productive of sputum and 8 smokers with a clinical diagnosis of chronic bronchitis, all of whom had normal lung function tests and methacholine airway responsiveness, and in 10 non-smokers with asthma, examined during an exacerbation. Sputum from asthmatic patients and subjects with corticosteroid-responsive cough contained eosinophils and metachromatic cells. Macrophages were by far the dominant cell type in sputum from subjects with chronic bronchitis. Airway inflammation with eosinophils and metachromatic cells is not always accompanied by increased airway responsiveness, and current definitions of obstructive airways disease may need to be revised.

Adult↗
PubMed1989

Inhalation of adenosine 5'-monophosphate increases methacholine airway responsiveness.

Airway hyperresponsiveness is a characteristic feature in asthmatic subjects, but the mechanism of the hyperresponsiveness is not known. The purpose of this study was to investigate whether methacholine airway responsiveness was increased 24 h after inhalation of adenosine 5'-monophosphate (AMP). Ten atopic asthmatic subjects and six atopic normal subjects were studied on 4 study days. On the 1st day, a methacholine inhalation test was performed, followed within 48 h by an AMP inhalation test. Seven days later the second AMP test was performed, and 24 h later the methacholine inhalation test was repeated. Response was measured using partial flow-volume curves, and the concentration required to cause a 40% fall in the partial flow-volume curve (PC40) was calculated. The geometric mean methacholine PC40 fell from 1.36 mg/ml on day 1 (before AMP inhalation) to 0.71 mg/ml on day 4 (24 h after AMP inhalation, P less than 0.01). There was no change in the mean PC40 for adenosine on the 2 study days (5.82 and 7.06 mg/ml, P greater than 0.1). These findings suggest that adenosine release may contribute to the increase in airway responsiveness after allergen challenge.

Adenosine Monophosphate↗
PubMed1986

The origin of airway hyperresponsiveness.

Consideration of the origin of airway hyperresponsiveness appears central to understanding the origin of asthma. Subjects with and without asthma differ both in the ease with which airway narrowing is produced by inhalation of histamine or methacholine and in the ability to demonstrate a maximal response to these agents. The latter appears, on present evidence, to be due to an added mechanism in asthma rather than the absence of a potent inhibitory process. Airway hyperresponsiveness is probably acquired during life as a result of airway reactions to various stimuli, although genetic factors such as atopy are likely to predispose the person to develop hyperresponsiveness. Environmental stimuli include inhaled allergens, chemical sensitizers, airway infections, immunization, and ozone. Allergen-induced airway hyperresponsiveness occurs in association with late-phase asthmatic responses. This and ozone-induced hyperresponsiveness have been demonstrated to be associated with release of chemical mediators and the cellular phase of inflammation. Their effect does not appear to be accounted for by increase in airway epithelial permeability, decrease in airway caliber, reflex bronchoconstriction, or beta-adrenoceptor blockade. The mechanism(s) responsible for the induced hyperresponsiveness are unknown but may involve airway epithelial damage, edema in and around the airway walls, stimulation of the noncholinergic excitatory or inhibition of the nonadrenergic inhibitory systems, or a change in function of airway smooth muscle. Airway hyperresponsiveness can be transient or persistent. Transient increases in responsiveness are almost certainly associated with mediator release and inflammation. It is not known whether persistent hyperresponsiveness is due to the same process, fired, for example, by leaky mediator-releasing cells and/or to some persisting change in neurogenic or smooth muscle function.

Allergens↗
PubMed1986

Interpretation of the variability of peak flow rates in chronic bronchitis.

Increased diurnal variation of expiratory flow rates has been documented in patients with chronic bronchitis, but this could be secondary to the disease process of bronchitis rather than an associated disease--namely, asthma. Peak expiratory flow was measured twice daily before and after inhalation of 200 micrograms salbutamol in 34 subjects with chronic bronchitis. The FEV1 ranged from 38% to 121% predicted. Diurnal variation (expressed as highest-lowest/highest (%)) was increased in 18 subjects, all but three of whom had airflow obstruction and an increase in methacholine airway responsiveness. There was only a weak correlation between diurnal variation and airway responsiveness (r = -0.54) or the severity of the airflow obstruction. This finding, together with the occurrence of an increase in diurnal variation without an increase in methacholine airway responsiveness in three subjects, suggests that the increased diurnal variation in chronic bronchitis may have a different underlying mechanism from that in asthma.

Airway Resistance↗
PubMed1986

Airway responsiveness to histamine or methacholine: advances in measurement and interpretation.

A number of topical aspects of histamine or methacholine inhalation tests were discussed. First, the reporting of results as the dose delivered to the mouth by the method of aerosol generation and inhalation may allow better interpretation of results between laboratories. However, this requires investigation. Second, the histamine or methacholine dose-response curve differs in asthmatics with a moderate to severe increase in airway responsiveness from asthmatics with a mild increase in responsiveness or nonasthmatics. In the latter groups, the dose-response curve is positioned to the right and has a maximal response plateau. The disappearance of this limited maximal airway narrowing in asthmatics appears to be due to added abnormalities. Third, histamine or methacholine inhalation tests provide a sensitive and specific measure of the presence of variable airflow obstruction (asthma). They are useful to validate the diagnosis when symptoms are suggestive but spirometry is normal. The symptoms of asthma are not specific, and without objective confirmation the diagnosis is frequently misjudged even by the specialist. Finally, airway hyperresponsiveness to histamine or methacholine is not diagnostic of asthma when chronic airflow limitation is present; hyperresponsiveness to isocapnic hyperventilation may be more specific.

Asthma↗
PubMed1986

Do physicians need objective measurements to diagnose asthma?

The frequency with which disagreement occurs between the clinician's diagnosis of asthma and the objective measurement of methacholine airway responsiveness is not known. We have examined this in 51 consecutive new adult patients presenting with symptoms consistent with asthma but with normal spirometry. Disagreement between the physician's assessment and the result of the methacholine test occurred in 20 patients (39%). Of these, 13 had a clinical diagnosis of asthma but normal responsiveness and 7 had an unexpected increase in methacholine responsiveness. There was no difference in the type of symptoms experienced whether or not there was agreement between the test and the physician's assessment. Thus, an objective measurement like a methacholine inhalation test is clinically useful when spirometry is normal. A normal methacholine test in the presence of symptoms suggestive of asthma should alert the physician to the need for further investigation.

Adult↗