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Biomedical subjects

D W Cockcroft

Publications and source records attributed to D W Cockcroft.

At least 55 records · Page 3Linked to original sources
PubMed1996

Inhaled corticosteroids do not prevent the development of tolerance to the bronchoprotective effect of salmeterol.

INTRODUCTION: Twice-daily inhaled salmeterol produces rapid reduction in its acute bronchoprotective effect against methacholine in patients with mild asthma. This investigation examined this effect in patients with moderate asthma who were using inhaled corticosteroids. SUBJECTS AND METHODS: Eight asthmatic volunteers who required inhaled corticosteroids for control of their symptoms and who were able to withhold treatment with beta 2-agonists for 4 weeks before and during the study participated in a double-blind, crossover, placebo-controlled study with two random-order treatment periods: inhaled salmeterol, 50 microg twice a day for seven doses, and placebo in similar fashion, with a 7-day or greater washout between these periods. Methacholine inhalation tests were done 1 h after doses 1, 3, 5, and 7, and then 24 h after the last dose of the study inhaler, 10 min post-200 microg salbutamol. RESULTS: Baseline FEV1 measurements before doses 3, 5, and 7 of salmeterol, ie, 12 h after salmeterol, were significantly higher than all other baseline values. Twenty-four hours after the last dose of salmeterol, the FEV1 was no different from that during the placebo period. The geometric mean methacholine concentration causing a 20% fall in FEV1 (PC20) following the third dose of salmeterol (6.8 mg/mL) was significantly lower than after the first dose of salmeterol (12.0 mg/mL; p=0.031), and this reduction of bronchoprotection persisted following doses 5 and 7. The methacholine PC20 10 min postsalbutamol measured after the salmeterol period was significantly lower than after placebo (5.6 vs 13.3 mg/mL; p<0.001). CONCLUSIONS: Tolerance to the acute bronchoprotective effect of salmeterol was significant after the first two doses and persisted after the seventh dose. Tolerance to the acute bronchoprotective effect of salbutamol was also significant after regular use of salmeterol for seven doses. These effects, in subjects using inhaled corticosteroids regularly, were similar to the those previously seen in patients with mild asthma using as-required beta 2-agonists only, indicating that tolerance is not prevented by use of inhaled corticosteroids.

Administration, Inhalation↗
PubMed1995

Recent trends in the use of inhaled beta 2-adrenergic agonists and inhaled corticosteroids in Saskatchewan.

OBJECTIVE: To examine recent trends in the use of inhaled beta 2-adrenergic agonists and inhaled corticosteroids for the treatment of asthma among Saskatchewan residents and to determine whether these trends are in keeping with widely publicized guidelines recommending a reduction in the use of agents to treat symptoms (i.e., inhaled beta 2-adrenergic agonists) and increased use of prophylactic agents (i.e., inhaled corticosteroids). DESIGN: Descriptive pharmacoepidemiologic study conducted with the use of data from the computerized database of the Saskatchewan Prescription Drug Plan. SETTING: Saskatchewan. PATIENTS: Saskatchewan residents 5 to 54 years of age who received one or more outpatient prescriptions for drugs to treat asthma (inhaled drugs, ingested beta 2-adrenergic agonists and ingested methylxanthines) from 1989 to 1993. OUTCOME MEASURES: Epidemiologic trends, calculated for each year: number of prescriptions per 1,000 persons; number of patients who received prescriptions for inhaled corticosteroids, inhaled beta 2-adrenergic agonists and any type of drug to treat asthma; mean number of such prescriptions per patient; and weighted mean amount of salbutamol, fenoterol and beclomethasone dispensed per patient. RESULTS: There has been an increase in the proportion of the population receiving prescriptions for drugs to treat asthma. The number of patients receiving these drugs per 1,000 people rose during the study period from 33.38 to 46.59 for any drug to treat asthma, from 24.70 to 33.77 for inhaled beta 2-adrenergic agonists and from 6.1 to 19.9 for inhaled corticosteroids. The mean number of prescriptions per patient decreased steadily for all drugs to treat asthma (from 5.34 in 1989 to 3.88 in 1993), for inhaled beta 2-adrenergic agonists (from 4.35 to 3.09) and for inhaled corticosteroids (from 2.98 to 2.25). The weighted mean amount of inhaled salbutamol dispensed per patient per year decreased by 40%, from 178.08 mg in 1989 to 109.14 mg in 1993. The weighted amount of fenoterol dispensed per patient per year declined even more, by 58%, from 387.91 mg in 1989 to 164.00 mg in 1993. Conversely, the weighted amount of inhaled beclomethasone dispensed per patient per year increased by 35% from 46.95 mg in 1989 to 63.50 mg in 1992, then dropped to 56.17 mg per year in 1993. CONCLUSION: These data demonstrate a substantial change in Saskatchewan in the prescribing of drugs to treat asthma; they suggest that many physicians responded to current guidelines advocating increased attention to prevention of airway inflammation in the treatment of asthma.

Administration, Inhalation↗
PubMed1995

Regular use of inhaled albuterol and the allergen-induced late asthmatic response.

BACKGROUND: We have recently demonstrated that a 2-week course of inhaled albuterol 200 micrograms four times daily caused a near doubling of the allergen-induced early asthmatic response. We hypothesized that this might extend to the more clinically relevant late asthmatic response. METHODS: We studied 11 patients with atopic asthma who were free from all medications including inhaled beta 2-agonists for more than 4 weeks. We performed a double-blind, random-order, crossover study, comparing the effect of 1-week treatment periods of albuterol 200 micrograms four times daily and placebo 2 puffs four times daily on the early and late asthmatic responses to the same dose of allergen. RESULTS: Regular use of albuterol did not influence the baseline forced expiratory volume in 1 second (FEV1) (3.40 vs 3.42 L, p = 0.84) or the baseline methacholine provocative concentration causing a 20% fall in FEV1 (PC20) (geometric mean, 2.4 mg/ml vs 1.9 mg/ml, p = 0.38). However, all aspects of the allergen-induced asthmatic response were increased. After the 1-week albuterol treatment, the early asthmatic response was slightly greater (21.1% vs 17.9% FEV1 fall, p = 0.26), the late response was greater (23.1% vs 13.2% FEV1 fall, p = 0.0027), and the allergen-induced increase in airway responsiveness (change in log methacholine PC20) was greater (0.37 vs 0.20, p = 0.045). CONCLUSIONS: One week of albuterol treatment (200 micrograms four times daily) increased the late asthmatic response and allergen-induced increase in airway responsiveness. This suggests that the combination of regular use of inhaled beta 2-agonist and allergen exposure may cause more airway inflammation than allergen exposure alone.

Administration, Inhalation↗
PubMed1995

Reproducibility of allergen-induced early and late asthmatic responses.

BACKGROUND: Constant-dose allergen inhalation challenges are frequently used to examine the effect of antiasthma drugs on the allergen-induced early and late asthmatic responses. The end-point measurements in such studies are the maximal early and late percent decreases in the forced expiratory volume in 1 second (FEV1). OBJECTIVE: Our purpose was to observe the reproducibility and to determine the sample sizes required for such studies. METHODS: Twenty-eight subjects with allergen-induced early and late responses were studied with two constant-dose allergen challenges separated by 2 to 12 weeks. The early response was measured as the maximum percent decrease in FEV1 during the first 2 hours and the late response as the maximum percent decrease in FEV1 between 3 to 7 hours. RESULTS: The mean +/- SEM early responses were 23.1% +/- 1.0% and 24.7% +/- 2.0%, whereas the mean late responses were 23.3% +/- 2.0% and 24.5% +/- 2.2%. Reproducibility of measurements were such that fewer than eight subjects are required, to show 50% attenuation of either the early or late response (with 90% power). CONCLUSIONS: The method of constant-dose allergen challenge is a sensitive tool for detecting changes in early and late asthmatic responses after the use of antiasthma medication.

Administration, Inhalation↗
PubMed1995

Interaction of inhaled beta 2 agonist and inhaled corticosteroid on airway responsiveness to allergen and methacholine.

Regular treatment with salbutamol increases airway responsiveness to allergen but not to methacholine and produces tolerance to the bronchoprotective effect of salbutamol. The current study addresses the effect of inhaled corticosteroid on these aspects of regular beta 2 agonist use. A group of 13 atopic asthmatic subjects free from all asthma medications and remote from allergen exposure were studied. We used a double-blind, random-order, crossover study to compare four 1-wk treatment periods with > or = 1 wk washout: placebo, salbutamol, 200 micrograms four times per day, budesonide, 400 micrograms four times per day, and the combination of salbutamol and budesonide. We measured the methacholine PC20 and the methacholine dose shift produced acutely by 200 micrograms salbutamol after 7 d and the allergen PC15 after 8 d treatment. Blinded medications were withheld for 8 to 10 h before measurements. The methacholine PC20 was not affected by regular salbutamol but increased significantly (p < 0.014) after both budesonide-containing regimens. Neither the dose shift nor its significant reduction by regularly used beta 2 agonist were influenced by the inhaled corticosteroid. The four allergen PC15 values were significantly different from each other. Compared with placebo, the allergen PC15 was 0.6 doubling doses lower after salbutamol (p = 0.021) and 1.3 doubling doses higher after budesonide (p < 0.001); the allergen PC15 was reduced by 0.53 doubling doses from this new baseline (p = 0.039) when salbutamol and budesonide were used together.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1995

Self-injection with olive oil. A cause of lipoid pneumonia.

A 48-year-old man with unipolar depression and a psychosexual problem concerning his body image was injecting his scrotum repeatedly with olive oil to increase the size of his genitals. He developed respiratory failure following accidental intravenous injection of olive oil and was found to have lipogranulomatous lesions in the lung and the scrotum.

Body Image↗
PubMed1995

Rapid onset of tolerance to the bronchoprotective effect of salmeterol.

INTRODUCTION: Twice-daily inhaled salmeterol for 4 weeks produces marked reduction in its acute bronchoprotective effect against methacholine. This investigation examined the onset of this effect over 5 days, and also assessed cross-tolerance with salbutamol. SUBJECTS AND METHODS: Ten asthmatic volunteers who were able to withhold beta 2-agonist therapy for 4 weeks before and during the study participated in a double-blind, crossover, placebo-controlled study with two random-order treatment periods: inhaled salmeterol, 50 micrograms twice a day for seven doses, and placebo in similar fashion. Methacholine inhalation tests were done 1 h after doses 1, 3, 5, and 7, and then 24 h after the last dose of the study inhaler 10 minutes after 200 micrograms of salbutamol. RESULTS: Baseline FEV1 value before doses 3, 5, and 7 of salmeterol (ie, 12 h after salmeterol) was significantly higher than all other (n = 7) values. Twenty-four hours after the last dose of salmeterol, the FEV1 was no different from that during the placebo period. The geometric mean methacholine concentration causing a 20% fall in FEV1 (PC20) after the first dose of salmeterol (6.1 mg/mL) was statistically similar to the value achieved 10 min after salbutamol after the placebo period (8.3 mg/mL), and these were significantly (analysis of variance, p < 0.00005) larger than the second, third, and fourth salmeterol days (3.4 mg/mL, 2.6 mg/mL, 1.9 mg/mL, respectively). The methacholine PC20 10 min after salbutamol measured after the salmeterol period was significantly lower than after placebo (2.3 mg/mL vs 8.3 mg/mL; p < 0.001). CONCLUSIONS: Tolerance to the acute bronchoprotective effect of salmeterol was significant after the first two doses and progressively increased to the seventh dose. Tolerance to the acute bronchoprotective effect of salbutamol was significant after regular use of salmeterol for seven doses.

Adrenergic beta-Agonists↗
PubMed1995

Management of acute severe asthma.

OBJECTIVE: This review presents a consensus on the emergency management of adult asthma. Management is discussed under six headings: assessment, asthma treatment, supportive treatment, complications, precipitating cause, and disposition/followup; the first four are undertaken concurrently. DATA SOURCES: The framework for this review is the 1994 "Guidelines for Emergency Management of Adult Asthma" produced by the Canadian Association of Emergency Physicians in collaboration with the Canadian Thoracic Society. This document is supported by 144 English language references in humans. STUDY SELECTION: Papers were selected to emphasize the major points of consensus. About 25% of the above references were included in the bibliography. RESULTS: Rapid assessment of the severely ill asthmatic patient must include objective features: vital signs, pulsus paradoxus, oxygen saturation, and expiratory flow rates. Asthma therapy should commence immediately with inhaled beta 2 agonist and systemic or ingested corticosteroid; inhaled anticholinergic is added initially or as early second-line treatment. Supportive treatment includes oxygenation, fluid-electrolyte balance, and nonpharmacologic relief of anxiety. When necessary, mechanical ventilation allowing "permissive hypercapnia" using low peak airway pressure (low volume and slow inspiratory flow rate) reduces the risk of barotrauma; the PaO2 and pH are maintained while allowing PaCO2 to rise. Early recognition and treatment of complications, especially pneumothorax, can be life-saving. Identification of precipitating factor(s) occasionally dictates initial therapy (anticholinergic for beta blocker-induced bronchospasm, epinephrine for asthma accompanying a systemic allergic reaction), but is most important as the first step to preventing future episodes. Disposition should be based on objective measurement of flow rates. CONCLUSION: Aggressive rapid management of severe asthma by these or similar guidelines should improve morbidity and mortality.

Acute Disease↗
PubMed1994

[Bronchial hyperreactivity other than that seen in asthma].

Although generally associated with asthma, bronchial hyper-responsiveness has been observed in several clinical situations. Indeed, it has been clearly shown that patients with allergic rhinitis exhibit frequently bronchial hyperresponsiveness. The latter may be an important factor in the development of chronic airway obstruction. Airway hyperresponsiveness to direct bronchoconstrictors, histamine and metacholine, is seen also in subjects with chronic airflow limitation. Several lines of reasoning suggest that this may be different than the airway hyperresponsiveness seen in asthmatics and may predominantly relate to the degree of airflow obstruction. Consequently, in the presence of resting airflow obstruction, histamine and metacholine tests are difficult to interpret vis-a-vis a diagnosis of asthma. Some studies suggest accelerated decline of lung function in subjects with chronic airflow limitation and airway hyperresponsiveness. In interstitial lung disease preliminary data form subjects with lung diseases localized to the pulmonary interstitium suggest no (or very little) tendency to airway hyperresponsiveness. However, more data are necessary. Subjects with bilateral lung transplantation appear to develop mild, generally asymptomatic airway hyperresponsiveness which has been suggested to be due to cholinergic denervation hyper-sensitivity. Finally, asthmatics and nonasthmatics both may develop increased degrees of airway responsiveness following viral respiratory tract infections. Virus-induced airway inflammation is likely important in the pathogenesis of asthma in some subjects.

Airway Obstruction↗
PubMed1993

Regular inhaled salbutamol and airway responsiveness to allergen.

Regular inhaled beta 2 agonist causes tolerance to the acute protective effect of beta 2 agonist against bronchoconstriction induced by chemical stimuli such as AMP, histamine, and methacholine. We examined a more clinically relevant stimulus, inhaled allergen, in a double-blind, cross-over, random-order trial in 13 mild atopic asthmatics, who had not used beta 2 agonist for at least 4 weeks. We compared regular inhaled salbutamol (200 micrograms four times daily for 2 weeks) with placebo (2 weeks) for effects on bronchodilator response, baseline methacholine, and allergen airway responsiveness, and on the acute protective effect of salbutamol against both stimuli. Baseline forced expiratory volume in 1 s (FEV1), bronchodilator response, and methacholine responsiveness were the same during both treatment periods. After regular salbutamol, the allergen PC20 (provocation concentration producing a 20% FEV1 decrease) fell by 0.91 (SD 0.66) (p = 0.0009) doubling doses, and the protective effects of salbutamol on methacholine and allergen were both significantly reduced (p = 0.026 and 0.025, respectively). Taking into account the reduced baseline allergen PC20, the post-salbutamol allergen PC20 was almost 2 doubling doses (1.94 [1.43], p < 0.01) lower during salbutamol treatment. Thus, 2 weeks of regular inhaled salbutamol increased airway responsiveness to allergen but not to methacholine, and caused tolerance to the protective effect of salbutamol on bronchoconstriction induced by both stimuli. These effects of inhaled beta 2 agonist provide further evidence to support detrimental effects of their regular use.

Administration, Inhalation↗
PubMed1993

Inhalant atopic sensitivity to grasshoppers in research laboratories.

BACKGROUND: Atopic sensitivity to insects, in both occupational and nonoccupational settings, is common. METHODS: A 26-year-old man with atopic asthma experienced worsened asthma and urticaria on exposure to grasshoppers in a research laboratory; he along with 16 other persons who work with grasshoppers from two laboratories and 26 control subjects were studied. The patient underwent a controlled allergen inhalation test with aqueous grasshopper dropping antigen. All subjects were assessed by means of a questionnaire. All but one (who refused because of severe skin reactions after contact with grasshoppers) had skin prick tests with three extracts of grasshopper and with grass pollen, cat dander, and Dermatophagoides farinae. RESULTS: The allergen challenge was positive with an isolated early asthmatic response (23% fall forced expiratory volume in 1 second [FEV1]) at 1:4096 (approximately 25 micrograms/ml), and a borderline fall in provocative concentration of methacholine causing a 20% fall in FEV1. Seven of 16 (43.8%) workers had positive grasshopper skin test results compared with one of 26 (3.8%) control subjects (p = 0.0052). Sensitization occurred even in otherwise nonatopic workers (5 of 12). Symptoms of asthma on exposure (n = 4) correlated better with positive skin test results than did cutaneous symptoms (n = 8). CONCLUSION: Atopic sensitization to grasshoppers in research laboratories is a significant occupational health problem.

Adult↗
PubMed1993

Beclomethasone given after the early asthmatic response inhibits the late response and the increased methacholine responsiveness and cromolyn does not.

BACKGROUND: Single doses of inhaled beclomethasone or inhaled cromolyn, given before allergen inhalation, inhibit allergen-induced late asthmatic responses (LARs) and increased airway responsiveness (delta log methacholine PC20). We hypothesized that when given 2 hours after allergen, beclomethasone might work better than cromolyn. METHODS: In 10 patients with mild, stable, atopic asthma with LARs or delta log PC20 or both, we performed a double-blind, double-dummy, random-order trial comparing a single dose of inhaled beclomethasone (500 micrograms), cromolyn (20 mg), and placebo, administered 2 hours after allergen challenge on LAR and delta log PC20. RESULTS: The treatment effect on LAR was significant (p < 0.001). The LAR after beclomethasone (7.3% +/- 6.1%) was significantly less than after cromolyn (20.4% +/- 15.2%) or placebo (26.4% +/- 8.2%); cromolyn was not different from placebo. There was a borderline treatment effect on delta log PC20 (p = 0.056) with beclomethasone (0.12 +/- 0.31) less than placebo (0.37 +/- 0.39) but not less than cromolyn (0.34 +/- 0.18). CONCLUSION: Beclomethasone (500 micrograms) administered 2 hours after allergen challenge markedly inhibited the LAR and had a small effect on allergen-induced airway responsiveness. Cromolyn (20 mg) was not effective on maximal LAR; a small effect on the early part of the LAR was suggested.

Adolescent↗