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Biomedical subjects

D W Cockcroft

Publications and source records attributed to D W Cockcroft.

At least 91 records · Page 5Linked to original sources
PubMed1990

Outpatient management of bronchial asthma.

The current approach to asthma treatment centers around the recognition that asthma is primarily an inflammatory condition; airway hyperresponsiveness and bronchospasm are secondary phenomena. Anti-inflammatory treatments that produce sustained improvement in airway hyperresponsiveness (environmental control, cromolyn, inhaled and ingested corticosteroids) are the mainstay of treatment to keep symptoms and bronchodilator use to a minimum. Adequate control of chronic asthma with clearly defined treatment goals, accompanied by early recognition and patient-initiated treatment of worsened asthma, generally with inhaled/ingested corticosteroid, can successfully reduce the high morbidity and the low, but significant, mortality from this common condition.

Asthma↗
PubMed1990

Occupational obstructive disorders: nonspecific airways obstruction and occupational asthma.

Airways obstruction as a result of occupational exposure may be divided into two categories on the basis of whether or not occupational asthma is present. The first category, nonspecific airways obstruction, takes place in the absence of occupational asthma, and demonstrates only modest changes in airways responsiveness. The second category, occupational asthma, usually has a causal relationship to exposure, and demonstrates marked changes in airways responsiveness. These distinctions are of use in diagnosis, treatment, and disability assessment.

Asthma↗
PubMed1990

Tolerance to reduction of oral steroid dosage in severely asthmatic patients receiving nedocromil sodium.

We examined the efficacy of nedocromil sodium as an oral steroid sparing agent in a group of 37 severe, oral steroid-dependent asthmatics. All were receiving daily or alternate-day prednisone. These patients had taken part in an earlier, 12-week double-blind trial of nedocromil sodium 16 mg daily by inhalation or matching placebo. They continued with test treatment (26 patients on nedocromil sodium and 11 on placebo) on a double-blind basis for a further 12 weeks. During this time, patients visited the clinic every 2 weeks, when asthma severity and symptoms were assessed. On the basis of these assessments, the dose of oral steroid was either decreased, or maintained at the same level, or the patient was withdrawn if the asthma had deteriorated to a clinically unacceptable level. The nedocromil sodium group was able to achieve a greater percentage reduction in oral steroid dose (P less than 0.05). The rate of withdrawal due to worsening asthma was 31% from active and 55% from placebo treatment. Trends in other variables (time before withdrawal and numbers of patients able to withstand complete removal of oral steroids) favoured nedocromil sodium but the differences between the groups were not statistically significant.

Adult↗
PubMed1990

Possible protective effect against chronic obstructive airways disease by the GC2 allele.

The frequencies of GC phenotypes in 104 patients with chronic obstructive airways disease (COAD) were compared with those in 413 control subjects. The distributions were significantly different with fewer patients with the GC 2 allele than expected (relative risks = 0.8, 0.7 and 0.5 for 2-2, 2-1S and 2-1F, respectively) and more 1F-1F patients than expected (relative risk = 4.8). These data suggest that the GC 2 allele exerts a protective effect, whereas 1F, when homozygous, increases the risk of developing COAD.

Alleles↗
PubMed1990

Ethnicity as a possible factor contributing to the development of chronic airflow limitation and asthma.

Race or ethnicity have occasionally been cited as possible factors contributing to the risk of developing obstructive lung disease. In a hospital based case-control study of Caucasian patients with asthma or chronic airflow limitation (CAL), we determined the frequency of each of five major European ethnic groups in the patients. We then compared the two patient groups to each other and to the frequencies reported by Canada Census and found significant differences in their ethnic constitution. Our results suggest that the British are more likely than other groups, especially North Eastern Europeans, to develop CAL, while North Eastern Europeans and Scandinavians are more likely to develop asthma. These differences could be due to genetic differences among the various groups or to environmental factors associated with particular ethnic groups. They suggest that ethnicity is an additional factor to consider in future epidemiological studies of CAL or asthma.

Adult↗
PubMed1989

Theophylline does not inhibit allergen-induced increase in airway responsiveness to methacholine.

Allergen-induced increase in airway hyperresponsiveness can be used as a model of airway inflammation for assessing antiasthma pharmacologic agents. Steroids and cromolyn, but not beta-agonists, inhibit this increase; theophylline, recently suggested as having anti-inflammatory effects, has not been evaluated in this model. Six atopic subjects with asthma and with late asthmatic responses (N = 5) and postallergen reduction in a provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) (N = 6) were studied. Sustained-release theophylline (Theo-Dur; Astra Pharmaceuticals Canada, Ltd., Mississauga, Canada), 300 mg, and placebo were administered single-blind twice daily for eight doses up to 1 hour before allergen inhalation; cromolyn sodium, 10 mg, was administered in a single dose 10 minutes before allergen inhalation on another day as a "positive control." Mean theophylline levels were in the low therapeutic range, 57 +/- 17 and 58 +/- 13 mumol/L 1 and 8 hours after the last tablet. The FEV1 was 7% and 9% greater after the seventh and eighth doses of theophylline versus placebo (p less than 0.05). Theophylline also produced a significant (p less than 0.05) twofold increase in methacholine PC20. There was a 40% (p = 0.06) reduction in early asthmatic fall in FEV1 and a 25% (not significant) reduction in late FEV1 fall when theophylline was compared to placebo. Theophylline did not influence the geometric mean allergen-induced fall in methacholine PC20 delta log PC20; this was true individually in five of the six subjects. By contrast, cromolyn sodium inhibited all aspects of the allergen response completely.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Appearance of allergen-induced increases in airway responsiveness only after repeated allergen inhalations in two subjects.

Observations in two subjects undergoing three allergen challenges for a drug study suggested 'priming' of the late sequelae, namely allergen-induced increase in airway responsiveness. Both subjects had rhinitis and asthma limited to the ragweed season, near normal out-of-season histamine PC20, and extreme IgE sensitivity to ragweed. Both had an isolated early response with no change in histamine PC20 after the first allergen challenge. Significant (3.5- to 5.8-fold) reductions in histamine PC20 occurred after the second and third allergen challenge in Subject 1, and after the third challenge in Subject 2; this was associated with equivocal 5-8% late responses. Such a 'priming' effect, the prevalence of which is not known, may be important in the pathogenesis of naturally occurring allergic asthma, and in the design of clinical trials involving repeated allergen inhalations.

Adolescent↗
PubMed1989

Effect of indomethacin on allergen-induced asthmatic responses.

Previous studies have suggested that inhibition of the cyclooxygenase pathway of arachidonic acid metabolism may suppress the late asthmatic responses to inhaled allergen. Both human and animal studies have suggested that prostanoids may also be involved in increases in airway responsiveness after ozone and allergen. We studied seven atopic subjects, who had a dual asthmatic response to inhaled allergen, during a control period and then after pretreatment with indomethacin (50 mg) or placebo twice daily for 2 days, administered in a randomized, double-blind manner. Indomethacin had no significant effect on the base-line airway responsiveness to histamine (P = 0.22) or the allergen-induced early or late asthmatic response (P = 0.49). However, indomethacin inhibited the increase in airway responsiveness (express as histamine PC20) after allergen inhalation. The log difference in preallergen to postallergen histamine PC20 was 0.49 +/- 0.08 (SE) during the control period, 0.46 +/- 0.08 (SE) after placebo (P = 0.81), and 0.22 +/- 0.10 (SE) after indomethacin (P = 0.02). Although indomethacin is useful for examining the role of cyclooxygenase products in asthmatic responses, it should not be considered in the treatment of asthma. We conclude that cyclooxygenase products are not significant mediators of allergen-induced early or late asthmatic responses but are involved in the pathogenesis of airway hyperresponsiveness after allergen inhalation.

Adult↗
PubMed1989

Ethnic differences in the prevalence of pulmonary airflow obstruction among grain workers.

World Health Organization data suggest that British males over 45 have a higher death rate from chronic bronchitis, emphysema, and asthma combined than do other Europeans. Although widely supposed that this is due to particularly unfavorable environmental factors in the British Isles, as well as a higher rate of tobacco consumption, ethnicity itself may be a significant factor in determining risk of obstructive airways disease. To test this hypothesis, we have analyzed the prevalence of airflow obstruction (100 x FEV1:FVC less than 68% and FEV1 less than 84 percent predicted) in Saskatchewan grain workers of British, German, and Eastern European ancestry using the Mantel-Haenszel odds ratio (OMH) and stepwise logistic regression. We found that the British grain workers had a significantly greater prevalence of airflow obstruction (OMH = 3.2; p less than 0.01) than the Eastern Europeans. We also found that ethnic origin made a significant contribution to the estimation of risk of airflow obstruction among grain workers independent of the effects of age and smoking.

Adolescent↗
PubMed1989

Importance of evaporative water losses during standardized nebulized inhalation provocation tests.

Evaporative water losses from jet nebulizers produce temperature drop, reduction in total nebulizer output with increased nebulization time, and increasing concentration of solute remaining in the nebulizer. These were documented and quantitated for the Wright nebulizer which is used for one histamine/methacholine inhalation test method. Indirect determination of nebulizer aerosol output, made by estimation of total sodium lost from the nebulizer, was about 25 percent of total output as determined by weight change. A similar tendency was seen for a De Vilbiss 40 nebulizer for both reduction in total nebulizer output with increasing duration of nebulization, and increased solute concentration remaining in the nebulizer. These data must be taken into account when standardizing inhalation provocation tests. Nebulizers should be calibrated under the same conditions that they are used during the test. Histamine and methacholine solutions should be discarded after a single use in the 2-min tidal breathing Wright nebulizer method.

Aerosols↗
PubMed1988

Lower prevalence of positive atopic skin tests in lung cancer patients.

Allergy prick skin testing was performed on 137 newly diagnosed patients with primary lung cancer and 137 age-(+/- 3 years) and sex-matched randomly selected control subjects. We also compared 38 patients with lung cancer and 38 of their closest in age, same-sex siblings. Demographic data, personal, medical, smoking and occupational histories were obtained by personal interview. We skin tested these individuals with a standard battery of seven common allergens and a diluent control. Fewer patients (35.8 percent) than control subjects (58.4 percent) responded with one or more positive skin reactions (p less than .005). There was no significant difference between patients (27.8 percent) and control subjects (37.2 percent) responding to more than one allergen. Fewer of the 38 sibling-matched patients had one or more positive skin tests (23.7 percent) than did their siblings (55.3 percent) (p less than .01). There were fewer patients with greater than one positive skin test (15.8 percent) than sibling control subjects (42.1 percent) (p less than .025). There were no differences in smoking pack-years between patients and siblings. Historic evidence of allergy was greater in both control groups compared to their matched cancer groups; p less than .05 for community controls, p less than .005 for sibling control subjects. These findings raise the possibility that atopy, by either immunologic or nonimmunologic means, protects against development of lung cancer, or alternately, that lung cancer affects immunologic status as gauged by (type 1) skin sensitivity.

Aged↗
PubMed1988

Airway hyperresponsiveness and late asthmatic responses.

Late inflammatory sequelae following allergen (and occupational low molecular weight sensitizing chemical) exposure, including the late asthmatic response and increased nonallergic airway responsiveness, are now felt to be more important in the pathogenesis of atopic allergic and occupational asthma than are the early bronchospastic responses. These late sequelae can be inhibited by sodium cromoglycate and by corticosteroids but not by bronchodilators. Recognition that allergic and occupational (and likely all forms of) asthma are inflammatory conditions underscores the rationale for the early use of anti-inflammatory therapeutic strategies in the management of asthma. Such "anti-inflammatory" therapeutic strategies include environmental control, sodium cromoglycate, and both inhaled and oral corticosteroids.

Adrenal Cortex Hormones↗
PubMed1988

Airway responsiveness to inhaled histamine in chronic obstructive airways disease. Chronic bronchitis vs emphysema.

Airway responsiveness to inhaled histamine was examined in two groups of carefully selected patients with nonasthmatic chronic obstructive airways disease (COAD). Twelve patients with chronic bronchitis and airflow obstruction but little emphysema and 13 with predominantly emphysema and airflow obstruction but little bronchitis were selected based on history, chest roentgenogram, and diffusing capacity for carbon monoxide (Dsb). Emphysema patients had less cough, less sputum, less chronic bronchitis, lower Dsb, and more radiographic evidence of vascular deficiency. There was no difference in anthropometric features, smoking history, atopic skin sensitivity, hemoglobin, blood eosinophilia, PaO2, PaCO2, ECG, lung volumes, or expiratory flow rates. The two groups had similar airway responsiveness to inhaled histamine; the geometric mean provocation concentrations producing a 20 percent FEV1 fall (PC20) was 0.56 mg/ml for the bronchitis patients and 0.28 mg/ml for the emphysema patients (p greater than 0.20). Regression of log histamine PC20 vs percent predicted FEV1 showed a high correlation in both groups (r = 0.73, p less than 0.01 in bronchitis and r = 0.79, p less than 0.001 in emphysema). The regression lines were almost identical. These data suggest that in COAD bronchial responsiveness to inhaled histamine is mainly due to the altered airway geometry, and that there is no difference in histamine responsiveness between patients with emphysematous COAD and nonemphysematous COAD with chronic bronchitis.

Aged↗