Biomedical subjects
Publications and source records attributed to D W Cockcroft.
A patient with a very rare benign bronchial tumour who presented in a most unusual manner is described. An endobrachial hamartoma was expectorated 24 hours after bronchoscopic manipulation for a suspected malignant tumour.
Explore the source record for details and available documents.
Repirinast, a novel ingested antiallergic asthma medication from Japan, was compared versus placebo on airway responsiveness to methacholine and was compared versus placebo and cromolyn on airway responses to allergen. In 14 patients with mild, stable, atopic asthma, we performed a double-blind, double-dummy, random-order trial with ingested repirinast 300 mg twice daily for 7 days, inhaled cromolyn 40 mg spincaps single dose, and double placebo on allergen-induced early (EAR) and late (LAR) asthmatic responses and increased airway responsiveness. In the 14 subjects, no difference occurred in methacholine PC20 after 6 days of repirinast or 6 days of placebo. In the 13 subjects who completed the allergen study, single-dose cromolyn significantly reduced the EAR by 63% and the LAR by 65% versus placebo (p < 0.02); repirinast was not significantly different from placebo, both the EAR and LAR being reduced by less than 10%. Allergen-induced increase in methacholine responsiveness was borderline (p = 0.052), and no significant drug effects occurred. In these models, a 1-week treatment period with repirinast, like other oral antiallergic asthma medications (e.g., ketotifen, fumarate), provides no protection against airway responses to methacholine or allergen.
Histamine provocative concentration causing a 20% drop in FEV1 (PC20) was measured in 500, randomly selected, young (20 to 29 years) university students. Participation was 500/619, or 81%. In this population, by a research assistant-administered questionnaire, we identified 17 subjects with current asthma, 16 with asthma only on allergen exposure, 19 with past (more than 1 year ago) asthma, 158 with rhinitis (77 atopic and 81 nonatopic subjects), and 290 subjects with neither asthma nor rhinitis. Histamine airway hyperresponsiveness (PC20 less than or equal to 8 mg/ml) was observed in 58 subjects and included the 17 subjects with current asthma, 6/16 with asthma only on allergen exposure, 2/19 subjects with previous asthma, 20/158 with rhinitis, and 13/290 subjects with neither asthma nor rhinitis. With "current symptomatic asthma" as the diagnosis and PC20 less than or equal to 8 mg/ml as the positive test, the sensitivity was 100%, the specificity was 93%, and the negative predictive value was 100%; the positive predictive value (for current symptoms of asthma) was only 29%. The strength of this test with a cutoff of 8 mg/ml is the high sensitivity, indicating that a PC20 greater than 8 mg/ml is likely to indicate that current asthma is not present. The weakness is the failure to predict current symptoms of asthma. As the cutoff is lowered, for example, to PC20, 1 mg/ml, the sensitivity falls to less than 50% and the positive predictive value approaches 100%. These data indicate that a PC20 greater than 8 (or 16) mg/ml rules out current asthma in most instances, whereas a PC20 less than 1 mg/ml is almost diagnostic of current asthma. Values between 1 and 8 mg/ml are intermediate in these regards.
Smoking and severe deficiency of protease inhibitor (Pi Z phenotype) both contribute significantly to the development of chronic obstructive pulmonary disease (COPD). The role of moderate Pi deficiency (Pi MZ phenotype) remains controversial. During a community-wide study of respiratory health which included 1,633 individuals, of whom 897 were women, we measured forced vital capacity (FVC), forced expired flow in 1 s (FEV1), midmaximum expired flow rate (MMFR), flow rate at 50 percent of FVC (Vmax50%) and flow rate at 25 percent of FVC above residual volume (Vmax25%). We carried out Pi phenotyping on 544 of these women, including 22 who were Pi MZ or FZ phenotypes. There were no statistically significant differences in mean pulmonary function (pf) values between the Pi MZ and Pi M women. Examination of residual pf values (difference between observed and expected) by means of multiple multivariate regression analysis revealed that in Pi MZ women, FEV1/FVC%, MMFR, Vmax50%, and Vmax25% had significantly greater values with increasing numbers of children, whereas there was no relationship in the Pi M women. These results suggest that some factors may interact differently in individuals with Pi M and MZ phenotypes. In addition, the results suggest that pregnancy or pregnancy-induced increased Pi levels may have significant effects on the pulmonary health of Pi MZ women.
Allergen-induced increase in airway responsiveness to histamine or methacholine provides a useful model for investigation of prophylactic or "antiinflammatory" asthma treatments. This can be inhibited by corticosteroids or by sodium cromoglycate but not by beta agonists or by theophylline. A single-blind, crossover, random-order trial was conducted to compare ketotifen, clemastine, and placebo in six atopic subjects undergoing allergen inhalation tests. Ketotifen, 2 mg; clemastine, 1 mg; and placebo one tablet were administered twice daily for four days (eight doses) up to and including one hour before allergen inhalation. None of the three produced a significant reduction in the allergen-induced early or late asthmatic responses, or in the allergen-induced fall in methacholine PC20. There was a subtle nonsignificant suggestion of a reduction in the early portion of the early asthmatic response induced by both ketotifen and clemastine. Both ketotifen and clemastine produced a similar 8-fold inhibition of histamine skin test endpoint indicating equal systemic H1 blocking effect at the time of allergen inhalation. Sodium cromoglycate, 10 mg, single dose, by metered dose inhaler ten minutes before allergen challenge, added as an unblinded "positive control", inhibitory effects on the allergen-induced late and presumed inflammatory sequelae. It is possible that longer treatment periods (several weeks or months) might prove effective.
A 25-year-old male chef developed symptoms of cough, wheezing, and dyspnea following repeated exposure to cooking lobster in his work environment. Skin prick tests to lobster, mixed shellfish, haddock, cod, oysters, and clams were strongly positive. Skin prick tests to other routine antigens were negative except for Alternaria fungal spores. Bronchial inhalation of aqueous lobster extract resulted in an isolated early asthmatic response.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We measured the concentration of inhaled histamine required to reduce the FEV1 by 20% (PC20) in seven asthmatic patients immediately following the inhalation of warm air (mean temperature +/- 1 SD, 21.1 +/- 1.1 degrees C) and following cold air inhalation (-10.2 +/- 5.0 degrees C). Patients breathed either warm or cold air for 10 min before 30-s challenges with doubling concentrations of aerosolized histamine that were nebulized while the subject breathed warm air. Before histamine inhalation minute ventilation (VI) was 8.41 +/- 1.38 L/min breathing warm air and 7.86 +/- 0.97 L/min breathing cold air. Respiratory heat exchange (RHE) was 0.25 +/- 0.05 kcal/min with warm air and 0.24 +/- 0.03 kcal/min with cold air. The PC20 obtained following cold air breathing (0.48 +/- 4.63 mg/ml) was lower than that following warm air breathing (0.85 +/- 4.60 mg/ml; p less than 0.02). We conclude that breathing cold air increases the bronchial reactivity to inhaled histamine in asthmatic patients.
Explore the source record for details and available documents.
A respiratory questionnaire, pulmonary function tests, and an examination of airways responsiveness were conducted on 20 swine farmers and 20 control subjects. The swine farmers represented almost the complete work force from 13 Hutterite colonies and had worked in confinement buildings with more than 2,000 swine (3,270 +/- 1,221 swine) for at least four hours (6.6 +/- 1.8 hours) per day for more than two years (10.5 +/- 7.5 years). The control subjects were randomly selected from outdoor city workers from the city of Saskatoon and were matched for gender, age (+/- 2 years), and smoking status. Eleven swine farmers (55 percent) had chronic cough, compared with three (15 percent) of the control subjects (p less than 0.01). Eight (40 percent) of the swine farmers had symptoms of wheezing, compared with three (15 percent) of the control subjects (p less than 0.05). The FEV1 was significantly lower in swine farmers (97.2 +/- 11.5 percent predicted) than in control subjects (106.0 +/- 12.0 percent of predicted) (p less than 0.05). Airways responsiveness was measured by methacholine challenge with doubling concentrations ranging from 0.25 to 256 mg/ml. The provocation concentrations resulting in a reduction of 10 percent (PC10) and 20 percent (PC20) in FEV1 were lower in swine farmers than in control subjects (PC10, 77.2 +/- 78.8 mg/ml vs 180.8 +/- 96.5 mg/ml; p less than 0.01; and PC20, 154.5 +/- 99.9 mg/ml vs 229.6 +/- 66.8 mg/ml; p less than 0.05). Twelve swine farmers (60 percent) had PC20 of less than 256 mg/ml, compared with three (15 percent) of the control workers (p less than 0.01). Fewer swine farmers demonstrated atopy as measured by skin prick tests than did control workers (21 percent vs 56 percent; p less than 0.05). These findings suggested that occupational exposure in swine confinement buildings is associated with mild increases of nonspecific, nonatopic airways responsiveness in swine farmers.
A 29-year-old woman presented with severe refractory intraoperative wheezing and airflow limitation that resolved spontaneously. Contrast-enhanced computed tomographic (CT) scan of the thorax confirmed a right-sided aortic arch. Variable intrathoracic large airway obstruction that worsened markedly when the patient was in a supine position and slightly more following intravascular volume expansion was shown on flow-volume studies. We postulate the right-sided aortic arch caused airflow obstruction that worsened intraoperatively because of position and intravenous fluids.
In this study we evaluated the role of thromboxane in causing allergen-induced early and late asthmatic responses and airway hyperresponsiveness in asthmatic subjects. Twelve atopic subjects with stable asthma and documented early and late asthmatic responses to an inhaled allergen were treated with placebo or CGS 13080, a specific thromboxane synthetase inhibitor, given orally (200 mg four times daily) for two days before, the day of, and the day after allergen inhalation. Treatments were administered in a double-blind, placebo-controlled, crossover fashion. The effect of pretreatment with CGS 13080 was examined on serum TxB2 levels and the magnitude of the asthmatic responses after inhaled allergen. Serum TxB2 levels increased significantly from 96 ng.ml-1 (SEM 29) 3 h after diluent to 151 ng.ml-1 (SEM 27) 3 h after allergen (p = 0.008). CGS 13080 pretreatment markedly inhibited the levels of TxB2 at all time points before and after inhaled allergen (p = 0.0001) and had a small but significant effect on the magnitude of the early asthmatic responses after allergen (p = 0.0009). CGS 13080 did not alter either late asthmatic responses, baseline airway responsiveness, or the increase in histamine airway responsiveness after allergen. These results suggest that allergen-induced early asthmatic responses, but not late responses or allergen-induced airway hyperresponsiveness, are partly caused by thromboxane release.
The efficacy of corticosteroids in chronic airflow limitation is variable and nonpredictable. We believe that the corticosteroid-induced improvement seen in a few subjects with chronic airflow limitation indicates coexistent bronchial asthma. Therefore, we hypothesize that by carefully excluding all features (other than corticosteroid response), either objective or subjective, that might be consistent with coexisting asthma, we could predict non-response to corticosteroids. Twenty patients with chronic airflow limitation related to cigarette smoking were chosen. Features that might suggest coexisting asthma were carefully excluded; these included rhinitis, nocturnal symptoms, atopy, large response to bronchodilator, and sputum or blood eosinophilia. Eighteen of these 20 subjects completed a double-blind random-order cross-over placebo-controlled trial of 30 mg of prednisone for 14 d (with a 14 d washout between treatments). There were no significant differences, individually or collectively, in objective or subjective determinations. Based on a greater than or equal to 250 mL improvement in FEV1, there were two placebo responders and two prednisone responders. Although it may be difficult to predict corticosteroid response in chronic airflow limitation, it appears that careful exclusion of 'asthmatic tendencies' may predict nonresponse to corticosteroids.
Some asthma triggers exert their major action through cellular inflammatory mechanisms, with resultant airway hyperreactivity to both allergenic and nonallergenic stimuli. Other triggers are simply bronchospastic, so that they do not increase vulnerability. Anti-inflammatory treatments are more important than purely bronchodilator therapy is for long-term control of 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.
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.