Search PubMed⌕ Search

Biomedical subjects

D W Cockcroft

Publications and source records attributed to D W Cockcroft.

At least 109 records · Page 6Linked to original sources
PubMed1988

Farming and exposure to chemicals in male lung cancer patients and their siblings.

We conducted a retrospective questionnaire study concerning farming and exposure to chemicals on 165 male lung cancer patients, mean age +/- SE, 64.2 +/- 1.0 years, and 165 closest in age male siblings, mean age 64.5 +/- 0.7 years. The patients were diagnosed as having primary lung cancer between January 1, 1979, and November 1, 1983. Among the lung cancer patients, 38.5% had a same-sex sibling eligible for inclusion and of these, 62.0% responded to the questionnaire. Mean pack-years of smoking for patients was 41.0 +/- 2.2 (n = 135) and among the siblings 36.9 +/- 2.4 (118) (P less than .002). The occupation of farming was present in 47.8% of 163 patients with known occupations as compared to 37.6% of 155 siblings with known occupations (not significant). Patients were consistently exposed more frequently to herbicides (P = .05), grains (P less than .015), and diesel fuels (P less than .005), and were consistently exposed to greater numbers of chemicals than were siblings (P less than .005). These findings raise the possibility that, in addition to smoking, farming and related exposures could be implicated in the etiology of lung cancer in men.

Aged↗
PubMed1987

Comparative effects of inhaled salbutamol, sodium cromoglycate, and beclomethasone dipropionate on allergen-induced early asthmatic responses, late asthmatic responses, and increased bronchial responsiveness to histamine.

Single-dose salbutamol (200 micrograms), beclomethasone dipropionate (200 micrograms), and sodium cromoglycate (SCG) (10 mg) administered by inhalation 10 minutes before allergen challenge were examined with regard to inhibition of allergen-induced early (EAR) and late (LAR) asthmatic responses and allergen-induced increase in bronchial responsiveness to inhaled histamine. Ten atopic subjects with asthma participated in a blinded, crossover, placebo-controlled trial. The EAR was inhibited by salbutamol and SCG but not by beclomethasone dipropionate or placebo (p less than 0.01). The LAR (p less than 0.01) and the allergen-induced increased bronchial responsiveness to histamine 7 hours (p less than 0.01) and 30 hours (p less than 0.05 and p less than 0.01 for various comparisons) were inhibited by SCG and beclomethasone diproprionate but not by salbutamol or placebo. The allergen-induced LAR and associated increased responsiveness are now believed to be more important clinically than the EAR. The clinical relevance of these results is to stress the importance of the prophylactic nonbronchodilator drugs (SCG and steroids) and the potential inadequacy of bronchodilators used alone in the treatment of both perennial and seasonal allergic asthma.

Administration, Inhalation↗
PubMed1987

Changes in bronchial responsiveness to histamine at intervals after allergen challenge.

Bronchial responsiveness to inhaled histamine was measured two, seven, and 30 hours after allergen inhalation challenge in 19 atopic subjects. The provocative histamine concentrations causing a 20% fall in FEV1 (PC20) at these three times were compared with the baseline value, with values obtained two and seven hours after diluent inhalation, and with those obtained five to seven days after allergen challenge in the 12 late responders. Seven subjects had allergen induced isolated early asthmatic responses (delta FEV1 22.6% (SD 6.6%)) with less than a 5% late fall in FEV1. There was no change in the six histamine PC20 values measured in these seven subjects; the geometric mean PC20 was 1.0-1.3 mg/ml on all six occasions. Twelve subjects had an allergen induced early asthmatic response (delta FEV1 26.3% (9.8%)) followed by a definite (greater than 15% delta FEV1, n = 7) or equivocal (5-15% delta FEV1, n = 5) late asthmatic response. The geometric mean histamine PC20 was not significantly different two hours after allergen inhalation either from baseline (0.67 v 0.78 mg/ml) or from that seen two hours after diluent (0.67 v 0.95). It was significantly reduced at seven (0.24 mg/ml) and at 30 hours (0.44 mg/ml) but had returned to baseline when repeated five to seven days later (0.74 mg/ml). In 10 subjects with a dual response who had a repeat antigen challenge the mean early and late response and delta PC20 at seven and 30 hours were similar. These data show that bronchial responsiveness to a non-allergic stimulus has not increased two hours after allergen inhalation following spontaneous recovery of the early asthmatic response but before the start of the late asthmatic response.

Adolescent↗
PubMed1987

Prediction of airway responsiveness to allergen from skin sensitivity to allergen and airway responsiveness to histamine.

Previous data have indicated that airway responsiveness to allergen, expressed as the provocation concentration causing a 20% FEV1 fall (PC20), was dependent on nonallergic airway responsiveness (histamine PC20) and sensitivity to allergen (skin sensitivity or end-point titration). From retrospective data in 24 subjects, we developed a formula to predict allergen PC20 and examined its accuracy prospectively in 26 new subjects undergoing allergen inhalation test with doubling allergen concentrations. Allergen PC20 (APC20) was predicted from histamine PC20 (HPC20) and skin sensitivity (SS) by the formula: Log10 (APC20) = 0.69 Log10 (HPC20 X SS) + 0.11 (r = 0.85). Allergen PC20 was accurately predicted in 6, and overestimated or underestimated by 1 doubling concentration in 11, by 2 concentrations in 6, by 3 concentrations in 3, and by greater than 3 concentrations in none. From the total of 50 subjects, a new relationship was developed: Log10 (APC10) = 0.68 log10 (HPC20 X SS) (r = 0.82) from which 46 of 50 (92%) of allergen PC20 values fall within 2 doubling concentrations of the regression line (and all within 3). Early airway responsiveness to a given allergen can be predicted within a +/- 8-fold range, which is better than some investigator's test reproducibility of +/- 1 log (10-fold). Allergen inhalation tests to determine early asthmatic responsiveness to different IgE-mediated allergens can probably be replaced by the simpler and safer determinations of allergen sensitivity (SS, RAST) and histamine or methacholine airway responsiveness.

Allergens↗
PubMed1987

Airway hyperresponsiveness: therapeutic implications.

In summary, this article has reviewed the importance of airway inflammation in the pathogenesis of asthma. Inflammatory triggering factors (allergen, low molecular weight sensitizing chemicals, viral URTI) are more important in the pathogenesis of asthma than the bronchospastic triggering factors. Likewise, anti-inflammatory treatment strategies (environmental control, sodium cromoglycate, steroids) are more important in the long-term control of asthma than are the purely bronchodilator strategies.

Adrenal Cortex Hormones↗
PubMed1987

Bronchial inhalation tests. II. Measurement of allergic (and occupational) bronchial responsiveness.

In summary, controlled allergen and occupational inhalation challenge tests represent a major undertaking with a predictable degree of patient discomfort and a significant risk of dangerous side effects. Tests must be well controlled so the responses can be differentiated from nonspecific (nonallergic) effects. There is probably very limited routine clinical usefulness for allergen inhalation tests. These tests, however, remain valuable for investigations into the pathogenesis of asthma and for studies on new therapeutic agents. Occupational challenge tests may be used for the diagnosis of occupational asthma, although safer more convenient methodologies may become available in the future. Occupational challenges, however, remain the only way to definitively document sensitivity to certain low molecular weight chemicals that cause occupational asthma by a process of sensitization but in which the immunopathogenesis has not been entirely worked out.

Airway Resistance↗
PubMed1986

Lymphocytic interstitial pneumonia and abdominal lymphoma complicating celiac sprue.

We report the development of lymphocytic interstitial pneumonia followed later by abdominal lymphoma in a 62-year-old woman with celiac sprue. She presented with dyspnea, cough, weight loss, and bibasilar pulmonary infiltrates. Lung biopsy demonstrated lymphocytic interstitial pneumonia and corticosteroid therapy resulted in clinical and radiological improvement. She remained well for just over a year until abdominal pain developed and investigation revealed an abdominal lymphoma. Chemotherapy effectively controlled the lymphoma while the lymphocytic interstitial pneumonia was satisfactorily managed by corticosteroid therapy. Although lymphoma is a well-recognized complication of celiac sprue, it is not associated with lymphocytic interstitial pneumonia, despite a number of other reports describing the occurrence of pulmonary disease in this disorder.

Abdominal Neoplasms↗
PubMed1986

Pi MZ phenotype and an increased prevalence of reported psoriasis in a community survey.

In a community survey of 953 adults we identified 40 who reported having had psoriasis. Eight of these cases were subsequently documented from physicians' records. alpha 1-Antitrypsin (alpha 1-AT) phenotyping identified 35 MZ individuals, 4 (11.4%) of whom reported psoriasis. Among the 918 non-MZ individuals 36 (3.9%) reported psoriasis, yielding a relative incidence of 3.2 (p less than 0.05). This is consistent with previous reports suggesting an association between moderate alpha 1-AT deficiency and psoriasis.

Adolescent↗
PubMed1986

Pulmonary function in Pi M and MZ grainworkers.

Twenty-eight men with the Pi MZ phenotype who have been employed in the Saskatchewan country grain elevators and thus regularly exposed to high levels of grain dust, were case matched for age, years of employment, employment status, smoking status, and smoking history with grainworkers of type Pi M. Individuals answered a questionnaire, had a chest roentgenogram, skin tests, and performed a battery of pulmonary function tests. There were no differences between the two groups in prevalence of symptoms or atopy. Although not statistically significant, the MZ group had three times as many individuals with abnormal roentgenograms suggestive of COPD as the M group. The Pi MZ grainworkers had consistently poorer mean results for the pulmonary function tests with significantly lower mean values for FEV1, FEV1/FVC, MMFR, and Vmax50, leading us to suggest that Pi MZ individuals may be at higher risk of COPD than Pi M individuals, but only in the presence of other risk factors such as grain dust exposure.

Adult↗
PubMed1985

Bronchial inhalation tests. I. Measurement of nonallergic bronchial responsiveness.

Bronchial inhalation test with histamine or methacholine are useful to measure the presence and degree of nonallergic bronchial hyperresponsiveness, a ubiquitous feature of current symptomatic asthma. Tests must be well standardized so that the test is reproducible and the results can be interpreted and compared with other investigators. The tests are safe and relatively simple to perform. Histamine and methacholine tests are useful in the diagnosis of asthma, in the assessment of its severity, in the diagnosis and follow-up of occupational asthma, and in the monitoring of various asthma treatments. It is suggested that a well standardized histamine or methacholine inhalation test should be available in all major pulmonary function laboratories.

Administration, Intranasal↗
PubMed1984

Recurrent nocturnal asthma after bronchoprovocation with Western Red Cedar sawdust: association with acute increase in non-allergic bronchial responsiveness.

Recurrent nocturnal asthma following a single exposure to Western Red Cedar sawdust was documented by measurements of peak flow rates in two sensitized subjects. The nocturnal asthma followed a dual asthmatic response in the first subject and a late (non-immediate) asthmatic response in the second. Both subjects developed a 10-fold reduction in the dose of histamine required to decrease the FEV1 by 20%. This cedar-induced increase in non-specific bronchial reactivity was maximal at the time of the recurrent nocturnal asthma, and persisted after nocturnal asthma had ceased and after FEV1 had returned to normal. We hypothesize that the enhanced non-specific bronchial reactivity which occurs following late asthmatic responses to bronchial challenge is the cause of recurrent nocturnal asthma following single exposure to a sensitizing agent.

Adult↗
PubMed1984

The effect of atropine on allergen-induced increases in bronchial responsiveness to histamine.

We examined the role of cholinergic mechanisms in causing the increase in histamine bronchial responsiveness that follows allergen exposure. Five stable adult atopic asthmatics received inhalation tests with histamine on 2 days after both placebo and a dose of atropine sulphate (18 mg nebulized during tidal breathing), which reduced saliva output. On a third day, an allergen inhalation test was carried out to stimulate a dual asthmatic response. When the FEV1 had returned to within 10% of baseline, the histamine test was repeated after placebo and atropine. Before allergen inhalation, atropine marginally increased the FEV1 (p = 0.12) and reduced bronchial responsiveness to histamine (p = 0.003). When allergen challenge had induced an increase in histamine responsiveness (p = 0.001), atropine again marginally increased FEV1 (p = 0.063) and reduced the responsiveness (p = 0.004) but did not return the responsiveness to the preallergen level (p = 0.023). There was no evidence that the magnitude of the atropine blockade of histamine responsiveness was different before and after allergen (p = 0.92). We conclude that cholinergic mechanisms are not likely to explain the increase in bronchial responsiveness that follows allergen-induced inflammation.

Adult↗
PubMed1984

Relationship between bronchial response to respiratory heat exchange and nonspecific airways reactivity in asthmatic patients.

In this study we have examined the relationship between the bronchial response to inhaled histamine and the bronchial response to breathing cold air at rest in nine control subjects and nine patients with asthma. Dried warm air (mean temp: +/- 1SD: 25.4 +/- 1.6 degrees C) and cold air (-19.7 +/- 2.6 degrees C) were breathed for 10 minutes each during quiet breathing at rest prior to as well as during both measurements of forced expired spirograms and the phase 3 slope of the single-breath oxygen test (delta N2/L). Subjects were also challenged with inhaled aerosolized histamine to determine the concentration required to reduce the forced expired volume in one second (FEV1) by 20 percent (PC20). Both asthmatic and control subjects had significantly greater respiratory heat exchange breathing cold as compared to warm air (p less than 0.01 in both cases). Control subjects did not change FEV1 or delta N2/L breathing cold air. Asthmatic patients increased delta N2/L from a mean warm air value of 2.41 +/- 1.31% N2/L to a mean cold air value of 5.39 +/- 4.55% N2/L (p less than 0.05). There was a significant linear correlation between the percent increase in delta N2/L from warm to cold air and 1/log10PC20 (r = -0.97, p less than 0.001) and also the percent decrease in FEV1 and log PC20 (r = -0.76, p less than 0.03) in the asthmatic patients. We conclude that cold air-induced alterations in ventilation/distribution and expired flow rates in asthmatic patients are related to pre-existing nonspecific airways reactivity.

Adolescent↗
PubMed1984

Pi type MZ and an increased risk of pneumonia.

Among 114 men of Pi type or MZ, 42% (17/40) of those of Pi type MZ reported having been told by a physician that they had had pneumonia at least once whereas only 18% (13/74) of those of Pi type M did so (p less than 0.05). This significant difference could not be accounted for by differences in age, smoking status, occupation or baseline lung function (FEV1). Examination of medical records of those reporting pneumonia for the preceding 20 years provided confirmation of the diagnosis of pneumonia and support for the association; 12% (5/40) of the MZ group but only 3% (2/74) of the M group had confirmed episodes of pneumonia during the preceding 20 years. Since alpha 1-antitrypsin has been implicated as a factor in inflammatory response, reduced levels may permit the development of more frequent and/or more serious episodes of pneumonia.

Adolescent↗