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Biomedical subjects

D W Cockcroft

Publications and source records attributed to D W Cockcroft.

At least 127 records · Page 7Linked to original sources
PubMed1984

Nighttime ventilation improves respiratory failure in secondary kyphoscoliosis.

Four patients with cardiorespiratory failure caused by secondary kyphoscoliosis were studied. Polycythemia, cor pulmonale, restrictive lung pattern (functional residual capacity (FRC), 17 to 27% predicted; vital capacity (VC), 11 to 23% predicted), and abnormal arterial blood gases, primarily hypoventilation (PaO2, 31 to 44 mm Hg; PaCO2, 52 to 73 mm Hg), were seen in all. Supplementary oxygen, digoxin, diuretics, 15 min of intermittent positive-pressure breathing with inspired pressure (PI) 25 cm H2O 4 times daily, and tracheostomy failed to produce improvement. However, 12 h of nighttime ventilation (NTV) with PI 28 to 35 cm H2O through a permanent tracheostomy proved effective. Within 72 h, dyspnea at rest, restless sleep, and frequent waking resolved. Within 8 to 22 days, the PaO2 was approximately 58 mmHg and the PaCO2 was approximately 41 mm Hg while breathing 21% oxygen spontaneously during the day. The right heart failure resolved within 2 to 7 wk, and the hemoglobin count decreased to approximately 165 g/L within 2 to 6 months. There was a mean increase of 700 ml (72%) in functional residual capacity and 430 ml (49%) in vital capacity. The patients were discharged 2 days to 5 wk after NTV commenced. Daytime activity increased, approaching a normal life style. The improvement was sustained over a mean follow-up period of 3.4 yr. Problems included recurrent episodes of tracheobronchitis, mild self-limiting hemoptysis, and speech modification. Nighttime ventilation may be an effective alternative for long-term treatment of cardiorespiratory failure caused by secondary kyphoscoliosis.

Adult↗
PubMed1983

Mechanism of perennial allergic asthma.

The early (immediate) allergic asthmatic response does not account for the clinical features of perennial asthma. However, the late response--now thought to be due to allergen-IgE reaction-and the increase in non-allergic bronchial reactivity that is seen in allergen-sensitive asthmatics and that follows the late response do suggest an explanation. If the increased non-allergic bronchial reactivity somehow enhances bronchial responsiveness to allergen there would, in perennial allergic asthma, be a vicious circle. It will not be easy to test, in the laboratory or clinically, the validity of this hypothesis, but there are important implications for diagnosis, treatment, and prevention.

Allergens↗
PubMed1983

Sporobolomyces: a possible cause of extrinsic allergic alveolitis.

A 28-year-old horseback rider presented with symptoms, chest radiograph, and pulmonary function tests suggestive of extrinsic allergic alveolitis related to exposure to a horse barn. Exposure to the barn produced symptoms, fever, and a fall in VC commencing 4 hr after exposure. Precipitins were positive against Sporobolomyces, suggesting this might be the causative agent; precipitins were negative against other fungi and horses. Lymphocyte stimulation to Sporobolomyces in vitro was positive in the patient and negative in two control subjects. Sporobolomyces was grown from straw in the barn. Cessation of exposure to this barn (but continued exposure to horses) has resulted in improvement in clinical condition. A survey for immunologic sensitivity to Sporobolomyces revealed that eight of 30 atopic subjects had positive wheal-and-flare prick skin tests to Sporobolomyces antigen, whereas none of 30 laboratory controls or 30 grain handlers had precipitins against Sporobolomyces. Sporobolomyces is a common fungus in cereal grain growing areas. Its spore size is less than 5 micron, consistent with other causative agents of this disorder. In this patient, positive precipitins and lymphocyte stimulation to Sporobolomyces and negative precipitins to other known causes of extrinsic allergic alveolitis provide circumstantial evidence that Sporobolomyces was the cause of the syndrome.

Adult↗
PubMed1983

Slope of the dose-response curve: usefulness in assessing bronchial responses to inhaled histamine.

The value of determining the slope of the histamine dose-response curve, in addition to the histamine provocation concentration producing a 20% reduction in FEV1 (PC20-FEV1), was assessed by analysis of histamine dose-response curves in 40 patients selected as having a wide range of increased non-specific bronchial responsiveness to inhaled histamine. The histamine dose-response curves were found to be fit the linear curve (dose v response, mean r2 = 0.97) better than the logarithmic curve (log dose v response, mean r2 = 0.93), the difference being significant (p less than 0.001). There was a strong negative correlation between the PC20-Fev1 and the slope (r = -0.98, p much less than 0.001) and a weak negative correlation between the PC20-FEV1 and the log-dose-response slope (r = -0.38, p greater than 0.05). Sixteen normal subjects and 16 asthmatic patients were compared on the basis of histamine dose-response curves measuring fal in sGaw. In this study there was no difference between r2 for the linear determination and for the logarithmic determination (0.91 v 0.90, p less than 0.05). The PC35-sGaw showed a strong negative correlation with the dose-response slope (r = -0.95, p much less than 0.01) and no correlation with the log-dose-response slope (r = 0.09, p greater than 0.05). In the two studies there appeared to be little information gained from the determination of either the dose-response slope or the log-dose-response slope. The slope and the PC20-FEV1 were equally reproducible, duplicate determinations showing less than a two-fold difference in 14 of 15 paired PC20 measurements and in 13 of 15 paired slope measurements. In summary, the slope of the histamine dose-response curve appears to fit the linear model better than the logarithmic model. It is feasible to calculate it from the results of a standardised histamine inhalation test; determination of either the slope or the log-dose-response slope, however, appears to add little useful information. It is recommended that bronchial provocation test results should be expressed in terms of a threshold concentration such as the PC20-FEV1 or the PC35-sGaw.

Adult↗
PubMed1983

Measurement of responsiveness to inhaled histamine using FEV1: comparison of PC20 and threshold.

Two methods of interpreting histamine inhalation dose-response curves were compared in 27 normal and 41 asthmatic subjects. The histamine provocation concentration producing a 20% fall (PC20) in forced expiratory volume in one second (FEV1) was calculated on the basis of the lowest FEV1 after inhalation of saline and the lowest value after inhalation of histamine. The histamine threshold was determined as the first histamine concentration causing the FEV1 to fall more than 2 SD below the mean of five pre-histamine (three pre-saline, two post-saline) FEV1 determinations. The PC20 was on average one doubling concentration larger than the threshold. The PC20 provided better discrimination between asthmatic and normal subjects than did the histamine threshold and was significantly more reproducible. These findings suggest that the histamine threshold may prove useful for studies on populations, particularly those with a low degree of responsiveness to histamine, because of the possibility of measuring a response at a lower histamine concentration. On the other hand, the PC20 is preferable for clinical use in individuals because of its better discriminating power and better reproducibility.

Adult↗
PubMed1983

Characteristics of airway tone during exercise in patients with asthma.

In 10 nonasthmatic subjects and 11 patients with asthma, we measured pulmonary resistance (RL), functional residual capacity (FRC), and specific conductance (sGaw) before, during, and after submaximal treadmill exercise. Nonasthmatic subjects did not change RL, FRC, or sGaw from base-line resting values during or after exercise. In patients with asthma, RL decreased significantly during exercise, both when exercise was begun from the control resting state and from conditions of elevated RL after a preceding period of exercise. When asthmatic patients inhaled a standardized dose of aerosolized histamine, the increase in RL during exercise was significantly less than the increase in RL when they breathed histamine at rest. When patients hyperventilated at rest with tidal volumes, breathing frequencies, and end-tidal CO2 tensions similar to those during exercise conditions, bronchodilatation also occurred, and the increase in RL following inhaled histamine during isocapnic hyperventilation was also less than at rest. Since bronchodilatation and inhibition of histamine-induced bronchoconstriction occur during both exercise and isocapnic hyperventilation, we suggest that the mechanism of bronchodilatation during exercise may not necessarily be related to metabolic factors associated with exercise.

Adolescent↗
PubMed1983

Unimodal distribution of bronchial responsiveness to inhaled histamine in a random human population.

The population distribution of bronchial responsiveness to inhaled histamine was examined in 300 randomly selected caucasian college students (aged 20 to 29 years). Bronchial responsiveness was measured as the histamine threshold, defined as the concentration producing an FEV1 fall greater than 2 SD below the mean of five prehistamine FEV1 measurements. The cumulative prevalence of asthma was 9.3 percent, including 2.7 percent with current asthma, 3.3 percent with asthma following allergen exposure only, and 3.3 percent with remote asthma. Allergic rhinitis was present in 10.7 percent; nonallergic rhinitis in 16.3 percent; 63.7 percent had neither asthma nor rhinitis. Histamine threshold ranged from unmeasurable (greater than 8 mg/ml) in 36 percent to 0.125 mg/ml in 0.3 percent. The distribution of histamine threshold values in the responsive range was unimodal, the asthmatic subjects representing a subgroup within the hyperresponsive distribution tail rather than a separate distribution peak. Examination of the FEV1 response to 8 mg/ml showed a range between 2.8 SD increase and 100 SD reduction; the population distribution of this variable was unimodal and log normal. We concluded that there is a continuous unimodal log normal distribution of bronchial responsiveness to inhaled histamine in a random human population. Rather than representing a separate (bimodal) peak or a sharp cutoff (of a unimodal tail), the asthmatic subjects show substantial overlap with the remainder of the population.

Adult↗
PubMed1983

Measurement of responsiveness to inhaled histamine: comparison of FEV1 and SGaw.

The histamine provocation concentration producing a 20% reduction in FEV1 (PC20-FEV1) and that producing a 35% reduction in SGaw (PC35-SGaw) were determined on two different days in 16 asthmatics and 27 normal subjects. The PC20-FEV1 showed good separation between asthmatics and normals. All asthmatics had PC20 less than 8 mg/ml and only one normal had a PC20 slightly below 8 mg/ml. Separation was not quite as good for PC35-SGaw. All asthmatics had a PC35 less than or equal to 3 mg/ml, but four (15%) normals also had a PC35 less than 3 mg/ml. Comparison of individual points revealed that the PC35-SGaw was consistently approximately four-fold lower than the PC20-FEV1 in normals, mildly hyperreactive asthmatics and moderately hyperreactive asthmatics, but was greater than or equal to PC20-FEV1 in markedly hyperreactive asthmatics. This is consistent with inspiration-induced inhibition of bronchoconstriction during PC20-FEV1 testing in the former groups and inspiration-induced enhancement of bronchoconstriction in the latter group. We conclude that the FEV1 is clinically acceptable to measure the response to a bronchoconstricting agent and that FEV may be preferable to SGaw because of better separation of asthmatics from other groups.

Adult↗
PubMed1983

Bronchial response to inhaled histamine in asymptomatic young smokers.

Non-specific bronchial response to inhaled histamine was measured in 21 young (21.2 +/- 1.9 years) asymptomatic smokers (2.9 +/- 2.1 pack years) and in 21 age, sex, and height matched asymptomatic controls. Following a 2 min inhalation of histamine 8 mg/ml, the smokers showed smaller reduction in FEV1 (3.4 +/- 3.3% vs 7.0 +/- 6.2%, p less than 0.05) and in MMF (7.6 +/- 15.6% vs 21.1 +/- 17.3%, p less than 0.02) than did the non-smokers. The threshold concentration of histamine was defined as that concentration where FEV1 consistently was greater than 2 SD below the mean of that obtained from 5 to 7 prehistamine spirograms. A histamine threshold between 2 and 8 mg/ml was detectable in seven smokers, and a threshold between 1 and 8 mg/ml was seen in 14 non-smokers. Histamine threshold was not measurable (i.e. greater than 8 mg/ml) in 14 smokers and seven non-smokers (p less than 0.05). Thus, these young asymptomatic smokers of brief duration failed to show increased response to histamine; in fact, they appeared to respond less to histamine than did matched controls. This may be the result of selection (who chooses to smoke) or alternatively it may be due to an acquired loss of sensitivity (development of tolerance) to inhaled irritants.

Adult↗
PubMed1982

Effect of pH on bronchial response to inhaled histamine.

In order to investigate the effect of pH on bronchial responsiveness to inhaled histamine, 15 subjects with non-specific bronchial hyperreactivity performed two histamine inhalation tests, one with unbuffered, and the other with buffered histamine acid phosphate solutions. The unbuffered histamine solutions were prepared with 0.9% sterile saline and had a pH range from 4.3 to 7.3, while the buffered histamine solutions were prepared with a phosphate buffer and had a pH range of 6.5 to 7.4. The two histamine inhalation tests were similar in all other regards. The geometric mean histamine provocation concentration required to produce a 20% reduction in FEV1 (PC20) was significantly lower for the unbuffered histamine (1.33 mg/ml) than for the buffered histamine (1.67 mg/ml), p less than 0.05. The two PC20s differed by less than one doubling dilution, the range of reproducibility of the test, in 12 of the 15 subjects. The pH effect was only noted when the pH of the histamine solutions was below five (histamine concentrations from one to eight mg/ml). We conclude that the acid pH of higher concentrations of histamine acid phosphate solutions has a slight but significant enhancing effect on the bronchial responsiveness to inhaled histamine.

Bronchi↗
PubMed1982

A new anodal alpha 1-antitrypsin variant associated with emphysema: Pi Bsaskatoon.

A new anodal alpha 1-antitrypsin (alpha 1 AT) variant was identified in a 48-yr-old woman with severe pulmonary emphysema. Isoelectric focusing produced extra bands lying between those of the Pi B and Pi C variants. The new variant was present in 2 of her 3 siblings, 5 of 11 offspring, and probably in her father, all in the heterozygous state. Mean serum alpha 1 AT concentrations and elastase inhibitory capacities were the same in variant and M offspring. The father had reported emphysema, the 2 variant siblings had documented emphysema, and 1 of 5 variant offspring had an area of focal emphysema. The Pi type M sibling and the remaining 10 offspring had no emphysema. Despite normal concentrations and activities, this new variant, which has been designated "Bsaskatoon," may be associated with the development of emphysema within this family.

Female↗
PubMed1982

Occupational asthma caused by cedar urea formaldehyde particle board.

Two carpenters developed asthma and rhinitis related to occupational exposure to a cedar urea formaldehyde (CUF) particle board. One patient developed nasal and chest symptoms and an equivocal early asthmatic response after CUF sawdust exposure, but not after spruce or western red cedar sawdust exposure; possible late asthmatic response may have been inhibited by beclomethasone treatment. The other patient developed marked nasal and chest symptoms and a dual asthmatic response after CUF exposure, but not after spruce or cedar exposure. Both patients developed increased bronchial responsiveness to inhaled histamine, which persisted for at least six days in the first patient, and which was associated with increased asthmatic symptoms of days' to weeks' duration in both. A previously unexposed asthmatic patient, with more markedly hyperreactive bronchi, developed no symptoms, no change on spirometric testing, and no change in histamine response after CUF exposure. Specific IgE antibodies directed against formaldehyde-human serum albumin conjugate could not be demonstrated using the radioallergosorbent test. This investigation documents the occurrence of occupational asthma caused by urea formaldehyde used as a bonding agent in particle boards. Absence of a response in a previously unexposed, more severe asthmatic patient suggests specific sensitization to some component of the urea formaldehyde resin complex had developed.

Asthma↗
PubMed1982

Standardization of inhalation provocation tests. Dose vs concentration of histamine.

The importance of histamine dose vs histamine concentration in determining the response to inhaled histamine was evaluated by comparing the effect of 30 sec and two min inhalation times on duplicate histamine inhalation tests in 15 asthmatic patients. The histamine provocation concentration required to produce a 20 percent FEV1 fall after 30 sec inhalations (30 sec PC20) was on average 3.6-fold greater than the two min PC20. Individually, ten of the 15 fell within the range of dose reproducibility (+/- one doubling dose), while five subjects fell outside this range, three with 30 sec PC20 less than twice two min PC20 and two with 30 sec PC20 greater than 8 X two min PC20. Seven subjects had duplicate measurements of both 30 sec PC20 and two min PC20; the two min PC20 was more reproducible than the 30 sec PC20 in all seven. The better reproducibility of the two min PC20 is likely due to a more reproducible inspiratory time over the two-minute breathing period. These findings have relevance in standardization of inhalation challenge tests, and in comparing results of such tests done by different techniques.

Asthma↗
PubMed1982

Correlation of bronchial responsiveness to diluent and to histamine.

Histamine inhalation tests were performed in 113 subjects, who were then classified by their response to histamine as normal (n = 26), mild bronchial hyperreactivity (n = 32), moderate bronchial hyperreactivity (n = 48) and marked bronchial hyperreactivity (n = 7). The response to inhaled sterile isotonic saline, the diluent, was measured as the percentage of change in FEV1 and the four groups were compared. Over-all there was a wide range of bronchial response to diluent, between +12 and -29% FEV1 change. There was little difference in the mean FEV1 change of the diluent (all less than 2%) in normals, mildly and moderately hyperreactive subjects. However, the markedly hyperreactive subjects were significantly more responsive to diluent than any other group, showing 11.7 +/- 4.4% FEV1 fall. We conclude that the mean bronchial responsiveness to diluent increases with increasingly severe nonspecific bronchial responsiveness to inhaled histamine.

Asthma↗