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Biomedical subjects

D W Cockcroft

Publications and source records attributed to D W Cockcroft.

At least 145 records · Page 8Linked to original sources

Lobar pneumonia caused by Mycoplasma pneumoniae.

Seven patients with Mycoplasma pneumoniae pneumonia presented with moderate to dense consolidation in one (in five patients) or more lobes. The diagnosis was suspected in five patients after failure to respond to 1 to 6 (average 2.6) antibiotics administered for 2 to 12 (average 7) days, and in one patient upon the development of hemolytic anemia. Clues to the diagnosis of nonbacterial pneumonia included a nonrespiratory viral-like prodromal period (in five), a nonproductive cough (in five), lack of rigors (in seven), recent "pneumonia" in family members (in ;three), normal total leukocyte and neutrophil counts (in six) and the absence of bacterial pathogens in smears and cultures of sputum (in all seven). The diagnosis of M. pneumoniae infection was supported by the presence of cold agglutinins (in a titre of 1.64 or greater) in ;the serum of five or six patients and was confirmed by diagnostic levels or increases in the titre of M. pneumoniae complement fixing antibodies. Awareness of the fact that M. pneumoniae can present as lobar consolidation and close attention to the clinical and laboratory data can usually suggest a nonbacterial cause and thus prevent delay in appropriate antibiotic treatment.

Adult↗

Pulmonary emphysema associated with the FZ alpha 1-antitrypsin phenotype.

In one family three brothers were found to have a moderate deficiency of alpha 1-antitrypsin associated with the unusual Pi (protease inhibitor) phenotype FZ. The Pi phenotypes of their six living siblings were found to be FM (in three), M (in two) and MZ (in one). The three FZ brothers all had moderate to severe obstructive airways disease, and two had at least moderately severe pulmonary emphysema. Additional risk factors included moderate cigarette smoking in two and prolonged exposure to grain dust in all three. The same risk factors applied to the six non-FZ siblings, but they had only mild symptoms and pulmonary dysfunction or no lung problems at all; one, a female smoker with the MZ phenotype, had probable early emphysema demonstrated radiologically. The three FZ men may have had reduced fertility, as they produced only 1 child among them, as compared with 39 among the other eight siblings. This family study thus suggests that individuals with the FZ phenotype are at risk for pulmonary emphysema and chronic obstructive airways disease, particularly in the presence of other risk factors, such as cigarette smoking and grain dust exposure.

Female↗

Standardization of inhalation provocation tests: influence of nebulizer output, particle size, and method of inhalation.

Standardization of inhalation tests requires a knowledge of factors that will affect the response. We measured the output and particle size of six types of nebulizers used for inhalation tests. Output varied considerably between nebulizers of different types (0.12 to 1.59 ml/min) and to a lesser extent between nebulizers of the same type. Particle size varied between 0.8 and 5.2 micrometer aerodynamic mass median diameter (AMMD). The influence of these two properties on bronchial response to inhaled methacholine was examined. Nebulizer output but not particle size (between 1.3 and 3.6 micrometer AMMD) altered the response. We also examined the effect of change in inspiratory time during inhalation from residual volume to total lung capacity on lung deposition of radiolabeled aerosol and on the provocative concentration of histamine required to reduce the 1-sec forced expiratory volume (FEV1) by 20% (PC20). A reduction in inspiratory time from 8 to 2 sec resulted in a lower total lung dose, relatively more aerosol deposited in central airways, and a higher PC20. The results emphasize the importance of keeping nebulizer output and pattern of breathing constant when performing inhalation provocation tests if consistent results are to be obtained.

Aerosols↗

Lung disease due to abuse of hairspray.

A case of pulmonary lipid granulomata in association with abuse of hairspray was studied. Light microscopic and ultrastructural examination of the lung biopsy specimen demonstrated distorted alveolar architecture, with marked increase in interstitial collagen. Multiple macrophages, both interstitial and intraalveolar, contained abundant lysosomes and lipid vacuoles. Stimulated mouse peritoneal macrophages were exposed to increasing concentrations of hairspray. Compared with control cells, the hairspray-exposed macrophages showed increased numbers of lysosomes as well as lipid vacuoles. These findings indicate that hairspray can induce pulmonary lesions.

Adult↗

Asthma caused by occupational exposure to a furan-based binder system.

A 50-yr-old mold maker developed severe asthma a few weeks after commencing work with a furan binder. Asthma recurred within hours of subsequent exposure and was confirmed by measurements every 2 hr of peak flow rate. The molds were prepared by mixing sand with a resin (containing furfuryl alcohol, paraformaldehyde, and xylene) and a catalyst (containing sulfuric acid, phosphoric acid, and butyl alcohol). Occupation-type exposure in the laboratory to the resin mixed with catalyst, and to pure furfuryl alcohol mixed with sulfuric acid or butyl alcohol, provoked late asthmatic responses and heightened nonallergic bronchial responsiveness to inhaled histamine. No changes were produced by the same exposures in an asthmatic volunteer with a similar degree of histamine bronchial responsiveness, or in the worker after exposure to resin alone and catalyst alone. Avoidance of exposure was followed by clearing of symptoms and return of histamine bronchial responsiveness towards normal. The findings identify the occurrence of specific bronchial responsiveness to volatile reaction product(s) of furfuryl alcohol following reaction with sulfuric acid or with butyl alcohol. The incidence of this problem needs investigation, especially since furan-based binder systems are replacing traditional methods.

Albuterol↗

Increased nonspecific bronchial reactivity in cigarette smokers with normal lung function.

Seventeen lifetime nonsmoking male teachers and 17 smoking male teachers with normal lung function were compared. The smokers showed a significantly greater prevalence of cough (p < 0.01), sputum production (p < 0.05), and wheezing (p < 0.01), but not dyspnea. There was no difference in the prevalence of a history of allergy, or the number of positive reactions to allergy prick skin tests, or in elevated serum IgE. Lung volumes, expiratory flow rates, specific airway conductance (SGaw), and the slope of phase III of the single breath O2 test were not significantly different. The geometric mean provocation concentration of histamine required to reduce the SGaw by 35% (PC35) was significantly lower in the smokers (1.84 mg/ml) than in the nonsmokers (4.83 mg/ml) (p < 0.005). Increased nonspecific bronchial reactivity may be a factor contributing to the development of airway obstruction in smokers.

Bronchi↗

Increased bronchial reactivity to inhaled histamine in nonsmoking grain workers with normal lung function.

We measured nonspecific bronchial reactivity to inhaled histamine in 26 lifetime nonsmoking grain handlers and 29 lifetime nonsmoking unexposed control subjects matched for age, sex and specific conductance. Routine lung function tests revealed a total lung capacity that was higher in control subjects than in workers (P less than 0.05) with no difference in other subdivisions of lung volume, or expiratory flow rates between the two groups. An index of allergy was significantly greater in the control subjects than in the grain workers (P less than 0.01). None of the grain handlers was sensitive to grain dust by history or by skin tests. Respiratory symptoms (cough, sputum, dyspnea, or wheezing) were more prevalent in the grain workers than in controls (P less than 0.05). The mean concentration of histamine required to reduce the specific conductance by 35 percent was 4.5 +/- 2.0 mg/ml in grain workers and 5.9 +/- 3.0 mg/ml in controls (P less than 0.05). Chronic exposure to grain dust in nonallergic individuals appears to be associated with both increased prevalence of respiratory symptoms and increased nonspecific bronchial reactivity when compared to nonexposed control subjects.

Adult↗

Volume adjustment of maximal midexpiratory flow. Importance of changes in total lung capacity.

In 21 of 100 consecutive subjects demonstrating greater than or equal to 10 percent increase in one second forced expired volume following 200 micrograms inhaled salbutamol, the forced expired flow over the middle half of the vital capacity (FEF25-75% was unchanged (n = 16) or fell greater than or equal to 10 percent (n = 5). Volume adjustment of FEF25-75%, to the same volume below total lung capacity (TLC) before and after administration of the bronchodilator resulted in significant increases in 18 of these 21 subjects. The volume-adjusted FEF25-75% increased more (98 percent) following 1500 micrograms inhaled metaproterenol in ten asthmatic subjects, and decreased more (53 percent) following inhalation of histamine in eight subjects, than did the standard FEF25-75% (44 percent increase and 34 percent decrease respectively). When the small changes in TLC which were seen following metaproterenol (4.4 +/- 4.1 percent reduction, p < 0.01) and histamine (11.0 +/- 7.2 percent increase, p < 0.001) were considered, and FEF25-75% volume adjusted so it was measured at the same absolute lung volume, greater changes were seen (198 percent increase after use of metaproterenol, and 75 percent decrease after use of histamine). When FEF25-75% is being examined following administration of a bronchodilator or a bronchoprovocation challenge, it should be volume-adjusted to absolute lung volume. When TLC cannot easily be determined repeatedly (eg routine pulmonary function studies), volume adjustment to the same volume below TLC is advised.

Bronchodilator Agents↗

Bronchial responsiveness to inhaled histamine and exercise.

Bronchial responsiveness to inhaled histamine and exercise was measured in 19 asthmatics. Histamine aerosol was inhaled to determine the provocative concentration producing a 20% fall in forced expired volume in one second (FEV1) (PC20). Exercise was performed on a treadmill and a cycle ergometer; following each procedure the percent fall in the FEV1 (delta FEV1) and the exercise lability (percent rise in FEV1 plus percent fall in FEV1) were calculated. Delta FEV1 and exercise lability after both forms of exercise were similar. PC20 correlated with delta FEV1 and exercise lability in both forms of exercise; however, the correlation with exercise lability was better. PC20 was more sensitive in demonstrating bronchial hyperresponsiveness. The close correlation between the level of bronchial responsiveness to histamine and exercise supports the view that release of endogenous chemical mediators is an important determinant of exercise-induced asthma. The treadmill exercise and cycle ergometry protocols were equally effective in producing exercise-induced asthma.

Administration, Intranasal↗

Nonspecific bronchial hyperreactivity after exposure to Western Red Cedar.

A 55-year-old nonatopic man presented with a 2-year history of progressively severe conjunctivitis, rhinitis, and asthma related to exposure to freshly cut red cedar. Chest roentgenogram, lung volumes, diffusing capacity for carbon monoxide, and expiratory flow rates were normal. A histamine inhalation test demonstrated mild, nonspecific bronchial hyperreactivity. After a 35-min cumulative exposure to Western Red Cedar sawdust in the laboratory, the patient developed a late asthmatic response. Bronchial reactivity to inhaled histamine increased significantly after exposure to red cedar in the laboraotry and again after natural exposure to red cedar at work. However, on both occasions forced expiraotry volume in one sec was decreased when compared to control values. Exposure to red cedar sawdust for 15 min was repeated in the laboratory, and histamine inhalation tests were performed the day before, for 4 consecutive days after, and 11 days after exposure. Before each test, one-sec forced expiratory volume, lung volumes, specific conductance, maximal expiratory flow rates at 25 and 50 per cent of vital capacity, closing capacity, and the slope of phase III from the single-breath O2 test were measured. Six hours after exposure to cedar, all measurements documented significant airway obstruction that persisted until the second day. Bronchial responsiveness to inhaled histamine also increased on the first 2 days after exposure to cedar, but this increase persisted on the third and fourth day when all other pulmonary function tests had returned to control values. Eleven days later, the bronchial hyperreactivity to inhaled histamine had also returned to control values. In a sensitized subject, exposure to Western Red Cedar induced a transient increase in nonspecific bronchial reactivity that was present in the absence of airflow obstruction. Factors other than decreased airway caliber are probably important in this phenomenon.

Bronchi↗

Nasal airway inspiratory resistance.

The relationship between transnasal pressure and nasal flow is markedly curvilinear during tidal breathing in man, and there is poor agreement among the results of various methods used to define this characteristic with a single number. We used Rohrer's equation (P = K1 V + K2 V2), where P = pressure and V = flow, and calculated values for K1 and K2 from 474 nasal inspiratory pressure/flow curves obtained from 34 human subjects by a standard method of posterior rhinometry. Nasal airway inspiratory resistance at an air flow of 0.4 liter per sec (NAIR0.4) was also calculated. Rohrer's equation was found by regression analysis to fit each curve well (0.86 less than r less than 0.9999; mean, 0.983). There was a strong correlation between NAIR0.4 and K2: NAIR 0.4 = 0.91 K2 + 0.39 (r = 0.97). Nasal congestion induced in 7 normal subjects with histamine resulted in larger changes in K2 and NAIR0.4 than K1. Patients given an intranasal corticosteroid aerosol (beclomethasone dipropionate) in a double blind crossover trial showed symptomatic improvement in nasal congestion (P less than 0.01) and significant decreases in K2 (P less than 0.02) and NAIR 0.4 (P less than 0.05), but no change in K1 (P greater than 0.2).

Adult↗

The effect of helium on nasal resistance and nasal flows.

Nasal inspiratory resistance and maximal inspiratory nasal flow were measured in 10 normal subjects while they breathed air and while they breathed a mixture of 80% helium and 20% O2. After the less dense helium-O2 mixture, there was a nonsignificant increase in K1 (15 +/- 93%), a 56 +/- 20% decrease in K2 (P less than 0.001), and a 48 +/- 20% increase in maximal inspiratory nasal flow (P less than 0.001). This is consistent with the accepted concept that K1 represents resistance to laminar flow and K2, resistance to nonlaminar flow (turbulent flow and/or flow due to convective acceleration), and that nonlaminar air flow predominates in the nose.

Airway Resistance↗

Is there a negative correlation between malignancy and respiratory atopy?

A history of respiratory atopy (seasonal hay fever or asthma) was sought among 218 patients with malignancy of endodermal origin (lung, gut, bladder, prostate), 104 patients with mesodermal malignancy (hematological, sarcomas, genitourinary system), 70 patients with ectodermal malignancy (skin and breast) and 303 age and sex matched controls. There was a significantly lower frequency of respiratory allergy in patients with endodermal malignancy when compared with their matched controls (6.4% compared to 13.2%, p less than 0.005). There were no significant differences among any of the other groups. Patients with respiratory atopy appeared to have some degree of protection against developing malignancies of endodermal origin. This may relate to immunologic factors, an inherent difference in the endodermal cell layer in atopic individuals or as yet undertermined factors.

Adult↗