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Biomedical subjects

D H Bryant

Publications and source records attributed to D H Bryant.

At least 19 recordsLinked to original sources

Allergy to laboratory animals among animal handlers.

OBJECTIVE: To determine the prevalence among laboratory animal handlers of allergy to laboratory animals and of asthma and the factors associated with their development. DESIGN: A cross-sectional survey. SETTING: Teaching and research institutions in Sydney, between January 1989 and December 1992. PARTICIPANTS: Laboratory animal handlers (teaching and research staff, animal house workers and animal husbandry students and teachers). MAIN OUTCOME MEASURES: Duration of exposure to laboratory animals, allergic symptoms on contact, skin reactivity to laboratory and domestic animal allergens and evidence of current asthma. RESULTS: 228 subjects were surveyed. Allergy symptoms occurred in 73 (56%) of the subjects exposed to laboratory animals for three months or more. This group also had significantly higher prevalences of skin reactivity to laboratory animal allergens (62%) and bronchial hyperresponsiveness (21%) than those with shorter exposure (14% and 8%, respectively). Atopic subjects exposed to laboratory animals (particularly those sensitised to domestic animals) and animal attendants (with a high intensity of exposure to laboratory animals) had significantly higher frequencies of skin reactivity to laboratory animals and asthma than other subjects (77% and 30%, respectively, among exposed atopic subjects and 84% and 33%, respectively, among animal attendants). CONCLUSIONS: Allergy to laboratory animals is an occupational hazard among laboratory animal handlers, especially for those who are atopic and sensitised to domestic animals, and may lead to the development of asthma. Screening for atopy and skin reactivity to laboratory animals before and during employment would enable those at risk to take precautions.

Adult

Radiation pneumonitis: a possible lymphocyte-mediated hypersensitivity reaction.

OBJECTIVE: To determine if unilateral thoracic irradiation results in a lymphoid alveolitis in both irradiated and unirradiated lung fields. DESIGN: A prospective, nonrandomized study. PATIENTS: Women receiving postoperative radiotherapy for carcinoma of the breast were evaluated both before and 4 to 6 weeks after radiotherapy. Findings after radiotherapy in 15 asymptomatic patients were compared with findings in a group of patients with clinical radiation pneumonitis. MEASUREMENTS: History, physical examination, chest radiograph, quantitative gallium lung scanning, respiratory function tests, bronchoalveolar lavage, and lavage lymphocyte subset analysis. RESULTS: After irradiation, lavage lymphocytes increased significantly (34.5% versus 46.8%; P = 0.01) in the 17 patients studied prospectively. There was an associated reduction in vital capacity (102.5% versus 95.5%; P = 0.04). Comparison of results in patients before treatment, after treatment without clinical pneumonitis, and after treatment with clinical pneumonitis showed a dramatic increase in total lymphocytes after irradiation (6.3 versus 9.4 versus 35.2 million, respectively; P = 0.005), particularly in those with clinical pneumonitis. Only in those with clinical pneumonitis was this accompanied by an increase in the gallium index (3.7 versus 3.4 versus 9.0, respectively; P < 0.001). Vital capacity was also progressively reduced (102.5% versus 96.9% versus 76.7%, respectively; P = 0.04), as was diffusing capacity (98.6% versus 91.4% versus 72.6%, respectively; P = 0.003). No statistical differences existed between irradiated and unirradiated sides of the chest in either lavage or gallium lung scan studies. CONCLUSION: In most patients, a lymphocytic alveolitis develops in both lung fields after strictly unilateral thoracic irradiation; this is more pronounced in patients developing clinical pneumonitis. These findings suggest that radiotherapy may cause a generalized lymphocyte-mediated hypersensitivity reaction.

Adult

Changes in epithelial lining fluid albumin associated with smoking and interstitial lung disease.

Albumin is an important plasma protein which is useful in the assessment of in vivo membrane permeability in the lung. In subjects with interstitial lung disease (ILD) the relationship between albumin recovered from bronchoalveolar lavage (BAL) and other markers of inflammatory activity may provide useful information of the pathogenesis of the disease process. Unfortunately, its measurement is hampered by the variable dilution in BAL fluid. In this study, urea was used as a marker of epithelial lining fluid (ELF) dilution allowing the calculation of an apparent epithelial lining fluid volume and adjusted albumin content. We examined the relationship between ELF albumin content and BAL cell counts, immunoglobulin content, respiratory function tests and gallium lung scans in both smokers and nonsmokers with and without interstitial lung disease. Forty seven subjects with connective tissue disease and interstitial lung disease and 51 subjects with either connective tissue disease but no pulmonary involvement or non pulmonary malignancy (18 current smokers) underwent BAL, gallium lung scans and respiratory function tests. The subjects with ILD were further subdivided into those with active ILD or bronchiolitis using cluster analysis. In smokers without ILD an increased ELF volume and a decrease in ELF albumin were found. Increased ELF albumin was related to increased age. In subjects with ILD, increased albumin was strongly correlated with increased BAL lymphocyte absolute and differential counts, which overwhelmed any age or smoking effect. These findings suggest a possible causal relationship between lung vascular permeability and lymphocyte numbers in subjects with interstitial lung disease and reinforce the need to consider smoking and age as confounding factors in BAL analysis.

Biomarkers

Drug-induced pulmonary disease.

OBJECTIVE: To review some of the types of drug-induced pulmonary disease reported in Australia. DATA SOURCES: Reports of pulmonary side effects made to the Australian Adverse Drug Reaction Advisory Committee between December 1972 and March 1991. Reports of drug-induced pulmonary disease from other countries are also reviewed. STUDY SELECTION: Only reports involving large patient numbers are included in the review to limit the bias likely from limited patient numbers. DATA EXTRACTION: The incidence of adverse responses to a range of commonly used drugs from other countries is compared with reports to the Australian Adverse Drug Reaction Advisory Committee in the last 19 years. DATA SYNTHESIS: Of adverse drug reactions reported in Australia in the last 19 years 7.7% were of a pulmonary side effect and 55% of these involved a syndrome of airway dysfunction. Bronchospasm and cough were the two most common symptoms of airway dysfunction and beta-blocking drugs and radio contrast media were the drug groups most commonly reported to cause them. These figures are similar to data reported from other countries. Some of the more commonly occurring types of drug-induced disease affecting either the airways or the lung interstices are reviewed. CONCLUSIONS: Medical practitioners should maintain a high index of clinical suspicion that any unexplained pulmonary disease could be caused by a drug. Most of these reactions are reversible if the drug is withdrawn in time and if additional appropriate measures are taken as required.

Adrenergic beta-Antagonists

Quantitative pulmonary gallium scanning in interstitial lung disease.

The mechanisms responsible for gallium uptake in chronic, non-infective, diffuse lung disease are not completely understood. This study attempted to clarify some of them. A lung/liver gallium index was calculated in 113 subjects, some normal and some with various interstitial lung diseases, predominantly those associated with connective tissue disease. The mean gallium index was significantly higher in the groups with active interstitial lung disease (5.7) and non-infective bronchiolitis (4.1) compared with non-smoking normals (3.0; P less than 0.05). To investigate the mechanisms responsible for gallium uptake, the gallium index was correlated with bronchoalveolar lavage findings, respiratory function tests and clinical features. Significant correlations (P less than 0.05) were found with age in non-smoking normals; lavage macrophages in smoking normals; age but no other parameter in bronchiolitis; lavage lymphocytes, lavage albumin and improvement in diffusion capacity for carbon monoxide in those with active interstitial lung disease. It is concluded that in normal smokers gallium uptake may be due to a macrophage-mediated process. Gallium uptake in active interstitial lung disease associated with connective tissue disease appears to be an immunological process in which transport and retention of gallium is associated with that of albumin.

Bronchiolitis

Effects of ipratropium bromide nebulizer solution with and without preservatives in the treatment of acute and stable asthma.

In a recent study, it was suggested that the preservatives in ipratropium bromide nebulizer solution may cause a paradoxic bronchoconstrictor response in 20 percent or more of patients with stable asthma. The frequency of this response in patients with acute asthma is unknown. The aim of this study was to examine the acute effects of the usual dose of nebulized ipratropium bromide (0.25 mg) in patients with either stable or acute asthma using formulations with and without added preservatives. Twenty-five patients with stable asthma and 25 patients with acute asthma were studied. Each subject was given preservative-containing ipratropium bromide, preservative-free ipratropium bromide, pH 7 preservative-free ipratropium bromide, and saline solution in random order using a double-blind crossover technique with at least 4 h between drug administrations. Very frequent measurements of FEV1 were made for 30 min after each drug administration and then 5 mg of albuterol was nebulized and the FEV1 was measured again after another 30 min. Changes in FEV1 were expressed as a percentage of the predicted FEV1. Paradoxic bronchoconstriction to ipratropium was detected in only one patient with acute asthma (12 percent fall in FEV1) but in none of the patients with stable asthma. A 6 percent fall in FEV1 change occurred with the saline solution in this subject suggesting that the response may have been a nonspecific one due to increased bronchial responsiveness. The mean response (+/- 1 SD) to albuterol plus either preservative-containing ipratropium, preservative-free ipratropium, or pH7 preservative-free ipratropium was significantly greater (p less than 0.05) than the response to albuterol alone both in the patients with acute asthma (25 +/- 12 percent, 27 +/- 15 percent, 26 +/- 15 percent, and 20 +/- 15 percent, respectively) and stable asthma (26 +/- 7 percent, 25 +/- 8 percent, 24 +/- 6 percent, and 22 +/- 9 percent) supporting the use of ipratropium bromide as an additional bronchodilator in patients with asthma who do not show a satisfactory response to nebulized beta-adrenergic agonist.

Aerosols

Smoking-induced changes in epithelial lining fluid volume, cell density and protein.

Bronchoalveolar lavage has proved a useful research technique for recovering cellular and molecular contents of the lower respiratory tract. Because the recovered fluid is variably diluted, an accurate estimation of molecular and cellular concentrations can only be made if the epithelial lining fluid volume recovered is also known. It has been suggested that smoking may alter epithelial lining fluid volume by reducing clearance or by stimulating production and, thus, affect the interpretation of bronchoalveolar lavage studies. In this study, urea was used as an endogenous marker of epithelial lining fluid volume in a comparison of 26 smokers and 31 nonsmokers. The mean epithelial lining fluid volume recovered from smokers was significantly greater than that of nonsmokers (2.4 +/- 1.40 ml vs 1.2 +/- 0.75 ml, p less than 0.005). The total cellular concentration in the bronchoalveolar lavage fluid in smokers was also greater (94.2 +/- 46 x 10(6) vs 33.9 +/- 21.5 x 10(6) cells per 300 ml lavage), even when corrected for bronchoalveolar lavage volume recovered (63.1 +/- 32.5 x 10(6) vs 24.9 +/- 13.3 x 10(6) cells per 100 ml recovered lavage fluid). This was true for macrophage, lymphocyte and neutrophil cell numbers. However, when corrected for the apparent epithelial lining fluid volume, only the macrophage count remained significantly higher in the smokers compared with nonsmokers (30.66 +/- 20.7 x 10(6) vs 18.21 +/- 8.6 x 10(6) macrophages.ml-1 ELF). In addition, concentrations of albumin and immunoglobulin M (IgM) were significantly lower in smokers after correction for epithelial lining fluid volume. These results highlight smoking as a confounding factor in the interpretation of bronchoalveolar lavage data.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchoalveolar Lavage Fluid

The differing patterns of interstitial lung involvement in connective tissue diseases.

Connective tissue disorders (CTD) have a relatively high incidence of pulmonary complications but their delineation has been hampered by difficulties inherent in the diagnostic techniques. One fresh approach to this problem is based on a clustering method that uses data from 8 separate investigations to cluster the patients into 4 distinctly separate categories representing normal nonsmoker, normal smokers, those with active interstitial lung disease and those with bronchiolitis. Using this method, a large group of patients with CTD have been examined to assess the nature and extent of their pulmonary complications. Subjects in the first cluster had a normal test profile across all variables, and included no current active smokers. The normal smoking cluster contained only smokers who had a high total lavage cell number with a relative increase in macrophages and a decrease in lymphocytes. In this group, all respiratory variables were normal with the exception of a mildly depressed DLCO, also known to be associated with smoking. The general characteristics of the active interstitial lung disease cluster was a markedly depressed DLCO indicating impaired gas exchange, and elevated gallium index, bronchoalveolar lavage (BAL) cell number and neutrophil and lymphocyte percentages, all indicating an active inflammatory process. However more careful analysis of this group suggested the presence of 2 subgroups, one with a lymphocytic alveolitis, and another with a neutrophilic alveolitis. The bronchiolitis cluster characteristics were a markedly depressed maximal mid expiratory flow rate and raised BAL lymphocyte percentage and gallium index. The distribution of patients within the cluster groupings suggested that Sjögren's syndrome, often an accompaniment of other CTD, is most frequently associated with pulmonary disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Smoking in hospitalised patients.

A survey was conducted in a large inner-city hospital to examine the extent of overt and covert smoking being carried out by patients while they were in hospital. There were 311 patients studied. Twenty percent of all patients tested admitted to smoking during their admission, and another 8% showed expired carbon monoxide levels indicative of recent smoking, but denied they had smoked. The percentage of any one ward that were smoking varied from 4% to 41%. Patients with cardiac and respiratory disease were much more likely to lie about their smoking than those with other diseases. Smokers were more than twice as likely to be readmitted for the same condition than nonsmokers.

Adolescent

Interstitial lung disease associated with connective tissue diseases. The use of statistical structure analysis in model development.

Interstitial lung disorders associated with the connective tissue diseases are thought to be quite common, but their precise analysis is fraught with difficulty because of the absence of a Gold Standard that, short of open lung biopsy, is not available. Analysis is hampered by the biologic variability in test results, large overlap between the normal and the disease population for individual tests, the confounding effect of smoking, and the complexities of viewing multidimensional data. In order to better define the pattern of the lung involvement, an entirely different approach has been adopted that is based on the use of graphic and clustering techniques to define the multivariate structure inherent in the data, then discriminant analysis to assign patients into distinct clusters. Using this approach it has been possible to group patients into four distinct clusters based on the result of respiratory function studies, gallium lung scan, bronchoalveolar lavage, and smoking status. These clusters are a normal smoking cluster and a normal nonsmoking cluster, a cluster of patients with active ILD, and a cluster with bronchiolitis. The validity of this method has been verified, and an algorithm has been developed that allows the assignment of any new patient entering the study into one of these clusters. This type of analysis offers a valuable new approach to the categorization of patients into distinct groups based on the results of multiple investigations.

Algorithms

Oxitropium bromide: an acute dose response study of a new anticholinergic drug in combination with fenoterol in asthma and chronic bronchitis.

The aim of this study was to compare the bronchodilator response of patients with either stable asthma or stable chronic bronchitis to the acute administration of oxitropium bromide and a beta agonist (fenoterol) when given both separately and together in order to determine the responses of these two groups of patients and the optimal doses of these agents when given in combination. The responses of 23 patients with asthma and 25 patients with chronic bronchitis to 400 micrograms of fenoterol, and 200 micrograms of oxitropium given either alone or together with 100, 200 or 400 micrograms of fenoterol was studied. The peak bronchodilator response to oxitropium bromide of the patients with chronic bronchitis was equivalent to the fenoterol response while, in the patients with asthma, the response to oxitropium bromide was approximately 30% of the response to fenoterol. In both groups of subjects the addition of oxitropium bromide to fenoterol significantly increased both the magnitude and the duration of the bronchodilator response without a significant increase in side effects. In both groups of subjects 200 micrograms of oxitropium bromide and 200 micrograms or more of fenoterol gave the optimal response.

Adult

Hypoxia during bronchoalveolar lavage.

The aim of this study was to determine the degree and duration of hypoxaemia during bronchoalveolar lavage (BAL) and to examine the effect of supplemental oxygen on this response. Transcutaneous oxygen tension (PO2) was recorded continuously in 22 patients having bronchoscopy alone (Group 1), and during BAL in patients with a variety of connective tissue disorders. Thirty eight of these patients were breathing room air (Group 2) and 28 were given supplemental oxygen (Group 3). The mean fall in PO2 in Group 1 was 12 +/- 3 mmHg and the PO2 in these subjects rose promptly to the initial value once the bronchoscopy was finished. The mean falls in Groups 2 and 3 were 24 +/- 4 and 32 +/- 5 mmHg and the mean times taken for the PO2 values to return to baseline after the procedure were 47 +/- 9 and 53 +/- 10 minutes respectively. The PO2 fell to less than 60 mmHg in 76% of the patients in Group 2 but in only 25% of those in Group 3. It is recommended that supplemental oxygen be given to all patients having BAL during and for one hour after the procedure and that oxygenation be monitored continuously throughout the bronchoscopy. Arterial blood gases should be always measured prior to bronchoscopy and BAL. In those cases where it is not possible to maintain the PaO2 at 70 mmHg or more the procedure should be undertaken with great care and with due consideration of the risk of the hypoxaemia that may occur.

Adult

The role of bronchoalveolar lavage in the assessment of diffuse lung diseases.

Bronchoalveolar lavage is a safe and simple technique for sampling the inflammatory cells of the lung. However, while its use in the evaluation of pulmonary pathogenic mechanisms is both well accepted and described, its clinical utility is more controversial. Marked variation in results may occur through variation in the lavage procedure. Standardisation of the lavage technique and laboratory processing of the specimen are essential for reliable results. This review examines the current clinical role of bronchoalveolar lavage in the assessment of patients with diffuse lung diseases, and immunocompromised patients with pulmonary infiltrates. In this latter category, for patients with Acquired Immunodeficiency Syndrome, lavage is of equal efficacy to lung biopsy and can establish the cause of pulmonary infiltrates in over 90% of cases. Bronchoalveolar lavage can detect abnormalities in patients with diffuse lung diseases prior to the development of irreversible fibrosis. Lavage features have been described for sarcoidosis, cryptogenic fibrosing alveolitis, extrinsic allergic alveolitis, connective tissue diseases, and asbestosis. In cryptogenic fibrosing alveolitis lavage data may be used to indicate a subsequent deterioration in the patient's condition, or predict a favourable response to therapy.

Alveolitis, Extrinsic Allergic

The presence of Sjögren's syndrome is a major determinant of the pattern of interstitial lung disease in scleroderma and other connective tissue diseases.

A number of patients with scleroderma, Sjögren's syndrome and other connective tissue diseases (CTD) were assessed to ascertain the prevalence of respiratory abnormalities as defined by bronchoalveolar lavage (BAL), standard respiratory function studies and gallium scan of the lung, and the relationship of these abnormalities to the presence or absence of dyspnea. These results suggest that respiratory symptoms are very common in CTD and in scleroderma, particularly if Sjögren's syndrome is also present. Our findings also suggest the presence of 2 patterns of interstitial lung involvement in scleroderma. In scleroderma alone this appears to be characterized by the presence of increased neutrophil proportions in the BAL, decreased DLCO, and no increase in gallium uptake within the lung. Where scleroderma is associated with Sjögren's syndrome, there is an increase in the proportion of lymphocytes in the BAL and respiratory symptoms are very prominent, the latter associated with an increase in gallium uptake within the lung. This suggests that Sjögren's is a major determinant of the pattern of interstitial lung disease seen in CTD.

Bronchoalveolar Lavage Fluid

Radiation-induced lung injury: a hypersensitivity pneumonitis?

Radiation pneumonitis occurs 6 to 12 weeks after thoracic irradiation, and is thought to be due to direct radiation-induced lung injury. Four patients who developed pneumonitis after unilateral thoracic irradiation for carcinoma of the breast were studied with bronchoalveolar lavage, gallium scan of the lung, and respiratory function tests. On the irradiated side of the chest, all four patients showed an increase in total cells recovered from the lavage fluid and a marked increase in the percentage of lymphocytes. When results for the unirradiated lung were compared with results for the irradiated lung, there was a comparable increase in total cells and percentage of lymphocytes. Gallium scans showed increases for both irradiated and unirradiated lungs. Prompt improvement was seen after corticosteroid therapy in all patients. The fact that abnormal findings occur equally in irradiated and unirradiated lung is inconsistent with simple direct radiation-induced injury and suggests an immunologically mediated mechanism such as a hypersensitivity pneumonitis.

Aged

Extension of pulmonary tuberculosis after fibreoptic bronchoscopy.

Two cases are described in which the diagnosis of pulmonary tuberculosis was suspected on both clinical and radiological grounds. Sputum smear and culture were negative for acid fast bacilli. Consequently a bronchoscopy and bronchial washings from the affected lobe were undertaken. While this procedure achieved a positive diagnosis of pulmonary tuberculosis, it also resulted in a significant extension of the disease.

Adult

Pulmonary manifestations of the acquired immunodeficiency syndrome.

Between 1983 and 1985, 71 patients with the acquired immunodeficiency syndrome (AIDS) were evaluated. Pulmonary manifestations were present in 42 patients (59%). Pneumocystis carinii pneumonia (PCP) was the most common pulmonary manifestation, present in 32 patients (45%). Other pulmonary findings were cytomegalovirus pneumonia (one patient), Candida pneumonia (one patient), cryptococcal pneumonia (one patient), bacterial pneumonia (three patients), nonspecific pneumonitis (three patients), Kaposi's sarcoma (one patient), and non-Hodgkin's lymphoma (one patient). The presenting features of PCP were reviewed and in seven patients the chest X-ray and blood gases were normal at the time of diagnosis of PCP. Bronchoscopy was a safe and useful technique for obtaining specimens for diagnosis promptly, and a combination of samples obtained by bronchial washings/brushings and transbronchial biopsy was found to give a higher diagnostic yield than any single sample. Drug side-effects were common during therapy, requiring change of therapy in 16 patients. At one month after diagnosis 16% of patients with PCP had died. PCP is a common pulmonary manifestation in patients with AIDS which is treatable and has an initially favourable outcome.

Acquired Immunodeficiency Syndrome