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Biomedical subjects

M Turner-Warwick

Publications and source records attributed to M Turner-Warwick.

At least 37 records · Page 2Linked to original sources

Epidemiology of nocturnal asthma.

To determine the frequency of nocturnal asthma in a non-hospital-based population, a survey was conducted of asthmatic patients being treated by primary care physicians in many parts of the United Kingdom. Seventy-four percent of the 7,729 patients who participated reported awakening at night at least once a week, and 64 percent reported awakening at least three times a week. Of 3,015 patients who regarded their asthma as mild, 26 percent reported awakening every night, suggesting that many patients underestimate the severity of their asthma. Patients with no nocturnal asthma generally had a lower frequency of allergic and nonallergic trigger factors, but no dominant feature distinguished these patients from those who did awaken at night. As perceived asthma severity increased, so did the number of drug types being prescribed, but no particular drug was identified as being associated with a lower frequency of nocturnal asthma. The frequency of nocturnal asthma found in the survey population (74 percent), in which 48 percent of the patients were using corticosteroid aerosols, was identical to that found in a survey conducted in 1971, when this medication was not yet available. Even though the sampling methods used in the two surveys were different, this finding indicates that the introduction of aerosol steroids has had little effect on the frequency of nocturnal asthma. Current use of existing medication alone may not eliminate the problem of nocturnal asthma, and new drugs and/or new dosing strategies may be needed to control this disabling symptom completely.

Asthma↗

Cryptogenic bilateral fibrosing pleuritis.

We describe four patients with bilateral pleural effusions progressing to diffuse pleural thickening for which we have been unable to find any evidence of an infective, embolic or occupational aetiology. In order to avoid confusion with diffuse pleural thickening attributable to asbestos-related disease, the term cryptogenic bilateral fibrosing pleuritis is suggested. The patients differed from those with pleural shadowing due to asbestos in that none of them gave a history of asbestos exposure, all were ill, presented with chest pain which was not always pleuritic in character, and had dyspnoea, cough or malaise. They had pleural effusions of variable size, pleural shadowing radiographically and raised sedimentation rates. Computed tomography revealed bilateral extensive pleural thickening in all cases. All four were HLA B44 positive. Histology showed that in all cases the pleura was thickened by fibrous tissue. Both layers were affected and the pleural space was often obliterated. Otherwise the pleural surface was covered by organizing fibrin. Focal collections of lymphocytes were often present when the fibrous tissue abutted on the subpleural fat. No asbestos bodies were seen in any of the cases and in one patient electron microscopic fibre counts showed no excess of asbestos. Pleural decortication was successful in three patients. In one of these, contralateral disease was successfully controlled with corticosteroids, but the fourth patient has not improved on corticosteroids.

Adult↗

Some connective tissue disorders of the lung.

Many connective tissue disorders involve the lungs. The same clinical syndrome may be associated with several distinctive types of pathology in different patients. Fibrosing alveolitis is a common feature of a number of different syndromes. An hypothesis is set out in schematic form which may help to account for some of these differences and emphasizes the potential importance of the pulmonary vasculature in pathogenesis.

Connective Tissue Diseases↗

Measures of the inflammatory response in cryptogenic fibrosing alveolitis.

Cryptogenic fibrosing alveolitis (CFA) is characterized by interstitial fibrosis and parenchymal inflammation. Eleven patients with CFA (10 proved by lung biopsy) were followed over 2 yr using clinical symptoms, radiographic change, and pulmonary function tests to adjust their treatment. Lung lavage, positron camera (PET) measurements of regional extravascular lung density (Dev), pulmonary blood volume (Vb), and the metabolic rate for 18F-deoxyglucose (MRglc), clearance of 99mTc-diethylenetriaminepentacetate (99mTc-DTPA) aerosol, and lung uptake of 67Ga were measured initially and at the end of the first year to give a profile of the inflammatory response. Compared with normal subjects, there was an increased percentage of neutrophils and eosinophils in the lung lavage, increased Dev (p less than 0.002) with no significant difference in Vb, increased MRglc (p less than 0.02), 99mTc-DTPA clearance (p less than 0.002), and 67Ga uptake (p less than 0.02). The smallest increases in Dev were seen in the two patients with most destruction shown by lung biopsy. There were inverse correlations between Dev and both FVC and TLC, but a direct correlation between Vb and transfer factor. 99mTc-DTPA clearance changed concordantly with clinical status and radiographic and respiratory function changes during the first year. If glucose utilization (MRglc) remained in the normal range between the initial and first yearly assessment, the patient improved or remained stable during the second year as shown by clinical status and radiographic and respiratory function measurements. If it rose or remained high, the patient's condition deteriorated.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Fine structural changes in idiopathic pulmonary haemosiderosis.

Lung biopsies from four children and two adults with idiopathic pulmonary haemosiderosis have been examined by transmission electron microscopy. No qualitative differences were identified between the children and the adults but the changes were more severe in the children. In each case the major damage involved the capillary endothelium and its basement membrane. Capillary endothelial swelling was very noticeable and in one case the endothelium was attenuated but gaps between endothelial cells were very difficult to find. Capillary narrowing and platelet aggregation were common. The capillary endothelial basement membrane showed focal thickening, particularly on the thick side of the air/blood barrier, but no electron dense deposits were identified. Degenerative changes in the alveolar epithelium were not so marked as those in the capillary endothelium and the epithelial basement membrane was normal except for haemosiderin deposition. Haemosiderin was also noted on elastin and within intra-alveolar macrophages. Other secondary changes included mild interstitial oedema and fibrosis. These findings indicate that the major site of damage is the alveolar capillary, but provide no evidence of the cause of the disease.

Adolescent↗

Mortality in cases of asbestosis diagnosed by a pneumoconiosis medical panel.

One hundred and fifty five male cases of asbestosis certified by the London Pneumoconiosis Medical Panel during 1968-74 were followed up during 1978-9, 4-11 (mean 7.5) years after certification. Fifty nine patients had died, 23 (39%) from lung cancer, 6 (10%) from mesothelioma, and 11 (19%) from other respiratory causes. The number of observed deaths was 2.25 times greater than expected and 7.4 times greater than expected for lung cancer. Adenocarcinoma was the commonest histological type but other cell types were also increased. Finger clubbing (p less than 0.01) and percentage of predicted FEV1 (p less than 0.01) were of value in predicting death, but increasing profusion of small opacities greater than 1/0 (ILO/U-C international classification of radiographs of pneumoconiosis, 1971), duration of exposure to asbestos, time from first exposure to asbestos, and percentage of predicted vital capacity and transfer factor did not predict death.

Adult↗

Significance of finger clubbing in asbestosis.

The prognostic significance of finger clubbing in asbestosis has been assessed in 167 cases certified by the London Pneumoconiosis Medical Panel from 1968 to 1974. Finger clubbing developed early in the clinical course of the disease and was associated with a lower gas transfer, a higher mortality and a greater likelihood of progression in intrapulmonary fibrosis than was found among cases without finger clubbing. Finger clubbing was not associated with heavier asbestos exposure. Its presence appears to be associated with a more severe form of disease.

Adult↗

Development of acute lung injury after the combination of intravenous bleomycin and exposure to hyperoxia in rats.

Pulmonary toxicity is an important adverse effect of bleomycin treatment. Very little is known of the mechanisms underlying the development of lung injury, especially after intravenous administration, or how it can be modulated. In this study acute lung injury induced by bleomycin has been examined in rats by assessment of alveolar lavage cell profiles, histological examination, and measurement of the total pulmonary extravascular albumin space. Intratracheal instillation of bleomycin 1.5 mg resulted in a severe pneumonitis with influx of inflammatory cells into the alveoli as assessed by alveolar lavage, oedema of the alveolar walls, and up to an eight fold increase in the total pulmonary extravascular albumin space, maximal at 72 hours. Intravenous bleomycin 0.15-5 mg produced no detectable injury when assessed in these ways. Exposure to hyperoxia (40-90%) after intravenous bleomycin, however, induced lung injury similar to that produced by intratracheal bleomycin. A much more severe injury followed administration of intravenous bleomycin after an exposure to hyperoxia, which itself resulted in lung injury; but lung injury was still detectable after bleomycin when the exposure to hyperoxia was insufficient to induce changes in control animals. Lung injury was not observed when the exposure to hyperoxia preceded bleomycin treatment. These results indicate the importance of oxygen in the pathways leading to acute lung injury following intravenous bleomycin. We conclude that exposure to oxygen might induce lung injury during and after bleomycin treatment, and suggest that in these circumstances oxygen therapy should be kept to a minimum.

Animals↗

Late relapse of desquamative interstitial pneumonia.

Late relapse in desquamative interstitial pneumonia (DIP) is poorly documented. We describe 2 cases of relapse after 7 and 12 yr of therapeutic remission. Lung biopsies taken initially and at the time of relapse showed very similar appearances on both occasions, with little increase in fibrosis in the second sample. Patients with DIP in remission should be followed indefinitely.

Adult↗

The value of serial bronchoalveolar lavages in assessing the clinical progress of patients with cryptogenic fibrosing alveolitis.

This study tested the hypothesis that changes in bronchoalveolar lavage (BAL) inflammatory cell profiles reflect the clinical progress of patients with cryptogenic fibrosing alveolitis (CFA) when followed for substantial periods of time with or without any form of treatment. Two or more bronchoalveolar lavages (mean, 3; maximum, 5) were performed on each of 32 patients who were followed for periods as long as 7 yr (mean, 2.5 yr, median, 4 yr). The majority were studied before and during treatments with prednisolone alone or with prednisolone and cyclophosphamide. A total of 90 lavages were performed, and the changes in BAL inflammatory cell percentage counts were compared with defined categories of clinical progress. At initial lavage, 97% of the patients had an increased percentage of at least 1 BAL cell type. On follow-up, 12 patients showed definite and sustained clinical improvement, and their serial lavage cell counts tended to return towards normal. Falls in neutrophils were significant in patients responding to prednisolone, whereas falls in eosinophils were significant in those responding to cyclophosphamide. By contrast, in patients who failed to improve, neutrophil and eosinophil counts tended to remain elevated. However, several nonresponders appeared to have clinically stable disease, demonstrating that persisting granulocytes are not necessarily paralleled by clinical deterioration. Consecutive BAL cell counts in the pair of samples before and after introduction of prednisolone showed no overall change in any lavage cell type to suggest that the drug has a general effect independent of clinical progress. A similar comparison for cyclophosphamide showed falls in eosinophil percentage counts, but these were mainly responders.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchi↗

Mast cells, atypical lymphocytes, and neutrophils in bronchoalveolar lavage in extrinsic allergic alveolitis. Comparison with other interstitial lung diseases.

Bronchoalveolar lavage (BAL) samples from exposed patients with extrinsic allergic alveolitis (EAA) contained mast cells in increased numbers in addition to lymphocytes. The counts rarely exceeded 0.5% in sarcoidosis, cryptogenic fibrosing alveolitis, or asbestosis or in control samples, but they were as much as 10-fold higher in EAA (p less than 0.001). Higher concentrations of histamine were demonstrated in EAA BAL-cell lysates, and histamine was released from cells challenged with anti-IgE. Electron microscopic examination confirmed that the cells were mast cells that differed from mast cells in dermal connective tissue and alveolar interstitial tissue but resembled bronchial subepithelial tissue mast cells in showing more features suggestive of activation. However, they showed more marked degranulation, and many were young. By light microscopy, they also resembled "mucosal" rather than "connective" tissue mast cells since granule staining was prevented by formaldehyde. Mast cell counts fell to normal after removal of patients from exposure, but lymphocyte increases, including atypical "blast" forms, persisted despite clinical recovery. Neutrophils were also increased before, but rarely after, removal. We suggest that EAA may provide an example of a human disease to support recent evidence that some delayed hypersensitivity disorders involve mast cells as well as lymphocytes.

Alveolitis, Extrinsic Allergic↗

The effects of iron and desferrioxamine on the lung injury induced by intravenous bleomycin and hyperoxia.

The development of acute lung injury in rats following the intravenous injection of bleomycin was assessed by measuring the total pulmonary extravascular albumin space. Intravenous bleomycin alone produced no evidence of lung injury, yet when combined with a simultaneous exposure to hyperoxia or simultaneous tracheal instillation of ferric iron or ascorbate a severe lung injury evolved. Neither ferric iron or ascorbate alone produced lung injury when assessed in this manner, and ferrous iron, ferritin and haemoglobin did not potentiate bleomycin induced lung injury. A continuous subcutaneous infusion of desferrioxamine enhanced hyperoxia induced lung injury, and had no modulating effect on the lung injury produced by combined intravenous bleomycin and hyperoxia. These results indicate that ferric iron can potentiate bleomycin induced lung injury, and that the metal chelator desferrioxamine can have adverse effects on the development of acute lung injury.

Animals↗

Sputum in asthma.

A detailed questionnaire concerning sputum production was completed by 130 patients with variable airflow limitation fulfilling conventional criteria for asthma. The mean age at onset was 17 years and 75% had positive prick skin tests. One hundred of 130 (79%) reported sputum production; 21% were non secretors. In 68% of those with sputum it was a constant feature from the onset. Increased volumes of sputum was associated with more severe asthma and disability and negative skin tests. An additional component of persisting airflow limitation was found more frequently in the group characterized by no sputum and large volumes. It was less common in those with small sputum volumes. Irrespective of volume, 43% of 130 fulfilled the conventional criteria for MRC chronic bronchitis but 57% of these were non-smokers. We conclude that asthma and chronic bronchitis are not mutually exclusive diagnoses; a history of regular sputum production may lead to the underdiagnosis of asthma and its consequent under-treatment.

Adolescent↗

Biochemical evidence for an increased and progressive deposition of collagen in lungs of patients with pulmonary fibrosis.

To assess the role of changes in lung collagen in pulmonary fibrosis, the content of this protein was measured in biopsy and autopsy lung from patients with cryptogenic fibrosing alveolitis (CFA), a fibrotic lung disorder of unknown cause. The collagen concentration was measured in lung samples from 21 patients with CFA (14 autopsy and seven open-lung biopsy) and 17 normal subjects; total lung collagen was determined in the right lung of 10 patients who died from CFA and the results were compared with those from 10 normal lungs. There was a wide variation in the collagen concentrations but the mean value (+/- SEM) for patients with CFA (217 +/- 13 mg/g dry weight) was significantly higher (P less than 0.02) than that of the controls (155 +/- 15 mg/g dry weight). The mean collagen concentration of the autopsy samples (243 +/- 20 mg/g dry weight) was significantly higher (P less than 0.05) than that of the biopsy samples (165 +/- 24 mg/g dry weight). The mean total collagen was markedly raised (P less than 0.001) in right lungs of patients with CFA (32.5 +/- 4.3 g) compared with normal lungs (14.0 +/- 1.1 g). When corrected for the predicted lung volume this difference in total lung collagen remained statistically significant (P less than 0.01, mean for patients 4.7 +/- 0.7 mg/ml, controls 2.3 +/- 0.2 mg/ml). These results demonstrate an increased deposition of lung collagen in this form of pulmonary fibrosis. They also suggest that there is a greater collagen concentration in lungs of patients with later disease, indicating a progressive deposition of collagen during the course of the disease.

Adult↗