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P L Haslam

Publications and source records attributed to P L Haslam.

68 records · Page 4Linked to original sources
PubMed1983

Cryptogenic fibrosing alveolitis: prediction of fibrogenic activity from immunohistochemical studies of collagen types in lung biopsy specimens.

Collagen immunofluorescence studies were performed on biopsy specimens from 25 patients with cryptogenic fibrosing alveolitis. We studied the relationship of these results to the clinical, radiological, and physiological assessments of disease activity during six-month periods before and after the lung biopsy; to the appearances on routine histological examination; to the inflammatory cell proportions in bronchoalveolar lavage fluid; and to the response to treatment. Positive associations were observed between the presence of type III collagen and disease activity before (p less than 0.015) and after (p less than 0.02) lung biopsy. These were independent of clinical and routine histological features. The type-III-positive group also contained nine of the 11 responding to treatment. None of the type-III-positive patients had a quiescent or stable course. In contrast, most patients with no type-III-collagen fluorescence had a stable course over the time of this study and did not improve on treatment. It is suggested that collagen typing may be an additional useful method of assessing potentially reversible disease in cryptogenic fibrosing alveolitis.

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PubMed1982

Impaired antibody-dependent cell-mediated cytotoxicity in cryptogenic fibrosing alveolitis (synonym: idiopathic pulmonary fibrosis).

Mononuclear cells from the blood of 26 patients with the 'autoimmune' connective tissue disorder cryptogenic fibrosing alveolitis (CFA) were examined in Chang cell cytotoxicity assays for their capacity to mediate antibody-dependent cell-mediated cytotoxicity (ADCC). The results showed an impairment for the group by comparison with a group of 45 normal healthy controls (P less than 0.01). The impairment was greater in patients with associated connective tissue disorders of other systems (CFA+CT) than in those having the lung disorder alone (lone CFA); (P less than 0.001). The reduction in ADCC showed a correlation with reducing counts of cells bearing Fc gamma G surface receptors (P less than 0.05), and with increasing levels of soluble immune complexes in the blood of these patients by C1q binding (P=0.05). Non-specific esterase staining indicated that the Fc gamma G rosetting cells were subpopulations of lymphocytes not monocytes. We therefore suggest that the observed ADCC impairment may be due to impairment of lymphocyte Fc receptor function, and we speculate that this may influence immune regulation.

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PubMed1981

Bronchoalveolar macrophages in sarcoidosis and cryptogenic fibrosing alveolitis.

Previous reports suggest that blood monocytes and tissue epithelioid cells in patients with sarcoidosis are "activated', but few studies have been undertaken on human alveolar macrophages. In the present study, bronchoalveolar lavage samples have been obtained from eighteen patients with sarcoidosis and these have been compared with twenty controls and twenty-nine patients with non-granulomatous chronic inflammatory interstitial lung disease (cryptogenic fibrosing alveolitis). Assessment of the functional state of the macrophages was made by measurements of C3b receptor sites on the cell membrane, intra and extracellular lysosomal enzyme (beta-D-glucosamidase) and the degree of spreading of macrophages on glass. C3b receptor sites and intracellular levels of lysosomal enzyme were significantly reduced in sarcoidosis compared to controls; levels of extracellular enzyme in the lavage supernatant fluid and macrophage spreading were similar to controls. These features suggest that alveolar macrophages from patients with sarcoidosis are not "activated'. By contrast, in cryptogenic fibrosing alveolitis, macrophages show a greater extracellular:intracellular ratio of lysosomal enzyme and more spreading, suggestive of "activation'.

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PubMed1981

Cryptogenic fibrosing alveolitis. Relationships of pulmonary physiology and bronchoalveolar lavage to response to treatment and prognosis.

A minority of patients with cryptogenic fibrosing alveolitis (idiopathic pulmonary fibrosis) respond to treatment with corticosteroids. The purpose of this study was to identify factors other than histologic features that relate to responsiveness and prognosis. An analysis of 120 patients on whom data were prospectively collected is reported. The relationships between pulmonary function measurements, differential cell counts on bronchoalveolar lavage fluid, physiologic response to treatment, and survival are discussed. Patients responding to treatment with corticosteroids or immunosuppressive drugs had more severe initial impairment of the FVC (p less than 0.0001) and a more recent onset of disease (p less than 0.001). Lavage cell counts showed that increased proportions of lymphocytes were associated with responsiveness to corticosteroids and good prognosis (p less than 0.001), whereas increased eosinophils or increased neutrophils without increased lymphocytes were associated with failure to respond (p less than 0.025), and increased eosinophils were associated with a greater likelihood or progressive deterioration (p less than 0.05). Life table comparisons of survival in different groups showed improved survival in patients responding to treatment (p less than 0.05). Among nonresponders, those with more severe impairment of the FVC had shorter survival (p less than 0.05). We concluded that physiologic and bronchoalveolar lavage data allow predictions of responsiveness to treatment and prognosis that are of practical value to clinicians.

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PubMed1981

Evidence of increased histamine levels of lung lavage fluids from patients with cryptogenic fibrosing alveolitis.

In this study we report a significant increase in histamine in lung lavage fluids from a group of 33 patients with lone cryptogenic fibrosing alveolitis (lone CFA), and from a group of 13 patients having CFA in association with other connective tissue disorders, when compared with findings for 13 smoking patient controls without peripheral lung disease (P less than 0.001, P less than 0.05 respectively). The increases were independent of smoking or treatment. Significant correlations were obtained between the raised histamine levels in CFA and increased levels of albumin and increased counts of neutrophils and eosinophils in the lavage fluids, and with more pronounced fibrosis in CFA lung biopsies.. Thus histamine is associated with features of inflammation relating to progressive or more severe disease. No significant increase in histamine was observed in a group of 22 patients with sarcoidosis, although 21 had evidence of disease involving the lung parenchyma. There were, however, significantly higher levels in the patients with X-ray evidence of upper lobe contraction, suggestive of "fibrosis" (P less than 0.025). The levels also showed a correlation with increasing counts of lavage neutrophils (P less than 0.005), a feature also associated with X-ray evidence of contraction in this group. Mast cells were readily identified in biopsies from 12 CFA patients suggesting that these cells may provide one possible source of histamine in CFA lungs. These observations raise the question whether histamine, and/or possibly other substances derived from mast cells, plays any role in amplifying inflammation associated with pulmonary fibrosis.

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PubMed1981

Pulmonary disorders associated with Sjögren's syndrome.

Pulmonary disease is recognized to occur as a complication of Sjögren's syndrome and we have studied 17 patients, the majority middle-aged women, with this association. Eight had sicca syndrome alone and nine had Sjören's syndrome in association with a connective tissue disease. Various pulmonary disorders were found: 10 had diseases mainly affecting pulmonary parenchyma (recurrent pneumonia, granulomatous infiltration, pseudolymphoma and fibrosing alveolitis) and six had disorders of the airways (bronchitis, bronchiectasis and asthma). One patient presented with a mediastinal immunoblastic lymphoma. To test the hypothesis that physical factors such as the retention of viscid mucus may play a part in the development of lung disease in Sjögren's syndrome, we have measured mucociliary clearance in patients with Sjögren's syndrome using 99Tc-labelled polystyrene particles. The mucociliary clearance rate was found to be normal from central airways and the whole lung clearance rate was significantly increased in Sjögren's syndrome compared with normal controls. The latter was attributed to the failure of penetrance of the radioaerosol into the periphery of the lung consistent with obstruction of small airways in Sjögren's syndrome. The patients with Sjögen's syndrome and lung disease were characterized by a number of immunological markers irrespective of the presence or type of associated connective tissue disorder. The commonest found were speckled antinuclear antibody by indirect immunofluorescence, antibodies to the acidic nuclear antigen B by counterimmunoelectrophoresis, increased serum DNA binding, increased levels of circulating immunoglubulins, rheumatoid factor in high titre and circulating soluble immune complexes as detected by Clq binding assay.

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PubMed1980

Complement activation during cardiopulmonary bypass.

Conversion of C3, the third component of complement, has been studied using a two-dimensional immunoelectrophoretic method. Evidence of C3 conversion has been obtained in stored donor blood, in patients during and after cardiac surgery involving cardiopulmonary bypass, and occasionally during thoractomy for pulmonary resection. It is suggested that complement activation is one factor contributing to tissue injury after cardiopulmonary bypass.

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PubMed1980

Bronchoalveolar lavage fluid cell counts in cryptogenic fibrosing alveolitis and their relation to therapy.

Bronchoalveolar lavage was used to sample inflammatory cells from the lungs of 51 patients with cryptogenic fibrosing alveolitis (CFA) (24 smokers, 12 ex-smokers, and 15 non-smokers). The smokers with CFA have been compared with 15 smoking control subjects in whom there was no radiographic abnormality or clinical evidence of chronic bronchitis. Significantly lower volumes of lavage fluid were recovered from the smokers with CFA (p < 0.001) and the fluid contained lower percentages of macrophages (p < 0.01), reflecting increased percentages of eosinophils (p < 0.001) and neutrophils (p < 0.01). Similar changes were seen in the ex-smokers and non-smokers. There was also an increase in the percentages of lymphocytes when the whole group of CFA patients was compared with the control subjects (p less than or equal to 0.05). No significant differences were found when patients with "lone" CFA were compared with those having associated systemic disease. The only feature distinguishing smokers from non-smokers with CFA was the presence of pigmented cytoplasmic inclusions in the macrophages from the smokers (p < 0.001). However, there were lower numbers of pigmented macrophages in the smoking CFA patients by comparison with the control subjects suggesting either a change in phagocytic capacity or turnover rate in this disease. Profiles of differential cell counts in individual patients showed that increases of eosinophils over 3% or neutrophils over 4% or both with lymphocyte counts of less than 11% related to a poor clinical response to corticosteroids, but lymphocyte percentages greater than 11% related to improvement (p < 0.05).

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PubMed1979

Circulating immune complexes in patients with cryptogenic fibrosing alveolitis.

Increased Clq binding levels have been obtained in serum from twenty-one (50%) of forty-two patients with cryptogenic fibrosing alveolitis (CFA) suggesting the presence of circulating immune complexes. There was a low frequency of positive results using a number of other tests for circulating immune complexes. The increased Clq binding levels were observed in six (35%) out of seventeen patients with lone lung involvement and in fifteen (60%) out of twenty-five patients with extrapulmonary connective tissue disorders. There was an especially close correlation between arthritis and elevated Clq binding. A strong correlation between Clq binding levels and levels of circulating rheumatoid factor (RF) and IgG, and enhancement in macrophage radiobioassay tests using RF-containing sera, suggested that RF might be involved in the circulating immune complexes in these patients. DNAase pre-treatment of sera did not influence the findings, and there was no correlation between Clq binding and levels of immunofluorescent ANA, C-reactive protein levels, or platelet counts. A weak correlation between Clq binding and erythrocyte sedimentation rates, and slightly lower binding levels in treated than untreated patients with 'lone' CFA suggested that binding levels may give some indication of disease activity and may in some instances be influenced by treatment.

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PubMed1978

Lymphocyte responses to phytohaemagglutinin in patients with asbestosis and pleural mesothelioma.

Quantitative impairment of lymphocyte responses to phytohaemagglutinin (PHA) has been demonstrated in six (21%) out of twenty-eight patients with asbestos-associated pulmonary fibrosis, in comparison with a group of unexposed normal controls. The impairment tended to occur in patients with fairly severe fibrosis, comparatively short duration of exposure to asbestos dust and with increases in serum immunoglobulin levels. One patient with asbestosis and an associated bronchial carcinoma also had depressed lymphocyte responses to PHA. These findings suggest a relationship between defective T-lymphocyte function and the fibrotic response in asbestosis. Whether it is also linked with the development of lung cancer, occurring either before or at a pre-clinical stage of tumour growth, and is of value in identifying patients especially at risk should now be explored in longitudinal studies. However, eight out of ten patients with asbestos-associated pleural mesothelioma and without lung fibrosis showed no evidence of impaired cellular immunity, either by in vitro testing with PHA or by vivo delayed hypersensitivity skin testing, indicating that impaired T-lymphocyte function is unlikely to be a common finding in all types of asbestos-associated malignancy.

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PubMedDate not supplied

Identification of inorganic dust particles in bronchoalveolar lavage macrophages by energy dispersive x-ray microanalysis.

This study shows that energy dispersive x-ray microprobe analysis to identify and quantify intracellular particles in macrophages obtained by the minimally invasive method of bronchoalveolar lavage (BAL) can detect inorganic dust exposures of many different kinds. Bronchoalveolar lavage macrophages from 22 patients have been examined. Twelve patients had occupational exposure to asbestos, talc, silica, hard metal or printing ink, while 10 had no known history of dust exposure. X-ray microprobe analysis identified particles which related to the known exposures, superimposed on a background of other particles related to smoking (kaolinite and mica) or to the general environment (silicon, titanium, and iron). The particle identification provided useful objective confirmation of the known exposures, except for silica, which could not be distinguished from the general background levels. X-ray microanalysis using BAL macrophages can be helpful for clarification of mixed dust exposures, to identify particles when light microscopy indicates retained dust in patients with no known history of exposure, and to monitor retained particles after removal from exposure.

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