PubMed Health⌕ Search

Biomedical subjects

H Reddel

Publications and source records attributed to H Reddel.

4 recordsLinked to original sources
PubMed1999

Differences between asthma exacerbations and poor asthma control.

BACKGROUND: Increased variation in peak expiratory flow (PEF) is characteristic of poorly controlled asthma, and measurement of diurnal variability of PEF has been recommended for assessment of asthma severity, including during exacerbations. We aimed to test whether asthma exacerbations had the same PEF characteristics as poor asthma control. METHODS: Electronic PEF records from 43 patients with initially poorly controlled asthma were examined for all exacerbations that occurred after PEF reached a plateau with inhaled corticosteroid treatment. Diurnal variability of PEF was compared during exacerbations, run-in (poor asthma control), and the period of stable asthma before each exacerbation. FINDINGS: Diurnal variability was 21.3% during poor asthma control and improved to 5.3% (stable asthma) with inhaled corticosteroid treatment. 40 exacerbations occurred in 26 patients over 2-16 months; 38 (95%) of exacerbations were associated with symptoms of clinical respiratory infection. During exacerbations, consecutive PEF values fell linearly over several days then improved linearly. However, diurnal variability during exacerbations (7.7%) was not significantly higher than during stable asthma (5.4%, p=0.1). PEF data were consistent with impaired response to inhaled beta2-agonist during exacerbations but not during poorly controlled asthma. INTERPRETATION: Asthmatics remain vulnerable to exacerbations during clinical respiratory infections, even after asthma is brought under control. Calculation of diurnal variability may fail to detect important changes in lung function. PEF variation is strikingly different during exacerbations compared with poor asthma control, suggesting differences in beta2-adrenoceptor function between these conditions.

Adolescent↗
PubMed1992

Human mesothelioma cells and asbestos-exposed mesothelial cells are selectively resistant to amosite toxicity: a possible mechanism for tumor promotion by asbestos.

To determine if asbestos exposure could contribute to mesothelial cell carcinogenesis by selection and/or expansion of an initiated cell population, we compared normal human pleural mesothelial cells to either human mesothelioma cell lines or mesothelial cells transfected with cancer-related genes for sensitivity to amosite fibers in vitro. Neither normal nor mesothelioma cells were directly stimulated to replicate or increase DNA synthesis by any of the asbestos exposure conditions tested. The potential selective effect of asbestos exposure was demonstrated by a differential sensitivity of normal mesothelial cells and mesothelioma cells to amosite: for example, up to 20-fold higher concentrations of amosite fibers were required to inhibit replication of mesothelioma cell lines than normal mesothelial cells. In addition, a significant resistance (4-fold) to amosite toxicity was observed for SV40 immortalized mesothelial cell lines that had previously been selected in vitro for resistance to asbestos. SV40 immortalized cells that have become tumorigenic after transfection with either Ha-ras or PDGF A-chain genes were not significantly more resistant to the cytotoxic effects of amosite than primary normal cells, and the primary cells were equally sensitive to amosite as mesothelial cells that were only immortalized by SV40. The sensitivity of normal mesothelial cells to asbestos does not appear to be simply a result of general fragility of the mesothelial cells, since similar levels of hydrogen peroxide and silica were cytotoxic for normal mesothelial cells and mesothelioma cell lines. Because mesothelioma cells have a greater resistance to asbestos cytotoxicity than normal mesothelial cells, we hypothesize that a differential resistance to cell killing by asbestos fibers in vivo may result in a selective expansion of an initiated or transformed cell population and thus contribute to the carcinogenesis process. Since tumorigenicity and asbestos resistance occur independently of one another in genetically altered mesothelial cell lines, genotypic and phenotypic alterations that lead to tumorigenic conversion may not be the same changes that provide resistance to cell killing by asbestos.

Asbestos↗