The prediction of in-flight hypoxaemia using non-linear equations.

BACKGROUND: Respiratory disease may cause profound hypoxaemia during flight. Previously derived linear equations poorly predict the need for supplemental oxygen during air travel. The current gold standard assessment is the hypoxic challenge test (HCT). Recent guidelines recommend HCT is performed for those patients with SpO2 < 95% at sea level. The HCT protocol is a costly and time consuming investigation. METHODS: Retrospective clinical and HCT data from 138 patients were applied to previous linear equations to assess predictive value. Novel non-linear predictive models (NLMs) were constructed from these data. The linear equations and the NLMs were then applied prospectively to 44 patients undergoing HCT. RESULTS: Overall, 39% of historic patients had a positive HCT (PaO2N2 <50 mmHg). Existing linear equations varied in sensitivity (52-87%) and specificity (40-74%) at predicting positive HCT results. Seven novel NLMs (NLM1 to NLM7) were developed from the historic dataset. All NLMs predicted PaO2N2 more accurately than the original linear equations when tested prospectively. The best fit was observed using NLM2 which uses PaO2RA and PaCO2RA as input terms. The NLMs are applicable to a broad range of conditions. CONCLUSIONS: The novel NLMs represent a low cost option for the prediction of significant hypoxia during flight and perform better than SpO2 in identifying those patients who require more formal assessment with HCT.

Asbestos exposure, lung cancer and asbestosis.

The relationship between asbestos exposure, lung cancer and asbestosis is reviewed. Studies have demonstrated the risk of lung cancer to be raised in asbestos-exposed workers whether asbestosis is present or not. Although increasing exposure increases the risk of disease, variability in estimation of fibre levels and in subject susceptibility should be borne in mind. Consensus opinion recommends that attribution of lung cancer to asbestos exposure should be based on clinical and occupational histories. The risk of lung cancer in those who both smoke and are exposed to asbestos is increased in a multiplicative way, putting subjects at very great risk.

Dynamics and clinical effects of nonferrous metals in the human body.

Pollution from toxic metal fumes and dusts occurs in many industrial situations. Exposed workers may experience occupational diseases directly related to poisoning from metallic elements. Studies have shown that the major route of absorption of metals is by inhalation. Once absorbed, distribution to various tissues and excretion from the body differ between metals. Multiphasic retention times have been described for many metals with a proportion of the body burden being eliminated very slowly. Biological half-lives range across many years. Whilst blood or urine levels of metals may reflect current exposure, once exposure ceases these levels may not be good indicators of remaining body burden. Acute and chronic health effects occur after exposure. A wide range of chronic disease including many respiratory diseases (emphysema, lung cancer, chronic obstructive pulmonary disease, fibrosis and asthma), together with neurological, haematological, hepatotoxic and nephrotoxic effects, has been reported.

Damp housing and asthma.

An allergic disposition has long been recognized as a risk factor for asthma. However, it has been suggested that, irrespective of genetic factors, exposure to environmental agents is of major importance in the development of asthma. In industrialized countries, people spend most of their time indoors and so environmental conditions inside the home may play an important role in asthma development. A review of studies examining the relationship between housing conditions and health in general or, more specifically, the relationship between respiratory symptoms/asthma and damp housing and mould has been carried out. These studies have shown that damp housing conditions are associated with increased prevalence of respiratory symptoms and asthma. The severity of asthma increases with an increasing quantity of dampness and mould in the home. It is suggested that damp conditions may, by a number of mechanisms, increase the allergenic burden so resulting in the development of asthma.

Hormonal, renal, and autonomic nerve factors involved in the excretion of sodium and water during dynamic salt and water loading in hypoxaemic chronic obstructive pulmonary disease.

BACKGROUND: Some patients with hypoxaemic chronic obstructive pulmonary disease (COPD) develop sodium and water retention and a subclinical autonomic neuropathy. The possibility that these might be associated has been investigated. METHODS: The ability of 24 patients with COPD to excrete a 6 ml/kg 2.7% intravenous saline or 15 ml/kg oral water load was studied and changes in plasma electrolyte levels, osmolality, plasma aldosterone and vasopressin levels, urinary volume and sodium content, glomerular filtration rate, renal blood flow, and cardiovascular autonomic nerve function were measured. Patients were divided into groups of eight: those in group A (controls) had mild COPD with a Pa02 of > 9 kPa and no oedema, patients in group B were more hypoxaemic but had never been oedematous, whilst those in group C were hypoxaemic and mildly oedematous at the time of the study. RESULTS: Patients in groups B and C excreted less sodium and water during saline loading and a lesser proportion of the water load. Patients in group C had a reduction in renal blood flow and glomerular filtration rate and all had a subclinical autonomic neuropathy, which was also found in three patients in group B. Their plasma aldosterone level was raised but did suppress appropriately on saline loading. Vasopressin levels were abnormally raised for the osmolality in patients in group C and in those with autonomic dysfunction throughout the water load and at 240 minutes after the salt load. Sodium and urine excretion was highly correlated with autonomic dysfunction, aldosterone levels at time zero, and renal blood flow. The 11 patients with autonomic dysfunction were more likely to be oedematous, more hypoxaemic, excreted much less urine and sodium, had lower glomerular filtration rate and renal blood flow, and higher aldosterone and vasopressin levels than the remaining patients. CONCLUSIONS: In patients with COPD the inability to excrete sodium and water is multifactorial. This is the first study to show that autonomic dysfunction is at least associated and might play an important part in the impaired sodium and water homeostasis seen in patients with severe COPD.

Effects of angiotensin converting enzyme inhibition on sodium excretion in patients with hypoxaemic chronic obstructive pulmonary disease.

BACKGROUND: Some patients with hypoxaemic chronic obstructive pulmonary disease (COPD) develop cor pulmonale with sodium and water retention. The sodium retention has been explained as a result of increased plasma levels of aldosterone. If this was true angiotensin converting enzyme (ACE) inhibition would be expected to lower plasma levels of aldosterone and improve the renal excretion of sodium. METHODS: Six patients with stable hypoxaemic COPD (PaO2 < 8.0 kPa) and a history of an oedematous exacerbation received an intravenous hypertonic saline load (6 ml/kg body weight of 2.7% saline over one hour) before and while taking 4 mg/day perindopril, an ACE inhibitor, for one month. Aldosterone, antidiuretic hormone (ADH), plasma and urine electrolyte levels, osmolality, and volume were measured over four hours. The repeatability of the saline load test was assessed in six patients with a similar severity of hypoxaemic COPD. For comparison the saline load test was also performed in six patients with mild COPD. RESULTS: The hypertonic saline load test results were repeatable. Perindopril reduced the mean (SD) plasma level of aldosterone from 142 (88) pg/ml to 54 (24) pg/ml at 0 minutes before the saline infusion, and from 64 (35) pg/ml to 30 (17) pg/ml after the infusion without improving the urinary volume or sodium excretion. Before starting treatment with perindopril 43.7 (6.9) mmol (20%) of the sodium load was excreted compared with 49.6 (7.9) mmol (22% of load) when taking perindopril. Patients with mild COPD excreted more sodium (77.6 (21.4) mmol (38.7% of load)) despite having similar plasma aldosterone levels to those in the patients receiving perindopril. CONCLUSIONS: Patients with stable hypoxaemic COPD have an impaired ability to excrete sodium which is not improved by the administration of an ACE inhibitor. ACE inhibition lowered the plasma level of aldosterone without improving sodium excretion. This suggests that the inability of patients with hypoxaemic COPD to excrete sodium is not caused by their increased plasma levels of aldosterone.

Hypothesis: exposure to solvents may cause fibrosing alveolitis.

The incidence of fibrosing alveolitis, which can be caused by many agents, is increasing. In a proportion of patients, the aetiology is unknown (cryptogenic fibrosing alveolitis), but it has been suggested that environmental factors may play an important, but unrecognized, role in its pathogenesis. A review of the literature suggests that there may be a link between exposure to solvents, widespread occupational pollutants, and fibrosing alveolitis. Experimental work in animals has shown that exposure to solvents produces changes in the lung similar to those found in fibrosing alveolitis. Occupational exposure to a wide number of solvents has been associated with the development of systemic sclerosis. Pulmonary involvement in systemic sclerosis is morphologically indistinguishable from fibrosing alveolitis, and a close relationship between the two diseases seems to exist. This close relationship and the experimental work linking solvent exposure to fibrosing alveolitis suggest that solvent exposure may be one cause of cryptogenic fibrosing alveolitis. Determination of any occupational exposure of patients with cryptogenic fibrosing alveolitis may help in the understanding and prevention of this disease.

Occupational siderosis and welders' lung: a review.

Siderosis of the lung is generally assumed to be a benign condition, not associated with respiratory symptoms. A review of the literature suggests that this assumption may be incorrect, and that siderosis may lead both to symptomatic and functional changes. It is known that iron ore miners have a raised lung cancer mortality, but this has been attributed to smoking, or exposure to tars or radon. Mortality studies among iron workers (haematite miners, welders, iron foundry and steel workers) show, however, that an association exists between working with iron and death, both from lung cancer and other respiratory causes. A number of surveys have examined respiratory function and symptoms among welders. These indicate that welding is associated with obstructive airways disease. The effect of the welding fume on respiratory function and symptoms can be as great as that of smoking. Iron has also been shown to cause fibrosis in some cases. Small functional changes of restriction and loss of lung compliance are often due to iron alone. The fibrosis may be enhanced by associated silica exposure. A number of constituents of welding fume could, along with iron, contribute to pulmonary changes. The presence of siderosis may act as a good marker of exposure to fume and any resulting disability.

Isoprenaline-induced changes in regional myocardial perfusion in the pathogenesis of myocardial necrosis.

Isoprenaline in a single dose induces impairment in perfusion of the subendocardial myocardium of the rat left ventricle. This defect in perfusion persists for up to 150 min and corresponds in distribution to the myocardial necrosis produced by similar doses of isoprenaline. It is mediated by the beta-receptors as it is prevented by beta-blockade with propranolol. It is considered that isoprenaline-induced myocardial necrosis represents myocardial infarction.

Quantitation of isoprenaline-induced changes in the ventricular myocardium.

Small doses of isoprenaline sulphate given intermittently produce a characteristic cardiopathy consisting of subendocardial scarring and myocardial hypertrophy. A morphometric technique was successfully applied to the quantitation of these changes. This technique improves the use of the isoprenaline model for the study of cardiac necrosis as statistical analysis can be applied and objective comparisons made. No hypertrophy was seen in the absence of myocardial necrosis which suggests that it is at least in part compensatory.