Quantifying errors in the estimation of tuberculosis mortality in a population of South African miners.

BACKGROUND: All-cause mortality, based on national tuberculosis programme (NTP) register deaths, may under- or overestimate tuberculosis (TB) specific mortality in the population. OBJECTIVE: To assess the factors influencing this measurement in a single large population with high TB prevalence and mortality. METHODS: Routinely collected data on TB cases and treatment outcomes were linked to population data from a cohort of South African miners from 1995 to 2008. Vital status and cause of death were determined from multiple sources, including the TB programme, death register and autopsy. RESULTS: The TB mortality rate, based on 430 deaths on the TB register, was 192/100,000 person-years (py). Many of these deaths (57%) were not caused by TB, and 483 TB deaths were identified outside the programme. Overall, there were 674 TB-specific deaths; the TB-specific mortality rate was 302/100,000 py. These deaths included 191 (28%) on the TB register, 23 (3%) among defaulters/transfers, 153 (23%) after anti-tuberculosis treatment and 307 (46%) in men who had never been on the programme. CONCLUSIONS: This study highlights methodological issues in estimating TB mortality. In this population, a method using the product of TB incidence and case fatality consistently underestimated TB mortality. Accurate estimates of TB-specific mortality are crucial for the proper evaluation of TB control programmes.

Assessment of reliability of lung function screening programs or longitudinal studies.

The aim was to determine reliability of lung function measurements performed according to recommendations of the American Thoracic Society (ATS) at a screening program in a large South African gold mine and to determine the usefulness of the reliability coefficient G for monitoring the reliability of lung function measurements in a mass screening program. The reliability coefficient G estimates the amount of random error of measurement, relative to the total variation in a measurement. The coefficient G was calculated as a correlation coefficient between two consecutive lung function tests performed within 6 mo, over a period of 43 mo on 3,378 miners. There was significant temporal variability in the reliability. For FEV(1), the coefficient G showed increased variability over the first 5 mo and stabilized at a value of 0.93 for the next 23 mo, after which it systematically declined over the next 15 mo. We estimated that in a large screening program, an optimal sample size of around 900 miners, examined randomly throughout the year, on a yearly basis, would provide a sufficient sample to examine monthly or quarterly fluctuation in the reliability. The value of the reliability coefficient G did not change when the time between two consecutive tests increased up to 15 mo. In conclusion, monitoring of lung function reliability in a screening program by the reliability coefficient G should improve data quality, and provide a measure on which the confidence in a decision-making process could be based when examining temporal changes in lung function for individual subjects.

Interaction of HLA phenotype and exposure intensity in sensitization to complex platinum salts.

The development of sensitization to inhaled allergens is determined by the interaction of multiple genetic and environmental influences. Occupational sensitization to low-molecular-weight chemicals allows a specific immunological response to an inhaled hapten to be studied in a well-defined population with characterized exposure. We investigated the workforce of a large platinum refinery exposed to ammonium hexachloroplatinate (ACP) to test the hypothesis that the development of IgE-associated sensitization to ACP was influenced by human leukocyte-associated antigen (HLA) phenotype, especially in those with lower ACP exposure. We performed HLA typing in 44 cases with a positive skin prick test to ACP, and 57 nonsensitized referents matched on age, race, duration of employment, and category of ACP exposure. An HLA-DR3 phenotype was more common among cases (odds ratio [OR] 2.3), and more so in those with low (OR infinite) than with high exposure (OR 1.6); HLA-DR6 was less common among the cases (OR 0.4), an association also stronger in the low-exposure group (OR 0.1 versus 0.5). These results provide evidence that HLA phenotype is a significant determinant of sensitization to complex platinum salts and for the first time show that the strength of this association varies with intensity of exposure to the sensitizing agent. They imply that as exposure-control measures are taken to prevent occupational sensitization and, by analogy, sensitization to allergens outside the workplace, disease incidence will increasingly be determined by genetic susceptibility.

Allergy to complex salts of platinum in refinery workers: prospective evaluations of IgE and Phadiatop status.

BACKGROUND: Experience has shown some variation in the associations between IgE, atopy, and sensitization to platinum salts. Clarification of these associations, and the value of the parameters in predicting and diagnosing sensitization of workers at risk, required prospective investigation. OBJECTIVES: Evaluation of total IgE and Phadiatop(R) status to establish baseline values, and changes during employment, predictive or associated with subsequent platinum salt sensitization. METHODS: A 24-month prospective study, in a South African primary platinum refinery, of a cohort of 78 healthy recruits without evidence of atopy (tested negative to skin prick test with common allergens). Subsequently they were categorized as 22 sensitized (positive skin prick test to platinum salts), 46 not sensitized (negative skin prick test and symptom free), and 10 symptomatic subjects not included in either category. RESULTS: (1) Pre-employment: four (18%) of the subsequently sensitized subjects and eight (17%) not sensitized were Phadiatop(R) positive. Levels of total IgE > 100 kU/L, present in 16 subjects were associated with positive Phadiatop(R) status and race. (2) During employment: Phadiatop(R) status converted from negative to positive in more sensitized (12/18) than unsensitized (6/38) subjects (P

Health effects of passive smoking in adolescent children.

OBJECTIVE AND DESIGN: To study the effects of passive smoking on health in adolescent schoolchildren by questionnaire, spirometry and laboratory investigations. SETTING: Two schools in the Vanderbijlpark area. PARTICIPANTS: Seven hundred and twenty-six high-school children of average age 16 years. OUTCOME MEASURES: Lung function, serological abnormality or historical (i.e. questionnaire) evidence of ill health. RESULTS: The prevalence of respiratory illness before and after 2 years, respiratory symptoms, earache over the past year, low birth weight and learning difficulties were found to be significantly increased in the children exposed to parenteral smoke in the home, especially those exposed to maternal smoking. Spirometric and laboratory parameters, however, were not affected by passive smoking.

Platinum salt sensitivity in refinery workers: incidence and effects of smoking and exposure.

OBJECTIVE: To measure the incidence of platinum salt sensitivity (PSS) in refinery workers and examine the influence of cigarette smoking and exposure to platinum salts on sensitisation. DESIGN: A prospective cohort study with examination of workers at quarterly intervals for 18 months, and again at 24 months. SETTING: A South African primary platinum refinery. SUBJECTS: 78 new recruits, selected by the refinery's usual procedure, without apparent atopy and in good respiratory health. RESULTS: After 24 months 32 (41%) subjects had been diagnosed PSS and were subsequently medically separated. Twenty two (28%) cases were confirmed by positive skin prick test to platinum salts, 10 (13%) cases were symptomatic but skin prick negative. Incidence of cases per 100 person-months was 1.9 skin prick positive and 0.8 negative. Risk of sensitisation was about eight times greater for smokers than non-smokers, and six times greater for high exposure than low exposure. CONCLUSION: Smoking and intensity of exposure were definitely associated with development of PSS. Positive responses to platinum salt skin prick test had a 100% positive predictive value for symptoms and signs of PSS if exposure continued.

Exercise, regardless of induced bronchoconstriction or inspired air conditions, does not alter airway reactivity.

The effects of exercise on asthmatic airway caliber are well recognized. Only a few studies, however, evaluated the effects of prior exercise on asthmatic airway reactivity. Eight asthmatic children (ages 10 to 16 years; mean, 12) performed histamine inhalation tests on three occasions assigned in random order: (1) control; (2) 40 to 60 min after exercise (6 min ergometer cycling) done while breathing cold dry (CD) air (temperature = -13 degrees C, relative humidity = 0 percent); and (3) 40 to 60 min after exercise done while breathing warm humid (WH) air (temperature = 33 degrees C, relative humidity = 100 percent). While there was a marked exercise-induced bronchoconstriction (EIB) in the CD test with a postexercise fall in FEV1 of 39.2 +/- 8 percent (mean +/- SEM), there was no EIB in the WH test (4.6 +/- 2 percent). There was no difference, however, in the geometric mean histamine concentration required to produce a 20 percent fall in FEV1 (PC20) among the CD, WH, and control tests (0.52 mg/ml, 0.60 mg/ml, and 0.55 mg/ml, respectively). Airway reactivity in asthmatic children is not influenced by a prior exercise challenge, independent of the conditions of the inspired air during the exercise. Moreover, exercise per se, regardless of development of EIB, does not change the reactivity.

Thalassemia: lung function with reference to iron studies and reactive oxidant status.

Pulmonary function tests were performed in 15 thalassemic patients (age 5 years 8 months to 18 years 6 months), receiving both regular transfusions and desferrioxamine, to determine the presence and nature of any abnormalities in lung function. Reactive oxidant production from neutrophils was measured simultaneously to ascertain if a causal relationship existed between free radical production and tissue damage in the lungs. Mean total lung capacity, mean residual volume, and mean forced vital capacity were significantly reduced, indicating a restrictive pattern of lung function abnormality. In addition, the carbon monoxide diffusion was low, and hypoxemia was present in 6 of 13 patients tested. These pulmonary function abnormalities did not correlate with age, cumulative volume of transfusion, or serum ferritin levels. In addition, neutrophil reactive oxidant status did not correlate with these or with pulmonary function parameters. These results indicate that neutrophil-derived oxygen free radicals do not appear to be a major cause of lung function abnormalities in thalassemics.

The Johannesburg cardiac rehabilitation programme.

Cardiac rehabilitation has become a generally accepted mode of treatment for patients suffering from coronary artery disease. The Johannesburg cardiac rehabilitation programme was started in 1982 and has rapidly grown to become one of the largest programmes in southern Africa. This paper describes the 387 patients admitted to the unit between June 1986 and July 1988 and evaluates the effects of a combined exercise training and lifestyle modification programme. The mean age on admission was 55 years for males and 58 years for females. Most patients were from social classes I and II. Myocardial infarction, coronary artery bypass graft and a combination of both were the most common reasons for admission (35.4%, 23% and 21.2% respectively). On admission 72.9% of patients were smokers, 26.3% had hypertension and 34.3% had hypercholesterolaemia. A 50% drop-out rate within 12 months of starting the programme was noted. An increase in peak oxygen uptake, weight and skinfold thickness reduction, and improvement in the lipogram were seen after 6 months in patients who complied well with the programme. Cardiac rehabilitation is a secondary preventive strategy that can complement traditional medical and surgical therapies.

Exercise-related cardiac arrest in cardiac rehabilitation. The Johannesburg experience.

Prescribed physical activity plays a major role in the rehabilitation of patients with coronary artery disease, and as with any other form of treatment its benefits must be weighed against its possible risks. This study attempted to establish the safety of cardiac rehabilitation as a medical intervention at the Johannesburg Cardiac Rehabilitation Centre from its inception in September 1982 to July 1988, and analyses the medical status of patients who suffered a cardiac arrest (CA) in order to determine possible factors predictive of sudden death. Between September 1982 and July 1988, 1,574 patients were admitted to the unit; 480,000 man-hours of exercises were accumulated with 4 episodes of CA, giving an incidence of CA of 1/120,000 patient-hours. Three of the 4 episodes were fatal, giving an incidence of fatal CA of 1/160,000 patient-hours. This incidence is acceptably low and comparable with other cardiac rehabilitation programmes, making exercise as prescribed at the Johannesburg Cardiac Rehabilitation Centre a safe form of medical intervention. Patients at risk of CA during exercise were essentially not identifiable, since they did not come from a group currently recognised as at particularly high risk. A combination of inferior infarction with occluded dominant right coronary artery, good collateralisation and asymptomatic ischaemia was present in all CA patients. The likelihood of these pathological features being predictors of exercise-related sudden death requires further investigation.

Growth hormone response to exercise in asthmatic and normal children.

Maximal growth hormone (GH) increments following exercise were compared in asthmatic (n = 14) and normal (n = 8) children. Exercise, which consisted of 6 min ergometer cycling while breathing cold dry (CD) air, induced asthma in all asthmatic patients but not in normal subjects. Baseline plasma GH levels were similar in both groups. Following exercise, however, asthmatic patients had significantly higher mean GH increments than normal subjects (14.8 vs 4.9 ng/ml, P less than 0.025). To evaluate the possible role of bronchoconstriction in the GH response all subjects exercised again, this time while breathing warm humid (WH) air. Despite the absence of exercise-induced asthma (EIA) while breathing WH air, asthmatic patients still had significantly higher mean GH increments than normal subjects (9.2 vs 2.3 ng/ml, P less than 0.05). We conclude that some asthmatic children show excessive GH secretion after exercise regardless of inspired air conditions or the development of EIA.

Elastase binding capacity of alpha 2-macroglobulin in plasma of patients with asthma or chronic obstructive pulmonary disease, without alpha 1-protease inhibitor deficiency.

The amidolytic activity of alpha 2-macroglobulin complexed with porcine pancreatic elastase (EC 3.4.21.11) was assayed using succinyl-trialanyl-p-nitroanilide. The levels of activity were compared in chronic obstructive pulmonary disease patients, asthma patients, and in healthy subjects with no record of lung disease. Levels of alpha 1-protease inhibitor were also determined and only those cases within the normal range for alpha 1-protease inhibitor were selected. Both the asthma cases and those with chronic obstructive pulmonary disease had levels of elastase-binding capacity related to alpha 2-macroglobulin which were significantly higher than the control groups.

Respiratory heat loss in exercise-induced asthma. Measurement and clinical application.

The theoretical considerations of conditioning inspired air and the application of the respiratory heat loss (RHL) formula are discussed. An on-line method for measuring RHL is described together with the apparatus for generating frigid dry and warm humid air. Exercise-induced asthma (EIA) was studied using these methods. Thirteen asthmatic and 6 normal children and adolescents participated in the study. Each subject undertook two submaximal exercise tests consisting of 6 minutes' ergometric cycling against a fixed load. One test was done while breathing cold dry air (mean temperature -22 degrees C and 0% relative humidity) and the other while breathing warm humid air (mean temperature 36 degrees C and 100% relative humidity). All the other exercise parameters (e.g. heart rate, minute ventilation, oxygen uptake) were carefully matched between the two tests. In the cold dry air tests with a mean RHL of 1,43 kcal/min, all asthmatic subjects developed EIA with a mean fall in forced expiratory volume in the 1st second (FEV1) of 48% from baseline. In the warm humid air tests with negligible RHL (0,02 kcal/min) none of the asthmatics developed EIA (mean fall in FEV1 5%). The difference between the two tests was highly significant (P less than 0,001). Neither air condition caused bronchospasm in the normal subjects. A dose-response relationship was obtained between the degree of RHL and corresponding fall in FEV1.

Reflex heart rate control in asthma. Evidence of parasympathetic overactivity.

The bronchial hyperreactivity characteristic of asthma may be related to enhanced parasympathetic nervous activity. We postulated that an abnormality in the autonomic control of airway caliber might be reflected by a parallel change in the reflex control of heart rate. We examined the heart-rate variations induced by deep breathing (respiratory sinus arrhythmia), the Valsalva maneuver, and standing up from the recumbent position in asthmatic subjects and nonasthmatic control subjects. The asthmatic patients had evidence of enhanced parasympathetic neural drive to the sinoatrial node, as manifested by a significantly greater magnitude of respiratory sinus arrhythmia, than the controls (p less than 0.0005). We were unable to induce a similar change in normal subjects by resistance breathing. A statistical analysis suggested the presence of a relationship between the magnitude of respiratory sinus arrhythmia and the degree of bronchial hyperreactivity in a group of asthmatic patients. Our results support the hypothesis that enhanced parasympathetic activity is an important factor in the pathogenesis of bronchial asthma.

A comparative assessment of carbuterol, fenoterol and hexoprenaline in allergic asthma.

Carbuterol tablets (2,0 mg) were compared with the tablets of fenoterol (2,5 mg) and hexoprenaline (1 mg). The three drugs were shown to be equally effective for a period of 4 hours, but carbuterol and fenoterol exerted a statistically significant bronchodilating action for 7 and 8 hours respectively, while the action of hexoprenaline lasted for 4 hours in the majority of patients. The aerosols of carbuterol (200 mg) and fenoterol (400 mg) appeared to be similar in inhibiting exercise-induced asthma, whereas hexoprenaline (200 mg) did not appear to be as effective.