Case-control study of severe life threatening asthma (SLTA) in a developing community.

BACKGROUND: Distinct risk factors for asthma death have not been identified in developing communities. This study was conducted to distinguish risk factors for severe life threatening asthma (SLTA), a proxy for asthma death, in a developing country. METHODS: A case-control study was performed at a University Hospital serving developing communities in the Western Cape Province, South Africa, over the period October 1997 to April 2000. Thirty consecutive patients with SLTA admitted to the intensive care unit (ICU) were compared with 60 chronic asthmatic patients, without a history of SLTA, who had attended the hospital outpatient respiratory clinic over the same period. RESULTS: The risk of SLTA in comparison with controls increased with female sex (odds ratio (OR) 3.3, 95% CI 1.2 to 9.6, p = 0.02), rural residence (OR 8.1, 95% CI 2.6 to 25.3, p = 0.0005), and absence of a formal income (OR 5.7, 95% CI 2 to 16.6, p = 0.002). Cases were more likely to have had more than one hospital admission in the previous year (OR 8, 95% CI 2.5 to 25.2, p = 0.0009) and more than one emergency room visit in the previous year (OR 4.4, 95% CI 1.19 to 16.4, p = 0.04). Patients with SLTA were less likely to use inhaled corticosteroids (OR 5.6, 95% CI 1.9 to 16.5, p = 0.003) and more likely to use inhaled fenoterol (OR 6, 95% CI 2.2 to 16.2, p = 0.0004). Patients with SLTA also had lower mean (SE) forced expiratory volume in 1 second (FEV(1)) measurements (66.9 (9.5)% predicted v 82.5 (4.0)% predicted; p = 0.03) and lower FEV1/FVC ratios (60.7 (4.1)% predicted v 69.6 (1.9)% predicted; p = 0.05) documented before the episode of SLTA. CONCLUSIONS: Risk factors for SLTA that are mainly analogous to those distinguished in other environments have been identified in a geographical area characterised by a third world socioeconomic context. Rural residence and poverty may increase the risk of SLTA.

Guideline for office spirometry in adults, 2004.

OBJECTIVE: To provide clinical guidelines for office spirometry in South Africa. OPTIONS: More stringent guidelines are required for diagnostic laboratories and research. OUTCOMES: To minimise variations in standard practice and improve the quality and usefulness of spirometry in the clinical setting. EVIDENCE: Recommendations are based on key international publications as well as research publications regarding reference values for South Africans. BENEFITS, HARM AND COSTS: The medical, social and economic benefits and costs of standardisation of office spirometry in South Africa were considered in the recommendations. VALIDATION: The document has been reviewed and endorsed by the South African Thoracic Society. CONCLUSIONS: The indications for spirometry must be specific and clear. Spirometry equipment must meet internationally accepted performance standards and carry proof of validation. Equipment must be regularly calibrated and maintained. Individuals performing spirometry must be adequately trained and demonstrate a high level of competence. Subject preparation, testing and quality control of results must be carried out according to published guidelines. Finally, test results must be interpreted according to current diagnostic guidelines, taking into account the purpose of the test, appropriateness of reference values and the clinical evaluation.

Reduced activation of peripheral blood neutrophils after late-phase asthmatic responses but not in mild stable asthma.

BACKGROUND: Asthma is a process of chronic allergic inflammation that may be worsened by the activation of neutrophils during acute exacerbations. OBJECTIVE: We investigated our hypothesis that changes in cellular activation may be detectable in peripheral blood (PB) during late-phase asthma and during clinical exacerbations. METHODS: Twenty-one stable asthmatics (9 on treatment with beta2-agonists only, 12 using inhaled corticosteroids) and 10 nonasthmatic volunteers were first compared using flow cytometry to measure beta2-integrin (CD11b/CD18) expression. Production of reactive oxygen species (ROS) was evaluated employing chemiluminescence. Next, 8 mild asthmatics were assessed using similar methods before and after allergen-induced late asthmatic reactions (LARs). Finally, 4 asthmatic subjects were evaluated over 3 months, and symptoms, peak expiratory flow (PEF) and ROS production were measured. Episodes of respiratory morbidity (exacerbations) were identified and their association with ROS production was examined. RESULTS: No differences were detected in adhesion molecule expression and ROS production comparing the normal and asthmatic groups. However, after development of the LAR, significant reductions in CD11b neutrophil expression (mean fluorescence intensity; MFI) were observed [before: 994 +/- 102 MFI (mean +/- SEM) versus after: 424 +/- 81 MFI; p < 0.01]. Furthermore, strong associations were found between decreases in CD11b and the severity of the LAR (r = 0.9; p < 0.02). In the clinical study, ROS production was significantly lower during exacerbations (median 43%; p < 0.05). Again, this measurement was significantly associated with reductions in PEF (r = 0.5, p < 0.03). CONCLUSIONS: In patients with mild stable asthma, no differences in the activation of circulating neutrophils were detectable compared to nonasthmatic individuals. During episodes of asthmatic airway obstruction, in the laboratory and in clinical disease, neutrophil activation decreased in PB, conceivably because activated cells may be preferentially sequestered in the lung.

Occupational respiratory diseases in South Africa--results from SORDSA, 1997-1999.

OBJECTIVES: To describe the nature and extent of work-related respiratory diseases reported to the national Surveillance of Work-related and Occupational Respiratory Diseases in South Africa (SORDSA) reporting scheme. The causative agents and industrial categories in which they occurred are also characterised. DESIGN: Voluntary monthly reporting of newly diagnosed cases by pulmonologists, occupational medicine practitioners and occupational health nurses. SETTING: Medical and occupational health referral centres in the nine provinces of South Africa. SUBJECTS: Cases were workers from non-mining industries or ex-miners, suffering from a newly diagnosed occupational respiratory disease, reported to SORDSA between October 1996 and December 1999. OUTCOME MEASURES: Frequencies of reported occupational respiratory disease by year, reporting source, province and sex. Frequencies of short- and long-latency diseases by industry and causative agent. RESULTS: There was incomplete reporting coverage of the nine provinces in the first 3 years. Reporting was most comprehensive from Gauteng, KwaZulu-Natal and the Western Cape. Diseases with long latency periods made up 76.2% of the cases. Pneumoconiosis, even in non-mining industries, was the most frequently reported disease, followed by inhalation accidents. Occupational asthma was the fourth most reported disease. Apart from the prominence of pneumoconiosis, the results obtained by SORDSA are similar to those from a British occupational lung disease surveillance scheme. This study showed that newly diagnosed cases of occupational lung disease occurred in many industries and were caused by a variety of agents. CONCLUSION: SORDSA has contributed insight into the nature, extent and distribution of occupational respiratory diseases in South Africa. It has also highlighted important causes of occupational respiratory diseases in South Africa, as well as hazardous industries. The data indicate that South Africa has a widespread occupational lung disease problem, and provide a platform for targeted prevention strategies.

Peak expiratory flow changes during experimental rhinovirus infection.

Rhinovirus (RV) colds are associated with asthma exacerbations and experimental infections are commonly used to investigate the mechanisms involved. However, a temporal association between experimental RV infections and falls in peak expiratory flow (PEF) have not been demonstrated. PEF was measured in 22 volunteers (11 normal, five atopic, six atopic asthmatic) who developed RV serotype 16 colds after inoculation. PEF was measured twice daily for 2 weeks prior and 6 weeks after RV infection and episodes of respiratory morbidity based on changes in PEF were defined using validated criteria. Six significant reductions in PEF were temporally related to the RV infections (in two (18%) normal, one (20%) atopic, three (50%) atopic asthmatic subjects, p=0.1) and occurred 4-9 days (median 6) after inoculation. Mean+/-SEM PEF at day 6 was 87.8+/-1.8% of the predicted value in the six subjects with reductions versus 99.4+/-1.4% pred in those without (p=0.01). Symptom scores were significantly different at day 6 in the two groups (10.6+/-1.9 versus 6.8+/-1.0, p=0.03), but no differences were noted in the viral culture scores and changes in nasal albumin. In subjects with significant PEF reduction, the decrease in the provocative concentration causing a 20% fall in the forced expiratory volume in one second (FEV1) (PC20) was 1.7+/-1.3 mg x mL(-1) versus 1.2+/-1.1 mg x mL(-1) in the negative group (p=0.06). The degree of seroconversion to RV was significantly higher in the group with reduced PEF (median change dilutions 8 versus 4, p=0.02). The results of the present study suggest that rhinovirus-associated, respiratory morbidity occurs during experimental infection in some but not all normal and asthmatic subjects and also that experimental colds are a valid model for the study of rhinovirus-associated airway symptoms and asthma exacerbations.

Treatment of progressive pulmonary sarcoidosis with cyclosporin A. A randomized controlled trial.

Conventional treatment of sarcoidosis is often only partially effective. We examined the effect of cyclosporin A (CsA) combined with prednisone for the treatment of sarcoidosis. Thirty-seven patients with biopsy-proven sarcoidosis were treated with either prednisone 20 mg/d in a prospectively tapered regimen (P) or with combination therapy consisting of prednisone 20 mg/d in a prospectively tapered regimen and cyclosporin A, 5 to 7 mg/kg/d (P-CsA) for up to 18 mo in an open-label randomized controlled trial. Evaluation was done at baseline and at 3, 9, and 18 mo of the degree of dyspnea, pulmonary function, chest radiographs, bronchoalveolar lavage (BAL), and adverse events. Criteria for a good therapeutic response, improvement, treatment failure, and relapse were defined. Thirty-seven patients were treated for at least 9 mo and 18 mo. Six patients in remission were included in an intention-to-treat-analysis at 18 mo. The groups did not differ significantly with respect to therapeutic response from baseline. A significant (p < 0.05) improvement was observed in dyspnea until 9 mo (P) and 18 mo (P-CsA), and in lung function until 9 mo (P) and 3 mo (P-CsA). BAL results showed a significant decrease in lymphocyte counts at 9 mo for the P group only (p < 0.05). More side effects were observed in the P-CsA group than in the P group, including elevation of the mean serum creatinine concentration at 3 and 9 mo (p < 0.05), and a doubling of the number of infections in this group. Relapse after an initially good therapeutic response occurred in two of nine patients in the P group and five of seven patients in the P-CsA group (p < 0.07). Although CsA may have theoretical benefits in the treatment of sarcoidosis, our results do not support its use in this disease.

Corticosteroids in the treatment of tuberculous pleurisy. A double-blind, placebo-controlled, randomized study.

Although several studies on tuberculous (TB) pleurisy suggest that the addition of corticosteroids to anti-TB therapy may have beneficial effects, these agents are not used routinely. To assess the effects of short-term oral prednisone therapy in TB pleurisy, 74 patients were randomly assigned in a double-blind fashion to treatment with either placebo or prednisone at a dose of 0.75 mg/kg/d for up to 4 weeks with gradual reduction over an additional 2 weeks. All subjects received a standard 3-drug anti-TB chemotherapy regimen for 6 months. TB pleurisy was diagnosed by histologic study and/or culture of pleural biopsy specimens obtained at thoracoscopy. Complete drainage of the effusion was performed simultaneously. Outcome measures were assessed periodically for 24 weeks, including indexes of morbidity and pleural thickening. After randomization, four patients were excluded from the final analysis. Of the 70 patients analyzed, 34 received prednisone and 36 received placebo. Demographic and clinical characteristics of the treatment groups were comparable at the time of hospital admission. Although a statistically significant improvement in symptoms occurred earlier in the prednisone group (8 weeks) than in the placebo group (12 weeks), between-group comparison showed no significant differences at any of the follow-up evaluations. The proportion of subjects in the prednisone group (53.1%) with residual pleural thickening at 6 months did not differ significantly from that of the placebo group (60%). Pleural effusions did not recur in any of the patients. Initial complete drainage of the effusion was associated with greater symptomatic improvement than any subsequent therapy. We conclude that standard anti-TB therapy and early complete drainage is adequate for the treatment of TB pleurisy. The addition of short-term oral prednisone therapy neither results in clinically relevant earlier symptom relief nor confers a beneficial effect on residual pleural thickening.