Guideline for the management of acute asthma in adults: 2013 update.

Acute asthma attacks (asthma exacerbations) are increasing episodes of shortness of breath, cough, wheezing or chest tightness associated with a decrease in airflow that can be quantified and monitored by measurement of lung function (peak expiratory flow (PEF) or forced expiratory volume in the 1st second) and requiring emergency room treatment or admission to hospital for acute asthma and/or systemic glucocorticosteroids for management. The goals of treatment are to relieve hypoxaemia and airflow obstruction as quickly as possible, restore lung function, and provide a suitable plan to avoid relapse. Severe exacerbations are potentially life-threatening and their treatment requires baseline assessment of severity, close monitoring, and frequent reassessment using objective measures of lung function (PEF) and oxygen saturation. Patients at high risk of asthma-related death require particular attention. First-line therapy consists of oxygen supplementation, repeated administration of inhaled short-acting bronchodilators (beta-2-agonists and ipratropium bromide), and early systemic glucocorticosteroids. Intravenous magnesium sulphate and aminophylline are second- and third-line treatment strategies, respectively, for poorly responding patients. Intensive care is indicated for severe asthma that is not responsive to first-line treatment. Antibiotics are only indicated when there are definite features of bacterial infection. Factors that precipitated the acute asthma episode should be identified and preventive measures implemented. Acute asthma is preventable with optimal control of chronic asthma.

Guideline for the management of chronic obstructive pulmonary disease--2011 update.

OBJECTIVE: To revise the South African Guideline for the Management of Chronic Obstructive Pulmonary Disease (COPD) based on emerging research that has informed updated recommendations. KEY POINTS: (1) Smoking is the major cause of COPD, but exposure to biomass fuels and tuberculosis are important additional factors. (2) Spirometry is essential for the diagnosis and staging of COPD. (3) COPD is either undiagnosed or diagnosed too late, so limiting the benefit of therapeutic interventions; performing spirometry in at-risk individuals will help to establish an early diagnosis. (4) Oral corticosteroids are no longer recommended for maintenance treatment of COPD. (5) A therapeutic trial of oral corticosteroids to distinguish corticosteroid responders from non-responders is no longer recommended. (6) Primary and secondary prevention are the most cost-effective strategies in COPD. Smoking cessation as well as avoidance of other forms of pollution can prevent disease in susceptible individuals and ameliorate progression. Bronchodilators are the mainstay of pharmacotherapy, relieving dyspnoea and improving quality of life. (7) Inhaled corticosteroids are recommended in patients with frequent exacerbations and have a synergistic effect with bronchodilators in improving lung function, quality of life and exacerbation frequency. (8) Acute exacerbations of COPD significantly affect morbidity, health care units and mortality. (9) Antibiotics are only indicated for purulent exacerbations of chronic bronchitis. (10) COPD patients should be encouraged to engage in an active lifestyle and participate in rehabilitation programmes. OPTIONS: Treatment recommendations are based on the following: annual updates of the Global Obstructive Lung Disease (GOLD), initiative, that provide an evidence-based comprehensive review of management; independent evaluation of the level of evidence in support of some of the new treatment trends; and consideration of factors that influence COPD management in South Africa, including lung co-morbidity and drug availability and cost. OUTCOME: Holistic management utilising pharmacological and nonpharmacological options are put in perspective. EVIDENCE: Working groups of clinicians and clinical researchers following detailed literature review, particularly of studies performed in South Africa, and the GOLD guidelines. BENEFITS, HARMS AND COSTS. The guideline pays particular attention to cost-effectiveness in South Africa, and promotes the initial use of less costly options. It promotes smoking cessation and selection of treatment based on objective evidence of benefit. It also rejects a nihilistic or punitive approach, even in those who are unable to break the smoking addiction. RECOMMENDATIONS: These include primary and secondary prevention; early diagnosis, staging of severity, use of bronchodilators and other forms of treatment, rehabilitation, and treatment of complications. Advice is provided on the management of acute exacerbations and the approach to air travel, prescribing long-term oxygen and lung surgery including lung volume reduction surgery. VALIDATION: The COPD Working Group comprised experienced pulmonologists representing all university departments in South Africa and some from private practice, and general practitioners. Most contributed to the development of the previous version of the South African guideline. GUIDELINE SPONSOR: The meeting of the Working Group of the South African Thoracic Society was sponsored by an unrestricted educational grant from Boehringer Ingelheim and Glaxo-Smith-Kline.

Efficacy of azathioprine as second-line treatment in pulmonary sarcoidosis.

BACKGROUND AND AIM OF WORK: Immunosuppressives such as azathioprine are occasionally used in sarcoidosis where corticosteroids cannot be used because of poor response, contraindications or unacceptable side effects. The aim of this study was to assess the efficacy and safety of azathioprine in the treatment of pulmonary sarcoidosis. METHODS: A retrospective study was performed on patients in the Respiratory Clinic of the university teaching hospital on all biopsy-proven sarcoid treated with azathioprine between 1969 and 1993 (n = 10). All had previously shown only partial (n = 6) or no (n = 4) response to high dose oral corticosteroids. Azathioprine in a dose of 100-150 mg was administered daily, while continuing a small dose of oral corticosteroid. Patients underwent regular clinical evaluation, pulmonary function testing and chest radiography. RESULTS: In one patient the course was too brief to evaluate (26 days). Two patients had significant and sustained improvement in lung function (vital capacity increasing from 72% to 89% and from 49% to 79% of predicted respectively, and transfer factor from 78% to 114% and from 27% to 49% of predicted respectively), and chest radiograph cleared. Two patients had short-lived improvement and steroid-sparing effect. In the remainder (n = 5), no benefit was observed. No patient responded to azathioprine who had failed to respond to high dose corticosteroids. There was no significant toxicity. CONCLUSIONS: Azathioprine may provide a safe alternative to corticosteroids when a steroid-sparing effect is required, but it is unlikely to be effective in patients who fail to respond to high dose corticosteroids and/or have radiographic evidence of significant fibrosis.

Lymphocyte and lymphocyte subset numbers in blood and in bronchoalveolar lavage and pleural fluid in various forms of human pulmonary tuberculosis at presentation and during recovery.

BACKGROUND: Lymphocytes have a central role in human defences against mycobacteria. A study was designed to assess the relation between lymphocyte responses and clinical pattern of disease, nutrition and recovery during treatment in patients with tuberculosis. METHODS: Lymphocyte numbers and subsets (on the basis of CD3, CD4, and CD8 monoclonal antibodies) were measured in peripheral blood and, where appropriate, bronchoalveolar lavage or pleural fluid of patients with different forms of pulmonary tuberculosis. Eleven had localised pulmonary tuberculosis, 18 miliary tuberculosis and seven a tuberculous pleural effusion. RESULTS: CD4 lymphocytes were found in greatly increased numbers in pleural fluid and were relatively depleted in the blood. Lymphocyte numbers in bronchoalveolar lavage fluid varied widely in localised pulmonary and miliary tuberculosis but were highest in lavage fluid from patients with miliary tuberculosis. This was due to an increase in CD8 lymphocytes, which were also increased in the blood. Lymphocyte numbers bore no relation to nutrition, symptom duration, or radiographic profusion scores. In miliary tuberculosis the time taken for the chest radiograph to clear (mean (SD) 17.6 (7.8) weeks) correlated with lymphocyte numbers in lavage fluid, especially CD8 cells (r = 0.74), but not with the patients' age or nutrition. After 8 weeks' treatment, total and CD4 lymphocyte numbers in lavage fluid showed a substantial increase. CONCLUSION: The association of CD8 cells with delayed recovery is compatible with suppression of the antimycobacterial action of macrophages. The switch to predominance of CD4 cells in lavage fluid during successful treatment supports the view that they may have a role in eliminating mycobacteria.

Relation between immunocytological features of bronchoalveolar lavage fluid and clinical indices in sarcoidosis.

This study was designed to determine whether cell populations in bronchoalveolar lavage fluid represent a reflection of disease activity in sarcoidosis. Bronchoalveolar lavage fluid cells were obtained from 22 patients with sarcoidosis and from 10 normal control subjects and investigated by immunocytological methods. A panel of monoclonal antibodies was used to determine the relative proportions of phenotypically distinct subsets of macrophages and lymphocytes in the patients with sarcoidosis and to correlate them with clinical indices, such as disease duration, serum angiotensin converting enzyme, the chest radiograph, and results of pulmonary function tests. Patients with sarcoidosis had a higher percentage than the normal subjects of macrophage like cells expressing RFD1 (a class II associated antigen preferentially expressed by dendritic cells), an epithelioid cell antigen (RFD9), and a circulating monocyte antigen (UCHMI). The increase in RFD1+ cells appeared to be due to detection of antigen by this antibody on cells that were also expressing phenotypic markers of classical tissue macrophages (RFD7). The lymphocytes in lavage fluid from patients with sarcoidosis were characterised by increased expression of activation markers, such as interleukin-2 receptors (anti-Tac+), HLA-DR (RFDR+), and "blast" forms (expressing above normal concentrations of CD7 antigen). This was associated with increased proportions of the CD4+ (helper-inducer) T cell subset. Patients with sarcoidosis whose clinical indices suggested activity showed an increased number of macrophages coexpressing RFD1 and RFD7 antigens, of macrophages expressing UCHM1 and lymphocytes expressing activation markers. The expression of these markers was also increased on lavage cells from patients with radiographic evidence of widespread disease (chest radiographic stage II and III), but there was no relation with disease duration, pulmonary function, or serum angiotensin converting enzyme activity. Immunocytological analysis of lavage cells offers a probe for studying the pathogenesis of sarcoidosis and may be of value in monitoring disease activity.

Deaths from asthma in Cape Town, 1980-1982.

During the 3-year period 1980 - 1982, 351 patients were certified as having died from asthma in the Cape Town City Council area. An additional cause of death was listed in 120 of these. Of the 231 patients certified as having died from asthma only, 179 (77.5%) were over 40 years of age. The circumstances surrounding death in 28 of the remaining 52 patients under the age of 40 years are described. Inadequate assessment and therapy were major contributing factors. The incidence of death from asthma in Cape Town is three times greater than in the UK. It is probable that this also applies in other parts of the RSA. There is a need for improved education of health care professionals and patients about this common disease and for better community facilities for its treatment.

Serum angiotensin converting enzyme in sarcoidosis: sensitivity and specificity in diagnosis: correlations with disease activity, duration, extra-thoracic involvement, radiographic type and therapy.

Serum angiotensin converting enzyme (SACE), despite certain limitations, has been found to be a useful adjunct to the diagnosis, assessment of disease activity, and management of sarcoidosis. The spectrofluorimetric assay was used to measure SACE in 50 normal controls, 76 patients with tuberculosis (42 pulmonary, 16 lymphatic and 18 military cases), 20 patients with cryptogenic fibrosing alveolitis, 50 patients with silicosis, three patients with extrinsic allergic alveolitis, 10 patients with Crohn's disease, two patients with Gaucher's disease, and 128 patients with sarcoidosis on 303 occasions (144 during periods judged as clinically active and 189 inactive). Our results show a normal range (mean +/- 2SD) of 19-54 nmol/ml/min. The false positive rate is 2 per cent in normal controls, 9.2 per cent in tuberculosis (38.9 per cent in military but 0 per cent in the other forms), 48 per cent in silicosis, 100 per cent in Gaucher's disease, and 0 per cent in the other diseases. The sensitivity, specificity, positive and negative predictive values were 58.1, 83.8, 83.8 and 58.1 per cent respectively. The sensitivity rose to 85.9 per cent if only those samples taken from patients in whom sarcoidosis was suspected on initial presentation were included, and 92.1 per cent if only those with clinically active sarcoidosis were included. The sensitivity of SACE as a diagnostic test in sarcoidosis is thus influenced by the relative frequency of active and inactive sarcoidosis. The specificity is influenced by the prevalence of military tuberculosis and silicosis, but is uninfluenced by other common varieties of interstitial lung disease such as cryptogenic fibrosing alveolitis and extrinsic allergic alveolitis, or by other non-pulmonary granulomatous disease. There was no correlation of the SACE level with age, sex, population group, associated other illness or duration of sarcoidosis. Statistically, SACE levels were significantly higher in patients with Types II and III chest radiographs as compared to Type I and 0, and also in those with additional clinically evident extra-thoracic disease e.g. in lymph node, eye and especially multiple systems. SACE also reflected clinical activity with levels being statistically significantly greater in those patients assessed as having active disease, although 7.9 per cent of these had normal levels. Our observations indicate that SACE levels correlate well with disease activity longitudinally, both in relation to spontaneous remission and steroid therapy, and are thus helpful in patient management.

Early gestational choriocarcinoma. A case report.

A focus of choriocarcinoma lying in the intervillous space was an unexpected finding in a 20-week placenta. The mother, after a short admission, died from choriocarcinomatous pulmonary emboli and acute cor pulmonale. A diagnosis of early choriocarcinoma associated with normal villi is therefore tenable.