Ethnic differences in the occurrence of the M1(ala213) haplotype of alpha-1-antitrypsin in asthmatic and non-asthmatic black and white South Africans.

An ethnic study of 175 individuals, comprising 65 black and 110 white South Africans, has shown a conclusive difference in the frequency of the M1(ala213) haplotype of alpha 1-antitrypsin (P < 0.00001). The M1(ala213) haplotype occurred more frequently in the black group. In the latter group, the frequency of the M1(ala213) haplotype was the same in both controls (0.55) and asthmatics (0.53). However, there was a significant difference in the frequencies (0.19 and 0.36) for the respective white groups (P < 0.01), the frequency of the M1(ala213) haplotype being much higher in the asthmatics. Apart from the above differences, there was also a difference in the elastase-inhibitory capacities of the homozygote phenotypes M1(val213) vs M1(ala213) (P < 0.0001), this capacity being lower in the latter phenotype. We conclude that the occurrence of the M1(ala213) allele of alpha 1-antitrypsin differs in various ethnic groups and may play a role in asthma.

A study of acute community-acquired pneumonia, including details of cardiac changes.

We prospectively studied 102 patients, aged 15-50 years, with acute community-acquired lobar pneumonia without underlying cardiorespiratory illness, admitted to Baragwanath Hospital May 1990-April 1991. Demographic, clinical, microbiological and laboratory data and negative prognostic features of these patients are described. In particular, we documented electrocardiographic changes and studied their possible relevance in patients with pneumonia. Electrocardiographic changes occurred in 32 patients (31%). The commonest changes were clockwise rotation (16%), followed by P. pulmonale (9.8%) and S1 Q3 T3 pattern (7.8%) Other changes included right axis deviation (n = 6), right bundle branch block (n = 3), ventricular extrasystoles (n = 2), atrial fibrillation (n = 1) and nodal rhythm (n = 1). These changes returned to normal in survivors after a mean of 2 days. The S1 Q3 T3 pattern was associated with cardiac enzyme leak (CK-MB fraction), hypoxia and a high Simplified Acute Physiology Score (SAPS). In addition, P. pulmonale, right axis deviation and clockwise rotation correlated with hypoxia and a high SAPS score. Clockwise rotation also correlated with serum (including cardiac fraction) enzymes leak (LDH and CK-MB fraction), and pulmonary artery pressure. The overall mortality rate was 10.8%, with no association between electrocardiographic changes and mortality. The negative prognostic factors documented were hypoxia (p < 0.0001), multilobar pulmonary consolidation (p < 0.0001), tachycardia (p = 0.0001), tachypnoea (p = 0.0002), renal dysfunction function (p = 0.0009), hypotension (systolic p < 0.02, diastolic p < 0.003), bacteraemia (p = 0.003), and serum (including cardiac fraction) enzymes leak: LDH (p < 0.02), CK (p < 0.002) and CK-MB fraction (p = 0.0002). These factors, with the exception of renal dysfunction, also correlated with the need for intensive care unit admission. Acute and reversible electrocardiographic changes are common in acute community-acquired lobar pneumonia. Electrocardiographic changes, especially those compatible with acute cor pulmonale and accompanied by cardiac enzyme (CK-MB fraction) leak, correlated with severity of illness but not with mortality.

Determinants of near fatality in acute severe asthma.

PURPOSE: The data extrapolated from cases of acute severe asthma that narrowly miss being fatal may prove valuable in the identification of the factors implicated in mortality. The purpose of this study was, therefore, to identify determinants of near fatality in patients with acute severe asthma. PATIENTS AND METHODS: We studied 81 patients with acute severe asthma in whom mechanical ventilation was required. Near fatality was defined as the occurrence of respiratory arrest and/or coma necessitating emergency tracheal intubation and resuscitation. In the cases that were not regarded as near fatal, tracheal intubation was performed electively because of deteriorating arterial blood gas values and/or the anticipation of exhaustion. Various continuous and categorical variables were compared in these two groups of patients. Patients with a hyperacute attack (period from onset of attack to mechanical ventilation less than 3 hours) were specifically sought and studied to determine the impact of such a course on near fatality. RESULTS: The "attack duration" (period from onset of attack to mechanical ventilation) was an important determinant of near fatality and of the subsequent clinical course. It was shorter in the group with a near-fatal episode (p < 0.03), and hyperacute attacks were uniformly near fatal. The attack duration correlated positively with the duration of the requirement for mechanical ventilation (p < 0.01). A longer attack duration was associated with an increased likelihood of the occurrence of major atelectasis (p < 0.01). There was no evidence of a relationship between near fatality and the side effects of bronchodilators as regards hypokalemia, arrhythmias, or cardiotoxicity. There was evidence of considerable under-treatment in the patient population as a whole, particularly in regard to the use of corticosteroids. CONCLUSIONS: A short attack duration is associated with an increased risk of near fatality in acute severe asthma. This is particularly evident in hyperacute attacks. Hyperacute attacks resolve rapidly once bronchodilator therapy has been instituted, suggesting that smooth muscle spasm is the predominant pathogenetic mechanism. The importance of routine anti-inflammatory therapy in mild to moderate asthma requires re-emphasis but, in addition, all patients should be provided with, and educated in the use of, bronchodilator rescue therapy, which should be available at all times. Despite current trends, the use of regular, prophylactic bronchodilator therapy in strict conjunction with anti-inflammatory agents may still be indicated. There is little evidence in the present data obtained from near-fatal cases to support the concept that cardiotoxicity related to bronchodilators contributes significantly to mortality from asthma.

A study of immunoglobulin G subclass levels in black and white patients with various forms of obstructive lung disease.

The association of various respiratory disorders with disturbances in immunoglobulin G (IgG) subclass levels is increasingly being recognised. This was a prospective study of the IgG subclass levels in 71 patients (37 white, 34 black) with various respiratory disorders associated with obstructive airways disease. Ten white patients with adult cystic fibrosis were studied, 4 of whom were colonised with Pseudomonas aeruginosa. Alterations in individual subclass levels were seen in these patients and abnormalities noted included a decrease in IgG3 and/or an increase in IgG1 and/or IgG2 levels. Of the 17 black and 16 white patients with asthma, 2 had absent IgG4 levels associated with severe and recurrent respiratory infections, 2 had deficient IgG3 and 1 decreased IgG1 levels. Several patients had increased levels of several IgG subclasses, of which IgG1 was the most commonly affected. Both atopy and recurrent chest infections occurred most often in the latter group of patients. In the studies of 17 black and 11 white patients with bronchiectasis, all but 3 white patients were shown to have some alteration in IgG subclass levels. The commonest deficiencies were an absence of IgG4 (3 cases), and an absence of all subclasses (2 cases). One of the latter patients had an associated deficiency of total IgG and IgM, and the other demonstrated pan-hypogammaglobulinaemia. Abnormalities of IgG subclass levels appear to be commonly associated with several respiratory disorders including recurrent infections, atopy and bronchiectasis.

Sarcoidosis in Johannesburg--a comparative study of black and white patients.

Fifty-one black and 31 white patients with histologically proven sarcoidosis were managed in the respiratory units of the Johannesburg and Hillbrow Hospitals between January 1965 and October 1987. A number of differences in the demographic, clinical and laboratory features of the disease were documented in the two groups. While none of the black patients presented with erythema nodosum, direct skin involvement was significantly more common (P less than 0.05), occurring in 59% of these patients. The mean serum angiotensin-converting enzyme level was raised in both groups, but hypercalcaemia occurred infrequently in black patients. Almost 60% of the patients received corticosteroids, and the clinical and objective response to therapy was not significantly different in the two groups. Before referral the diagnosis was often labelled tuberculosis in the black patients who had frequently received antituberculosis chemotherapy. The tuberculin skin test is helpful, since it was negative in all but 2 black patients with sarcoidosis.

Quantification and assessment of viability of Pneumocystis carinii organisms by flow cytometry.

Analysis of drug efficacy in animal models of Pneumocystis carinii pneumonia requires an accurate method of quantification of organisms, as well as a means of assessing viability. Lung homogenates were prepared from a colony of athymic nude F344 rats experiencing a spontaneous outbreak of P. carinii pneumonia. With the fluorescent nucleic acid stain propidium iodide, flow cytometric analysis was able to quantify P. carinii cysts and trophozoites reproducibly. As this stain is excluded by living cells, this method was also used to assess the viability of organisms. Application of this technique to analysis of bronchoalveolar lavage specimens was demonstrated.

Respiratory health status of children in the eastern Transvaal highveld.

A study was undertaken to determine if there were detectable effects on the respiratory health status of children resident in the eastern Transvaal highveld as a consequence of their exposure to community air pollution, comparing them with children in areas ostensibly less polluted. A prevalence study was conducted in white schoolchildren from 11 schools in the eastern Transvaal highveld (1,031 children) and from 11 schools in non-polluted towns in the Transvaal (978 children). A questionnaire was completed by each child's mother, and height and weight were measured and spirometry recorded on a vitalograph. Cough, wheeze, asthma and chest illnesses were more frequently reported from polluted areas compared with non-polluted areas, taking into account parental smoking and home cooking fuel (odds ratios 1.34, 1.20, 1.15 and 1.88, respectively). After correcting for age, children in the polluted area were 0.83 cm shorter (P = 0.035). However, there were no significant differences in forced vital capacity and forced expiratory volume in 1 second after standardising for height, age, parental smoking and home cooking fuel. We conclude that, in children, exposure to pollution in the eastern Transvaal highveld may cause respiratory symptoms and chest illness and may affect height but does not measurably affect lung function, as assessed by spirometry.

Cryptogenic fibrosing alveolitis. A study of an indigenous African population.

Cryptogenic fibrosing alveolitis (CFA) has not been described previously in any large group of indigenous African patients. This was a retrospective study of 46 such patients diagnosed as having CFA during a 73-month period. The clinical spectrum of illness was similar to that of other groups studied worldwide. Cigarette smoking was associated with a poorer outcome and is a potentially preventable cause of deterioration.

Severe immune thrombocytopenia and the development of skin infarctions in a patient with an overlap syndrome.

A 49-year-old woman with clinical features of systemic lupus erythematosus, systemic sclerosis, Sjögren's and the antiphospholipid syndromes developed severe immune thrombocytopenia and skin infarctions. Both complications responded to immunosuppressive agents.

Meningococcaemia complicated by myocarditis. A report of 2 cases.

Two cases of myocarditis complicating meningococcal septicaemia are presented. Neisseria meningitidis infection with bacteraemia is a common entity but the important complication of myocarditis has not often been described. The autopsy findings in 1 of the 2 patients described further illustrates the significance of myocarditis. The pathology, clinical presentation and management of this complication are briefly discussed.

Ankylosing spondylitis lung disease and Mycobacterium scrofulaceum.

The development of apical pulmonary fibrosis and bullous disease is a rare but well recognized extra-articular manifestation of ankylosing spondylitis (AS). The fibrobullous disease is usually asymptomatic and diagnosed at an incidental radiological examination. When symptoms do develop, they are usually due to superimposed colonization or infection by bacteria, fungi or mycobacteria. Only six cases of non-tuberculous mycobacterial superinfection in AS have been reported. We report a patient with AS and progressive apical fibrobullous disease in whom Mycobacterium scrofulaceum was repeatedly cultured over a 12-year period.

Transbronchial biopsy during mechanical ventilation.

The diagnostic yield and risks of transbronchial biopsy (TBB) during mechanical ventilation were assessed in 13 patients with progressive pulmonary infiltrates. TBB was of considerable diagnostic value in ten patients and useful in excluding potentially treatable infections in the remaining three patients. Complications included two pneumothoraces, pulmonary hemorrhage in one case, and supraventricular tachycardia in another. No fatalities were attributable to TBB. TBB proved to be a relatively safe procedure, with a high diagnostic yield in these critically ill patients.

Multiple pulmonary cavities--an unusual complication of Pneumocystis carinii pneumonia.

Cavitation is a most unusual radiological feature of Pneumocystis carinii pneumonia (PCP). Autopsy evidence of cavities in PCP is poorly documented. We describe a case of fatal PCP occurring in a patient with the acquired immune deficiency syndrome; the PCP was associated with radiological as well as autopsy evidence of large intrapulmonary cavities. These cavities are ascribed to Pneumocystis carinii infection, since other possible causes were excluded.

'Low-dose' corticosteroid prophylaxis against fat embolism.

The effect of 'low-dose' corticosteroids (9 mg/kg methylprednisolone), given after skeletal trauma, on the incidence of the fat embolism syndrome and isolated arterial hypoxemia was studied in 42 controls and 40 steroid-treated subjects. Fat embolism occurred in ten controls (23.8%) and one steroid-treated subject (2.5%) (p = 0.01). A further 44 subjects developed isolated hypoxemia. This was severe (PaO2 less than 50 mm Hg) in seven of 32 controls (21.9%) and one of 39 steroid-treated subjects (2.6%) (p = 0.01). The overall incidence of hypoxemia was 67.1%, affecting 33 controls (78.6%) and 22 steroid-treated patients (55%) (p less than 0.05). The degree of hypoxemia was severe (PaO2 less than 50 mm Hg) in 12 controls (28.6%) and two (5%) of the steroid-treated subjects (p = 0.005). No control subject died or required mechanical ventilation. One steroid-treated subject without fat embolism died of a fulminant infection. Although methylprednisolone in a relatively low dose provides protection against fat embolism and pulmonary dysfunction after skeletal trauma, the safety of this therapy requires further evaluation.

Pneumocystis carinii pneumonia.

Pneumocystis carinii pneumonia (PCP) has become one of the most important of the opportunistic pulmonary infections of the 1980s. In view of the rapidly expanding population of immunosuppressed patients, many more cases of PCP may be expected in the future. The history, microbiology, pathogenesis, pathology, clinical and laboratory features, diagnosis, treatment, course and prognosis of this disease are reviewed.

Pneumocystis carinii pneumonia in Johannesburg.

Pneumocystis carinii pneumonia is today an opportunistic infection of major importance, occurring in immunosuppressed patients. Twelve cases of P. carinii pneumonia were seen by the Pulmonology Unit in Johannesburg between November 1984 and December 1985. The clinical presentation, laboratory and radiographic features, method of diagnosis, treatment, complications of therapy and outcome of these 12 cases are described.

Retinal complications in the acquired immunodeficiency syndrome. A case report.

Increasing numbers of patients with the acquired immunodeficiency syndrome (AIDS) are being reported. In the US literature the eye complications have been well documented but because so few cases of AIDS have been reported in South Africa, the retinal complications are largely unknown to those treating these patients. The retinal complications are due to cytomegalovirus (CMV) retinitis. The patient described here developed the typical signs in both eyes. It is essential to examine the fundi of AIDS patients regularly. The presence of cotton-wool spots always precedes CMV retinitis, which leads to blindness; it is also of prognostic significance since all reported patients with CMV retinitis have died.