Pneumocystis carinii pneumonia in HIV infected patients from South Africa.

OBJECTIVE: To compare the spectrum of pulmonary disease in human immunodeficiency virus positive patients of African and European origin, with particular reference to Pneumocystis carinii pneumonia. DESIGN: Descriptive study with retrospective record review. SETTING: Tertiary care, university teaching hospitals in Johannesburg, South Africa. SUBJECTS: Sixty seven HIV-infected patients and 36 HIV-negative renal transplant patients (who served as controls) whose sputa were negative for tuberculosis and Pneumocystis carinii, and who had fibreoptic bronchoscopic evaluation for pulmonary disease between January 1985 and August 1992. MEASUREMENTS: Histological and cytological evaluation of pulmonary diseases. RESULTS: In the HIV infected group Pneumocystis carinii pneumonia was the most frequent disease in patients of both African and European origin but occurred less commonly in Africans than in Europeans (27.3% and 58.8%, respectively; p = 0.01). There was no statistically significant difference between patients of African and European origin in the frequency of any other diagnosis. In the renal transplant group the most frequent diagnosis was non-specific interstitial pneumonitis (Africans 33.3%, Europeans 37.0%), followed by Pneumocystis carinii pneumonia (Africans 22.2%, European 14.8%). There was no difference between HIV-infected and renal transplant patients in the frequency of any diagnosis. CONCLUSION: Pneumocystis carinii pneumonia should be considered in the diagnosis of HIV-infected African patients with pulmonary disease whose sputum smears for tuberculosis are negative.

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.

Alpha-1-protease inhibitor in bronchial asthma: phenotypes and biochemical characteristics.

The prevalence of the different phenotypes of alpha 1-protease inhibitor (alpha 1PI) was investigated in a group of 90 asthmatic patients and compared with that of a control group of 240 individuals representing the general population. The M2M2 phenotype occurred more frequently in the asthmatic group (p = 0.015). Plasma samples of 51 of the asthmatic patients randomly selected from the different phenotype groups identified were studied for the absolute plasma values of alpha 1-PI and the inhibitory capacity of plasma for porcine pancreatic elastase, and compared with those from 21 nonasthmatic individuals of the M1M1 phenotype. Although the asthmatic patients had higher absolute alpha 1PI values (p = 0.04), the plasma elastase inhibitory capacity was markedly reduced compared with the nonasthmatic subjects (p = 0.01). The functional efficiency of alpha 1PI from asthmatic patients of the M1M1, M1M2, and M2M2 phenotypes was significantly decreased compared with that of the nonasthmatic M1M1 individuals. Functional deficiency of alpha 1PI may be important in the pathogenesis of the inflammatory process that characterizes bronchial asthma.

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.

Comparison of bacteraemic community-acquired lobar pneumonia due to Streptococcus pneumoniae and Klebsiella pneumoniae in an intensive care unit.

In a study of 41 consecutive patients with bacteraemia-associated community-acquired lobar pneumonia due to Streptococcus pneumoniae and Klebsiella pneumoniae an attempt was made to determine whether distinguishing criteria of disease due to these organisms could be identified according to demographic features and the results of initial clinical and laboratory investigations. Such information would aid in the early initiation of appropriate antimicrobial therapy. The most significant difference between the two groups of patients was the lower platelet count in the K. pneumoniae group (p less than 0.005). In addition leucopenia (p less than 0.05), higher serum albumin (p less than 0.05), and the male sex (p less than 0.05) featured with an increased frequency in patients with pulmonary infection due to K. pneumoniae. Initial antimicrobial therapy in critically ill patients with community-acquired lobar pneumonia and thrombocytopenia, particularly when associated with leucopenia and in male patients, should include agents effective against K. pneumoniae.

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.

The hormonal response to exercise in asthma.

The hormonal responses to exercise of 10 asthmatic patients and 12 normal subjects were compared by studying the changes in the plasma levels of growth hormone, prolactin, adrenocorticotropic hormone (ACTH) and cortisol induced by treadmill running. The asthmatic patients demonstrated absence of the plasma cortisol response to exercise (peak increment -15 +/- 21 (SEM) vs 108 +/- 34 nmol.l-1 p less than 0.02). None of these patients were being treated with systemic corticosteroids and there was no difference between the responses of users and non-users of beclomethasone dipropionate. The results suggest the presence of an impaired adrenocortical response to the stress of physical exercise in asthma and indicate the need for detailed evaluation of hypothalamic-pituitary-adrenal function in patients with the disease.

Metabolic and hormonal responses to salbutamol in asthma. Evidence of beta-adrenergic overactivity?

The possibility that beta-adrenergic hyposensitivity may be involved in the pathogenesis of bronchial asthma remains a controversial issue. The hormonal, metabolic and cardiovascular responses to selective beta 2-adrenergic stimulation with salbutamol were compared in 11 asthmatic and 11 non-asthmatic subjects. There was no consistent difference between the two groups in the plasma free fatty acid, glucose and potassium responses, or in the cardiovascular variables studied, but the asthmatic patients demonstrated a marked dose-dependent hyperinsulinaemic response to salbutamol. Although this phenomenon cannot be accounted for with certainty, it may be a manifestation of pancreatic beta-adrenergic overactivity which would not be in keeping with the concept of generalised hyposensitivity of beta-adrenergic mechanisms in asthma. The present results provide a clear demonstration of the difficulties involved in attempts to relate extrapulmonary autonomic phenomena to the pathogenesis of bronchial asthma.

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.

Initial hormonal and metabolic profile in critically ill patients with community-acquired lobar pneumonia.

A prospective study of 18 critically ill patients with community-acquired lobar pneumonia was undertaken at Hillbrow Hospital, Johannesburg, in order to document the initial plasma hormonal and substrate profile as part of the stress response to the infection. The results of these studies, carried out before therapy, were compared with the results in a group of healthy fasting adults. Highly significant (P less than or equal to 0.005) increases in the mean plasma levels of adrenaline, noradrenaline, human growth hormone, cortisol, glucose and free fatty acids were noted in the study group, with a lesser increase in the prolactin concentration (P less than or equal to 0.01). The levels of dopamine, glucagon, insulin and adrenocorticotrophin did not show any significant change. No significant differences were found in the hormonal profile when comparing survivors with non-survivors. The neuro-endocrine hormonal and metabolic responses in pneumonia appear to be similar to those seen in other stress situations and failure of the initial stress response does not appear to contribute to the mortality of critically ill patients with community-acquired lobar pneumonia.

The diagnostic yield of prebronchoscopy sputa and bronchial washings in patients with biopsy-proven pulmonary tuberculosis.

We report on a series of 35 patients with pulmonary tuberculosis diagnosed by flexible fibre-optic bronchoscopy and transbronchial lung biopsy after 3 sputum specimens had been microscopy-negative. This study re-evaluates this invasive procedure. Additional prebronchoscopy specimens of expectorated sputum yielded the diagnosis in 7 of 16 cases (43.8%) on microscopy. Sputum culture results were positive in 12 of 33 (36.4%). Pleural fluid culture was diagnostic in 1 case, and in another miliary tuberculosis was demonstrated on bone marrow trephine biopsy. The availability of these results could therefore have obviated the need for bronchoscopy in 14 of the 35 patients (40%). Bronchial washings were positive for acid-fast bacilli on microscopic examination in 13 of 34 cases (38.2%) and culture-positive in only 18 of 34 (52.9%), and should therefore not be the sole procedure utilised when bronchoscopy is performed. Transbronchial lung biopsy remains a valuable procedure to confirm pulmonary tuberculosis in patients whose sputum is culture-negative for mycobacteria.

A reevaluation of sputum microscopy and culture in the diagnosis of pulmonary tuberculosis.

This prospective study was undertaken to determine the interpretation of "scanty-positive" acid-fast bacilli on microscopy and to reevaluate simultaneous microscopy and culture of sputum for the accurate diagnosis of pulmonary tuberculosis (PTB). A total of 2,560 specimens were processed from 727 patients. There were 435 positive specimens (17.0 percent), originating from 139 patients, 10 by microscopy only, 176 by culture only, and 249 on both microscopy and culture. Review of the hospital records showed that 107 patients had PTB, 1 had Mycobacterium kansasii colonization, and 31 were thought not to have PTB. Sensitivity and specificity were 53.1 and 99.8 percent for microscopy, 81.5 and 98.4 percent for culture, and 77.6 and 100 percent for microscopy and culture, respectively. Seventy-five microscopy specimens (46 patients) were reported as scanty-positive, of which five (four patients) were deemed false positives, yielding a positive predictive value of 93.3 percent. In those patients with positive sputum microscopy, acid-fast bacilli were detected in one of the first four specimens. Seven isolates (three patients) were mycobacteria other than tubercle (0.27 percent of specimens and 1.6 percent of mycobacteria cultured). Despite the ready availability of laboratory evidence of disease, only 73 percent of cases were diagnosed by ward staff and 36 percent notified by the primary physician. Eleven patients (10.3 percent) died, six of whom had not received diagnoses of PTB before death. Sputum microscopy and culture remains reliable despite Bayesian predictions when applied to a population with a decreasing incidence of tuberculosis.

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.

Community-acquired pneumonia of diverse aetiology: prognostic features in patients admitted to an intensive care unit and a "severity of illness" core.

In a retrospective study of 73 patients with community-acquired lobar pneumonia of diverse aetiology admitted to an intensive care unit, an attempt was made to identify those factors among the demographic and clinical features and results of initial laboratory investigations that were predictive of the ultimate outcome. A lower mean white cell count (p = 0.03), platelet count (p = 0.02), total serum protein (p = 0.005) and albumin (p = 0.02) and a higher mean serum creatinine (p = 0.03) and phosphate level (p = 0.02) appeared to be predictive of a poor prognosis. The most significant variable predictive of mortality, was the presence of bacteraemia (p = 0.0005). Severity of illness scoring systems by omitting microbiological data appear to underestimate predicted patient mortality. The mortality rate of critically ill patients with community-acquired lobar pneumonia remains high, despite advances in antimicrobial chemotherapy and intensive care unit facilities, particularly in the presence of certain negative prognostic factors of which the presence of bacteraemia is the most important.

Pneumococcal bacteraemia in adults in a low socio-economic urban population.

Between January 1984 and December 1985, 183 adult patients, subsequently shown to have pneumococcal bacteraemia, were admitted. Of these infections, nine were caused by penicillin-resistant strains, and three of these were resistant to other antibiotics. The organisms from 150 patients were serotyped/grouped. The primary site of infection was lung in 90 per cent of patients. Among the patients with pneumonia, those with serovar 3 strains accounted for most intensive care unit admissions, most cases requiring inotropic drugs, and mechanical ventilation and had the highest complication rate and mortality. Findings which predicted the need for intensive care included higher age, elevated concentrations of serum urea, creatinine, and phosphate and lower levels of total serum protein, albumin and calcium. Twenty-four patients died of whom 23 had pneumonia. The case fatality rate among all of the patients admitted to the intensive care unit was 60 per cent and among those not admitted to the unit, 9.2 per cent. Of the patients who died, 41.7 per cent did so within the first five days of admission. The prophylactic use of polyvalent pneumococcal vaccine in industrial workers from low socio-economic groups should be carefully considered.

Nocturnal events related to "morning dipping" in bronchial asthma.

The mechanism of early morning bronchospasm in asthma was investigated by analyzing circadian variations in the plasma levels of cortisol, ACTH, epinephrine, and norepinephrine, as well as in the serum neutrophil chemotactic activity and heart rate in asthmatic patients with (n = 6) and without (n = 7) "morning dipping" and normal subjects. Findings suggested that an exaggerated nocturnal nadir in plasma cortisol levels may precipitate "morning dipping" in some patients with asthma.

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.