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.

The mechanisms responsible for anaemia in leprosy were studied prior to the institution of therapy in 56 patients with active disease. Haematological indices, iron‐related measurements, inflammatory markers and erythropoietin levels were assessed, with bone‐marrow studies being performed on anaemic patients. Anaemia was more common in the patients with lepromatous leprosy (85.7%) than it was in the rest of the group (19%). The lepromatous group exhibited the disordered iron transport of the anaemia of chronic disorders in that they had a significantly lower mean serum iron level (P< 0.05), and a mildly raised serum ferritin concentration. Anaemic lepromatous patients also showed a blunted erythropoietin response compared with controls with noninflammatory anaemia. A subgroup of five anaemic subjects displayed apparently adequate transport of iron to the erythroid marrow (normal percentage transferrin saturations and appropriate sideroblast counts) and the blunted erythropoietin response appeared to be the dominant factor in the pathogenesis of their anaemia. Analysis of inflammatory markers revealed that while the erythrocyte sedimentation rate was very high in the lepromatous subjects, there was no concomitant rise in C‐reactive protein concentration. This suggests the presence of a disordered cytokine‐mediated acute phase response in the condition.

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.