Bulletin of the International Union against Tuberculosis and Lung Disease最新文献

Statistics for deaths from asthma yield widely variable mortality rates between countries. Validation studies show significant inaccuracies in certification of cause of death in older subjects, and probable underreporting of asthma deaths in some countries, explaining some of the international differences noted. The introduction of the ninth revision of the World Health Organisation International Classification of Diseases brought a step increase in reported asthma mortality rates in 1979, but the last decade has seen a gradual increase in mortality rates in many countries, especially in young people, not explained by this change in code. Diagnostic transfer does not adequately explain these increases. Individuals at risk of death from asthma are more likely to be non-caucasian, non-compliant, and young, with a history of previous life-threatening episodes, hospital admissions, and precipitous attacks. Studies of circumstances of death have emphasized overreliance on beta-agonists and underuse of corticosteroids as two primary deficiencies in management, but there remains debate about the causality of the association between increased asthma mortality and increased usage of beta-agonists. The gradual increase in asthma mortality seen in New Zealand over the last 40 years, with episodic increases in the rising baseline, together with similar but more gradual changes in other countries, raises concerns about whether current treatment practices may adversely affect asthma severity and mortality. Further studies are required to validate asthma mortality statistics, and to establish causation of deaths.

The aim of this paper is to outline, in the light of present understanding of the disease, some of the likely causes for the increasing prevalence and mortality associated with asthma in different communities in the world. It seems important both to understand the causes of asthma and to taking action to reverse the trends. There is an increasing sense of urgency in addressing the problems of morbidity and mortality caused by asthma. In this regard the respiratory community is a long way behind the cardiovascular community who have been documenting the risk factors for vascular disease for many years. In the absence of a reliable definition of asthma, it is difficult to make definite statements about trends in its prevalence, morbidity and mortality. Nevertheless, as already summarised, asthma appears to be an increasing problem. the trend towards increasing deaths in some countries is particularly worrying. The mortality data are most accurate for the 5 to 34 year olds and this paper is confined to reviewing data from this age group.

Between January 1 and June 30, 1988, 30 (39.5%) of 76 staff members tested at a health clinic in Florida had positive tuberculin skin test reactions. This case-control study showed that people whose skin test converted were more likely than those whose skin test did not convert to have been present while patients were being treated with aerosolized pentamidine (odds ratio = 15.0; 95% confidence interval = 1.4 - 730.0) and to have worked on the first floor of the clinic (odds ratio = 9.3; 95% confidence interval = 1.1 - 420). The clinic building was poorly ventilated, and aerosolized pentamidine treatments were given in a room from which the air tended to flow into the hallway. Aerosolized pentamidine should be administered in a well-ventilated area from which the air is exhausted directly outside. All persons who are given such treatments should first be screened for tuberculosis. Use of trade names is for identification only and does not constitute endorsement by the Public Health Services or the U.S. Department of Health and Human Services.

Chronic airways obstruction is a common cause of morbidity and mortality in Canada. It may progress to hypoxic respiratory failure and then to death. Only a few studies of the prevalence of chronic airways obstruction have been reported from Canada, but a number of studies have been reported from the United States and the United Kingdom, countries with similar socioeconomic conditions and ethnic compositions to those in Canada. The prevalence of chronic airflow limitation in these studies averages 9.3%. In each study, tobacco smoke exposure is the most prominent etiologic agent. Other contributing factors identified in the studies are air pollution, occupational exposure, respiratory infections and childhood respiratory illness. Endogenous modifiers of these risk factors demonstrated in the published studies include age, elevated peripheral blood leukocyte count and familial factors. Although epidemiologic studies have been able to identify the prevalence of functional impairment associated with chronic airways obstruction, risk factors associated with its development and modifiers of these risk factors, it is not possible to determine the prevalence of severe chronic airways obstruction resulting in hypoxemic respiratory failure. An estimate of this prevalence has been calculated based on certain assumptions. It was assumed that patients dying of chronic airways obstruction were likely, in a high proportion of cases, to have hypoxemic respiratory failure. It has been demonstrated that only one-half of all patients dying of chronic airways obstruction are correctly designated on death certificates. It was assumed, conservatively, that the median survival of patients with hypoxemic respiratory failure is two years. From these assumptions, it was estimated that the prevalence of hypoxemic respiratory failure in 1986 in Canada was 100 per 100,000 population. This is higher than the present rate of oxygen therapy, indicating that some patients currently eligible for this treatment may not be receiving it.

After infection with M. tuberculosis, about 5% of individuals develop progressive tuberculosis during the following two years and an additional 5% delayed reactivation. The genetic and acquired factors which place individuals at risk of tuberculosis are partly defined; however, the connection of the susceptibility to the host immune response is much less clear. Recent studies have examined the basis for the immunosuppression that is a concomitant of tuberculosis. Direct stimulation of monocytes primed during the course of tuberculous infection by mycobacterial peptides appears to be responsible for suppression of PPD-induced responses. Increased expression and release of interleukin-2 receptors and transforming growth-factor beta are associated with and may contribute to such suppression by monocytes. Additional studies have addressed the generation of immunity or immunosuppression. Ingestion of live M. tuberculosis by monocytes leads to selective expansion of gamma-delta T cells as opposed to CD4 lymphocytes. This may be relevant to the innate response to infection with M. tuberculosis as well as immunoregulatory circuits. Increased understanding of the basis for immunosuppression is of intrinsic interest as regards regulation of specific pathways of immune reactivity in an infectious disease of humans and may provide some insight into factors predisposing to tuberculosis.

Detailed analysis of mycobacterial proteins originally identified by their prominent interaction with the host immune system reveals a number of interesting biochemical characteristics. M. tuberculosis antigens with molecular weights of 71, 65 and 12 kilodaltons (kD) belong to highly conserved heat shock protein families. A group of closely related antigens with molecular weights around 30 kD are major secreted antigens which share the ability to bind to fibronectin. Antigens with molecular weights of 38 kD and 19 kD are probably lipoproteins with a role in nutrient transport, while the 23 kD antigen is the superoxide dismutase enzyme of M. tuberculosis. It is anticipated that further studies along these lines will generate information of importance to the understanding of the lifestyle of mycobacteria in vivo and also to the elucidation of immune mechanisms in mycobacterial disease.

Active tuberculosis is now recognized as a frequent and serious complication of infection with the human immunodeficiency virus (HIV), the causative agent of AIDS. HIV mediated alteration in host defenses against mycobacteria contribute to the magnitude and severity of this problem. HIV can affect a variety of cellular mechanisms important in the restriction of mycobacterial growth. Qualitative and quantitative defects in T lymphocyte function result from direct HIV infection of cells expressing the CD4 epitope, and can severely limit the production of macrophage activating cytokines capable of inducing an anti-mycobacterial state in cells of monocyte lineage. In addition, macrophages themselves are susceptible to HIV infection, and have been shown to be defective with respect to a variety of host defense functions. Both T4 lymphopenia and HIV infected macrophages are present in the lower respiratory tract of HIV infected individuals, a circumstance which likely underlies the unique susceptibility of HIV infected to tuberculosis.

In the present stage of development where tuberculosis mortality has lost its statistical significance because of effective chemotherapy, it is generally recognized that the most reliable measure of the extent of the tuberculosis problem in a population is the "annual tuberculosis infection rate" or incidence of infection. In countries where infection with the bovine type of tubercle bacilli no longer exists, as is the case in the majority of low prevalence countries, the annual infection rate expresses that proportion of the population under study which will be primarily infected, or reinfected with tubercle bacilli from a human source in the course of one year. The annual tuberculosis infection rate is also the best measure for following the trend of the tuberculosis problem in a given population and for evaluating the total effects of organized efforts to control tuberculosis.