Host defence to pulmonary mycosis.

OBJECTIVE: To provide a basic understanding of the mechanisms of host defense to pathogenic fungi. This will help physicians understand why some patients are predisposed to fungal infections and update basic scientists on how microbial immunology applies to fungal disease. DATA SOURCES: English articles from 1966 to present were identified from a MEDLINE search. STUDY SELECTION: Articles were identified by a MEDLINE search of 'exp lung/' or 'exp lung diseases/' and 'exp fungi/'. The titles and abstracts were screened to identify articles that contained salient information pertaining to host defense of respiratory mycoses. DATA EXTRACTION: Information was summarized from the articles pertaining to host defense of pulmonary mycosis that had been identified by the MEDLINE search. DATA SYNTHESIS: Fungi represent a unique and highly diverse group of pathogenic organisms that have become an increasingly prevalent cause of life-threatening illness. A worldwide increase in persons with immunodeficiency has been a major contributing factor to the increase in fungal disease. As a result, clinicians are faced with an expanding array of fungal infections that pose diagnostic and therapeutic challenges. The respiratory tract is the route of acquisition for many important fungal infections; thus, understanding the host defense in the lung is an essential component of understanding host defense to fungal disease. With this understanding, fungi may be divided on the basis of the predilection of certain mycosis for specific immune defects. CONCLUSIONS: By separating fungi based on the host immune defects that predispose to disease, in conjunction with traditional divisions based on the geographic distribution of fungi, clinicians are able to focus their diagnostic efforts and to identify fungal pathogens better. In addition, an understanding of the normal host defense mechanisms that serve to control fungal infections is essential to the development of novel antifungal therapies.

Recommendations for reducing the effect of grain dust on the lungs. Canadian Thoracic Society Standards Committee.

OBJECTIVE: To assess the appropriateness of the current Canadian standards for exposure to grain dust in the workplace. OPTIONS: The current permissible exposure limit of 10 mg of total grain dust per cubic metre of air (expressed as mg/m3) as an 8-hour time-weighted average exposure, or a lower permissible exposure limit. OUTCOMES: Acute symptoms of grain-dust exposure, such as cough, phlegm production, wheezing and dyspnea, similar chronic symptoms, and spirometric deficits revealing obstructive or restrictive disease. EVIDENCE: Articles published from 1924 to December 1993 were identified from Index Medicus and the bibliographies of pertinent articles. Subsequent articles published from 1994 (when the recommendations were approved by the Canadian Thoracic Society Standards Committee) to June 1996 were retrieved through a search of MEDLINE, and modification of the recommendations was not found to be necessary. Studies of interest were those that linked measurements of total grain dust levels to the development of acute and chronic respiratory symptoms and changes in lung function in exposed workers. Papers on the effects of grain dust on workers in feed mills were not included because other nutrients such as animal products may have been added to the grain. Unpublished reports (e.g., to Labour Canada) were included as sources of information. VALUES: A high value was placed on minimizing the biological harm that grain dust has on the lungs of grain workers. BENEFITS, HARMS AND COSTS: A permissible exposure limit of 5 mg/m3 would control the short-term effects of exposure to grain dust on workers. Evidence is insufficient to determine what level is needed to prevent long-term effects. The economic implications of implementing a lower permissible exposure limit have not been evaluated. RECOMMENDATIONS: The current Canadian standards for grain-dust exposure should be reviewed by Labour Canada and the grain industry. A permissible exposure level of 5 mg/m3 is recommended to control short-term effects. Further measurements that link the levels of exposure to respiratory health effects in workers across Canada should be collected to establish an exposure-response relation and possible regional differences in the effects of grain dust. VALIDATION: There has been no external review of these recommendations. However, the American Conference of Governmental Industrial Hygienists has recommended an 8-hour average exposure limit of 4 mg/m3 for wheat, oats and barley.

Increased production and immunohistochemical localization of transforming growth factor-beta in idiopathic pulmonary fibrosis.

Transforming growth factor-beta (TGF-beta) can regulate cell growth and differentiation as well as production of extracellular matrix proteins. Elevated production of TGF-beta has been associated with human and rodent chronic inflammatory and fibrotic diseases. Using immunohistochemical staining, we have examined lung sections of patients with advanced idiopathic pulmonary fibrosis (IPF), a disease characterized by chronic inflammation and fibrosis and demonstrated a marked and consistent increase in TGF-beta production in epithelial cells and macrophages when compared to patients with nonspecific inflammation and those with no inflammation or fibrosis. In patients with advanced IPF, intracellular staining with anti-LC (1-30) TGF-beta antibody was seen prominently in bronchiolar epithelial cells. In addition, epithelial cells of honeycomb cysts and hyperplastic type II pneumocytes stained intensely. Anti-CC (1-30) TGF-beta antibody, which reacts with extracellular TGF-beta, was localized in the lamina propria of bronchioles and in subepithelial regions of honeycomb cysts in areas of dense fibroconnective tissue deposition. The close association of subepithelial TGF-beta to the intracellular form in advanced IPF suggests that TGF-beta was produced and secreted primarily by epithelial cells. Because of the well-known effects of TGF-beta on extracellular matrix formation and on epithelial cell differentiation, the increased production of TGF-beta in advanced IPF may be pathogenic to the pulmonary fibrotic and regenerative responses seen in this disease.