Cardiopulmonary morbidity

In addition to size, PM mass and number concentrations, volatility, morphology and chemical composition (e.g. organic, metal, salt content) are critical factors to be considered in the assessment of risk. The evidence regarding the relationship between airborne PM mass exposures (i.e. PM2.5) and patterns of cardiopulmonary morbidity and mortality is quite solid. It is not clear, however, what chemical constituents may be particularly responsible for the observed effects. 

Exposures to ambient particulate matter (PM), especially fine PM with an aerodynamic radius of 2.5 pm (PM2.5), have been consistently related to increases in mortality and morbidity (Dockery et al. 1993 Burnett et al. 1999). The effects of ambient PM exposures on certain vulnerable populations such as the elderly, those with compromised cardiopulmonary health and children are of particular concern. A number of studies have demonstrated, for instance, that exposure to air pollution is associated with reductions in lung function and growth, asthma, allergic rhinitis and respiratory infections in children (Janssen et al. 2003 Brauer et al. 2007). Among other things, their susceptibility can be attributed to the immaturity of their respiratory defence mechanisms and higher permeability of their airways to air pollutants compared to adults. 

Complement activation has been associated with leukostasis in the pulmonary vasculature, granulocytopenia, anaphylactoid reactions, hypotension, pyrogenic reactions, amyloid formation in the joints of long-term renal patients, and cardiopulmonary complications (Chenoweth, 1988). This has led to the development of surface-modified RC membranes less complement activating (see Section 18.4.1.2). However, the controversial results obtained in many reported clinical trials comparing treatments of renal failure with membranes known to activate or not to activate complement have not yet shown a significant impact on patients mortality or morbidity. 

There are statistically significant associations between combustion-derived particles and elevations in mortality and morbidity, particularly among elderly persons with cardiopulmonary disease. The mechanism(s) by which these particles exert their effect is unknown, but may also involve generation of oxidants from transition metals present on these particles. Additionally, the size and acidity of PM 10 may contribute to its toxicity, as may organic or biological compounds found on the surface of these particles. 

An understanding of the mechanisms whereby inhaled particles cause acute morbidity and mortality has not yet been realized. Epidemiological evidence suggests that cardiopulmonary disease is a primary predecessor of these outcomes (8). Many of these studies have further suggested the importance of investigating fine and ultrafine particles as the primary particulate culprits. 

To date, increased pulmonary inflammation and decrements in pulmonary function have been clearly associated with C APs exposure in animals with cardiopulmonary disease. Normal animals are also not immune to the effects of inhaled particulate matter these animals have exhibited significant, albeit less severe, lung injury following particle exposure. The future of these studies lies in the investigation of the signaling pathways that are responsible for the sudden mortality observed. Given these data, it is clear that these pathways should be further delineated to develop potential measures to prevent sudden mortality and morbidity in exposed populations. 

Irritants and allergens activate sensory nerves directly or by the release of mediators from inflammatory cells. Although mast cells and basophils appear to have some capacity to release mediators on exposure to irritants, direct evidence of the physiological responses from irritant-induced mediator release is sparse. It is a very attractive hypothesis that this type of nonimmune activation of inflammatory cells releases mediators of the anaphylactic responses to constitute an amplification mechanism contributing to the increase in morbidity and mortality in persons with compromised cardiopulmonary function or hyperresponsiveness to irritants and allergens. 

If we are to understand the influence of inhaled irritants and allergens on humans and their contribution to morbidity and mortality, the potential systemic effects of irritants in humans and animal models of allergic hyperresponsiveness and eompromised cardiopulmonary function must be evaluated and the mechanisms of these responses delineated. 

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