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Article Excerpt
ABSTRACT: Although the organisms that cause community-acquired pneumonia are similar in diabetic and nondiabetic patients, those who have diabetes mellitus (DM) may have more severe disease and a poorer prognosis. Elevated blood glucose levels are associated with worse outcomes in patients with pneumonia, and the mortality risk may be as high as 30% in patients with uncontrolled DM. Thus, appropriate treatment--and possibly prevention--of bacterial pneumonia should include aggressive efforts directed at glycemic control. Other respiratory infections, such as influenza, tuberculosis, and fungal pneumonia, also are associated with greater morbidity in patients with DM. Diabetic patients with tuberculosis are more likely to present with bilateral lung involvement and pleural effusions.
KEY WORDS: Pneumonia, Diabetes mellitus, MRSA, Influenza, Tuberculosis, Fungal infections
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Diabetes mellitus (DM) is a complex metabolic disorder that is characterized by hyperglycemia and is associated with increasing incidence, morbidity, and mortality. According to the World Health Organization (WHO), 180 million persons have DM and 5% of deaths worldwide can be attributed to this disease. Also, there is evidence that DM is associated with an increased risk of infections and with more severe clinical consequences of such infections. (1-3)
The mechanisms that lead to excess morbidity and mortality are related in part to the host immune defects associated with DM. Coexisting conditions, such as vascular, renal, and cardiovascular diseases, and the various interventions associated with such diseases, contribute significantly to the increased incidence and complexity of infections in patients with DM.
In this article, we will briefly review the immunological and respiratory changes associated with DM. Then we will focus on the challenges of community-acquired pneumonia (CAP) and nosocomial pneumonia in patients with DM.
EFFECTS OF DIABETES
Immunological changes
The airways and alveoli are constantly exposed to microbes, but normal host defense mechanisms can often protect the lungs. In the upper respiratory tract, aerodynamic filtration, mucociliary clearance, cough mechanism, and neurological reflexes prevent aspiration and remove large particles. (4) In the lower respiratory tract, defenses include bronchus-associated lymphoid tissue, opsonins (IgA and IgG), surfactant, extracellular chemotactic factors, alveolar macrophages, and pathogen-specific immune responses involving dendritic cells and T and B lymphocytes. (5)
Overall, the immune response is impaired in persons with DM. Several aspects of cellular immune function--chemotaxis, adherence, phagocytosis, and intracellular killing-are adversely affected by hyperglycemia. Anaerobic conditions in the tissue that are created by vascular compromise and inflammatory response further impair the immune response.
Intracellular killing is altered because hyperglycemia impairs Fc gamma receptor-mediated phagocytosis by neutrophils through inhibition of protein kinase C. (6,7) In addition, intracellular killing is impaired because nicotinamide adenine dinucleotide phosphate is consumed by the polyol pathway, thus depleting the amount available for free radical formation. (8,9) It has been demonstrated that insulin improves impaired cellular immune functions, both directly and through better glycemic control. (10-13)
The cell-mediated immune response also is weakened in DM. The diabetic state causes an increase in levels of proinflammatory cytokines, such as tumor necrosis factor [alpha], interleukin (IL)-1B, IL-18, and IL-16. These cytokines promote insulin resistance by decreasing glucose transporter protein 4 receptors and increasing lipolysis. The elevated levels of these cytokines can be reversed by insulin and improved metabolic control. (7,8) The humoral immune response, however, appears to be preserved, as evidenced by the adequate response to influenza, pneumococcal, and hepatitis B vaccines. (14)
Respiratory effects
Pulmonary function may be adversely affected by DM. The mechanical function of the lungs has been evaluated in a number of studies, but the results are contradictory. Some studies have shown reduction in forced vital capacity, forced expiratory volume in 1 second, total lung capacity, and end-expiratory volume, all of which are the result of decreased elastic recoil. (15-17) However, other studies have shown that pulmonary function is predominantly preserved in persons with DM. (18-20)
The pathophysiology of lung abnormalities in patients who have DM is believed to involve microangiopathic changes in the basement membrane of pulmonary blood vessels and respiratory epithelium, as well as nonenzymatic glycosylation of tissue protein. (21) Autopsies of patients with DM have revealed thickening of alveolar epithelia, vascular hyalinosis, and pulmonary microangiopathy. (22,23) The increased thickness of the alveolar septa leads to diminished diffusion of oxygen. (16,18-20,24-26)
The extent of the changes in lung tissue seems to be associated with the level of glycemic control, while the changes in pulmonary capillaries mirror the degree of retinopathy, nephropathy, and neuropathy. (27) Persons with DM also are susceptible to pulmonary infections because of an increased risk of aspiration secondary to gastroparesis, diminished cough reflex, and disordered sleep patterns. (24,28)
PULMONARY INFECTIONS
Acute respiratory infections are the number 1 cause of mortality globally, with more than 4.5 million deaths a year. In the United States, pneumonia is the sixth most common cause of death and the most prevalent cause of infectious disease -related mortality. (29)
Chronic underlying conditions, such as immunosuppression, generally increase the risk of pneumonia. However, the evidence of an increased risk of pneumonia in persons with DM is inconsistent. Most research has not shown clearly that pneumonia is more likely to develop in the overall diabetic population. However, the evidence is stronger when subsets of the population are examined. For example, Lipsky and associates (30) and Muller and associates (1) reported an increased risk of pneumonia among elderly persons with DM. Zanobetti and Schwartz (31) identified DM as a risk factor for pneumonia among patients younger than 40 years.
It has also been reported that persons with DM may be more likely to have recurrent pneumonia. (14) Some studies have linked diabetes with higher...
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