Disease susceptibility

The progression from exposure to sensitization and disease in CBD hinges partly on an individuals genetic susceptibility. The seminal observation was made in a study by Richeldi et al. (101) demonstrating an increased frequency of MHC human leukocyte antigen (HLA) DPBl with a glutamic acid residue at 

Depending on the amount, form, and route of exposure to beryllium, various diseases may result, ranging from acute or chronic lung disease, dermatologic disease, or cancer. As the respiratory disease and dermatologic disease are most common, they are the focus of this section. 

Beryllium-related pulmonary manifestations exist on a continuum from acute inhalational injury to acute pneumonitis, beryllium sensitization, and the chronic form, that has been called berylliosis, chronic berylliosis, and which is now known as chronic beryllium disease (CBD). 

Exposure to elevated concentrations of beryllium, usually in the 25 pg/m range or greater, (120) can result in inflammation of the upper and lower respiratory tract and airways, tracheitis, bronchiolitis, pulmonary edema, and a lymphocyte-predominant chemical pneumonitis (12,121-123). Although significantly less common than CBD, acute beryllium disease stiU occurs globally. In 2004, nine cases were reported from a South Korean liquid metal factory where measured beryllium exposures ranged from 3.13 to 112.3 pg/m (12). The manifestations 

The primary therapeutic intervention is removal from exposure. Corticosteroids, oxygen, rest, and even ventilatory support, if needed, are part of an appropriate treatment regimen. The signs and symptoms of acute chemical pneumonitis may resolve within several weeks to several months. In its most severe form, this acute disease may be fatal. Approximately 17% of the acute cases in the Beryllium Case Registry progressed to CBD (122). It is unclear whether return to work and further beryllium exposure is safe for individuals who have experienced the acute pneumonitis. 

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There is a polygenic inheritance pattern which may account for disease susceptibility and expression.7 Family... 

Target genes involved in dmg response can also be involved in disease susceptibility. For example, polymorphisms of the cholesteryl ester transfer protein (CETP) are associated with both coronary atherosclerosis and response to pravastatin [22]. 

Ethnic variation in allele frequencies can lead to important differences in disease susceptibility, outcome and drug metabolism [68, 69]. In addition to single nucleotide polymorphisms, variable number of tandem repeat (VNTR) regions have been shown to have functional significance. 

Feys, B. J., Wiermer, M., Bhat, R. A., Moisan, L. J., Medina-Escobar, N., Neu, C., Cabral, A. and Parker, J. E. (2005). Arabidopsis senescence-associated genelOl stabilizes and signals within an enhanced disease susceptibility 1 complex in plant innate immunity. Plant Cell 17, 2601-13. 

Thipyapong P, Hunt M and Steffens, J. 2004. Antisense down regulation of polyphenol oxidase results in enhanced disease susceptibility. Planta 220 105—117. 

Maraganore, D. M.,Lesnick,T. G.,Elbaz, A. etal. UCHL1 is a Parkinson s disease susceptibility gene. Ann. Neurol. 55 512-521,2004. 

FIGURE 3.1 Sch ematic showing factors which influence infectious disease susceptibility. 

Rice, C.D., and Arkoosh, M.R., Immunological indicators of environmental stress and disease susceptibility in fishes, in Biological Indicators of Stress in Aquatic Ecosystem Stress, Adams, S.M., Ed., American Fisheries Society Publications, Bethesda, 2002, 187. 

Selgrade, M.K., Starnes, D.M., Illing, J.W., Daniels, M.J., and Graham, J.A. 1989. Effects of phosgene exposure on bacterial, viral, and neoplastic lung disease susceptability in mice. Inhalation Toxicol. 1 243-259. 

Although ancients and moderns alike have called attention to variability and individuality as factors particularly related to disease susceptibility and moderns have recognized that variability is indispensable to evolution, comparatively little research time and effort have been devoted to definitive study in physiology and biochemistry as to precisely how so-called normal individuals differ from each other. Such study necessarily involves repeated observations on the same individuals, in contrast to a series of single observations on representative populations. No attempt to bring together the available biochemical material on normal variation has been previously made so far as I know. 

Another modern exponent of studying constitution in relation to disease susceptibility was Wade H. Brown of the Rockefeller Institute, whose findings in the field of anatomy have already been mentioned (p. 19).6 A few quotations from his work will serve to illustrate the best medical thinking of his time with relation to the problem under consideration. Regarding constitution he says ... 

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