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Disease relevance of Emphysema


Psychiatry related information on Emphysema

  • Stratification of patients into those with and without macroscopic emphysema (EMPH+, EMPH-, respectively), with comparable physical activity levels on the basis of previous observations, revealed lower values for La threshold and GLU in EMPH+ patients [6].
  • We believe that the issue of neonatal screening for alpha 1-antitrypsin deficiency should be reexamined because augmentation therapy for adults with emphysema is now available, and screening followed by family-based smoking intervention may lead to a nonsmoking life-style [7].
  • This is the first reported case of isolated retropharyngeal emphysema caused by ingestion of the amphetamine derivatives "Ecstasy" and "Speed". The same complication has been reported with marihuana, cocaine, and heroin abuse [8].

High impact information on Emphysema

  • Pulmonary function may improve after surgical resection of the most severely affected lung tissue (lung-reduction surgery) in patients with diffuse emphysema [9].
  • Although elastase has been proposed as the primary enzyme responsible for emphysematous lung damage, this study provides evidence that other extracellular matrix proteases could play a role in emphysema [10].
  • This pathology is strikingly similar to the morphological changes observed in human emphysema and therefore implicates interstitial collagenase as a possible etiological agent in the disease process [10].
  • Replacement therapy for alpha 1-antitrypsin deficiency associated with emphysema [11].
  • Finally, increased lung ceramides in individuals with smoking-induced emphysema suggests that ceramide upregulation may be a crucial pathogenic element and a promising target in this disease that currently lacks effective therapies [12].

Chemical compound and disease context of Emphysema


Biological context of Emphysema


Anatomical context of Emphysema


Gene context of Emphysema

  • Here we report that Itgb6-null mice develop age-related emphysema that is completely abrogated either by transgenic expression of versions of the beta6 integrin subunit that support TGF-beta activation, or by the loss of Mmp12 [3].
  • IFN-gamma causes emphysema and alterations in pulmonary protease/antiprotease balance when expressed in pulmonary tissues [25].
  • Role of CCR5 in IFN-gamma-induced and cigarette smoke-induced emphysema [26].
  • Targeted ablation of the surfactant protein D (SP-D) gene caused chronic inflammation, emphysema, and fibrosis in the lungs of SP-D (-/-) mice [27].
  • These results suggest that changes in FLCN may have an important role in the development of PSP and, more importantly, of emphysema, a chronic pulmonary disease that often leads to formation of bullous lesions and lowered pulmonary function [28].

Analytical, diagnostic and therapeutic context of Emphysema


  1. Dietary n-3 polyunsaturated fatty acids and smoking-related chronic obstructive pulmonary disease. Atherosclerosis Risk in Communities Study Investigators. Shahar, E., Folsom, A.R., Melnick, S.L., Tockman, M.S., Comstock, G.W., Gennaro, V., Higgins, M.W., Sorlie, P.D., Ko, W.J., Szklo, M. N. Engl. J. Med. (1994) [Pubmed]
  2. Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome. Neptune, E.R., Frischmeyer, P.A., Arking, D.E., Myers, L., Bunton, T.E., Gayraud, B., Ramirez, F., Sakai, L.Y., Dietz, H.C. Nat. Genet. (2003) [Pubmed]
  3. Loss of integrin alpha(v)beta6-mediated TGF-beta activation causes Mmp12-dependent emphysema. Morris, D.G., Huang, X., Kaminski, N., Wang, Y., Shapiro, S.D., Dolganov, G., Glick, A., Sheppard, D. Nature (2003) [Pubmed]
  4. Cephalosporin antibiotics can be modified to inhibit human leukocyte elastase. Doherty, J.B., Ashe, B.M., Argenbright, L.W., Barker, P.L., Bonney, R.J., Chandler, G.O., Dahlgren, M.E., Dorn, C.P., Finke, P.E., Firestone, R.A. Nature (1986) [Pubmed]
  5. alpha 1-antitrypsin deficiency detection by direct analysis of the mutation in the gene. Kidd, V.J., Wallace, R.B., Itakura, K., Woo, S.L. Nature (1983) [Pubmed]
  6. Exercise-induced lactate increase in relation to muscle substrates in patients with chronic obstructive pulmonary disease. Engelen, M.P., Schols, A.M., Does, J.D., Gosker, H.R., Deutz, N.E., Wouters, E.F. Am. J. Respir. Crit. Care Med. (2000) [Pubmed]
  7. Long-term follow-up of a cohort of children with alpha-1-antitrypsin deficiency. Wall, M., Moe, E., Eisenberg, J., Powers, M., Buist, N., Buist, A.S. J. Pediatr. (1990) [Pubmed]
  8. Ecstasy induced retropharyngeal emphysema. Onwudike, M. Journal of accident & emergency medicine. (1996) [Pubmed]
  9. Improvement in pulmonary function and elastic recoil after lung-reduction surgery for diffuse emphysema. Sciurba, F.C., Rogers, R.M., Keenan, R.J., Slivka, W.A., Gorcsan, J., Ferson, P.F., Holbert, J.M., Brown, M.L., Landreneau, R.J. N. Engl. J. Med. (1996) [Pubmed]
  10. Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema. D'Armiento, J., Dalal, S.S., Okada, Y., Berg, R.A., Chada, K. Cell (1992) [Pubmed]
  11. Replacement therapy for alpha 1-antitrypsin deficiency associated with emphysema. Wewers, M.D., Casolaro, M.A., Sellers, S.E., Swayze, S.C., McPhaul, K.M., Wittes, J.T., Crystal, R.G. N. Engl. J. Med. (1987) [Pubmed]
  12. Ceramide upregulation causes pulmonary cell apoptosis and emphysema-like disease in mice. Petrache, I., Natarajan, V., Zhen, L., Medler, T.R., Richter, A.T., Cho, C., Hubbard, W.C., Berdyshev, E.V., Tuder, R.M. Nat. Med. (2005) [Pubmed]
  13. Retinoic acid treatment abrogates elastase-induced pulmonary emphysema in rats. Massaro, G.D., Massaro, D. Nat. Med. (1997) [Pubmed]
  14. Influence of cadmium and other trace metals on human alpha1-antitrypsin: an in vitro study. Chowdhury, P., Louria, D.B. Science (1976) [Pubmed]
  15. Monensin and the prevention of tryptophan-induced acute bovine pulmonary edema and emphysema. Hammond, A.C., Carlson, J.R., Breeze, R.G. Science (1978) [Pubmed]
  16. Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Hautamaki, R.D., Kobayashi, D.K., Senior, R.M., Shapiro, S.D. Science (1997) [Pubmed]
  17. Inhibition of VEGF receptors causes lung cell apoptosis and emphysema. Kasahara, Y., Tuder, R.M., Taraseviciene-Stewart, L., Le Cras, T.D., Abman, S., Hirth, P.K., Waltenberger, J., Voelkel, N.F. J. Clin. Invest. (2000) [Pubmed]
  18. Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke-induced emphysema in mice. Rangasamy, T., Cho, C.Y., Thimmulappa, R.K., Zhen, L., Srisuma, S.S., Kensler, T.W., Yamamoto, M., Petrache, I., Tuder, R.M., Biswal, S. J. Clin. Invest. (2004) [Pubmed]
  19. Evaluation of "at risk" alpha 1-antitrypsin genotype SZ with synthetic oligonucleotide gene probes. Nukiwa, T., Brantly, M., Garver, R., Paul, L., Courtney, M., LeCocq, J.P., Crystal, R.G. J. Clin. Invest. (1986) [Pubmed]
  20. Functional alpha 1-protease inhibitor in the lower respiratory tract of cigarette smokers is not decreased. Stone, P.J., Calore, J.D., McGowan, S.E., Bernardo, J., Snider, G.L., Franzblau, C. Science (1983) [Pubmed]
  21. Elastase release from human alveolar macrophages: comparison between smokers and nonsmokers. Rodriguez, R.J., White, R.R., Senior, R.M., Levine, E.A. Science (1977) [Pubmed]
  22. Limited proteolysis by macrophage elastase inactivates human alpha 1-proteinase inhibitor. Banda, M.J., Clark, E.J., Werb, Z. J. Exp. Med. (1980) [Pubmed]
  23. Elastin fragments drive disease progression in a murine model of emphysema. Houghton, A.M., Quintero, P.A., Perkins, D.L., Kobayashi, D.K., Kelley, D.G., Marconcini, L.A., Mecham, R.P., Senior, R.M., Shapiro, S.D. J. Clin. Invest. (2006) [Pubmed]
  24. New insights into the assembly of extracellular microfibrils from the analysis of the fibrillin 1 mutation in the tight skin mouse. Gayraud, B., Keene, D.R., Sakai, L.Y., Ramirez, F. J. Cell Biol. (2000) [Pubmed]
  25. Interferon gamma induction of pulmonary emphysema in the adult murine lung. Wang, Z., Zheng, T., Zhu, Z., Homer, R.J., Riese, R.J., Chapman, H.A., Shapiro, S.D., Elias, J.A. J. Exp. Med. (2000) [Pubmed]
  26. Role of CCR5 in IFN-gamma-induced and cigarette smoke-induced emphysema. Ma, B., Kang, M.J., Lee, C.G., Chapoval, S., Liu, W., Chen, Q., Coyle, A.J., Lora, J.M., Picarella, D., Homer, R.J., Elias, J.A. J. Clin. Invest. (2005) [Pubmed]
  27. Increased metalloproteinase activity, oxidant production, and emphysema in surfactant protein D gene-inactivated mice. Wert, S.E., Yoshida, M., LeVine, A.M., Ikegami, M., Jones, T., Ross, G.F., Fisher, J.H., Korfhagen, T.R., Whitsett, J.A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  28. A 4-bp deletion in the Birt-Hogg-Dubé gene (FLCN) causes dominantly inherited spontaneous pneumothorax. Painter, J.N., Tapanainen, H., Somer, M., Tukiainen, P., Aittomäki, K. Am. J. Hum. Genet. (2005) [Pubmed]
  29. Biochemical efficacy and safety of monthly augmentation therapy for alpha 1-antitrypsin deficiency. Hubbard, R.C., Sellers, S., Czerski, D., Stephens, L., Crystal, R.G. JAMA (1988) [Pubmed]
  30. Transcription factor Nrf2 plays a pivotal role in protection against elastase-induced pulmonary inflammation and emphysema. Ishii, Y., Itoh, K., Morishima, Y., Kimura, T., Kiwamoto, T., Iizuka, T., Hegab, A.E., Hosoya, T., Nomura, A., Sakamoto, T., Yamamoto, M., Sekizawa, K. J. Immunol. (2005) [Pubmed]
  31. Excessive neutrophil elastase in bronchoalveolar lavage fluid in subclinical emphysema. Yoshioka, A., Betsuyaku, T., Nishimura, M., Miyamoto, K., Kondo, T., Kawakami, Y. Am. J. Respir. Crit. Care Med. (1995) [Pubmed]
  32. Lack of a relationship of elastin peptide level to emphysema assessed by CT scans. Frette, C., Jacob, M.P., Defouilloy, C., Atassi, C., Kauffmann, F., Pham, Q.T., Bignon, J. Am. J. Respir. Crit. Care Med. (1996) [Pubmed]
  33. Human collagenase (matrix metalloproteinase-1) expression in the lungs of patients with emphysema. Imai, K., Dalal, S.S., Chen, E.S., Downey, R., Schulman, L.L., Ginsburg, M., D'Armiento, J. Am. J. Respir. Crit. Care Med. (2001) [Pubmed]
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