Não há cura para a doença, mas muitos indivíduos, especialmente não fumantes, têm expectativas de vida normais.[5]American Thoracic Society/European Respiratory Society Statement. Standards for the diagnosis and management of individuals with alpha 1-antitrypsin deficiency. Am J Respir Crit Care Med. 2003 Oct 1;168(7):818-900.
https://www.atsjournals.org/doi/full/10.1164/rccm.168.7.818
http://www.ncbi.nlm.nih.gov/pubmed/14522813?tool=bestpractice.com
[57]Seersholm N, Kok-Jensen A, Dirksen A. Survival of patients with severe alpha-1 antitrypsin deficiency with special reference to non-index cases. Thorax. 1994;49:695-698.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC475060/pdf/thorax00299-0073.pdf
http://www.ncbi.nlm.nih.gov/pubmed/8066566?tool=bestpractice.com
Doença pulmonar
Entre 50% e 72% das mortes relacionadas com a deficiência de alfa 1-antitripsina (AAT) são causadas por insuficiência respiratória, o que inclui um maior percentual de mortes em comparação à insuficiência hepática.[23]Larsson C. Natural history and life expectancy in severe alpha 1-antitrypsin deficiency, Pi Z. Acta Med Scand. 1978;204:345-351.
http://www.ncbi.nlm.nih.gov/pubmed/309708?tool=bestpractice.com
[61]Alpha-1-Antitrypsin Deficiency Registry Study Group. Survival and FEV1 decline in individuals with severe deficiency of alpha 1-antitrypsin. Am J Respir Crit Care Med. 1998;158:49-59.
http://www.ncbi.nlm.nih.gov/pubmed/9655706?tool=bestpractice.com
[97]Dawkins PA, Dowson LJ, Guest PJ, et al. Predictors of mortality in alpha 1-antitrypsin deficiency. Thorax. 2003;58:1020-1026.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1746543/pdf/v058p01020.pdf
http://www.ncbi.nlm.nih.gov/pubmed/14645964?tool=bestpractice.com
Evidências sugerem que a idade mediana de morte na deficiência de AAT seja de 40 anos para fumantes e de 65 anos para não fumantes, em função de enfisema de início precoce e doença pulmonar progressiva.[23]Larsson C. Natural history and life expectancy in severe alpha 1-antitrypsin deficiency, Pi Z. Acta Med Scand. 1978;204:345-351.
http://www.ncbi.nlm.nih.gov/pubmed/309708?tool=bestpractice.com
O volume expiratório forçado no primeiro segundo (VEF1) deve ser usado como preditor da sobrevida nesses pacientes, pois estabeleceu-se uma correlação entre a mortalidade a 2 anos e o VEF1 >35%.[98]Seersholm N, Dirksen A, Kok-Jensen A. Airways obstruction and two-year survival in patients with severe alpha-1 antitrypsin deficiency. Eur Respir J. 1994;7:1985-1987.
http://www.ncbi.nlm.nih.gov/pubmed/7875269?tool=bestpractice.com
As taxas de declínio no VEF1 vão de 47 a 80 mL/ano em pessoas que nunca fumaram, de 41 a 81 mL/ano em ex-fumantes e de 61 a 316 mL/ano em fumantes.[45]Janus ED, Phillips NT, Carrell RW. Smoking, lung function, and alpha-1-antitrypsin deficiency. Lancet. 1985;1:152-4.
http://www.ncbi.nlm.nih.gov/pubmed/2857224?tool=bestpractice.com
[46]Wu MC, Eriksson S. Lung function, smoking and survival in severe alpha 1-antitrypsin deficiency, PiZZ. J Clin Epidemiol. 1988;41:1157-1165.
http://www.ncbi.nlm.nih.gov/pubmed/3264848?tool=bestpractice.com
[47]Piitulainen E, Eriksson S. Decline in FEV1 related to smoking status in individuals with severe alpha-1 antitrypsin deficiency (PiZZ). Eur Respir J. 1999;13:247-251.
http://erj.ersjournals.com/cgi/reprint/13/2/247
http://www.ncbi.nlm.nih.gov/pubmed/10065663?tool=bestpractice.com
A terapia de aumento de AAT é eficaz em retardar as evidências radiográficas de doença pulmonar, e também contribui para a diminuição da mortalidade.[60]Dirksen A, Dijkman JH, Madsen F, et al. A randomized clinical trial of alpha 1-antitrypsin augmentation therapy. Am J Respir Crit Care Med. 1999;160:1468-1472.
http://www.ncbi.nlm.nih.gov/pubmed/10556107?tool=bestpractice.com
[61]Alpha-1-Antitrypsin Deficiency Registry Study Group. Survival and FEV1 decline in individuals with severe deficiency of alpha 1-antitrypsin. Am J Respir Crit Care Med. 1998;158:49-59.
http://www.ncbi.nlm.nih.gov/pubmed/9655706?tool=bestpractice.com
A taxa de sobrevida em 5 anos após transplante de pulmão é de aproximadamente 50%.[79]Hosenpud JD, Novick RJ, Breen TJ, et al. The registry of the International Society for Heart and Lung Transplanation: twelfth official report. J Heart Lung Transplant. 1995;14:805-815.
http://www.ncbi.nlm.nih.gov/pubmed/8800714?tool=bestpractice.com
[80]Levine SM, Anzueto A, Peters JI, et al. Medium term functional results of single-lung transplantation for end stage obstructive lung disease. Am J Respir Crit Care Med. 1994;150:398-402.
http://www.ncbi.nlm.nih.gov/pubmed/8049821?tool=bestpractice.com
[81]Christie JD, Edwards LB, Kucheryavaya AY, et al. The registry of the International Society for Heart and Lung Transplantation: twenty-eighth adult lung and heart-lung transplant report - 2011. J Heart Lung Transplant. 2011;30:1104-1122.
http://www.jhltonline.org/article/S1053-2498%2811%2901089-8/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/21962018?tool=bestpractice.com
A sobrevida mediana é de 6.3 anos.[81]Christie JD, Edwards LB, Kucheryavaya AY, et al. The registry of the International Society for Heart and Lung Transplantation: twenty-eighth adult lung and heart-lung transplant report - 2011. J Heart Lung Transplant. 2011;30:1104-1122.
http://www.jhltonline.org/article/S1053-2498%2811%2901089-8/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/21962018?tool=bestpractice.com
Doença hepática
Pacientes que têm o fenótipo PI*ZZ e não manifestam sintomas pulmonares têm maior probabilidade de ter cirrose e, por fim, insuficiência hepática.[26]Eriksson S. Alpha 1-antitrypsin deficiency: natural course and therapeutic strategies. In: Boyer J, Blum HE, Maier KP, et al, eds. Cirrhosis and its development. Falk Symposium 115. Dordrecht, Netherlands: Kluwer Academic; 2000:307-315.
A fibrose hepática foi detectada em 20% a 36% dos adultos assintomáticos com deficiência de AAT de PI*ZZ, enquanto a prevalência relatada de cirrose varia de 2% a 43%.[5]American Thoracic Society/European Respiratory Society Statement. Standards for the diagnosis and management of individuals with alpha 1-antitrypsin deficiency. Am J Respir Crit Care Med. 2003 Oct 1;168(7):818-900.
https://www.atsjournals.org/doi/full/10.1164/rccm.168.7.818
http://www.ncbi.nlm.nih.gov/pubmed/14522813?tool=bestpractice.com
[27]Hamesch K, Mandorfer M, Pereira VM, et al. Liver Fibrosis and Metabolic Alterations in Adults With alpha-1-antitrypsin Deficiency Caused by the Pi*ZZ Mutation. Gastroenterology. 2019 Sep;157(3):705-719.e18.
https://www.doi.org/10.1053/j.gastro.2019.05.013
http://www.ncbi.nlm.nih.gov/pubmed/31121167?tool=bestpractice.com
[28]Clark VC, Marek G, Liu C, et al. Clinical and histologic features of adults with alpha-1 antitrypsin deficiency in a non-cirrhotic cohort. J Hepatol. 2018 Dec;69(6):1357-1364.
https://www.doi.org/10.1016/j.jhep.2018.08.005
http://www.ncbi.nlm.nih.gov/pubmed/30138687?tool=bestpractice.com
A prevalência de cirrose é maior entre idosos com PI*ZZ que nunca fumaram; um terço dos pacientes com idade avançada e com um fenótipo homozigoto morrerá de complicações relacionadas à hipertensão portal e a câncer hepático primário.[5]American Thoracic Society/European Respiratory Society Statement. Standards for the diagnosis and management of individuals with alpha 1-antitrypsin deficiency. Am J Respir Crit Care Med. 2003 Oct 1;168(7):818-900.
https://www.atsjournals.org/doi/full/10.1164/rccm.168.7.818
http://www.ncbi.nlm.nih.gov/pubmed/14522813?tool=bestpractice.com