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. 2018 Sep-Oct;44(5):383-389.
doi: 10.1590/S1806-37562017000000420.

The patient profile of individuals with Alpha-1 antitrypsine gene mutations at a referral center in Brazil

[Article in English, Portuguese]
Manuela Brisot Felisbino  1 , Frederico Leon Arrabal Fernandes  2 , Maria Cecília Nieves Maiorano de Nucci  2 , Regina Maria de Carvalho Pinto  2 , Emilio Pizzichini  1 , Alberto Cukier  2
Affiliations

The patient profile of individuals with Alpha-1 antitrypsine gene mutations at a referral center in Brazil

[Article in English, Portuguese]
Manuela Brisot Felisbino et al. J Bras Pneumol. 2018 Sep-Oct.

Abstract
in English, Portuguese

Objective: The clinical, functional, radiological and genotypic descriptions of patients with an alpha-1 antitrypsin (A1AT) gene mutation in a referral center for COPD in Brazil.

Methods: A cross-sectional study of patients with an A1AT gene mutation compatible with deficiency. We evaluated the A1AT dosage and genotypic, demographic, clinical, tomographic, and functional characteristics of these patients.

Results: Among the 43 patients suspected of A1AT deficiency (A1ATD), the disease was confirmed by genotyping in 27 of them. The A1AT median dosage was 45 mg/dL, and 4 patients (15%) had a normal dosage. Median age was 54, 63% of the patients were male, and the respiratory symptoms started at the age of 40. The median FEV1 was 1.37L (43% predicted). Tomographic emphysema was found in 77.8% of the individuals. The emphysema was panlobular in 76% of them and 48% had lower lobe predominance. The frequency of bronchiectasis was 52% and the frequency of bronchial thickening was 81.5%. The most common genotype was Pi*ZZ in 40.7% of participants. The other genotypes found were: Pi*SZ (18.5%), PiM1Z (14.8%), Pi*M1S (7.4%), Pi*M2Z (3.7%), Pi*M1I (3.7%), Pi*ZMnichinan (3.7%), Pi*M3Plowell (3.7%), and Pi*SF (3.7%). We did not find any significant difference in age, smoking load, FEV1, or the presence of bronchiectasis between the groups with a normal and a reduced A1AT dosage, neither for 1 nor 2-allele mutation for A1ATD.

Conclusions: Our patients presented a high frequency of emphysema, bronchiectasis and bronchial thickening, and early-beginning respiratory symptoms. The most frequent genotype was Pi*ZZ. Heterozygous genotypes and normal levels of A1AT also manifested significant lung disease.

Objetivo:: Caracterização clínica, funcional, radiológica e genotípica dos pacientes portadores de mutações do gene da alfa-1 antitripsina (A1AT) em um centro de referência em doença pulmonar obstrutiva crônica (DPOC) no Brasil.

Métodos:: Estudo transversal de pacientes com mutação no gene da A1AT compatível com deficiência. Foram avaliadas características genotípicas, demográficas, clínicas, tomográficas, de função pulmonar, e dosagem de A1AT.

Resultados:: De 43 pacientes suspeitos para deficiência de alfa-1 antitripsina (DA1AT), a doença foi confirmada por genotipagem em 27. A mediana da dosagem de A1AT foi de 45 mg/dL, e 4 pacientes (15%) apresentavam dosagens normais. A idade mediana foi de 54 anos, 63% dos participantes eram do sexo masculino e a idade do início dos sintomas prevalente foi aos 40 anos. A mediana do volume expiratório forçado no primeiro segundo (VEF1) foi de 1,37 L (43% do previsto). Enfisema tomográfico foi encontrado em 77,8% dos indivíduos, sendo panlobular em 76% e de predomínio em lobos inferiores em 48%. A frequência de bronquiectasias foi de 52%, e a de espessamento brônquico, de 81,5%. O genótipo mais encontrado foi Pi*ZZ (40,7%). Os demais genótipos foram: Pi*SZ (18,5%), Pi*M1Z (14,8%), Pi*M1S (7,4%), Pi*M2Z (3,7%), Pi*M1I (3,7%), Pi*ZMnichinan (3,7%), Pi*M3Plowell (3,7%) e Pi*SF (3,7%). Não encontramos diferença significativa para idade, carga tabágica, VEF1 e presença de bronquiectasias entre os grupos com dosagem de A1AT normal versus alterada, nem entre 1 alelo versus 2 alelos com mutação para DA1AT.

Conclusões:: Nossos pacientes apresentaram alta frequência de enfisema, bronquiectasias e espessamento brônquico, com início precoce dos sintomas respiratórios. O genótipo mais frequente foi Pi*ZZ, embora genótipos heterozigotos e níveis normais de A1AT também tenham se manifestado com doença pulmonar significativa.

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Figures

Figure 1
Figure 1. Flowchart of the patients included in the study.
See this image and copyright information in PMC

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