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

Abstract

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.

Comparison of COVID-19 outcomes with alpha-1-antitrypsin deficiency prevalence: A cross-sectional study.

“…It provides approximately 90% of the protection against elastolytic activity caused by elastase released from neutrophils in the lower respiratory tract. 5,14,15 Very few people infected with the SARS-CoV-2 virus develop respiratory failure that requires mechanical ventilation. This clinical situation associated with high mortality shows a wide geographic variation.…”

Subdiagnóstico: Uma limitação ao seguimento de deficiência de alfa 1 antitripsina no paciente com DPOC

“…3 Os critérios para a suspeição e investigação de A1ATD incluem: início precoce do enfisema (menos de 45 anos); enfisema em não fumantes; enfisema desproporcional à carga tabágica; enfisema em pacientes com casos de A1ATD na família; bronquiectasia de causa desconhecida; adolescentes com um padrão obstrutivo persistente e/ou adolescentes com vasculite positiva para anticorpos citoplasmáticos antineutrófilos citoplasmáticos. 1,8,9 O paciente analisado em questão, tinha diag-nóstico estabelecido para DPOC desde os 33 anos de idade, com sintomatologia grave e TC com achados de enfisema predominante em bases pulmonares. Apesar disso, não havia sido realizada uma triagem para a detecção de A1ATD, ocasionando em situação de subdiagnóstico durante 30 anos.…”

Update on and future perspectives for the diagnosis of alpha-1 antitrypsin deficiency in Brazil

“…(9) Três estudos realizados no Brasil constataram que a triagem sistemática da DAAT em pacientes com DPOC aumentou as chances de identificação de pacientes com mutações no gene SERPINA1. (16,39,40)…”

“… 9 Three studies undertaken in Brazil found that systematic screening for AATD in COPD patients increased the chances of identifying patients with mutations in the SERPINA1 gene. 16 , 39 , 40 …”