Objective: To determine the prevalence of alpha 1-antitrypsin (AAT) deficiency (AATD)
April 1, 2017
Objective: To determine the prevalence of alpha 1-antitrypsin (AAT) deficiency (AATD) as well as allele frequency in COPD patients in Brazil. in this subset of 24 patients was as follows: PI*MS in 3 (12.5%); PI*MZ in 13 (54.2%); PI*SZ in 1 (4.2%); PI*SS in 1 (4.2%); and PI*ZZ in 6 (25.0%). In the sample as a whole the overall prevalence of AATD was 2.8% and the prevalence of the PI*ZZ genotype (severe AATD) was 0.8% Conclusions: The prevalence of AATD in COPD patients in Brazil is similar to that found in most countries ABT-492 and reinforces the recommendation that AAT levels be measured in all COPD patients. gene located on the long arm of chromosome 14 (14q32.1) and inhibits neutrophil elastase trypsin and protease-3. 3 5 6 Although smoking is usually a major cause of airflow obstruction it is estimated that only 15-30% of smokers develop COPD. 7 – 9 Despite the clear association between smoking and COPD the effects of smoking vary across individuals. 10 Studies have shown that AATD can increase the impact of smoking around the lungs resulting in an increased rate of decline in lung function and early emphysema in smokers. Mutant ABT-492 S and Z alleles are the most commonly involved in severe AATD. 11 12 The fact that this Brazilian populace is usually racially diverse and includes immigrants from European countries where the frequency of alleles involved in early lung changes is usually ABT-492 high suggests that AATD is usually underdiagnosed in the country. Despite the estimated 5-7 million COPD patients in Brazil 13 the prevalence of AATD in this populace remains unknown as does allele frequency. Therefore the objective of the present study was to assess the prevalence of AATD as well as allele frequency in COPD patients from five Brazilian says. METHODS Study design The present study was approved by the Research Ethics Committee of the Federal University of S?o Paulo (Protocol no. 0633/10) located in the city of S?o Paulo Brazil as well as by the research ethics committees of all participating centers. Between July of 2011 and August of 2012 1 73 COPD patients followed at any of the six participating centers (two in northeastern Brazil two in southeastern Brazil one in southern Brazil and one in central-western Brazil) were evaluated. Patients The inclusion criteria were as follows: being 40 years of age or older; having been diagnosed with COPD (on the basis of clinical ABT-492 history and spirometry results including a post-bronchodilator percent predicted FEV1/FVC ratio-FEV1/FVC%-below the lower limit of normal); and having been stable for at least four weeks. 14 The exclusion criteria were as follows: having been diagnosed with any other lung disease or systemic disease that can increase serum AAT levels (including infections and inflammatory processes); having previously been diagnosed with AATD; being a relative of an index ABT-492 case of AATD; and having asthma (Physique 1). Physique 1 Flowchart of the patients included in the study and their distribution by participating center. UNIFESP: Universidade Federal de S?o Paulo ; HSPE-SP: Hospital do Servidor Público Estadual de S?o Paulo ; HGG: Hospital Geral de … The goal was to include 200 COPD patients from each participating center. At the end of the study period no more patients were added to the study regardless of whether or not the desired number of patients had been achieved for each center. Spirometry The reference values for calculating percent predicted FVC percent SIRT1 predicted FEV1 and FEV1/FVC% were based on the National Health and Nutrition Examination Survey equations. 15 Spirometry was performed with a portable spirometer (Easy One(r); ndd Medical Technologies Inc. Andover MA USA). At all participating centers the American Thoracic Society acceptability and reproducibility criteria were used. 16 Quantification of AAT The study was divided into three phases. In the first phase all patients underwent determination of AAT levels in dried blood spot (DBS) samples in order to identify those with a possible diagnosis of AATD. In the second phase patients with DBS AAT levels ≤ 2.64 mg/dL (suspected AATD) ABT-492 underwent determination of serum AAT levels. 17 Finally in the third phase patients with serum AAT levels of < 113 mg/dL underwent genotyping. In case of conflicting results between serum AAT measurements and genotyping genetic sequencing was performed (Physique 2). To determine the sensitivity and specificity of the.