Deficiencia de alfa-1 antitripsina y neumotórax espontáneo. ¿Solo una coincidencia? / Alpha-1 antitrypsin deficiency and spontaneous pneumothorax. Just a coincidence?

Resumen La deficiencia de alfa-1 antitripsina (AAT) es uno de los trastornos hereditarios más frecuentes y con mayor incidencia en pacientes con enfermedad pulmonar obstructiva crónica (EPOC). Se desconoce su prevalencia en aquellos con neumotórax espontáneo. El objetivo fue estimar la prevalencia de deficiencia de AAT en sujetos con neumotórax espontáneo. El estudio fue prospectivo y de corte transversal en pacientes con neumotórax espontáneo primario. Se excluyeron aquellos con neumotórax secundario. Se realizó cuantificación de AAT en suero por nefelometría y posterior genotipificación rápida (PCR en tiempo real) para detectar los alelos de deficiencia más prevalentes (Z y S) en aquellos con concentraciones séricas ≤ 120 mg/dl. Se incluyeron 58 pacientes con neumotórax espontáneo primario. La edad promedio fue de 34 ± 13 años con predominio de sexo masculino (72%) y alta prevalencia de tabaquismo actual y pasado (60%). Del total, el 26% (IC95%: 15-39) presentó concentraciones de AAT ≤ 120mg/dl. Encontramos 7 formas deficitarias (12%; IC 95%: 5-23%). Un paciente presentó una forma grave Pi*ZZ (1.7%), 3 fueron heterocigotos Z (5.2%) y 3 heterocigotos S (5.2%). La prevalencia de variantes deficitarias de AAT fue alta en este grupo con neumotórax espontáneo.

Abstract Alpha-1 antitrypsin (AAT) deficiency is one of the most common inherited disorders with a higher incidence in patients with chronic obstructive pulmonary disease (COPD). Its prevalence in patients with spontaneous pneumothorax is unknown. The objective was to estimate the prevalence of AAT deficiency in patients with spontaneous pneumothorax. This was a prospective cross-sectional study, in patients with spontaneous pneumothorax, where those with secondary pneumothorax were excluded. Quantification of serum AAT by nephelometry and subsequent rapid genotyping (real time PCR) was performed, in order to detect the most prevalent deficiency alleles (Z and S) in those subjects with serum AAT concentrations ≤ 120 mg/dl. Fifty-eight patients with primary spontaneous pneumothorax were included. The average age was 34 ± 13 years with male predominance (72%) and high prevalence of current and past smoking (60%). Twenty six percent of them (95% CI: 15-39) presented AAT serum concentrations ≤ 120mg/dl. We found 7 deficiency variants (12%; IC 95%: 5-23%). One patient presented a severe Pi*ZZ form (1.7%), 3 were heterozygotes Z (5.2%) and 3 heterozygotes S (5.2%). The prevalence of AAT deficient variants was high in patients with spontaneous pneumothorax.

Prevalence of alpha-1 antitrypsin deficiency and allele frequency in patients with COPD in Brazil / Prevalência da deficiência de alfa-1 antitripsina e frequência alélica em pacientes com DPOC no Brasil

ABSTRACT Objective: To determine the prevalence of alpha 1-antitrypsin (AAT) deficiency (AATD), as well as allele frequency, in COPD patients in Brazil. Methods: This was a cross-sectional study involving 926 COPD patients 40 years of age or older, from five Brazilian states. All patients underwent determination of AAT levels in dried blood spot (DBS) samples by nephelometry. Those with DBS AAT levels ≤ 2.64 mg/dL underwent determination of serum AAT levels. Those with serum AAT levels of < 113 mg/dL underwent genotyping. In case of conflicting results, SERPINA1 gene sequencing was performed. Results: Of the 926 COPD patients studied, 85 had DBS AAT levels ≤ 2.64 mg/dL, and 24 (2.6% of the study sample) had serum AAT levels of < 113 mg/dL. Genotype distribution 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 and reinforces the recommendation that AAT levels be measured in all COPD patients.

RESUMO Objetivo: Determinar a prevalência da deficiência de alfa 1-antitripsina (AAT), bem como a frequência alélica, em pacientes com DPOC no Brasil. Métodos: Estudo transversal com 926 pacientes com DPOC, com 40 anos ou mais, oriundos de cinco estados brasileiros. Todos os pacientes foram submetidos a dosagem de AAT em amostras de sangue seco por meio de nefelometria. Aqueles em que a concentração de AAT no sangue seco foi ≤ 2,64 mg/dl foram submetidos a dosagem sérica de AAT. Aqueles em que a concentração sérica de AAT foi < 113 mg/dl foram submetidos a genotipagem. Quando os resultados foram discrepantes, foi realizado o sequenciamento do gene SERPINA1. Dos 926 pacientes com DPOC estudados, 85 apresentaram concentração de AAT em sangue seco ≤ 2,64 mg/dl, e 24 (2,6% da amostra) apresentaram concentração sérica de AAT < 113 mg/dl. A distribuição genotípica nesse subgrupo de 24 pacientes foi a seguinte: PI*MS, em 3 (12,5%); PI*MZ, em 13 (54,2%); PI*SZ, em 1 (4,2%); PI*SS, em 1 (4,2%); e PI*ZZ, em 6 (25,0%). Na amostra estudada, a prevalência global da deficiência de AAT foi de 2,8% e a prevalência do genótipo PI*ZZ (deficiência grave de AAT) foi de 0,8%. Conclusões: A prevalência da deficiência de AAT em pacientes com DPOC no Brasil é semelhante àquela encontrada na maioria dos países e reforça a recomendação de que se deve medir a concentração de AAT em todos pacientes com DPOC.

[ prevalence of the alpha-1 antitrypsin deficiency in patients with chronic obstructive pulmonary disease]

Alpha 1-antitrypsin deficiency [AATD] is one of the genetic risk factors in the patients suffering from chronic obstructive pulmonary disease [COPD]. The exact number of Iranians suffering from this disease is yet not known. Therefore, the aim of this study was to determine the prevalence of the deficiency of AAT enzyme in patients suffering from COPD. The topical test of AAT serum was conducted on 125 patients affected by COPD who had referred to Ekbatan Hospital of Hamadan in 2007. The diagnoses of COPD in these patients dad been confirmed through history and spirometerty test before and after bronchodilator inhalation and the outcomes had been confirmed based on GOLD regulations. In other words, after separation of serum from blood, the specific antibody of AAT was added to the sample. The AAT serum level was read according to nephelometry measurement and the results were given in g/L. The gathered data were then analyzed using SPSS software program and statistical tests such as T-test and chi[2] [p<0.05]. Out of 125 patients, 91 were male and 34 patients were female [2.7/1]. The mean age was 63 +/- 12 years and the mean AAT serum in the patients was between 0.710g/L and 2.696g/L [mean 1.311 +/- 0.364g/L]. Almost all of the male patients had history of smoking [91%] and this smoking and its dose [Pack/Year] were significantly related to the severity of COPD. There was no significant relation between plasma levels of AAT and smoking, age or sex. The average age of patients suffering from COPD in rational AAT deficiency was significantly lower. However, the severity of symptoms had no significant difference between patients with normal levels of AAT. Based on the findings of this study, no case of exact deficiency of AAT was found in patients suffering from COPD admitted to Ekbatan Hospital of Hamadan. Regarding geographical location and number of the samples, the possibility of prevalence of this disease in Hamadan is much lower than that of European countries. However, the relative deficiency of AAT [20% in this study] was higher than the amounts obtained from similar studies in European countries