# Prevalence of Alpha-1 Antitrypsin Deficiency Alleles in a Lithuanian Cohort of Wheezing Small Children

## TL;DR

The study finds that certain genetic variants linked to a lung disease in adults are more common in young children with wheezing, suggesting a possible early genetic link to future lung issues.

## Contribution

The study reports a novel comparison of AATD allele frequencies in wheezing children to those in adults with COPD and the general population.

## Key findings

- The frequency of Pi*Z alleles in wheezing children is significantly higher than in the general population and similar to adult COPD patients.
- No association was found between AAT genotypes and the severity of wheezing in children.
- The findings suggest a potential genetic predisposition linking early childhood wheezing to COPD in adulthood.

## Abstract

What are the main findings?
Alpha-1 antitrypsin phenotypes are linked to both chronic obstructive pulmonary disease in adults and wheezing syndrome in preschool children.The frequency of Z* and S* alleles in a cohort of wheezing preschool children is higher than in the general population and similar to that in adults with chronic obstructive pulmonary disease.

Alpha-1 antitrypsin phenotypes are linked to both chronic obstructive pulmonary disease in adults and wheezing syndrome in preschool children.

The frequency of Z* and S* alleles in a cohort of wheezing preschool children is higher than in the general population and similar to that in adults with chronic obstructive pulmonary disease.

What is the implication of the main finding?
Our data open the way for further research on the role of both homozygous and heterozygous variants of alpha-1 antitrypsin in the development of preschool wheezing.Stratification of the heterogeneous syndrome of preschool wheezing allows us to search for chronic obstructive pulmonary disease-related wheezing phenotype/endotype and start the disease-specific prophylactic in early childhood.

Our data open the way for further research on the role of both homozygous and heterozygous variants of alpha-1 antitrypsin in the development of preschool wheezing.

Stratification of the heterogeneous syndrome of preschool wheezing allows us to search for chronic obstructive pulmonary disease-related wheezing phenotype/endotype and start the disease-specific prophylactic in early childhood.

Severe inherited alpha-1 antitrypsin deficiency (AATD) is an autosomal genetic condition linked to chronic obstructive pulmonary disease (COPD). The significance of heterozygous, milder deficiency variants (PiSZ, PiMZ, PiMS) is less clear. We studied AATD genotypes in 145 children (up to 72 months old) with assessed wheezing severity using the Pediatric Respiratory Assessment Measure (BCCH PRAM score). A control group of 74 children without airway obstruction was included. AAT concentration and Pi phenotype were determined from dry blood spot samples using nephelometry and real-time PCR; PiS and PiZ alleles were identified by isoelectrofocusing. Among the wheezers, the Pi*S allele incidence was 2.07% (3 cases) and the Pi*Z allele was 6.9% (10 cases). The Pi*Z allele frequency was higher in wheezers compared to controls (44.8% vs. 20.27%) and the general Lithuanian population (44.8% vs. 13.6%) and was similar to adult COPD patients in Lithuania: Pi*S 10.3% vs. 15.8% and Pi*Z 44.8% vs. 46.1%. No association was found between AAT genotypes and wheezing severity. Finding that wheezer children exhibit a frequency of Z* and S* alleles like that found in adults with COPD suggests a potential genetic predisposition that links early wheezing in children to the development of COPD in adulthood. Larger cohort studies are needed to confirm this finding.