Alpha-1 Antitrypsin and Wheezing in Early Childhood: Pilot Study

Background: Alpha-1 antitrypsin (AAT) deficiency is an inherited disorder in which the plasma levels are diminished and affected people carry an increased risk of early onset of chronic obstructive pulmonary disease (COPD). Wheezing in early childhood is associated with acute respiratory infections and certain wheezing phenotypes have clinical features similar to COPD (Kerkhof M, 2014).

Objective and methods: Preschool children who present with an acute episode of wheezing are enrolled, clinically evaluated and blood samples are taken. AAT evaluation includes plasma level assessement by nephelometry, phenotyping by isoelectric focusing and genotyping by real-time polymerase chain reaction. In case of uncertainty, SERPINA1 gene sequencing is performed. Primary endpoint is the association between AAT variants and clinical wheezing phenotypes as defined by the European Respiratory Society (Brand P, 2014).

Results: 28 wheezing children (median age 19.1 months; 13 female) were enrolled in a prospective pilot study. The majority of children (85.8%) had wheezing episodes due to viral respiratory infection. The mean level of AAT was 162.4 mg/dl (range 87-215). Two cases (7.1%) of PiM1M1, one (3.5%) PiMS and one (3.5%) PiMZ were detected. Normal genotype (PiMM) was found in others. The 3-year-old child with PiMS genotype had a wheezing episode with more severe respiratory distress although his AAT levels were normal (140 mg/dl). The 2-year-old child with a PiMZ genotype (AAT level 87 mg/dl) experienced virus-induced wheezing with mild respiratory impairment. Both children had no history of atopy nor second-hand smoke exposure. We found no association between AAT concentration and respiratory distress severity nor with the time of first wheezing episode.

Conclusions: The pilot study has identified three cases of viral induced wheezing with uncommon genetic variants of AAT and normal AAT levels. Further research is needed to better understand the effects of AAT genotype not related to its concentration.