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Protease inhibitor variants in children and young adults with chronic asthma
Insights
Children with chronic asthma and alpha-1-antitrypsin (AAT) Pi variants showed reduced bronchodilator responsiveness. Consider AAT Pi testing for young asthma patients unresponsive to treatment.
Area of Science:
- Pulmonology
- Genetics
Background:
- Alpha-1-antitrypsin (AAT) deficiency is a genetic condition that can increase the risk of lung disease.
- Chronic asthma affects many children and young adults, with varying responses to treatment.
Purpose of the Study:
- To investigate the association between alpha-1-antitrypsin (AAT) phenotypes and clinical characteristics in young asthma patients.
- To determine if AAT Pi variants influence asthma severity and treatment response.
Main Methods:
- Systematic medical histories and pulmonary function tests were conducted on 26 children and young adults with chronic asthma.
- Subjects were categorized into two groups: 10 with Pi variant AAT phenotypes and 16 with normal Pi phenotypes.
- Incidence of AAT Pi variants was assessed in a larger cohort of Caucasian subjects.
Main Results:
- The incidence of AAT Pi variants was 20.4% in Caucasian subjects aged 7-21 years with chronic asthma.
- Patients with Pi variant phenotypes required more bronchodilators and long-term corticosteroids.
- The Pi variant group showed significantly less responsiveness to bronchodilator inhalation compared to the Pi normal group.
- A higher incidence of chronic obstructive lung disease was observed in parents, siblings, and grandparents of Pi abnormal probands.
Conclusions:
- The Pi heterozygous state, particularly Pi MZ, should be considered in young asthma patients unresponsive to bronchodilators and requiring prolonged corticosteroid therapy.
- AAT Pi variant testing may aid in identifying individuals with potentially more severe or treatment-resistant asthma.
Abstract:
The results of systematic medical histories and pulmonary function tests on 26 children and young adults, 10 with Pi variant alpha1-antitrypsin phenotypes and 16 Pi normals, are reported. These subjects were selected from 57 consecutive patients who had chronic asthma. The incidence of Pi variants was 20.4% among 46 Caucasian subjects (ages seven to 21 years). The Pi variant patients required more bronchodilators and long-term corticosteroid therapy. Among the parents and siblings, 50% of those with abnormal Pi type had chronic obstructive lung disease. Grandparents of the Pi abnormal probands had greater incidence of chronic obstructive lung disease (P less than 0.05). Baseline specific airways conductance and maximal midexpiratory flow rates did not discriminat between the two groups. However, bronchodilator inhalation showed the Pi variant group to be significantly less responsive than the Pi normal group. Pi heterozygous state, particularly Pi MZ, should be considered when a young person with chronic asthma is unresponsive to adequate doses of bronchodilators and needs prolonged use of corticosteroids.