Alpha-1-Antitrypsin Deficiency and Its Association with Atopy in Asthmatics
Literature mentions the coincidence of asthma and alpha-1-antitrypsin deficiency, which is caused by a mutation in the SERPINA1 gene. The aim of the study presented below was to determine whether the clinical symptoms of asthma differ between patients with and without this mutation.
Clinical manifestations of AAT deficiency
The deficiency of the serine protease inhibitor alpha-1-antitrypsin (AAT) is caused by a mutation in the SERPINA1 gene located on the long arm of chromosome 14. In our population, the most common alleles are M (normal), S (moderate serum AAT levels), and Z (severe deficiency).
AAT inhibits airway inflammation caused by neutrophil elastase. Its deficiency could thus predispose to the development of airway hyperreactivity. Although the etiology of asthma and AAT deficiency is different, initial symptoms may be similar, and the patient is often treated for asthma.
Methodology and course of the study
Based on AAT serum concentration determination, a total of 58 adults (53% women, average age 56.7 years) treated for mild to moderate asthma at an outpatient clinic were included in a study conducted at an Italian university hospital in Parma from September 2018 to December 2019. Patients with other lung diseases were not included in the study. All underwent mutation analysis of the SERPINA1 gene to determine the genotype. The precondition for this analysis was a serum AAT concentration ≤ 113 mg/dl or > 133 mg/dl + clinical symptoms and/or family history related to AAT deficiency. The study population was then divided into two groups according to the detected genotype: 36 patients without AAT deficiency (genotype MM) and 22 with AAT deficiency.
To assess asthma symptoms and control, the Asthma Control Test was used. All patients were also asked about smoking history. Atopy was determined using skin prick tests with common inhaled allergens, allergic reactions (rhinoconjunctivitis), and total serum IgE concentration. Specific IgE levels were measured in patients chronically using antihistamines. In the context of blood count and differential examination, the number of eosinophils was determined. Spirometric lung function tests were then performed to measure FEV1 (forced expiratory volume in 1 second), FVC (forced vital capacity), and FEV1/FVC, along with a methacholine bronchoprovocation test to determine bronchial hyperreactivity and measurement of exhaled nitric oxide (FENO).
Results
13 out of 58 patients (22%) were former smokers. The average serum AAT concentration was 108.5 mg/dl, with 16 patients (73%) having levels ranging from 50−100 mg/dl. No patients had a severe AAT deficiency (< 50 mg/dl).
The severity of asthma did not significantly differ between patients with and without AAT deficiency. Functional lung tests showed mild obstruction with FEV1 ranging from 57 to 134%. Among the 22 patients with AAT deficiency, the genotype distribution was: 11 patients with PI*MS, 9 with PI*MZ, 1 with PI*MMMalton, and 1 with PI*SS. There were no noticeable clinical differences between patients with PI*MS and PI*MZ genotypes, with the only difference being the average serum AAT concentration.
The only difference between the groups was the presence of atopy (positive prick test and/or specific IgE concentration in the range of 3.50–17.49 kU/l for at least one allergen), which was observed in 43 patients (74%). It was higher in patients with AATD (90.9 vs. 63.9%; p = 0.031). These patients also showed a higher incidence of allergic symptoms (77.3 vs. 47.2%; p = 0.030), and most exhibited skin hypersensitivity more to common inhaled seasonal than year-round allergens (70 vs. 30%).
Conclusion
A significantly higher incidence of atopy and allergic symptoms was observed in asthmatics with AAT deficiency compared to patients without the SERPINA1 gene mutation. In the context of AAT deficiency screening, specialists should pay more attention to asthma symptoms.
However, the study is limited by the absence of a control group of patients with atopy without asthma diagnosis. To verify the results, a future multicenter study with a larger number of subjects will be necessary.
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Source: Aiello M., Frizzelli A., Pisi R. et al. Alpha-1 antitrypsin deficiency is significantly associated with atopy in asthmatic patients. J Asthma 2020 Oct 19: 1–8, doi: 10.1080/02770903.2020.1827421 [Epub ahead of print].
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