Deficit Alpha-1-Antitrypsin as an Underestimated Problem? What a Survey Among European Experts Revealed
Alpha-1-antitrypsin deficiency (AATD) is a congenital disorder caused by mutations in the SERPINA1 gene. Although it is very well described, it is considered underdiagnosed and undertreated. A recent international survey conducted among specialists on this issue aimed to determine the current situation in Europe.
Introduction
Alpha-1-antitrypsin (AAT) is a protein produced in the liver that functions as a protease inhibitor in the body. In the event of its deficiency, timely inactivation of various enzymes, including neutrophil elastase in lung tissue, does not occur, which can lead to lung tissue degradation resulting in the development of emphysema. Accumulation of dysfunctional AAT in hepatocytes can lead to cholestatic liver disease in some patients.
AATD often remains undiagnosed. Treatment may be symptomatic in milder cases, but for genotypes leading to severe forms of the disease (PI*ZZ and PI*SZ), causal treatment in the form of purified human AAT administration is indicated, which can not only improve symptoms but also slow the progression of the disease.
Survey Among Experts
The authors of the presented study aimed to determine the extent to which AATD is correctly diagnosed in Europe and the availability of treatment. Physicians involved in AATD diagnosis and treatment across Europe were invited to complete an online questionnaire consisting of 58 questions related to the population size of their respective countries, AATD diagnosis, and especially the treatment options available in their country. Fifteen doctors from 14 centers in 13 European countries (Belgium, Czech Republic, France, Ireland, Italy, Hungary, Germany, the Netherlands, Poland, Portugal, Austria, Spain, and the United Kingdom) completed the surveys.
Results
All respondents considered the diagnosed case rate in their country to be low. A total of 77% of survey participants estimated that AATD is diagnosed in only about 15% of cases in their country. The main reason cited was the low awareness among treating physicians.
Diagnosis determination also takes longer than five years from the onset of the first symptoms in most countries. While screening for this condition is available in some countries, comprehensive screening does not seem cost-effective to the surveyed experts. Instead, targeted screening in populations affected by certain lung diseases (emphysema, bronchiectasis, newly diagnosed chronic obstructive pulmonary disease) and other, non-respiratory diseases (liver diseases, panniculitis) was deemed more appropriate. Screening within the patient’s family (especially siblings) should be standard practice.
The questionnaire also covered the best modalities for monitoring disease progression from a clinical perspective. Most respondents preferred spirometry over quantitative computed tomography (qCT) for clinical practice; qCT was considered more suitable for monitoring participants in clinical studies. Monitoring patients' quality of life should also be a key indicator.
Symptomatic treatment of AATD patients in most countries included bronchodilators and inhaled corticosteroids. The availability of causal treatment varied widely in the surveys – patients were most frequently causally treated in France and Germany (roughly 60% of diagnosed cases), while virtually no patients were causally treated in the United Kingdom and Hungary. Most physicians suggested initiating treatment in patients with moderate disease severity. Some emphasized the need to increase the dose beyond the recommended amount if sufficient levels of AAT are not achieved, during exacerbations, and in patients with rapid disease progression. The main factor affecting treatment comfort was considered to be the reduced frequency of infusions (e.g., 1× every two weeks, as is common in the Czech Republic) and the ability to self-administer infusions (currently available only in the Czech Republic, France, Ireland, and Poland).
Conclusion
The above survey clearly showed that AATD is underdiagnosed and undertreated in most European countries, although data across Europe are very heterogeneous. It is necessary to raise awareness of this disease and thus support screening in patients with newly emerged chronic obstructive pulmonary disease, bronchiectasis, adult-onset asthma, and family members of individuals with AATD.
(epa)
Source: Horváth I., Canotilho M., Chlumský J. et al. Diagnosis and management of α-antitrypsin deficiency in Europe: an expert survey. ERJ Open Res 2019; 5: 00171-2018, doi: 10.1183/23120541.00171-2018.
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