Author
Summary: Gabi Niethammer, as published in Alpha1 Journal 1/2023.
Seeking and finding the rare
Doctors often associate alpha-1 antitrypsin deficiency only with COPD and pulmonary emphysema, but alpha-1 is involved in much more! Therefore, it is all the more important to better educate the medical community about the specific characteristics of AATD through symposia, congresses, and publications.
Differentiation of the different Alpha-1 types
- Healthy gene carriers who have an increased risk of developing the disease, but who never develop symptoms, regardless of whether they are heterozygous or homozygous affected.
- Infants with early childhood cholestasis, who are therefore noticeable due to prolonged jaundice and/or poor liver function.
- People over 50 with liver fibrosis or cirrhosis, who consequently have an increased risk of liver cancer.
- Young patients with asthma, which, if left untreated, can potentially trigger a fixed obstruction, similar to COPD, 30 years later.
- Pure emphysema patients who can slip through the cracks if gas exchange (diffusion capacity) is not measured.
- Patients with bronchiectasis, rarely also with vasculitis or panniculitis
Overall, we know far too little about the more than 150 gene variants of alpha-1 antitrypsin deficiency, yet we want to consider all facets in treatment; therefore, data from registry studies are important to capture even rare manifestations of symptoms/changes.
Calculation of the number of affected individuals
Historically, AATM likely originated around 2,000 years ago among the Vikings. The exact number of affected individuals is currently unclear, as different studies arrive at varying figures depending on the underlying definitions.
Based on the different definitions for the Stuttgart area and extrapolated to Germany as a whole, the speaker calculated the potential number of affected individuals in April 2023: The Pneumology Practice in the Center (PiZ) is the second largest Alpha-1 Center in Germany, after Marburg. 50 of the Alpha-1 patients are under 50 years old, and 60 are female. More than 50 have a diagnosis of asthma or asthma with COPD, while only 15 have the classic diagnosis of COPD or pulmonary emphysema.
Data from April 2023 revealed that in Stuttgart, of an estimated nearly 12,000 PI*MZ cases, only 131 have been diagnosed, and of 125 calculated PI*ZZ cases, only 43 are receiving treatment. There are therefore significant discrepancies between the presumed number of affected individuals and the actual number of recorded patients, and an even higher number of unreported cases can be assumed based on the estimated prevalence rates.
The goal must be to ensure that individuals with heterozygous or homozygous alpha-1 syndrome are not only discovered at age 55, after 40 years of smoking, with a catastrophic FEV1 and significantly impaired gas exchange. To achieve this goal, alpha-1 should be detected as early as possible, then monitored and, if necessary, treated.
Disease patterns and intervention options over time
Early childhood
- Increased liver risk
Children and young people
- Allergy/Asthma with specific immunotherapy
- Career choice advice
- Advice on the particular dangers of inhaling cigarette smoke
- Advice on alcohol consumption, lack of exercise and weight
Adults, in addition to
- COPD / Emphysema
- Liver fibrosis, cirrhosis
- Advice on oxygen and substitution therapy
Older people, in addition to
- Respiratory therapy
- Rehabilitation
- COPD treatment
Prevalence of PI*ZZ occurrence (Greulich et al 2017)
- 10/100,000 among 0-29 year olds
- 16/100,000 among 30-44 year olds
- 28/100,000 among 45- to 59-year-olds
- 39/100,000 in 60-74 year olds
Early monitoring and good education regarding symptoms, risks, possible therapies and career choices can help avoid damage and prevent fixed obstruction in asthma, COPD and loss of gas exchange surface area in pulmonary emphysema.
On the other hand, early monitoring can also lead to anxiety and depression, influence family planning and structure, trigger stigmatization and discrimination, and create uncertainty regarding various insurance policies.
Alpha-1 diagnostics
The serum level measurement as a first step costs just €10.70. If laboratory levels are abnormal, or especially in cases of Alpha-1 deficiency, genotyping is then performed.
A distinction must be made between diagnostic and predictive genetic testing. If someone already has a liver or respiratory disease, bronchiectasis, vasculitis, or panniculitis, then any physician is permitted to perform alpha-1 genetic testing, as it is diagnostically justified. After receiving the results, the patient should then be offered the opportunity for genetic counseling.
However, if healthy relatives wish to be tested for Alpha-1, the genetic test may only be performed after a consultation with a specialist geneticist, as it concerns the clarification of future diseases and is therefore a predictive test. It is a criminal offense if the physician orders the test without this consultation.
According to the speaker's experience, the known, published laboratory levels of the genotypes do not always correspond to those he actually measures in his practice.
The discrepancy is particularly high in the PI*MZ and PI*SZ genotypes, meaning that in young people, the alpha-1 level can be within the normal range, yet a heterozygous deficiency is still present! Many doctors, lacking experience with alpha-1, fail to take this into account, which can lead to misdiagnosis and underdiagnosis.
Diagnostic pathway
The medical history for asthma and COPD differs. While asthmatics often present with symptoms in childhood or adolescence, have little or no smoking experience, suffer from discomfort during exercise, and have a morning nose-blowing problem, COPD is characterized by progressive symptoms. The affected individual has likely smoked for more than 20 years, has a history of chronic bronchitis, no allergies, and may have comorbidities such as heart attack, stroke, or cancer. Lung function tests in these cases show a significant decline in lung capacity.
Quit smoking first!
Alpha-1 and smoking = No-Go! The ideal way to quit smoking is a step-by-step plan with motivational speeches, evidence-based apps, medication, and long-term support in individual or group training sessions.
Treatment of asthma (chronic respiratory inflammation)
There is a 5-step therapy with combined medications, in which cortisone is the first step.
Treatment of COPD
Double bronchodilator therapy is initiated very early. Triple therapy, involving inhaled corticosteroids, is only added if the patient experiences frequent exacerbations. It is a significant improvement that long-acting bronchodilators combined with inhaled corticosteroids are no longer available for COPD; instead, corticosteroids are only prescribed if the patient experiences frequent exacerbations or, for example, if their blood eosinophil count exceeds 300. COPD is a systemic disease, and therefore, treatment must also address and treat other conditions such as osteoporosis, skeletal muscle wasting, reflux, weight loss, or mental health disorders.
Conclusion
The comprehensive treatment of Alpha-1 patients includes the following steps:
- Identify risks early and thereby prevent disease
- Lung function and diffusion, at least once in a lifetime for every PI*MZ,
- Allergy tests may be necessary; regular check-ups are also better.
- Diagnostic/predictive genotyping (be careful with insurance companies)
- Career guidance
- Family counseling, family planning counseling
- Modification of risk behavior (smoking = quitting smoking, alcohol)
- Regular monitoring of lungs and liver
- Inhalational asthma therapy
- Allergy treatment (specific immunotherapy)
- Inhalational COPD therapy
- Augmentation therapy (substitution)
- A healthy, balanced diet to maintain a healthy liver
- Weight management
- Sufficient exercise and sport
- Vaccinations (pneumococcal, influenza, pertussis, corona, zoster)
- Respiratory therapy, pulmonary exercise, rehabilitation
- Long-term oxygen therapy (LTOT)
- Lung volume reduction
- Lung transplantation
