Table of Contents
Introduction:
Alpha 1 antitrypsin deficiency is a rare genetic disorder that affects the lungs and liver. The symptoms of lung damage include cough, wheezing, and shortness of breath. These symptoms are similar to other common conditions such as asthma. Emphysema is a type of chronic obstructive pulmonary disease (COPD). It affects three million individuals in the United States.
What Is Alpha-1 Antitrypsin Deficiency Emphysema?
AATD emphysema is a condition caused by AATD. AATD is an inherited condition that runs through the family. It causes damage to your lungs and liver. Sometimes, it may affect your skin. AATD occurs due to low levels of alpha-1 antitrypsin (AAT).
AAT is a protein produced by the liver. Its function is to protect your lungs from damage. Its deficiency in your body causes emphysema (chronic progressive lung disease affecting air sacs, leading to breathing difficulties). Emphysema causes damage to the air sacs in the lungs, leading to breathing problems.
Individuals affected by AATD produce abnormal AAT proteins from their liver. These AAT proteins cannot reach their bloodstream effectively. Due to this type of deficiency, their lungs are more vulnerable to the damage. The lung damage occurs due to enzymes called neutrophil elastase. These enzymes can degrade the lung tissue, leading to emphysema.
What Is the Pathogenesis of Emphysema in AATD?
Emphysema in AATD occurs due to an imbalance of enzymes called proteolytic enzymes (proteases) and antiprotease enzymes. The imbalance of these enzymes takes place in the lungs, leading to lung tissue destruction. The mechanisms of pathogenesis include:
AATD:
AAT is a protein produced by the liver. It inhibits the enzyme neutrophil elastase. Neutrophil elastase is an enzyme secreted by neutrophils. The secretion of elastase occurs during inflammation. These enzymes can degrade elastin and connective tissues of the lungs.
In the AATD condition, the AAT produced by the mutated gene called SERPINA 1 is misfolded and secreted in low numbers from the liver. This leads to insufficient AAT proteins in the plasma and lungs. This leads to emphysema later in life. This type of cause is called the genetic cause of emphysema.
AAT deficiency cannot inhibit the neutrophil elastase enzymes, leading to the destruction of lung tissues.
Unchecked Neutrophil Elastase Activity:
Whenever there is an infection, environmental pollutants, or smoking in your lungs, the neutrophils are increased in the lungs. These neutrophils produce elastase enzymes in the lungs.
In AATD, due to insufficient AAT proteins that inhibit the elastase enzymes, it cannot be done effectively. Hence, these neutrophil elastases destroy alveolar walls leading to emphysema.
Elastin Degradation and Alveolar damage:
Elastin is important to maintain the elasticity of the lungs. When there is destruction of elastin, enlargement of the air spaces and loss of lung recoil occur. These are the characteristics of emphysema.
Inflammatory and Oxidative Stress Response:
AATD can cause chronic lung inflammation. This further leads to increased levels of cytokines and oxidative stress. Cytokines include interleukin 8 (IL-8) and tumor necrosis factor (TNF)-⍺.
Oxidants released from smoking and infection tend to inactivate AAT that are present in low numbers. This accelerates the destruction of the lungs.
The inflammatory response also leads to the accumulation of more neutrophils in the lungs. This further leads to an imbalance of enzymes. The imbalance of protease and antiprotease leads to lung destruction.
Do You Know the Clinical Manifestations of AATD-related Emphysema?
The clinical manifestations of AATD vary from one individual to another. These may be influenced by factors such as environmental exposures, genetic mutations, and lifestyle choices.
Symptoms of AAT-related emphysema include:
Pulmonary Manifestations:
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COPD: AATD has a genetic risk for COPD. This condition exhibits symptoms like shortness of breath, wheezing, chronic cough with sputum production, and decreased capacity to do exercises.
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Emphysema: In this condition, we can observe the destruction of alveoli. This condition affects the lower lobes of the lungs and is generally observed among those aged 20-50 years.
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Asthma-like Symptoms: Some individuals experience wheezing and bronchial destruction. These symptoms may mislead the diagnosis as asthma instead of AATD.
How to Diagnose AATD-Related Emphysema?
AATD is a genetic disorder, and affected individuals usually have a family history of lung and liver diseases, especially among nonsmokers. Hence, genetic testing and alpha-1 antitrypsin levels are crucial for the diagnosis of AATD.
The diagnosis process involves a combination of clinical evaluation, laboratory tests, and imaging tests. AATD is usually not diagnosed until the symptoms of COPD occur.
Clinical evaluation can provide information about the early onset of emphysema, particularly at the age below 45 years, lower lobe predominant emphysema, symptoms such as chronic cough, wheezing, dyspnea that are confused for asthma, family history of AATD, worsening lung function, even after stopping the smoking habit.
The diagnostic tests include:
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Blood Tests: These are done to know about the levels of AAT. This may be combined with gene testing to confirm the genotype.
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Arterial Blood Gas (ABG) Test: This test is done to know the levels of oxygen and carbon dioxide in the blood.
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Chest X-rays: Chest X-rays and computed tomography of the chest were done to determine lung damage.
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Electrocardiogram (ECG) and Echocardiogram: These are done to know about changes in the heart that occur in COPD.
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Pulse Oximetry Test: This test helps to determine oxygen levels in the blood.
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Spirometry Test: It is a breathing test that helps to know how much air is exhaled. It is also known to be a pulmonary function test.
If an individual is aware of a family history of AATD, the person may ask his doctor to conduct a blood test to know about the levels of AAT in their body.
What Are the Treatment and Management Strategies for AATD-related emphysema?
The treatment and management strategies help to achieve a reduction in lung damage, relieve symptoms of AATD, and slow down the progression of the disease.
Treatment of AATD-related emphysema is the same as emphysema. These include:
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Inhaled bronchodilators are used to relieve airways to breathe better.
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Oral corticosteroids are used to treat inflammation present in the lungs. They are given during acute phases.
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Inhaled corticosteroids are used in the case of severe emphysema with frequent exacerbations.
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Antibiotics are given for acute attacks caused by bacterial infections.
Additionally, the healthcare provider may advise to take vaccinations for
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COVID 19.
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Viral influenza.
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Streptococcus pneumonia.
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Bordetella pertussis.
Supportive Therapy:
Supportive therapy is the same as for COPD patients. These include:
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Pulmonary rehabilitation.
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Nutritional support.
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Supplemental oxygen if needed.
Augmentation Therapy or Replacement Therapy:
In this therapy, AAT is used to increase their levels. These are given intravenously every week. This therapy is to be done for life long to maintain AAT levels.
Lung Transplant:
A lung transplant may be considered at the end stage of lung disease caused by AATD.
Emerging Therapies:
These emerging therapies focus on gene therapy approaches. These therapies help correct gene mutations and increase the production of AAT. One of these is CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas 9 (it is a powerful gene editing technology to treat genetic issues).
Ongoing Clinical Trial:
One of these trials includes SPARTA (Study of ProlAstin-c Randomized Therapy with Alpha-1 augmentation). This focuses on evaluating the efficacy and safety of different doses of Prolastin-C (a form of alpha-1 antitrypsin).
Conclusion
AATD is a genetic disorder that runs in the family. It may not be diagnosed and left undetected even sometimes. It causes emphysema through certain mechanisms. Hence, a thorough knowledge of the condition is necessary. Knowing about the disease helps in identifying the condition early. Early diagnosis helps achieve effective treatment. There is no prevention for this condition. But it can be tackled well if recognized early.
Key Takeaways from iCliniq
AATD is a genetic disease that cannot be prevented but can be effectively managed if identified early. Early diagnosis is the key to breathing easier and longer.
