Scientists have long pointed out the similarities between asthma and alpha-1 antitrypsin deficiency (AATD), which can predispose one to developing lung disease. AAT is a serine proteinase inhibitor produced in the lungs; its main purpose is to inhibit neutrophil elastase. In smokers, neutrophil elastase is upregulated in the lung. Importantly, neutrophils as inflammation mediators and drivers of bronchial constriction can be present in both AATD and asthma.
AATD, as the name suggests, is a condition in which the levels of AAT are reduced in circulation. One of the most devastating effects of AATD is the damage it does to the lungs; excessive neutrophil elastase degrades the lung extracellular matrix, alveolar structures, and blood vessels.
“Individuals with AATD are therefore at increased risk of developing pulmonary disease, especially emphysema, which is often found in the basal areas of the lung,” Miravitlles wrote in the European Respiratory Review.
Patients with AATD can experience a combination of pathologies associated with the disease. For example, at more mature stages of AATD, the pulmonary, hepatic, and skin systems become involved. Initial pulmonary damage eventually gives way to chronic obstructive pulmonary disease (COPD), bronchiectasis, and emphysema.
Read more about AATD etiology
When lung pathologies start to come into the picture, studies have shown that patients’ quality of life becomes significantly compromised. A number of studies have indicated that the onset of COPD in a patient with AATD is a significant cause of reduced quality of life compared to patients with AATD alone.
Lung pathology in AATD functions almost as a benchmark of how severe the disease is, and it is lung disease combined with liver disease that causes the majority of the problems experienced by patients in AATD. In severe cases, caregivers may be needed to administer routine care to patients with advanced AATD.
A Treatable but Common Condition
Asthma, unlike AATD, is characterized almost exclusively by its respiratory symptoms. In Biochemical Pharmacology, Tan and colleagues wrote, “Asthma is a disorder characterized by chronic airway inflammation with respiratory symptoms and expiratory airflow limitation that vary in intensity and time.”
The good news about asthma is that most patients can control it using conventional preventer therapy. The bad news is that it remains a significant problem in the world, eating up precious healthcare resources. This disease is estimated to affect approximately 300 million individuals across the world.
The mechanisms underpinning asthma are well-known: persistent airway inflammation leading to airway hyperresponsiveness. Mucous hypersecretion then occurs. The combination of these abnormalities causes the airways to remodel altogether, permanently limiting airflow.
We have already mentioned that most individuals recover from asthma using conventional drugs; others simply grow out of it. For the slim population of individuals for whom an asthma diagnosis can be life-threatening, there is still no broad consensus on long-term management. Emergency protocols apply in emergency settings, but what about controlling asthma on a daily basis?
In this regard, omalizumab has proven to be a promising drug. It reduces up to half of asthma exacerbations and might even reduce the need for a patient to be on oral corticosteroids. Studies have demonstrated that the drug can also reduce hospitalization for patients with severe asthma.
Common Clinical Features
So how can clinicians tell the difference between AATD and asthma? A good place to start is to compare the common clinical features of the two diseases. Both AATD and asthma can result in wheezing, cough, dyspnea, episodic association with environmental triggers and infection, and allergies.
This huge overlap of symptoms means that some physicians are hesitant to diagnose AATD in a patient who already has a diagnosis of asthma. In fact, studies have suggested that one of the causes for a delay in the correct diagnosis of AATD is confusion due to a huge portion of its clinical manifestations overlapping with that of asthma.
Scientists have estimated that patients with asthma generally experience a 5-year delay in the diagnosis of AATD, presumably due to the difficulties in identifying patterns of AATD once a diagnosis of asthma has been made.
Read more about AATD patient education
A clever way to get around this problem (as physicians often have to make decisions in extraordinarily gray areas) is to recommend genetic testing for AATD in all patients with COPD, emphysema, or asthma in whom incompletely reversible airflow obstruction can be observed. This means that physicians should lower their threshold for suspecting AATD in patients with some respiratory diseases.
In Asthma, Izquierdo and colleagues neatly summed up why it is important for AATD to be correctly diagnosed in a patient with asthma: “Clinical implications of identifying asthma in patients with known AATD and AATD in patients with known asthma are profound as medications and interventions may vary depending on if the coexisting diagnosis is identified.”
Izquierdo M, Rawal H, Armstrong M, Marion CR. Alpha-1 asthma overlap syndrome: a clinical overview. Curr Allergy Asthma Rep. 2022;10.1007/s11882-022-01036-z. doi:10.1007/s11882-022-01036-z
Tan R, Liew MF, Lim HF, Leung BP, Wong WSF. Promises and challenges of biologics for severe asthma. Biochem Pharmacol. 2020;179:114012. doi:10.1016/j.bcp.2020.114012
Miravitlles M, Herepath M, Priyendu A, et al. Disease burden associated with alpha-1 antitrypsin deficiency: systematic and structured literature reviews. Eur Respir Rev. 2022;31(163):210262. doi:10.1183/16000617.0262-2021