Alpha-1 Antitrypsin Deficiency — A Missed Opportunity in COPD?

Abstract

Adults with AATD are susceptible to the premature development of lung diseases such as emphysema, chronic bronchitis, bronchiectasis, and asthma. Patients with AATD usually present with exertional breathlessness, wheeze, cough, and frequent pulmonary exacerbations often, but not exclusively with a background history of smoking [19]. Symptoms usually begin from the age of 30 and the clinical suspicion for underlying asthma or chronic obstructive COPD Clinical Perspectives 34

α1-Antitrypsin deficiency and chronic respiratory disorders

“…Controversial results have been published revealing chronic obstructive pulmonary disease (COPD) risk among protease inhibitor (Pi)MZ heterozygotes. A normal protease/antiprotease balance exists in healthy (MM) individuals, in which high levels of MAAT surround the resting neutrophil [8]. During exposure to increasing levels of interleukin (IL)-8 the cell moves down a concentration gradient of AAT and up a gradient of IL-8, thus leading to neutrophil migration to the area of inflammation [2].…”

“…In smoking MZ individuals, reactive oxygen species in cigarette smoke inactivate AAT, resulting in a protease/antiprotease imbalance with increased amounts of neutrophil elastase. Polymerisation of ZAAT protein and increased amounts of IL-8 intensify neutrophil influx into the MZ lung, which could facilitate the development of COPD [2,8]. In fact, ZAAT polymers found within lungs can also fuel inflammation in the AAT deficiency [3].…”

Alpha-1 Antitrypsin Deficiency Today: New Insights in the Immunological Pathways

“…Indeed, while textbooks describe AATD as a condition with a distinctive presentation (early onset, panacinar emphysema and predominantly involving lower lobes) in the clinical practice, signs and symptoms of pulmonary involvement in AATD patients often closely resemble those of ‘common' COPD, or even asthma. Dyspnea is the cardinal symptom of AATD, but patients show a high prevalence of cough, phlegm, wheezing and even a significant degree of bronchodilator reversibility (as much as 50%) [3,13]. Similar to other forms of emphysema, the dyspnea in patients with AATD is initially evident only with strenuous exertion, but, over the years, it eventually limits even mild activities.…”

“…Furthermore, recent advance in imaging techniques also permitted the identification of bronchiectasis in a significant proportion of patients with AATD. The symptoms of bronchiectasis are often difficult to distinguish in the context of COPD, but it suggests that the prevalence and impact of airway disease in AATD may be underestimated [13,16]. …”

Clinical utility of alpha-1 proteinase inhibitor in the management of adult patients with severe alpha-1 antitrypsin deficiency: a review of the current literature

“…The use of alternative sources of AAT, including transgenic human AAT production in other mammals, and the application of recombinant technology for AAT production in yeast may ultimately reduce production costs 3. Unfortunately, the use of AAT isolated from transgenic sheep milk may cause allergic reactions in humans, including possible hypersensitivity pneumonitis, and a trial of this product was consequently terminated 36,37.…”