<p>New Patient-Centric Approaches to the Management of Alpha-1 Antitrypsin Deficiency</p>

Abstract

Alpha-1 antitrypsin deficiency (AATD) is a rare and underdiagnosed genetic predisposition for COPD and emphysema and other conditions, including liver disease. Although there have been improvements in terms of awareness of AATD and understanding of its treatment in recent years, current challenges center on optimizing detection and management of patients with AATD, and improving access to intravenous (IV) AAT therapythe only available pharmacological intervention that can slow disease progression. However, as an orphan disease with geographically dispersed patients, international cooperation is essential to address these issues. To achieve this, new European initiatives in the form of the European Reference Network for Rare Lung Diseases (ERN-LUNG) and the European Alpha-1 Research Collaboration (EARCO) have been established. These organizations are striving to address the current challenges in AATD, and provide a new platform for future research efforts in AATD. The first objectives of ERN-LUNG are to establish a quality control program for European AATD laboratories and create a disease management program for AATD, following the success of such programs in the United States. The main purpose of EARCO is to create a pan-European registry, with the aim of understanding the natural history of the disease and supporting the development of new treatment modalities in AATD and access to AAT therapy. Going further, other patient-centric initiatives involve improving the convenience of intravenous AAT therapy infusions through extended-interval dosing and self-administration. The present review will discuss the implementation of these initiatives and their potential contribution to the optimization of patient care in AATD.

<p>Ultra Long-Acting β-Agonists in Chronic Obstructive Pulmonary Disease</p>

“…123,124 Although only a small proportion of individuals with COPD have alpha-1-antitrypsin deficiency, recognition of the genetic mutations that cause reduced functional alpha-1-antitrypsin within the lung and increased risk of emphysema leads to specific therapy with alpha-1-antitrypsin replacement. 125,126 The current mainstays of COPD maintenance therapy consist of three classes of inhaled medications: β-agonists, muscarinic antagonists, and corticosteroids. Bronchodilators started as short-acting medications such as albuterol and ipratropium with durations of effect lasting from 2 to 6 h. Next, long-acting medications with effects lasting up to 12 h were discovered and, most recently, ultralong acting drugs that only require daily dosing have been developed and clinically tested.…”

“… 123 , 124 Although only a small proportion of individuals with COPD have alpha-1-antitrypsin deficiency, recognition of the genetic mutations that cause reduced functional alpha-1-antitrypsin within the lung and increased risk of emphysema leads to specific therapy with alpha-1-antitrypsin replacement. 125 , 126 …”

Management of lung disease in alpha-1 antitrypsin deficiency: what we do and what we do not know

“…90 For studies to determine the impact on quality of life, longer evaluations on larger sample sizes are required, which can be difficult to achieve in studies on rare diseases. 96 Patient registries may be the answer to obtaining data on quality of life as they can recruit much larger numbers of patients and follow them for many years. 96 What is the ideal route or dose of therapy with AAT?.…”

“…96 Patient registries may be the answer to obtaining data on quality of life as they can recruit much larger numbers of patients and follow them for many years. 96 What is the ideal route or dose of therapy with AAT?. There is growing interest in the inhaled route of AAT administration as initial studies showed that more AAT reaches the lungs via inhalation than through the IV route (14.6% versus 2%, respectively).…”

“… 96 Patient registries may be the answer to obtaining data on quality of life as they can recruit much larger numbers of patients and follow them for many years. 96 …”