Alpha-1 Antitrypsin Deficiency (AATD)


Pulmonary Rehabilitation Therapy

Pulmonary rehabilitation for alpha-1 antitrypsin deficiency (AATD) consists of outpatient or home-based programs that target individuals with chronic lung diseases, typically chronic obstructive pulmonary disease (COPD). These programs attempt to improve quality of life in those with COPD through managing and attempting to reduce dyspnea, increasing exercise tolerance, minimizing flare-ups and episodes of hospitalization, and improving overall well-being. These programs may also be beneficial to individuals with AATD-related COPD following surgical interventions, such as lung transplantation (single or double) or lung volume reduction surgery (rarely used in AATD).1 

An interdisciplinary medical team consisting of a respiratory or physical therapist, a nurse, a pulmonologist, a psychologist or social worker, and a nutritionist or dietitian coordinates and provides services over a period of 8 to 12 weeks.1 Upon discharge, the exercises and techniques learned while in the program must be reinforced at home to maintain the progress made during rehabilitation.  

Services provided include:1

  • Exercise training, including aerobic conditioning and strength training to combat deconditioning, shortness of breath, exercise intolerance, and loss of muscle mass common in COPD
  • Inspiratory muscle training including diaphragmatic and segmental breathing exercises and use of inspiratory (and possibly expiratory) resistance devices
  • Neuromuscular electrical stimulation to assist in muscle strengthening and providing a means of combating muscle atrophy without inducing dyspnea
  • Development of a nutrition plan to combat pulmonary cachexia, to avoid specific foods or supplements that might accelerate the disease process, and to educate patients with AATD-related COPD to eat smaller meals more frequently throughout the day in a way that maintains adequate caloric intake, while reducing the likelihood of breathing discomfort when the patient becomes too full   
  • Patient education, including proper scheduling and dosage of medications, smoking cessation, breathing strategies, and modification of activities of daily living, to conserve energy
  • Psychosocial and behavioral counseling to counter depression and anxiety, which is common in those experiencing shortness of breath and decreased quality of life due to chronic illnesses

Supportive Respiratory Therapy

Supportive respiratory therapy includes supplemental oxygen therapy and chest physical therapy to improve oxygenation, reduce dyspnea, and assist with airway clearance. 

Supplementation using oxygen may be performed in the hospital temporarily during an exacerbation of AATD-related COPD or at home for longer term management of advanced disease stages. Oxygen is usually delivered through nasal cannula or a face mask that is attached to an oxygen canister or ventilator. Oxygen supplementation reduces symptoms of hypoxia and fatigue, which enables those with chronic lung diseases to remain more active to improve quality of life.2

The primary intervention used in chest physical therapy is postural drainage and percussion,  which helps with clearance of mucus that accumulates in the lungs in individuals who have expiratory airflow obstruction and struggle to clear their airways naturally. Those with AATD-related COPD, bronchiectasis, and recurrent respiratory infections may benefit from this intervention. Postural drainage involves positioning of the patient at specific angles to facilitate drainage of the secretions from a particular lobe of the lung, while percussion occurs simultaneously to this positioning.3 Percussion involves the therapist clapping over the region with cupped hands to loosen the secretions to be expectorated. Mechanical vibrators and high-frequency chest oscillators (inflatable vests which vibrate at high frequency) may alternatively be utilized to mobilize secretions.3 

Contraindications for postural drainage and percussion include:3

  • Vertebral or rib fractures
  • Increased risk of bleeding
  • Hemoptysis 
  • Severe osteoporosis
  • Intolerance of positioning required for the intervention

Alternative methods of airway clearance to reduce hypoxia include suctioning, ultra-low frequency airway oscillation devices, positive expiratory pressure devices to open airways, and use of controlled breathing patterns to assist with oxygenation.4 Suctioning uses a small plastic tube that is placed through the nose down into the trachea to clear upper airway secretions via gentle vacuuming. 

While complications to these interventions are rare, they may include aspiration of the mobilized secretions or position-related hypoxia.4 

Augmentation Therapy

Intravenous augmentation therapy specifically targets AATD’s low to non-existent levels of serum alpha-1 antitrypsin (AAT) protein. Augmentation therapy infuses purified pooled human plasma AAT into the venous system of an individual with AATD on a weekly basis for optimal efficacy.5 The objective of this therapy is to raise the serum concentration of AAT above the protective threshold to decelerate alveolar lung tissue destruction by neutrophil elastase enzymes.6 A half dozen identified preparations of purified AAT pooled human plasma are available in the US, including Prolastin, Prolastin-C, Aralast, Aralast NP, Zemaira, and Glassia.6,7 Intravenous augmentation therapy is recommended for non-smoking individuals with AATD-related lung disease and those with AATD-induced necrotizing panniculitis.8 Augmentation therapy is not recommended for individuals with AATD who continue to smoke, who have undergone liver transplantation, who have no airflow obstruction despite bronchiectasis or emphysema, and who have the MZ genotype of AATD. It is not meant to treat liver disease associated with AATD.7 Optimal efficacy of augmentation therapy is demonstrated when treating individuals with forced expiratory volume (FEV1) levels that are 65% or less of predicted values. There is a considerable lack of supporting evidence for anything greater than this level of FEV1 decline.8 

Gene Therapy

This form of therapy for individuals with AATD is currently under investigation in ongoing clinical trials. AATD-targeted gene therapy utilizes genome-editing techniques such as intramuscular or intrapleural adenovirus administration. The adenovirus carries the normal AAT SERPINA1 gene needed to produce consistent levels of AAT from non-hepatic organ sites.9

References 

  1. Levine AR, Stankiewicz J. Overview of pulmonary rehabilitation. Merck Manual Consumer Version. Accessed June 11, 2021.
  2. Oxygen therapy. American Lung Association. Accessed June 11, 2021.
  3. Levine AR, Stankiewicz J. Chest physical therapy. Merck Manual Consumer Version. Accessed June 11, 2021.
  4. Levine AR, Stankiewicz J. Chest physiotherapy. Merck Manual Professional Version. Accessed June 11, 2021.
  5. Wewers MD, Casolaro MA, Sellers SE, et al. Replacement therapy for alpha 1-antitrypsin deficiency associated with emphysema. N Engl J Med. 1987; 316(17):1055-1062. doi:10.1056/NEJM198704233161704
  6. Stoller JK, Aboussouan LS. A review of α1-antitrypsin deficiency. Am J Respir Crit Care Med. 2012; 185(3):246-259. doi:10.1164/rccm.201108-1428CI
  7. Alpha-1 antitrypsin deficiency. National Organization for Rare Disorders (NORD). Accessed June 7, 2021. 
  8. Robert A. Sandhaus MD, Gerard Turino MD, Mark L. Brantly MD, et al. The diagnosis and management of alpha-1 antitrypsin deficiency in the adult. Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation. 2016; 3(3):668-682.
  9. Lorincz R, Curiel DT. Advances in alpha-1 antitrypsin gene therapy.Am J Respir Cell Mol Biol. 2020;63(5):560-570. doi:10.1165/rcmb.2020-0159PS

Article reviewed by Harshi Dhingra, MD on July 1, 2021.

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