Effect Of Augmentation Therapy Research Articles

Diagnosis and augmentation therapy for alpha-1 antitrypsin deficiency: current knowledge and future potential.

The underdiagnosis of alpha-1 antitrypsin (AAT) deficiency (AATD) has been recognized for many years, yet little progress has been made in treatment of the disease. In this review, we summarize the AATD disease process as well as its diagnosis and treatment by AAT augmentation therapy. AATD is a rare autosomal disease that primarily affects the lungs and liver. AATD is associated with an increased susceptibility to developing pulmonary emphysema. The specific pharmacological treatment for AATD is intravenous administration of exogenous AAT. Augmentation therapy with AAT increases serum and pulmonary epithelial AAT levels, restores anti-elastase capacity, and decreases inflammatory mediators in the lung. Augmentation therapy reduces the loss of lung density over time, thus slowing progression of the disease. The effects of augmentation therapy on outcomes, such as frequency/duration of flare-ups, quality of life, lung function decline and mortality, are assessed. Wider testing for AATD, potentially through primary care physicians, could result in earlier treatment and better outcomes for individuals with AATD-induced lung respiratory disease.

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

Management of lung disease in patients with alpha-1 antitrypsin deficiency (AATD) includes both non-pharmacological and pharmacological approaches. Lifestyle changes with avoidance of environmental pollutants, including tobacco smoke, improving exercise levels and nutritional status, all encompassed under a disease management program, are crucial pillars of AATD management. Non-pharmacological therapies follow conventional treatment guidelines for chronic obstructive pulmonary disease. Specific pharmacological treatment consists of administering exogenous alpha-1 antitrypsin (AAT) protein intravenously (augmentation therapy). This intervention raises AAT levels in serum and lung epithelial lining fluid, increases anti-elastase capacity, and decreases several inflammatory mediators in the lung. Radiologically, augmentation therapy reduces lung density loss over time, thus delaying disease progression. The effect of augmentation therapy on other lung-related outcomes, such as exacerbation frequency/length, quality of life, lung function decline, and mortality, are less clear and questions regarding dose optimization or route of administration are still debatable. This review discusses the rationale and available evidence for these interventions in AATD.

A Computational Internal Model to Quantify the Effect of Sensorimotor Augmentation on Motor Output.

The aging process, as well as neurological disorders, causes a decline in sensorimotor functions, which can often bring degraded motor output. As a means of compensation for such sensorimotor deficiencies, sensorimotor augmentation has been actively investigated. Consequently, exoskeleton devices or functional electrical stimulation could augment the muscle activity, while textured surfaces or electrical nerve stimulations could augment the sensory feedback. However, it is not easy to precisely anticipate the effects of specific augmentation because sensory feedback and motor output interact with each other as a closed-loop operation via the central and peripheral nervous systems. A computational internal model can play a crucial role in anticipating such an effect of augmentation therapy on the motor outcome. Still, no existing internal sensorimotor loop model has been represented in a complete computational form facilitating the anticipation. This paper presents such a computational internal model, including numerical values representing the effect of sensorimotor augmentation. With the existing experimental results, the model performance was evaluated indirectly. The change of sensory gain affects motor output inversely, while the change of motor gain did not change or minimally affects the motor output.Clinical Relevance- The presented computational internal model will provide a simple and easy tool for clinicians to design therapeutic intervention using sensorimotor augmentation.

BRONCHIECTASIS IN ALPHA-1 ANTITRYPSIN DEFICIENCY: A SINGLE-CENTER REVIEW

SESSION TITLE: Asthma and Comorbid Disease SESSION TYPE: Original Investigations PRESENTED ON: 10/10/2018 08:45 AM - 09:45 AM PURPOSE: Alpha-1 Antitrypsin Deficiency (A1ATD) is a genetic disease that results in abnormal alpha-1 antitrypsin protein polymers which cannot be released from hepatocytes. This results in low circulating alpha-1 antitrypsin and hepatotoxicity. Alpha-1 antitrypsin has a protective effect in the lungs by neutralizing pro-inflammatory enzymes, such as neutrophil elastase, and sufficiently low levels can result in emphysema.1 Bronchiectasis has also been associated with A1ATD since the original description of the disease.2 Augmentation therapy has been shown to have beneficial pulmonary effects in patients with emphysema, but outcome data in patients with bronchiectasis and the effects of augmentation therapy is lacking. METHODS: Patients with A1ATD and alpha-1 carrier status evaluated at Mayo Clinic Rochester from January 1, 2000 to October 1, 2016 were included in this retrospective review. Data relating to demographics, exacerbations, spirometry, and other causes of bronchiectasis were extracted. Patients with fewer than 12 months of augmentation therapy were excluded from outcome comparisons. RESULTS: 122 patients were included in the final analysis, of which 47 (38.5%) had bronchiectasis. 10 patients with bronchiectasis had MZ or MS genotypes. Compared to those without bronchiectasis, patients with bronchiectasis had a higher mean baseline rate of pulmonary exacerbations (0.73/year vs. 0.28/year, p=0.003). 34 patients received augmentation therapy, including 18 patients with bronchiectasis. Compared to patients without bronchiectasis who also received augmentation, those with bronchiectasis had a faster mean rate of decline in DLCO (-0.56 vs. +0.51 mL/min/mmHg/year, p=0.010), and a higher mean rate of post-treatment exacerbations (+1.28/year vs +0.5/year, p=0.011). Comparing patients with bronchiectasis and emphysema who did and did not receive augmentation, those who received augmentation therapy had more exacerbations compared to their baseline (+0.53/year vs. -0.31/year, p=0.019) and lower mean baseline percent predicted forced expiratory volume in one second (FEV1%) (46.5% vs. 67.8%, p=0.006) and DLCO (12.9 vs. 18.9 mL/min/mmHg, p=0.015), although the change over time was not significantly different. CONCLUSIONS: Bronchiectasis is a common finding in A1ATD, and is not exclusive to patients with ZZ genotypes. Patients with bronchiectasis in this cohort had higher rates of pulmonary exacerbations, regardless of treatment with augmentation therapy. CLINICAL IMPLICATIONS: The role of augmentation therapy for patients with bronchiectasis in the absence of emphysema is unclear and warrants additional studies. DISCLOSURES: No relevant relationships by Megan Dulohery Scrodin, source=Web Response No relevant relationships by Gregory Stroh, source=Web Response

Therapeutics: Alpha-1 Antitrypsin Augmentation Therapy.

Subjects with alpha-1 antitrypsin deficiency who develop pulmonary disease are managed following general treatment guidelines, including disease management interventions. In addition, administration of intravenous infusions of alpha-1 proteinase inhibitor (augmentation therapy) at regular schedules is a specific therapy for individuals with AATD with pulmonary involvement.This chapter summarizes the manufacturing differences of commercially available formulations and the available evidence of the effects of augmentation therapy. Biologically, there is clear evidence of in vivo local antiprotease effects in the lung and systemic immunomodulatory effects. Clinically, there is cumulative evidence of slowing lung function decline and emphysema progression. The optimal dose of augmentation therapy is being revised as well as more individualized assessment of who needs this therapy.