Alpha 1-antitrypsin Deficiency (AATD)

* To define the course of AATD-associated liver disease. * To use the obtained samples for biomedical research which includes: 1. Search for serum-based disease biomarkers and the associated molecular pathways. 2. Multi-omic spatial analysis of human AATD-LD.

This is a Phase 1/2, open-label, multi-center, dose escalation (Part 1), dose expansion (Part 2), and single repeat dose (Part 3) study to evaluate the safety, tolerability, efficacy, and PK/PD parameters of TSRA-196 in adults with the PiZZ genotype who have lung and/or liver disease associated with severe alpha-1 antitrypsin deficiency (AATD)

Brief Summary: This study aims to find out if a genetic condition called Alpha-1 Antitrypsin Deficiency (AATD) is more common in people who have shortness of breath and signs of airway obstruction on their breathing tests. Alpha-1 antitrypsin (AAT) is a protein that protects the lungs from damage. AATD is an inherited condition where the body does not make enough of this protein, which can lead to lung diseases like emphysema, especially in smokers. Investigators hypothesize that low AAT levels or related genetic mutations may be a contributing factor to airway obstruction in patients complaining of shortness of breath. To test this, investigators will recruit patients from our outpatient clinic who are being evaluated for shortness of breath and are having a standard breathing test (spirometry). Investigators will measure their AAT levels and test for the most common genetic mutations that cause AATD using a small blood sample. Investigators will then compare the AAT levels and genetic results between different groups of patients, such as smokers and non-smokers with and without airway obstruction. Investigators will also see if the severity of a patient's shortness of breath is related to their AAT levels. The goal is to improve the detection of AATD in this patient population, which could lead to better diagnoses and specific treatments for those who have this condition.