Study Finds Stable Long-Term HRQoL in Patients with AATD-Associated Lung Disease

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Patients with AATD-associated lung disease on augmentation therapy participating in a health management program experienced negligible changes in self-perceived health status.

Health-related quality of life (HRQoL) is associated with key baseline parameters of chronic obstructive pulmonary disease (COPD) severity in patients with alpha-1 antitrypsin deficiency (AATD)-associated lung disease, according to findings from a recent study.1

Using St. George’s Respiratory Questionnaire (SGRQ) to evaluate patient-perceived changes in health status, the study reported long-term stability in HRQoL and found the rate of change in SGRQ scores was linked to modified Medical Research Council (mMRC) dyspnea scale, exacerbation frequency, productive cough, and use of oxygen.1

An inherited genetic disorder that increases the risk of emphysema, cirrhosis, and panniculitis, AATD is the most common genetic cause of liver disease in children and affects people who have 2 copies of the SERPINA1 gene that produces an abnormal type of alpha-1 antitrypsin. Having AATD increases the risk of developing aggressive, early-onset COPD and increases susceptibility to lung disease and liver disease.2

“The burden of AATD-associated lung disease is often more pronounced than in COPD without AATD due to the development of pulmonary symptoms at a younger age, leading to significant impairment in quality of life,” Radmila Choate, PhD, MPH, research assistant professor in the department of epidemiology at the University of Kentucky College of Public Health, and colleagues wrote.1

To examine the trajectory of SGRQ scores indicative of HRQoL in a cohort of patients with AATD-associated lung disease and determine factors associated with longitudinal change, investigators conducted telephone interviews with participants of AlphaNet, a not-for-profit health management organization for individuals with AATD in the US who are prescribed augmentation therapy. Participants are followed regularly by AlphaNet Coordinators who provide education and support, connect AlphaNet participants with various disease-related resources, and collect data to assist disease management.1

AlphaNet participants with ≥ 3 SGRQ measurements collected between 2009 and 2019 and baseline data for clinically important variables were included in the present analyses. HRQoL was measured using the SGRQ, a multi-dimensional, standardized, 50-item instrument validated for telephone administration and designed to measure the impact of obstructive airway disease on patients’ overall health and daily activities. It is divided into 3 sections: symptoms, measuring distress caused by pulmonary symptoms; activity, describing physical activities that cause or are limited by dyspnea; and impact, assessing social and psychological effects of the disease.1

Of the 4694 AlphaNet participants considered for the study, 2456 (52.3%) met the inclusion criteria and were included. Among the cohort, the mean age was 57.1± 9.9 years, 47% of patients were female, and the baseline mean SGRQ total score was 44.7± 18.9. Investigators noted the mean values of the subscale scores at baseline were 46.8 ± 22.7 for symptoms, 63.5 ± 24.6 for activities, and 33.3 ± 18.9 for impact.1

Overall, HRQoL remained stable, with SGRQ total and impact domain scores showing no significant change over time. While the SGRQ activity score showed a slight deterioration over time with an annual increase of 0.25 units/year, the SGRQ symptoms score showed a minor improvement of −0.32 units/year.1

Upon analysis, individuals with greater mMRC grades at baseline had greater improvement in HRQoL over time compared to those with lower mMRC grades and better SGRQ at baseline (P <.0001). Similarly, individuals reporting a greater number of exacerbations at baseline had a greater change in their SGRQ total score (P = .064).1

Further analysis revealed SGRQ symptoms subscale score showed greater improvement over time in individuals reporting productive cough at baseline compared to those not reporting this symptom (P = .0002). Age was also linked to the rate of change of SGRQ, with symptoms subscale score trajectories showing gradual improvement for all age groups over time but with a greater improvement in younger adults (P = .046).1

Investigators pointed out several potential limitations to these findings, including the unavailability of data on certain factors potentially associated with HRQoL; the self-reported nature of the data used in the study; and the lack of generalizability to the general population of people with AATD-associated lung disease outside of AlphaNet.1

“HRQoL is an important patient-reported measure of respiratory health in AATD-associated lung disease, considering the absence of a cure and the emphasis on disease management,” investigators concluded.1 “We observed long-term stability in HRQoL and an association between the rate of change in SGRQ and key baseline parameters of COPD severity, such as mMRC, exacerbation frequency, productive cough, and use of oxygen in individuals with AATD-associated lung disease participating in a disease management program.”


  1. Choate R, Holm KE, Sandhaus RA, et al. Long-Term SGRQ Stability in a Cohort of Individuals with Alpha-1 Antitrypsin Deficiency-Associated Lung Disease. Int J Chron Obstruct Pulmon Dis. 2024;19:889-900.
  2. Cincinnati Children’s. Alpha-1 Antitrypsin Deficiency (AATD). Health Library. January 2024. Accessed May 29, 2024.