Long-Term SGRQ Stability in a Cohort of Individuals with Alpha-1 Antitrypsin Deficiency-Associated Lung Disease

Abstract

Background

Health-related quality of life (HRQoL) assessments such as St. George’s Respiratory Questionnaire (SGRQ) are often used as outcome measures to evaluate patient-perceived changes in health status among individuals with lung disease. Several factors have been linked to deterioration in SGRQ, including symptoms (dyspnea, wheezing) and exercise intolerance. Whether these findings apply to individuals with alpha-1 antitrypsin deficiency (AATD) remains incompletely studied. This longitudinal study examines the trajectory of SGRQ scores in a cohort of United States individuals with AATD-associated lung disease and defines factors associated with longitudinal change.

Methods

Individuals with AATD-associated lung disease enrolled in AlphaNet, a disease management program, who had ≥3 SGRQ measurements collected between 2009 and 2019, and baseline data for clinically important variables were included in these analyses. Data collected after lung transplants were excluded. Mixed-effects model analyses were used to evaluate the changes in SGRQ total and subscale scores over time and by modified Medical Research Council (mMRC) Scale, use of oxygen, age, sex, productive cough, and exacerbation frequency at baseline. Sensitivity analyses were conducted to examine the potential effect of survivor bias.

Results

Participants (n=2456, mean age 57.1±9.9 years, 47% female) had a mean SGRQ total score of 44.7±18.9 at baseline, 48% used oxygen regularly, and 55% had ≥2 exacerbations per year. The median length of follow-up was 6 (IQR 3–9) years. The SGRQ total score and subscales remained stable throughout the observation period. Age, mMRC categories, presence or absence of productive cough, frequency of exacerbations, and use of oxygen at baseline were significantly associated with the rate of change of SGRQ total (p<0.0001).

Conclusion

We observed long-term stability in HRQoL and an association between the rate of change in SGRQ and baseline mMRC, exacerbation frequency, productive cough, and use of oxygen in this cohort of individuals with AATD-associated lung disease.

Keywords:

• COPD
• alpha-1 antitrypsin deficiency
• quality of life

Acknowledgments

The authors would like to thank the AlphaNet Coordinators and participants for their contributions to this study.

The abstract of this paper was presented at the American Thoracic Society 2023 International Conference as a poster presentation with interim findings. The poster’s abstract was published in the “Abstract Issue” of the American Journal of Respiratory and Critical Care Medicine 2023, Volume 207: https://www.atsjournals.org/doi/pdf/10.1164/ajrccm-conference.2023.207.1_MeetingAbstracts.A1567

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

Dr Radmila Choate reports research support for AlphaNet. Dr Kristen Holm is affiliated with AlphaNet and reports personal fees from AlphaNet, outside the submitted work. Dr Robert Sandhaus is affiliated with AlphaNet and reports contract payments to AlphaNet, Inc. for Disease Management Services from Grifols and CSL Behring; grants to AlphaNet for Disease Management Services from Takeda, grants from Vertex for investigations in multicenter clinical trial at National Jewish Health and Inhibrx. In addition, he is also the data monitoring committee member for Takeda Alpha-1 liver therapy trial, advisory committee member for Grifols, CSL Behring, Beam, Kooro Bio, Intellia, ADARx, ARespo, Evolve, and Vertex. Some of these companies paid travel expenses. Dr David Mannino reports personal fees from AstraZeneca, GlaxoSmithKline, Regeneron, and Genentech, outside the submitted work. Dr Charlie Strange is a medical director of AlphaNet and reports personal fees and/or non-financial support from AlphaNet and Inhibrx. He also reports grants/personal fees from Grifols, Takeda, CSL Behring, Dicerna, from Inhibrx, and Vertex, outside the submitted work. The authors report no other conflicts of interest in this work.

Additional information

Funding

This study was supported by an unrestricted research grant from AlphaNet.