Deterioration of quality of life is associated with the exacerbation frequency in individuals with alpha-1-antitrypsin deficiency – analysis from the German Registry

Abstract

Background

Alpha-1-antitrypsin deficiency (AATD) is a rare hereditary disease that is associated with a higher risk to develop chronic obstructive pulmonary disease and liver cirrhosis. Previous cross-sectional studies on AATD individuals have shown a relationship between worse St George’s Respiratory Questionnaire (SGRQ) scores and elevated exacerbation rate or high cigarette consumption. There is a lack of longitudinal data on the relationship between the exacerbation rate and worsening of SGRQ during disease. The aim of this study was to provide not only cross-sectional data but also information about the deterioration in quality of life over a follow-up period up to 7 years (median follow-up period of 3.33 years).

Methods

We investigated questionnaire-based data of the German AATD registry concerning the relationship between SGRQ and exacerbation frequency, smoking history, forced expiratory volume in 1 second (FEV₁) and carbon monoxide diffusion capacity (DLCO) first in cross-sectional analysis and later in longitudinal analysis.

Results

Eight hundred sixty-eight individuals with protease inhibitor ZZ (PiZZ) genotype with an average age of 52.6±12.8 years had an SGRQ score of 45.7±20.6. SGRQ significantly correlated with the exacerbation frequency within the last 2 years (r=0.464; P<0.001), smoking history (r=0.233; P<0.001), FEV₁ (r=−0.436; P<0.001), DLCO (r=−0.333; P<0.001), and patients’ age (r=0.292; P<0.001). Individuals with occupational dust exposure had significantly worse quality of life (P<0.001). Mean annual deterioration of SGRQ in all patients with available follow-up data (n=286) was 1.21±4.45 points per year. Univariate and multivariate analysis showed a significant relationship between worsening of SGRQ/year and exacerbation frequency in the follow-up period (r=0.144; P=0.015).

Conclusion

Worsening of SGRQ is associated with the exacerbation frequency in individuals with PiZZ AATD.

Keywords:

• SGRQ
• quality of life
• AATD
• alpha-1-antitrypsin deficiency
• COPD
• exacerbations
• emphysema
• FEV₁

Supplementary materials

Table S1 Linear multivariate regression analysis: association between SGRQ total-score and age and nicotine consumption adjusted for sex, augmentation therapy and occupational dust exposure

Table S2 Linear multivariate regression analysis: association between SGRQ total-score and exacerbation frequency adjusted for sex, augmentation therapy and occupational dust exposure

Table S3 Linear multivariate regression analysis: association between SGRQ total-score and FEV₁ (% pred.) adjusted for sex, augmentation therapy and occupational dust exposure

Table S4 Linear multivariate regression analysis: association between SGRQ total-score and DLCO (% pred.) adjusted for sex, augmentation therapy and occupational dust exposure

Table S5 Linear multivariate regression analysis: association between annual change in SGRQ total-score and exacerbation frequency adjusted for sex, age, augmentation therapy and occupational dust exposure

Acknowledgments

The AATDR was supported by grants from the EU PAAIR, the Bundesministerium für Bildung und Forschung COSYCONET/ASCONET (BMBF 01GI1001) to RB and CV, and supported by a grant from Bayer/Talecris/Grifols from 2003 until 2012. The study was supported by a donation of the Bumm family to the Saarland University.

Availability of data and materials: The data sets of the AATDR are located at the Department of Internal Medicine V – Pulmonology, Allergology, Intensive Care Medicine, Saarland University Hospital, Homburg, Germany and are available from the corresponding author on reasonable request.

Author contributions

NB, PML, CV, RB, and SF contributed to conception of the study, patient recruitment and original data collection and interpretation. MS contributed to the patient recruitment. SW supported the statistical analysis. The authors alone are responsible for the content and the writing of the paper. All authors contributed toward data analysis, drafting and revising the paper and agree to be accountable for all aspects of the work.

Disclosure

RB, SF and CV have obtained research support and travel sponsoring from Talecris/Grifols and CSL Behring. CV has received honoraria for speaking engagements and for chairing a research prize committee from Talecris/Grifols. PML has received speaker fees from Talecris/Grifols. The authors report no other conflicts of interest in this work.