TABLE 3

Quality of life review: St George's Respiratory Questionnaire (SGRQ) scores in patients with alpha-1 antitrypsin deficiency (AATD)

First author, year [ref.]Population/ treatmentSubjects nTime pointSGRQ scores Main SGRQ outcomes
TotalSymptomsActivityImpact
Bernhard,  2017 [79]AATD (PiZZ): never-smokers22336.9±21.844.5±23.845.3±26.828.7±21.5In contrast to never- and intensive (ex-) smokers, moderate-smoking PiSZ individuals had a significantly better SGRQ total score (p=0.020) and fewer exacerbations (p=0.037) than individuals with a PiZZ genotype.
AATD (PiSZ): never-smokers3322.5±21.635.0±23.925.2±29.616.7±19.3
AATD (PiZZ): moderate (ex-) smokers (0<pack-years<30)49146.9±19.855.7±22.758.3±22.637.3±21.0
AATD (PiSZ): moderate (ex-) smokers (0<pack-years<30)4438.9±25.643.3±28.248.8±30.429.0±24.3
AATD (PiZZ): intensive (ex-) smokers (≥30 pack-years)12653.2±16.562.8±19.767.5±18.141.9±18.7
AATD (PiSZ): intensive (ex-) smokers (≥30 pack-years)3359.8±19.062.1±20.771.6±20.149.2±22.3
Piitulainen,  2017 [80]AATD (PiZZ): never-smokers1523.7 (0–56.3)2.5 (0–78.4)6.0 (0–59.5)0 (0–47.6)PiZZ current smokers had a significantly higher median SGRQ activity score than the PiZZ never-smokers (p=0.032).# PiMM current smokers had significantly higher SGRQ activity (p<0.001), symptom (p<0.001) and total (p=0.001) scores than PiMM never-smokers.
AATD (PiZZ): former smokers405.0 (0–34.4)7.5 (0–52.2)8.8 (0–41.1)0 (0–24.2)
AATD (PiZZ): current smokers1914.2 (2.9–20.1)18.4 (5.9–36.3)24.6 (6.0–47.7)#2.8 (0–8.7)
AATD (PiSZ): never-smokers1526.2 (61.8)11.8 (0–58.9)12.2 (0–66.9)0 (0–59.9)
AATD (PiSZ): former smokers404.7 (2.0–7.3)5.5 (0–18.4)12.2 (6.0–18.5)0 (0–0)
AATD (PiSZ): current smokers1913.937.818.514.2
Luisetti, 2015 [81]AATD52Baseline29.8±26.3Patients who received AAT therapy had poorer baseline QoL versus patients who did not receive AAT therapy (p=0.001).
AATD index cases35Baseline41.2±24.4
AATD non-index cases17Baseline6.3±8.3
AATD + AAT therapy18Baseline52.7±20.6
AATD without AAT therapy19Baseline28.0±21.8
Gauvain, 2015 [76]AATD273Baseline49.0±20.052.5±22.063.6±22.339.4±22.2The number of exacerbations in the past year was significantly associated with SGRQ score (R=0.36; p<0.0001) and SGRQ scores had the strongest association with dyspnoea (R=0.65; p<0.0001). Multivariate analysis suggested that 57% of the variability seen in SGRQ scores resulted from dyspnoea (p<0.0001), DLCO (% predicted) (p<0.001), chronic bronchitis (p=0.002), age (p=0.0088) and 6-min walk distance (p=0.037).
AATD: females101Baseline52.7±20.7
AATD: males172Baseline46.8±18.2
Bradi, 2015 [82]AATD + AAT therapy241 year50±14AAT therapy status was significantly correlated with SGRQ scores when controlling for baseline FEV1 (p=0.014).
AATD without AAT therapy34±22
Stolk, 2003 [14]AATD22Baseline32.4±20.1Changes in lung density as measured by CT scan (15th percentile point and relative area <–950 HU) were correlated with SGRQ total scores (R= –0.56, p=0.007 and R=0.6, p=0.003, respectively).
AATD2230 monthsCFB: 6.5 (–2.9–17.5)
Annunziata,  2021 [73]AATD16Baseline18.0±3.0All the questionnaires completed at 3 months showed an increase in score compared with the questionnaire completed during the last hospital administration session (p<0.01).
AATD163 months22.6±3.3
Schramm, 2020 [83]AATD (PiZZ)8412.014.018.87.3There was no significant difference in SGRQ score between PiZZ ever-smokers and never-smokers, but PiZZ ever-smokers had significantly higher scores in all categories compared with never-smoking controls (symptom p=0.04, activity p=0.01, impact p=0.03, total p<0.01).
Never-smoking control723.84.57.81.0
Sandhaus,  2020 [84]AATD (PiZZ or worse) + AAT therapy655Annual worsening of SGRQ total was on average 1.3 points per year worse in control group patients versus those receiving AAT therapy (95% CI 0.41–2.19, p=0.004).
AATD without AAT therapy655
Crossley, 2020 [85]AATD18745.2 (3.3–62.1)Median SGRQ score was 45.2 (33.3–62.1) and related to the GOLD stage (p<0.001). There were significant correlations between QoL measures and spirometry, as measured by FEV1 (% predicted), FVC (% predicted), FEV1/FVC (%) and with gas transfer coefficient (% predicted) and gas trapping as measured by RV/TLC (%) (p<0.01 all comparisons). Total SGRQ correlated significantly with CT density, although the relationship was weak (r2<0.1).
AATD plus COPD or emphysema
 Hogarth, 2019 [86]AATD + severe emphysema20Baseline55.2±16.0After 6 months, SGRQ had decreased substantially compared with baseline in patients fitted with an endobronchial valve.
206 monthsCFB: –14.3±12.9
2012 monthsCFB: –8.2±12.9
 Durkan, 2019 [87]AATD + COPD30NR36.5±18.542.4±41.624.9±17.3For the same level of COPD impairment, PiZZ patients presented with lower SGRQ scores than PiMM patients.
 Stockley, 2018 [88]AATD (without obstruction)84Baseline14.0 (4.8–5.5)30.9 (11.7–57.1)12.2 (0–41.6)5.8 (0–21.4)Baseline SGRQ scores were correlated with baseline FEV1 in patients with AATD with or without COPD (r2=0.34, p<0.0001). Annual SGRQ decline was greater for patients with AATD diagnosed with COPD who had a rapid FEV1 decline.
AATD + COPD370Baseline48.2 (33.9–62.4)62.5 (46.2–78.6)60.4 (47.4–79.7)34.9 (21.3–49.9)
AATD with no FEV1 decline35Baseline16.2 (4.8–35.5)35 (11.7–57.1)23.3 (0–41.6)11.2 (0–21.4)
AATD with FEV1 decline22Baseline11.5 (33.9–62.4)30.5 (46.2–78.6)11.7 (47.4–79.7)5.3 (21.3–49.9)
AATD + COPD with no FEV1 decline72Baseline51.8 (35.0–63.3)62.4 (51.5–78.1)66.6 (47.7–80.9)35.6 (22.3–49.5)
AATD + COPD with FEV1 decline189Baseline45.2 (30.5–61.5)60.5 (42.9–74.6)59.5 (41.4–79.9)34.1 (17.0–47.2)
AATD (without obstruction)84Annual decline0.2 (–0.8–1.1)0.00 (−2.5–2.0)0.00 (−0.8–1.4)0.14 (−0.5–0.9)
AATD + COPD370Annual decline0.7 (–0.8–2.4)0.21 (−2.3–2.1)1.2 (−0.5–3.6)0.4 (−1.1–2.2)
AATD with no FEV1 decline35Annual decline0.04 (–0.7–0.8)–0.2 (–3.0–1.6)0.05 (–1.4–1.3)0.03 (–0.6–0.7)
AATD with FEV1 decline22Annual decline0.5 (–1.0–1.9)0.9 (–1.5–2.3)0.9 (0.0–3.0)0.3 (–1.0–1.3)
AATD + COPD with no FEV1 decline72Annual decline0.5 (–0.8–1.5)–0.2 (–1.9–1.3)0.7 (–0.4–2.3)0.1 (–0.9–1.5)
AATD + COPD with FEV1 decline189Annual decline1.07 (–1.1–2.9)0.5 (–2.6–2.7)1.5 (–0.5–4.3)0.7 (–1.0–3.0)
 Karl, 2017 [75]AATD + COPD131NR44.8±17.2No significant differences in SGRQ scores were observed between patients with AATD diagnosed with COPD who were recipients and non-recipients of AAT therapy.
AATD + COPD + AAT therapy106NR46.6±16.4
AATD + COPD without AAT therapy25NR37.5±20.2
 Chapman, 2015 [12]AATD + emphysema + A1P1 therapy93Baseline44.3±17.146.5±22.762.1±18.633.6±18.4Improvements were reported in only the SGRQ symptom domain after 24 months of treatment.
AATD + emphysema + placebo87Baseline42.4±18.044.1±24.860.1±21.431.4±17.6
AATD + emphysema + AAT therapy9324 monthsCFB: 1.4±11.1CFB: –1.4±16.7CFB: 1.7±12.4CFB: 2.1±14.8
AATD + emphysema + placebo8724 monthsCFB: 2.2±11.7CFB: 2.0±20.1CFB: 2.6±13.5CFB: 1.8±12.5
 Ponce, 2014 [89]AATD + COPD573Baseline46.0±17.8Poorer SGRQ scores were observed in obese versus non-obese AATD patients diagnosed with COPD.
AATD + COPD5735 years51.0±17.7
 Holm, 2013 [90]AATD + COPD57848.5±19.4AATD patients diagnosed with COPD had an SGRQ total score almost 5 points higher than non-AATD patients diagnosed with COPD when adjusting for demographic and health characteristics.
 Lascano, 2010 [91]AATD + COPD + AAT therapy: overweight2411 year47.2±16.0SGRQ scores were higher in obese patients versus patients with a normal BMI; however, the obese patients had similar FEV1 to the normal BMI group, but more comorbidity. Underweight patients had worse QoL and significantly lower FEV1 versus normal BMI individuals.
AATD + COPD + AAT therapy: obese1041 year48.7±17.1
AATD + COPD + AAT therapy: morbidly obese611 year55.5±17.1
AATD + COPD + AAT therapy: normal BMI2041 year43.4±16.6
 Campos, 2009 [74]AATD + COPD + AAT therapy922Baseline48.1±18.4Subjects with frequent exacerbations had the worst baseline HRQoL scores, as well as more physician visits, emergency room visits and hospitalisations.
AATD + COPD + AAT therapy; no exacerbations83Baseline37.3±17.333.1±43.557.5±23.427.0±16.5
AATD + COPD + AAT therapy; 1–2 exacerbations per year391Baseline44.5±16.643.0±22.164.1±21.233.6±16.5
AATD + COPD + AAT therapy; ≥3 exacerbations per year448Baseline52.4±16.554.0±21.471.0±20.541.2±17.6
 Dawkins, 2009 [92]AATD + COPD with fast FEV1 decline3349.6±20.1SGRQ total scores in fast decliners as measured by FEV1 were not significantly different from middle or slow decliners.
AATD + COPD with middle FEV1 decline3456.2±18.5
AATD + COPD with slow FEV1 decline3451.6±24.7
AATD with other comorbidity
 Stone, 2016 [93]AATD + lung transplant32Baseline64.2±2.575.4±2.593 (73–95)50.1±2.9Pre-transplant, although matched for FEV1, the transplant group had worse health status. Post-transplant, physiology and health status improved significantly (p<0.002).
AATD + no transplant48Baseline55.3±2.067.4±2.279 (59–91)40.3±2.4
AATD + pre-transplant14Baseline67.5 (51.0–77.8)76.5 (64.5–88.5)93.0 (4.8–98.3)50.0 (31.3–65.5)
AATD + post-transplant141 year7.5 (5.0–13.8)14.0 (9.0–30.3)11.0 (1.3–20.3)4.5 (1.0–9.5)
 Dowson, 2002 [78]AATD with chronic sputum expectoration5064.4 (48.3–74.4)75.6 (68.0–83.7)82.9 (60.4–100)49.9 (33.0–62.7)Patients with chronic sputum expectoration had worse health status, as assessed by SGRQ (p<0.01 for all domains), than patients who did not.
AATD without chronic sputum expectoration6742.0 (23.9–59.5)47.6 (28.9–66.7)59.5 (32.7–86.3)28.9 (11.7–47.6)

Data are presented as mean±sd or median (range), unless otherwise stated. PiSZ/ZZ: Pi (or SERPINA1 gene) SZ and ZZ alleles; AAT: alpha-1 antitrypsin; QoL: quality of life; DLCO: diffusing capacity of the lung for carbon monoxide; FEV1: forced expiratory volume in 1 s; CFB: change from baseline; CT: computed tomography; GOLD: Global Initiative for Chronic Obstructive Lung Disease; FVC: forced vital capacity; RV: residual volume; TLC: total lung capacity; NR: not reported; A1P1: α1 proteinase inhibitor; BMI: body mass index; HRQoL: health-related QoL. #: p=0.032 versus PiZZ never-smokers.