B44-07 Systematic Literature Review on Quantitative Computed Tomography and Clinical and Patient Reported Outcomes in Alpha-1 Antitrypsin Deficiency

Abstract Rationale Quantitative computed tomography (qCT) densitometry provides an objective measure of emphysema severity in alpha-1 antitrypsin deficiency (AATD) that is complementary to spirometric indices of airflow obstruction in assessing parenchymal destruction, the central pathognomonic feature of AATD. This study assessed the relationship between qCT densitometry and clinical and patient-reported outcomes (PROs) in AATD. Methods Literature searches were conducted on 26 September 2025. Two reviewers independently screened abstracts and full texts; data extraction was performed by one reviewer and validated by a second. We included studies of adults with AATD assessing the relationship between 15th percentile lung density (PD15) and/or low-attenuation area percentage below −950 Hounsfield units (LAA% −950 HU) and pulmonary function tests, PROs, morbidity outcomes, and mortality. The review was registered in PROSPERO (CRD420251146249). Results Eighteen publications reporting ten unique studies were included (three clinical trials; seven observational). Mean age ranged from 47-60 years; most cohorts were predominantly male with ZZ genotype. Ex-smokers comprised 49%-91%; three studies included current smokers (4%-22%). Baseline mean FEV1% predicted was 45%-59%, indicating moderate-severe airflow obstruction. Studies used PD15 alone (n = 6), LAA% −950 HU (n = 1), or both (n = 3). PD15 showed significant correlations with FEV1% predicted in four studies (r = 0.31 to 0.61), FEV1 (mL) in two (r = 0.26 to 0.42), FEV1/FVC in two (r = 0.51 to 0.59), and FVC in one (r = 0.30). LAA% −950 HU correlated negatively with FEV1% predicted in four studies (r = −0.75 to − 0.45) and with FEV1/FVC in one (r = −0.65). Two studies linked changes in qCT to changes in FEV1 (mL): PD15 (r = 0.32 to 0.58) and LAA% −950 HU (r = −0.40 to − 0.25), consistent with worse lung function as parenchymal destruction increases. One study generated a minimum clinically important difference (MCID) for lung density decline: −1.87 g/L/year (range, −1.53 to − 2.20) and an absolute lung density change MCID of − 2.04 g/L (range, −1.83 to − 2.30), both associated with lung function and mortality. Significant associations with exacerbations were observed in four studies, St George’s Respiratory Questionnaire in three, and with mortality in one. No studies assessed associations with lung transplantation or hospitalizations. Conclusions Consistent correlations were noted between CT derived measures of emphysema and lung function, symptoms, and morbidity. These data provide support for the use of quantitative CT lung density as an objective, relevant outcome for emphysema progression in patients with AATD. This abstract is funded by: Sanofi