Predictors of mortality in  1-antitrypsin deficiency

Abstract

Background: Lung density measurements by computed tomography have previously been found to be a more sensitive indicator of disease progression in emphysema of a 1 -antitrypsin deficiency than lung function measurements. The aim of this study was to investigate the predictive potential of several parameters, including CT scanning, for mortality in patients with severe a 1 -antitrypsin deficiency. Methods: Over a 5 year period, 256 patients with a 1 -antitrypsin deficiency (PiZ phenotype) were assessed, of whom 254 underwent lung function testing and 197 had thoracic CT scans. Lung function, CT scans, health status (St George's Respiratory Questionnaire, SGRQ), and other clinical data of survivors and non-survivors were compared and these parameters were applied to survival analyses. Results: There were 22 deaths in this patient cohort, 10 of which were classified as ''respiratory'' deaths. Baseline lung function parameters (forced expiratory volume in 1 second (FEV 1 ), carbon monoxide transfer coefficient (KCO)), and CT scores were significantly lower in the non-survivors than in the survivors. 170 of the 256 patients had complete data for entry into multiple regression analyses (Cox proportional hazards model). In the univariate analysis, upper zone expiratory scan had the best association with all cause (p = 0.001) and respiratory mortality (p,0.001), whereas FEV 1 (p = 0.158 all cause, 0.015 respiratory) and KCO (p = 0.002 all cause, 0.012 respiratory) had poorer associations with mortality. Only age gave further independent predictive information regarding all cause or respiratory mortality when the CT scan was entered into the survival analyses. Conclusions: CT scanning predicts respiratory and all cause mortality in a 1 -antitrypsin deficiency and appears to be superior to lung function parameters, especially FEV 1 .

COPD in individuals with the PiMZ alpha-1 antitrypsin genotype

“…The strength of these studies is moderate, and better when emphysema is quantified independently of spirometric variables. Because CT emphysema is correlated to mortality in AAT deficiency while lung function is not [47], these studies are sufficient to demonstrate an increased risk for COPD in MZ subjects.…”

Rate of progression of lung function impairment in α1-antitrypsin deficiency

“…The fast-decline tertile and slow-decline tertile were compared, using univariate and multivariate analyses, for differences in the following parameters, assessed at baseline: sex; body mass index (BMI); acute reversibility to bronchodilator (BDR; defined by ATS criteria; o200 mL change in FEV1 and 12% change from baseline FEV1 after 400 mg inhaled salbutamol [10]); smoking status; chronic bronchitis (UK Medical Research Council criteria [11]); age; health status scores, from the 36-item short-form health survey (SF-36) physical and mental component scores, and St George's Respiratory Questionnaire total score; exacerbation rates characterised as type 1 and 2 as described by ANTHONISEN [12], derived from self-reported retrospective recall on an annual questionnaire; baseline FEV1 (% pred); baseline KCO (% pred); and extent of emphysema on computed tomography (CT) scan (inspiratory and expiratory films, lower and upper zones) using the voxel index (-910 HU) as described previously [13].…”

Exploring the role of CT densitometry: a randomised study of augmentation therapy in α1-antitrypsin deficiency

“…Furthermore, while CT densitometry is a more sensitive measure of emphysema progression and a better predictor of mortality than lung function [16], CT lung density decline also relates to progressive reduction in FEV1 [14]. Although these studies have led to the acceptance of this relatively novel technique, subsequent technological advances and a continued lack of consensus on methodology make further exploratory studies necessary.…”