There is No Fast Track to Identify Fast Decliners in Alpha-1 Antitrypsin Deficiency by Spirometry: A Longitudinal Study of Repeated Measurements

Abstract

James A Stockley,1 Robert A Stockley,2 Elizabeth Sapey3 1Lung Function & Sleep Department, University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2GW, UK; 2Respiratory Department, University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2GW, UK; 3PIONEER Health Data Hub in Acute Care, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, B15 2GW, UKCorrespondence: Elizabeth SapeyPIONEER Health Data Hub in Acute Care, Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham, B15 2GW, UKEmail [email protected]: It is known that lung function decline in Alpha-1 Antitrypsin Deficiency (AATD) varies. Those with a rapid decline are at highest risk of poorer outcomes but may benefit most from targeted treatments including augmentation therapy. Current evidence suggests rapid decliners can be identified after 3 years of serial follow-up. It would be advantageous to identify these patients over a shorter time period, especially in mild disease.Methods: Post-bronchodilator spirometry was performed every 6 months for a total of 18 months (4 measurements) by PiZZ AATD patients (ex- or never-smokers) either without spirometric COPD or with mild COPD. Where possible, retrospective spirometry data were included. Decline was assessed using 2 (baseline and 6 month) or four measurements (including baseline, 6, 12 and 18 months) and compared to retrospective decline rates using annual measurements over 3 years.Results: Seventy-two PiZZ AATD patients were included, with 27 having at least three years of retrospective, annual spirometry. 18-month progression obtained by linear regression showed variable degrees of change with 29 showing no decline, 8 showing slow decline and 35 showing rapid decline. Bland-Altman plots showed that there was no overall agreement between predicted rate of decline using data obtained over 6 months and that obtained over 18 months. Furthermore, there was no agreement between rate of decline from either 6 or 18 months’ data when compared to data collected over 3 years. The positive predictive value for rapid decline with 18 months of data compared to 3 years was only 50.0%.Conclusion: This study suggests serial lung function over 18 months cannot identify AATD patients who have rapidly declining lung function. There is an urgent need for different biomarkers to help identify these patients at the earliest opportunity.Keywords: lung function, decline, obstructive airways disease, alpha-1 antitrypsin deficiency

Keywords

• lung function
• decline
• obstructive airways disease
• alpha 1 antitrypsin deficiency