Small airways dysfunction and “early” COPD due to alpha-1 antitrypsin deficiency

<bold>Background:</bold> There is increasing interest in small airways dysfunction (SAD) as the earliest physiological evidence of developing COPD. Previously we have shown that low maximal mid-expiratory flow (MMEF) in Alpha-1 Antitrypsin Deficiency (AATD) subjects is associated with a faster rate of FEV1 decline on average (Stockley J et al ERJ 2017;49:1602055). We sought to determine if other tests previously proposed as markers of SAD could show similar potential. <bold>Methods:</bold> Group 1 (n=33) had FEV1/FVC>70% and MMEF >80% pred (no SAD, no COPD) and Group 2 (n=24) had FEV1/FVC>70% and MMEF<80% predicted (SAD, no COPD). We compared area under the expiratory flow-volume curve (AEX), lung clearance index (LCI), oscillometry (R5-R20, X5, Fres), and total/effective specific resistance (SRtot, SReff) by plethysmography using an independent t-test or Mann Whitney-U test, depending on distribution. <bold>Results:</bold> AEX, two oscillometry parameters (X5 and Fres), and SRtot were different in Group 2 (Table 1). <table-wrap><object-id>erj;64/suppl_68/PA3474/TB1</object-id><object-id>T1</object-id><object-id>TB1</object-id><table><colgroup><col></col><col></col><col></col><col></col></colgroup><tbody><tr><td></td><td>Group 1</td><td>Group 2</td><td>p</td></tr><tr><td>AEX %Pred</td><td>121.4 (4.1)</td><td>96.5 (5.2)</td><td><0.0001</td></tr><tr><td>LCI</td><td>7.70 (7.01, 8.96)</td><td>8.77 (7.88, 9.88)</td><td>ns</td></tr><tr><td>R5-R20</td><td>0.020 (0.001, 0.054)</td><td>0.029 (0.020, 0.049)</td><td>ns</td></tr><tr><td>XS</td><td>-0.673 (0.005)</td><td>-0.908 (0.007)</td><td><0.01</td></tr><tr><td>Fres</td><td>8.78 (7.76, 10.92)</td><td>11.26 (8.76, 12.81)</td><td>0.02</td></tr><tr><td>SReff %Pred</td><td>60.9 (52.6, 75.5)</td><td>68.5 (60.0, 81.6)</td><td>ns</td></tr><tr><td>SRtot %Pred</td><td>82.5 (3.8)</td><td>93.7 (4.9)</td><td>0.04</td></tr></tbody></table></table-wrap> Table 1: Comparisons in AATD between Group 1 and Group 2. Data presented as Mean (SE) or Median (LQ,UQ). <bold>Conclusions:</bold> In AATD, there are other markers of SAD beyond MMEF that may identify patients with early disease and could potentially identify more rapid FEV1 decliners, although this will need future investigation. Most of these are non-volitional and may be more achievable than spirometry.