Table 3.
Effects of PI Types Z and S and Additional Rare SERPINA1 Variants on Lung Function, Emphysema, and Related Phenotypes in Non-Hispanic White Individuals
| Number of RVs | Additive P Value | 0RVs vs. 1RV | 1RV vs. 2RVs | 0RVs vs. 2RVs | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 0RVs | 1RV | 2RVs | β (SE)/OR (95% CI) | P Value | β (SE)/OR (95% CI) | P Value | β (SE)/OR (95% CI) | P Value | ||
| Total non-Hispanic white individuals, n | 1,411 | 259 | 21 | — | — | — | — | — | ||
| Post-BD lung function | ||||||||||
| Post-BD, FEV1% predicted | 72.6 (25.6) | 69.1 (25.9) | 50.2 (25.7) | 8.13 × 10−5 | −1.42 (0.82) | 0.08 | −8.71 (2.84) | 0.002 | −11.0 (2.66) | 3.58 × 10−5 |
| Post-BD, FVC% predicted | 90.5 (17.7) | 90.0 (17.8) | 84.8 (20.4) | 0.23 | 0.27 (0.55) | 0.62 | −3.14 (1.97) | 0.11 | −2.98 (1.80) | 0.1 |
| Post-BD, FEV1/FVC ratio | 0.59 (0.16) | 0.57 (0.16) | 0.44 (0.16) | 1.22 × 10−6 | −0.01 (0.01) | 0.005 | −0.06 (0.02) | 0.001 | −0.08 (0.02) | 3.52 × 10−6 |
| Post-BD, FEF25–75 % predicted | 55.7 (40.2) | 50.4 (38.8) | 27.1 (31.2) | 3.31 × 10−6 | −0.03 (0.01) | 0.004 | −0.10 (0.03) | 0.002 | −0.14 (0.03) | 1.69 × 10−5 |
| GOLD grade 2 or higher, n (%) | 748 (53.0%) | 155 (59.8) | 18 (85.7) | 0.001 | 1.30 (0.98–1.74) | 0.07 | 6.13 (1.99–26.8) | 0.007 | 4.71 (1.48–20.9) | 0.0009 |
| 3-yr longitudinal lung function, n | 1,214 | 223 | 16 | — | — | — | — | — | ||
| Annual rate of change, FEV1, L/yr | −0.04 (0.13) | −0.05 (0.15) | −0.14 (0.16) | 0.007 | −0.004 (0.005) | 0.42 | −0.05 (0.02) | 0.01 | −0.05 (0.02) | 0.001 |
| Annual rate of change, FVC, L/yr | −0.04 (0.23) | −0.04 (0.22) | −0.16 (0.34) | 0.04 | −0.001 (0.008) | 0.93 | −0.07 (0.03) | 0.01 | −0.07 (0.03) | 0.009 |
| Annual rate of change, FEV1/FVC per year | −0.006 (0.03) | −0.007 (0.03) | −0.02 (0.02) | 0.06 | −0.0005 (0.001) | 0.6 | −0.007 (0.004) | 0.09 | −0.008 (0.004) | 0.02 |
| Computed tomography scan–based measures | ||||||||||
| Emphysema, TLC % area ≤ −950 HFU | 7.83 (9.86) | 9.43 (11.0) | 17.2 (13.2) | 2.53 × 10−9 | 0.04 (0.01) | 0.049 | 0.19 (0.06) | 0.002 | 0.26 (0.06) | 1.47 × 10−5 |
| Air trapping, residual volume % area ≤ −856 HFU | 25.4 (20.8) | 27.3 (21.3) | 46.5 (21.7) | 8.03 × 10−6 | 0.03 (0.01) | 0.08 | 0.17 (0.04) | 0.0005 | 0.23 (0.05) | 2.89 × 10−6 |
| Small airway disease, PRMfSAD, % | 21.6 (15.1) | 22.2 (14.4) | 34.4 (13.3) | 9.25 × 10−5 | 0.02 (0.01) | 0.16 | 0.13 (0.04) | 0.002 | 0.17 (0.04) | 2.34 × 10−5 |
| Alpha-1 antitrypsin concentration, n | 922 | 162 | 13 | |||||||
| Alpha-1 antitrypsin concentration, mg/ml* | 2.05 (0.45) | 1.62 (0.42) | 0.92 (0.52) | 2.0 × 10−46 | −0.22 (0.02) | 5.47 × 10−33 | −0.36 (0.06) | 1.73 × 10−7 | −0.56 (0.06) | 1.22 × 10−19 |
Definition of abbreviations: BD = bronchodilator; CI = confidence interval; FEF25–75 = forced expiratory flow, midexpiratory phase; GOLD = Global Initiative for Chronic Obstructive Lung Disease; HFU = Hounsfield units; OR = odds ratio; PI = protease inhibitor; PRMfSAD = parametric response mapping of functional small airway disease; RV = rare variant.
Subjects with 0RVs, 1RV, and 2RVs, including PI types Z and S, were compared. Data are shown as mean (SD) unless otherwise indicated. Regression-based analyses of lung function are adjusted by study site, age, sex, body mass index, and pack-years smoking history. Log-transformed percentage predicted FEF25–75 also adjusted for post-BD percentage predicted FVC and longitudinal, annualized rate of change for baseline lung function as a percentage of predicted. Computed tomography scan–based measures of emphysema (−950 HFU or less [% bilateral lung area ≤ −950]), air trapping (−856 HFU or less [% bilateral lung area ≤ −856]), and PRMfSAD measures log-transformed for analysis and also adjusted for height.
Alpha-1 antitrypsin concentrations also adjusted for C-reactive protein.