COPDの重症度分類と臨床フェノタイプの関連

論文No915

Phenotype of Spirometric Impairment in an Aging Population

Carlos A. Vaz Fragoso, Gail McAvay, Peter H. Van Ness, Richard Casaburi, Robert L. Jensen, Neil MacIntyre, H. Klar Yaggi, Thomas M. Gill, and John Concato

American Journal of Respiratory and Critical Care Medicine, Vol. 193, No. 7 (2016), pp. 727-735.

doi: 10.1164/rccm.201508-1603OC

＜背景＞
Global Lung Initiative (GLI) は年齢ごとに肺機能障害の基準（ＣＯＰＤの軽症、中等症、重症や拘束性障害を含む）を提供している。
しかし、呼吸に関連したフェノタイプとの関係については評価されていない。

＜目的＞
ＧＬＩ定義の肺機能障害における呼吸に関連したフェノタイプを評価する。

＜方法＞
COPDGene（１０１３１名、４５－８１歳、平均４４．３pack-yearの喫煙歴）において、
肺機能検査、呼吸困難感（修正ＭＲＣグレード２以上）、低い呼吸器健康関連ＱＯＬ（ＳＧＲＱスコアで２５以上）、運動能力低下（６分間歩行が３９１ｍ未満）、気管支拡張薬への反応性（ＦＥＶ１変化率１２％以上、絶対値２００ｍＬ以上の増加）、ＣＴによる気腫化（５％以上）とガスとらえこみ（１５％以上）を評価した。

＜結果＞
ＧＬＩ分類による正常肺機能は５１００名（５０．３％）、軽症ＣＯＰＤ６６９名（６．６％）、中等症ＣＯＰＤ（８６５名（８．５％）、重症ＣＯＰＤ２５２２名（２４．９％）、拘束性障害９７５名（９．６％）であった。
正常肺機能群と比べて、呼吸に関連したフェノタイプが軽症、中等症、重症ＣＯＰＤでみつかった。
補正オッズ比で以下のとおりである。
呼吸困難感：1.31 (1.10–1.56), 2.20 (1.81–2.68), and 10.73 (8.04–14.33)。
健康関連ＱＯＬが低い：1.49 (1.28–1.75), 2.69 (2.08–3.47), and 14.61 (10.09–21.17)。
運動能力が低い：1.11 (0.94–1.31), 1.58 (1.33–1.88), and 4.58 (3.42–6.12)。
気管支拡張薬への反応性：2.76 (2.24–3.40), 5.18 (4.29–6.27), and 6.21 (5.06–7.62)。
肺気腫：4.86 (3.16–7.47), 6.41 (4.09–10.05), and 17.79 (10.79–29.32)。
スとらえこみ：3.92 (3.12–4.93), 5.20 (3.82–7.07), and 16.28 (9.71–27.30)。
拘束性障害も中等症ＣＯＰＤと同程度に複数の呼吸関連フェノタイプと関連したが、
肺気腫とガスとらえこみとは関連しなかった。

＜感想＞
ＧＬＩによるＣＯＰＤの重症度分類は臨床的な症状の程度と相関を示すことが確認されたようです。

Rationale: The Global Lung Initiative (GLI) provides age-appropriate criteria for establishing spirometric impairment, including mild, moderate, and severe chronic obstructive pulmonary disease (COPD) and restrictive pattern, but its association with respiratory-related phenotypes has not been evaluated.

Objectives: To evaluate respiratory-related phenotypes in GLI-defined spirometric impairment.

Methods: In COPDGene (N = 10,131 patients; age range, 45–81 yr; average smoking history, 44.3 pack-years), we evaluated spirometry, dyspnea (modified Medical Research Council grade, ≥2), poor respiratory health-related quality of life (St. George’s Respiratory Questionnaire total score, ≥25), poor exercise performance (6-minute-walk distance, <391 m), bronchodilator reversibility (FEV₁ change, >12% and ≥200 ml), and computed tomography–diagnosed emphysema and gas trapping (>5% and >15% of lung, respectively).

Measurements and Main Results: GLI established normal spirometry in 5,100 patients (50.3%), mild COPD in 669 (6.6%), moderate COPD in 865 (8.5%), severe COPD in 2,522 (24.9%), and restrictive pattern in 975 (9.6%). Relative to normal spirometry, graded associations with respiratory-related phenotypes were found for mild, moderate, and severe COPD, with respective adjusted odds ratios (95% confidence intervals) as follows: dyspnea—1.31 (1.10–1.56), 2.20 (1.81–2.68), and 10.73 (8.04–14.33); poor respiratory health-related quality of life—1.49 (1.28–1.75), 2.69 (2.08–3.47), and 14.61 (10.09–21.17); poor exercise performance—1.11 (0.94–1.31), 1.58 (1.33–1.88), and 4.58 (3.42–6.12); bronchodilator reversibility—2.76 (2.24–3.40), 5.18 (4.29–6.27), and 6.21 (5.06–7.62); emphysema—4.86 (3.16–7.47), 6.41 (4.09–10.05), and 17.79 (10.79–29.32); and gas trapping—3.92 (3.12–4.93), 5.20 (3.82–7.07), and 16.28 (9.71–27.30). Restrictive pattern was also associated with multiple respiratory-related phenotypes at a level similar to moderate COPD, but it was otherwise not associated with emphysema (0.89 [0.60–1.32]) or gas trapping (1.15 [0.92–1.42]).

Conclusions: GLI-defined spirometric impairment establishes clinically meaningful respiratory disease, as validated by graded associations with respiratory-related phenotypes.