論文No2038
Systemic Markers of Inflammation in Smokers With Symptoms Despite Preserved Spirometry in SPIROMICS
Suresh Garudadri, Prescott G. Woodruff, MeiLan K. Han, Jeffrey L. Curtis, R. Graham Barr, Eugene R. Bleecker, Russell P. Bowler, Alejandro Comellas, Christopher B. Cooper, Gerard Criner, Mark T. Dransfield, Nadia N. Hansel, Robert Paine III, Jerry A. Krishnan, Stephen P. Peters, Annette T. Hastie, Fernando J. Martinez, Wanda K. O'Neal, David J. Couper, Neil E. Alexis, Stephanie A. Christenson
CHEST, Volume 155, Issue 5, p908–917, 2019.
＜背景＞
肺機能で気流閉塞のない既喫煙者において慢性呼吸器症状、増悪のようなイベントはよく起こる。
このサブグループにおける呼吸器疾患の病理生物学はよくわかっていない。
一部はCOPDや喘息と重なる基礎的な炎症によるのかもしれない。
我々は肺機能が保存されている喫煙者における症状、増悪、疾患重症度は、喘息でよくみられる
タイプ２炎症というよりはCOPDでみられる全身性炎症マーカーと関連しているのではないかと考えた。
＜方法＞
COPDに関連する炎症マーカー（CRP、フィブリノゲン、可溶性腫瘍壊死因子受容体(sTNFRSF1A, sTNFRSF1B)、血中／喀痰好中球）と
タイプ２炎症（IgE, 血中／喀痰中好酸球）を肺機能の保たれた(気管支拡張薬投与後のFEV1/FVC ≥ 0.70)
喫煙者で測定した（COPDにおけるSPIROMICS研究）。
我々はこれらのマーカーと呼吸器症状負荷（CATスコア10以上、慢性気管支炎）、増悪、６分間歩行距離、FEV1との関連を検討した。
＜結果＞
CRPは研究登録前１年の呼吸器症状負荷（CATスコア10以上、慢性気管支炎）、増悪回数と関連した。
sTNFRSF1AはCATスコアによる症状負荷と関連した。
CRPとsTNFRSF1Aレベルは６分間歩行距離と負の相関があった。
IgEや好酸球はこれらと関連しなかった。
＜感想＞
肺機能が正常の喫煙者においてCRPや可溶性腫瘍壊死因子受容体といった炎症マーカーが増加しており、
COPDの病態とのオーバーラップが示唆されたようです。
Background
Chronic respiratory symptoms and exacerbation-like events are common among ever-smokers without airflow limitation on spirometry. The pathobiology of respiratory disease in this subgroup remains poorly defined, but may be due to underlying inflammation that overlaps with COPD or asthma. We hypothesized that symptoms, exacerbations, and functional measures of disease severity among smokers with preserved spirometry would be associated with markers of systemic inflammation, similar to what is reported in bone fide COPD, rather than elevated type 2 inflammation, which is often present in asthma.
Methods
We measured inflammatory markers associated with COPD (C-reactive protein [CRP], fibrinogen, soluble tumor necrosis factor receptors [sTNFRSF1A and sTNFRSF1B], and blood/sputum neutrophils) and type 2 inflammation (IgE and blood/sputum eosinophils) in smokers with preserved spirometry (postbronchodilator FEV1/FVC ≥ 0.70) from the Subpopulations and Intermediate Outcome Measures In COPD Study (SPIROMICS). We evaluated the relationship of these markers with respiratory symptom burden (dichotomized by a COPD assessment test score cutoff of 10, diagnosis of chronic bronchitis), exacerbations, 6-minute walk distance, and lung function on the basis of FEV1.
Results
CRP was associated with increased symptom burden (on the basis of COPD assessment test score and diagnosis of chronic bronchitis) and a greater number of exacerbations in the year before study enrollment. sTNFRSF1A was associated with symptom burden on the basis of COPD assessment test score. CRP and sTNFRSF1A levels negatively correlated with 6-minute walk distance. IgE and eosinophils were not associated with these outcomes.
Conclusions
Markers of inflammation including CRP and sTNFRSF1A are enriched among symptomatic smokers with preserved spirometry, suggesting an overlap with the underlying pathophysiology of COPD.