title: Impaired endothelium-dependent vasodilator response in patients with pulmonary fibrosis.
abstract: BACKGROUND
  Recent epidemiological evidence indicates an association between cardiovascular diseases and pulmonary fibrosis. The vascular endothelium acts to maintain vascular homeostasis through multiple mechanisms and impaired endothelial function can contribute to the development, progression and clinical expression of atherosclerosis.
  
  
  METHODS
  We consecutively recruited 39 newly-diagnosed chronic interstitial pneumonitis/fibrosis patients without any specific etiology. We assessed endothelium-dependent vasodilator response of patients using digital pulse amplitude tonometry and compared the reactive hyperemia index (RHI) with age-, sex- and body mass index-matched control subjects (n = 30). We further investigated the relationships between RHI and clinical characteristics, laboratory cardiovascular risk factors, disease-related factors and circulating levels of inflammatory biomarkers.
  
  
  RESULTS
  RHI was significantly lower in patients with chronic interstitial pneumonitis/fibrosis than in control subjects (p = 0.02). While circulating levels of total cholesterol, triglycerides, HbA1c and fasting glucose did not differ significantly between groups, patients with chronic interstitial pneumonitis/fibrosis had significantly lower high density lipoprotein levels and higher low density lipoprotein levels as compared with control subjects. Regarding disease-related factors, RHI was significantly associated with the diffusing capacity for carbon monoxide, alveolar-arterial oxygen pressure difference, 6-min walk distance and end-exercise oxygen saturation. Additionally, circulating levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were inversely correlated with RHI.
  
  
  CONCLUSIONS
  We confirmed a possible link between pulmonary fibrosis and cardiovascular disease by demonstrating an impairment of endothelium-dependent vasodilator response, which was significantly associated with the severity of pulmonary fibrosis and circulating levels of adhesion molecules.
authors.affiliation: Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Japan.
authors.forename: Kensaku
authors.initials: K
authors.lastname: Aihara
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Handa
authors.forename: Sonoko
authors.initials: S
authors.lastname: Nagai
authors.forename: Kiminobu
authors.initials: K
authors.lastname: Tanizawa
authors.forename: Kohei
authors.initials: K
authors.lastname: Ikezoe
authors.forename: Kizuku
authors.initials: K
authors.lastname: Watanabe
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Chihara
authors.forename: Yuka
authors.initials: Y
authors.lastname: Harada
authors.forename: Chikara
authors.initials: C
authors.lastname: Yoshimura
authors.forename: Toru
authors.initials: T
authors.lastname: Oga
authors.forename: Neiko
authors.initials: N
authors.lastname: Ozasa
authors.forename: Kazuko
authors.initials: K
authors.lastname: Uno
authors.forename: Kazuo
authors.initials: K
authors.lastname: Chin
authors.forename: Michiaki
authors.initials: M
authors.lastname: Mishima
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002245:Carbon Dioxide / Q000097:blood; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D045462:Endothelium-Dependent Relaxing Factors; D005260:Female; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008365:Manometry / Q000379:methods; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D011658:Pulmonary Fibrosis / Q000097:blood / Q000503:physiopathology*; D014057:Tomography, X-Ray Computed; D014664:Vasodilation / Q000502:physiology
chemical_list: D015415:Biomarkers; D045462:Endothelium-Dependent Relaxing Factors; D018836:Inflammation Mediators; D008055:Lipids; D002245:Carbon Dioxide; D010100:Oxygen