Impaired endothelium-dependent vasodilator response in patients with pulmonary fibrosis

• Published in: Respiratory medicine 2013-02, Vol.107 (2), p.269-275
• Main Authors: Aihara, Kensaku, Handa, Tomohiro, Nagai, Sonoko, Tanizawa, Kiminobu, Ikezoe, Kohei, Watanabe, Kizuku, Chihara, Yuichi, Harada, Yuka, Yoshimura, Chikara, Oga, Toru, Ozasa, Neiko, Uno, Kazuko, Chin, Kazuo, Mishima, Michiaki
• Format: Article
• Language: English
• Subjects: Aged; Biological and medical sciences; Biomarkers - blood; Body Mass Index; Carbon Dioxide - blood; Cardiovascular disease; Case-Control Studies; Cholesterol; Digital pulse amplitude tonometry; Endothelial function; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Endothelium-Dependent Relaxing Factors; Female; Humans; Hyperemia - physiopathology; Inflammation Mediators - blood; Lipids - blood; Low density lipoprotein; Lungs; Male; Manometry - methods; Medical sciences; Middle Aged; Oxygen - blood; Partial Pressure; Pneumology; Pulmonary fibrosis; Pulmonary Fibrosis - blood; Pulmonary Fibrosis - physiopathology; Pulmonary/Respiratory; Reactive hyperemia; Respiratory system : syndromes and miscellaneous diseases; Tomography, X-Ray Computed; Vasodilation - physiology
• ISSN: 0954-6111; 1532-3064
• DOI: 10.1016/j.rmed.2012.10.005

Summary 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.