Lung function, inflammation, and endothelin-1 in congenital heart disease-associated pulmonary arterial hypertension
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background-—Breathlessness is the most common symptom in people with pulmonary arterial hypertension and congenital heart
disease (CHD-APAH), previously thought to be caused by worsening PAH, but perhaps also by inflammation and abnormalities of
lung function. We studied lung function and airway inflammation in patients with CHD-APAH and compared the results with controls.
Methods and Results-—Sixty people were recruited into the study: 20 CHD-APAH, 20 CHD controls, and 20 healthy controls.
Spirometry, gas transfer, whole body plethysmography and lung clearance index, 6-minute walk distance, and medical research
council dyspnea scoring were performed. Inflammatory markers and endothelin-1 levels were determined in blood and induced
sputum. The CHD-APAH group had abnormal lung function with lung restriction, airway obstruction, and ventilation heterogeneity.
Inverse correlations were shown for CHD-APAH between medical research council dyspnea score and percent predicted peak
expiratory flow (r= 0.5383, P=0.0174), percent predicted forced expiratory flow rate at 50% of forced vital capacity (r= 0.5316,
P=0.0192), as well as for percent predicted forced expiratory volume in 1 s (r= 0.6662, P=0.0018) and percent predicted forced
vital capacity (r= 0.5536, P=0.0186). The CHD-APAH patients were more breathless with lower 6-minute walk distance (360 m
versus 558 m versus 622 m, P=0.00001). Endothelin-1, interleukin (IL)-b, IL-6, IL-8, tumor necrosis factor a, and vascular
endothelial growth factor were significantly higher in CHD-APAH than controls. Serum endothelin-1 for CHD-APAH correlated with
airflow obstruction with significant negative correlations with percent predicted forced expiratory flow rate at 75% of forced vital
capacity (r= 0.5858, P=0.0135).
Conclusions-—Raised biomarkers for inflammation were found in CHD-APAH. Significant abnormalities in airway physiology may
contribute to the dyspnea but are not driven by inflammation as assessed by circulating and sputum cytokines. A relationship
between increased serum endothelin-1 and airway dysfunction may relate to its bronchoconstrictive properties. (J Am Heart
Assoc. 2018;7:e007249. DOI: 10.1161/JAHA.117.007249.)
disease (CHD-APAH), previously thought to be caused by worsening PAH, but perhaps also by inflammation and abnormalities of
lung function. We studied lung function and airway inflammation in patients with CHD-APAH and compared the results with controls.
Methods and Results-—Sixty people were recruited into the study: 20 CHD-APAH, 20 CHD controls, and 20 healthy controls.
Spirometry, gas transfer, whole body plethysmography and lung clearance index, 6-minute walk distance, and medical research
council dyspnea scoring were performed. Inflammatory markers and endothelin-1 levels were determined in blood and induced
sputum. The CHD-APAH group had abnormal lung function with lung restriction, airway obstruction, and ventilation heterogeneity.
Inverse correlations were shown for CHD-APAH between medical research council dyspnea score and percent predicted peak
expiratory flow (r= 0.5383, P=0.0174), percent predicted forced expiratory flow rate at 50% of forced vital capacity (r= 0.5316,
P=0.0192), as well as for percent predicted forced expiratory volume in 1 s (r= 0.6662, P=0.0018) and percent predicted forced
vital capacity (r= 0.5536, P=0.0186). The CHD-APAH patients were more breathless with lower 6-minute walk distance (360 m
versus 558 m versus 622 m, P=0.00001). Endothelin-1, interleukin (IL)-b, IL-6, IL-8, tumor necrosis factor a, and vascular
endothelial growth factor were significantly higher in CHD-APAH than controls. Serum endothelin-1 for CHD-APAH correlated with
airflow obstruction with significant negative correlations with percent predicted forced expiratory flow rate at 75% of forced vital
capacity (r= 0.5858, P=0.0135).
Conclusions-—Raised biomarkers for inflammation were found in CHD-APAH. Significant abnormalities in airway physiology may
contribute to the dyspnea but are not driven by inflammation as assessed by circulating and sputum cytokines. A relationship
between increased serum endothelin-1 and airway dysfunction may relate to its bronchoconstrictive properties. (J Am Heart
Assoc. 2018;7:e007249. DOI: 10.1161/JAHA.117.007249.)
Date Issued
2018-02-14
Date Acceptance
2018-01-09
Citation
Journal of the American Heart Association : Cardiovascular and Cerebrovascular Disease, 2018, 7 (4)
ISSN
2047-9980
Publisher
Wiley
Journal / Book Title
Journal of the American Heart Association : Cardiovascular and Cerebrovascular Disease
Volume
7
Issue
4
Copyright Statement
© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made (https://creativecommons.org/licenses/by-nc-nd/4.0/).
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Identifier
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Subjects
Science & Technology
Life Sciences & Biomedicine
Cardiac & Cardiovascular Systems
Cardiovascular System & Cardiology
congenital heart disease
inflammation
lung
pulmonary circulation
pulmonary hypertension
EISENMENGER-SYNDROME
AIRWAY-OBSTRUCTION
CYSTIC-FIBROSIS
SPUTUM
GUIDELINES
SURVIVAL
PLASMA
ADULTS
EXERCISE
THERAPY
Publication Status
Published
Article Number
ARTN e007249