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Zeder, K.
Clinical and histopathological changes in chronic obstructive pulmonary disease with severe pulmonary hypertension
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2023. pp.

Authors Med Uni Graz:: Zeder Katarina Eleonora
Advisor:: Brcic Luka; Kovacs Gabor; Olschewski Horst
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Abstract:: Rationale Severe pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) was until recently defined by elevated mean pulmonary arterial pressure (mPAP) ≥ 35mmHg or ≥ 25mmHg in combination with decreased cardiac index < 2L/min/m2. Severe PH is frequently associated with dismal prognosis despite less severe airway obstruction and the term “pulmonary vascular phenotype” has been introduced. The hemodynamic cut-offs for the definition of severe PH were, however, not evidence based and histologic correlates of the vascular phenotype in COPD are lacking. We aimed to assess prognostic pulmonary hemodynamic thresholds and quantify histological remodeling of pulmonary arteries, airways and parenchyma in lung tissue samples of COPD patients with severe PH and compare findings to COPD patients with mild PH, no PH, donors and idiopathic PAH (IPAH). Methods We analyzed all COPD patients undergoing right heart catheterization between 2003-2018 at our clinic and assessed prognostic cut-offs by regression analysis. For histological remodeling we quantified changes in thickness of layers of pulmonary arteries, airways and degree of emphysema with dedicated software. Comparisons were assessed by mixed models. Results We included n=139 COPD patients for the clinical and n=61 lung tissue samples (n=41 COPD, n=10 donors, n=10 IPAH) for the histological analysis. After adjusting for airflow obstruction, age and sex, pulmonary vascular resistance (PVR) proved to be the strongest predictor of mortality with the best cut-off for all-cause mortality at 5 wood units (WU; HR 2.59 [95%CI 1.58-4.27], p<0.001). COPD patients with PVR > 5 WU presented with less severe airflow obstruction (p=0.005). In histology, COPD patients with severe PH had less emphysema (mean interseptal distance 169µm vs 279µm, p<0.001), less mucus-producing cells and inflammatory cells in airway epithelium (15% vs 22%, p=0.063 and 5% vs 7%, p=0.058) and stronger remodeled pulmonary arteries (p<0.001) compared to COPD patients with mild PH. Conclusion This thesis provides first evidence for a pulmonary vascular phenotype in COPD, which is clinically characterized by a strongly elevated PVR and histologically by pronounced vascular remodeling, less inflammation in airway epithelium as well as less emphysema as compared to COPD with no severe pulmonary hypertension.