Severe Pulmonary Hypertension Associated With Emphysema: A New Phenotype?

doi:10.1378/chest.11-2816

Chest

Volume 142, Issue 6, December 2012, Pages 1654-1658

https://doi.org/10.1378/chest.11-2816 Get rights and content

Mild to moderate precapillary pulmonary hypertension (PH) is a common complication of COPD and has typically been related to severe airflow limitation associated with chronic hypoxemia. Previous studies focusing specifically on patients with emphysema found that worsening PH was associated with progression of airflow obstruction. In the present report, we describe a new phenotype of COPD with severe precapillary PH in patients presenting with progressive dyspnea, normal spirometry, severely reduced diffusion capacity of the lung for carbon monoxide, and high-resolution CT scans of the chest showing diffuse centrilobular emphysema.

Section snippets

Case Report

We report three elderly, male, heavy smokers, who presented with progressive dyspnea, marked hypoxemia, and hypocapnia (Table 1). On evaluation by an experienced radiologist, a helical angioscan of the chest excluded pulmonary thromboembolic disease but was notable for diffuse emphysema with no evidence of interstitial lung disease (Fig 1). Quantitative measures of emphysema for the whole lung (CT scan emphysema score) were performed using lung density software on a dedicated CT scan

Discussion

Mild to moderate PH has been reported in up to one-third of patients with COPD and has typically been related to severe airflow limitation associated with chronic hypoxemia.1, 4 Previous studies focusing specifically on patients with emphysema found that worsening PH was associated with progression of airflow obstruction.6, 7 Classically, PH in emphysema has been attributed to several factors, including hypoxia leading to reactive vasoconstriction and pulmonary vascular remodeling, the loss of

Acknowledgments

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Humbert has relationships with drug companies including Actelion Pharmaceuticals Ltd; AstraZeneca; Bayer; Chiesi Ltd; GlaxoSmithKline; Eli Lilly and Company; Merck & Co, Inc; Novartis AG; Takeda Pharmaceuticals International GmbH; Pfizer, Inc; Stallergenes; Teva Pharmaceuticals; and United Therapeutics Corp. In addition to being an investigator in trials involving these companies,

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Cited by (21)

A diffuse lung emphysema, severe pulmonary hypertension and lack of airflow limitation
2017, Respiratory Medicine Case Reports
Citation Excerpt :
Almost all patients in these studies [1,2,4] had significant pulmonary emphysema on computed tomography (CT). Recently, Adir et al. [6] reported three cases of severe PH with marked diffuse lung emphysema but normal spirometry results. No study has reported the pathological assessment in this disease.
Pulmonary veno-occlusive disease is characterized by remodeling of pulmonary arteries, capillaries and venules. We report a case of diffuse lung emphysema and pulmonary veno-occlusive disease with the characteristic of having no airflow limitation. A very low diffusing capacity for carbon monoxide and results of high-resolution computed tomography of the chest suggested pulmonary veno-occlusive disease. The diagnosis was confirmed on histological analysis after lung transplantation. The combination of results of the computed tomography of the chest and the histological analysis suggested a relationship between diffuse lung emphysema and remodeling of pulmonary vessels. A distinctive pattern of mild-to-moderate airflow limitation in patients with chronic obstructive pulmonary disease and severe pulmonary hypertension has been described. This observation of the combination of diffuse emphysema, pulmonary veno-occlusive disease and no airflow limitation supports further pathophysiological studies on severe pulmonary hypertension in chronic obstructive pulmonary disease.
Pulmonary vascular abnormalities in chronic obstructive pulmonary disease undergoing lung transplant
2013, Journal of Heart and Lung Transplantation
Citation Excerpt :
All in all, these findings reinforce the view that the severity of pulmonary emphysema in this cohort may be a major determinant of pulmonary hypertension. Our findings concur with the recent association between diffuse centrilobular emphysema and severe pulmonary hypertension reported by Adir et al.33 Of note that total lung capacity was inversely associated with the thickness of pulmonary artery walls.
Little is known about the structure and function relationships of pulmonary vessels in the most severe chronic obstructive pulmonary disease (COPD) spectrum. We investigated morphometric, cellular, and physiologic characteristics of pulmonary arteries from COPD patients undergoing bilateral lung transplant.
Seventeen patients with very severe COPD (forced expiratory volume in 1 second, 24% ± 7%) were assessed using inert gas exchange and pulmonary hemodynamics while breathing ambient air and 100% oxygen. Morphometry, in vitro reactivity to hypoxia, and inflammatory cell counts of pulmonary arteries were measured in explanted lungs.
Patients had moderate ventilation-perfusion imbalance along with mild release of hypoxic pulmonary vasoconstriction. Mild pulmonary hypertension was observed in 7 patients. Explanted lungs had predominant emphysema with mild small airway involvement. In vitro reactivity was modestly altered, with relatively preserved endothelium-dependent relaxation, and vascular remodelling was discrete, with intense CD8⁺ T lymphocytes infiltrate. In vitro reactivity correlated with pulmonary vascular resistance (on ambient air) and oxygen-induced pulmonary artery pressure changes. Patients with pulmonary hypertension had more severe morphologic and physiologic emphysema.
In end-stage COPD patients undergoing lung transplant, pulmonary vascular involvement is unexpectedly modest, with low-grade endothelial dysfunction. In this sub-set of COPD patients, pulmonary emphysema may constitute the major determinant of the presence of pulmonary hypertension.
Pulmonary hypertension in chronic obstructive and interstitial lung diseases
2013, International Journal of Cardiology
Citation Excerpt :
On HR-CT, PH may be revealed by an increased size of the main pulmonary artery, but studies have shown that this finding was poorly correlated to MPAP in IPF patients [34]. However, HR-CT is important for classification of PH, because patients with severe precapillary PH, severe emphysema on high-resolution computed tomography, and normal spirometry have been described [35]. Therefore, HR-CT should be performed before excluding the diagnosis of PH related to lung disease.
The purpose of the present review is to summarize the current knowledge on PH in relation to COPD and ILD from a clinical perspective with emphasis on diagnosis, biomarkers, prevalence, impact, treatment, and practical implications.
PH in COPD and ILD is associated with a poor prognosis, and is considered one of the most frequent types of PH. However, the prevalence of PH among patients with COPD and ILD is not clear. The diagnosis of PH in chronic lung disease is often established by echocardiographic screening, but definitive diagnosis requires right heart catheterization, which is not systematically performed in clinical practice. Given the large number of patients with chronic lung disease, biomarkers to preclude or increase suspicion of PH are needed. NT-proBNP may be used as a rule-out test, but biomarkers with a high specificity for PH are still required.
It is not known whether specific treatment with existent drugs effective in pulmonary arterial hypertension (PAH) is beneficial in lung disease related PH. Studies investigating existing PAH drugs in animal models of lung disease related PH have indicated a positive effect, and so have case reports and open label studies. However, treatment with systemically administered pulmonary vasodilators implies the risk of worsening the ventilation–perfusion mismatch in patients with lung disease. Inhaled vasodilators may be better suited for PH in lung disease, but new treatment modalities are also required.
Vascular remodelling in idiopathic pulmonary fibrosis patients and its detrimental effect on lung physiology: potential role of endothelial-to-mesenchymal transition
2022, ERJ Open Research
Pulmonary function testing in COPD: looking beyond the curtain of FEV1
2021, npj Primary Care Respiratory Medicine
Vascular injury in chronic obstructive pulmonary disease
2021, Pulmonary Vascular Disorders

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Selected ReportsSevere Pulmonary Hypertension Associated With Emphysema: A New Phenotype?

Section snippets

Case Report

Discussion

Acknowledgments

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Chronic cor pulmonale

Heart

Severe pulmonary hypertension and chronic obstructive pulmonary disease

Am J Respir Crit Care Med

Selected Reports
Severe Pulmonary Hypertension Associated With Emphysema: A New Phenotype?