Pulmonary Hypertension in Chronic Lung Disease and Hypoxia

Publication Date: December 1, 2018


It is important that defining PH should not be undertaken during an acute exacerbation, but under stable conditions.

Haemodynamic evaluation of PH severity should be contextualised within the extent of the underlying lung disease, which is best gauged through a combination of physiological and imaging assessment.

Any decision for individualised treatment should follow a goal-orientated approach with predefined treatment targets, to be stopped if these targets are not met after a predefined time period.

When to perform right heart catheterisation (RHC)

RHC should be performed in patients with CLD when significant PH is suspected and the patient's management will likely be influenced by RHC results, including referral for transplantation, inclusion in clinical trials or registries, treatment of unmasked left heart dysfunction, or compassionate use of therapy.

RHC may be considered when:

Clinical worsening, progressive exercise limitation and/or gas exchange abnormalities are not deemed attributable to ventilatory impairment.
An accurate prognostic assessment is deemed sufficiently important.

Pressure measurements during RHC

As a result of exaggerated changes in intrathoracic pressures during the breathing cycle in patients with lung disease, a floating average over several breaths (without a breath hold) is suggested for measurement of mean pressures, including the pulmonary capillary wedge pressure.

We suggest adapting the definition for PH in the context of CLD-PH:

CLD without PH (mPAP <21 mmHg, or mPAP 21–24 mmHg with pulmonary vascular resistance (PVR) <3 Wood Units (WU)).
CLD with severe PH (mPAP ≥35 mmHg, or mPAP ≥25 mmHg with low cardiac index (<2.0 L·min−1·m−2)) (CLD-severe PH).
The rationale for the choice of mPAP ≥35 mmHg as a cut-off for severe PH follows previously presented evidence. There are currently no valid data to support the routine use of acute vasodilator testing in CLD-PH.
When there is uncertainty whether to classify a patient with lung disease and PH into group 1 or group 3, then the patient should be referred to centres with expertise in both PH and CLD.

Treatment of PH due in CLD: evidence for appropriate risk–benefit balance of PAH-targeted therapy

The underlying lung disease should be optimally treated according to current guidelines.


Although preliminary evidence suggests that currently available vasoactive medications may have a benefit in COPD-PH patients with mPAP ≥35 mmHg, further studies are required before PAH therapies can be recommended.

Idiopathic interstitial pneumonias

Riociguat and ambrisentan are both contraindicated in IIP-PH.
There is no evidence of benefit for other endothelin receptor antagonists in IIP-PH. Data on the use of sildenafil in IIP-PH is conflicting, while evidence for prostanoid therapy is too limited for any current recommendations.

Combined pulmonary fibrosis and emphysema

Treatment options remain limited with currently little evidence to support PAH therapies in this disease.


At present, no PAH-targeted therapy can routinely be recommended for patients with sarcoidosis-PH.

Other CLDs

Clinical experience and case series suggest beneficial effects of drugs approved for PAH in some patients with pulmonary Langerhans cell histiocytosis and lymphangioleiomyomatosis, but the lack of robust data precludes firm recommendations for any of these other conditions.

Recommendations for treatment of different patient groups with CLD and PH

Patients with mild obstructive or restrictive lung disease, in whom CT analysis shows no gross parenchymal or airway abnormalities and who present with clinically relevant PH. Whether such patients have PAH (group 1) with concomitant lung disease or PH due to lung disease (group 3) remains a diagnostic dilemma (see earlier). Therefore, these patients should be referred to an expert centre.

Patients with more severe obstructive and/or restrictive lung disease (IPF with FVC <70% of predicted, COPD with FEV1 <60% of predicted) and accompanying less severe PH (mPAP 20–24 mmHg with PVR3 WU, or mPAP 25–34 mmHg). These groups represent the majority of patients presenting with CLD-PH. Current data do not support therapy with PAH-approved drugs in these patients. Moreover, as the limitation in exercise capacity in these patients is largely due to ventilatory and not circulatory impairment, any functional benefit from PAH treatment is questionable. Vascular changes may, however, contribute to disease progression and future studies addressing this aspect of the disease may be a worthy endeavour.

Patients with more severe obstructive and/or restrictive lung disease and severe PH as defined earlier (mPAP35 mmHg; severe COPD-PH, severe ILD-PH, severe CPFE-PH). These patients have a poor prognosis and should be referred to a centre with expertise in both PH and CLD for individualised patient care. These patients should preferably be included in RCTs if available.
Patients with “end-stage” obstructive and/or restrictive lung diseases and associated PH. In these advanced cases, life-preserving measures, such as mechanical ventilatory or extracorporeal membrane oxygenation support, should only be considered as a bridge to transplantation. Patients in any of these groups may be candidates for lung transplantation, an option that should be part of the management algorithm if all else fails and they are otherwise appropriate candidates. RCTs should address whether PAH-approved drugs may improve functional ability, quality of life, prolong time to clinical worsening, improve survival or provide a bridge to transplantation. In the absence of such trials, decisions on individualised patient care should be made in the context of expert centres.

Specific aspects of PH in systemic sclerosis

In the absence of RCTs, SSc patients with PH and more than minimal fibrosis on high-resolution CT should be referred to expert centres for individualised treatment.

Hypoventilation and hypoxia-associated PH

The mainstay treatment of OHS is non-invasive ventilation, which does not, however, always correct the PH.

PH at high altitude

Re-exposure to normal PIO2 is the primary treatment of high-altitude PH. Long-term treatment studies with vasodilators are largely missing.

Recommendation Grading




Pulmonary Hypertension in Chronic Lung Disease and Hypoxia

Authoring Organization

Publication Month/Year

December 1, 2018

Document Type


External Publication Status


Country of Publication


Inclusion Criteria

Female, Male, Adult, Older adult

Health Care Settings

Ambulatory, Emergency care, Hospital, Long term care, Operating and recovery room

Intended Users

Social worker, physician, paramedic emt, nurse, genetics, nurse practitioner, physician assistant


Assessment and screening, Diagnosis, Prevention, Management, Treatment

Diseases/Conditions (MeSH)

D006976 - Hypertension, Pulmonary, D008171 - Lung Diseases, D002908 - Chronic Disease, D000860 - Hypoxia


pulmonary hypertension, idiopathic pulmonary fibrosis, idiopathic interstitial pneumonia, sarcoidosis, Chronic lung disease, hypoxia, emphysema, lung vasculature, hypoxaemia