O8. Hypoxaemia and pulmonary hypertension

Identify and treat hypoxaemia and pulmonary hypertension (Cranston 2005) [evidence level I].


Hypoxaemia in COPD patients should be identified and corrected with long term oxygen therapy as this has been shown to improve survival and quality of life (Nocturnal Oxygen Therapy Trial Group 1980, Medical Research Council Working Party 1981 (see O8.1). Hypoxaemia is best screened for using pulse oximetry, however should be confirmed using arterial blood gas (ABG) measurement. Use of ABGs also allows for the detection of hypercapnia which may complicate long term oxygen use. The indication for long term oxygen use are:

  • Arterial PaO2 less than or equal to 55mmHg or
  • Arterial PaO2 less than or equal to 59mmHg in the presence of pulmonary hypertension, right heart failure or polycythaemia

Pulmonary hypertension

The definition of pulmonary hypertension (PHT) was revised in 2009. PHT is now defined as a mean Pulmonary Artery Pressure (PAP) > 25mmHg at rest measured by right heart catheterization (Simonneau 2009). PAP assessed during exercise is no longer part of the definition.  PHT was seen in approximately 50% of patients with severe emphysema (FEV1 27% of predicted) studied as part of the National Emphysema Treatment Trial (NETT) (Scharf 2002) but only 5% of these patients had moderate to severe PHT (mean PAP > 35mmHg). In these patients, no correlation was found between PaO2 and mean PAP although FEV1, Pulmonary Capillary Wedge Pressure and DLCO were correlated in a multiple regression model. In those COPD patients with severe PHT, hypoxaemia, reduced DLCO and PAP are often more impaired than would be expected for their degree of airflow obstruction (Chaouat 2005). There are several postulated mechanisms for PHT in COPD (Chaouat 2008). The presence of PHT is associated with a worse prognosis (Chaouat 2008) and increased hospitalisation (Kessler 1999). This has resulted in several small studies of non selective and selective vasodilators.

No pharmacological therapies have shown to be effective to date. An early study of the non selective dihydropyrodine calcium antagonist vasodilator felodipine in COPD showed improved haemodynamics (Sajkov 1993). However, the low efficacy and high adverse effect profile make such drugs an unattractive option. The first report of a selective pulmonary vasodilator, nitric oxide (NO) in stable COPD (Barbera 1996) was disappointing in that hypoxia was exacerbated, presumably through the mechanism of worsening ventilation/perfusion (V/Q) mismatching. A subsequent 40 patient randomised trial assessed “pulsed” (a burst at the start of inspiration) NO and demonstrated that improved haemodynamics without exacerbation of hypoxia (Vonbank 2003) was possible. No further randomised controlled trials of selective pulmonary vasodilators in COPD patients have yet been published. Although endothelin-1 receptor antagonists and other agents have been used to treat non-COPD-related PHT, a trial of bosentan in COPD (Stolz 2008) once again induced adverse effects on gas exchange and quality of life. Similarly, two randomised controlled trials of the phosphodiesterase-5 inhibitor sildenafil failed to demonstrate improvements in cardiac output, 6MWT or maximal workload on cardiopulmonary exercise testing in COPD patients (Holverda 2008, Rietema 2008). Well designed trials of agents which selectively dilate the pulmonary vascular bed without worsening V/Q mismatching are urgently needed.

PHT and right heart failure may be complications of acute exacerbations of COPD. Therapy in these patients has generally been directed at reversing hypoxia and hypercapnia with bronchodilators, corticosteroids, antibiotics as well as supplemental oxygen and ventilatory support. A 16 patient randomised placebo controlled trial of IV prostacycline showed no benefit, but exacerbated hypoxia in patients receiving conventional therapy including mechanical ventilation for an acute exacerbation of COPD (Archer 1996).

Thus, there are no data at present that clearly support the use of vasodilators generally in COPD patients with PHT. However severe PHT is uncommon in patients with even advanced emphysema. As such, where appropriate, a careful search for other potential causes of PHT should be undertaken and an alternative diagnosis considered.

Chest x-rays may show enlargement of proximal pulmo­nary arteries, but right ventricular enlargement is difficult to detect because of hyperinflation. Right axis deviation and P pulmonale on ECG may be difficult to detect because of low voltage traces (also a result of hyperinflation). Multifocal atrial tachycardia and atrial fibrillation are common. A pulmonary artery to aorta ratio of greater than one as measured on CT chest has been used as a marker of possible pulmonary hypertension. Wells et al used this measure in over 1,000 subjects and prospectively found its presence lead to an significantly increased risk of future exacerbations odds ratio, 3.44; 95% CI, 2.78 to 4.25; P<0.001 (Wells 2012) [evidence level III-2].

Retrospective data from 60 patients with severe COPD who had undergone CT chest, transthoracic echocardiography and right heart catheterisation showed that a CT chest pulmonary artery to aorta ratio greater than one was 73% sensitive and 84% specific for pulmonary hypertension with right heart catheter as the gold standard. This was significantly more sensitive and specific than transthoracic echocardiography (Iyer 2014)[evidence level IV].

Echocardiography is the best non-invasive method of assessing pulmonary hypertension but image quality is reduced by hyperinflation. This can be clarified using the more invasive procedure of trans-oesophageal echocardiography. Patients with COPD may have poor quality images on transthoracic examination and transoesophageal echocardiography may be frequently needed. Echocardiography is indicated in patients with severe disease, or when symptoms seem out of proportion to the severity of airflow limitation. Estimation of pressure relies on at least some tricuspid regurgitation. Other findings include mid-systolic closure of the pulmonic valve and increased right ventricular wall thickness.