Pulmonary Hypertension in COPD: are we only seeing the tip of the iceberg?

Pulmonary hypertension (PH) is a frequent¹ complication in chronic obstructive pulmonary disease (COPD) and it has significant implications for morbidity² and mortality³. The latest European Society of Cardiology/European Respiratory Society guidelines recognize PH associated with lung disease (classified as Group 3 PH) as a common form of PH⁴, with COPD being the most common underlying lung disease in the group.

The global prevalence of COPD is estimated to be approximately 300-400 million people aged 30-79 years old, which corresponds to 8-10% of the population in that age range⁵. PH, defined according to different thresholds of mean pulmonary artery pressure in the last decades, has previously been described in a wide range of COPD patients varying greatly from 18 to 91% depending on the criteria used⁶. Even if one assumed the lower prevalence of PH in COPD patients, we would still be facing a prevalence of approximately 54 million patients globally. This high prevalence is influenced by the common risk factor of smoke exposure (mainly from tobacco), the leading cause of COPD but also associated with pulmonary endothelial dysfunction even in patients who have not developed COPD⁷.

Registry data has enabled the recognition of differences in mortality between COPD patients with mild-moderate or severe PH; the latter group being more rare⁶ (1-13%) but exhibiting a markedly worse prognosis^3,8. The diagnosis of PH requires performance of a right heart catheterization. It is difficult to advocate for this in the absence of an intervention. Indeed, whether pulmonary vasodilatory therapies have a role in PH due to COPD remains to be determined⁴.  However, there is preliminary data showing a beneficial effect of pulmonary vasodilators in patients with COPD and severe PH⁹. It is recommended that when there is suspicion of severe PH, patients should be referred to a PH expert center for inclusion in a randomized-controlled trial or consideration of off-label treatment⁴. The prevalence of severe PH in COPD may indeed be considerable: even considering the lowest estimates this might still affect approximately 3 million people worldwide. Furthermore, the spectrum of phenotypes in COPD may be more varied¹⁰ than the mere distinction based upon hemodynamic severity, as shown by the recent description of a specific pulmonary vascular phenotype (characterized by the concomitance of mild airflow obstruction, severe hypoxemia and PH)¹¹. There is much yet to be learnt about COPD-PH and indeed about the role of the vasculature in COPD. Perhaps there needs to be a broadening in thinking and clinical trials, beyond the confines of the narrowed airways to the allure and promise of adjunctive vasculocentric therapies.  

The Innovative Drug Design Initiative lead by the Pulmonary Vascular Research Institute is promoting an expert consensus from clinicians, researchers, patients, regulatory agencies and industry representatives that aims to guide future research efforts to disentangle the understanding of PH and the vasculature in COPD.