Infection in pulmonary vascular diseases: Would another consortium really be the way to go?

[first paragraph of article]There has been a clear engagement by the medical community with pulmonary hypertension after the approval of targeted therapies and the introduction of more therapeutic modalities in the last 18 years. The increasing number of scientific sessions and conferences was inevitable. Major initial interest was from the developed countries, which concentrated on prevalent etiologies: primary (later called idiopathic) pulmonary arterial hyposecretion and secondary to connective tissue disorders currently both classified as Class I. Unfortunately, a lesser consideration was given to other causes of pulmonary hypertension such as secondary to left heart failure (Class II) or hypoxic pulmonary disease (Class III). This is presumably due to both the complexity and the multifactorial etiologies of these causes and the lack of availability of targeted therapies. 

There has been a clear engagement by the medical community with pulmonary hypertension after the approval of targeted therapies and the introduction of more therapeutic modalities in the last 18 years. The increasing number of scientific sessions and conferences was inevitable. Major initial interest was from the developed countries , which concentrated on prevalent etiologies: primary (later called idiopathic) pulmonary arterial Hypertension and secondary to connective tissue disorders -currently both classified as Class I 1,2 . Unfortunately, a lesser consideration was given to other causes of pulmonary hypertension such as secondary to left heart failure (Class II) or hypoxic pulmonary disease (Class III). This is presumably due to both the complexity and the multifactorial etiologies of these causes and the lack of availability of targeted therapies.
On the other hand the developing world, where 6 billion people live, showed less attention to pulmonary hypertension where the pattern and etiologies differ from the developed countries 3,4 . It is difficult to estimate the real extent of pulmonary hypertension in the developing countries due to the lack of proper epidemiological investigations 4 . Figure 1 shows some hypothetical suggestions for the difference of pulmonary hypertension in developing versus developed countries based on the available observations and data. We estimated the risk of subjects developing pulmonary hypertension to be four to six times higher in developing countries compared to developed regions.
A wide variety of infectious diseases can contribute to the causation of pulmonary vascular diseases (PVD) and consequently pulmonary hypertension in the developing world. Over 200 million people (80% of which are in Africa) are affected by schistosomiasis, which may cause PVD in half of them 5 and the clinical presentation of pulmonary hypertension in 7-15% of them 6,7 . Other Helminthic diseases can induce pulmonary hypertension such as Wuchereria bancrofti, a threadlike worm that causes filariasis (elephantiasis) 8,9 . Clonorchis sinensis (Chinese liver fluke), which is a widespread parasite in southeast Asia, has been associated with cases of pulmonary hypertension 10 . Some investigators reported other parasitic diseases such as hydatid cysts inducing pulmonary hypertension 11 . Viral infection, mainly HIV which is a global disease, can cause pulmonary hypertension in 0.5 to 5% of infected patients 12 . The condition can be exacerbated by using addictive drugs 13,14 found in many herbal remedies in the developing regions. Other viral infections, such as human herpesvirus-8, showed evidence of PVD 15,16 . Recent initial reports suggest that fungal infections, like P. brasiliensis which causes paracoccidioidomycosis in Brazil, can cause PVD in patients and lab animals 17,18 . Some bacterial infections, such as B. Pertussis, may trigger pulmonary hypertension 19 . Other bacterial infections that cause granulomatous reactions in the lungs, like tuberculosis, have been suspected, but not fully evaluated. Indeed, recent cases and communications from Africa and India suggest the potential role of tuberculosis in PVD 20,21 .
There are no real efforts being made to understand the role of infection in PVD despite being one of the major causes of PVD globally, with the exception of some recent work with schistosomiasis and HIV. There are no well-conducted epidemiological studies. Furthermore, co-exposure with more than one infection can be an issue, for example, in some parts of Africa over 50% of patients infected with HIV are co-infected with schistosomiasis 12 .
It is clear that more effort is needed to investigate the role of infection in PVD and consequently pulmonary hypertension for many reasons: 1. Infection is the major cause of pulmonary hypertension globally, making it a prime example of a condition with an unmet medical need. 2. The study of infection will enhance our understanding of the complexity of pulmonary vascular disease pathophysiology. 3. Infection will involve complicated inflammatory and immunological reactions, the two factors that have been increasingly implicated in the pathophysiology of PVD in general 22,23 . Therefore, studying infection in PVD will help to enhance the understanding of the role of inflammation in PVD which helps to assess the role of inflammation in other conditions like the connective tissue diseases that are more complex to investigate.

Studying infection in PVD might help the development of new pulmonary
hypertension therapies which can also be a valuable clinical tool in the investigation of new potential therapies.
Therefore, more systematic and coherent efforts are needed to study the role of infection in PVD. To help achieve this task, we first need to consider educational efforts to raise awareness globally and to focus the attention of clinicians in identifying and The meeting established the basic framework of this consortium based on the above aims and tasks. It will support collaboration on grant applications and exchange ideas and research. The consortium will extend membership to experts from various disciplines to work together.
Thus, the answer to the title of this editorial is ''Yes'', we need another consortium to tackle the most forgotten and neglected cause of PVD worldwide. We hope this consortium will help and find support in the years to come to answer many questions about this condition.