Dr Lan Zhao (LZ): It is a great honor to interview Professor Xiancheng Cheng on this occasion during the PVRI annual meeting. Professor Cheng was my mentor in the late 1980s when I was in China. He is retired now, but he still plays a significant role in the field of pulmonary vascular diseases in China. I would like to take this opportunity to ask Professor Cheng to tell about his life in this field, and of course the history of PVDs in China.
First of all, I will ask Professor Cheng to start with a brief introduction of himself, and to also tell us the early history of the clinical and experimental research of pulmonary vascular disease in China.
Professor Xiansheng Cheng (XC):
Thank you, Dr Zhao, for your interview. I am sorry that I do not speak English very well. So I will do the interview in Chinese.
I was a graduate student in 1963 in Fuwai, and my project was focused on “the changes in gases and acid-base balance of blood in patients with cor pulmonale”. This led my research on pulmonary vascular disease and hemodynamics and became my lifetime career. In 1972, the Health Minister of the Chinese government assigned me to lead a team, consisting of 6 doctors, to establish the first workgroup of Cor Pulmonale. This then progressed as the first Pulmonary Vascular Disease Center in China. The workgroup focused on the prevention, diagnosis and treatment of cor pulmonale (or pulmonary heart disease) in China, including the diagnosis by ECG, chest X-ray, echocardiography, blood gases and acid-base and pulmonary function testing. We also took great interest in the hemodynamics of cor pulmonale caused by COPD at rest and during exercise, and defined the patients as the “dominant pulmonary hypertension” and “latent pulmonary hypertension or latent cor pulmonale”. The latter includes the contemporary concept of “exercise-induced pulmonary hypertension”. Then the National Collaborative Network of Pulmonary Heart Disease was established, and I served as the general secretary of the organization. In the past 25 years, seven pulmonary heart disease conferences have been held for exchanging experiences in research on hemodynamics and right heart function, as well as clinical studies. Indeed, it has been 40 years in total since the beginning of our efforts in the fields, and we have been awarded prizes for our contributions and achievements in China.
In the 1980s, we started to work with the obliterative pulmonary hypertension. In 1986 we got the grant from the “seventh five-year plan” of the Chinese government, which covered two parts: study on primary pulmonary hypertension (PPH), and chronic thromboembolic pulmonary hypertension (CTEPH). We performed hemodynamics and acute vasodilation tests (nifedipine sublingually), and drug efficacy in 115 obliterative pulmonary hypertension (46 CTEPH and 69 PPH). We found that about 20% patients suffered from an elevation in pulmonary pressure rather than a pressure decrease during testing, which validated the hemodynamic test before taking calcium channel antagonists. Meanwhile, we also investigated the relationship between hemodynamic index and pathology of congenital heart disease associated with pulmonary arterial hypertension. The open lung biopsies were performed in 81 patients with indication of borderline for surgery operations- among these patients, we had 59 patients with pathological lesions I-II/IV grades, and 11 of them had bidirectional shunt and cyanosis and they were still operable.
In 1985, I got the WHO scholarship and started my study with the famous pulmonary vascular pathologist, professor Wagenvoort, in the Netherlands. With him, I studied the morphological changes included in the plexiform lesions in PAH associated with congenital heart disease and pathological changes in pulmonary vessels in rheumatic valvular diseases. I found endothelial cell proliferation and medial hypertrophy, and that luminal narrowing occurred generally in the early stage. Along with the disease progression, vascular smooth muscle cells disappeared with extensive endothelial and medial fibrosis. My result indicated that vasodilators had no effects in these irreversible vascular lesions. When I came back to China, I instructed my student Dr. Zhi-Hong Liu to explore the collagen deposits in vascular walls and medical intervention for the process in the pulmonary vessels, and concluded that the structural changes may be the pathogenesis of pulmonary vascular disease which is now recognised as vascular remodeling. From then on, I extended my research from the PH caused by COPD to a larger scale, including the functional and structural change in the whole pulmonary circulation and right ventricle.
I wrote a book in 1993 entitled Pulmonary Vascular Diseases. I developed my theory on the definition of pulmonary vascular disease, with the concept that the structural and/or functional disorders of the whole or local pulmonary circulation are due to primary or secondary pulmonary vessel lesions. In 1991, based on the 241 in-patients with PVD in my hospital, I proposed a new classification system of PVDs including both large and small vessels, arteries and veins, congenital and acquired disorders. Unfortunately, until now, there is no classification of PVDs in the world. I suggest that PVRI should take a broader view to explore the whole pulmonary vascular disorders and establish the classification of PVDs.
Professor Wagenvoort suggested the small vessel lesions are divided into seven categories: type 1, plexogenic arteriopathy; type 2, thromboembolic PVD; type 3, pulmonary venous hypertension PVD; type 4, pulmonary veno-occlusive disease; type 5, hypoxic pulmonary hypertension PVD; type 6, pulmonary vascular changes due to lung disease ; type 7, pulmonary vascular changes associated with reduced blood flow. Each class contains a large spectrum of different disorders of pulmonary arteries and veins. These definitions and classifications are not complete, however, it is of importance in helping us form a thorough understanding of the extent of the field of pulmonary vascular diseases. We should take a broad view to observe the whole pulmonary circulation and right heart function, rather than focus on only the pulmonary arterial hypertension or pulmonary embolism, since the field contains hundreds of unexplored diseases and it also requires interdisciplinary knowledge for doctors and scientists in the field, especially the cardiologists and pulmonologists. For these reasons, I would give an example of Professor Fishman, a former president of American Heart Association. He was not only an expert in cardiology, but also a respiratory physiologist, and he wrote an excellent book called The Pulmonary Circulation: Normal and Abnormal.
LZ: Thank you very much for your introduction of PVD in China, what a fascinating history as well as the story of your lifetime contributions. You began your research on cor pulmonale in the 1970s, and gradually progressed into the “world of PVDs”, especially the pulmonary embolism research in 1980s. I appreciate very much your concept from 1991 that we should take a broad view in the PVD field, and pay attention to the right heart function, and the importance thereof for the new classifications of PVDs. I hope these ideas will give the doctors and scientists in the field a new vision for the future, indeed, the interdisciplinary combined efforts of cardiologists and pulmonologists are important for an in depth understanding of PVDs. Could you please tell us a bit more about the development of PVDs in the recent 10-15 years?
XC: As mentioned above, on the basis of our previous work in the 1970s-1980s, in the 1990s we carried out research on pulmonary embolism (PE) sponsored by National Key Project in China, which contains studies on COPD, PH, and PE. In the 2000s, the Chinese government supported the research further, and included right ventricular dysfunction into the National Key Project, paying great attention to the field of PVDs. In 2013, Chinese government issued its new grants plan and “The Molecular Mechanism and Intervention of Pulmonary Hypertension” is listed as the top priority on the projects of National Natural Science Fund. The period from 1970s to 1980s was really a tough time. My views were not accepted by the Chinese Association of Cardiology or the Chinese Association of Respiration. Recently the situation has changed, there are two workshops of PVDs in China, one of which belongs to Chinese Association of Cardiology, while the other belongs to Chinese Thoracic Society.
LZ: In recent years, you have actively participated in the international conferences and discussions. I am very impressed by your enthusiasm, you have always come up with your own opinion based on your years’ of clinical and experimental experiences. Especially, I want to mention the book on Right Heart Disease, which has been published recently, in which you described your original idea about right ventricular dysfunction, that will influence the view of cardiology and respiratory physicians in China.
XC: My concept of “right ventricular system” derives from the basic fact that the survival of patients with left heart diseases are mostly depending on their right ventricular function rather than left ventricular function deterioration. CHD-PAH patients have a significantly better prognosis than IPAH patients because they have better right ventricular function. Therefore, the research on the mechanism of right ventricular adaption and the compensation which integrated with pulmonary circulation is very important. Meantime, the left ventricle contributes to about 20-40% of right heart function, and the other 30-50% pressure in right ventricle was completed by Interventricular septum. So when we explore the right ventricular function, we must take into consideration the influence of the left ventricle, Interventricular septum, and pericardium. It is a integrative system centered on the right ventricle, that covers a good co-ordination of interdependence between ventricles, right ventricle-pulmonary circulation unit , biventricular “motor” of interventricular septum, and pericardium.
LZ: I have read your book and I am sure it will impress and help a lot of doctors in China. In recent years, you played an active role in the PVRI and attended most of the annual meetings. You have not only brought the advanced knowledge back to China, but also exchanged your ideas and experience with experts from all over the world. Could you please talk about your experience with the PVRI?
XC: As I have mentioned, I started my researches on PVDs in the 1970s. At that time, no attention was paid to this field, and some works we made were unrecognized, and I felt like an orphan who was fighting alone without understanding or support. I have always dreamt to find a place to belong. Fortunately, five years ago, I got to know the Pulmonary Vascular Research Institute (PVRI), I finally found my family, and I was so excited. My experiences and research have finally found a place – the expertise in the PVRI understood and recognised me, and I joined the organization. I attended the 3rd and 6th meetings of PVRI and I began to advertise PVRI in China: I wrote an article to introduce the principle, structure, research area and the nature of PVRI in China Medical Tribune. I care about the Institute. I think it is my responsibility to support organisations like the PVRI. Compared to the Lisbon meeting in Portugal, in the Istanbul meeting I witnessed a tremendous progress of the PVRI, in its management, coordination, content and the multi-disciplinary involvement.
I wish that the Institute will develop well and I hope PVRI will take a wider scope including PVDs and right ventricular diseases. In addition, I heard that the Excellence Cluster of Cardio-Pulmonary System (ECCPS) was established in Germany, and that reflects a trend towards the integrated system of the cardio-pulmonary system.
I want to emphasize that pulmonary hypertension consists of heterogenous entities which contain complex processes in aspects of etiology, pathogenesis, clinical features, diagnosis, treatment and prognosis. By creating comparisons between these diseases, I believe that we could find the common pathway in the disorders and cure the disease by targeting it.
I think PVRI has started to take strategic vision about the development of the field, and it has put the focus on understanding the pulmonary structural remodelling, the coordination of multiple disciplines and the training of the next generation in the field. I believe these will promote the rapid development of PVRI.
In summary, to me the PVRI is like a warm family and I sincerely hope it will further develop into a great academic society that will promote better understanding of the disease. It will play a leading role in the PVD world. Finally, thank you Dr Zhao for your interview.