Research progress of Chinese medicine in treatment of IPF(idiopathic pulmonary fibrosis)

Luo Hili(罗海丽), Ci Lingling(蔡玲玲), Sun Song(孙凇), Co Ting(曹婷),Wu Meiho(吴美超), Wu Zhisong(吴志松), Fn Morong(樊茂蓉),nd Wng Shuhen(王书臣 )＊

a: Traditional Chinese Medicine Hospital of Miyun District of Beijing 101500, China

b: Dongfang Hospital, the Second Affiliated Hospital of Beijing University of Chinese Medicine, Beijing 100078, China

c: Xiyuan Hospital of Chinese Academy of Traditional Chinese Medicine, Beijing 100091, China

Research progress of Chinese medicine in treatment of IPF(idiopathic pulmonary fibrosis)

Luo Haili(罗海丽)a, Cai Lingling(蔡玲玲)b, Sun Song(孙凇)b, Cao Ting(曹婷)b,Wu Meichao(吴美超)b, Wu Zhisong(吴志松)b, Fan Maorong(樊茂蓉)c,and Wang Shuchen(王书臣 )c＊

a: Traditional Chinese Medicine Hospital of Miyun District of Beijing 101500, China

b: Dongfang Hospital, the Second Affiliated Hospital of Beijing University of Chinese Medicine, Beijing 100078, China

c: Xiyuan Hospital of Chinese Academy of Traditional Chinese Medicine, Beijing 100091, China

Idiopathic pulmonary interstitial fibrosis is one of the respiratory refractory diseases, and the incidence rate is on the rise. At present, the effect of western medicine is not ideal and the side effects are obvious, while the traditional Chinese medicine shows good curative effect on the disease. This paper makes a summary on the traditional Chinese medicine theory in treating idiopathic pulmonary interstitial fibrosis in recent years.

Idiopathic pulmonary interstitial fibrosis;Chinese medicine; Research progress

Idiopathic pulmonary interstitial fibrosis (IPF)is a chronic inflammatory interstitial lung disease and the cause of IPF is still unknown. IPF shows a characteristic histopathologic pattern known as usual interstitial pneumonia. It mainly manifests as diffuse pulmonary alveolitis, disorder of alveolar unit structural and pulmonary fibrosis. According to the finding of Martinez1, there were 89% of IPF patients died of sudden and unexpected acute exacerbations, of which 47% of the direct cause of death was acute exacerbation of interstitial fibrosis. Western medicine is not effective to them, while Chinese medicine has better effect on them.

THE ATTRIBUTION OF THE DISEASE NAME

There is no disease name in Chinese medicine literature which iscompletely corresponding to idiopathic pulmonary interstitial fibrosis. The symptoms of the disease are usually seen from the diseases of lung withered, gasp syndrome, lung paralysis, cough,and lung-distension. Most scholars attributed it to the category of traditional Chinese medicine, lung paralysis,withered lungd, and collateral disease. The name of lung paralysis was from theNei Jing(Huangdi’s canon of Internal Medicine), the chapter ofSuWenmentioned about paralysis: Patient of lung paralysis was tired of asthma and vomit; and the three evil gases included wind, cold and humid, which mix together consisting“Bi Zheng” ... skin numbness was not cured, it was accompanied with the evil, which would affect the lung. According toSuwen’ s record about paralysis,“Bi” gathered in the lung ... it would lead to death when getting into the viscera, which showed the poor prognosis of lung paralysis. In Han Dynasty,Zhang Zhongjingput forward the name of withered lung for the first time, and made effective prescription ofMaimendongDecoction and licorice and dried ginger decoction. For collateral disease,Ye Tianshirepeatedly referred to that illness of early stage at the Jing level and long illness at the collateral, and Jing was the host climatic Qi and collateral was the main blood; early Qi was located at Jing, it would harm the blood and enter into collateral, which was the theory of chronic diseases transforming to collateral inA Guide to Clinical Practice with Medical Record.

The people who agree to lung paralysis theory think that the pathogenesis of lung disease lie incollaterals,blood stagnation and classical medical books on the meridian obstruction pathology hold the same opinion; People holding withered lung theory believe that the pathogenesis of blood includes deficiency,characteristics of losingRu Yang, at the same time,from the aspect of the form, pulmonary fibrosis in the latestage shows that lungs will become smaller and harder, loss of lung function, which arelike long illness and lung lobes are weak; The nature of collateral disease is in collateral block, which means the fl ow of blood is poor, and it belongs to the category of blood stasis. The patient of pulmonary fibrosis has the clinical manifestations of blood stasis, such as lips cyanosis,dark purple tongue, therefore, pulmonary fibrosis is a traditional Chinese medicine collateral disease.

We believe that lung paralysis and collateral disease have meridian paralysis barrier mechanism, however,the name of lung paralysis involving viscera is more comprehensive than collateral disease. Thus, collateral disease can be classified as lung paralysis category.Lung paralysis and pulmonary withered can be used as the diagnosis of Traditional Chinese Medicine disease name for pulmonary interstitial fibrosis, to show the different stages of the disease, and under certain conditions, they can interact with each other, and there is a mutual evolution from the lung paralysis to pulmonary withered.

ETIOLOGY AND PATHOGENESIS OF TRADITIONAL CHINESE MEDICINE

As for the etiology and pathogenesis of the disease,different people have different views. There are some conclusions based on recent researches that scholars have made on the pathogenesis of the disease.Zhang Yueying2holds that the lung fibrosis is caused by the deficiency thoracic qi and sinking of great Qi in chest, the pathogenesis is that the meridians of the lungs are closed, and there is blood stagnation, so treating the disease should focus on tonifying Qi, then promoting blood circulation to remove blood stasis,such kind of treatment should be insisted on all the time.Cui HongshengandJiang Liangduo3think that the poisonous lung collateral is the basic pathogenesis of interstitial lung disease development. Diving from the source of poison, it can be divided into exogenous toxin and endogenous poisonous toxin. The former one is from the outside, which includes the direct experience of the external toxin. The latter one is produced by the body’s physiological or pathological products that cannot be discharged in time because of organs and blood disorders,Li PeiandZhang Wei4believe that the first condition of pulmonary fibrosis is vital Qi deficiency, and the deficiency and phlegm stasis lung are the key pathogenesis since Qi deficiency in the development of pulmonary fibrosis plays an important role.Zhang Mingyuan5summarizes that the pathogenesis of pulmonary fibrosis is the evil nostalgia based on lung Qi deficiency, phlegm, blood stasis,retained fl uid, and cold and heat evil, blocking the lungs,and ultimately leads to a virtual and evil coexistence.Zhang Guicai6thinks that the disease is in the lungs, it involves the spleen and kidney, the virtual real standard and the actual situation is mixed. The virtual means spleen and lung deficiency, and the standard is for the phlegm and blood stasis in the lungs.

Based on the summary of the views of doctors, we believe that the disease occurs because the virtual real standard and the actual situation is mixed, the virtual is for the lung, spleen, kidney deficiency, the standard is for phlegm, blood stasis, heat poison and so on. In the early stage of the disease, the pulmonary meridian paralysis is the main pathogenesis characteristics;in chronic disease period, pulmonary collateral and vein emptiness exist at the same time, which is the pathogenesis of the actual situation, and pulmonary paralysis and pulmonary atrophy exist at the same time; at the late stage, the pathogenesis of Qi and blood is from the lung, heart and kidney, lacking of blood,vein emptiness, with the main pathogenesis of it being virtual.

DIALECTICAL TREATMENT OF TRADITIONAL CHINESE MEDICINE

At present, the etiology and pathogenesis,differentiation of symptoms and signs, and the classification of syndrome of IPIF are not the same, its treatment also has its own characteristics.

Wang Haitong, Wu Weiping, etc7divided IPF into mild, moderate and severe three periods, Which included disease onset complicated with six excesses and chronic deferred, chronic sub-acute stage, during which the principal points were to reinforce the healthy qi, secure the root, activate blood and resolve stasis, special attention should be given to nourishing the kidney according to vicissitudes of vital qi and pathogens, blood-activating and stasis-dissolving medicinal should be added for nourishing the blood and activating blood circulation properly; stage of fighting against six excesses by relieving exterior syndrome and reducing phlegm and diffusing the lung as the principal points, with the drugs for tonifying qi and nourishing yin or replenishing qi and activating blood; treatment varied for the terminally advanced respiratory failure and prosperous pathogen with asthenic healthy qi. To sum up, we should choose the method, prescription,Chinese medicine on the basis of symptom changes.

Peng Fuli8treated the IPF by stages with differentiation of syndrome and corresponding treatment, in the early course of the disease, syndrome of lung-spleen qi deficiency and syndrome intermingled with phlegm and blood stasis, in the medium stage,it was divided into syndrome of lung-spleen yin deficiency, syndrome of phlegm-heat and blood stasis and syndrome of dual deficiency of lung-kidney of qi and yin, and syndrome of spleen-kidney yang deficiency was common syndrome at the advanced stage of IPIF, it was divided into syndrome of yin deficiency with water flood，syndrome of yang deficiency with water flood and syndrome of dual deficiency of yin and yang.

Jia Xinhua and others9believed that the two most important aspects were treating the root and treating the tip, in the alveolitis stage, treating the symptoms was as a general rule, wind-heat, dryness-heat and phlegmheat were more common in the clinical practice, and it was also mixed with syndrome of qi deficiency and yin deficiency, treatment lied in clearing heat and resolving phlegm, tonifying qi to produce fluid as the principle. In the fibrosis stage, treating the root was the general principle, dialectical treatment of TCM divided the causes into deficiency of genuine qi and excess of pathogenic factor, deficiency complicated with excess, the deficiency of genuine qi was split into dual deficiency of qi and blood and deficiency of collateral,the excess of pathogenic factor is intermingled with phlegm and blood stasis, treatment should reduce the excessive and replenish the deficiency by both smoothing and tonifying.

Fan Maorong and others10believed in differentiating syndrome of deficiency ben and excessive biao was the first thing during clinical treatment, the lesion location is in lung first, progressive disease will harm lung qi and yin, the syndrome of dual deficiency of qi and yin is the important type of chronic sub-acute stage, in the advanced stage, the location of the disease developed from the lung and kidney to the heart and kidney, on the basis of deficiency Ben. It was always followed by syndrome of excessive biao, in the standard licence, blood was the most common syndrome,and the syndrome of excessive biao always appeared, deficiency ben and excessive biao always appeared simultaneously and they were interrelated.

Fu Yi and others11simplified the disease, according to them, the disease was divided into two periods:①The early stage (Fei bi) was characterized by phlegm or dampness-turbidity accumulating with stagnant blood and insufficiency of pectoral qi, treatment should lie in resolving phlegm (purging turbidity) and promoting blood circulation as the principle, which was supplemented with enriching pectoral qi; ②The advanced stage (Fei Wei) was characterized by lung and kidney deficiency, phlegm and blood stasis,treatment should be in tonifying lung and kidney,resolving phlegm and dredging collateral.

CONCLUSION

Combined with the above views, we suggest that the IPF should be treated according to stages, which should be divided into early stage, chronic sub-acute stage and advanced stage. Phlegm, blood stasis, heat and toxin were the most common obstruction of lung collateral in the early stage, which belong to phlegm stagnation type, dampness-heat type and blood stasis type, should be treated with promoting blood circulation

for removing blood stasis, clearing the lung, resolving phlegm and dispelling stasis to unblock collateral;in the chronic sub-acute stage, deficiency of genuine qi and excess of pathogenic factor and deficiency complicated with excess was most common, which was divided into pulmonary collateral obstruction,lung-qi deficiency, deficiency due to excess, deficiency complicated with excess, among which qi deficiency,blood stasis and phlegm were most common types,and it should be treated with the method of reducing the excessive and replenishing the deficiency by both smoothing and tonifying, which meant tonifying qi and nourishing yin, resolving phlegm to unblock collateral,activating blood and resolving stasis; in the advanced stage,dual deficiency of qi and blood and deficiency of collateral were most important, the characteristics of its pathogenesis included collateral being void and defenceless and phlegm accumulating with stagnation,which belonged to deficiency of qi and blood,phlegm and blood stasis, which was mainly treated by strengthening the body resistance, adding drugs to resolve phlegm and remove blood stasis properly.

1 Martinez FJ, SafrinS, WeyckerD, et al. The clinical course of patients with idiopathic pulmonary fibrosis. Ann Intren Med, 2005, 142(12Pt1):963-967.

2 Zhang YY. Discussion on treating Feibi from Ye Tianshi.Beijing J TCM, 2004, 23(6):340-341.

3 Cui HS, Wu WP, Jiang LD. Injury of feiluo and pulmonary interstitial fibrosis. J Tradit Chin Med, 2007, 48(9):858-859.

4 Li P, Zhang W. Description on pathogenesis of pulmonary fibrosis from Qixu. Jiangsu J Tradit Chin Med, 2014,46(9):12-13.

5 Zhang MY, Li JZ. Discussion on pathogenesis of pulmonary interstitial fibrosis in TCM. Hebei J TCM, 2016,38(9):1398-1399.

6 Zhang GC, Zhou XM. Analysis of idiopathic pulmonary fibrosis in TCM. Guangming Tradit Chin Med, 2013,28(12): 2463-2464.

7 Wang HT, Wu WP. Discussion on treating diffuse pulmonary interstitial fibrosis in TCM. Chinese J of Information on TCM, 1996, 3(7):25-26.

8 Peng FL. Treating Pulmonary Interstitial Fibrosis in TCM. J clincal and experimental med, 2009, 8(5):116.

9 Jia XH, Chen XH, Zhang XC. Discussion on treating DILD by TCM syndrome differentiation. Acta Chinese Med and Pharmacology, 2012, 40(5):3-5.

10 Fan MR, Han KH, Wang SC, et al. A study on TCM syndromes of idiopathic pulmonary interstitial fibrosis.Beijing J Tradit Chin Med, 2012, 31(4):252-253.

11 Fu Y, Yu XL, Wei DX, et al. Discussion on treating idiopathic pulmonary interstitial fibrosis with TCM. Chinese J Information on Tradit Chin Med, 2016, 23(7):108-110.

Funding:Name: Clinical study of FeiXianTong Decoction improving activity tolerance in patients with idiopathic pulmonary fibrosis. Subject is from Beijing municipal commission of science and technology (number: Z131107002213053)

*Corresponding author:Email: luohaili8@aliyun.com

(Accepted: March 19, 2017)