Background Idiopathic pulmonary fibrosis (IPF) is a dreadful disease characterized by
progressive impairment in quality of life, increasingly limited physical function, and an
early death from respiratory failure. IPF is the most common and predominantly lethal form of
the idiopathic interstitial pneumonias, with an associated median survival of only 2 to 3
years. The etiology of this chronic and progressive fibrotic lung disease is unknown,
although potential risk factors such as cigarette smoking and other environmental exposures
have been described. In a study published in 2006 based on a United States healthcare claims
database, the prevalence of IPF was between 14-42.7 per 100,000, depending on whether narrow
or broad case-finding criteria was used. IPF is more commonly seen in patients between 40 to
70 years of age. The risk of death as a result of IPF also increases with age, with a hazard
ratio of 0.25 for patients younger than 50 years and a longer median survival amongst those
younger than 50 (116.4 months compared to 62.8 months). IPF occurs more commonly in men than
in women and also progress faster and result in worse survival in men. The IPF mortality rate
in the United States was found to be 61.2 deaths per 1,000,000 in men and 54.5 per 1,000,000
in women, nevertheless, the death rate in women is increasing at a faster rate than in men.
Age-adjusted mortality has been found to be greater among whites than blacks and is
increasing at a higher rate among whites when compared to other racial and ethnic groups.
There is no effective treatment for IPF, although pirfenidone and nintedanib have been
approved for treatment of IPF, with benefit in slowing down lung function decline. At
present, the only intervention that improves survival in select patients with IPF is lung
transplantation. With this to look forward to, it is no surprise that patients and their
physicians are desperate for treatment options that might change the outcome. Traditional
Chinese herbal medicine has been an important source to treat this ailment.
Traditional Chinese medicine (TCM) has dealt with IPF for long time. A condition similar to
pulmonary fibrosis can be found in Chinese literature thousands years ago. A disease termed
"Fei Wei" was described and is similar to IPF in definition, pathophysiology, and treatment.
It was reported that the disease was extremely difficult to treat. Other TCM terms of
respiratory disease similar to IPF were "short breath", "cough", "lung inflation", and "Fei
Bi".
In recent years, TCM has renewed its focus on pulmonary fibrosis and other respiratory
illnesses because of SARS (Severe Acute Respiratory Syndrome), a viral infection which spread
in China in late 2002 and 2003. SARS infection resulted in pulmonary fibrosis in a number of
individuals who contracted SARS, although the pathophysiology of pulmonary fibrosis resulting
from SARS may differ from that of IPF, the fibrosis can be reversible. In TCM, the
pathophysiology for IPF is a complex of group of terms: Feng (Wind-external factor), Re
(Heat-inflammation), Tan (Phlegm), Yu (Congestion). Treatment may vary according to the
phases of the disease, symptoms, and individuals.
IPF causes pulmonary interstitial chronic inflammation, immune complex deposition in the lung
interstitium into fibroblasts and collagen eventually leads to the destruction of lung
tissue. In TCM terms, this represents Blockage of Heat in the lung. With Heat in the
pulmonary mass, the Lung loses the function of controlling Qi, hence the patients suffers
difficulty in breathing, has no air suction, has shortness of breath, dry cough, wheezing,
and other symptoms.
In China, herbal medicine is the main treatment for IPF. Research has shown the effectiveness
of traditional Chinese herbs formulations developed to treat IPF. The Individual herbs of the
formula have been widely used to improve pulmonary function.
Current evidence Chinese herbal medicine formula used in the proposed study. Our empirical evidence suggests that one Chinese herbal medicine formula PROLUNG has
considerable benefit in the treatment of IPF. Individual herbs of the formula are listed as
follows (weight in granule preparation):
Huang Qi (Radix Astragali Membranaceus): 2 g Dan Shen (Radix Salviae Miltiorrhizae): 1 g
Jiang Huang (Rhizoma Curcumae Longae): 1 g Yin Xing (Semen Gingko Bilobae): 1 g Mai Men Dong
(Tuber Ophiopogonis Japonoci): 1 g Bai He (Bulbus Lilii): 1g Jin Yin Hua (Flos Lonicerae
Japonicae): 1 g Zi Su Ye (Folium Perillae Frutescentis): 1 g Yin Yang Huo (Herba Epimedii):
1g. The therapeutic effects in treating IPF: One study in animal model of IPF has shown that
treatment with an herbal formula including Ginseng, Mai Men Dong, Tao Ren, Chi Shao, Neu Xi,
Jie Geng, Dang Gui, Di Hung, Ban Xia, Gan Cao, Zhi Ke, and Hong Hua inhibited B cell
hyperactivity, which may be related to fibrosis. IPF patients treated with a combination of
traditional Chinese herbs and drugs improve faster and remain free of IPF longer than
patients treated with drugs alone. One 2-month study was performed in 12 patients with IPF to
find out the effect of a combination of Dang Shen, Huang Qi, Sha Shen, Mai Men Dong, Dang
Gui, Dan Shen, Chuan Xiong, Sang Bei Pi, Xing Ren, Bai Guo, Huang Qin, Ban Xia, Ma Huang, and
Gan Cao. The patients were exclusively provided with the Chinese herb formulation except when
the illness worsened. The results have shown an improvement in dyspnea and cyanosis and an
increase in PO2 (partial pressure of oxygen) in 5 of the 12 patients.
Dan Shen (Radix Salviae Miltiorrhizae): Dan Shen and its purified active component IH764-3,
have been shown to prevent pulmonary fibrosis induced with bleomycin. The Chinese herb
formulation blocks the expression of TGF-alpha1 and inhibits the activity of fibroblast
growth factor when administered 24 hours after bleomycin-induction. Dan Shen has also been
used successfully in the treatment of allergic rhinitis by bilateral injection into the
inferior nasal choncha.
Huang Qi (Radix Astragali Membranaceus): Astragaloside is the main ingredient in Huang Qi,
and is known to have antiinflammatory, anti-fibrotic, and immunoregulatory properties. It was
reported to improve lung functions in mice experimentally induced chronic asthma by reducing
the amount of hydroxyproline, an indicator of pulmonary fibrotic activity. The administration
of Huang Qi in a population with history of bronchial asthma, allergic rhinitis, and chronic
bronchitis, Huang Qi prevents against pulmonary tract infections. Among 30 patients with IPF
treated with Huang Qi in combination with other Chinese herb formulations, 3.87% showed
larger increase in diffusing capacity of the lung for carbon monoxide (DLCO) as compared with
patients treated with prednisone in a clinical study. A combination of Huang Qi, Dan Shen and
prednisone was given to 19 patients who had a 3.75% greater improvement in total lung
capacity, a 4.01% greater improvement in vital capacity, and a 3.78% greater increase in DLCO
than 19 other patients who exclusively received prednisone. Dan Shen and Huang Qi were
components in an herbal combination that resulted in 3- and 5- year survival rates in
subjects with IPF.
Jiang Huang (Rhizoma Curcumae Longae): Jiang Huang's anti-inflammatory properties have been
established in rats. Curcumin, which is derived from Jiang Huang, also has anti-carcinogenic
and antioxidant characteristics. Curcumin can limit the expression of tumor growth factor- β
(TGF-β). It can also reduce TGF-β signaling in renal fibroblasts in vitro. It has been shown
to limit hydroxyproline levels in the lungs of mice exposed to bleomycin and to prevent
alveolitis in mice with bleomycin-induced IPF.
Yin Xing (Semen Gingko Bilobae): Yin Xing is recommended to treat chronic cough, asthma,
chronic wheezing, phlegm, and chronic voice loss. The bronchodilation and expectorant
properties of Yin Xing have been established.
Mai Men Dong (Tuber Ophiopogonis Japonoci): For chronic dry cough and sore throat, Mai Men
Dong is a recommended treatment. Mai Men Dong in combination with other traditional Chinese
herbs was shown to be effective in the treatment of allergic asthma in children.
Bai He (Bulbus Lilii): Bai He is recommended to be used in combination with other herbs, in
the treatment of dry cough, bronchiectasis, and hemoptysis and alone in the treatment of lung
abcesses.
Jin Yin Hua (Flos Lonicerae Japonicae): Jin Yin Hua is recommended to treat pneumonia,
bronchitis, and upper respiratory tract infections in general in combination with other
herbs.
Zi Su Ye (Folium Perillae Frutescentis): Zi Su Ye improves bronchodilation, decreases
bronchioli excretions and relieves bronchiospasms.
Yin Yang Huo (Herba Epimedii): Yin Yang Huo has expectorant, antiasthmatic, and antitussive
actions. Yin Yang Huo has shown effectiveness to treat chronic bronchitis.
Toxic profiles and herb interactions: Individual herbs used in the formula are in general
safe and well tolerated within therapeutic doses. Dan Shen increased the effect of warfarin
when the two medications are taken together. Dan Shen also increased the activity of liver
enzymes involved in drug metabolism, thereby increasing drug metabolism rates. Jiang Huang
may also exacerbate the effects of warfarin.
