<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03274544</url>
  </required_header>
  <id_info>
    <org_study_id>UW 17-283</org_study_id>
    <nct_id>NCT03274544</nct_id>
  </id_info>
  <brief_title>Clinical Trial of Chinese Herbal Medicine for Idiopathic Pulmonary Fibrosis (IPF)</brief_title>
  <official_title>The Effectiveness of an Empirical Chinese Medicine Formulation for Idiopathic Pulmonary Fibrosis: an Open Label Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Queen Mary Hospital, Hong Kong</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The University of Hong Kong</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This open label clinical study will be conducted in School of Chinese Medicine Clinics at The&#xD;
      University of Hong Kong (HKU) to preliminarily determine whether treatment with the herbal&#xD;
      formula PROLUNG could improve Idiopathic Pulmonary Fibrosis (IPF) symptoms, respiratory&#xD;
      function and the quality of life of patients with IPF compared with pretreatment baseline. We&#xD;
      propose to recruit 30 participants. The diagnosis and screening will be conducted by&#xD;
      respiratory physicians. Those who meet the inclusion criteria will be referred by the expert&#xD;
      to the PI. The PI will prescribe the formula in granule form to the participants in&#xD;
      Traditional Chinese medicine (TCM) Clinics as usual. Patients will receive 6 months of the&#xD;
      herbal treatment and 7 visits.&#xD;
&#xD;
      Annual rate of change in forced expiratory vital capacity (FVC) will serve the primary&#xD;
      outcome. The St. George's Respiratory Questionnaire (SGRQ) will be used to additionally&#xD;
      assess respiratory functions. A standard questionnaire will be administered to obtain&#xD;
      information on age, sex, marital status, education, social class, smoking behaviour and&#xD;
      respiratory diseases. Other outcome measures include the 36-Item Short Form Survey (SF-36)&#xD;
      and the World Health Organization Quality of Life assessment instrument (WHOQOLBREF) by each&#xD;
      participant after enrollment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background Idiopathic pulmonary fibrosis (IPF) is a dreadful disease characterized by&#xD;
      progressive impairment in quality of life, increasingly limited physical function, and an&#xD;
      early death from respiratory failure. IPF is the most common and predominantly lethal form of&#xD;
      the idiopathic interstitial pneumonias, with an associated median survival of only 2 to 3&#xD;
      years. The etiology of this chronic and progressive fibrotic lung disease is unknown,&#xD;
      although potential risk factors such as cigarette smoking and other environmental exposures&#xD;
      have been described. In a study published in 2006 based on a United States healthcare claims&#xD;
      database, the prevalence of IPF was between 14-42.7 per 100,000, depending on whether narrow&#xD;
      or broad case-finding criteria was used. IPF is more commonly seen in patients between 40 to&#xD;
      70 years of age. The risk of death as a result of IPF also increases with age, with a hazard&#xD;
      ratio of 0.25 for patients younger than 50 years and a longer median survival amongst those&#xD;
      younger than 50 (116.4 months compared to 62.8 months). IPF occurs more commonly in men than&#xD;
      in women and also progress faster and result in worse survival in men. The IPF mortality rate&#xD;
      in the United States was found to be 61.2 deaths per 1,000,000 in men and 54.5 per 1,000,000&#xD;
      in women, nevertheless, the death rate in women is increasing at a faster rate than in men.&#xD;
      Age-adjusted mortality has been found to be greater among whites than blacks and is&#xD;
      increasing at a higher rate among whites when compared to other racial and ethnic groups.&#xD;
      There is no effective treatment for IPF, although pirfenidone and nintedanib have been&#xD;
      approved for treatment of IPF, with benefit in slowing down lung function decline. At&#xD;
      present, the only intervention that improves survival in select patients with IPF is lung&#xD;
      transplantation. With this to look forward to, it is no surprise that patients and their&#xD;
      physicians are desperate for treatment options that might change the outcome. Traditional&#xD;
      Chinese herbal medicine has been an important source to treat this ailment.&#xD;
&#xD;
      Traditional Chinese medicine (TCM) has dealt with IPF for long time. A condition similar to&#xD;
      pulmonary fibrosis can be found in Chinese literature thousands years ago. A disease termed&#xD;
      &quot;Fei Wei&quot; was described and is similar to IPF in definition, pathophysiology, and treatment.&#xD;
      It was reported that the disease was extremely difficult to treat. Other TCM terms of&#xD;
      respiratory disease similar to IPF were &quot;short breath&quot;, &quot;cough&quot;, &quot;lung inflation&quot;, and &quot;Fei&#xD;
      Bi&quot;.&#xD;
&#xD;
      In recent years, TCM has renewed its focus on pulmonary fibrosis and other respiratory&#xD;
      illnesses because of SARS (Severe Acute Respiratory Syndrome), a viral infection which spread&#xD;
      in China in late 2002 and 2003. SARS infection resulted in pulmonary fibrosis in a number of&#xD;
      individuals who contracted SARS, although the pathophysiology of pulmonary fibrosis resulting&#xD;
      from SARS may differ from that of IPF, the fibrosis can be reversible. In TCM, the&#xD;
      pathophysiology for IPF is a complex of group of terms: Feng (Wind-external factor), Re&#xD;
      (Heat-inflammation), Tan (Phlegm), Yu (Congestion). Treatment may vary according to the&#xD;
      phases of the disease, symptoms, and individuals.&#xD;
&#xD;
      IPF causes pulmonary interstitial chronic inflammation, immune complex deposition in the lung&#xD;
      interstitium into fibroblasts and collagen eventually leads to the destruction of lung&#xD;
      tissue. In TCM terms, this represents Blockage of Heat in the lung. With Heat in the&#xD;
      pulmonary mass, the Lung loses the function of controlling Qi, hence the patients suffers&#xD;
      difficulty in breathing, has no air suction, has shortness of breath, dry cough, wheezing,&#xD;
      and other symptoms.&#xD;
&#xD;
      In China, herbal medicine is the main treatment for IPF. Research has shown the effectiveness&#xD;
      of traditional Chinese herbs formulations developed to treat IPF. The Individual herbs of the&#xD;
      formula have been widely used to improve pulmonary function.&#xD;
&#xD;
      Current evidence Chinese herbal medicine formula used in the proposed study&#xD;
&#xD;
      Our empirical evidence suggests that one Chinese herbal medicine formula PROLUNG has&#xD;
      considerable benefit in the treatment of IPF. Individual herbs of the formula are listed as&#xD;
      follows (weight in granule preparation):&#xD;
&#xD;
      Huang Qi (Radix Astragali Membranaceus): 2 g Dan Shen (Radix Salviae Miltiorrhizae): 1 g&#xD;
      Jiang Huang (Rhizoma Curcumae Longae): 1 g Yin Xing (Semen Gingko Bilobae): 1 g Mai Men Dong&#xD;
      (Tuber Ophiopogonis Japonoci): 1 g Bai He (Bulbus Lilii): 1g Jin Yin Hua (Flos Lonicerae&#xD;
      Japonicae): 1 g Zi Su Ye (Folium Perillae Frutescentis): 1 g Yin Yang Huo (Herba Epimedii):&#xD;
      1g&#xD;
&#xD;
      The therapeutic effects in treating IPF: One study in animal model of IPF has shown that&#xD;
      treatment with an herbal formula including Ginseng, Mai Men Dong, Tao Ren, Chi Shao, Neu Xi,&#xD;
      Jie Geng, Dang Gui, Di Hung, Ban Xia, Gan Cao, Zhi Ke, and Hong Hua inhibited B cell&#xD;
      hyperactivity, which may be related to fibrosis. IPF patients treated with a combination of&#xD;
      traditional Chinese herbs and drugs improve faster and remain free of IPF longer than&#xD;
      patients treated with drugs alone. One 2-month study was performed in 12 patients with IPF to&#xD;
      find out the effect of a combination of Dang Shen, Huang Qi, Sha Shen, Mai Men Dong, Dang&#xD;
      Gui, Dan Shen, Chuan Xiong, Sang Bei Pi, Xing Ren, Bai Guo, Huang Qin, Ban Xia, Ma Huang, and&#xD;
      Gan Cao. The patients were exclusively provided with the Chinese herb formulation except when&#xD;
      the illness worsened. The results have shown an improvement in dyspnea and cyanosis and an&#xD;
      increase in PO2 (partial pressure of oxygen) in 5 of the 12 patients.&#xD;
&#xD;
      Dan Shen (Radix Salviae Miltiorrhizae): Dan Shen and its purified active component IH764-3,&#xD;
      have been shown to prevent pulmonary fibrosis induced with bleomycin. The Chinese herb&#xD;
      formulation blocks the expression of TGF-alpha1 and inhibits the activity of fibroblast&#xD;
      growth factor when administered 24 hours after bleomycin-induction. Dan Shen has also been&#xD;
      used successfully in the treatment of allergic rhinitis by bilateral injection into the&#xD;
      inferior nasal choncha.&#xD;
&#xD;
      Huang Qi (Radix Astragali Membranaceus): Astragaloside is the main ingredient in Huang Qi,&#xD;
      and is known to have antiinflammatory, anti-fibrotic, and immunoregulatory properties. It was&#xD;
      reported to improve lung functions in mice experimentally induced chronic asthma by reducing&#xD;
      the amount of hydroxyproline, an indicator of pulmonary fibrotic activity. The administration&#xD;
      of Huang Qi in a population with history of bronchial asthma, allergic rhinitis, and chronic&#xD;
      bronchitis, Huang Qi prevents against pulmonary tract infections. Among 30 patients with IPF&#xD;
      treated with Huang Qi in combination with other Chinese herb formulations, 3.87% showed&#xD;
      larger increase in diffusing capacity of the lung for carbon monoxide (DLCO) as compared with&#xD;
      patients treated with prednisone in a clinical study. A combination of Huang Qi, Dan Shen and&#xD;
      prednisone was given to 19 patients who had a 3.75% greater improvement in total lung&#xD;
      capacity, a 4.01% greater improvement in vital capacity, and a 3.78% greater increase in DLCO&#xD;
      than 19 other patients who exclusively received prednisone. Dan Shen and Huang Qi were&#xD;
      components in an herbal combination that resulted in 3- and 5- year survival rates in&#xD;
      subjects with IPF.&#xD;
&#xD;
      Jiang Huang (Rhizoma Curcumae Longae): Jiang Huang's anti-inflammatory properties have been&#xD;
      established in rats. Curcumin, which is derived from Jiang Huang, also has anti-carcinogenic&#xD;
      and antioxidant characteristics. Curcumin can limit the expression of tumor growth factor- β&#xD;
      (TGF-β). It can also reduce TGF-β signaling in renal fibroblasts in vitro. It has been shown&#xD;
      to limit hydroxyproline levels in the lungs of mice exposed to bleomycin and to prevent&#xD;
      alveolitis in mice with bleomycin-induced IPF.&#xD;
&#xD;
      Yin Xing (Semen Gingko Bilobae): Yin Xing is recommended to treat chronic cough, asthma,&#xD;
      chronic wheezing, phlegm, and chronic voice loss. The bronchodilation and expectorant&#xD;
      properties of Yin Xing have been established.&#xD;
&#xD;
      Mai Men Dong (Tuber Ophiopogonis Japonoci): For chronic dry cough and sore throat, Mai Men&#xD;
      Dong is a recommended treatment. Mai Men Dong in combination with other traditional Chinese&#xD;
      herbs was shown to be effective in the treatment of allergic asthma in children.&#xD;
&#xD;
      Bai He (Bulbus Lilii): Bai He is recommended to be used in combination with other herbs, in&#xD;
      the treatment of dry cough, bronchiectasis, and hemoptysis and alone in the treatment of lung&#xD;
      abcesses.&#xD;
&#xD;
      Jin Yin Hua (Flos Lonicerae Japonicae): Jin Yin Hua is recommended to treat pneumonia,&#xD;
      bronchitis, and upper respiratory tract infections in general in combination with other&#xD;
      herbs.&#xD;
&#xD;
      Zi Su Ye (Folium Perillae Frutescentis): Zi Su Ye improves bronchodilation, decreases&#xD;
      bronchioli excretions and relieves bronchiospasms.&#xD;
&#xD;
      Yin Yang Huo (Herba Epimedii): Yin Yang Huo has expectorant, antiasthmatic, and antitussive&#xD;
      actions. Yin Yang Huo has shown effectiveness to treat chronic bronchitis.&#xD;
&#xD;
      Toxic profiles and herb interactions: Individual herbs used in the formula are in general&#xD;
      safe and well tolerated within therapeutic doses. Dan Shen increased the effect of warfarin&#xD;
      when the two medications are taken together. Dan Shen also increased the activity of liver&#xD;
      enzymes involved in drug metabolism, thereby increasing drug metabolism rates. Jiang Huang&#xD;
      may also exacerbate the effects of warfarin.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Difficulty in recruiting eligible patients&#xD;
  </why_stopped>
  <start_date type="Actual">August 14, 2018</start_date>
  <completion_date type="Actual">June 1, 2020</completion_date>
  <primary_completion_date type="Actual">May 27, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Annual rate of change in forced expiratory vital capacity (FVC)</measure>
    <time_frame>Baseline, 6 month</time_frame>
    <description>Annual rate of change in forced expiratory vital capacity (FVC) will serve the primary outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in SGRQ score</measure>
    <time_frame>Baseline, 1 month, 2 month, 3 month, 4 month, 5 month, 6 month</time_frame>
    <description>The St. George's Respiratory Questionnaire (SGRQ) will be used to additionally assess respiratory functions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in SF-36 score</measure>
    <time_frame>Baseline, 1 month, 2 month, 3 month, 4 month, 5 month, 6 month</time_frame>
    <description>The 36-Item Short Form Survey (SF-36) is a 36-question questionnaire to assess the quality of life of a participant in terms of physical and mental health.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in WHOQOL-BREF score</measure>
    <time_frame>Baseline, 1 month, 2 month, 3 month, 4 month, 5 month, 6 month</time_frame>
    <description>The WHOQOL-BREF measures the physical and psychological health, the social relationships, and the environment of an individual.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in adverse events</measure>
    <time_frame>Baseline, 1 month, 2 month, 3 month, 4 month, 5 month, 6 month</time_frame>
    <description>All patients will be monitored for adverse reactions of any kind including but not limited to idiosyncratic allergic reactions to some components of the treatment.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Idiopathic Pulmonary Fibrosis</condition>
  <arm_group>
    <arm_group_label>PROLUNG</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Herbal formula treatment PROLUNG in additional to current therapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>PROLUNG</intervention_name>
    <description>Chinese herbal medicine formula PROLUNG with individual herbs of the formula are listed as follows (weight in granule preparation):&#xD;
Huang Qi (Radix Astragali Membranaceus): 2 g&#xD;
Dan Shen (Radix Salviae Miltiorrhizae): 1 g&#xD;
Jiang Huang (Rhizoma Curcumae Longae): 1 g&#xD;
Yin Xing (Semen Gingko Bilobae): 1 g&#xD;
Mai Men Dong (Tuber Ophiopogonis Japonoci): 1 g&#xD;
Bai He (Bulbus Lilii): 1g&#xD;
Jin Yin Hua (Flos Lonicerae Japonicae): 1 g&#xD;
Zi Su Ye (Folium Perillae Frutescentis): 1 g&#xD;
Yin Yang Huo (Herba Epimedii): 1g</description>
    <arm_group_label>PROLUNG</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Either gender aged 40-75;&#xD;
&#xD;
          -  Has a diagnosis of IPF, made by a respiratory expert based on International&#xD;
             Classification of Diseases (ICD-10);&#xD;
&#xD;
          -  No participation in another clinical study within 4 weeks of study start.&#xD;
&#xD;
          -  Participation in this study must be voluntary and not coerced.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have received lung transplantation.&#xD;
&#xD;
          -  Any condition that may compromise patient safety.&#xD;
&#xD;
          -  Pregnant women or women trying to become pregnant will be excluded from the study.&#xD;
&#xD;
          -  History of drug or alcohol abuse within 6 months of study start.&#xD;
&#xD;
          -  History of immunocompromise, including a positive HIV test result.&#xD;
&#xD;
          -  Impaired liver and renal functions.&#xD;
&#xD;
          -  Known allergies to any Chinese herbs and participants with numerous or severe&#xD;
             allergies to any allergen.&#xD;
&#xD;
          -  Pre-existing conditions including renal failure, chronic renal problems, chronic&#xD;
             hepatitis, other pulmonary problems, diabetes, and heart problems will be excluded&#xD;
             from the study.&#xD;
&#xD;
          -  Either mentally incompetent or are unable to give informed consent because of the&#xD;
             language barrier.&#xD;
&#xD;
          -  Taking the following drugs, even as part of their current treatment regimen for IPF:&#xD;
             pirfenidone, nintedanib, antiplatelet drugs (including aspirin, clopidogrel (Plavix),&#xD;
             and dipyridamole (Persantine), anticoagulant drugs (including warfarin (Coumadin),&#xD;
             enoxparin (Lovenox), and heparin), cardiac glycosides (e.g. digoxin), sedatives and&#xD;
             sedative-containing drugs (including barbiturates, narcotic analgesics,&#xD;
             benzodiazepines, and antihistamines), and traditional Chinese herbal medicines or&#xD;
             granules, or other herbal medicines or supplements.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zhang-Jin ZHANG, MMed, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>zhangzj@hku.hk</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Queen Mary Hospital</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Hong Kong</country>
  </location_countries>
  <reference>
    <citation>Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, Lynch DA, Ryu JH, Swigris JJ, Wells AU, Ancochea J, Bouros D, Carvalho C, Costabel U, Ebina M, Hansell DM, Johkoh T, Kim DS, King TE Jr, Kondoh Y, Myers J, Muller NL, Nicholson AG, Richeldi L, Selman M, Dudden RF, Griss BS, Protzko SL, Schunemann HJ; ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011 Mar 15;183(6):788-824. doi: 10.1164/rccm.2009-040GL.</citation>
    <PMID>21471066</PMID>
  </reference>
  <reference>
    <citation>Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2006 Oct 1;174(7):810-6. doi: 10.1164/rccm.200602-163OC. Epub 2006 Jun 29.</citation>
    <PMID>16809633</PMID>
  </reference>
  <reference>
    <citation>Navaratnam V, Fleming KM, West J, Smith CJ, Jenkins RG, Fogarty A, Hubbard RB. The rising incidence of idiopathic pulmonary fibrosis in the U.K. Thorax. 2011 Jun;66(6):462-7. doi: 10.1136/thx.2010.148031. Epub 2011 Apr 27.</citation>
    <PMID>21525528</PMID>
  </reference>
  <reference>
    <citation>Erbes R, Schaberg T, Loddenkemper R. Lung function tests in patients with idiopathic pulmonary fibrosis. Are they helpful for predicting outcome? Chest. 1997 Jan;111(1):51-7. doi: 10.1378/chest.111.1.51.</citation>
    <PMID>8995992</PMID>
  </reference>
  <reference>
    <citation>King TE Jr, Tooze JA, Schwarz MI, Brown KR, Cherniack RM. Predicting survival in idiopathic pulmonary fibrosis: scoring system and survival model. Am J Respir Crit Care Med. 2001 Oct 1;164(7):1171-81. doi: 10.1164/ajrccm.164.7.2003140.</citation>
    <PMID>11673205</PMID>
  </reference>
  <reference>
    <citation>Han MK, Murray S, Fell CD, Flaherty KR, Toews GB, Myers J, Colby TV, Travis WD, Kazerooni EA, Gross BH, Martinez FJ. Sex differences in physiological progression of idiopathic pulmonary fibrosis. Eur Respir J. 2008 Jun;31(6):1183-8. doi: 10.1183/09031936.00165207. Epub 2008 Mar 5.</citation>
    <PMID>18321929</PMID>
  </reference>
  <reference>
    <citation>Gribbin J, Hubbard RB, Le Jeune I, Smith CJ, West J, Tata LJ. Incidence and mortality of idiopathic pulmonary fibrosis and sarcoidosis in the UK. Thorax. 2006 Nov;61(11):980-5. doi: 10.1136/thx.2006.062836. Epub 2006 Jul 14.</citation>
    <PMID>16844727</PMID>
  </reference>
  <reference>
    <citation>Olson AL, Swigris JJ, Lezotte DC, Norris JM, Wilson CG, Brown KK. Mortality from pulmonary fibrosis increased in the United States from 1992 to 2003. Am J Respir Crit Care Med. 2007 Aug 1;176(3):277-84. doi: 10.1164/rccm.200701-044OC. Epub 2007 May 3.</citation>
    <PMID>17478620</PMID>
  </reference>
  <reference>
    <citation>Rafii R, Juarez MM, Albertson TE, Chan AL. A review of current and novel therapies for idiopathic pulmonary fibrosis. J Thorac Dis. 2013 Feb;5(1):48-73. doi: 10.3978/j.issn.2072-1439.2012.12.07.</citation>
    <PMID>23372951</PMID>
  </reference>
  <reference>
    <citation>Antonio GE, Wong KT, Hui DS, Wu A, Lee N, Yuen EH, Leung CB, Rainer TH, Cameron P, Chung SS, Sung JJ, Ahuja AT. Thin-section CT in patients with severe acute respiratory syndrome following hospital discharge: preliminary experience. Radiology. 2003 Sep;228(3):810-5. doi: 10.1148/radiol.2283030726. Epub 2003 Jun 12.</citation>
    <PMID>12805557</PMID>
  </reference>
  <reference>
    <citation>Chan KS, Zheng JP, Mok YW, Li YM, Liu YN, Chu CM, Ip MS. SARS: prognosis, outcome and sequelae. Respirology. 2003 Nov;8 Suppl(Suppl 1):S36-40. doi: 10.1046/j.1440-1843.2003.00522.x.</citation>
    <PMID>15018132</PMID>
  </reference>
  <reference>
    <citation>Xie L, Liu Y, Fan B, Xiao Y, Tian Q, Chen L, Zhao H, Chen W. Dynamic changes of serum SARS-coronavirus IgG, pulmonary function and radiography in patients recovering from SARS after hospital discharge. Respir Res. 2005 Jan 8;6(1):5. doi: 10.1186/1465-9921-6-5.</citation>
    <PMID>15638943</PMID>
  </reference>
  <reference>
    <citation>Yang J, Cui Y, Kolb M. How useful is traditional herbal medicine for pulmonary fibrosis? Respirology. 2009 Nov;14(8):1082-91. doi: 10.1111/j.1440-1843.2009.01644.x.</citation>
    <PMID>19909458</PMID>
  </reference>
  <reference>
    <citation>Hsu CH, Lu CM, Chang TT. Efficacy and safety of modified Mai-Men-Dong-Tang for treatment of allergic asthma. Pediatr Allergy Immunol. 2005 Feb;16(1):76-81. doi: 10.1111/j.1399-3038.2005.00230.x.</citation>
    <PMID>15693916</PMID>
  </reference>
  <reference>
    <citation>Zhou L, Zuo Z, Chow MS. Danshen: an overview of its chemistry, pharmacology, pharmacokinetics, and clinical use. J Clin Pharmacol. 2005 Dec;45(12):1345-59. doi: 10.1177/0091270005282630.</citation>
    <PMID>16291709</PMID>
  </reference>
  <reference>
    <citation>Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete measure of health status for chronic airflow limitation. The St. George's Respiratory Questionnaire. Am Rev Respir Dis. 1992 Jun;145(6):1321-7. doi: 10.1164/ajrccm/145.6.1321.</citation>
    <PMID>1595997</PMID>
  </reference>
  <reference>
    <citation>Jones PW, Quirk FH, Baveystock CM. The St George's Respiratory Questionnaire. Respir Med. 1991 Sep;85 Suppl B:25-31; discussion 33-7. doi: 10.1016/s0954-6111(06)80166-6.</citation>
    <PMID>1759018</PMID>
  </reference>
  <reference>
    <citation>Kalantar-Zadeh K, Kopple JD, Block G, Humphreys MH. Association among SF36 quality of life measures and nutrition, hospitalization, and mortality in hemodialysis. J Am Soc Nephrol. 2001 Dec;12(12):2797-2806. doi: 10.1681/ASN.V12122797.</citation>
    <PMID>11729250</PMID>
  </reference>
  <reference>
    <citation>Yao CF, Jiang SL. [Prevention and treatment of pulmonary-fibrosis by traditional Chinese medicine]. Zhong Xi Yi Jie He Xue Bao. 2003 Sep;1(3):234-8. doi: 10.3736/jcim20030327. Chinese.</citation>
    <PMID>15339572</PMID>
  </reference>
  <reference>
    <citation>Costabel U, King TE. International consensus statement on idiopathic pulmonary fibrosis. Eur Respir J. 2001 Feb;17(2):163-7. doi: 10.1183/09031936.01.17201630. No abstract available.</citation>
    <PMID>11334114</PMID>
  </reference>
  <reference>
    <citation>Mannino DM, Etzel RA, Parrish RG. Pulmonary fibrosis deaths in the United States, 1979-1991. An analysis of multiple-cause mortality data. Am J Respir Crit Care Med. 1996 May;153(5):1548-52. doi: 10.1164/ajrccm.153.5.8630600.</citation>
    <PMID>8630600</PMID>
  </reference>
  <reference>
    <citation>Jin Gui Yao Lue (Essentials from the Golden Cabinet), written by Zhang Zhong-jing (about 150-219) in Later Han Dynasty.</citation>
  </reference>
  <reference>
    <citation>Huangdi Neijing (The Book of Yellow Emperor's: a classic of internal medicine) written during the period 475-225 b.C. as a dialogue between the mythical Emperor Huangdi and his physician Qibo.</citation>
  </reference>
  <reference>
    <citation>Tang ling Hua, Li Chun sheng. special onset of diffuse interstitial pulmonary fibrosis treated 13 cases reported. Traditional Chinese Medicine, 1997, 38 (1): 34 ~ 36.</citation>
  </reference>
  <reference>
    <citation>Zhang. L. 1999. A Case Report on Chronic Lymphocytic Leukemia. Journal of Traditional Chinese Medicine Alumni 1: 15.</citation>
  </reference>
  <reference>
    <citation>Chen, J.K., Chen, T.T. 2004. Chinese Medical Herbology and Pharmacology. City of Industry, CA: Art of Medicine Press, Inc. 1267pp.</citation>
  </reference>
  <reference>
    <citation>Fruehauf, H. 1997. The Gingko. Cultural Background and Medicinal Usage in China. Journal of Chinese Medicine 55: 13-16.</citation>
  </reference>
  <reference>
    <citation>Bensky, D., Clavey, S., Stöger, E. 2004. Chinese Herbal Medicine Materia Medica, 3rd Edition. Seattle: Eastland Press, Inc. 1311pp.</citation>
  </reference>
  <reference>
    <citation>World Health Organization 1993. WHOQoL Study Protocol. WHO (MNH7PSF/93.9).</citation>
  </reference>
  <reference>
    <citation>World Health Organization. 2004. WHO Quality of Life-BREF (WHOQOL-BREF). http://www.who.int/substance_abuse/research_tools/whoqolbref/en/, http://www.who.int/substance_abuse/research_tools/en/english_whoqol.pdf Accessed 09 April 2011.</citation>
  </reference>
  <reference>
    <citation>Murphy, B., Herrman, H., Hawthorne, G., Pinzone, T., Evert, H. 2000. Australian WHOQoL instruments: User's manual and interpretation guide. Australian WHOQoL Field Study Centre, Melbourne, Australia.</citation>
  </reference>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>September 4, 2017</study_first_submitted>
  <study_first_submitted_qc>September 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <last_update_submitted>April 26, 2021</last_update_submitted>
  <last_update_submitted_qc>April 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The University of Hong Kong</investigator_affiliation>
    <investigator_full_name>Prof. Zhang Zhang-Jin</investigator_full_name>
    <investigator_title>Professor, Associate Director (Clinical Affairs)</investigator_title>
  </responsible_party>
  <keyword>Idiopathic Pulmonary Fibrosis</keyword>
  <keyword>Chinese Medicine</keyword>
  <keyword>Herbal Medicine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulmonary Fibrosis</mesh_term>
    <mesh_term>Idiopathic Pulmonary Fibrosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03274544
org study id: UW 17-283
nct id: NCT03274544
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This open label clinical study will be conducted in School of Chinese Medicine Clinics at The
      University of Hong Kong (HKU) to preliminarily determine whether treatment with the herbal
      formula PROLUNG could improve Idiopathic Pulmonary Fibrosis (IPF) symptoms, respiratory
      function and the quality of life of patients with IPF compared with pretreatment baseline. We
      propose to recruit 30 participants. The diagnosis and screening will be conducted by
      respiratory physicians. Those who meet the inclusion criteria will be referred by the expert
      to the PI. The PI will prescribe the formula in granule form to the participants in
      Traditional Chinese medicine (TCM) Clinics as usual. Patients will receive 6 months of the
      herbal treatment and 7 visits.

      Annual rate of change in forced expiratory vital capacity (FVC) will serve the primary
      outcome. The St. George's Respiratory Questionnaire (SGRQ) will be used to additionally
      assess respiratory functions. A standard questionnaire will be administered to obtain
      information on age, sex, marital status, education, social class, smoking behaviour and
      respiratory diseases. Other outcome measures include the 36-Item Short Form Survey (SF-36)
      and the World Health Organization Quality of Life assessment instrument (WHOQOLBREF) by each
      participant after enrollment.
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Annual rate of change in forced expiratory vital capacity (FVC)
time frame: Baseline, 6 month
description: Annual rate of change in forced expiratory vital capacity (FVC) will serve the primary outcome.
measure: Changes in SGRQ score
time frame: Baseline, 1 month, 2 month, 3 month, 4 month, 5 month, 6 month
description: The St. George's Respiratory Questionnaire (SGRQ) will be used to additionally assess respiratory functions.
measure: Changes in SF-36 score
time frame: Baseline, 1 month, 2 month, 3 month, 4 month, 5 month, 6 month
description: The 36-Item Short Form Survey (SF-36) is a 36-question questionnaire to assess the quality of life of a participant in terms of physical and mental health.
measure: Changes in WHOQOL-BREF score
time frame: Baseline, 1 month, 2 month, 3 month, 4 month, 5 month, 6 month
description: The WHOQOL-BREF measures the physical and psychological health, the social relationships, and the environment of an individual.
measure: Changes in adverse events
time frame: Baseline, 1 month, 2 month, 3 month, 4 month, 5 month, 6 month
description: All patients will be monitored for adverse reactions of any kind including but not limited to idiosyncratic allergic reactions to some components of the treatment.
arm group label: PROLUNG
arm group type: Experimental
description: Herbal formula treatment PROLUNG in additional to current therapy
intervention type: Other
intervention name: PROLUNG
description: Chinese herbal medicine formula PROLUNG with 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
arm group label: PROLUNG
criteria: 
gender: All
minimum age: 40 Years
maximum age: 75 Years
healthy volunteers: No
last name: Zhang-Jin ZHANG, MMed, PhD
role: Principal Investigator
affiliation: zhangzj@hku.hk
facility: 
country: Hong Kong
citation: Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, Lynch DA, Ryu JH, Swigris JJ, Wells AU, Ancochea J, Bouros D, Carvalho C, Costabel U, Ebina M, Hansell DM, Johkoh T, Kim DS, King TE Jr, Kondoh Y, Myers J, Muller NL, Nicholson AG, Richeldi L, Selman M, Dudden RF, Griss BS, Protzko SL, Schunemann HJ; ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011 Mar 15;183(6):788-824. doi: 10.1164/rccm.2009-040GL.
PMID: 21471066
citation: Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2006 Oct 1;174(7):810-6. doi: 10.1164/rccm.200602-163OC. Epub 2006 Jun 29.
PMID: 16809633
citation: Navaratnam V, Fleming KM, West J, Smith CJ, Jenkins RG, Fogarty A, Hubbard RB. The rising incidence of idiopathic pulmonary fibrosis in the U.K. Thorax. 2011 Jun;66(6):462-7. doi: 10.1136/thx.2010.148031. Epub 2011 Apr 27.
PMID: 21525528
citation: Erbes R, Schaberg T, Loddenkemper R. Lung function tests in patients with idiopathic pulmonary fibrosis. Are they helpful for predicting outcome? Chest. 1997 Jan;111(1):51-7. doi: 10.1378/chest.111.1.51.
PMID: 8995992
citation: King TE Jr, Tooze JA, Schwarz MI, Brown KR, Cherniack RM. Predicting survival in idiopathic pulmonary fibrosis: scoring system and survival model. Am J Respir Crit Care Med. 2001 Oct 1;164(7):1171-81. doi: 10.1164/ajrccm.164.7.2003140.
PMID: 11673205
citation: Han MK, Murray S, Fell CD, Flaherty KR, Toews GB, Myers J, Colby TV, Travis WD, Kazerooni EA, Gross BH, Martinez FJ. Sex differences in physiological progression of idiopathic pulmonary fibrosis. Eur Respir J. 2008 Jun;31(6):1183-8. doi: 10.1183/09031936.00165207. Epub 2008 Mar 5.
PMID: 18321929
citation: Gribbin J, Hubbard RB, Le Jeune I, Smith CJ, West J, Tata LJ. Incidence and mortality of idiopathic pulmonary fibrosis and sarcoidosis in the UK. Thorax. 2006 Nov;61(11):980-5. doi: 10.1136/thx.2006.062836. Epub 2006 Jul 14.
PMID: 16844727
citation: Olson AL, Swigris JJ, Lezotte DC, Norris JM, Wilson CG, Brown KK. Mortality from pulmonary fibrosis increased in the United States from 1992 to 2003. Am J Respir Crit Care Med. 2007 Aug 1;176(3):277-84. doi: 10.1164/rccm.200701-044OC. Epub 2007 May 3.
PMID: 17478620
citation: Rafii R, Juarez MM, Albertson TE, Chan AL. A review of current and novel therapies for idiopathic pulmonary fibrosis. J Thorac Dis. 2013 Feb;5(1):48-73. doi: 10.3978/j.issn.2072-1439.2012.12.07.
PMID: 23372951
citation: Antonio GE, Wong KT, Hui DS, Wu A, Lee N, Yuen EH, Leung CB, Rainer TH, Cameron P, Chung SS, Sung JJ, Ahuja AT. Thin-section CT in patients with severe acute respiratory syndrome following hospital discharge: preliminary experience. Radiology. 2003 Sep;228(3):810-5. doi: 10.1148/radiol.2283030726. Epub 2003 Jun 12.
PMID: 12805557
citation: Chan KS, Zheng JP, Mok YW, Li YM, Liu YN, Chu CM, Ip MS. SARS: prognosis, outcome and sequelae. Respirology. 2003 Nov;8 Suppl(Suppl 1):S36-40. doi: 10.1046/j.1440-1843.2003.00522.x.
PMID: 15018132
citation: Xie L, Liu Y, Fan B, Xiao Y, Tian Q, Chen L, Zhao H, Chen W. Dynamic changes of serum SARS-coronavirus IgG, pulmonary function and radiography in patients recovering from SARS after hospital discharge. Respir Res. 2005 Jan 8;6(1):5. doi: 10.1186/1465-9921-6-5.
PMID: 15638943
citation: Yang J, Cui Y, Kolb M. How useful is traditional herbal medicine for pulmonary fibrosis? Respirology. 2009 Nov;14(8):1082-91. doi: 10.1111/j.1440-1843.2009.01644.x.
PMID: 19909458
citation: Hsu CH, Lu CM, Chang TT. Efficacy and safety of modified Mai-Men-Dong-Tang for treatment of allergic asthma. Pediatr Allergy Immunol. 2005 Feb;16(1):76-81. doi: 10.1111/j.1399-3038.2005.00230.x.
PMID: 15693916
citation: Zhou L, Zuo Z, Chow MS. Danshen: an overview of its chemistry, pharmacology, pharmacokinetics, and clinical use. J Clin Pharmacol. 2005 Dec;45(12):1345-59. doi: 10.1177/0091270005282630.
PMID: 16291709
citation: Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete measure of health status for chronic airflow limitation. The St. George's Respiratory Questionnaire. Am Rev Respir Dis. 1992 Jun;145(6):1321-7. doi: 10.1164/ajrccm/145.6.1321.
PMID: 1595997
citation: Jones PW, Quirk FH, Baveystock CM. The St George's Respiratory Questionnaire. Respir Med. 1991 Sep;85 Suppl B:25-31; discussion 33-7. doi: 10.1016/s0954-6111(06)80166-6.
PMID: 1759018
citation: Kalantar-Zadeh K, Kopple JD, Block G, Humphreys MH. Association among SF36 quality of life measures and nutrition, hospitalization, and mortality in hemodialysis. J Am Soc Nephrol. 2001 Dec;12(12):2797-2806. doi: 10.1681/ASN.V12122797.
PMID: 11729250
citation: Yao CF, Jiang SL. [Prevention and treatment of pulmonary-fibrosis by traditional Chinese medicine]. Zhong Xi Yi Jie He Xue Bao. 2003 Sep;1(3):234-8. doi: 10.3736/jcim20030327. Chinese.
PMID: 15339572
citation: Costabel U, King TE. International consensus statement on idiopathic pulmonary fibrosis. Eur Respir J. 2001 Feb;17(2):163-7. doi: 10.1183/09031936.01.17201630. No abstract available.
PMID: 11334114
citation: Mannino DM, Etzel RA, Parrish RG. Pulmonary fibrosis deaths in the United States, 1979-1991. An analysis of multiple-cause mortality data. Am J Respir Crit Care Med. 1996 May;153(5):1548-52. doi: 10.1164/ajrccm.153.5.8630600.
PMID: 8630600
citation: Jin Gui Yao Lue (Essentials from the Golden Cabinet), written by Zhang Zhong-jing (about 150-219) in Later Han Dynasty.
citation: Huangdi Neijing (The Book of Yellow Emperor's: a classic of internal medicine) written during the period 475-225 b.C. as a dialogue between the mythical Emperor Huangdi and his physician Qibo.
citation: Tang ling Hua, Li Chun sheng. special onset of diffuse interstitial pulmonary fibrosis treated 13 cases reported. Traditional Chinese Medicine, 1997, 38 (1): 34 ~ 36.
citation: Zhang. L. 1999. A Case Report on Chronic Lymphocytic Leukemia. Journal of Traditional Chinese Medicine Alumni 1: 15.
citation: Chen, J.K., Chen, T.T. 2004. Chinese Medical Herbology and Pharmacology. City of Industry, CA: Art of Medicine Press, Inc. 1267pp.
citation: Fruehauf, H. 1997. The Gingko. Cultural Background and Medicinal Usage in China. Journal of Chinese Medicine 55: 13-16.
citation: Bensky, D., Clavey, S., Stöger, E. 2004. Chinese Herbal Medicine Materia Medica, 3rd Edition. Seattle: Eastland Press, Inc. 1311pp.
citation: World Health Organization 1993. WHOQoL Study Protocol. WHO (MNH7PSF/93.9).
citation: World Health Organization. 2004. WHO Quality of Life-BREF (WHOQOL-BREF). http://www.who.int/substance_abuse/research_tools/whoqolbref/en/, http://www.who.int/substance_abuse/research_tools/en/english_whoqol.pdf Accessed 09 April 2011.
citation: Murphy, B., Herrman, H., Hawthorne, G., Pinzone, T., Evert, H. 2000. Australian WHOQoL instruments: User's manual and interpretation guide. Australian WHOQoL Field Study Centre, Melbourne, Australia.
responsible party type: Principal Investigator
investigator affiliation: The University of Hong Kong
investigator full name: Prof. Zhang Zhang-Jin
investigator title: Professor, Associate Director (Clinical Affairs)
mesh term: Pulmonary Fibrosis
mesh term: Idiopathic Pulmonary Fibrosis
mesh term: Fibrosis