<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/NCT03259022</url>
  </required_header>
  <id_info>
    <org_study_id>IIBSP-BRO-2015-92</org_study_id>
    <nct_id>NCT03259022</nct_id>
  </id_info>
  <brief_title>Bronchial Infection in Patients With COPD and Frequent Exacerbations.</brief_title>
  <official_title>Bronchial Infection in Patients With COPD and Frequent Exacerbations; Role of Innate Immunity and the Use of an Electronic Nose for Diagnosis.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Hypothesis:&#xD;
&#xD;
        1. Innate immunity is altered in certain patients with COPD and frequent exacerbations, a&#xD;
           fact that makes them more susceptible to being infected by bacteria.&#xD;
&#xD;
        2. The electronic nose is able to detect patterns of specific VOCs for exacerbations of&#xD;
           infectious origin.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Bronchial infection has been described as the leading cause of COPD exacerbations. Different&#xD;
      studies with invasive endoscopic techniques have demonstrated the presence of bacteria in the&#xD;
      air in 40-70% of exacerbations of the disease. In addition, these patients have a higher&#xD;
      concentration of cells and proinflammatory cytokines in the airway. This increased&#xD;
      inflammation is associated with more frequent and more severe exacerbations, which worsen&#xD;
      this vicious circle.&#xD;
&#xD;
      It is not known why some patients with COPD are more susceptible than others to bronchial,&#xD;
      acute or chronic infection. Recent studies have suggested the importance of lung innate&#xD;
      immunity, both humoral (proteins with antibiotic activity, inflammatory mediators) and cell&#xD;
      (neutrophils, macrophages) as the key to the defense of the lung against infectious agents&#xD;
      external factor. There may be a bidirectional relationship between immune response and&#xD;
      bronchial infection in COPD exacerbations.&#xD;
&#xD;
      Te main objectives of our study are: 1. To study the expression of mucin, PAM and TLR in the&#xD;
      airway of patients with COPD and frequent exacerbations (FE) and its relationship with the&#xD;
      infection of the airway. 2. Determine the patterns of volatile organic compounds (VOCs)&#xD;
      detected by electronic nose associated with bronchial infection in patients with COPD and FE.&#xD;
&#xD;
      Secondary objectives: 1. To study the relationship between the expression of mucin, PAM and&#xD;
      TLR with pulmonary and systemic inflammation. 2. To study the relationship between the&#xD;
      expression of mucin, PAM and TLR with bronchial bacterial load. 3. To study the expression of&#xD;
      mucin, PAM and TLR at the time of COPD exacerbations and subsequent clinical phase stability.&#xD;
      4. Determine VOC patterns for specific pathogens (H. influenzae, S. pneumoniae, P.&#xD;
      aeurginosa). 5. To study the time evolution of patterns of VOCs after a COPD exacerbation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>November 2016</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">July 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Relationship between infection and airway innate immunity of patients with COPD and frequent exacerbations.</measure>
    <time_frame>6 months</time_frame>
    <description>Mucine levels will be determined with ELISA kits</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Association between volatile organic compounds (VOCs) detected by an electronic nose and bronchial infection in patients with COPD and frequent exacerbations.</measure>
    <time_frame>6 months</time_frame>
    <description>The patterns of specific volatile organic compounds in echaled air will be determined with electronic nose device.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Relationship between airway innate immunity and systemic inflammation.</measure>
    <time_frame>6 months</time_frame>
    <description>Mucin levels will be determined with ELISA kits</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relationship between airway innate immunity and bronchial bacterial load.</measure>
    <time_frame>6 months</time_frame>
    <description>Mucin levels will be determined with ELISA kits.</description>
  </secondary_outcome>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Pulmonary Disease, Chronic Obstructive</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Quantitative sputum culture, oral lavage, peripheral blood and exhaled air intake will be&#xD;
      conducted.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        COPD patients with frequent exacerbations.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Diagnosis of COPD according to national and international guidelines.&#xD;
&#xD;
          2. Presence of ≥ 2 exacerbations requiring admission in the last 12 months.&#xD;
&#xD;
          3. Signature of informed consent.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Presence of other lung diseases&#xD;
&#xD;
          2. terminal concomitant disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Oriol Sibila, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Oriol Sibila, PhD</last_name>
    <phone>932 91 90 00</phone>
    <email>osibila@santpau.cat</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hospital de la Santa Creu i Sant Pau</name>
      <address>
        <city>Barcelona</city>
        <zip>08026</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Oriol Sibila, PhD</last_name>
      <phone>932 91 90 00</phone>
      <email>osibila@santpau.cat</email>
    </contact>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <reference>
    <citation>Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, Stockley RA, Sin DD, Rodriguez-Roisin R. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65. doi: 10.1164/rccm.201204-0596PP. Epub 2012 Aug 9.</citation>
    <PMID>22878278</PMID>
  </reference>
  <reference>
    <citation>Miravitlles M, Soler-Cataluna JJ, Calle M, Molina J, Almagro P, Quintano JA, Riesco JA, Trigueros JA, Pinera P, Simon A, Rodriguez-Hermosa JL, Marco E, Lopez D, Coll R, Coll-Fernandez R, Lobo MA, Diez J, Soriano JB, Ancochea J. Spanish guideline for COPD (GesEPOC). Update 2014. Arch Bronconeumol. 2014 Jan;50 Suppl 1:1-16. doi: 10.1016/S0300-2896(14)70070-5. No abstract available.</citation>
    <PMID>24507959</PMID>
  </reference>
  <reference>
    <citation>Anzueto A, Sethi S, Martinez FJ. Exacerbations of chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2007 Oct 1;4(7):554-64. doi: 10.1513/pats.200701-003FM.</citation>
    <PMID>17878469</PMID>
  </reference>
  <reference>
    <citation>Seemungal TA, Donaldson GC, Bhowmik A, Jeffries DJ, Wedzicha JA. Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000 May;161(5):1608-13. doi: 10.1164/ajrccm.161.5.9908022.</citation>
    <PMID>10806163</PMID>
  </reference>
  <reference>
    <citation>Soler-Cataluna JJ, Martinez-Garcia MA, Roman Sanchez P, Salcedo E, Navarro M, Ochando R. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax. 2005 Nov;60(11):925-31. doi: 10.1136/thx.2005.040527. Epub 2005 Jul 29.</citation>
    <PMID>16055622</PMID>
  </reference>
  <reference>
    <citation>Wedzicha JA, Seemungal TA. COPD exacerbations: defining their cause and prevention. Lancet. 2007 Sep 1;370(9589):786-96. doi: 10.1016/S0140-6736(07)61382-8.</citation>
    <PMID>17765528</PMID>
  </reference>
  <reference>
    <citation>Hurst JR, Vestbo J, Anzueto A, Locantore N, Mullerova H, Tal-Singer R, Miller B, Lomas DA, Agusti A, Macnee W, Calverley P, Rennard S, Wouters EF, Wedzicha JA; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010 Sep 16;363(12):1128-38. doi: 10.1056/NEJMoa0909883.</citation>
    <PMID>20843247</PMID>
  </reference>
  <reference>
    <citation>Soler N, Ewig S, Torres A, Filella X, Gonzalez J, Zaubet A. Airway inflammation and bronchial microbial patterns in patients with stable chronic obstructive pulmonary disease. Eur Respir J. 1999 Nov;14(5):1015-22. doi: 10.1183/09031936.99.14510159.</citation>
    <PMID>10596683</PMID>
  </reference>
  <reference>
    <citation>Sethi S, Murphy TF. Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med. 2008 Nov 27;359(22):2355-65. doi: 10.1056/NEJMra0800353. No abstract available.</citation>
    <PMID>19038881</PMID>
  </reference>
  <reference>
    <citation>Mizgerd JP. Respiratory infection and the impact of pulmonary immunity on lung health and disease. Am J Respir Crit Care Med. 2012 Nov 1;186(9):824-9. doi: 10.1164/rccm.201206-1063PP. Epub 2012 Jul 12.</citation>
    <PMID>22798317</PMID>
  </reference>
  <reference>
    <citation>Roy MG, Livraghi-Butrico A, Fletcher AA, McElwee MM, Evans SE, Boerner RM, Alexander SN, Bellinghausen LK, Song AS, Petrova YM, Tuvim MJ, Adachi R, Romo I, Bordt AS, Bowden MG, Sisson JH, Woodruff PG, Thornton DJ, Rousseau K, De la Garza MM, Moghaddam SJ, Karmouty-Quintana H, Blackburn MR, Drouin SM, Davis CW, Terrell KA, Grubb BR, O'Neal WK, Flores SC, Cota-Gomez A, Lozupone CA, Donnelly JM, Watson AM, Hennessy CE, Keith RC, Yang IV, Barthel L, Henson PM, Janssen WJ, Schwartz DA, Boucher RC, Dickey BF, Evans CM. Muc5b is required for airway defence. Nature. 2014 Jan 16;505(7483):412-6. doi: 10.1038/nature12807. Epub 2013 Dec 8.</citation>
    <PMID>24317696</PMID>
  </reference>
  <reference>
    <citation>Thornton DJ, Rousseau K, McGuckin MA. Structure and function of the polymeric mucins in airways mucus. Annu Rev Physiol. 2008;70:459-86. doi: 10.1146/annurev.physiol.70.113006.100702.</citation>
    <PMID>17850213</PMID>
  </reference>
  <reference>
    <citation>Kirkham S, Kolsum U, Rousseau K, Singh D, Vestbo J, Thornton DJ. MUC5B is the major mucin in the gel phase of sputum in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008 Nov 15;178(10):1033-9. doi: 10.1164/rccm.200803-391OC. Epub 2008 Sep 5.</citation>
    <PMID>18776153</PMID>
  </reference>
  <reference>
    <citation>Fujisawa T, Chang MM, Velichko S, Thai P, Hung LY, Huang F, Phuong N, Chen Y, Wu R. NF-kappaB mediates IL-1beta- and IL-17A-induced MUC5B expression in airway epithelial cells. Am J Respir Cell Mol Biol. 2011 Aug;45(2):246-52. doi: 10.1165/rcmb.2009-0313OC. Epub 2010 Oct 8.</citation>
    <PMID>20935193</PMID>
  </reference>
  <reference>
    <citation>Yang D, Biragyn A, Hoover DM, Lubkowski J, Oppenheim JJ. Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense. Annu Rev Immunol. 2004;22:181-215. doi: 10.1146/annurev.immunol.22.012703.104603.</citation>
    <PMID>15032578</PMID>
  </reference>
  <reference>
    <citation>Harder J, Meyer-Hoffert U, Teran LM, Schwichtenberg L, Bartels J, Maune S, Schroder JM. Mucoid Pseudomonas aeruginosa, TNF-alpha, and IL-1beta, but not IL-6, induce human beta-defensin-2 in respiratory epithelia. Am J Respir Cell Mol Biol. 2000 Jun;22(6):714-21. doi: 10.1165/ajrcmb.22.6.4023.</citation>
    <PMID>10837369</PMID>
  </reference>
  <reference>
    <citation>Parameswaran GI, Sethi S, Murphy TF. Effects of bacterial infection on airway antimicrobial peptides and proteins in COPD. Chest. 2011 Sep;140(3):611-617. doi: 10.1378/chest.10-2760. Epub 2011 Feb 24.</citation>
    <PMID>21349930</PMID>
  </reference>
  <reference>
    <citation>Medzhitov R. Toll-like receptors and innate immunity. Nat Rev Immunol. 2001 Nov;1(2):135-45. doi: 10.1038/35100529.</citation>
    <PMID>11905821</PMID>
  </reference>
  <reference>
    <citation>Berenson CS, Wrona CT, Grove LJ, Maloney J, Garlipp MA, Wallace PK, Stewart CC, Sethi S. Impaired alveolar macrophage response to Haemophilus antigens in chronic obstructive lung disease. Am J Respir Crit Care Med. 2006 Jul 1;174(1):31-40. doi: 10.1164/rccm.200509-1461OC. Epub 2006 Mar 30.</citation>
    <PMID>16574934</PMID>
  </reference>
  <reference>
    <citation>Berenson CS, Kruzel RL, Eberhardt E, Dolnick R, Minderman H, Wallace PK, Sethi S. Impaired innate immune alveolar macrophage response and the predilection for COPD exacerbations. Thorax. 2014 Sep;69(9):811-8. doi: 10.1136/thoraxjnl-2013-203669. Epub 2014 Mar 31.</citation>
    <PMID>24686454</PMID>
  </reference>
  <reference>
    <citation>Vidal S, Bellido-Casado J, Granel C, Crespo A, Plaza V, Juarez C. Flow cytometry analysis of leukocytes in induced sputum from asthmatic patients. Immunobiology. 2012 Jul;217(7):692-7. doi: 10.1016/j.imbio.2011.11.008. Epub 2011 Dec 2.</citation>
    <PMID>22204819</PMID>
  </reference>
  <reference>
    <citation>Buszewski B, Kesy M, Ligor T, Amann A. Human exhaled air analytics: biomarkers of diseases. Biomed Chromatogr. 2007 Jun;21(6):553-66. doi: 10.1002/bmc.835.</citation>
    <PMID>17431933</PMID>
  </reference>
  <reference>
    <citation>Hanson CW 3rd, Thaler ER. Electronic nose prediction of a clinical pneumonia score: biosensors and microbes. Anesthesiology. 2005 Jan;102(1):63-8. doi: 10.1097/00000542-200501000-00013.</citation>
    <PMID>15618788</PMID>
  </reference>
  <reference>
    <citation>Fens N, Zwinderman AH, van der Schee MP, de Nijs SB, Dijkers E, Roldaan AC, Cheung D, Bel EH, Sterk PJ. Exhaled breath profiling enables discrimination of chronic obstructive pulmonary disease and asthma. Am J Respir Crit Care Med. 2009 Dec 1;180(11):1076-82. doi: 10.1164/rccm.200906-0939OC. Epub 2009 Aug 27.</citation>
    <PMID>19713445</PMID>
  </reference>
  <reference>
    <citation>Sibila O, Garcia-Bellmunt L, Giner J, Merino JL, Suarez-Cuartin G, Torrego A, Solanes I, Castillo D, Valera JL, Cosio BG, Plaza V, Agusti A. Identification of airway bacterial colonization by an electronic nose in Chronic Obstructive Pulmonary Disease. Respir Med. 2014 Nov;108(11):1608-14. doi: 10.1016/j.rmed.2014.09.008. Epub 2014 Sep 19.</citation>
    <PMID>25269711</PMID>
  </reference>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>September 7, 2016</study_first_submitted>
  <study_first_submitted_qc>August 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 23, 2017</study_first_posted>
  <last_update_submitted>August 21, 2017</last_update_submitted>
  <last_update_submitted_qc>August 21, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 23, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bronchitis</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03259022
org study id: IIBSP-BRO-2015-92
nct id: NCT03259022
lead sponsor: 
has dmc: No
Hypothesis:

        1. Innate immunity is altered in certain patients with COPD and frequent exacerbations, a
           fact that makes them more susceptible to being infected by bacteria.

        2. The electronic nose is able to detect patterns of specific VOCs for exacerbations of
           infectious origin.
Bronchial infection has been described as the leading cause of COPD exacerbations. Different
      studies with invasive endoscopic techniques have demonstrated the presence of bacteria in the
      air in 40-70% of exacerbations of the disease. In addition, these patients have a higher
      concentration of cells and proinflammatory cytokines in the airway. This increased
      inflammation is associated with more frequent and more severe exacerbations, which worsen
      this vicious circle.

      It is not known why some patients with COPD are more susceptible than others to bronchial,
      acute or chronic infection. Recent studies have suggested the importance of lung innate
      immunity, both humoral (proteins with antibiotic activity, inflammatory mediators) and cell
      (neutrophils, macrophages) as the key to the defense of the lung against infectious agents
      external factor. There may be a bidirectional relationship between immune response and
      bronchial infection in COPD exacerbations.

      Te main objectives of our study are: 1. To study the expression of mucin, PAM and TLR in the
      airway of patients with COPD and frequent exacerbations (FE) and its relationship with the
      infection of the airway. 2. Determine the patterns of volatile organic compounds (VOCs)
      detected by electronic nose associated with bronchial infection in patients with COPD and FE.

      Secondary objectives: 1. To study the relationship between the expression of mucin, PAM and
      TLR with pulmonary and systemic inflammation. 2. To study the relationship between the
      expression of mucin, PAM and TLR with bronchial bacterial load. 3. To study the expression of
      mucin, PAM and TLR at the time of COPD exacerbations and subsequent clinical phase stability.
      4. Determine VOC patterns for specific pathogens (H. influenzae, S. pneumoniae, P.
      aeurginosa). 5. To study the time evolution of patterns of VOCs after a COPD exacerbation.
observational model: Cohort
time perspective: Prospective
measure: Relationship between infection and airway innate immunity of patients with COPD and frequent exacerbations.
time frame: 6 months
description: Mucine levels will be determined with ELISA kits
measure: Association between volatile organic compounds (VOCs) detected by an electronic nose and bronchial infection in patients with COPD and frequent exacerbations.
time frame: 6 months
description: The patterns of specific volatile organic compounds in echaled air will be determined with electronic nose device.
measure: Relationship between airway innate immunity and systemic inflammation.
time frame: 6 months
description: Mucin levels will be determined with ELISA kits
measure: Relationship between airway innate immunity and bronchial bacterial load.
time frame: 6 months
description: Mucin levels will be determined with ELISA kits.
Quantitative sputum culture, oral lavage, peripheral blood and exhaled air intake will be
      conducted.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 45 Years
maximum age: 80 Years
healthy volunteers: No
last name: Oriol Sibila, PhD
role: Principal Investigator
affiliation: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
last name: Oriol Sibila, PhD
phone: 932 91 90 00
email: osibila@santpau.cat
facility: 
status: Recruiting
contact: 
country: Spain
citation: Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, Stockley RA, Sin DD, Rodriguez-Roisin R. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65. doi: 10.1164/rccm.201204-0596PP. Epub 2012 Aug 9.
PMID: 22878278
citation: Miravitlles M, Soler-Cataluna JJ, Calle M, Molina J, Almagro P, Quintano JA, Riesco JA, Trigueros JA, Pinera P, Simon A, Rodriguez-Hermosa JL, Marco E, Lopez D, Coll R, Coll-Fernandez R, Lobo MA, Diez J, Soriano JB, Ancochea J. Spanish guideline for COPD (GesEPOC). Update 2014. Arch Bronconeumol. 2014 Jan;50 Suppl 1:1-16. doi: 10.1016/S0300-2896(14)70070-5. No abstract available.
PMID: 24507959
citation: Anzueto A, Sethi S, Martinez FJ. Exacerbations of chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2007 Oct 1;4(7):554-64. doi: 10.1513/pats.200701-003FM.
PMID: 17878469
citation: Seemungal TA, Donaldson GC, Bhowmik A, Jeffries DJ, Wedzicha JA. Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000 May;161(5):1608-13. doi: 10.1164/ajrccm.161.5.9908022.
PMID: 10806163
citation: Soler-Cataluna JJ, Martinez-Garcia MA, Roman Sanchez P, Salcedo E, Navarro M, Ochando R. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax. 2005 Nov;60(11):925-31. doi: 10.1136/thx.2005.040527. Epub 2005 Jul 29.
PMID: 16055622
citation: Wedzicha JA, Seemungal TA. COPD exacerbations: defining their cause and prevention. Lancet. 2007 Sep 1;370(9589):786-96. doi: 10.1016/S0140-6736(07)61382-8.
PMID: 17765528
citation: Hurst JR, Vestbo J, Anzueto A, Locantore N, Mullerova H, Tal-Singer R, Miller B, Lomas DA, Agusti A, Macnee W, Calverley P, Rennard S, Wouters EF, Wedzicha JA; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010 Sep 16;363(12):1128-38. doi: 10.1056/NEJMoa0909883.
PMID: 20843247
citation: Soler N, Ewig S, Torres A, Filella X, Gonzalez J, Zaubet A. Airway inflammation and bronchial microbial patterns in patients with stable chronic obstructive pulmonary disease. Eur Respir J. 1999 Nov;14(5):1015-22. doi: 10.1183/09031936.99.14510159.
PMID: 10596683
citation: Sethi S, Murphy TF. Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med. 2008 Nov 27;359(22):2355-65. doi: 10.1056/NEJMra0800353. No abstract available.
PMID: 19038881
citation: Mizgerd JP. Respiratory infection and the impact of pulmonary immunity on lung health and disease. Am J Respir Crit Care Med. 2012 Nov 1;186(9):824-9. doi: 10.1164/rccm.201206-1063PP. Epub 2012 Jul 12.
PMID: 22798317
citation: Roy MG, Livraghi-Butrico A, Fletcher AA, McElwee MM, Evans SE, Boerner RM, Alexander SN, Bellinghausen LK, Song AS, Petrova YM, Tuvim MJ, Adachi R, Romo I, Bordt AS, Bowden MG, Sisson JH, Woodruff PG, Thornton DJ, Rousseau K, De la Garza MM, Moghaddam SJ, Karmouty-Quintana H, Blackburn MR, Drouin SM, Davis CW, Terrell KA, Grubb BR, O'Neal WK, Flores SC, Cota-Gomez A, Lozupone CA, Donnelly JM, Watson AM, Hennessy CE, Keith RC, Yang IV, Barthel L, Henson PM, Janssen WJ, Schwartz DA, Boucher RC, Dickey BF, Evans CM. Muc5b is required for airway defence. Nature. 2014 Jan 16;505(7483):412-6. doi: 10.1038/nature12807. Epub 2013 Dec 8.
PMID: 24317696
citation: Thornton DJ, Rousseau K, McGuckin MA. Structure and function of the polymeric mucins in airways mucus. Annu Rev Physiol. 2008;70:459-86. doi: 10.1146/annurev.physiol.70.113006.100702.
PMID: 17850213
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responsible party type: Sponsor
mesh term: Bronchitis
mesh term: Pulmonary Disease, Chronic Obstructive
sharing ipd: Undecided