Acute Exacerbations of Chronic BronchitisCOPD

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					    Acute Exacerbations of
   Chronic Bronchitis/COPD
             Sanjay Sethi MD
      Professor and Division Chief
Pulmonary, Critical Care and Sleep Medicine
       University at Buffalo, SUNY
           ssethi@buffalo.edu
              Disclosures

Research Funding
  AZ, Bayer, BI, Pfizer
Consultant
  AZ, Bayer, BI, GSK, MedImmune, Mpex,
  Novartis, Pfizer, Sanofi-Aventis
Speakers Bureau
  AZ, Bayer, BI, Pfizer
             AECOPD: Perception vs Reality


         Perception                           Reality
      A nuisance                          Contributes to:
      problem with no
                                            Cost of health
      serious
                                            care
      consequences
                                            (35-45%)
                                            Poor quality of life
                                            Mortality
                                            Progression of
                                            lung disease
Mannino et al. MMWR 2002;51(SS-6):1-16
Andersson et al. Resp Med 2002;96:700-8
        Outcome of AECOPD

In ICU patients
  Hospital mortality                24 %
In hospitalized patients
  Hospital mortality              6 - 12 %
In ER patients
  Relapse (repeat ER visit)                22 - 32 %
In outpatients
  Treatment failure rate                 13 - 33 %

    Seneff et al JAMA 1995, Murata et al Ann Emerg Med 1991, Adams et al
                                                             Chest 2000
AECOPD: Mechanisms
                               Smoking/irritants
Impaired host defenses:
 respiratory viruses
 new strains of bacteria
 environmental irritants



             Acute          Impaired lung defense
             cycle



    Acute on chronic
     inflammation
   (pathogen + host-
 mediated inflammatory      Progressive loss of lung
        factors)           function and deteriorating
                                  quality of life
      Etiology of AECOPD

Non-infectious
                             Bacteria




   Virus

                         Bacteria and
                            Virus
                 Papi et al AJRCCM 2006;173:1114-21
       Etiology of AECOPD: Bacteria
          Microbe                      Role in Exacerbations
Haemophilus influenzae       20-30%
Streptococcus pneumoniae     10-15%
Moraxella catarrhalis        10-15%
Pseudomonas aeruginosa       5-10%, more in advanced disease
Enterobacteriaceae           Isolated in advanced disease, ? significance
Haemophilus haemolyticus     Isolated frequently, unlikely cause
Haemophilus parainfluenzae Isolated frequently, unlikely cause
Staphylococcus aureus        Isolated infrequently, unlikely cause

                                           Sethi S and Murphy TF NEJM 2008
     Etiology of AECOPD: Viruses
     Atypical Bacteria and Fungi
              Microbe             Role in Exacerbations
Rhinovirus                    20-25%
Parainfluenza                 5-10%
Influenza                     5-10%
Respiratory syncytial virus   5-10%
Coronavirus                   5-10%
Adenovirus                    3-5%
Human metapneumovirus         3-5%
Chlamydophila pneumoniae      3-5%
Mycoplasma pneumoniae         1-2%
Pneumocystis jiroveci         Undefined
                                     Sethi S and Murphy TF NEJM 2008
           AECOPD: Bacterial etiology
             Sputum culture studies

                              Stable
                                               25 patients
                              Exacerbation
     %
                                                  Outpatient clinic
60
                       59.9                       every 2 weeks
                               57.0
50                                                for 4 years
                                                  Sputum culture
40
                37.2
30       33.1
                                               1886 clinic visits
20
                                                  116 exacerbations
10                                                1870 stable

0
            SP          NTHI
                                      Gump et al. ARRD 1976;113:465-473
                              COPD Study Clinic: New strain isolation
                                       and exacerbation

                                                                           New strain +
                                                                           New strain –
                         50                                   *    *p<0.05                        Relative risk (95% CI)
Exacerbation frequency




                                                       48.8
                                                                                                  of exacerbation:
                         40
                                     *                                 *                          Any   2.15 (1.83–2.63)
                               33                                 32
                         30                       *                                               NTHI 1.69 (1.37–2.09)
                                           26.2
                                                                                                  MC    2.96 (2.39–3.67)
                         20
                                              17.1        16.6
                                                                       18             18.2        SP    1.77 (1.14–2.75)
                                    15.4
                                                                               13.6
                         10                                                                       PA    0.61 (0.21–1.82)

                         0
                               Any         NTHI         MC         SP            PA
                                                      Pathogen                               Sethi et al. NEJM 2002;347:465-71
        Exacerbation of COPD
       Sputum Culture Studies
                                        45
            Frequency of exacerbation
                                        40
                                        35
                                        30
                                                                      PA positive
                                        25
                                        20
                                                                      PA negative
                                        15
                                        10
                                         5
                                         0
                                             Culture   Acquisition
Conclusion. Acquisition of a new strain of P. aeruginosa
is associated with exacerbation.
                                                 Murphy et al. Am J Resp Crit Care Med 177: 853, 2008
      Bacterial detection in COPD
      Culture vs. Quantitative PCR
Pathogen    Culture +       Quantitative p value
            (n = 403)       PCR +
                            (n=403)
SP (%)      23/403 (6.4)    77/403 (17.4) <0.0001
HI (%)      46/403 (11.4)   69/403 (17.4)   0.002
MC (%)      36/403 (8.9)    70/403 (19.1)   <0.0001
PA (%)      20/403 (4.9)    28/403 (6.9)    0.30
All 4 (%)   125/403         245/403         <0.0001
            (31.0)          (60.8)

                                            Sethi et al ATS 2009
Bacterial detection in COPD
Culture vs. Quantitative PCR




                       Sethi et al ATS 2009
                Viral AECOPD
          Culture and Serology studies
                                Percentage of total viral isolates
          n        %       Rhino       Infl   Para RSV Corona Adeno
                   Viral                      infl
Total     1081
Mean      135      36      38          26     15     11     10         3
Range     42-522   20–61 0-78          0-45 0-39     0-40   6-18       0-10


Comments 8                 7                                4
         studies           studies                          studies




                                Carilli 1964, Eadie 1966, McNamara 1969, Lamy 1974,
                                Gump 1976, Buscho 1978, Smith 1980, McHardy 1980
Viral Detection by PCR in AECOPD
  50

  45
                                                                          x
                                                                         E acerbation
  40
                                                                         Stable
  35

  30

  25

  20

  15

  10

   5

   0
                                    RV




                                                                     V
                                         Pr i fu n a
                         I fu n a
               hn vr s




                                                       Cr n vr s
       Tt l


              Ri o i u




                                          aanl e z
        oa




                                                        oo a i u
                         nl e z


                                     S




                                                                   MP



                                                       Papi et al AJRCCM 2006;173:1114-21
Procalcitonin Guided Antibiotic Use
            in AECOPD
                  • ? Symptom resolution
                  • Unique Health Care System
                  • Microbiological
                  consequences of very short
                  antibiotic courses




                                 Scheutz et al,
                                 JAMA 2009;
                                 302:1059
            Conclusions
Exacerbations of COPD are important
Majority of exacerbations are infectious in
origin
Sputum culture is inadequate to diagnose
exacerbation
Molecular diagnostic techniques have
greater sensitivity
Biomarkers could be useful

				
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