Bronchoscopy in Asthma

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					           Bronchoscopy in Asthma

                DR.T.MOHAN KUMAR , MD.AB.DPPR.FCCP
                   DR.N.BHUVANESWARI , MBBS.DIH
                    DR.S.ARUL MOZHI , MBBS.DTCD
                  DEPARTMENT OF PULMONOLOGY &
                           CRITICAL CARE
                     SRI RAMAKRISHNA HOSPITAL,
                            COIMBATORE.
                             TAMIL NADU


09/12/00             DR.T.M.K./JAIPUR                1
             BIOPSIES IN ASTHMA


           Involvement and granulation of mast cells
           Recruitment and de granulation of eosinophils
           Homogenous thickening of basement membrane
           Sub epithelial fibrosis
           Activation of T-lymphocytes predominantly CD4+
           subset




09/12/00                 DR.T.M.K./JAIPUR                   2
Bronchial biopsy showing intact surface epithelium (arrow),
sub epithelial tissue with inflammatory cells, glands(G)
bronchial smooth muscle (M)




09/12/00               DR.T.M.K./JAIPUR                       3
   Reticular basement membrane thickens (B) early in
   asthmatic process and this can be measured




09/12/00               DR.T.M.K./JAIPUR                4
Structural & inflammatory changes in biopsies


    Now done in mild to moderate asthma
    There is an association between loss of epithelium
    and airway hyper responsiveness
    Structural changes occur in mild as well as severe
    asthma like homogenous thickening of the
    basement membrane(subepithelial reticular layer)
    Activation of T-lymphocytes,presence of fibroblasts
    & myofibroblasts occur in mild to moderate asthma

09/12/00             DR.T.M.K./JAIPUR                 5
                        Eosinophil undergoing
                        cytolysis (arrow) in mild
                        atopic asthma

                        fibroblast (F)
                        reticular basement
                        membrane (B)




09/12/00   DR.T.M.K./JAIPUR                         6
 Negative relationship between number of CD8 T cells and
 measurement of FEV1 seen in COPD which is important in
 differenciating from asthma




09/12/00              DR.T.M.K./JAIPUR                     7
Gene expression & cell type
           Pro inflammatory cytokine, interleukin (IL)-
           5 in association with CD4+ T-Lymphocyte,
           is seen in symptomatic asthmatics.
           IL-4, IL-5 & IL-10 predominate in allergic
           inflammatory profile in the biopsies, and
           using reverse transcriptase-polymerase
           chain reaction (RT-PCR) to bronchial
           biopsies this has been verified

09/12/00                DR.T.M.K./JAIPUR              8
Bronchial biopsy in moderate asthmatic showing cells expressing the gene
for interleukin-5 beneath the areas of epithelium




09/12/00                   DR.T.M.K./JAIPUR                                9
  A mylofibroblast (MF) with a lymphocyte (L) present in biopsy after 24
  hours of exposure to allergen




09/12/00                    DR.T.M.K./JAIPUR                               10
                 Bronchial brush biopsies




           For epithelial cells and airway inflammation




09/12/00                   DR.T.M.K./JAIPUR               11
Bronchial brush biopsies


   Majority of cells are ciliated & goblet epithelial cells
   In stable asthmatics , increased percent of
   eosinophil granulates are found(>0.65% eosinophil
   count diagnostic)
   Mast cells in brush biopsy samples is increased in
   asthma according to severity
   Human leukocyte antigen & intercellular adhesion
   molecule in asthma is increased along with
   prostagladinE2


09/12/00              DR.T.M.K./JAIPUR                    12
           Eosinophils in brush biopsies in patients & healthy controls




09/12/00                       DR.T.M.K./JAIPUR                           13
     CORRELATION BETWEEN EOSINOPHILIC CATIONIC PROTEINS &
     EOSINOPHILS IN ASTHMATICS . CORRELATION p<0.01




09/12/00               DR.T.M.K./JAIPUR                     14
              BRONCHOALVEOLAR LAVAGE




           TESTS FOR AIRWAY INFLAMMATION


09/12/00           DR.T.M.K./JAIPUR        15
   INTERLEUKIN-5 MESSENGER RIBONUCLEIC ACID
   EXPRESSION BY BAL CELLS FROM ATOPIC ASTHMATICS




09/12/00           DR.T.M.K./JAIPUR             16
           Consequences and side effects of BAL


   Alveolar infiltration: < 10% cases,usually
   subside by 48 h
   Crackles: within 24 h over dependent areas
   Wheezing: in hyper reactivity patients up to 1-2
   weeks
   Bronchospasm: rarely in normoreactive, more
   frequent in hypereactive patients



09/12/00               DR.T.M.K./JAIPUR               17
Consequences & side effects of BAL


       Lung function : transient decrease in FEV1, VC,
       PEF, PaO2
       Epithelial integrity: no effect but decrease in ciliary
       motility
       Bleeding: insignificant


09/12/00               DR.T.M.K./JAIPUR                    18
Patient risk factors

           Extensive lung infiltrates(>50% of overall lung
           area)
           PaO2 below 60 mm Hg
           O2 saturation below90%
           FEV1 below 1L
           Prothrombin time below 50%
           Platelet count below 20,000 per ml
           Significant ECG changes


09/12/00                DR.T.M.K./JAIPUR                     19
    Clinical application of BAL


           To analyze cells, mediators, proteins and enzymes
           obtained from alveolar spaces
           In stable mild asthmatics, no distinctive cellular
           profile, but the number of eosinophils, neutrophils,
           platelets, epithelial cells, metachromatic cells are
           increased
           Several studies show the inflammatory cells
           present in asthmatic lung may be variable
           depending on stage, severity & type

09/12/00                 DR.T.M.K./JAIPUR                  20
Clinical application:2

   In mild asthmatics: increase in cells and albumin,
   specific IgE, histamine, prostaglandins,
   leukotreines & lipoxins
   Platelet activating factor, mast cells increased in
   mild asthmatics even during the asymptomatic
   period
   In nocturnal asthmatics, histamine levels very high

09/12/00            DR.T.M.K./JAIPUR                     21
Clinical application:3

      Mast cells with high levels of tryptase after
      allergen challenge
      Plasma protein concentrations increase after
      allergen challenge
      Neutrophil, eosinophil, lymphocyte counts
      increases in BAL within 4 h of allergen
      bronchoprovocation in asthmatics

09/12/00             DR.T.M.K./JAIPUR                 22
Clinical application 4

       Macrophages suddenly appear after local
       challenge, with increase after 48 h with
       increased levels of beta-glucuronidase after
       bronchial challenge. Reason not known
       Stimulated alveolar macrophages liberate
       thromboxane B2, leukotreine B4 & 5HETE


09/12/00            DR.T.M.K./JAIPUR             23
Therapeutic application of BAL
      Removal of mucus plugs in status asthmaticus
      Assessment of cellular effects after therapy
      Lavage in mild asthmatics show inflammatory
      mediators & cells
      Good tool as research
      Use as a Investigative tool controversial
      Used for more ten years now

09/12/00             DR.T.M.K./JAIPUR                24
conclusions


       Inflammation is present even in mild asthma
       In addition to eosinophils,T-lymphocytes & a variety
       of cytokines play an important role in asthma
       The concept of delayed asthmatic response after
       allergen exposure and its relation to cellular
       inflammation and airway hyper responsiveness is
       established

09/12/00              DR.T.M.K./JAIPUR                 25
Conclusions :2

           Lavage or endobronchial biopsy has not
           identified parameters which help in the
           diagnosis , assessment of disease severity,
           prognosis or likelihood to respond to specific
           therapies.
           The exact relationship between parameters of
           lavage compared with mucosal biopsy and how
           they are related airway hyper reactivity and
           clinical syndrome remains poorly understood.

09/12/00                DR.T.M.K./JAIPUR                26
Conclusions:3


           Currently FOB with lavage or biopsy is only a
           research tool for specimen retrieval to help
           characterize and express inflammation.
           These techniques have contributed immensely
           to our understanding of asthma pathogenesis,
           presently these techniques do not have any
           practical role or clinical usefulness.

09/12/00                DR.T.M.K./JAIPUR                   27
                 THANK YOU

09/12/00   DR.T.M.K./JAIPUR   28

				
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posted:10/2/2012
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