evaluation of airway inflammation: bronchoscopy

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Assoc. Prof. Dr. Murat SEZER Vakıf Gureba Training and Research Hospital

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EVALUATION OF AIRWAY INFLAMMATION: BRONCHOSCOPY. Assoc. Prof . Dr. Murat SEZER Vakıf Gureba Training and Research Hospital. Bronchoscopy. - PowerPoint PPT Presentation

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  • Assoc. Prof. Dr. Murat SEZERVakf Gureba Training and Research Hospital

  • BronchoscopyIn the early 1970s, Reynolds and Newball were among the first to report their experience with fiberoptic bronchoscopy and bronchial (bronchoalveolar) lavage (BAL) in order to obtain respiratory cells and secretions from human volunteers for in vitro analysis.Reynolds HY, Newball HH. J Lab Clin Med 1972; 84: 55973

    However, it was not until approximately 10 years later that studies were initiated in subjects with asthmaGodard PJ, Chaintreuil M, Damon M, et al. J Allergy Clin Immunol 1982; 70: 8893

  • BronchoscopyBALEndobronchial brushingForceps biopsyTransbronchial biopsy made it possible to evaluate the inflammation and remodelling within the lungs

  • BronchoscopyThese bronchoscopic studies let us have in vivo information about

    The role of inflammatory cells and mediators that play a role in asthma,

    The severity of the disease

  • BronchoscopyStudies in asthmatic patients revealed that there is a correlation between inflammatory cell infiltration, activation state of the released cytokines and physiological parameters.

    Kraft M, Djukanovic R, Wilson S, et al. Am J Respir Crit Care Med 1996; 154: 1505-10Kavuru MS, Dweik RA, Thomassen MJ. Clin Chest Med 1999; 20: 153-89

  • BronchoscopyThe interventional studies also gather new information that can highlight the efficacy of current therapies and their mechanisms of action

    Djukanovic R, Wilson JW, Britten KM, et al. Am Rev Respir Dis 1992; 145: 669-74Jeffery PK, Godfrey RWA, Adelroth E, et al. Am Rev Respir Dis 1992; 145: 890-9Anonymous. J Allergy Clin Immunol 1991; 88: 808-14

  • BronchoscopyThese studies increased our knowledge about

    Pathophysiology of the allergic asthma and allergic rhinitis

    Similarities and differences of the airway

    Histology of the subtypes of persisting asthma

    Busse WW, Wanner A, Adams K, et al. Am J Respir Crit Care Med 2005; 807: 16

  • Bronchoalveolar LavageGenerally it is well tolerated but it can cause a decline in pulmonary function testsBAL alone or together with other procedures do not significantly change the existing tissue inflammation, airway obstruction and airway hyperresponsiveness

    Krug N, Teran LM, Redington AE, et al. Am J Respir Crit Care Med 1996; 53: 1391-7Van Vyve T, Chanez P, Bousquet J, et al. Am Rev Respir Dis 1992; 46: 116-21

  • Bronchoalveolar LavageCough and postbronchoscopic fever can follow BAL

    Hypoksemia is less common due to standard use of oxygen inhalation during bronchoscopy

    Van Vyve T, Chanez P, Bousquet J, et al. Am Rev Respir Dis 1992; 46: 116-21

  • Bronchoalveolar LavageStudies of BAL in asthma have revealed increased numbers and activation of inflammatory cells and higher levels of mediators when compared to subjects without asthma

    Asthma subjects show increased numbers of BAL eosinophils, even when the disease is mild and stable

    Bousquet J, Chanez P, Lacoste JY, et al. N Engl J Med 1990; 3: 1033-9

  • Bronchoalveolar LavageMacrophage activation has been described in symptomatic asthma and with nocturnal exacerbationsWenzel SE, Trudeau JB, Westcott JY, et al. J Allergy Clin Immunol 1994; 94: 870-81

    While BAL neutrophilia is not a predominant feature of mild to moderate asthma, it has been described in response to occupational challenge with isocyanate or grain dust and endotoxin-contaminated allergen extracts

    Hunt LW, Gleich GJ, Ohnishi T, et al. Am J Respir Crit Care Med 1994; 149: 1471-5

    Deetz DC, Jagielo PJ, Quinn TJ, et al. Am J Respir Crit Care Med 1997; 155: 254-9

  • Bronchoalveolar LavageSubgroups of the cells that are obtained with BAL can be evaluated

    In the BAL fluid of asthmatic patients eosinophil count and CD5+ T-lymphocytes with CD25 were significantly increased, while CD3, CD4, CD8, CD16/CD56 and CD19 percentages were not significantly different from that of control subjects

    Harmanc E, Glba Z, zdemir N, et al. Tuberk Toraks 2001; 49: 187-92

  • Bronchoalveolar LavageMany mediators and cytokines have been detected in BAL fluid of asthma patients, including:IL-1IL-6IL-2IL-10IL-4GM-CSFIL-5TNF-

    Zangrilli JG, Peters SP. Cytokines in allergic airway disease. In Busse WW, Holgate ST, eds. Asthma and Rhinitis. Blackwell Scientific Publications, Cambridge. 1995, 426436.

  • Bronchoalveolar LavageOther studies have noted increased levels of mRNA for several cytokines in BAL cells, including:TNF-IL-4GM-CSFIL-5IL-1IL-6IL-2IL-13IL-3

    Zangrilli JG, Peters SP. Cytokines in allergic airway disease. In Busse WW, Holgate ST, eds. Asthma and Rhinitis. Blackwell Scientific Publications, Cambridge. 1995, 426436.

  • Bronchoalveolar LavageOther mediators detected in BAL fluid include:

    LeukotrienesProstaglandinsHistamineTryptaseSoluble adhesion molecules

  • Bronchoalveolar LavageBronchoalveolar lavage has also been performed to evaluate the effects of asthma therapies (corticosteroids, theophylline, beta-agonists, cromolyn sodium, nedocromil sodium, cetirizine, leukotriene inhibitors, etc.) on parameters of airway inflammation

  • Bronchial BiopsyThe use of bronchial biopsy for research purposes in asthma was first reported in 1977

    Molina C, Brun J, Coulet M, et al. Immunopathology of the bronchial mucosa in late onset asthma. Clin Allergy 1977; 7: 13745

    Bronchial biopsy provides valuable insight into the morphology of the asthmatic airways, enabling detailed study of the epithelium, basement membrane, and submucosa

    Djukanovic R. Bronchial biopsies. In Holgate ST, Busse W, eds. Asthma and Rhinitis. Blackwell Scientific Publications, Boston. 1994, 118129.

  • Bronchial BiopsyImmunohistochemical studies of bronchial biopsies have enabled quantification of the inflammatory cells, such as mast cells, eosinophils, and T lymphocytes, and the extent of activation of these cellsDjukanovic R, Wilson JW, Britten KM, et al. Am Rev Respir Dis 1990; 142: 86371Azzawi M, Bradley B, Jeffery PK, et al. Am Rev Respir Dis 1990; 142: 140713

  • Bronchial BiopsyUsing transmission electron microscopy, it has been possible to study the ultrastructure of inflammatory cellsAzzawi M, Bradley B, Jeffery PK, et al. Am Rev Respir Dis 1990; 142: 140713

    The immunogold technique has localized cytokines to ultrastructural elements of cells and adhesion molecules within the epithelium

    Lackie P, Baker JE, Gunthert U, et al. Am J Respir Cell Mol Biol 1997; 16: 1422

  • Bronchial BiopsyKraft and colleagues reported the first study in which transbronchial biopsies were obtained in asthma subjects. Prominent tissue eosinophilia was seen at 4:00 A.M. in asthma subjects with nocturnal decline in pulmonary functions compared to asthmatic subjects without nocturnal asthma.

    Kraft M, Djukanovic R, Wilson S, et al. Am J Respir Crit Care Med 1996; 154: 150510

  • Bronchial BrushingThe techniques of BAL and bronchial brushing not only provide complementary histologic information but also cells for in vitro study

    The majority of cells obtained by brushing are bronchial epithelial cells

    Bronchial epithelial cells release inflammatory mediators and participate in airway immune responses as antigenpresenting cells

  • Bronchial BrushingBronchial epithelial cells from asthmatic subjects have also been shown to have enhanced expression of HLA-DR and ICAM-1 compared with normal subjects

    Vignola AM, Campbell AM, Chanez P, et al. Am Rev Respir Dis 1993; 148: 68994

    They can also release mediators relevant to the pathogenesis of asthma, such as 15-hydroxy-eicosatetranoic acid (15 HETE), prostaglandin E2, and fibronectin

    Campbell AM, Chanez P, Vignola AM, et al. Am Rev Respir Dis 1993; 147: 52934

  • Bronchial BrushingEpithelial cells from asthmatic subjects have also enhanced expression of GM-CSF, which decreases following treatment with inhaled steroids

    Sousa AR, Poston RN, Lane SJ, et al. Am Rev Respir Dis 1993; 147: 155761

  • Segmental Allergen ChallengeThe majority of patients with asthma have allergic sensitivities that can be used to provoke airway inflammation

    Aerosolized allergen challenge results in the development of bronchial obstruction, airway hyperresponsiveness, eosinophilic infiltration and activation, increased superoxide production, and other indices of inflammation

    de Monchy JGR, Kauffman HF, Venge P, et al. Am Rev Respir Dis 1985; 131: 3736 Diaz P, Gonzalez MC, Galleguillos FR, et al. Am Rev Respir Dis 1989; 139: 13839 Calhoun WJ, Bush RK. J Allergy Clin Immunol 1990; 86: 30613

  • Segmental Allergen ChallengeOnly a small and variable fraction of the dose delivered by the nebulizer actually reaches the lower airway

    Moreover, the site of deposition is unknown unless radiotracers are used, and in any case is uncontrolled

    Finally, the quantity of allergen that can be delivered is limited by safety considerations due to airway obstruction

  • Segmental Allergen ChallengeUsing segmental allergen challenge allergen dosing and localization are more precise, because allergen is delivered to a specific airway segment under direct visualization

    Multiple segments can safely be challenged with different antigen doses (for doseresponse studies)

    The same dose can be used in multiple segments (for kinetic or interventional studies)

    Calhoun WJ, Jarjour NN, Gleich GJ, et al. J Allergy Clin Immunol 1996; 98:S46S50.

    Kane GC, Pollice M, Kim CJ, et al. J Allergy Clin Immunol 1996; 97:64654.

    Shaver JR, Zangrilli JG, Cho SK, et al. Am J Respir Crit Care Med 1997; 155:4428.

  • Segmental Allergen ChallengeThe degree of generalized bronchial obstruction is less than that seen with aerosol challenge, and the degree of inflammation is greater

    Calhoun WJ, Jarjour NN, Gleich GJ, et al. Am Rev Respir Dis 1993; 147: 146571

    Instrumentation and BAL per se do not evoke generalized pulmonary inflammation

    Calhoun WJ, Reed HE, Moest D, et al. Am Rev Respir Dis 1992; 145: 31725

    Jarjour NN, Calhoun WJ. Am Rev Respir Dis 1990; 142: 1003

  • Segmental Allergen ChallengeSAC localizes allergen challenge to the small airways, which are sites of inflammation and bronchial obstruction in asthma

    Saetta M, DiStefano A, Rosina C, et al. Am Rev Respir Dis 1991; 143: 13843

    Kraft M, Djukanovic R, Wilson S, et al. Am J Respir Crit Care Med 1996; 154: 150510

    Wagner EM, Liu MC, Weinmann GG, et al. Am Rev Respir Dis 1990; 141: 5848

  • Segmental Allergen ChallengeWhile SAC is a powerful tool for studying allergen-driven airway inflammation, care should be taken when extrapolating SAC findings to natural exacerbations of asthma

  • Segmental Allergen ChallengeWenzel and colleagues showed that the concentration of leukotriene C4 was significantly greater after endobronchial allergen challenge in asthmatics compared to nonasthmatic atopics

    Wenzel SE, Larsen GL, Johnston K, et al. Am Rev Respir Dis 1990; 142: 1129

    Preliminary data suggest that failure to secrete IL-10 after allergen challenge might also differentiate allergic asthma from allergic rhinitis subjects

    Calhoun WJ, Hinton KL, Brick JJ, et al. Am J Respir Crit Care Med 1996; 153: A881

  • Segmental Allergen ChallengeShaver and colleagues reported that the increase in BAL eosinophils and IL-5 in response to antigen SAC were similar in allergic asthmatic and allergic nonasthmatic subjects

    Interestingly, subjects with documented late asthmatic response to whole lung challenge showed the strongest cellular and cytokine responses to SAC

    Shaver JR, OConnor JJ, Pollice M, et al. Am J Respir Crit Care Med 1993; 152: 118997