Small airway inflammation in asthma

Respiratory Research

Qutayba Hamid¹  Pota Christodoulopoulos¹  Meri K Tulic¹ 

[1] Meakins-Christie Laboratories, McGill University, Montreal, Canada

关键词: small airways;    peripheral airways;    asthma;    allergic inflammation;   

Others  :  1227430
DOI  :  10.1186/rr83

 received in 2001-06-27, accepted in 2001-07-18,  发布年份 2001

【 摘 要 】

Asthma was originally described as an inflammatory disease that predominantly involves the central airways. Pathological and physiological evidence reported during the past few years suggests that the inflammatory process extends beyond the central airways to the peripheral airways and the lung parenchyma. The small airways are capable of producing T-helper-2 cytokines, as well as chemokines, and they have recently been recognized as a predominant site of airflow obstruction in asthmatic persons. The inflammation at this distal site has been described as more severe than large airway inflammation. These findings are of great clinical significance, and highlight the need to consider the peripheral airways as a target in any therapeutic strategy for treatment of asthma.

【 授权许可】

   
2001 BioMed Central Ltd

【 图 表 】

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【 参考文献 】

• [1]Curschmann H: Exudative bronchiolitis and its relationship with asthma nervosa [in German]. Dtsch Arch Klin Med 1882, 32:1-34.
• [2]Djukanovic R, Wilson JW, Lai CK, Holgate ST, Howarth PH: The safety aspects of fiberoptic bronchoscopy, bronchoalveolar lavage, and endobronchial biopsy in asthma. Am Rev Respir Dis 1991, 143:772-777.
• [3]Bentley AM, Meng Q, Robinson DS, Hamid Q, Kay AB, Durham SR: Increases in activated T lymphocytes, eosinophils, and cytokine mRNA expression for interleukin-5 and granulocyte/macrophage colony-stimulating factor in bronchial biopsies after allergen inhalation challenge in atopic asthmatics. Am J Respir Cell Mol Biol 1993, 8:35-42.
• [4]Hamid Q, Song Y, Kotsimbos TC, Minshall E, Bai TR, Hegele RG, Hogg JC: Inflammation of small airways in asthma. J Allergy Clin Immunol 1997, 100:44-51.
• [5]Minshall EM, Hogg JC, Hamid QA: Cytokine mRNA expression in asthma is not restricted to the large airways. J Allergy Clin Immunol 1998, 101:386-390.
• [6]Taha RA, Minshall EM, Miotto D, Shimbara A, Luster A, Hogg JC, Hamid QA: Eotaxin and monocyte chemotactic protein-4 mRNA expression in small airways of asthmatic and nonasthmatic individuals. J Allergy Clin Immunol 1999, 103:476-483.
• [7]Carroll N, Cooke C, James A: The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics. Eur Respir J 1997, 10:292-300.
• [8]Faul JL, Tormey VJ, Leonard C, Burke CM, Farmer J, Horne SJ, Poulter LW: Lung immunopathology in cases of sudden asthma death. Eur Respir J 1997, 10:301-307.
• [9]Christodoulopoulos P, Leung DY, Elliott MW, Hogg JC, Muro S, Toda M, Laberge S, Hamid QA: Increased number of glucocorticoid receptor-beta-expressing cells in the airways in fatal asthma. J Allergy Clin Immunol 2000, 106:479-484.
• [10]Kraft M, Djukanovic R, Wilson S, Holgate ST, Martin RJ: Alveolar tissue inflammation in asthma. Am J Resp Crit Care Med 1996, 154:1505-1510.
• [11]Kraft M, Martin RJ, Wilson S, Djukanovic R, Holgate ST: Lymphocyte and eosinophil influx into alveolar tissue in nocturnal asthma. Am J Respir Crit Care Med 1999, 159:228-234.
• [12]Carroll N, Carello S, Cooke C, James A: Airway structure and inflammatory cells in fatal attacks of asthma. Eur Respir J 1996, 9:709-715.
• [13]Synek M, Anto JM, Beasley R, Frew AJ, Halloway L, Lampe FC, Lloreta JL, Sunyer J, Thornton A, Holgate ST: Immunopathology of fatal soybean dust-induced asthma. Eur Respir J 1996, 9:54-57.
• [14]Weibel ER: Morphometry of the Human Lung. New York: Academic Press;. 1963.
• [15]Macklem PT, Mead J: Resistance of central and peripheral airways measured by a retrograde catheter. J Appl Physiol 1967, 22:395-401.
• [16]Brown R, Woolcock AJ, Vincent NJ, Macklem PT: Physiological effects of experimental airway obstruction with beads. J Appl Physiol 1969, 27:328-335.
• [17]Mead J, Takishima T, Leith D: Stress distribution in lungs: a model of pulmonary elasticity. J Appl Physiol 1970, 28:596-608.
• [18]Sly PD, Willet KE, Kano S, Lanteri CJ, Wale J: Pirenzepine blunts the pulmonary parenchymal response to inhaled methacholine. Pulm Pharmacol 1995, 8:123-129.
• [19]Peták F, Hantos Z, Adamicza Á, Asztalos T, Sly PD: Methacholine-induced bronchoconstriction in rats: effects of intravenous vs. aerosol delivery. J Appl Physiol 1997, 82:1479-1487.
• [20]Ludwig MS, Romero PV, Bates JH: A comparison of the dose-response behavior of canine airways and parenchyma. J Appl Physiol 1989, 67:1220-1225.
• [21]Suki B, Petak F, Adamicza A, Hantos Z, Lutchen KR: Partitioning of airway and lung tissue properties: comparison of in situ and open-chest conditions. J Appl Physiol 1995, 79:861-869.
• [22]Sato J, Suki B, Davey BLK, Bates JHT: Effect of methacholine on low-frequency mechanics of canine airways and lung tissue. J Appl Physiol 1993, 75:55-62.
• [23]Romero PV, Robatto FM, Simard S, Ludwig MS: Lung tissue behavior during methacholine challenge in rabbits in vivo. J Appl Physiol 1992, 73:207-212.
• [24]Tepper R, Sato J, Suki B, Martin JG, Bates JHT: Low-frequency pulmonary impedance in rabbits and its response to inhaled methacholine. J Appl Physiol 1992, 73:290-295.
• [25]Ingenito EP, Davision B, Fredberg JJ: Tissue resistance in the guinea pig at baseline and during methacholine constriction. J Appl Physiol 1993, 75:2541-2548.
• [26]Salerno FG, Moretto A, Dallaire M, Ludwig MS: How mode of stimulus affects the relative contribution of elastance and hysteresivity to changes in lung tissue resistance. J Appl Physiol 1995, 78:282-287.
• [27]Tulic MK, Wale JL, Petak F, Sly PD: Muscarinic blockade of methacholine induced airway and parenchymal lung responses in anaesthetised rats. Thorax 1999, 54:531-537.
• [28]Ohrui T, Sekizawa K, Yanai M, Morikawa M, Jin Y, Sasaki H, Takishima T: Partitioning of pulmonary responses to inhaled methacholine in subjects with asymptomatic asthma. Am Rev Respir Dis 1992, 146:1501-1505.
• [29]Van Brabandt H, Cauberghs M, Verbeken E, Moerman P, Lauweryns JM, Van de Woestijne KP: Partitioning of pulmonary impedance in excised human and canine lungs. J Appl Physiol 1983, 55:1733-1742.
• [30]Ingram RHJ: Physiological assessment of inflammation in the peripheral lung of asthmatic patients. Lung 1990, 168:237-247.
• [31]Wagner EM, Bleecker ER, Permutt S, Liu MC: Direct assessment of small airways reactivity in human subjects. Am J Respir Crit Care Med 1998, 157:447-452.
• [32]Yanai M, Sekizawa K, Ohrui T, Sasaki H, Takishima T: Site of airway obstruction in pulmonary disease: direct measurement of intrabronchial pressure. J Appl Physiol 1992, 72:1016-1023.
• [33]Wagner EM, Liu MC, Weinmann GG, Permutt S, Bleecker ER: Peripheral lung resistance in normal and asthmatic subjects. Am Rev Respir Dis 1990, 141:584-588.
• [34]Wiggs BR, Bosken C, Pare PD, James AL, Hogg JC: A model of airway narrowing in asthma and in chronic obstructive pulmonary disease. Am Rev Respir Dis 1992, 145:1251-1258.
• [35]Kuwano K, Bosken CH, Pare PD, Bai TR, Wiggs BR, Hogg JC: Small airways dimensions in asthma and in chronic obstructive pulmonary disease. Am Rev Respir Dis 1993, 148:1220-1225.
• [36]Petak F, Hall GL, Sly PD: Repeated measurements of airway and parenchymal mechanics in rats by using low-frequency oscillations. J Appl Physiol 1998, 84:1680-1686.
• [37]Sly PD, Hayden MJ, Petak F, Hantos Z: Measurements of low-frequency respiratory impedance in infants. Am J Respir Crit Care Med 1996, 154:161-166.
• [38]Hall GL, Hantos Z, Petak F, Wildhaber JH, Tiller K, Burton PR, Sly PD: Airway and respiratory tissue mechanics in normal infants. Am J Respir Crit Care Med 2000, 162:1397-1402.
• [39]Hall GL, Hantos Z, Wildhaber JH, Petak F, Sly PD: Methacholine responsiveness in infants assessed with low frequency forced oscillation and forced expiration techniques. Thorax 2001, 56:42-47.
• [40]Woolcock AJ: Effects of drugs on small airways. Am J Respir Crit Care Med 1998, 157(suppl):203-207.
• [41]Huber HL, Koessler KK: The pathology of bronchial asthma. Arch Intern Med 1922, 30:689-760.
• [42]Dunnill MS: The pathology of asthma, with special reference to changes in the bronchial mucosa. J Clin Pathol 1960, 13:27-33.
• [43]Dunnill MS, Massarella GR, Anderson JA: A comparison of the quantitative anatomy of the bronchi in normal subjects, in status asthmaticus, in chronic bronchitis and in emphysema. Thorax 1969, 24:176-179.
• [44]Hamid QA: Peripheral inflammation is more important than central inflammation . Respir Med 1997, 91:11-12.
• [45]Haley KJ, Sunday ME, Wiggs BR, Kozakewich HP, Reilly JJ, Mentzer SJ, Sugarbaker DJ, Doerschuk CM, Drazen JM: Inflammatory cell distribution within and along asthmatic airways. Am J Respir Crit Care Med 1998, 158:565-572.
• [46]Saetta M, Di Stefano A, Rosina C, Thiene G, Fabbri LM: Quantitative structural analysis of peripheral airways and arteries in sudden fatal asthma. Am Rev Respir Dis 1991, 143:138-143.
• [47]Kraft M: The distal airways: are they important in asthma? Eur Respir J 1999, 14:1403-1417.
• [48]Kraft M, Vianna E, Martin RJ, Leung DYM: Nocturnal asthma is associated with reduced glucocorticoid receptor binding affinity and decreased steroid responsiveness at night. J Allergy Clin Immunol 1999, 103:66-71.
• [49]Wenzel SE, Szefler SJ, Leung DY, Sloan SI, Rex MD, Martin RJ: Bronchoscopic evaluation of severe asthma. Persistent inflammation associated with high dose glucocorticoids. Am J Respir Crit Care Med 1997, 156:737-743.
• [50]Djukanovic R, Wilson JW, Britten KM, Wilson SJ, Walls AF, Roche WR, Howarth PH, Holgate ST: Effect of an inhaled corticosteroid on airway inflammation and symptoms in asthma. Am Rev Respir Dis 1992, 145:669-674.
• [51]Booth H, Richmond I, Ward C, Gardiner PV, Harkawat R, Walters EH: Effect of high dose inhaled fluticasone propionate on airway inflammation in asthma. Am J Respir Crit Care Med 1995, 152:45-52.
• [52]Jeffery PK, Godfrey RW, Adelroth E, Nelson F, Rogers A, Johansson SA: Effects of treatment on airway inflammation and thickening of basement membrane reticular collagen in asthma. A quantitative light and electron microscopic study. Am Rev Respir Dis 1992, 145:890-899.
• [53]Esmailpour N, Hogger P, Rabe KF, Heitmann U, Nakashima M, Rohdewald P: Distribution of inhaled fluticasone propionate between human lung tissue and serum in vivo. Eur Respir J 1997, 10:1496-1499.
• [54]Dolovich MB, Rhem R, Gerrard L, Coates G: Lung deposition of coarse CFC vs fine HFA pMDI earosols of beclomethasone dipropionate (BDP) in asthma [abstract]. Am J Respir Crit Care Med 2000, 161:A33.
• [55]Leach CL, Davidson PJ, Boudreau RJ: Improved airway targeting with the CFC-free HFA-beclomethasone metered-dose inhaler compared with CFC-beclomethasone. Eur Respir J 1998, 12:1346-1353.
• [56]Busse WW, Brazinsky S, Jacobson K, Stricker W, Schmitt K, Vanden Burgt J, Donnell D, MRPharm S, Hannon S, Colice GL: Efficacy response of inhaled beclomethasone dipropionate in asthma is proportional to dose and is improved by formulation with a new propellant. J Allergy Clin Immunol 1999, 104:1215-1222.
• [57]Vanden Burgt JA, Busse WW, Martin RJ, Szefler SJ, Donnell D: Efficacy and safety overview of a new inhaled corticosteroid, QVAR (hydrofluoroalkane-beclomethasone extrafine inhalation aerosol), in asthma [review]. J Allergy Clin Immunol 2000, 106:1209-1226.
• [58]Goldin JG, Tashkin DP, Kleerup EC, Greaser LE, Haywood UM, Sayre JW, Simmons MD, Suttorp M, Colice GL, Vanden Burgt JA, Aberle DR: Comparative effects of hydrofluoroalkane and chlorofluorocarbon beclomethasone dipropionate inhalation on small airways: assessment with functional helical thin-section computed tomography. J Allergy Clin Immunol 1999, 104(suppl):258-267.
• [59]Marshall BG, Wangoo A, Harrison LI, Young DB, Shaw RJ: Tumour necrosis factor-alpha production in human alveolar macrophages: modulation by inhaled corticosteroid. Eur Respir J 2000, 15:764-770.
• [60]Muller NL, Miller RR: Diseases of the bronchioles: CT and pathological findings. Radiology 1995, 196:3-12.