Journal Information
Vol. 15. Issue 3.
Pages 443-460 (May - June 2009)
Share
Share
Download PDF
More article options
Vol. 15. Issue 3.
Pages 443-460 (May - June 2009)
Full text access
Avaliação da inflamação das vias aéreas. Vias áreas superiores e compartimento broncopulmonar
Visits
1412
Luísa Geraldes1, Ana Todo-Bom2, Carlos Loureiro2, Mota Pinto3
1 Interna do 5.° ano da especialidade de Imunoalergologia dos HUC
2 Assistente Hospitalar Graduado em Imunoalergologia dos HUC
3 Serviço de Imunoalergologia, Departamento de Ciências Pneumológicas e Alergológicas dos Hospitais da Universidade de Coimbra, Av. Bissaya Barreto e Praceta, 3000-075 Coimbra
This item has received
Article information
Resumo

Faz-se uma revisão sobre métodos de avaliação da inflamação nas vias aéreas que contribuam para o diagnóstico, terapêutica e prognóstico de patologias como a rinossinusite e a asma. Serão também considerados métodos susceptíveis de fornecer informação relevante sobre inflamação na DPOC.

A inflamação crónica das vias aéreas condiciona fenómenos obstrutivos objectivados na função respiratória basal, na hiperreactividade brônquica e nasal e em quadros clínicos de dificuldade respiratória. A tomografia computorizada informa sobre as dimensões do lúmen, a espessura das paredes brônquicas e os índices de densidade pulmonar, alterações que decorrem da inflamação e remodelação das vias aéreas.

Um processo inflamatório localizado nas vias respiratórias é susceptível de ser detectado por modificações em marcadores sistémicos de inflamação.

Os métodos directos recorrem a análise imunoistoquímica de tecidos e de fluidos em condições basais ou após estimulação. Os eosinófilos aumentam em biópsias, lavados nasais e broncoalveolares na asma e na rinite e modificam-se com a terapêutica. Ocorrem alterações nas proteínas e expressão de RNAm de mediadores envolvidos na activação celular.

A expectoração induzida identifica inflamação eosinofílica que se relaciona inversamente com a função ventilatória.

Em cada ciclo respiratório o ar é enriquecido em compostos voláteis produzidos no decurso da respiração celular. A FENO é o biomarcador mais estudado e os seus níveis estão elevados na asma.

No condensado do ar expirado identificam-se espécies reactivas de oxigénio, derivados de membrana, citocinas e quimiocinas pró-inflamatórias.

Se a avaliação não invasiva da inflamação for fidedigna e reprodutível, será imprescindível na monitorização das doenças das vias aéreas.

Palavras chave:
Asma
exames auxiliares de diagnóstico
inflamação
rinite
Abstract

It is done a review of evaluation methods of the inflammation in upper airways and bronchi used for diagnosis, therapeutic approach and prognosis of pathologies like rhinosinusitis and asthma. It is also analysed methods that supply relevant information of inflammation in COPD.

The chronic inflammation of the airways is associated to respiratory distress, obstruction in basal lung function tests and to bronchial and nasal hyperreactivity. Computerized tomography informs about lumen dimensions, bronchial walls thickness and pulmonary density. These changes are associated to inflammation and to remodelling of the airways.

Localized inflammation in respiratory tract can be detected by modifications of systemic inflammatory markers.

The direct evaluation of inflammatory airways changes are based on immune, histological and chemical analysis of lung tissue obtained by biopsies and by fluids recoil in basal conditions or after stimulation. The eosinophils are increased in biopsies and in nasal and bronchoalveolar lavage in asthma and rhinitis and can change with therapy. Proteins and mRNA expression of cellular activation mediators are also observed.

The induced sputum identifies eosinophilic inflammation that is inversely associated with lung function parameters.

In each respiratory cycle the air is enriched in organic volatile compounds produced by cellular breathing. FENO is the bio marker more deeply studied in asthma and its increase is well documented in this disorder.

In the exhaled air condensed, reactive oxygen species, membrane mediators, cytokines, and chemokines are identified.

If the non invasive evaluation of inflammation became reliable and reproducible it will be indispensable in monitoring the airways diseases.

Keywords:
Asthma
evaluation methods
inflammation
rhinitis
Full text is only aviable in PDF
Bibliografia
[1.]
Global Initiative for Asthma. Global strategy for asthma management and prevention. Washington, DC: National Institutes of Health; National Heart, Lung and Blood Institute, 2003. Updated 2004. NIH publication No. 02-3659. Available at: http://www.ginasthma.com (accessed Jun 2005).
[2.]
Global initiative for chronic obstructive lung disease. Global strategy for the diagnosis management and prevention of chronic obstructive pulmonary disease Bethesda, MD: World Health Organization and US National Heart, Lung and Blood Institute, 2003.
[3.]
C.E. Brightling, F.A. Symon, S.S. Birring, P. Bradding, A.J. Wardlaw, I.D. Pavord.
Comparison of airway immunopathology of eosinophilic bronchitis and asthma.
Thorax, 58 (2003), pp. 528-532
[4.]
L. McCormack.
Enright.
Making the Diagnosis of Asthma Respiratory Care, 53 (2008), pp. 583-590
[5.]
Ward C.
Inter-relationships between airway inflammation, reticular basement membrane thickening and bronchial hyper-reactivity to methacholine in asthma; asystematic bronchoalveolar lavage and airway biopsy analysis.
Clin Exp Allergy, 35 (2005), pp. 1565-1571
[6.]
D.W. Cockcroft, B.E. Davis.
Mechanisms of airway hyperresponsiveness.
J Allergy Clin Immunol, 118 (2006), pp. 551-559
[7.]
R.O. Crapo, R. Casaburi, A.L. Coates, P.L. Enright, J.L. Hankinson, C.G. Irvin, et al.
Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999.
Am J Respir Crit Care Med, 161 (2000), pp. 309-329
[8.]
D.C. Grootendorst, K.F. Rabe.
Mechanisms of bronchial hyperreactivity in asthma and chronic obstructive pulmonary disease.
Proc Am Thorac Soc, 1 (2004), pp. 77-87
[9.]
C. Porsbjerg, L. Rasmussen, S.F. Thomsen, J.D. Brannan, S.D. Anderson, V. Backer.
Response to mannitol in asymptomatic subjects with airway hyper-responsiveness to methacholine.
Clin Exp Allergy, 37 (2007), pp. 22-28
[10.]
P. Sheahan, R.M. Walsh, M.A. Walsh, R.W. Costello.
Induction of nasal hyper-responsiveness by allergen challenge in allergic rhinitis: the role of afferent and efferent nerves.
Clin Exp Allergy, 35 (2005), pp. 45-51
[11.]
L. Ketai, M. Harkins, K.L. Fiato, G.K. Iwamoto.
Exhaled nitric oxide and bronchial wall thickening in asthmatics during and after acute exacerbation: evidence of bronchial wall remodeling.
J Asthma, 42 (2005), pp. 667-671
[12.]
V. Marchac, S. Emond, T. Mamou-Mani, C. Le Bihan-Benjamin, M. Le Bourgeois, J. De Blic.
Thoracic CT in pediatric patients with difficult-to-treat asthma.
AJR Am J Roentgenol, 179 (2002), pp. 1245-1252
[13.]
L. Ketai, C. Coutsias, S. Williamson, V. Coutsias.
Thin-section CT evidence of bronchial thickening in children with stable asthma: bronchoconstriction or airway remodeling?.
Acad Radiol, 8 (2001), pp. 257-264
[14.]
N. Jain, R.A. Covar, M.C. Gleason, J.D. Newell Jr., E.W. Gelfand, J.D. Spahn.
Quantitative computed tomography detects peripheral airway disease in asthmatic children.
Pediatr Pulmonol, 40 (2005), pp. 211-218
[15.]
T. Ueda, A. Niimi, H. Matsumoto, M. Takemura, T. Hirai, M. Yamaguchi.
Role of small airways in asthma: investigation using high-resolution computed tomography.
J Allergy Clin Immunol, 118 (2006), pp. 1019-1025
[16.]
J. de Blic, P. Scheinmann.
The use of imaging techniques for assessing severe childhood asthma.
J Allergy Clin Immunol, 119 (2007), pp. 808-810
[17.]
S. Samee, T. Altes, P. Powers, E.E. de Lange, J. Knight-Scott, G. Rakes.
Imaging the lungs in asthmatic patients by using hyperpolarized helium-3 magnetic resonance: assessment of response to methacholine and exercise challenge.
J Allergy Clin Immunol, 111 (2003), pp. 1205-1211
[18.]
Dourado M. Fisiopatologia laboratorial. In: Mota Pinto, A. Fisiopatologia – Fundamentos e aplicações. Lidel Edições técnicas 2007: 23–28.
[19.]
M. Fujita, S. Ueki, W. Ito, T. Chiba, M. Takeda, N. Saito, H. Kayaba.
C-Reactive protein levels in the serum of asthmatic patients.
Ann Allergy Asthma Immunol, 99 (2007), pp. 48-53
[20.]
A. Todo-Bom, A. Mota Pinto, S. Vale Pereira, V. Alves, M. Dourado, M. Santos Rosa, et al.
Substance P in long-lasting asthma:Immunoinflammatory pathways.
Allergy Clin Immunol Int – J World Allergy Org, 18 (2006), pp. 242-248
[21.]
P.H. Black.
Stress and the inflammatory response: A review of neurogenic inflammation.
Brain Behav Immun, 16 (2002), pp. 622-653
[22.]
A. Barbato, G. Turato, S. Baraldo, E. Bazzan, F. Calabrese, C. Panizzolo, et al.
Epithelial damage and angiogenesis in the airways of children with asthma.
Am J Respir Crit Care Med, 174 (2006), pp. 975-981
[23.]
T. Suzuki, C.W. Chow, G.P. Downey.
Role of innate immune cells and their products in lung immunopathology.
Int J Biochem Cell Biol, 40 (2008), pp. 1348-1361
[24.]
L.A. Laitinen, A. Laitinen, A. Altraja, I. Virtanen, M. Kämpe, B.G. Simonsson, S.E. Karlsson, L. Håkansson, P. Venge, H. Sillastu.
Bronchial biopsy findings in inter-mittent or “early” asthma.
J Allergy Clin Immunol, 98 (1996), pp. S33-S540
[25.]
S. Siddiqui, V. Mistry, C. Doe, K. Roach, A. Morgan, A. Wardlaw, I. Pavord, P. Bradding, C. Brightling.
Airway hyperresponsiveness is dissociated from airway wall structural remodelling.
J Allergy Clin Immunol, 122 (2008), pp. 335-341
[26.]
E. Sutherland, R. Martin.
Airway inflammation in chronic obstructive pulmonary disease: Comparisons with asthma.
JAllergy Clin Immunol, 112 (2003), pp. 819-827
[27.]
P.K. Jeffery, T. Haahtela.
Allergic rhinitis and asthma: inflammation in a one-airway condition.
BMC Pulm Med, 30 (2006), pp. S5
[28.]
A. Barczyk, W. Pierzcha, O. Kon, B. Cosio, I. Adcock, P. Barnes.
Cytokine production by bronchoalveolar lavage T lymphocytes in chronic obstructive pulmonary disease.
J Allergy Clin Immunol, 117 (2006), pp. 1484-1492
[29.]
J.N. Francis, I. Sabroe, C.M. Lloyd, S.R. Durham, S.J. Till.
Elevated CCR6+ CD4+ T lymphocytes in tissue compared with blood and induction of CCL20 during the asthmatic late response.
Clin Exp Immunol, 152 (2008), pp. 440-447
[30.]
G. Ciprandi, I. Cirillo, C. Klersy, M. Tosca, G. Marseglia.
Nasal eosinophils and reversibility to the decongestion test in patients with perennial allergic rhinitis.
Allergy Asthma Proc, 28 (2007), pp. 292-295
[31.]
R. Salib, L. Lau, P. Howarth.
The novel use of the human nasal epithelial cell line RPMI 2650 as an in vitro model to study the influence of allergens and cytokines on transforming growth factor-b gene expression and protein release.
Clin Exp Allergy, 35 (2005), pp. 811-819
[32.]
D. Powel, R. Huskisson, A. Carney, D. Jenkins, A. McEuen, A. Walls, N. Jones.
Mucosal T-cell phenotypes in persistent atopic and nonatopic rhinitis show an association with mast cells.
Allergy, 59 (2004), pp. 204-212
[33.]
V.J. Erpenbeck, J.M. Hohlfeld, B. Volkmann, A. Hagenberg, H. Geldmacher, A. Braun, N. Krug.
Segmental allergen challenge in patients with atopic asthma leads to increased IL-9 expression in bronchoalveolar lavage fluid lymphocytes.
J Allergy Clin Immunol, 111 (2003), pp. 1319-1327
[34.]
P. Bhavsar, M. Hew, N. Khorasani, A. Torrego, P.J. Barnes, I. Adcock, K.F. Chung.
Relative corticosteroid insensitivity of alveolar macrophages in severe asthma compared with non-severe asthma.
Thorax, 63 (2008), pp. 784-790
[35.]
M.W. Johansson, E.A. Kelly, W.W. Busse, N.N. Jarjour, D.F. Mosher.
Up-regulation and activation of eosinophil integrins in blood and airway after segmental lung antigen challenge.
J Immunol, 180 (2008), pp. 7622-7635
[36.]
L. Borish.
Allergic rhinitis: Systemic inflammation and implications for management.
J Allergy Clin Immunol, 112 (2003), pp. 1021-1031
[37.]
G. Braunstahl, S. Overbeek, A. Kleinjan, J. Prins, H. Hoogsteden, W. Fokkens.
Nasal allergen provocation induces adhesion molecule expression and tissue eosinophilia in upper and lower airways.
J Allergy Clin Immunol, 107 (2001), pp. 469-476
[38.]
A. Miadonna, N. Milazzo, M. Lorini, A. Sala, A. Tedeschi.
Nasal neutrophilia and release of myeloperoxidase induced by nasal challenge with platelet activating factor: different degrees of responsiveness in atopic and nona topic subjects.
J Allergy Clin Immunol, 97 (1996), pp. 947-954
[39.]
Woodruff, P. Relationship between airway inflammation, hyperresponsiveness, and obstruction in asthma. J Allergy Clin Immunol 200;108: 753–758.
[40.]
L. Catherine.
Airway inflammation assessed by invasive and noninvasive means in severe asthma: Eosinophilic and noneosinophilic phenotypes.
J Allergy Clin Immunol, 118 (2006), pp. 1033-1039
[41.]
F. Deveci, N. Ilhan, T. Turgut, N. Akpolat, G. Kirkil, M.H. Muz.
Glutathione and nitrite in induced sputum from patients with stable and acute asthma compared with controls.
Ann Allergy Asthma Immunol, 93 (2004), pp. 91-97
[42.]
A. Jatakanon, S. Lim, S.A. Kharitonov, K.F. Chung, P.J. Barnes.
Correlation between exhaled nitric oxide, sputum eosinophils, and methacholineresponsiveness in patients with mild asthma.
Thorax, 53 (1998), pp. 91-95
[43.]
L.J. Dupont, F. Rochette, M.G. Demedts, G.M. Verleden.
Exhaled nitricoxide correlates with airway hyperresponsiveness in steroid-naivepatients with mild asthma.
Am J Respir Crit Care Med, 157 (1998), pp. 894-898
[44.]
D. Taylor.
Nitric oxide as a clinical guide for asthma management.
J Allergy Clin Immunol, 117 (2006), pp. 259-262
[45.]
A. Sergei, Kharitonov, P.J. Barnes.
FCCP exhaled biomarkers.
Chest, 130 (2006), pp. 1541-1546
[46.]
M. Profita, S. La Grutta, E. Carpagnano, L. Riccobono, R. Di Giorgi, A. Bonanno, E. Pace, G. Bonsignore, J. Bousquet, A. Vignola, M. Gjomarkaj.
Noninvasive methods for the detection of upper and lower airway inflammation in atopic children.
J Allergy Clin Immunol, 118 (2006), pp. 1068-1074
[47.]
J. Travers, S. Marsh, S. Aldington, M. Williams, P. Shirtcliffe, A. Pritchard, M. Weatherall, R. Beasley.
Reference ranges for exhaled nitric oxide derived from a random community survey of adults.
Am J Respir Crit Care Med, 176 (2007), pp. 238-242
[48.]
J.D. Boot, M.L. de Kam, M.A. Mascelli, B. Miller, R.G. van Wijk, H. de Groot, A.F. Cohen, Z. Diamant.
Nasal nitric oxide: longitudinal reproducibility and the effects of a nasal allergen challenge in patients with allergic rhinitis.
[49.]
L.E. Donnelly, P.J. Barnes.
Expression of heme oxygenase in human airway epithelial cells.
Am J Respir Cell Mol Biol, 24 (2001), pp. 295
[50.]
K. Zayasu, K. Sekizawa, S. Okinaga, et al.
Increased carbon monoxide in exhaled air of asthmatic patients.
Am J Respir Crit Care Med, 156 (1997), pp. 1140
[51.]
C.G. Uasuf, A. Jatakanon, A. James, et al.
Exaled carbon monoxide in childhood asthma.
J Pediatr, 135 (1999), pp. 569
[52.]
P. Pearson, S. Lewis, J. Britton, A. Fogarty.
Exhaled carbon monoxide levels in atopic asthma: a longitudinal study.
Respir Med, 99 (2005), pp. 1292-1296
[53.]
M.T. Ramírez-Prieto, F. García-Río, J. Villamor.
Role of oxidative stress in respiratory diseases and its monitoring.
Med Clin, 127 (2006), pp. 386-396
[54.]
S. Dragonieri.
An electronic nose in the discrimination of patients with asthma and controls.
J Allergy Clin Immunol, 120 (2007), pp. 856-862
[55.]
M. Barreto, M. Pia Villa, C. Olita, S. Martella, G. Ciabattoni, P. Montuschi.
8-Isoprostane in exhaled breath condensate (EBC) and exercise-induced bronchoconstriction in asthmatic children and adolescents.
Chest, (2008), pp. 27
[56.]
J.O. Steiss, S. Rudloff, E. Landmann, C. Rückes-Nilges, K.P. Zimmer, H. Lindemann.
Effect of inhaled corticosteroid treatment on exhaled breath condensate leukotriene E(4) in children with mild asthma.
Allergy Asthma Proc, 29 (2008), pp. 371-375
[57.]
B. Kiełbasa, A. Moeller, M. Sanak, J. Hamacher, M. Hutterli, A. Cmiel, A. Szczeklik, J.H. Wildhaber.
Eicosanoids in exhaled breath condensates in the assessment of childhood asthma.
Pediatr Allergy Immunol, 19 (2008), pp. 660-669
[58.]
Z. Zietkowski, M.M. Tomasiak, R. Skiepko, A. Bodzenta-Lukaszyk.
RANTES in exhaled breath condensate of stable and unstable asthma patients.
Respir Med, 102 (2008), pp. 1198-1202
[59.]
C. Coop, L.L. Hagan, J.P. Dice.
Exhaled breath condensate pH in the evaluation of asthma.
Allergy Asthma Proc, 29 (2008), pp. 51-54
[60.]
R. Accordino, A. Visentin, A. Bordin, S. Ferrazzoni, E. Marian, F. Rizzato, C. Canova, R. Venturini, P. Maestrelli.
Long-term repeatability of exhaled breath condensate pH in asthma.
Respir Med, 102 (2008), pp. 377-381
[61.]
I. Romieu, A. Barraza-Villarreal, C. Escamilla-Nuñez, A.C. Almstrand, D. Diaz-Sanchez, P.D. Sly, A.C. Olin.
Exhaled breath malondialdehyde as a marker of effect of exposure to air pollution in children with asthma.
J Allergy Clin Immunol, 121 (2008), pp. 903-909
[62.]
Z. Zietkowski, R. Skiepko, M.M. Tomasiak, Bodzenta-Lukaszyk A.
Endothelin-1 in exhaled breath condensate of stable and unstable asthma patients.
Respir Med, 102 (2008), pp. 470-474
[63.]
K. Kostikas, G. Papatheodorou, K. Ganas, K. Psathakis, P. Panagou, S. Loudikes.
pH in expired breath condensate of patients with inflammatory airway diseases.
Am J Respir Crit Care Med, 165 (2002), pp. 1364-1370
[64.]
G.L. Piacentini, D. Peroni, E. Crestani, F. Zardini, A. Bodini, S. Costella, A. Boner.
Exhaled air temperature in asthma: methods and relationship with markers of disease.
Clin Exp Allergy, 37 (2007), pp. 415-419
[65.]
I. Horvath, J. Hunt, P.J. Barnes, et al.
Exhaled breath condensate: methodological recommendations and unresolved questions.
Eur Respir J, 26 (2005), pp. 523-548
[66.]
P. Montuschi.
Indirect monitoring of lung inflammation.
Nat Rev Drug Discov, 1 (2002), pp. 238-242
[67.]
K. Kostikas, A. Koutsokera, S. Papiris, K.I. Gourgoulianis, S. Loukides.
Exhaled breath condensate in patients with asthma: implications for application in clinical practice.
Clin Exp Allergy, 38 (2008), pp. 557-565
Copyright © 2009. Sociedade Portuguesa de Pneumologia
Download PDF
Pulmonology
Article options
Tools

Are you a health professional able to prescribe or dispense drugs?