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Am. J. Respir. Crit. Care Med., Volume 159, Number 4, April 1999, 1043-1051

Clinical Control and Histopathologic Outcome of Asthma when Using Airway Hyperresponsiveness as an Additional Guide to Long-Term Treatment

JACOB K. SONT, LUUK N. A. WILLEMS, ELISABETH H. BEL, J.HAN J. M. van KRIEKEN, JAN P. VANDENBROUCKE, PETER J. STERK, and the AMPUL Study Group

Departments of Pulmonology, Clinical Epidemiology, and Pathology, Leiden University Medical Center; and Asthma Management Project University Leiden (AMPUL) Study Group, Leiden, The Netherlands

According to international guidelines, the level and adjustment of antiinflammatory treatment for asthma are based solely on symptoms and lung function. We investigated whether a treatment strategy aimed at reducing airway hyperresponsiveness (AHR strategy) in addition to the recommendations in the existing guidelines (reference strategy) led to: (1) more effective control of asthma; and (2) greater improvement of chronic airways inflammation. To accomplish this, we conducted a randomized, prospective, parallel trial involving 75 adults with mild to moderate asthma who visited a clinic every 3 mo for 2 yr. At each visit, FEV1 and AHR to methacholine were assessed, and subjects kept diaries of symptoms, beta 2-agonist use, and peak expiratory flow (PEF). Medication with corticosteroids (four levels) was adjusted according to a stepwise approach (reference strategy), to which four severity classes of AHR were added (AHR strategy). At entry and after 2 yr, bronchial biopsies were obtained by fiberoptic bronchoscopy. Patients treated according to the AHR strategy had a 1.8-fold lower rate of mild exacerbations than did patients in the reference strategy group (0.23 and 0.43 exacerbation/yr/patient, respectively). FEV1 also improved to a significantly greater extent in the AHR strategy group (p =< 0.05). In bronchial biopsies this was accompanied by a greater reduction in thickness of the subepithelial reticular layer in the AHR strategy group than in the reference strategy group (mean difference [95% confidence interval (CI): 1.7 µm (0.2 to 3.1) µm]). The changes in AHR in both strategy groups were correlated with eosinophil counts in the biopsies (r = -0.48, p = 0.003). We conclude that reducing AHR in conjunction with optimizing symptoms and lung function leads to more effective control of asthma while alleviating chronic airways inflammation. This implies a role for the monitoring of AHR or other surrogate markers of inflammation in the long-term management of asthma.




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P.J.F.M. Merkus, W. van Pelt, J.C. van Houwelingen, L.E.M. van Essen-Zandvliet, E.J. Duiverman, K.F. Kerrebijn, and P.H. Quanjer
Inhaled corticosteroids and growth of airway function in asthmatic children
Eur. Respir. J., June 1, 2004; 23(6): 861 - 868.
[Abstract] [Full Text] [PDF]

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 ChestHome page
D.-W. Perng, H.-Y. Huang, Y.-C. Lee, and R.-P. Perng
Leukotriene Modifier vs Inhaled Corticosteroid in Mild-to-Moderate Asthma: Clinical and Anti-inflammatory Effects
Chest, May 1, 2004; 125(5): 1693 - 1699.
[Abstract] [Full Text] [PDF]

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 Annals of Clinical & Laboratory ScienceHome page
G. Riccioni, C. Di Ilio, and N. D'Orazio
Pharmacological Treatment of Airway Remodeling: Inhaled Corticosteroids or Antileukotrienes?
Ann. Clin. Lab. Sci., April 1, 2004; 34(2): 138 - 142.
[Abstract] [Full Text] [PDF]

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 Proc Am Thorac SocHome page
D. C. Grootendorst and K. F. Rabe
Mechanisms of Bronchial Hyperreactivity in Asthma and Chronic Obstructive Pulmonary Disease
Proceedings of the ATS, April 1, 2004; 1(2): 77 - 87.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
R. Leigh, R. Ellis, J. N. Wattie, J. A. Hirota, K. I. Matthaei, P. S. Foster, P. M. O'Byrne, and M. D. Inman
Type 2 Cytokines in the Pathogenesis of Sustained Airway Dysfunction and Airway Remodeling in Mice
Am. J. Respir. Crit. Care Med., April 1, 2004; 169(7): 860 - 867.
[Abstract] [Full Text] [PDF]

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 ChestHome page
C. Wubbel, M. J. Asmus, G. Stevens, S. E. Chesrown, and L. Hendeles
Methacholine Challenge Testing*: Comparison of the Two American Thoracic Society-Recommended Methods
Chest, February 1, 2004; 125(2): 453 - 458.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
P. Maestrelli
Natural History of Adult-Onset Asthma: Insights from Model of Occupational Asthma
Am. J. Respir. Crit. Care Med., February 1, 2004; 169(3): 331 - 332.
[Full Text] [PDF]

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 The Annals of PharmacotherapyHome page
J. M Tovar and J. G Gums
Monitoring Pulmonary Function in Asthma and COPD: Point-of-Care Testing
Ann. Pharmacother., January 1, 2004; 38(1): 126 - 133.
[Abstract] [Full Text] [PDF]

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 ChestHome page
G. L. Colice
The Seduction of Asthma Severity Categorization
Chest, December 1, 2003; 124(6): 2054 - 2056.
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 ChestHome page
P.-H. Wang, P.-H. Kuo, C.-L. Hsu, H.-D. Wu, Y.-S. Chang, S.-H. Kuo, and P.-C. Yang
Diagnostic Value of Negative Expiratory Pressure for Airway Hyperreactivity
Chest, November 1, 2003; 124(5): 1762 - 1767.
[Abstract] [Full Text] [PDF]

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 Arch. Dis. Child.Home page
P L P Brand and R J Roorda
Usefulness of monitoring lung function in asthma
Arch. Dis. Child., November 1, 2003; 88(11): 1021 - 1025.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
A. Niimi, H. Matsumoto, M. Takemura, T. Ueda, K. Chin, and M. Mishima
Relationship of Airway Wall Thickness to Airway Sensitivity and Airway Reactivity in Asthma
Am. J. Respir. Crit. Care Med., October 15, 2003; 168(8): 983 - 988.
[Abstract] [Full Text] [PDF]

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 ChestHome page
H. O. Koskela, L. Hyvarinen, J. D. Brannan, H.-K. Chan, and S. D. Anderson
Sensitivity and Validity of Three Bronchial Provocation Tests To Demonstrate the Effect of Inhaled Corticosteroids in Asthma
Chest, October 1, 2003; 124(4): 1341 - 1349.
[Abstract] [Full Text] [PDF]

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 J. Pharmacol. Exp. Ther.Home page
R. K. Kumar, C. Herbert, P. S. Thomas, L. Wollin, R. Beume, M. Yang, D. C. Webb, and P. S. Foster
Inhibition of Inflammation and Remodeling by Roflumilast and Dexamethasone in Murine Chronic Asthma
J. Pharmacol. Exp. Ther., October 1, 2003; 307(1): 349 - 355.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
P. Jeffery, S. Holgate, and S. Wenzel
Methods for the Assessment of Endobronchial Biopsies in Clinical Research: Application to Studies of Pathogenesis and the Effects of Treatment
Am. J. Respir. Crit. Care Med., September 15, 2003; 168(6): S1 - 17.
[Full Text] [PDF]

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 Eur Respir JHome page
T.F. Reiss, J.M. Edelman, and J.F. Heyse
From the Authors
Eur. Respir. J., September 1, 2003; 22(3): 568 - 569.
[Full Text] [PDF]

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 Arch. Dis. Child.Home page
S Panditi and M Silverman
Perception of exercise induced asthma by children and their parents
Arch. Dis. Child., September 1, 2003; 88(9): 807 - 811.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
C. Combescure, P. Chanez, P. Saint-Pierre, J-P. Daures, H. Proudhon, and P. Godard
Assessment of variations in control of asthma over time
Eur. Respir. J., August 1, 2003; 22(2): 298 - 304.
[Abstract] [Full Text] [PDF]

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 ChestHome page
M. Kraft, R. J. Martin, S. C. Lazarus, J. V. Fahy, H. A. Boushey, R. F. Lemanske Jr., and S. J. Szefler
Airway Tissue Mast Cells in Persistent Asthma: Predictor of Treatment Failure When Patients Discontinue Inhaled Corticosteroids
Chest, July 1, 2003; 124(1): 42 - 50.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
G.F. Joos and B. O'Connor
Indirect airway challenges
Eur. Respir. J., June 1, 2003; 21(6): 1050 - 1068.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
J. K. Sont, W. I. de Boer, W. A. A. M. van Schadewijk, K. Grunberg, J. H. J. M. van Krieken, P. S. Hiemstra, and P. J. Sterk
Fully Automated Assessment of Inflammatory Cell Counts and Cytokine Expression in Bronchial Tissue
Am. J. Respir. Crit. Care Med., June 1, 2003; 167(11): 1496 - 1503.
[Abstract] [Full Text] [PDF]

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 ThoraxHome page
A R A Sovijarvi, T Haahtela, H J Ekroos, A Lindqvist, A Saarinen, T Poussa, and L A Laitinen
Sustained reduction in bronchial hyperresponsiveness with inhaled fluticasone propionate within three days in mild asthma: time course after onset and cessation of treatment
Thorax, June 1, 2003; 58(6): 500 - 504.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
S. La Grutta, R. Gagliardo, F. Mirabella, G. B. Pajno, G. Bonsignore, J. Bousquet, V. Bellia, and A. M. Vignola
Clinical and Biological Heterogeneity in Children with Moderate Asthma
Am. J. Respir. Crit. Care Med., June 1, 2003; 167(11): 1490 - 1495.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
G. P. Currie, D. K. C. Lee, K. Haggart, C. E. Bates, and B. J. Lipworth
Effects of Montelukast on Surrogate Inflammatory Markers in Corticosteroid-treated Patients with Asthma
Am. J. Respir. Crit. Care Med., May 1, 2003; 167(9): 1232 - 1238.
[Abstract] [Full Text] [PDF]

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 ThoraxHome page
D B Price, D Hernandez, P Magyar, J Fiterman, K M Beeh, I G James, S Konstantopoulos, R Rojas, J A van Noord, M Pons, et al.
Randomised controlled trial of montelukast plus inhaled budesonide versus double dose inhaled budesonide in adult patients with asthma
Thorax, March 1, 2003; 58(3): 211 - 216.
[Abstract] [Full Text] [PDF]

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 ThoraxHome page
G. Strube, C Ward, D Reid, and E H Walters
Revision of BTS guidelines for treatment of asthma
Thorax, March 1, 2003; 58(3): 280 - 280.
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 Am. J. Respir. Crit. Care Med.Home page
A. Chetta, A. Zanini, A. Foresi, M. Del Donno, A. Castagnaro, R. D'Ippolito, S. Baraldo, R. Testi, M. Saetta, and D. Olivieri
Vascular Component of Airway Remodeling in Asthma Is Reduced by High Dose of Fluticasone
Am. J. Respir. Crit. Care Med., March 1, 2003; 167(5): 751 - 757.
[Abstract] [Full Text] [PDF]


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