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Am. J. Respir. Crit. Care Med., Volume 160, Number 5, November 1999, 1532-1539

Neutrophilic Inflammation in Severe Persistent Asthma

ANON JATAKANON, CARINA UASUF, WAZIM MAZIAK, SAM LIM, KIAN FAN CHUNG, and PETER J. BARNES

Department of Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom

Airway inflammation in severe asthma is not well characterized but may involve neutrophils. We have compared induced sputum profiles in patients with asthma of varying severity and normal control subjects. We have also measured exhaled nitric oxide (NO) as a noninvasive marker of inflammation. Asthma severity was based on clinical features before treatment and the minimum medication required to maintain asthma control at the time of sputum induction, and classified as (1) mild: treated with inhaled beta 2-agonist occasionally (n = 23; FEV1, 91%; peak expiratory flow (PEF) variability, 10.5%), (2) moderate: requiring medium dose inhaled steroids to maintain control (n = 16; FEV1, 88%; PEF variability, 9.1%), and (3) severe: despite using inhaled and oral steroids (n = 16; FEV1, 61%; PEF variability, 36.2%). The asthmatic patients were nonsmokers with evidence of airway hyperresponsiveness or reversible airway obstruction, and free of respiratory tract infection for at least 6 wk. Sputum revealed significantly increased neutrophil numbers in severe asthma (53.0 [38.4- 73.5]%, p < 0.05) compared with mild asthma (35.4 [29.8-46.1]%) and normal control subjects (27.7 [20.6-42.2]%). Interleukin-8 (IL-8) and neutrophil myeloperoxidase (MPO) levels were increased in asthmatic patients, with the highest levels in severe asthma. Eosinophil numbers were increased in both mild and severe asthma, but interleukin-5 (IL-5) levels were highest in mild asthma, whereas eosinophil cationic protein (ECP) levels were highest in severe asthma. Exhaled NO levels were highest in asthmatic untreated with corticosteroids, but there was no significant difference between asthmatics using corticosteroids (Groups 2 and 3), regardless of clinical asthma severity. This confirms the role of eosinophils in asthma but suggests a potential role of neutrophils in more severe asthma. Jatakanon A, Uasuf C, Maziak W, Lim S, Chung KF, Barnes PJ. Neutrophilic inflammation in severe persistent asthma.




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Thorax, July 1, 2002; 57(7): 643 - 648.
[Abstract] [Full Text] [PDF]

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C. Bonnans, I. Vachier, C. Chavis, P. Godard, J. Bousquet, and P. Chanez
Lipoxins Are Potential Endogenous Antiinflammatory Mediators in Asthma
Am. J. Respir. Crit. Care Med., June 1, 2002; 165(11): 1531 - 1535.
[Abstract] [Full Text] [PDF]

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A.A. Acuna, J. Gabrijelcic, E.M. Uribe, R. Rabinovich, J. Roca, J.A. Barbera, K.F. Chung, and R. Rodriguez-Roisin
Fluticasone propionate attenuates platelet-activating factor-induced gas exchange defects in mild asthma
Eur. Respir. J., May 1, 2002; 19(5): 872 - 878.
[Abstract] [Full Text] [PDF]

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W Anees, V Huggins, I D Pavord, A S Robertson, and P S Burge
Occupational asthma due to low molecular weight agents: eosinophilic and non-eosinophilic variants
Thorax, March 1, 2002; 57(3): 231 - 236.
[Abstract] [Full Text] [PDF]

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S A Little, M W Sproule, M D Cowan, K J Macleod, M Robertson, J G Love, G W Chalmers, C P McSharry, and N C Thomson
High resolution computed tomographic assessment of airway wall thickness in chronic asthma: reproducibility and relationship with lung function and severity
Thorax, March 1, 2002; 57(3): 247 - 253.
[Abstract] [Full Text] [PDF]

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J. M. Schuh, K. Blease, and C. M. Hogaboam
CXCR2 Is Necessary for the Development and Persistence of Chronic Fungal Asthma in Mice
J. Immunol., February 1, 2002; 168(3): 1447 - 1456.
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L. Michalec, B. K. Choudhury, E. Postlethwait, J. S. Wild, R. Alam, M. Lett-Brown, and S. Sur
CCL7 and CXCL10 Orchestrate Oxidative Stress-Induced Neutrophilic Lung Inflammation
J. Immunol., January 15, 2002; 168(2): 846 - 852.
[Abstract] [Full Text] [PDF]

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J.C. Kips
Cytokines in asthma
Eur. Respir. J., July 2, 2001; 18(34_suppl): 24S - 33s.
[Abstract] [Full Text] [PDF]

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K.F. Chung
Cytokines in chronic obstructive pulmonary disease
Eur. Respir. J., July 2, 2001; 18(34_suppl): 50S - 59s.
[Abstract] [Full Text] [PDF]

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P.J. Barnes
Cytokine modulators as novel therapies for airway disease
Eur. Respir. J., July 2, 2001; 18(34_suppl): 67S - 77s.
[Abstract] [Full Text] [PDF]

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S. A. KHARITONOV and P. J. BARNES
Exhaled Markers of Pulmonary Disease
Am. J. Respir. Crit. Care Med., June 1, 2001; 163(7): 1693 - 1722.
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D N R Payne, N M Wilson, A James, H Hablas, C Agrafioti, and A Bush
Evidence for different subgroups of difficult asthma in children
Thorax, May 1, 2001; 56(5): 345 - 350.
[Abstract] [Full Text]

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I. Strickland, K. Kisich, P. J. Hauk, A. Vottero, G. P. Chrousos, D. J. Klemm, and D. Y.M. Leung
High Constitutive Glucocorticoid Receptor {beta} in Human Neutrophils Enables Them to Reduce Their Spontaneous Rate of Cell Death in Response to Corticosteroids
J. Exp. Med., February 26, 2001; 193(5): 585 - 594.
[Abstract] [Full Text] [PDF]

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H. Gong Jr., W. S. Linn, S. L. Terrell, K. R. Anderson, and K. W. Clark
Anti-inflammatory and Lung Function Effects of Montelukast in Asthmatic Volunteers Exposed to Sulfur Dioxide
Chest, February 1, 2001; 119(2): 402 - 408.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
S. Wenzel
Proceedings of the ATS Workshop on Refractory Asthma . Current Understanding, Recommendations, and Unanswered Questions
Am. J. Respir. Crit. Care Med., December 1, 2000; 162(6): 2341 - 2351.
[Full Text]

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T. HANAZAWA, S. A. KHARITONOV, and P. J. BARNES
Increased Nitrotyrosine in Exhaled Breath Condensate of Patients with Asthma
Am. J. Respir. Crit. Care Med., October 1, 2000; 162(4): 1273 - 1276.
[Abstract] [Full Text] [PDF]

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E. A. BECKY KELLY, W. W. BUSSE, and N. N. JARJOUR
Increased Matrix Metalloproteinase-9 in the Airway after Allergen Challenge
Am. J. Respir. Crit. Care Med., September 1, 2000; 162(3): 1157 - 1161.
[Abstract] [Full Text]

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R. GAGLIARDO, P. CHANEZ, A. M. VIGNOLA, J. BOUSQUET, I. VACHIER, P. GODARD, G. BONSIGNORE, P. DEMOLY, and M. MATHIEU
Glucocorticoid Receptor alpha and beta in Glucocorticoid Dependent Asthma
Am. J. Respir. Crit. Care Med., July 1, 2000; 162(1): 7 - 13.
[Abstract] [Full Text]


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