Am. J. Respir. Crit. Care Med., Volume 161, Number 4, April 2000, 1185-1190

Increased Neutrophil Numbers and IL-8 Levels in Airway Secretions in Acute Severe Asthma
Clinical and Biologic Significance

CLAUDIA L. ORDOÑEZ, THOMAS E. SHAUGHNESSY, MICHAEL A. MATTHAY, and JOHN V. FAHY

The Departments of Pediatrics, Medicine, Anesthesia, and the Cardiovascular Research Institute, University of California, San Francisco, California

The inflammatory events in the airways at the time of acute respiratory failure from acute severe asthma are poorly understood. To determine the patterns of cellular inflammation in the airways in acute severe asthma, we analyzed tracheal aspirates collected within 12 h of intubation from patients intubated emergently for acute severe asthma (n = 10) and from patients intubated electively for nonpulmonary surgery (n = 14). The number of neutrophils in tracheal aspirates from asthma patients was 10 times higher than normal (4.2 [0.6 to 335.0] [median, range] versus 0.4 [0.009 to 9.4] × 10⁶/ml, p = 0.001), and there was a strong trend for a positive relationship between neutrophil number and duration of intubation (r_s = 0.64, p = 0.06). Although eosinophil numbers were also significantly higher than normal (0.5 [0.0 to 23.3] versus 0.0 [0.0 to 0.1] × 10⁶/ml, p = 0.003), the numbers of eosinophils were 8-fold less than neutrophils, and there was no significant correlation between eosinophil number and duration of intubation (r_s = 0.4, p = 0.26). Interleukin-8 (IL-8), a chemoattraction for neutrophils, was 19 times higher than normal in tracheal aspirates from asthmatic patients (75.0 [9.0 to 168.0] versus 4.0 [0.08 to 24.0] ng/ml, p < 0.05) and correlated significantly with the neutrophil number (r_s = 0.77, p = 0.03). Furthermore, the IL-8 levels correlated positively with the duration of mechanical ventilation (r_s = 0.74, p = 0.03). Surprisingly, the number of neutrophils increased significantly during the period of intubation in the asthmatic subjects, possibly because of intravenous corticosteroid treatment. We conclude that neutrophils are the dominant inflammatory leukocyte characterizing airway inflammation in acute severe asthma that requires mechanical ventilation, and that IL-8 is an important mediator of this neutrophilia.

This article has been cited by other articles:

				J. V. Fahy Eosinophilic and Neutrophilic Inflammation in Asthma: Insights from Clinical Studies Proceedings of the ATS, May 1, 2009; 6(3): 256 - 259. [Abstract] [Full Text] [PDF]

				R. S. Zaheer, R. Koetzler, N. S. Holden, S. Wiehler, and D. Proud Selective Transcriptional Down-Regulation of Human Rhinovirus-Induced Production of CXCL10 from Airway Epithelial Cells via the MEK1 Pathway J. Immunol., April 15, 2009; 182(8): 4854 - 4864. [Abstract] [Full Text] [PDF]

				P-R. Burgel and J. A. Nadel Epidermal growth factor receptor-mediated innate immune responses and their roles in airway diseases Eur. Respir. J., October 1, 2008; 32(4): 1068 - 1081. [Abstract] [Full Text] [PDF]

				S. Ying, B. O'Connor, J. Ratoff, Q. Meng, C. Fang, D. Cousins, G. Zhang, S. Gu, Z. Gao, B. Shamji, et al. Expression and Cellular Provenance of Thymic Stromal Lymphopoietin and Chemokines in Patients with Severe Asthma and Chronic Obstructive Pulmonary Disease J. Immunol., August 15, 2008; 181(4): 2790 - 2798. [Abstract] [Full Text] [PDF]

				M. Swee, C. L. Wilson, Y. Wang, J. K. McGuire, and W. C. Parks Matrix metalloproteinase-7 (matrilysin) controls neutrophil egress by generating chemokine gradients J. Leukoc. Biol., June 1, 2008; 83(6): 1404 - 1412. [Abstract] [Full Text] [PDF]

				D. C. Newcomb, U. S. Sajjan, D. R. Nagarkar, Q. Wang, S. Nanua, Y. Zhou, C. L. McHenry, K. T. Hennrick, W. C. Tsai, J. K. Bentley, et al. Human Rhinovirus 1B Exposure Induces Phosphatidylinositol 3-Kinase-dependent Airway Inflammation in Mice Am. J. Respir. Crit. Care Med., May 15, 2008; 177(10): 1111 - 1121. [Abstract] [Full Text] [PDF]

				K. A. Brant and J. P. Fabisiak Nickel Alterations of TLR2-Dependent Chemokine Profiles in Lung Fibroblasts Are Mediated by COX-2 Am. J. Respir. Cell Mol. Biol., May 1, 2008; 38(5): 591 - 599. [Abstract] [Full Text] [PDF]

				K. Page, K. M. Lierl, V. S. Hughes, P. Zhou, J. R. Ledford, and M. Wills-Karp TLR2-Mediated Activation of Neutrophils in Response to German Cockroach Frass J. Immunol., May 1, 2008; 180(9): 6317 - 6324. [Abstract] [Full Text] [PDF]

				A. M. Akk, P. M. Simmons, H. W. Chan, E. Agapov, M. J. Holtzman, M. H. Grayson, and C. T. N. Pham Dipeptidyl Peptidase I-Dependent Neutrophil Recruitment Modulates the Inflammatory Response to Sendai Virus Infection J. Immunol., March 1, 2008; 180(5): 3535 - 3542. [Abstract] [Full Text] [PDF]

				C. Thompson, A. Cloutier, Y. Bosse, C. Poisson, P. Larivee, P. P. McDonald, J. Stankova, and M. Rola-Pleszczynski Signaling by the Cysteinyl-Leukotriene Receptor 2: INVOLVEMENT IN CHEMOKINE GENE TRANSCRIPTION J. Biol. Chem., January 25, 2008; 283(4): 1974 - 1984. [Abstract] [Full Text] [PDF]

				S. Wiehler and D. Proud Interleukin-17A modulates human airway epithelial responses to human rhinovirus infection Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L505 - L515. [Abstract] [Full Text] [PDF]

				K. Maneechotesuwan, S. Essilfie-Quaye, S. A. Kharitonov, I. M. Adcock, and P. J. Barnes Loss of Control of Asthma Following Inhaled Corticosteroid Withdrawal Is Associated With Increased Sputum Interleukin-8 and Neutrophils Chest, July 1, 2007; 132(1): 98 - 105. [Abstract] [Full Text] [PDF]

				Y. Qiu, J. Zhu, V. Bandi, K. K Guntupalli, and P. K Jeffery Bronchial mucosal inflammation and upregulation of CXC chemoattractants and receptors in severe exacerbations of asthma Thorax, June 1, 2007; 62(6): 475 - 482. [Abstract] [Full Text] [PDF]

				H. Huang, A. Lavoie-Lamoureux, K. Moran, and J.-P. Lavoie IL-4 stimulates the expression of CXCL-8, E-selectin, VEGF, and inducible nitric oxide synthase mRNA by equine pulmonary artery endothelial cells Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1147 - L1154. [Abstract] [Full Text] [PDF]

				J. L Simpson, T. V Grissell, J. Douwes, R. J Scott, M. J Boyle, and P. G Gibson Innate immune activation in neutrophilic asthma and bronchiectasis Thorax, March 1, 2007; 62(3): 211 - 218. [Abstract] [Full Text] [PDF]

				A. S. Saffar, M. P. Alphonse, L. Shan, K. T. HayGlass, F. E. R. Simons, and A. S. Gounni IgE Modulates Neutrophil Survival in Asthma: Role of Mitochondrial Pathway J. Immunol., February 15, 2007; 178(4): 2535 - 2541. [Abstract] [Full Text] [PDF]

				J. K. Bentley, D. C. Newcomb, A. M. Goldsmith, Y. Jia, U. S. Sajjan, and M. B. Hershenson Rhinovirus Activates Interleukin-8 Expression via a Src/p110{beta} Phosphatidylinositol 3-Kinase/Akt Pathway in Human Airway Epithelial Cells J. Virol., February 1, 2007; 81(3): 1186 - 1194. [Abstract] [Full Text] [PDF]

				C. Thompson, A. Cloutier, Y. Bosse, M. Thivierge, C. L. Gouill, P. Larivee, P. P. McDonald, J. Stankova, and M. Rola-Pleszczynski CysLT1 Receptor Engagement Induces Activator Protein-1- and NF-{kappa}B-Dependent IL-8 Expression Am. J. Respir. Cell Mol. Biol., December 1, 2006; 35(6): 697 - 704. [Abstract] [Full Text] [PDF]

				C M McDougall and P J Helms Neutrophil airway inflammation in childhood asthma Thorax, September 1, 2006; 61(9): 739 - 741. [Full Text] [PDF]

				G. Paone, L. A. Stevens, R. L. Levine, C. Bourgeois, W. K. Steagall, B. R. Gochuico, and J. Moss ADP-ribosyltransferase-specific Modification of Human Neutrophil Peptide-1 J. Biol. Chem., June 23, 2006; 281(25): 17054 - 17060. [Abstract] [Full Text] [PDF]

				M. Tsoumakidou, E. Papadopouli, N. Tzanakis, and N. M. Siafakas Airway Inflammation and Cellular Stress in Noneosinophilic Atopic Asthma Chest, May 1, 2006; 129(5): 1194 - 1202. [Abstract] [Full Text] [PDF]

				S. J. Park, M. T. Wiekowski, S. A. Lira, and B. Mehrad Neutrophils Regulate Airway Responses in a Model of Fungal Allergic Airways Disease J. Immunol., February 15, 2006; 176(4): 2538 - 2545. [Abstract] [Full Text] [PDF]

				M. C. Rose and J. A. Voynow Respiratory Tract Mucin Genes and Mucin Glycoproteins in Health and Disease Physiol Rev, January 1, 2006; 86(1): 245 - 278. [Abstract] [Full Text] [PDF]

				S. Chakrabarti, J. M. Zee, and K. D. Patel Regulation of matrix metalloproteinase-9 (MMP-9) in TNF-stimulated neutrophils: novel pathways for tertiary granule release J. Leukoc. Biol., January 1, 2006; 79(1): 214 - 222. [Abstract] [Full Text] [PDF]

				D. C. Newcomb, U. Sajjan, S. Nanua, Y. Jia, A. M. Goldsmith, J. K. Bentley, and M. B. Hershenson Phosphatidylinositol 3-Kinase Is Required for Rhinovirus-induced Airway Epithelial Cell Interleukin-8 Expression J. Biol. Chem., November 4, 2005; 280(44): 36952 - 36961. [Abstract] [Full Text] [PDF]

				K. Maneechotesuwan, S. Essilfie-Quaye, S. Meah, C. Kelly, S. A. Kharitonov, I. M. Adcock, and P. J. Barnes Formoterol Attenuates Neutrophilic Airway Inflammation in Asthma Chest, October 1, 2005; 128(4): 1936 - 1942. [Abstract] [Full Text] [PDF]

				B. D. Levy, C. Bonnans, E. S. Silverman, L. J. Palmer, G. Marigowda, E. Israel, and for the Severe Asthma Research Program, National H Diminished Lipoxin Biosynthesis in Severe Asthma Am. J. Respir. Crit. Care Med., October 1, 2005; 172(7): 824 - 830. [Abstract] [Full Text] [PDF]

				M. Arjomandi, A. Witten, E. Abbritti, K. Reintjes, I. Schmidlin, W. Zhai, C. Solomon, and J. Balmes Repeated Exposure to Ozone Increases Alveolar Macrophage Recruitment into Asthmatic Airways Am. J. Respir. Crit. Care Med., August 15, 2005; 172(4): 427 - 432. [Abstract] [Full Text] [PDF]

				A V Kamath, I D Pavord, P R Ruparelia, and E R Chilvers Is the neutrophil the key effector cell in severe asthma? Thorax, July 1, 2005; 60(7): 529 - 530. [Full Text] [PDF]

				A. Linden, M. Laan, and G. P. Anderson Neutrophils, interleukin-17A and lung disease Eur. Respir. J., January 1, 2005; 25(1): 159 - 172. [Abstract] [Full Text] [PDF]

				H. Hata, T. Yoshimoto, N. Hayashi, T. Hada, and K. Nakanishi IL-18 together with anti-CD3 antibody induces human Th1 cells to produce Th1- and Th2-cytokines and IL-8 Int. Immunol., December 1, 2004; 16(12): 1733 - 1739. [Abstract] [Full Text] [PDF]

				J. A. Voynow, B. M. Fischer, D. E. Malarkey, L. H. Burch, T. Wong, M. Longphre, S. B. Ho, and W. M. Foster Neutrophil elastase induces mucus cell metaplasia in mouse lung Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1293 - L1302. [Abstract] [Full Text] [PDF]

				J. L. Booth, K. M. Coggeshall, B. E. Gordon, and J. P. Metcalf Adenovirus Type 7 Induces Interleukin-8 in a Lung Slice Model and Requires Activation of Erk J. Virol., April 15, 2004; 78(8): 4156 - 4164. [Abstract] [Full Text] [PDF]

				A. Pastva, K. Estell, T. R. Schoeb, T. P. Atkinson, and L. M. Schwiebert Aerobic Exercise Attenuates Airway Inflammatory Responses in a Mouse Model of Atopic Asthma J. Immunol., April 1, 2004; 172(7): 4520 - 4526. [Abstract] [Full Text] [PDF]

				M. Kawaguchi, F. Kokubu, S. Matsukura, K. Ieki, M. Odaka, S. Watanabe, S. Suzuki, M. Adachi, and S.-K. Huang Induction of C-X-C Chemokines, Growth-Related Oncogene {alpha} Expression, and Epithelial Cell-Derived Neutrophil-Activating Protein-78 by ML-1 (Interleukin-17F) Involves Activation of Raf1-Mitogen-Activated Protein Kinase Kinase-Extracellular Signal-Regulated Kinase 1/2 Pathway J. Pharmacol. Exp. Ther., December 1, 2003; 307(3): 1213 - 1220. [Abstract] [Full Text] [PDF]

				K. Yasui, H. Kanda, T. Iwanami, and A. Komiyama Increased serum concentration of urinary trypsin inhibitor with asthma exacerbation Eur. Respir. J., November 1, 2003; 22(5): 739 - 742. [Abstract] [Full Text] [PDF]

				Y. Qiu, J. Zhu, V. Bandi, R. L. Atmar, K. Hattotuwa, K. K. Guntupalli, and P. K. Jeffery Biopsy Neutrophilia, Neutrophil Chemokine and Receptor Gene Expression in Severe Exacerbations of Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., October 15, 2003; 168(8): 968 - 975. [Abstract] [Full Text] [PDF]

				E. R. McFadden Jr. Acute Severe Asthma Am. J. Respir. Crit. Care Med., October 1, 2003; 168(7): 740 - 759. [Abstract] [Full Text] [PDF]

				A. Brown, K. Farmer, L. MacDonald, N. Kalsheker, D. Pritchard, C. Haslett, J. Lamb, and J.-M. Sallenave House Dust Mite Der p 1 Downregulates Defenses of the Lung by Inactivating Elastase Inhibitors Am. J. Respir. Cell Mol. Biol., September 1, 2003; 29(3): 381 - 389. [Abstract] [Full Text] [PDF]

				J. Gabrijelcic, A. Acuna, M. Profita, A. Paterno, K.F. Chung, A.M. Vignola, and R. Rodriguez-Roisin Neutrophil airway influx by platelet-activating factor in asthma: role of adhesion molecules and LTB4 expression Eur. Respir. J., August 1, 2003; 22(2): 290 - 297. [Abstract] [Full Text] [PDF]

				J.R. Gordon, V.A. Swystun, F. Li, X. Zhang, B.E. Davis, P. Hull, and D.W. Cockcroft Regular salbutamol use increases CXCL8 responses in asthma: relationship to the eosinophil response Eur. Respir. J., July 1, 2003; 22(1): 118 - 126. [Abstract] [Full Text] [PDF]

				G. S. Whitehead, J. K. L. Walker, K. G. Berman, W. M. Foster, and D. A. Schwartz Allergen-induced airway disease is mouse strain dependent Am J Physiol Lung Cell Mol Physiol, July 1, 2003; 285(1): L32 - L42. [Abstract] [Full Text] [PDF]

				M. Miyamoto, O. Prause, M. Sjostrand, M. Laan, J. Lotvall, and A. Linden Endogenous IL-17 as a Mediator of Neutrophil Recruitment Caused by Endotoxin Exposure in Mouse Airways J. Immunol., May 1, 2003; 170(9): 4665 - 4672. [Abstract] [Full Text] [PDF]

				L. F. Flores-Suarez, J. Cabiedes, A. R. Villa, F. J. van der Woude, and J. Alcocer-Varela Prevalence of antineutrophil cytoplasmic autoantibodies in patients with tuberculosis Rheumatology, February 1, 2003; 42(2): 223 - 229. [Abstract] [Full Text] [PDF]

				P. W. Hellings, A. Kasran, Z. Liu, P. Vandekerckhove, A. Wuyts, L. Overbergh, C. Mathieu, and J. L. Ceuppens Interleukin-17 Orchestrates the Granulocyte Influx into Airways after Allergen Inhalation in a Mouse Model of Allergic Asthma Am. J. Respir. Cell Mol. Biol., January 1, 2003; 28(1): 42 - 50. [Abstract] [Full Text] [PDF]

				R A O'Donnell and A J Frew Is there more than one inflammatory phenotype in asthma? Thorax, July 1, 2002; 57(7): 566 - 568. [Full Text] [PDF]

				J Douwes, P Gibson, J Pekkanen, and N Pearce Non-eosinophilic asthma: importance and possible mechanisms Thorax, July 1, 2002; 57(7): 643 - 648. [Abstract] [Full Text] [PDF]

				C. E. Jones and K. Chan Interleukin-17 Stimulates the Expression of Interleukin-8, Growth-Related Oncogene-alpha , and Granulocyte-Colony-Stimulating Factor by Human Airway Epithelial Cells Am. J. Respir. Cell Mol. Biol., June 1, 2002; 26(6): 748 - 753. [Abstract] [Full Text] [PDF]

				C. A. Pettersen and K. B. Adler Airways Inflammation and COPD* : Epithelial-Neutrophil Interactions Chest, May 1, 2002; 121(5_suppl): 142S - 150S. [Abstract] [Full Text] [PDF]

				M. Laan, L. Palmberg, K. Larsson, and A. Linden Free, soluble interleukin-17 protein during severe inflammation in human airways Eur. Respir. J., March 1, 2002; 19(3): 534 - 537. [Abstract] [Full Text] [PDF]

				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]

				M. J. TOBIN Asthma, Airway Biology, and Allergic Rhinitis in AJRCCM 2000 Am. J. Respir. Crit. Care Med., November 1, 2001; 164(9): 1559 - 1580. [Full Text] [PDF]

				J.-P. LAVOIE, K. MAGHNI, M. DESNOYERS, R. TAHA, J. G. MARTIN, and Q. A. HAMID Neutrophilic Airway Inflammation in Horses with Heaves Is Characterized by a Th2-type Cytokine Profile Am. J. Respir. Crit. Care Med., October 15, 2001; 164(8): 1410 - 1413. [Abstract] [Full Text] [PDF]

				D. D'AMBROSIO, M. MARIANI, P. PANINA-BORDIGNON, and F. SINIGAGLIA Chemokines and Their Receptors Guiding T Lymphocyte Recruitment in Lung Inflammation Am. J. Respir. Crit. Care Med., October 1, 2001; 164(7): 1266 - 1275. [Full Text] [PDF]

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

				J. A. Wilder, D. S. Collie, D. E. Bice, Y. Tesfaigzi, C. R. Lyons, and M. F. Lipscomb Ovalbumin aerosols induce airway hyperreactivity in naive DO11.10 T cell receptor transgenic mice without pulmonary eosinophilia or OVA-specific antibody J. Leukoc. Biol., April 1, 2001; 69(4): 538 - 547. [Abstract] [Full Text]

				N. E. Alexis, J. Soukup, S. Nierkens, and S. Becker Association between airway hyperreactivity and bronchial macrophage dysfunction in individuals with mild asthma Am J Physiol Lung Cell Mol Physiol, February 1, 2001; 280(2): L369 - L375. [Abstract] [Full Text] [PDF]

				P.A.B. Wark, S.L. Johnston, I. Moric, J.L. Simpson, M.J. Hensley, and P.G. Gibson Neutrophil degranulation and cell lysis is associated with clinical severity in virus-induced asthma Eur. Respir. J., January 1, 2001; 19(1): 68 - 75. [Abstract] [Full Text] [PDF]