Chest
Volume 119, Issue 5, May 2001, Pages 1329-1336
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Clinical Investigations
ASTHMA
Heterogeneity of Airway Inflammation in Persistent Asthma: Evidence of Neutrophilic Inflammation and Increased Sputum Interleukin-8

https://doi.org/10.1378/chest.119.5.1329Get rights and content

Study objectives:

To identify the characteristics of airway inflammation in persistent asthma and to examine the role of neutrophilic inflammation in noneosinophilic persistent asthma.

Methods:

Nonsmoking adults (n = 56) with persistent asthma and healthy control subjects (n = 8) underwent hypertonic saline solution challenge and sputum induction. Selected sputum portions were dispersed with dithiothreitol and assayed for total cell count, cellular differential, supernatant eosinophil cationic protein (ECP), myeloperoxidase, and interleukin (IL)-8.

Results:

We identified two distinct inflammatory patterns. Typical eosinophilic inflammation occurred in 41% of subjects, whereas the remainder exhibited noneosinophilic asthma (59%). Both neutrophil percentage and absolute neutrophil counts were increased in subjects with noneosinophilic asthma (64%, 283 × 106/mL) compared to eosinophilic asthma (14%, 41 × 106/mL) and control subjects (34%, 49 × 106/mL; p = 0.0001). Myeloperoxidase was elevated in both noneosinophilic (280 ng/mL) and eosinophilic groups (254 ng/mL) compared with control subjects (82 ng/mL; p = 0.002). Sputum IL-8 levels were highest in subjects with noneosinophilic asthma (45 ng/mL) compared to eosinophilic asthma (9.6 ng/mL) and control subjects (3.5 ng/mL; p = 0.0001). Neutrophils correlated with IL-8 levels (r = 0.72). ECP was highest in subjects with eosinophilic asthma (2,685 ng/mL) compared with noneosinophilic asthma (1,081 ng/mL) and control subjects (110 ng/mL; p = 0.0001).

Conclusion:

Induced-sputum analysis in persistent asthma identifies two different inflammatory patterns. The most common pattern is noneosinophilic, associated with a neutrophil influx and activation, which may be mediated by IL-8 secretion. There is heterogeneity of airway inflammation in persistent asthma, which indicates differing mechanisms and may impact on treatment responses.

Section snippets

Subjects

Nonsmoking adults with persistent symptomatic asthma and healthy control subjects were recruited from the Respiratory Outpatient Clinic of the John Hunter Hospital and by advertisement (control subjects). Subjects were identified from a list of consecutive attendances to the respiratory clinic and were assessed for participation in this study. We screened 78 subjects with a diagnosis of asthma receiving high-dose inhaled corticosteroids, and identified 56 subjects who met the inclusion

Results

The 56 subjects with persistent asthma (Table 1) reported a long history of asthma and were receiving high-dose inhaled corticosteroids. Eleven subjects (20%) had mild persistent asthma, 26 subjects (46%) had moderate persistent asthma, and 19 subjects (34%) had severe persistent asthma. The subjects with severe persistent asthma were older with more severe airway obstruction and more severe airway hyperresponsiveness (p < 0.05). The eight control subjects (one male subject) were aged 35 years

Discussion

This study has confirmed that there is heterogeneity of airway inflammation in persistent asthma and identified evidence of neutrophilic inflammation and IL-8 secretion in noneosinophilic asthma. Using induced sputum, we could identify two distinct patterns of airway inflammation. The first pattern was a typical eosinophilic inflammation, where the percentage of eosinophils was increased and there was eosinophil degranulation with elevated ECP. Most subjects, however, had persistent symptoms

ACKNOWLEDGMENT

We thank H. Burgess, K. Fakes, N. Timmins, and A. Wilson for their technical assistance, and G. Sheather for preparation of the article.

References (32)

  • ID Pavord et al.

    Non-eosinophilic corticosteroid unresponsive asthma

    Lancet

    (1999)
  • National Asthma Education and Prevention Program. Expert panel report 2. Guidelines for the diagnosis and management of...
  • SE Wenzel et al.

    Bronchoscopic evaluation of severe asthma: persistent inflammation associated with high dose corticosteroids

    Am J Respir Crit Care Med

    (1997)
  • SE Wenzel et al.

    Evidence that severe asthma can be divided pathologically into two inflammatory subtypes with distinct physiologic and clinical characteristics

    Am J Respir Crit Care Med

    (1999)
  • MO Turner et al.

    Exacerbations of asthma without sputum eosinophilia

    Thorax

    (1995)
  • MZ Norzila et al.

    Interleukin-8 secretion and neutrophil recruitment accompanies induced sputum eosinophil activation in children with acute asthma

    Am J Respir Crit Care Med

    (1999)
  • B Vrugt et al.

    Mucosal inflammation in severe glucocorticoid dependent asthma

    Eur Respir J

    (1999)
  • Y Cai et al.

    Persistence of sputum eosinophilia in children with controlled asthma compared with healthy children

    Eur Respir J

    (1998)
  • I Pin et al.

    Use of induced sputum cell counts to investigate airway inflammation in asthma

    Thorax

    (1992)
  • S Sur et al.

    Sudden-onset fatal asthma: a distinct entity with few eosinophils and relatively more neutrophils in the airway submucosa?

    Am Rev Respir Dis

    (1993)
  • JV Fahy et al.

    Prominent neutrophilic inflammation in sputum from subjects with asthma exacerbation

    J Allergy Clin Immunol

    (1995)
  • SH Twaddell et al.

    Assessment of airway inflammation in children with acute asthma using induced sputum

    Eur Respir J

    (1996)
  • LM Teran et al.

    Role of nasal interleukin-8 in neutrophil recruitment and activation in children with virus-induced asthma

    Am J Respir Crit Care Med

    (1997)
  • RJ Knudson et al.

    The maximum expiratory flow volume curve: normal standards, variability and effects of age

    Am Rev Respir Dis

    (1976)
  • PG Gibson et al.

    Epidemiologic association of airway inflammation with asthma symptoms and airway hyperresponsiveness in childhood

    Am J Respir Crit Care Med

    (1998)
  • KL Woolley et al.

    Eosinophil apoptosis and the resolution of airway inflammation in asthma

    Am J Respir Crit Care Med

    (1996)
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