Asthma, Rhinitis, Other Respiratory Diseases
Relationship between airway inflammation, hyperresponsiveness, and obstruction in asthma☆,☆☆

https://doi.org/10.1067/mai.2001.119411Get rights and content

Abstract

Background: Although the role of eosinophils in airway inflammation in chronic asthma has been extensively studied, a role for neutrophils has not been well characterized. Furthermore, prior studies have not systematically sought or controlled for factors that might confound the relationship between cellular markers of inflammation and physiologic measures of airway function. Objective: The purpose of this study was to determine whether eosinophilic and neutrophilic inflammation independently contribute to abnormalities of airway function in asthma. Methods: Multivariate analysis of data collected during screening and enrollment of 205 asthmatic adults for clinical trials was conducted to examine the relationships between cellular inflammation in induced sputum and FEV1 and methacholine responsiveness (PC20) while confounding factors were controlled for. Results: We found that age, sex, ethnicity, and use of inhaled corticosteroids were important confounding factors of the relationship between cellular inflammation and airway function. When these factors were controlled for, multivariate analysis showed that eosinophil percentage in induced sputum is independently associated with lower FEV1 and lower PC20 (P = .005 and P = .005, respectively). In the same models, increased sputum neutrophil percentage is independently associated with lower FEV1 (P = .038) but not with PC20 (P = .49). Conclusions: These results suggest that both eosinophilic inflammation and neutrophilic inflammation independently contribute to abnormalities of FEV1 in asthma. Therapies directed specifically at control of neutrophilic inflammation might be useful in improving airway caliber in patients with chronic asthma. (J Allergy Clin Immunol 2001;108:753-8.)

Section snippets

Subjects

Data had been entered into a database (Filemaker Pro 3.0, Filemaker Inc, Santa Clara, Calif) on 205 nonsmoking subjects with stable asthma who had undergone standardized 12-minute sputum induction, spirometry, and methacholine challenge during enrollment in outpatient asthma studies performed during the past 5 years at the Asthma Research Center at the University of California, San Francisco. The subject population comprised all individuals with asthma who participated in outpatient clinical

Patient characteristics

A total of 205 subjects for whom spirometry, methacholine challenge, and sputum data were available were identified (Table I).

. Characteristics of the 205 subjects with asthma

CharacteristicValue*
Age (y): mean ± SD33.0 ± 9.1
Sex: female114 (56%)
Ethnicity
 White140 (68%)
 African American25 (12%)
 Hispanic18 (9%)
 Other22 (11%)
On inhaled corticosteroids83 (40%)
Percent of predicted FEV1
 <60%17 (8%)
 61% to 80%76 (37%)
 >80%112 (55%)
PC20: median (interquartile range)0.41 (0.18, 1.05)
*Presented as number (percent)

Discussion

Our multivariate models suggest that both eosinophilic inflammation and neutrophilic inflammation in sputum are independently associated with degree of chronic airway obstruction, as measured by FEV1. With regard to bronchial hyperreactivity, sputum eosinophilia shows a relationship with PC20 whereas sputum neutrophilia does not. The finding that sputum neutrophilia relates to FEV1 but not to PC20 was surprising. Although the mechanisms governing chronic airway narrowing and chronic airway

Acknowledgements

We thank Hofer Wong, Martha Birch, Theresa Ward, Lisa Musumeci, Elika Rad, and Jack Covington for coordination of patient enrollment and Jane Liu for her expertise in the cytologic analysis of induced sputum.

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    ☆

    Financial support: Dr Woodruff is supported by the NIH Multidisciplinary Training Program in Lung Disease HL-07185 and Dr Fahy by RO1 HL-61662. Subjects were initially recruited during studies supported by the NHLBI ACRN U10 HL-51823, NR-03995, and SCOR/PPG P01 HL-56385 and during studies supported by Novartis, Boehringer-Ingelheim, Texas Biotechnology, and Pharmacia & Upjohn.

    ☆☆

    Reprint requests: John V. Fahy, MD, Box 0130, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143.

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