Am. J. Respir. Crit. Care Med., Volume 164, Number 5, September 2001, 749-753

Sputum Induction in Severe Asthma by a Standardized Protocol
Predictors of Excessive Bronchoconstriction

ANNEKE ten BRINKE, CINDY de LANGE, AEILKO H. ZWINDERMAN, KLAUS F. RABE, PETER J. STERK, and ELISABETH H. BEL

Departments of Pulmonary Diseases and Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands

Sputum induction is a noninvasive method to evaluate airway inflammation. We investigated whether it can be safely and successfully performed in patients with severe, difficult-to-control asthma, and whether the patients at risk can be identified. Ninety-three severe asthmatics were included, all symptomatic despite inhaled corticosteroids ( 1,600 µg/d) and long-acting ₂-agonists > 1 yr. Patients with a postbronchodilator FEV₁ < 1 L and < 50% predicted were excluded from participation. Sputum induction was performed according to a strict protocol, using 0.9%, 3.0%, and 4.5% NaCl inhalation. In 74% (CI: 64 to 83%) of patients an adequate sputum sample could be obtained. Twenty-two percent (CI: 14 to 33%) developed excessive bronchoconstriction (decrease in FEV₁ > 15% from baseline) despite the continuing use of long-acting bronchodilators and pretreatment with 400 µg salbutamol. The decrease in FEV₁ was associated with increased use of rescue short-acting ₂-agonists in the previous 2 d (r_s = 0.51, p = 0.002), lower postbronchodilator FEV₁ (r_s = 0.31, p = 0.004), and lower provocative concentration of histamine causing a 20% reduction in FEV₁ (PC₂₀) (r_s = 0.52, p < 0.001). Recent use of short-acting ₂-agonist increased the risk for excessive bronchoconstriction 10.2-fold (CI: 1.2 to 109.8). In conclusion, sputum induction can be safely and successfully performed in patients with severe, difficult-to-control asthma if a standardized protocol is used. However, severe bronchoconstriction may occur despite regular use of long-acting ₂-agonist and pretreatment with salbutamol 400 µg. In particular, patients who have used additional short-acting ₂-agonists as rescue medication during the days preceding the induction, are at high risk.

Keywords: asthma; bronchoconstriction; safety; saline solution, hypertonic; sputum

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