When interpreting spirometric results, many factors are related to the methods selected by the laboratory to assess bronchodilator response including drug, dosage, and method of delivery.

BlonshineSpirometry remains the primary pulmonary function test used to assess respiratory dysfunction. The National Asthma Education and Prevention Program recommends spirometry pre- and post-administration of a bronchodilator in the assessment of patients with asthma. This article will review testing principles associated with evaluating a response to a bronchodilator and the interpretation of the spirometric results. Although multiple variables may impact the test results, many factors are related to the methods selected by the laboratory to assess bronchodilator response. n The American Thoracic Society (ATS)1 and the American Association for Respiratory Care (AARC)2 have published documents that outline recommendations for standardization. The primary factors to standardize are drug, dosage, and method of delivery. Each of these should be documented on the final report.

The most common assessment is evaluating the response to b-adrenergics. Pulmonary function changes in response to other medications may also be assessed by spirometry. It is common to use spirometry in clinical studies to evaluate the response to new medications prior to release by the Food and Drug Administration. It may be necessary to withhold bronchodilators prior to testing. If so, standard withholding times have been outlined by the ATS.1

Medication Delivery
The method selected for delivery of the drug is an important consideration. The method of administering the medication may have a profound effect on the results. The purpose of the testing is to assess a response to a medication and not delivery methods. The two methods generally selected are meter-dose inhaler (MDI) or small volume nebulizer (SVN). To maximize lung deposition of medications delivered with MDIs, a holding chamber is recommended. Other methods of delivery may be selected for specific medications or clinical research.

Medication Dosage
Uniform consensus on the dose of the bronchodilator to use in testing has not been reached. The specific bronchodilator selected and dosing may also be dependent on the clinical question asked of the test. A 2001 study attempted to determine the dose of inhaled terbutaline that could safely achieve the greatest number of positive tests in patients with chronic obstructive pulmonary disease (COPD).3 In a prospective study, 150 patients with stable COPD were tested pre- and post-administration of terbutaline. The mean age of the participants was 67.4 years with a mean forced expiratory volume in the first second (FEV1) of 1.14 L or 41% of the predicted value. Three consecutive doses of 500 mg of inhaled terbutaline were administered with spirometry performed after each one. The authors concluded that the higher dose of terbutaline (1,500 mg) was more useful in identifying patients with a significant degree of reversibility and was well tolerated. Another study4 has evaluated the response to ipratropium bromide (IB) in patients with COPD who did not respond to inhaled terbutaline. Sixty patients with stable COPD who showed a negative response after inhaling 1,500 mg of terbutaline were studied. The patients were randomly assigned to placebo or 200 mg of IB. Spirometric studies were completed at 30- and 60-minute postadministration. The authors concluded that the response to IB was positive with high doses in more than half of the COPD patients who did not respond to terbutaline. This study continues to reinforce that the specific medication and dose delivered impact the bronchodilator response. As many as 20% to 30% of patients will be positive to one agent and not another.

Post-testing should occur in a time frame that matches the onset of action to peak effect for the bronchodilator delivered. In most cases, short-acting b-agonists are delivered with a short interval required prior to post-testing. The AARC document2 recommends a minimum of 15 minutes.

Interpreting Test Results
Multiple factors impact the response to a bronchodilator. Some patients will respond to one type of bronchodilator, but not to another. The response may also be variable at different testing sessions to the same type of medication. The lack of response to a specific bronchodilator in one testing session does not preclude the use of bronchodilators or anti-inflammatory agents. Treating patients with a bronchodilator is a clinical decision.

Interpretation is based on both an absolute and a percent change in lung function post-bronchodilator.5 The primary spirometry indices used are the forced vital capacity (FVC) and FEV1. The ATS suggests an increase of 12% and 200 mL in the FVC and/or FEV1. Other indices may be reported such as the forced expiratory flow after 50% of the FVC has been expired (FEF50%). These flows are dependent on lung volume and therefore should be isovolume corrected.

A 1996 study attempted to quantify the degree of disagreement in interpretation of spirometry, the definition of the airway obstruction, and response to bronchodilators as described in different publications.6 The degree of disagreement for evaluating the response to a bronchodilator was 24% (this implies 53.3% of possible maximal disagreement). Every original article whose title or summary referred to asthma, chronic obstructive lung disease, or chronic airflow obstruction published in Chest or Thorax from July 1991 to July 1993 was examined. Five different definitions of a positive response to a bronchodilator were identified. An increase in FEV1 >15% of the initial value was the most frequent (76%). The ATS published interpretation recommendations for spirometry in 1991 that suggested the current increase of 12% and 200 mL in FVC and FEV1.5 The authors concluded that disagreement in the interpretation of conventional spirometry often exists. The definition of obstruction and reversibility in clinical trials is not uniform. The authors caution that great care must be taken when extrapolating the results from one publication to another since the composition of its samples could be substantially different.

Predictor of Mortality
Understanding the relationship between reversible airflow obstruction and the prognosis of asthma and COPD is an important consideration. The maximal level of lung function that can be attained is a predictor of survival. In a 1999 study, Hansen et al7 asked if the reversibility to a corticosteroid and a bronchodilator is an independent predictor of prognosis or just another component of the maximal attainable lung function. Subjects with asthma or COPD were evaluated pre- and post-bronchodilator over a 6-year period (1983-1988). Vital statistics were obtained by September 1997 and the relationship between mortality and age, gender, smoking, FEV1, and reversibility was examined. Age, smoking, and FEV1 were significant predictors of mortality. When the authors controlled for baseline FEV1, the bronchodilator and corticosteroid reversibility was significantly associated with better survival. The next step was to control for the best FEV1. When this step was completed, the reversibility was not significant or predictive. Although they may both contribute to survival prediction, it is only related to how well they modify FEV1. Therefore, the authors concluded that reversibility does not influence survival in subjects with moderate to severe asthma or COPD.

The assessment of airway obstruction and reversibility with spirometry is a mainstay in the evaluation of patients with respiratory diseases. Maximizing the FEV1 relates to the overall prognosis in asthma and COPD. Standardizing the medication delivered, dose, and method of delivery decreases the variability in the testing methodology. It allows comparison of data from multiple sources and trending of data for an individual patient.

Susan Blonshine, BS, RRT, RPFT, FAARC, is the director of Technical Education Consultants, Mason, Mich.

1. American Thoracic Society Pulmonary Laboratory Management and Procedure Manual. New York: ATS; 1998.
2. American Association for Respiratory Care Clinical Practice Guideline: Spirometry, 1996 update. Respir Care. 1996;41:629-636.
3. Rodriguez-Carballeira M, Heredia JL, Rue M, Quintana S, Gomez L. The bronchodilator test with increasing doses of terbutaline in chronic obstructive pulmonary disease patients. Pulm Pharmacol Ther. 2001;14:61-65.
4. Rodriguez-Carballeira M, Heredia JL, Gomez L, Quintana S, Vinas C. Contribution of ipratropium bromide to the bronchodilator test in patients with chronic obstructive pulmonary disease. Pulm Pharmacol Ther. 1999;12:43-85.
5. American Thoracic Society. Lung function testing: selection of reference values and interpretative strategies. Am Rev Respir Dis. 1991;144:1202-1218.
6. Quadrelli SA, Roncoroni AJ, Porcel G. Analysis of variability in interpretation of spirometric tests. Respiration. 1996;63:131-136.
7. Hansen EF, Phanareth K, Laursen LC, Kok-Jensen A, Dirksen A. Reversible and irreversible airflow obstruction as predictor of overall mortality in asthma and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999;159:1267-1271.

Additional Reading
Respiratory Clinics of North America. Pediatric Asthma. Philadelphia: WB Saunders; 2000.
Respiratory Clinics of North America. Pulmonary Function Testing: Trends and Techniques. Philadelphia: WB Saunders; 1997.