Performance Characteristics of Spirometry With Negative Bronchodilator Response and Methacholine Challenge Testing and Implications for Asthma Diagnosis

Abstract

BACKGROUND:In patients with a history suggestive of asthma, diagnosis is usually confirmed by spirometry with bronchodilator response (BDR) or confirmatory methacholine challenge testing (MCT). RESEARCH QUESTION: We examined the proportion of participants with negative BDR testing who had a positive MCT (and its predictors) result and characteristics of MCT, including effects of controller medication tapering and temporal variability (and predictors of MCT result change), and concordance between MCT and pulmonologist asthma diagnosis.STUDY DESIGN AND METHODS: Adults with self-reported physician-diagnosed asthma were recruited by random-digit dialing across Canada. Subjects performed spirometry with BDR testing and returned for MCT if testing was nondiagnostic for asthma. Subjects on controllers underwent medication tapering with serial MCTs over 3 to 6 weeks. Subjects with a negative MCT (the provocative concentration of methacholine that results in a 20% drop in FEV 1 [PC 20 ] > 8 mg/mL) off medications were examined by a pulmonologist and had serial MCTs after 6 and 12 months.RESULTS: Of 500 subjects (50.5 AE 16.6 years old, 68.0% female) with a negative BDR test for asthma, 215 (43.0%) had a positive MCT. Subjects with prebronchodilator airflow limitation were more likely to have a positive MCT (OR, 1.90; 95% CI,. MCT converted from negative to positive, with medication tapering in 18 of 94 (19.1%) participants, and spontaneously over time in 25 of 165 (15.2%) participants. Of 231 subjects with negative MCT, 28 (12.1%) subsequently received an asthma diagnosis from a pulmonologist.

Diagnosing asthma and chronic obstructive pulmonary disease

“…However, first-line asthma therapy includes inhaled corticosteroids, which have downstream biological effects that require a longer washout period to mitigate their impact on test sensitivity. 27 Providers who encounter patients already taking prescribed therapy but without an objective diagnosis of asthma or COPD, or who start patients on therapy while awaiting objective testing, should ask patients to hold their bronchodilator use before spirometry testing. For patients with suspected COPD, this is often all that will be required to rule in or rule out the diagnosis (see Figure 1).…”

“…4 Although this finding is sufficient to make the diagnosis, if a bronchodilator response is absent, it does not rule out asthma. Among patients suspected of having asthma, about 40% will have a falsely negative bronchodilator response test result 27 and require a methacholine challenge test for diagnosis. For COPD, diagnosis simply requires the presence of obstruction on postbronchodilator spirometry, and no further testing is required in most cases.…”

Addressing Reduced Laboratory-Based Pulmonary Function Testing During a Pandemic

“…In fact, operating characteristics of exhaled nitric oxide measurement for asthma diagnosis were clearly superior to those of spirometry with bronchodilator testing in a recent review. 51 Moreover, traditional challenge studies are not only cumbersome to carry out, but also produce variable responses in different subpopulations of patients with asthma and depending on the challenge used. 52 Arguably, recognizing and managing airways inflammation is a more important treatment decision in asthma than the decision to use albuterol for symptoms, and exhaled nitric oxide has been suggested as a predictor of inhaled corticosteroid responsiveness is patients with asthma or asthma-like symptoms.…”

Asthma diagnosis: into the fourth dimension

“…However, spontaneous variations in BHR also occurred during follow-up at 6 months and 12 months in 15% of patients irrespective of seasonal or medication changes. 96 Even in the absence of changes in lung physiology, asthma treatment or symptom scores, considerable biological inflammatory changes have been observed in repeated endobronchial biopsies in stable asthmatics obtained 1 month apart. 97 Sputum inflammatory phenotypes are unstable in children with asthma over 12 months, independent of asthma medications or disease control.…”