Baseline Spirometry as a Predictor of Positive Methacholine Challenge Testing for Exertional Dyspnea

John C. Hunninghake*, Sarah B. McCullough, James K. Aden, Jackie A. Hayes, Edward T. McCann, Michael J. Morris

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


BACKGROUND: There are several tests recommended by the American Thoracic Society (ATS) to evaluate for airway hyper-responsiveness (AHR), one of which is methacholine challenge testing (MCT). Few studies have examined the correlation of baseline spirometry to predict AHR in MCT, especially in the younger, relatively healthy military population under clinical evaluation for symptoms of exertional dyspnea. The study aim was to retrospectively correlate baseline spirometry values with MCT responsiveness. METHODS: This study is a retrospective review of all MCT performed at Brooke Army Medical Center/Wilford Hall Medical Center over a 12-y period; all completed studies were obtained from electronic databases. The following parameters were analyzed from the studies: baseline FEV1, FVC, FEV1/FVC, mid-expiratory flow (FEV25-75%), FEV25–75%/FVC. Studies were categorized based on baseline obstruction, restriction, FEF25–75% lower limit of normal, and response to bronchodilator testing (if completed); these values were compared based on methacholine reactivity and severity. RESULTS: Methacholine challenge studies (n = 1,933) were reviewed and categorized into reactive (n = 577) and nonreactive (n = 1,356) as determined by ATS guidelines. The mean baseline FEV1 (% predicted) with MCT reactivity was 88.0 ± 13.0% versus no MCT reactivity was 92.7 ± 13.0% (P <.001). The mean baseline FVC (% predicted) was 93.1 ± 13.7% versus 95.3 ± 13.5% (P <.001). The mean baseline FEV25–75% (% predicted) was 80.0 ± 22.1% versus 89.0 ± 23.4% (P <.001). Based on partition analysis, methacholine reactivity was most prevalent with baseline obstruction, n = 115 (43%), and in the absence of obstruction, when the FEF25–75% (% predicted) was below 0.70, n = 111 (40%). The negative predictive value with normal spirometry was 73%. CONCLUSIONS: The analysis of baseline spirometry prior to MCT proved useful in the evaluation of exertional dyspnea in a military population. The presence of airways obstruction (FEV1/FVC < lower limit of the normal range) followed by a reduction in FEV25–75% < 70% predicted showed a positive correlation with underlying AHR. In patients with exertional dyspnea and normal baseline spirometry, the use of the FEF25–75% may be a useful surrogate measurement to predict reactivity during MCT and consideration for additional testing or treatment.

Original languageEnglish
Pages (from-to)694-701
Number of pages8
JournalRespiratory Care
Issue number6
StatePublished - 2022
Externally publishedYes


  • FEF
  • airway hyperreactivity
  • baseline spirometry
  • exertional dyspnea
  • methacholine challenge testing
  • military population


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