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

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.

A Comparison of Global Lung Initiative 2012 with Third National Health and Nutrition Examination Survey Spirometry Reference Values. Implications in Defining Obstruction.

RATIONALE: Obstructive lung disease is diagnosed by a decreased ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC); however, there is no universally accepted lower limit of normal for the FEV1/FVC ratio. Current established reference values use the Third National Health and Nutrition Examination Survey (NHANES III) database. In 2012, the Global Lung Initiative (GLI) introduced GLI12, which is a compilation reference set that uses standard deviation values to define normal spirometry. OBJECTIVES: To evaluate the changes in classification of obstructive spirometry with use of GLI12 compared with NHANES III in a heterogeneous, multiracial population. METHODS: We evaluated the spirometry studies conducted in our pulmonary function laboratory between January 2005 and December 2015. NHANES III reference equations were calculated to predict lower limits of normal for FEV1, FVC, and FEV1/FVC. GLI12 values were established using European Respiratory Society published computer software. FEV1 severity was graded using 2005 American Thoracic Society guidelines for NHANES III and using z-score-based criteria for GLI12. Asymmetric partition analysis evaluated agreement between the reference sets. RESULTS: A total of 11,888 studies were evaluated. Obstruction was diagnosed in 2,857 studies using NHANES III versus 2,489 studies using GLI12. Agreement regarding the presence or absence of obstruction occurred in 2,483 of studies with obstruction and 9,025 studies without obstruction (agreement, 96.8%; κ = 0.91). Of the studies with obstruction, 1,595 had agreement in severity grading. Overall, agreement regarding obstruction and severity grading occurred in 10,620 studies, representing 89.3% of all studies. A total of 380 studies (3.2%) had discordance regarding the presence or absence of obstruction, 34.0% (844 of the 2,483 obstruction studies) had a one-degree of change in FEV1 disease severity scoring, with 44 cases (1.8%) that had changes of two categories in FEV1 severity scores. No studies had greater than two degrees of change. Asymmetric partition analysis suggested that the highest clinically significant changes were seen in older individuals, particularly African American men older than 65. CONCLUSIONS: Our evaluation suggests that there is moderate overall agreement between NHANES III and GLI12. We found a 3.2% change in classification of obstruction when transitioning from NHANES III to GLI12. When incorporating a z-score-based FEV1 and GLI12 reference set, 10.7% of the spirometry studies had a change in their categorization. The disagreement between the two datasets was most pronounced in elderly subjects. Although we cannot endorse one reference set over the other, we highlight the potential implications of adopting the GLI12 reference sets and suggest caution when interpreting spirometry in the elderly.

Congenital pulmonary airway malformation in the asymptomatic adult: A rare presentation.

Congenital Pulmonary Airway Malformation (CPAM) is a rare developmental abnormality of the lower respiratory tract, primarily diagnosed in the neonatal period. The most concerning sequelae for patients with CPAM are recurrent respiratory infections and malignancy. Rarely discovered in asymptomatic adults, CPAM presents challenging questions for management. We describe such a case and discuss the risks and benefits of resection.

Exercise-associated Excessive Dynamic Airway Collapse in Military Personnel.

RATIONALE: Evaluation of military personnel for exertional dyspnea can present a diagnostic challenge, given multiple unique factors that include wide variation in military deployment. Initial consideration is given to common disorders such as asthma, exercise-induced bronchospasm, and inducible laryngeal obstruction. Excessive dynamic airway collapse has not been reported previously as a cause of dyspnea in these individuals. OBJECTIVES: To describe the clinical and imaging characteristics of military personnel with exertional dyspnea who were found to have excessive dynamic collapse of large airways during exercise. METHODS: After deployment to Afghanistan or Iraq, 240 active U.S. military personnel underwent a standardized evaluation to determine the etiology of persistent dyspnea on exertion. Study procedures included full pulmonary function testing, impulse oscillometry, exhaled nitric oxide measurement, methacholine challenge testing, exercise laryngoscopy, cardiopulmonary exercise testing, and fiberoptic bronchoscopy. Imaging included high-resolution computed tomography with inspiratory and expiratory views. Selected individuals underwent further imaging with dynamic computed tomography. MEASUREMENTS AND MAIN RESULTS: A total of five men and one woman were identified as having exercise-associated excessive dynamic airway collapse on the basis of the following criteria: (1) exertional dyspnea without resting symptoms, (2) focal expiratory wheezing during exercise, (3) functional collapse of the large airways during bronchoscopy, (4) expiratory computed tomographic imaging showing narrowing of a large airway, and (5) absence of underlying apparent pathology in small airways or pulmonary parenchyma. Identification of focal expiratory wheezing correlated with bronchoscopic and imaging findings. CONCLUSIONS: Among 240 military personnel evaluated after presenting with postdeployment exertional dyspnea, a combination of symptoms, auscultatory findings, imaging, and visualization of the airways by bronchoscopy identified six individuals with excessive dynamic central airway collapse as the sole apparent cause of dyspnea. Exercise-associated excessive dynamic airway collapse should be considered in the differential diagnosis of exertional dyspnea.

Inspiratory flow-volume curve evaluation for detecting upper airway disease.

BACKGROUND: The 2005 American Thoracic Society/European Respiratory Society guidelines on spirometry emphasize examination of the inspiratory curve of the flow-volume loop for evidence of intrathoracic or extrathoracic upper airway obstruction. We sought to determine how frequently evaluations are performed for abnormal inspiratory curves. METHODS: We retrospectively reviewed all examinations performed in our pulmonary function testing laboratory over a 12-month period (n = 2,662). In patients with normal spirometry or a mild restrictive defect, we inspected the inspiratory curves for truncation, flattening, or absent loop. With patients who had an abnormal inspiratory curve, we examined 3 flow-volume loops to determine if more than one loop showed an inspiratory abnormality, and to assess changes in the mid-flow ratio (ratio of forced expiratory flow at 50% of the forced expiratory volume to forced inspiratory flow at 50% of the forced inspiratory volume), and we used the loop that had the best inspiratory and expiratory curves. We reviewed the medical records for underlying disease processes and evidence of upper airway evaluation. RESULTS: One hundred twenty-three patients (4.6%) had an abnormal inspiratory curve. Sixty-nine (56%) of those 123 patients had inspiratory abnormalities on > 2 flow-volume loops. Evaluation of the inspiratory abnormality was undertaken in only 17% of all patients, and 30% of patients who had consistently abnormal inspiratory curves. A specific etiology was identified in 52% of the evaluated patients. Vocal cord dysfunction was the most frequent diagnosis. Utilizing the loop that had the combination of the best inspiratory and expiratory curves decreased the mid-flow ratio from 3.07 +/- 1.63 to 1.77 +/- 1.15. CONCLUSIONS: An abnormal inspiratory curve in the presence of otherwise normal spirometry should prompt an evaluation for the etiology. If one of the flow-volume inspiratory curves shows an abnormality, all the inspiratory curves from that PFT session should be reviewed, and if more than one inspiratory curves is abnormal, both anatomical and functional evaluation should be undertaken for intrathoracic and extrathoracic upper airway obstruction.