Faculty Bibliography

RATIONALE: Obesity is characterized by increased systemic and pulmonary blood volumes (pulmonary vascular congestion). Concomitant abnormal alveolar membrane diffusion suggests subclinical interstitial edema. In this setting, functional abnormalities should encompass the entire distal lung including the airways. OBJECTIVES: We hypothesize that in obesity: 1) pulmonary vascular congestion will affect the distal lung unit with concordant alveolar membrane and distal airway abnormalities; and 2) the degree of pulmonary congestion and membrane dysfunction will relate to the cardiac response. METHODS: 54 non-smoking obese subjects underwent spirometry, impulse oscillometry (IOS), diffusion capacity (DLCO) with partition into membrane diffusion (DM) and capillary blood volume (VC), and cardiac MRI (n = 24). Alveolar-capillary membrane efficiency was assessed by calculation of DM/VC. MEASUREMENTS AND MAIN RESULTS: Mean age was 45+/-12 years; mean BMI was 44.8+/-7 kg/m2. Vital capacity was 88+/-13% predicted with reduction in functional residual capacity (58+/-12% predicted). Despite normal DLCO (98+/-18% predicted), VC was elevated (135+/-31% predicted) while DM averaged 94+/-22% predicted. DM/VC varied from 0.4 to 1.4 with high values reflecting recruitment of alveolar membrane and low values indicating alveolar membrane dysfunction. The most abnormal IOS (R5 and X5) occurred in subjects with lowest DM/VC (r2 = 0.31, p<0.001; r2 = 0.34, p<0.001). Cardiac output and index (cardiac output / body surface area) were directly related to DM/VC (r2 = 0.41, p<0.001; r2 = 0.19, p = 0.03). Subjects with lower DM/VC demonstrated a cardiac output that remained in the normal range despite presence of obesity. CONCLUSIONS: Global dysfunction of the distal lung (alveolar membrane and distal airway) is associated with pulmonary vascular congestion and failure to achieve the high output state of obesity. Pulmonary vascular congestion and consequent fluid transudation and/or alterations in the structure of the alveolar capillary membrane may be considered often unrecognized causes of airway dysfunction in obesity.

We agree that the "holy grail" of pulmonary physiologists is a test that detects early chronic airway disease. While Dr. Enright remains "cautiously optimistic" that FOT can serve this purpose, there are sufficient data to mitigate his caution.

Detection of airway disease by physiologic testing was initially described using spirometry to determine vital capacity and expiratory airflow under maximal effort to distinguish obstructive from restrictive disease processes. Subsequently, Dubois demonstrated direct assessment of airway resistance using plethysmography and in a separate publication described the precursor of the forced oscillation technique to measure respiratory system resistance. This review addresses the question of whether direct assessment of resistance by forced oscillation provides diagnostic information equivalent or superior to standard assessment of airflow rates by spirometry.

INTRODUCTION: Abnormality in distal lung function may occur in obesity due to reduction in resting lung volume; however, airway inflammation, vascular congestion and/or concomitant intrinsic airway disease may also be present. The goal of this study is to 1) describe the phenotype of lung function in obese subjects utilizing spirometry, plethysmography and oscillometry; and 2) evaluate residual abnormality when the effect of mass loading is removed by voluntary elevation of end expiratory lung volume (EELV) to predicted FRC. METHODS: 100 non-smoking obese subjects without cardio-pulmonary disease and with normal airflow on spirometry underwent impulse oscillometry (IOS) at baseline and at the elevated EELV. RESULTS: FRC and ERV were reduced (44+/-22, 62+/-14% predicted) with normal RV/TLC (29+/-9%). IOS demonstrated elevated resistance at 20 Hz (R20, 4.65+/-1.07 cmH2O/L/s); however, specific conductance was normal (0.14+/-0.04). Resistance at 5-20 Hz (R5-20, 1.86+/-1.11 cmH2O/L/s) and reactance at 5 Hz (X5, -2.70+/-1.44 cmH2O/L/s) were abnormal. During elevation of EELV, IOS abnormalities reversed to or towards normal. Residual abnormality in R5-20 was observed in some subjects despite elevation of EELV (1.16+/-0.8 cmH2O/L/s). R5-20 responded to bronchodilator at baseline but not during elevation of EELV. CONCLUSIONS: This study describes the phenotype of lung dysfunction in obesity as reduction in FRC with airway narrowing, distal respiratory dysfunction and bronchodilator responsiveness. When R5-20 normalized during voluntary inflation, mass loading was considered the predominant mechanism. In contrast, when residual abnormality in R5-20 was demonstrable despite return of EELV to predicted FRC, mechanisms for airway dysfunction in addition to mass loading could be invoked.

INTRODUCTION: Impulse oscillometry (IOS) has been used to demonstrate distal airway dysfunction in symptomatic WTC exposed patients despite normal spirometry. However, it remains to be determined whether the respiratory symptoms can be attributed to the observed functional abnormalities. The present study was designed to assess the simultaneous relationship between the onset of respiratory symptoms and IOS abnormalities in patients undergoing bronchoprovocation for diagnostic evaluation. METHODS: Methacholine challenge testing (MCT) was performed in 113 symptomatic WTC dust exposed patients with normal spirometry that were enrolled WTC Environmental Health Center treatment program. In addition to spirometry, the MCT protocol included performance of IOS and assessment of respiratory symptoms (cough, dyspnea, chest tightness). IOS parameters included resistance at 5 and 20Hz (R⁵ and R₂₀) and frequency dependence of resistance assessed as the difference between these parameters (R_5-20). The PC20 for FEV₁, was used to categorize bronchial hyperreactivity (BHR) as negative (>16mg/ml), borderline (4-16mg/ml) or positive (<4mg/ml). RESULTS: The cohort was 58% female with mean age 49+/-12yr and BMI 29+/-5 kg/m². Baseline spirometry was within normal limits (FEV₁ 98+/-13% predicted, FEV₁/FVC 80+/-4%). Approximately 58% demonstrated abnormal baseline R₅ or R_5-20 indicating respiratory dysfunction despite normal spirometry. MCT revealed BHR, as assessed by spirometry, in 49/113 patients (43%). An additional 27 patients became symptomatic at methacholine doses <4mg/ml despite minimal change in FEV₁ (<5% decrement). All of these patients demonstrated increased R₅, R₂₀ and R_5-20 that coincided with onset of symptoms; median (IQR) increases were 23% (16-41), 13% (7-20), and 92% (39-138), respectively. Following bronchodilator administration, respiratory symptoms resolved and IOS parameters returned towards baseline. CONCLUSIONS: During bronchoprovocation, development of symptoms may coincide with development of distal airway dysfunction as assessed by IOS, even in absence of change in FEV₁. Findings reversed with bronchodilator administration reinforcing the link between symptoms and distal airway dysfunction