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IntroductionAbnormality 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.Methods100 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.ResultsFRC 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.ConclusionsThis 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.

There is an increasing awareness of the role of distal airways in the pathophysiology of obstructive lung diseases including asthma and chronic obstructive pulmonary disease. We hypothesize that during induced bronchoconstriction: 1) disparity between distal and proximal airway reactivity may occur; and 2) changes in distal airway function may explain symptom onset in subjects with minimal FEV(1) change. 185 subjects underwent methacholine challenge testing (MCT). In addition to spirometry, oscillometry was performed at baseline and after maximum dose of methacholine; 33/185 also underwent oscillometry after each dose. Oscillometric parameters included resistance at 5 and 20 Hz (R(5), R(20)) and heterogeneity of distal airway mechanics assessed by frequency dependence of resistance 5-20 Hz (R(5-20)) and reactance area (AX). R(5) varied widely during MCT (range -0.8 - 11.3 cmH(2)O/L/s) and correlated poorly with change in FEV(1) (r = 0.17). Changes in R(5) reflected changes in both R(20) and R(5-20) (r = 0.59, p<0.05; r = 0.87, p<0.0001). However, R(20) increased only 0.3 cmH(2)O/L/s, while R(5-20) increased 0.7 cmH(2)O/L/s for every 1cmH(2)O/L/s change in R(5,) indicating predominant effect of distal airway mechanics. 9/33 subjects developed symptoms despite minimal FEV(1) change (<5%), while R(5) increased 42% due to increased distal airway heterogeneity. These data indicate disparate behavior of proximal airway resistance (FEV(1) and R(20)) and distal airway heterogeneity (R(5-20) and AX). Distal airway reactivity may be associated with methacholine-induced symptoms despite absence of change in FEV(1). This study highlights the importance of disparity between proximal and distal airway behavior, which has implications in understanding pathophysiology of obstructive pulmonary diseases and their response to treatment.

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