Obesity, airway hyperresponsiveness, and inflammation

Epidemiological data indicate that obesity is a risk factor for asthma, but the mechanistic basis for this relationship is not established. Here we review data from human subjects and animal models investigating the relationship between obesity and airway hyperresponsiveness, a characteristic feature of asthma. We discuss obesity as a state of chronic systemic inflammation resulting from interactions between adipocytes and adipose tissue macrophages that are recruited to obese adipose tissue. Finally, we focus on the possibility that aspects of this inflammation, particularly obesity-related changes in TNF-α, leptin, and adiponectin, may contribute to airway hyperresponsiveness in obesity. Determining how obesity promotes asthma may uncover novel therapeutic strategies that are effective in the obese asthmatic subject.

Obesity and asthma: lessons from animal models

Epidemiological data indicate that obesity is a risk factor for asthma. These data are supported by observations in several murine models of obesity. Ob/ob, db/db, and Cpefatmice each exhibit innate airway hyperresponsiveness, a characteristic feature of asthma. These mice also respond more vigorously to common asthma triggers, including ozone. Here we discuss the implications of these data with respect to several mechanisms proposed to explain the relationship between obesity and asthma: 1) common etiologies; 2) comorbidities; 3) mechanical factors; and 4) adipokines. We focus on the role of adipokines, especially TNF-α, IL-6, leptin, and adiponectin. Understanding the mechanistic basis for the relationship between obesity and asthma may lead to novel therapeutic strategies for treatment of the obese asthmatic subject.

Optimal ventilation waveforms for estimating low-frequency respiratory impedance

We present a broad-band optimal ventilator waveform (OVW), the concept of which was to create a computer-driven ventilator waveform containing increased energy at specific frequencies (f). Values of f were chosen such that nonlinear harmonic distortion and intermodulation were minimized. The phases at each f were then optimized such that the resulting flow waveform delivered sufficient volume to maintain gas exchange while minimizing peak-to-peak airway opening pressure. Simulations with a linear anatomically consistent branching airway model and a nonlinear viscoelastic model showed that respiratory resistance (Rrs) and elastance (Ers) estimates at 0.1–2 Hz from the OVW are far superior to those from a standard step ventilator waveform (SVW) during healthy and obstructed conditions and that the OVW reduces the influences of harmonic interactions. Using a servo-controlled oscillator, we applied individual sine waves, an OVW containing energy at 0.15625–2.4 Hz, and an SVW to healthy humans and one symptomatic asthmatic subject before and after bronchodilation. The OVW was markedly superior to the SVW and always provided smooth estimates of Rrs and Ers. Before bronchodilation in the asthmatic subject Rrs was highly elevated and Ers was markedly increased with f; after bronchodilation the level of Rrs and the f dependence of Ers decreased. Although based on results from only one asthmatic subject, these data suggest a dominant influence of airway constriction and lung inhomogeneities during asthmatic bronchoconstriction that is alleviated by bronchodilators. These and other results indicate that the OVW approach has high potential for simultaneously probing f and amplitude dependence in the mechanical properties of clinical subjects during physiological breathing conditions and perhaps during dynamic bronchoconstriction.