Increased Lung Volume as a Potential Therapy for Bronchoconstriction in Asthma of Obesity

Rationale: Late-onset non-allergic asthma in obesity is hypothesized to involve enhanced distal airway closure and air-trapping secondary to abnormally collapsible airway walls. If this is true, obese asthmatics might respond to therapies such as positive end-expiratory pressure (PEEP), which maintains airways open by elevating resting end-expiratory lung volume. We hypothesized that PEEP will both prevent the development of and reverse established bronchoconstriction in obese individuals with asthma. To test our hypothesis, we examined the effect of PEEP on airway mechanics during and after methacholine in obese participants with late-onset non-allergic asthma (LONA). We quantified bronchoconstriction using respiratory system impedance (Zrs). Methods: In obese patients with LONA asthma, we first determined the concentration of aerosolized methacholine causing a 20% decline in FEV 1 (PC 20 ). At four subsequent visits performed in a random order, Zrs was measured over 8 min using a modified flexiVent ventilator (Scireq, Montreal, Canada). Participants were given their PC 20 concentration of methacholine for the first 4.5 min, then methacholine was stopped while Zrs measurements continued for the next 3.5 min. During two visits, no PEEP was applied; at a third visit, PEEP 10 was applied both during and after methacholine (PEEP 10-10); at a forth visit, PEEP 10 was applied only after methacholine (PEEP 0-10). Measured Zrs was fit to a two-compartment series model of the respiratory system, providing values for the resistances and elastances of the central and peripheral compartments. We also obtained Ax and Ar as the areas under the curves of the imaginary and real parts, respectively, of Zrs vs. frequency. Ax and Ar provide integrative measures of the degree and heterogeneity of airway narrowing and derecruitment. Results: Twelve obese participants with LONA asthma (BMI: 42.88.7 kg/m 2 , 45.27.0 years, 8 females) completed the study protocol. PEEP 10 during methacholine reduced central and peripheral airway resistance and elastance, Ax, and Ar compared to no PEEP (Figure PEEP 10 after methacholine significantly reduced central resistance, Ax, and central and peripheral elastance. Conclusion: During methacholine administration, PEEP keeps both central and peripheral airways dilated and airspaces open, thereby mitigating bronchoconstriction. We therefore propose that PEEP serve as a potential therapy to prevent and reverse bronchoconstriction in obese individuals with asthma.

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