Effect of acute ozone induced airway inflammation on human sympathetic nerve traffic: a randomized, placebo controlled, crossover study

Jens Tank, Heike Biller, Karsten Heusser, Olaf Holz, André Diedrich, Theodor Framke, Armin Koch, Anika Grosshennig, Wolfgang Koch, Norbert Krug, Jens Jordan, Jens M Hohlfeld, Jens Tank, Heike Biller, Karsten Heusser, Olaf Holz, André Diedrich, Theodor Framke, Armin Koch, Anika Grosshennig, Wolfgang Koch, Norbert Krug, Jens Jordan, Jens M Hohlfeld

Abstract

Background: Ozone concentrations in ambient air are related to cardiopulmonary perturbations in the aging population. Increased central sympathetic nerve activity induced by local airway inflammation may be one possible mechanism.

Methodology/principal findings: To elucidate this issue further, we performed a randomized, double-blind, cross-over study, including 14 healthy subjects (3 females, age 22-47 years), who underwent a 3 h exposure with intermittent exercise to either ozone (250 ppb) or clean air. Induced sputum was collected 3 h after exposure. Nineteen to 22 hours after exposure, we recorded ECG, finger blood pressure, brachial blood pressure, respiration, cardiac output, and muscle sympathetic nerve activity (MSNA) at rest, during deep breathing, maximum-inspiratory breath hold, and a Valsalva maneuver. While the ozone exposure induced the expected airway inflammation, as indicated by a significant increase in sputum neutrophils, we did not detect a significant estimated treatment effect adjusted for period on cardiovascular measurements. Resting heart rate (clean air: 59±2, ozone 60±2 bpm), blood pressure (clean air: 121±3/71±2 mmHg; ozone: 121±2/71±2 mmHg), cardiac output (clean air: 7.42±0.29 mmHg; ozone: 7.98±0.60 l/min), and plasma norepinephrine levels (clean air: 213±21 pg/ml; ozone: 202±16 pg/ml), were similar on both study days. No difference of resting MSNA was observed between ozone and air exposure (air: 23±2, ozone: 23±2 bursts/min). Maximum MSNA obtained at the end of apnea (air: 44±4, ozone: 48±4 bursts/min) and during the phase II of the Valsalva maneuver (air: 64±5, ozone: 57±6 bursts/min) was similar.

Conclusions/significance: Our study suggests that acute ozone-induced airway inflammation does not increase resting sympathetic nerve traffic in healthy subjects, an observation that is relevant for environmental health. However, we can not exclude that chronic airway inflammation may contribute to sympathetic activation.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Examples of integrated muscle sympathetic…
Figure 1. Examples of integrated muscle sympathetic nerve activity recorded at about 19–22 hours after exposure to clean air or to ozone in two subjects.
Figure 2. Individual values of muscle sympathetic…
Figure 2. Individual values of muscle sympathetic nerve activity (burst frequency in bursts/min) measured after clean air and ozone exposure at rest (top), at the end of maximum inspiratory apnea (middle) and during late phase II of the Valsalva maneuver (bottom) for subjects exposed first to clean air (empty circles, n = 4) and for subjects exposed first to ozone (filled circles, n = 7).

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