Tracheal section is an independent predictor of asthma in patients with nasal polyposis

Highlights

• Whether impaired lung function is a consequence or a cause of asthma is debated.

• Based on fractal description of airway tree, tracheal section would impact the entire tree.

• We show that reduced tracheal section is a risk factor for asthma.

Abstract

Airway anatomy could be a risk factor for asthma in susceptible patients with airway hyperresponsiveness. This anatomy can be described by only two parameters, the tracheal cross-sectional area and the homothety ratio, which describes the reduction of calibre at each subsequent generation. Thus, we hypothesized that the tracheal area would be linked to the risk of asthma presence.

Tracheal area (measured by acoustic reflexion method) and airway responsiveness to metacholine (expressed as Dose Response Slope) were evaluated in 71 consecutive adult patients with nasal polyposis and normal baseline lung function.

Hyperresponsiveness was evidenced in 30/71 patients (42%), and 20/71 patients (28%) were asthmatics. Forced expiratory flows were related to tracheal areas (mean value: 3.22 ± 1.32 cm²). In a logistic multivariate analysis, tracheal area and the degree of responsiveness were independent predictors of asthma.

In conclusion, this study suggests that airway anatomy, crudely assessed by tracheal section, is an independent determinant of asthma.

Introduction

Impaired lung function is a consistent finding in asthmatic patients (Sears et al., 2003). But whether this impairment is a consequence or a cause of asthma is open to debate. There are several arguments sustaining the hypothesis that airway morphology is a risk factor for asthma (presence of symptoms) in susceptible patients with airway hyperresponsiveness (AHR). The study of Sears and colleagues showed that lung function is constantly impaired throughout childhood in patients with persistent asthma in adulthood, a phenomenon known as tracking (Sears et al., 2003). However, the slopes of change in FEV₁/FVC were similar in asthmatic patients and healthy controls (Sears et al., 2003). Subsequently, Haland and colleagues demonstrated that reduced lung function at birth was associated with an increased risk of asthma by 10 years of age (Haland et al., 2006), strongly suggesting that underlying anatomy is a main risk factor for asthma. Based on theoretical arguments, the whole human bronchial tree anatomy can be described by only two factors, the tracheal cross-sectional area and the homothety factor (diameter of daughter bronchus over diameter of parental bronchus), which describes the reduction of calibre at each subsequent generation (Bokov et al., 2010). The tracheal section is highly variable from subject to subject, which partly explains the wide variability of instantaneous flows in the healthy population (Osmanliev et al., 1982), which is further sustained by the wide standard deviations of their predicted values (Stanojevic et al., 2008). Consequently, one may hypothesize that the tracheal area is a determinant of the calibres of the whole bronchial tree and would be linked to the risk of asthma development in susceptible patients with AHR.

To evaluate this hypothesis, patients with nasal polyposis prospectively underwent lung function assessment including spirometry and a metacholine challenge test, and non invasive tracheal section measurement using acoustic reflexion method (Hoffstein and Fredberg, 1991). We selected this specific population because the prevalence of both AHR and asthma is elevated in this setting (Delclaux et al., 2008, Mahut et al., 2012), and because nasal polyposis would not constitute a bias for airway anatomy, which may allow the generalization of the results to the whole asthmatic population.