Changes in the Lung Clearance Index as Measured by Multiple-breath Washout, in Pediatric Patients With Asthma After Challenge With Inhaled Steroids and Short-acting Bronchodilator

The method most used to measure lung function, have been the spirometric tests, which generally reflect the function of the airway of highest caliber and elastic retraction of the lung. However, its use in clinical practice is limited by physiological variability and inconsistency in the measurements, therefore its value as a predictor of peripheral obstruction has been questioned. The Lung Clearance Index (LCI) is a simple measure of ventilation heterogeneity derived from multiple breath-washout (MBW) curve, that can be used after challenge with a short action bronchodilator and inhaled steroids, both in the conductive and acinar airways. Patients with moderate and severe asthma are characterized by an abnormality in both, conductive and the acinar airway. The LCI is one index derived from the concentration curves obtained during MBW to quantify the inefficiency in gas mixing of the lungs. A phase III slope analysis of the MBW curve can distinguish maldistribution of ventilation due to structural changes (acinar vs conductive lung zone). The conductive MBW index of ventilation heterogeneity is related to proximal lung structure, where convection dominates gas transport. The acinar MBW index of ventilation heterogeneity is related to peripheral lung, where convection-diffusion interaction occurs. Therefore the following research question could be: what are the abnormalities in the heterogeneity of ventilation in pediatric patients with a diagnosis of asthma, both mild and moderate, with respect to the healthy population, measured by MBW and whether these alterations persist using conventional treatment with inhaled steroids and B2 agonists short-acting.

The general objetive will be to identify changes in the LCI (heterogeneity of ventilation) retrieved from the MBW curve in children with diagnosis of mild and moderate asthma, before and after challenge with short-acting B2 agonists and after one month of treatment with knowledge dose of inhaled steroid.

Specific objectives;

1. . Difference in the baseline results of spirometry and LCI (derived form the MBW curve), between the control health group, and children with mild and moderate asthma.
2. . Changes in LCI (acinar or conductive ventilation heterogeneity) obtained from the MBW curve, from the baseline values and after challenge with short-acting B2 agonist and with inhaled steroids between groups of patients with mild or moderate asthma.
3. . Determine whether the alterations in the LCI of patients with mild and moderate asthma are originated from acinar or from the conductive airway.

Methodology. The LCI is calculated with the cumulative volume exhaled (CVE) during MBW test, divided between the functional residual capacity (FRC). This index is the number of turnovers of lung volume that the patient must breathe to clean the lungs of tracer gas (1/40th of the initial concentration). The expiratory N2 concentration will be plotted against volume changes between Total Lung Capacity (TLC) and Residual Volume (RV), and the slope (dN2) of the N2 alveolar plateau will be calculated by computer analysis of the best-fit line through phase III of the expiratory volume-concentration curve. The measurements will be accepted only if the vital capacity (VC) during the MBW is within 10% of the VC. During the MBW test, patients most perform a slow, full inspiratory and expiratory VC maneuver at inspiratory and expiratory flow rates of approximately 0.5 l/s.The VC will be obtained from the spirometry test.