Background

Previous reports suggest that peripheral airways are associated with asthma control. Patient history, although subjective is used largely to assess asthma control in children because spirometry is many times normal. Impulse oscillometry (IOS) is an objective non-invasive measurement of lung function, which has the potential to examine independently both small and large airway obstruction.

Objective

To determine the utility of IOS in assessing asthma control in children.

Methods

Asthmatic and healthy children (6–17 yrs) were enrolled in the study. Spirometry and IOS (resistance at 5 and 20 Hz, R5 and R20, respectively, reactance at 5 Hz, X5, resonant frequency, Fres, and area under the reactance curve between 5 Hz and Fres, AX) were collected in triplicate before and after a bronchodilator was administered. The physicians were blinded to the IOS measurements and assessed asthma control using ATS guidelines.

Results

Small airway IOS measurements, including R5-20, X5, Fres and AX, of children with uncontrolled asthma (n=44) were significantly different from those of controlled asthmatic (n=57) and healthy (n=14) children, especially prior to the administration of a bronchodilator. However, there was no difference in large airway IOS (R20). No differences were found between controlled asthmatic and healthy children in any of the endpoints. ROC analysis showed cut-points for baseline R5-20 (1.5 cmH₂O·L⁻¹·s) and AX (9.5 cmH₂O·L⁻¹) that effectively discriminated controlled versus uncontrolled asthma (AUC=0.86 and 0.84), and correctly classified more than 80% of the population.

Conclusion

Uncontrolled asthma is associated with small airways dysfunction, and IOS may be a reliable non-invasive method to assess asthma control in children.

Exhaled nitric oxide (NO) is altered in asthmatic subjects with exercise-induced bronchoconstriction (EIB). However, the physiological interpretation of exhaled NO is limited because of its dependence on exhalation flow and the inability to distinguish completely proximal (large airway) from peripheral (small airway and alveolar) contributions. We estimated flow-independent NO exchange parameters that partition exhaled NO into proximal and peripheral contributions at baseline, postexercise challenge, and postbronchodilator administration in steroid-naive mild-intermittent asthmatic subjects with EIB (24-43 yr old, n = 9) and healthy controls (20-31 yr old, n = 9). The mean +/- SD maximum airway wall flux and airway diffusing capacity were elevated and forced expiratory flow, midexpiratory phase (FEF(25-75)), forced expiratory volume in 1 s (FEV(1)), and FEV(1)/forced vital capacity (FVC) were reduced at baseline in subjects with EIB compared with healthy controls, whereas the steady-state alveolar concentration of NO and FVC were not different. Compared with the response of healthy controls, exercise challenge significantly reduced FEV(1) (-23 +/- 15%), FEF(25-75) (-37 +/- 18%), FVC (-12 +/- 12%), FEV(1)/FVC (-13 +/- 8%), and maximum airway wall flux (-35 +/- 11%) relative to baseline in subjects with EIB, whereas bronchodilator administration only increased FEV(1) (+20 +/- 21%), FEF(25-75) (+56 +/- 41%), and FEV(1)/FVC (+13 +/- 9%). We conclude that mild-intermittent steroid-naive asthmatic subjects with EIB have altered airway NO exchange dynamics at baseline and after exercise challenge but that these changes occur by distinct mechanisms and are not correlated with alterations in spirometry.

Background: The exhaled nitric oxide (eNO) signal is a marker of inflammation, and can be partitioned into proximal [J'aw(NO) (nl/s), maximum airway flux] and distal contributions [CA(NO)(ppb), distal airway/alveolar NO concentration]. We hypothesized that J'awNO and CANO are selectively elevated in asthmatics, permitting identification of four inflammatory categories with distinct clinical features. Methods: In 200 consecutive children with asthma, and 21 non-asthmatic, non-atopic controls, we measured baseline spirometry, bronchodilator response, asthma control and morbidity, atopic status, use of inhaled corticosteroids, and eNO at multiple flows (50, 100, and 200 ml/s) in a cross-sectional study design. A trumpet-shaped axial diffusion model of NO exchange was used to characterize J'awNO and CANO. Results: J'awNO was not correlated with CANO, and thus asthmatic subjects were grouped into four eNO categories based on upper limit thresholds of non-asthmatics for J'aw(NO) (>= 1.5 nl/s) and CA(NO) (>= 2.3 ppb): Type I (normal J'aw(NO) and CA(NO)), Type II (elevated J'aw(NO) and normal CA(NO)), Type III (elevated J'aw(NO) and CA(NO)) and Type IV (normal J'aw(NO) and elevated CA(NO)). The rate of inhaled corticosteroid use (lowest in Type III) and atopy (highest in Type II) varied significantly amongst the categories influencing J'aw(NO), but was not related to CA(NO), asthma control or morbidity. All categories demonstrated normal to near-normal baseline spirometry; however, only eNO categories with increased CA(NO) (III and IV) had significantly worse asthma control and morbidity when compared to categories I and II. Conclusions: J'aw(NO) and CA(NO) reveal inflammatory categories in children with asthma that have distinct clinical features including sensitivity to inhaled corticosteroids and atopy. Only categories with increase CANO were related to poor asthma control and morbidity independent of baseline spirometry, bronchodilator response, atopic status, or use of inhaled corticosteroids.