Changes In R5 Research Articles

Changes in fractional exhaled nitric oxide, forced expiratory volume in one second, and forced oscillation technique parameters over three years in adults with bronchial asthma managed under Yokohama Seibu Hospital’s coordinated care system

BackgroundIn western Yokohama, our hospital and primary care clinics manage adults with asthma via a coordinated care system. We investigated the changes in the fractional expired nitric oxide (FeNO), forced expiratory volume in 1 second (FEV1), and forced oscillation technique (FOT) parameters over 3 years in a cohort of patients in our collaborative system.MethodsFrom 288 adults with well controlled asthma managed under the Yokohama Seibu Hospital coordinated care system between January 2009 and May 2018, we selected 99 subjects to undergo spirometry, FeNO and FOT testing over 3 years and analyzed the changes in these parameters.ResultsOf the 99 patients enrolled, 17 (17.2%) experienced at least one exacerbation (insufficiently controlled (IC)), whereas, 82 (82.8%) remained in well controlled during the 3-year study period. Of well-controlled patients, 54 patients (54.5%) met the criteria for clinical remission under treatment (CR); the remaining 28 patients did not meet the CR criteria (WC). There were no differences in FeNO, FEV1, or FOT parameters at baseline among the IC, WC, and CR groups. The levels of FEV1 decreased gradually, whereas the levels of FeNO decreased significantly over 3 years. The levels of percent predicted FEV1 (%FEV1) significantly increased. We also observed significant improvement in FOT parameters; reactance at 5 Hz (R5), resonant frequency (Fres), and integral of reactance up to the resonant frequency (AX). The CR group demonstrated significant relationships between the change in FeNO and the change in FEV1 and between the change in FEV1 and the change in FOT parameters. No significant correlations emerged in the IC or WC group.ConclusionThe decrease in FeNO and increase in %FEV1, we observed in all study participants suggest that the coordinated care system model benefits patients with asthma. Although it is difficult to predict at baseline which patients will experience an exacerbation, monitoring changes in FeNO and FEV1 is useful in managing patients with asthma. Furthermore, monitoring changes in R5, Fres, and AX via forced oscillation technique testing is useful for detecting airflow limitation.

A Longitudinal Study of Respiratory Mechanics in Pregnant Women with Obesity and Overweight.

Respiratory mechanics and the role of sex hormones in pregnancy are not well elucidated. We examined longitudinal and positional changes in lung mechanics in pregnancy and investigated the role of sex hormones. A longitudinal study enrolled 135 women with obesity in early pregnancy. Fifty-nine percent of women identified as White; median body mass index at enrollment was 34.4kg/m2. Women with respiratory disease were excluded. We obtained measurements of airway resistance and respiratory system reactance in various positions using impedance oscillometry and sex hormones in early and late pregnancy. With pregnancy progression, there was a significant increase in resonant frequency (Fres) (p = 0.012), integrated area of low frequency reactance (AX) (p = 0.0012) and R5-R20Hz (p = 0.038) in the seated position,and a significant increase in R5Hz (p = 0.000), Fres (p = 0.001), AX (p < 0.001 = 0.000), and R5-R20Hz (p = 0.014) in the supine position. Compared to the seated position, the supine position was associated with a significant increase in R5Hz, R20Hz, X5Hz, Fres, and AX in early (p-values < 0.026) and late pregnancy (p-values ≤ 0.001). Changes in progesterone levels between early and late pregnancy predicted the change in R5, Fres, and AX (p-values ≤ 0.043). Resistive and elastic loads increase with pregnancy progression and a change in body position from seated to supine increases resistive and elastic loads in both early and late pregnancies. The increase in airway resistance is primarily related to an increase in peripheral rather than central airways resistance. There was an association between the change in progesterone levels and airway resistance.

Effects of Milk Amazake on Skin Elasticity, Hydration, and Transepidermal Water Loss: An 8-Week Double-Blind, Randomized, Controlled Trial.

Amazakes made from rice and koji mold are rich in nutrients, such as groups of vitamin B, minerals, essential amino acids, and oligosaccharides, and can improve skin moisturization. However, there are few reports on milk amazake, made from milk and koji mold. Therefore, in this double-blind, randomized controlled trial, we investigate the effect of milk amazake on skin function. Healthy women and men (n = 40) were randomly allocated to the milk amazake or placebo group. The test beverage was consumed once daily for 8 weeks. Skin elasticity, hydration, and transepidermal water loss (TEWL) were measured at baseline and at weeks 4 and 8, and all subjects completed the trial. Skin elasticity (R2 and R5) at 8 weeks was significantly increased in the milk amazake group compared with baseline. In addition, changes in R5 in the milk amazake group were significantly higher than those in the placebo group. Conversely, TEWL, an evaluation item of skin moisturizing function at 8 weeks, was significantly decreased in the active group compared with baseline. In conclusion, milk amazake may be useful as a functional food for improving skin function.

Impulse oscillometry (IOS) for detection of exercise induced bronchoconstriction in children with asthma ages 6–15 years

Objectives To determine the discriminatory value of various impulse oscillometry (IOS) parameters, and to find the cutoff value of the appropriate parameter for identifying exercise-induced bronchoconstriction (EIB) in children with asthma. Methods This cross-sectional study was conducted in India from October 2016 to March 2018 in children with asthma who were 6–15 years of age. One hundred and five children were enrolled and subjected to pre-exercise IOS and spirometry followed by free running treadmill test as an exercise challenge. All children could achieve minute ventilation >17.5–21 times of FEV1 during the exercise challenge test. Then, IOS and spirometry were performed at 10 ± 2, 20 ± 2, and 30 ± 2 min post-exercise challenge. EIB was defined as reduction of FEV1 ≥10% within 30 min of exercise. For purposes of analysis, the children were grouped into two categories: “EIB Present” or “EIB Absent”. Results The prevalence of EIB in our study was 20.95% (n = 22). ΔR5max percentage within 30 min post-exercise (AUC 0.74; 95% CI: 0.64, 0.84) had the best discriminating capacity among all IOS parameters for identifying EIB. A cutoff value of 14.1% increase in R5 within 30 min post-exercise was obtained for detection of EIB (sensitivity—95.45%, specificity—50.6%, PPV—33.87% and NPV—97.67%). Conclusions A percentage change in R5 with a cutoff value of 14.1% increase post-exercise had the best discriminatory capacity among all IOS parameters for detection of EIB in children with asthma. However, low positive predictive value (PPV) with high negative predictive value (NPV) made this cutoff value more apt to rule out EIB.

Airwave oscillometry and spirometry in children with asthma or wheeze

Objective Lung function testing is used in diagnosing asthma and assessing asthma control. Spirometry is most commonly used, but younger children can find performing this test challenging. Non-volitional tests such as airwave oscillometry (AOS) may be helpful in that population. We compared the success of spirometry and AOS in assessing bronchodilator responsiveness in children. Methods AOS was conducted alongside routine lung function testing. Resistance at 5 Hz (R5), the difference between the resistance at 5 and 20 Hz (R5-20) and the area under the reactance curve (AX) were assessed. Patients between 5 and 16 years old attending clinic with wheeze or asthma were assessed. Patients performed AOS, followed by spirometry and were then given 400 µg salbutamol; the tests were repeated 15 minutes later. Results Lung function testing was performed in 47 children of whom 46 (98%) and 32 (68%) performed acceptable baseline oscillometry and spirometry, respectively (p < 0.001). Children unable to perform acceptable spirometry were younger (7.35, range: 5.4–10.3 years) than those who could (10.4, range: 5.5–16.9 years), p < 0.001. The baseline z-scores of AOS R5 correlated with FEV1 (r = 0.499, p = 0.004), FEF75 (r = 0.617, p < 0.001), and FEV1/FVC (r = 0.618, p < 0.001). There was a positive bronchodilator response assessed by spirometry (change in FEV1 ≥ 12%) in eight children which corresponded to a change in R5 of 36% (range: 30%–50%) and a change in X5 of 39% (range: 15%–54%). Conclusions Oscillometry is a useful adjunct to spirometry in assessing young asthmatic children’s lung function. The degree of airway obstruction, however, might affect the comparability of the results of the two techniques.

Comparison of Impulse Oscillometry with Spirometry to Assess Lung Function in Children with Sickle Cell Disease (SCD)

▪BACKGROUNDSpirometry is a validated pulmonary function test (PFT) for assessment of airway function in older children and adults, including children with SCD. However, it is not consistently reliable in children less than 6 years of age. Impulse oscillometry (IOS), a technique to evaluate airway obstruction via assessment of airway resistance, has been validated for use in children as young as 3 years, but has not been used widely in children with SCD.OBJECTIVEThe primary objective was to examine the correlation between spirometry and oscillometry in assessment of airway obstruction and bronchodilator response in children with SCD > 6 years old, in order to assess its utility in our patient population. The a priori hypothesis is oscillometry correlates well with spirometry in assessment of airway function and bronchodilator responsiveness in children with SCD.METHODSAfter IRB approval, this prospective study was offered to all eligible patients followed in our sickle cell clinic who fulfilled age criteria and were due for a clinical PFT study. Clinical and laboratory data on the participants were collected from medical records. Symptoms of asthma and airway hyper-responsiveness were assessed using the modified ISAAC questionnaire prior to lung function testing. Airway function was concurrently assessed pre-and post-bronchodilator using oscillometry (area of reactance, AX; airway resistance at 5Hz, R5) and spirometry (forced expiratory volume in 1 second, FEV1; forced mid-expiratory flow, FEF25-75).A Wilcoxon Signed-Rank test was run to compare the pre and post predicted percentages for AX, R5, FEV1 and FEF25-75. Next, Pearson's test for correlation was run to analyze the correlation between percent change from baseline for all variables (AX, R5, FEV1 and FEF25-75). McNemar's exact test was used to compare the proportion of improved patients for AX, R5, and FEV1, FEF25-75. All statistical tests were performed at the 5% significance level.RESULTSTwenty-three (23) out of 31 consented participants completed oscillometry and spirometry successfully. Of the participants studied, 20/23 were African American and 16/23 were male. The age range was 7.3 - 14.7 years at time of study and the SCD genotypes included HbSS (16/23), HbSC (3/23), HbSβ+thalassemia (2/23) and HbSβ°thalassemia (2/23). Of the 22 questionnaire respondents, 10 described a history of asthma symptoms (wheezing, whistling in chest, wheezing with exercise or coughing at night), but only 4/22 reported experiencing symptoms in the preceding 12 months.We correlated the percent change from baseline between FEV1 vs. AX (r2 = -0.15, p= 0.49) and FEV1 vs R5 (r2 = -0.48, p = 0.02), as well as between FEF25-75 vs. AX (r2 = -0.24, p= 0.28) and FEF25-75 vs. R5 (r2 = -0.54, p= 0.008). We then compared the percentage of patients with improved bronchodilator response in FEV1 vs. AX (21.74 vs 65.22%; p= 0.0063) and FEV1 vs. R5 (21.74 vs 56.52%; p= 0.02) as well as FEF25-75 vs. AX (39.13 vs. 65.22%; p= 0.11) and FEF25-75 vs. R5 (39.13 vs. 56.52%; p= 0.29)CONCLUSIONOur findings suggest that airway function as denoted by percent changes in FEV1 and FEF25-75 (spirometry) better correlate with R5 (oscillometry) than AX and that percent change in R5 can serve as a good measure of airway obstruction in children with SCD who are unable to perform spirometry. In addition, a higher proportion of SCD patients showed improved bronchodilator response in oscillometry (AX, R5) when compared to spirometry (FEV1 , FEF25-75 ), suggesting that impulse oscillometry may be more sensitive in detecting bronchodilator responsiveness in children with SCD when compared to spirometry, even in children without acute symptoms of asthma or airway hyper-responsiveness. Prospective studies of oscillometry in younger children with SCD are necessary to evaluate its role in SCD pulmonary disease. DisclosuresNo relevant conflicts of interest to declare.

Lung function is associated with tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) levels in school-aged children

BackgroundTumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine with inflammatory and apoptotic properties. A complex relationship exists between TRAIL and the lung where both elevated TRAIL and TRAIL deficiency are associated with lung impairment. In neonatal mice, TRAIL is thought to translate respiratory infections into chronic lung disease but the association between TRAIL and lung function in childhood has not been assessed. AimTo assess the cross-sectional relationship between TRAIL levels and lung function in school-aged children. MethodsThe study cohort consisted of 170 school-aged children attending four schools in Malmö, Sweden. Lung volumes, impulse oscillometry (IOS) and serum TRAIL were measured for all children. Linear regression was used to assess changes in lung function per 1-SD increase in TRAIL. General linear models were used to assess mean lung function by tertiles (T) of TRAIL. ResultsMean age was 9.9 years (±0.6). A 1-SD increase in TRAIL was associated with lower values of FEV1 and FEV1/VC (change in FEV1 (L) and FEV1/VC ratio: −0.047, p-value 0.002, and −0.011, p-value 0.020, respectively) and higher values of lung resistance (change in R5 and R20 (kPa/(L/s)): 0.035, p-value <0.001 and 0.027, p-value 0.004, respectively). These associations remained significant after excluding children with pre-existing lung disease. Higher TRAIL levels were associated with more negative values for X5 in general linear models (Mean X5 (kPa/(L/s)) in T1 (low TRAIL): −0.193 vs T3 (high TRAIL): −0.216, p-value 0.026). ConclusionsHigh TRAIL levels are significantly associated with markers of pulmonary airflow obstruction in school-aged children.

Assessment of within-breath impulse oscillometry parameters in children with asthma.

Impulse oscillometry (IOS) measures respiratory resistance and reactance during tidal breaths and is a convenient tool for evaluation of lung function. Respiratory resistance and reactance can be measured separately during inspiration and expiration (inspiratory-expiratory analysis). We investigated the differences in inspiratory-expiratory measurements obtained using IOS between children with and without asthma. We analyzed 819 subjects aged 4-18 years, including asthmatic children (n = 600) and controls (n = 219). Asthma was diagnosed in accordance with the American Thoracic Society/European Respiratory Society guideline. Spirometry and IOS were performed in all subjects. In whole-breath analysis, the asthma group had higher resistance at 5 Hz (R5) and reactance area (AX) and lower reactance at 5 Hz (X5) than the control groups. In inspiratory-expiratory analysis, the asthma group showed increased expiratory R5 and AX and decreased expiratory X5 when compared with the control group. The absolute changes in R5, X5, and AX values between inspiration and expiration were greater in children with asthma than those in controls (0.138 ± 0.195 vs 0.102 ± 0.162, P = 0.014; -0.106 ± 0.200 vs -0.086 ± 0.434, P < 0.001 and 0.460 ± 11.63 vs 0.398 ± 2.88, P = 0.002, respectively). Inspiratory-expiratory IOS analysis differentiated asthmatic children from control subjects, reflecting airway narrowing on expiration in pediatric asthma. The changes in R5, X5, and AX between inspiration and expiration can be a useful index for diagnosis of asthma in children without assessment of the response to a bronchodilator.

Contribution of rostral fluid shift to intrathoracic airway narrowing in asthma.

In asthma, supine posture and sleep increase intrathoracic airway narrowing. When humans are supine, because of gravity fluid moves out of the legs and accumulates in the thorax. We hypothesized that fluid shifting out of the legs into the thorax contributes to the intrathoracic airway narrowing in asthma. Healthy and asthmatic subjects sat for 30 min and then lay supine for 30 min. To simulate overnight fluid shift, supine subjects were randomized to receive increased fluid shift out of the legs with lower body positive pressure (LBPP, 10-30 min) or none (control) and crossed over. With forced oscillation at 5 Hz, respiratory resistance (R5) and reactance (X5, reflecting respiratory stiffness) and with bioelectrical impedance, leg and thoracic fluid volumes (LFV, TFV) were measured while subjects were seated and supine (0 min, 30 min). In 17 healthy subjects (age: 51.8 ± 10.9 yr, FEV1/FVC z score: -0.4 ± 1.1), changes in R5 and X5 were similar in both study arms (P > 0.05). In 15 asthmatic subjects (58.5 ± 9.8 yr, -2.1 ± 1.3), R5 and X5 increased in both arms (ΔR5: 0.6 ± 0.9 vs. 1.4 ± 0.8 cmH2O·l-1·s-1, ΔX5: 0.3 ± 0.7 vs. 1.1 ± 0.9 cmH2O·l-1·s-1). The increases in R5 and X5 were 2.3 and 3.7 times larger with LBPP than control, however (P = 0.008, P = 0.006). The main predictor of increases in R5 with LBPP was increases in TFV (r = 0.73, P = 0.002). In asthmatic subjects, the magnitude of increases in X5 with LBPP was comparable to that with posture change from sitting to supine (1.1 ± 0.9 vs. 1.4 ± 0.9 cmH2O·l-1·s-1, P = 0.32). We conclude that in asthmatic subjects fluid shifting from the legs to the thorax while supine contributed to increases in the respiratory resistance and stiffness.NEW & NOTEWORTHY In supine asthmatic subjects, application of positive pressure to the lower body caused appreciable increases in respiratory system resistance and stiffness. Moreover, these changes in respiratory mechanics correlated positively with increase in thoracic fluid volume. These findings suggest that fluid shifts from the lower body to the thorax may contribute to overnight intrathoracic airway narrowing and worsening of asthma symptoms.

The role of impulse oscillometry in detecting airway dysfunction in athletes

Background: Impulse oscillometry (IOS) has previously been proposed to provide greater sensitivity than spirometry when employed with indirect bronchoprovocation testing for the diagnosis of airway dysfunction in athletes. However, this recommendation is based on a highly selected population of symptomatic patients. Objective: To compare IOS, spirometry and respiratory symptoms following indirect bronchoprovocation in a screened cohort of athletes. Methods: One hundred and one recreational athletes were recruited. Respiratory symptoms were assessed via the Dyspnoea-12 questionnaire. Spirometry and IOS were performed pre and post a eucapnic voluntary hyperpnoea (EVH) challenge. Results: Ninety-four athletes completed the study. Sixteen athletes (17%) were positive for airway dysfunction based on spirometry (i.e. ≥10% fall in FEV1) and 17 athletes (18%) based on IOS (i.e. ≥50% increase in R5). Only nine athletes (10%) met both diagnostic thresholds. A poor relationship was observed between respiratory symptoms (i.e. Dyspnoea-12 score) and all spirometry and IOS variables. A direct relationship was observed between percentage change in R5 (r = 0.65), Z5 (r = 0.68), RF (r = 0.65), AX (r = 0.69) and the maximum fall in FEV1 (ΔFEV1max; p < 0.001). A weak relationship was observed between R20 (r = 0.27), X5 (r = 0.37) and ΔFEV1max (p < 0.01). Conclusion: Impulse oscillometry and spirometry do not concur precisely following indirect bronchoprovocation. However, IOS detects additional cases of airway dysfunction in athletes and therefore may provide diagnostic value in this population. Further work is required to establish diagnostic thresholds and fully determine the place of IOS in screening athletes for airway dysfunction.

Regional differences in bronchial reactivity assessed by respiratory impedance

We used the Impulse Oscillometric System (IOS) to gain information concerning the distribution of hyper-reactivity along the bronchial tree during methacholine challenge test (MCT).37 subjects underwent MCT until reaching the provocative dose (PD20). At each dose, we estimated respiratory resistance at 5 and 20Hz (R5, R20), and reactance at 5Hz (X5). In non-responsive subjects (N=14) no changes in R5, R20, and X5 were observed during MCT. In responsive subjects, a wide spectrum of responses was found concerning frequency dependence and PD20. We describe two phenotypes representing the extremes of response. For PD20>400μg (N=13), MCT caused equal changes of resistance/reactance on varying oscillation frequencies, suggesting a homogeneous bronchoconstriction along the bronchial tree. For PD20<200μg (N=10), a remarkable frequency dependence was observed, with increase in R5, no change in R20, and decrease in X5, suggesting hyper-responsiveness of the distal airways paralleled by a change in visco-elastic properties of lung parenchyma.

Disparity Between Proximal and Distal Airway Reactivity During Methacholine Challenge

There is an increasing awareness of the role of distal airways in the pathophysiology of obstructive lung diseases including asthma and chronic obstructive pulmonary disease. We hypothesize that during induced bronchoconstriction: 1) disparity between distal and proximal airway reactivity may occur; and 2) changes in distal airway function may explain symptom onset in subjects with minimal FEV1 change. 185 subjects underwent methacholine challenge testing (MCT). In addition to spirometry, oscillometry was performed at baseline and after maximum dose of methacholine; 33/185 also underwent oscillometry after each dose. Oscillometric parameters included resistance at 5 and 20 Hz (R5, R20) and heterogeneity of distal airway mechanics assessed by frequency dependence of resistance 5–20 Hz (R5–20) and reactance area (AX). R5 varied widely during MCT (range -0.8 – 11.3 cmH2O/L/s) and correlated poorly with change in FEV1 (r = 0.17). Changes in R5 reflected changes in both R20 and R5–20 (r = 0.59, p<0.05; r = 0.87, p<0.0001). However, R20 increased only 0.3 cmH2O/L/s, while R5–20 increased 0.7 cmH2O/L/s for every 1cmH2O/L/s change in R5, indicating predominant effect of distal airway mechanics. 9/33 subjects developed symptoms despite minimal FEV1 change (<5%), while R5 increased 42% due to increased distal airway heterogeneity. These data indicate disparate behavior of proximal airway resistance (FEV1 and R20) and distal airway heterogeneity (R5–20 and AX). Distal airway reactivity may be associated with methacholine-induced symptoms despite absence of change in FEV1. This study highlights the importance of disparity between proximal and distal airway behavior, which has implications in understanding pathophysiology of obstructive pulmonary diseases and their response to treatment.

Impulse oscillometry in COPD: Identification of measurements related to airway obstruction, airway conductance and lung volumes

Impulse oscillometry system (IOS) assesses pulmonary resistance and reactance. We set out to investigate which IOS measurements are related to airflow obstruction, airway conductance and lung volumes in chronic obstructive pulmonary disease (COPD). Ninety-four COPD patients were recruited and 58 agreed to follow up after 1 year. IOS measurements (R5, R20, X5 & Fres), body plethysmography (sGaw, FRC, TLC, RV & IC) and spirometry (FEV(1)) were performed. Pearson or Spearman correlation determined the relationships between IOS and other measurements. R5, X5 and Fres were all significantly associated (p<0.05) with FEV(1), sGaw, TLC, RV and IC. However, R20 was not related to any of these measurements except for RV. The strongest associations were observed between FEV(1) and the reactance measurements X5 (r=0.48) and Fres (r=-0.44), and sGaw with X5 (r=0.47) and Fres (r=0.51). The r values for the associations with TLC and IC were all <0.25. There was no statistically significant change in the FEV(1), R5, X5 or Fres after 1 year, but R20 significantly increased over the year. The changes in R5 and R20 did not significantly correlate with the changes in FEV(1). In contrast, X5 changes were significantly related to FEV(1) changes over 1 year (r=-0.27, p=0.05), while for Fres changes there was a trend to statistical significance (p=0.08). IOS reactance measurements are more closely related than resistance measurements to other pulmonary function measurements in COPD patients. The IOS reactance measurements appear to be indicative of changes in pulmonary compliance caused by airflow obstruction.

Lung Function Measured by Impulse Oscillometry and Spirometry Following Eucapnic Voluntary Hyperventilation

The efficacy of impulse oscillometry (IOS) to measure airway calibre change is not fully established. To evaluate lung function change after eucapnic voluntary hyperventilation (EVH), and to compare IOS indices with spirometric maximal expiratory flow measurements. Twenty subjects (10 airway hyperresponsive [AHR+] and 10 normal [AHR--]) underwent IOS and spirometry before and for 15 min after 6 min EVH (inhaling 5% CO2, 21% O2, balance N2) at a target ventilation of 30 times the baseline value of the forced expiratory volume in 1 s (FEV1) at 20 degrees C. AHR+ was defined by a fall in FEV1 of 10% or greater from baseline after a provoking challenge. Airway resistance at 5 Hz (R5), reactance at 5 Hz, resonant frequency (Fres), area of reactance integrated from 5 Hz to Fres (AX), and FEV1 were determined. No baseline spirometry values correlated with falls in FEV1. Baseline R5 and AX values correlated with peak falls in FEV1 (r= -0.51 and -0.46, respectively; P< 0.05). AHR+ subjects demonstrated greater per cent peak falls in FEV1 than did AHR- subjects following EVH (30.6 +/- 14.0% versus 7.5 +/- 2.6%, respectively; P<0.05). Changes in R5, Fres, reactance and AX were greater for AHR+ subjects than for AHR- subjects and correlated with a fall in FEV1 (r= -0.74, -0.70, 0.69 and -0.73, respectively; P<0.05). At a designated specificity of 80%, the per cent change in R5 (50% or greater) and post-EVH AX (12 cm H2O/L or greater) yielded sensitivities to a 10% fall in FEV1 of 90%. IOS is an acceptable measure to determine AHR and can supplement spirometry in lung function evaluation.