ORIGINAL ARTICLE Year : 2021  Volume : 35  Issue : 1  Page : 2226 Diagnostic accuracy of respiratory impedance parameters to detect airflow obstruction in adults Sajal De Department of Pulmonary Medicine, National Institute for Research in Environmental Health, Kamla Nehru Hospital Building, Gandhi Medical College Campus, Bhopal, Madhya Pradesh, India Correspondence Address: OBJECTIVE: The present study was aimed to evaluate the diagnostic accuracy of impedance parameters to detect airflow obstruction and the severity of airflow obstruction in adults. METHODS: The spirometry parameters (forced expiratory volume in 1 s [FEV_{1}], forced vital capacity [FVC], FEV_{1}/FVC, FVC_{3}/FVC, and FEF_{2575}) and respiratory impedance parameters (R5, R19, R_{519}, and X5) measured by forced oscillation technique of consecutive 299 adults (male: 186) were included in the present analysis. The Spearman correlation coefficient (ρ) was used to assess the correlations of impedance parameters with spirometry indices. The area under the curve (AUC) was used to assess respiratory impedance parameters' diagnostic accuracy. RESULTS: The mean age of the study population was 54.1 ± 12.3 years, and 99 individuals (33%) had airflow obstruction (FEV_{1}/FVC < 0.70) in spirometry. All spirometry indices (% of predicted) showed a weak negative correlation with R5, R19, R_{519}, and weak positive correlation with X5. The R5 >142% predicted and X5 >136% predicted had the maximum AUC (0.75) with a sensitivity of up to 56% and specificity up to 86% to identify airflow obstruction. The impedance parameters showed low concordance with the severity of airflow obstruction. CONCLUSION: Respiratory impedance parameters had insufficient sensitivity to diagnose airflow obstruction and the severity of obstruction in adults. Thus, impedance parameters cannot a substitute for spirometry in diagnosing obstructive lung function.
Introduction Spirometry is an essential and most commonly used lung function test for diagnosing, managing and monitoring obstructive airway diseases such as asthma and chronic obstructive pulmonary diseases (COPD). The forceful expiratory maneuver of spirometry has a high potential for aerosol generation. In the current COVID19 pandemic situation, lung function tests with less risk of infection spread during the maneuvers are increasingly sought. Among the various alternatives to spirometry, measurement of the respiratory impedance is one of them.[1] Respiratory impedance is measured by various techniques such as the forced oscillation technique (FOT) or impulse oscillometry (IOS) or Airway Oscillometry Methods. In all these techniques, pressure waves of various frequencies are superimposed on the tidal breaths, and respiratory impedance is calculated by analyzing the resulting changes in pressure and flow relationships. Respiratory impedance comprises respiratory system resistance (Rrs) and reactance (Xrs). The ratio of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) <0.70 is conventionally considered as a marker of airflow obstruction in the spirometry of adults. FEV1% of predicted are used to classify the severity of airflow obstruction. Spirometry has insufficient sensitivity to detect early obstructive airway diseases when the diseases predominately involve the small airways.[2] The small airways (airways with an internal diameter of <2 mm) contribute only 20%–30% of total airway resistance, therefore known as the “silent zone of the lung.” The maximal midexpiratory flow rate (MMEF) of spirometry is conventionally considered a functional assessment of small airways. The ratio of FEV3/FVC is also proposed as a surrogate for small airway function in spirometry.[3] The importance of the respiratory impedance parameters in managing asthma and COPD is well documented.[4] The maneuvers of impedance measurements involve normal tidal breathing, thus have a lower risk of aerosol generation. The advantage of impedance is that it can be repeated multiple times without much discomfort to subjects and require little cooperation. Sick and elderly often not able to perform acceptable spirometry on repeated attempts. Therefore, diagnosing airflow obstruction by spirometry in these populations is challenging, and impedance parameters can be an alternative. The usefulness of impedance parameters as an alternative to spirometry in diagnosing airflow obstruction and the severity of airflow obstruction has never been reported from the Indian subjects. The present study aimed to assess the relationship of respiratory resistance (Rrs) and reactance with spirometry indices of adult subjects and evaluate the diagnostic accuracy of impedance parameters to detect airflow obstruction and airflow obstruction severity. Methods Study design The present study was a retrospective analysis of spirometry and impedance parameters of consecutive adult subjects carried out from April 2018 to November 2019 at Bhopal (India). Both FOT and spirometry were carried out on the same day, and FOT were performed before spirometry. Both spirometry and respiratory impedance parameters meet the American Thoracic Society (ATS)/European Respiratory Society (ERS) recommendations for acceptability and reproducibility criteria.[5],[6] The Institutional Ethics Committee approved the study protocol. The study protocol adhered to the Declaration of Helsinki guidelines, and no consent from participants was taken as the study was a retrospective analysis of lung function data. Spirometry The spirometry was performed in the sitting position and as per ATS/ERS guideline using PowerCube Diffusion+ (GANSHORN Medizin Electronic, Germany). The spirometry indices included in the present analysis were FVC, FEV1, FEV1/FVC, FEV3/FVC, and MMEF (FEF2575). The North Indian regression equations of spirometry indices were used to estimate the predicted normal values, and a lower limit of normal (LLN) was set at the 5th percentile.[7] If FVC ≥ LLN and FEV1/FVC ≥0.7, then lung function was categorized as normal. If FEV1/FVC was <0.70, then lung function was categorized as an obstructive pattern. Restrictive lung function was defined as FVC < LLN and FEV1/FVC ≥0.70, and these lung function data were excluded from the analysis. Based on FEV1% of predicted, the severity of obstruction was classified. The airflow obstruction was mild to moderate if FEV1% of predicted ≥50% and severe to very severe if FEV1%predicted <50%. Forced oscillation technique The respiratory resistance (Rrs) and reactance were measured at 5, 11, and 19 Hz by using Resmon Pro Full device® (RestechSrl, Milan, Italy) as per the ERS guideline. During the procedure, the nose clip was applied, the cheeks were supported, and tests were carried out in the sitting position with the neck in a comfortable and neutral position. The Rrs and Xrs values were expressed as the mean values of entire breathing cycles (wholebreath) and mean values of entire inspiration (inspiratory) and of entire expiration (expiratory) expiration. The mean parameters obtained during three acceptable tests (i.e., coefficient of variability of R5 of three tests <15%) were retained for analysis. The impedance parameters used in the present study were: (1) whole breath resistance at 5 Hz (R5) and 19 Hz (R19), indices of total and proximal airway resistance, respectively; (2) difference in resistance between R5 and R19 (R519); (3) wholebreath respiratory reactance at 5 Hz (X5); (4) △X5: The difference between the inspiratory and expiratory Xrs at 5 Hz. The predicted values, percentage of predictive values, upper limit of normal (ULN), and LLN of respiratory impedance parameters were calculated by using regression equations of Indian adults.[8] Statistics The statistical analysis was carried out by IBM® SPSS® Version 25 (IBM corp., Armonk, NY). The mean with standard deviation was used to describe the distribution of variables. Spearman's rankorder correlation (ρ) was used to assess the correlations between respiratory impedance parameters and spirometry indices. The validity of beyond normal impedance parameters (i.e., >ULN or < LLN) to diagnose airflow obstruction (FEV1/FVC < 0.70) was examined by calculating sensitivity, specificity, positive predictive value, negative predictive value along with 95% confidence intervals. The Receiver Operating Characteristics (ROC) curve for the diagnosis of airflow obstruction (FEV1/FVC <0.70) and small airways obstruction (MMEF < LLN) were constructed and quantified via the area under the curve (AUC) with the 95% confidence interval. A P < 0.05 was considered statistically significant. Results A total of 340 individuals performed both acceptable spirometry and respiratory impedance measurements during the study period. The data of 51 individuals with restrictive spirometry were excluded from the analysis. Therefore, the data of 299 individuals (male 186) were included in the present analysis, and out of them, 99 individuals had airflow obstruction in spirometry. The severity of airflow obstruction was as follows: 68% had mild to moderate, and 32% had severe to very severe obstruction. The mean age of the study population was 54.1 ± 12.3 years. The demographic characteristics of the study population are presented in [Table 1].{Table 1} Correlations of respiratory impedance with spirometry indices The Spearman correlation coefficient (ρ) for respiratory impedance parameters with spirometry indices (% predicted) are presented in [Table 2]. All impedance parameters showed a weak correlation coefficient (ρ < 0.46) with spirometry indices. The correlation coefficient of withinand wholebreath Rrs and Xrs with spirometry indices were not significantly different (data are not shown). Both R5 and R519 demonstrated weak negative correlations, and X5 demonstrated weak positive correlations with all spirometry indices. The correlation coefficient of △ X5 with all spirometry indices mostly had a little higher correlation as compared to X5. The correlation coefficient of all impedance parameters with small airway function parameters of spirometry, i.e., MMEF and FEV3/FVC was very close to each other. Among the impedance parameters, R5% predicted had the highest correlation coefficient with all spirometry indices.{Table 2} Diagnostic accuracy and optimum cutoff values The ROC curve analysis [Figure 1] for accuracy to diagnose airflow obstruction by respiratory impedance parameters revealed that both R5 and X5 had similar AUC (0.75), followed by R19 (AUC: 0.66) and R519 (AUC: 0.66). The sensitivity and specificity of the best cut of values of impedance parameters to detect airflow obstruction were ranged from 53% to 56% and 76%–85%, respectively [Table 3].{Figure 1}{Table 3} The diagnostic performance of > ULN of R5, R19, and R519 and < LLN of X5 to diagnose the severity of airflow obstruction is presented in [Table 4]. All impedance parameters, except for R19 had both low sensitivity and low specificity to diagnose the severity of airflow obstruction.{Table 4} The diagnostic accuracy of impedance parameters to detect small airways obstruction, i.e., MMEF < LLN are presented in [Table 5]. Among all impedance parameters, R5 >119% of predicted had the highest sensitivity (72%), and X5 >142% of predicted had the highest specificity (86%) to diagnose MMEF < LLN.{Table 5} Discussion In the present observational study, the relationship of respiratory impedance measured by FOT with spirometry indices was assessed. Whether the impedance parameters can be used as an alternative to spirometry to detect airflow obstruction and the severity of obstruction were also investigated. The Rrs component of respiratory impedance measures the amount of energy required to propagate the pressure waves and the Xrs component measures the amount of recoil generated against the pressure waves. At lower frequency, for example, 5 Hz, pressure wave travels up to the lung periphery and provides information on the entire respiratory system. Higher frequency pressure waves, i.e., 19 Hz cannot penetrate deep inside the lung and provide information primarily related to the central airways. It is suggested that ventilation defects in small airways lead to a higher magnitude of Xrs values at a lower frequency i.e., X5.[3] Traditionally, the difference in resistance between lower and higher frequency i.e., R519 or R520 is considered as a status of small airway function. However, recent research suggests that R519 represents the frequency dependence of Rrs, i.e., ventilation inhomogeneity.[9] With the increase in airway resistance Rrs values increase, and X5 became more negative. Previous investigators examined the relationship of respiratory impedance with spirometry indices in other ethnicity, and measurements were done mostly by IOS. Shirai and Kurosawa. reported both withinand wholebreath impedance parameters had a significant correlation with spirometry indices. The ρ values for FEV1%, FEV1/FVC, and MMEF% with R5, R20, and R520 in their study varied from ‒0.24 to ‒0.58; and with X5 from 0.34 to 0.44.[10] Wei et al. reported the ρ value for R5 and X5 with FEV1, FEV1% predicted, FEV1/FVC, MMEF% predicted of COPD patients varied from ‒0.25 to 0.32 and 0.47 to 0.57 respectively.[11] Mori et al. observed the correlation of impedance parameters with spirometry indices was variable across the healthy, COPD, and asthma patients.[12] Yamamoto et al. found that both FEV1 and FVC had moderated, and FEV1/FVC had a weak correlation with impedance parameters.[13] They also found the regression equations of FEV1 and FVC generated by FOT parameters were very accurate with the predicted values. Shirai and Kurosawa found respiratory impedance parameters weakly correlated spirometry parameters of wellcontrolled asthma patients.[10] Like earlier studies, the current study's impedance parameters also showed a significant but moderate to weak correlation with spirometry indices, including FEV1/FVC. COPD patients usually have higher △ X5 i.e., expiratory flow limitation due to loss of elastic recoil property of the lung and Shirai and Kurosawa observed △ X5 in bronchial asthma did not correlate with any of the spirometry indices.[10] Whereas, △X5 in the present study showed a significant correlation with all spirometry indices and the correlation coefficient is mostly higher as compared to X5, except for FVC%.[10] This was maybe due to a higher number of COPD patients in the current study population. The involvement of small airways is common in both COPD and bronchial asthma. Pisi et al. examined the relationship of impedance with spirometry in a cohort of bronchial asthma with normal FEV1 values.[14] The found MMEF significantly correlates with R520 (r = ‒0.38, P = 0.027), but not with X5. MMEF% of the present study population showed a significant but weak correlation with all impedance parameters. The correlation of FEV3/FVC with impedance parameters was not explored earlier. The correlation coefficient of FEV3/FVC with impedance parameters of the present study was a little higher as compared to MMEF% predicted. The correlation of impedance parameters with spirometry indices is mostly weak as spirometry and FOT measure different lung function aspects and cannot be equated with each other. The diagnostic performance of impedance parameters to identify airflow obstruction in COPD patients was examined by Wei et al.[11] Thy observed AUC of R5 and X5 with FEV1% pred <50% varied from 0.71 to 0.76. In the current study, the most accepted airflow obstruction criteria in spirometry, i.e., FEV1/FVC <0.70 was used as it is conventionally considered a gold standard. However, the AUC of both R5 and X5 in the present study to detect airflow obstruction was found to be very similar to above the study, and the cutoff values had low diagnostic capacity. The present study was the first to examine the AUC of impedance parameters to detect the conventional small airway function parameter of spirometry, i.e., MMEF < LLN. The cutoff values of R5 (119% of predicted) showed the highest sensitivity (72%). The beyond normal impedance parameters, i.e., parameters < LLN or > UNN, had a low sensitivity to identify mild to moderate airflow obstruction. conclusion The impedance parameters had a weak to moderate correlation with spirometry indices. The impedance parameters had a limited potential to diagnose airflow obstruction and the severity of airflow obstruction. Therefore, the respiratory impedance parameters cannot substitute for spirometry diagnosing airflow obstruction and severity of obstruction. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. References


