Abstract
Respiratory system reactance changed over 5 years and the initial level predicted the rate of change in COPD patients http://ow.ly/ONzz308E3aD
To the Editor:
Since the landmark study of the natural history of chronic obstructive pulmonary disease (COPD) by Fletcher and Peto [1], lung function decline has been an issue of great concern and an important therapeutic target. The annual decline in forced expiratory volume in 1 s (FEV1) is generally used as a marker of disease progression. A review of large longitudinal studies found that the mean rate of FEV1 decline was highest at Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II (47–79 mL·year−1), indicating the need for treatment at earlier stages of the disease [2].
The forced oscillation technique (FOT) is a noninvasive method that is used to measure respiratory system resistance (Rrs) and reactance (Xrs) during tidal breathing. Its clinical application has recently progressed worldwide with the spread of commercially available broadband frequency FOT devices. Because correlations between forced oscillatory parameters and spirometric indices are modest, complementary use of both tests may provide useful information regarding lung function [3]. In this study, we assessed whether there would be a long-term change in forced oscillatory parameters and whether the initial FOT index levels could predict the rate of change in these parameters, the so-called “horse-racing effect” [4], in a cohort of patients with COPD.
We retrospectively collected clinical data of outpatients who underwent FOT and spirometry on the same day at a 5-year interval at Shizuoka General Hospital (Shizuoka, Japan) between 2010 and 2015. Subjects included 24 male patients (mean values: age 75 years, body mass index 21.9 kg·m−2, smoking history 68 pack-years, FEV1 1.65 L and FEV1 z-score −3.18). All patients satisfied the GOLD definition of COPD and had been receiving medication, including long-acting muscarinic antagonists, long-acting β2-agonists, inhaled corticosteroids or sustained-release theophylline. COPD grading was based on the GOLD classification and FEV1/height2 (L·m−2) [5]. The patients were clinically stable and had no exacerbations for ≥1 month before the examination. Broadband frequency FOT and spirometry were performed using MostGraph-01 and CHESTAC-33 (Chest M.I., Tokyo, Japan), respectively. We used Rrs at 5 and 20 Hz (R5 and R20, respectively) and the difference between R5 and R20 (R5–R20) as indicators of the frequency dependence of Rrs. In addition, we used Xrs at 5 Hz (X5), which reflects elastic and inertial properties of the lung; resonant frequency (Fres), where Xrs crosses zero and the elastic and inertial forces are equal in magnitude and opposite; and a low-frequency reactance area (AX), which is an integral of X5 to Fres. Oscillatory indices were expressed as mean values during a respiratory cycle. To determine pulmonary function while receiving daily treatment, medications were not withdrawn before FOT and spirometry, and measured data were expressed as post-bronchodilator values. FEV1 z-scores were derived from the Global Lung Function Initiative reference equations that adjust for age, sex, height and race [6]. The FOT indices were normally distributed after transforming into natural log (R5, R20, Fres and AX), square root (R5–R20) or exponential (X5) values. Rrs and Xrs z-scores were derived from the reference values of MostGraph measures for the middle-aged and elderly Japanese population (n=784) who participated in annual health check-ups [7]. Comparisons between baseline and after 5 years were made using the paired t-test. Correlations between variables were performed using Pearson's correlation coefficient. A p-value of <0.05 was considered significant. EZR (version 1.27; Saitama Medical Center, Jichi Medical University, Saitama, Japan) was used for statistical analyses.
FEV1 and Xrs indices, including X5, Fres and AX, significantly changed at the 5-year interval (mean absolute values: FEV1 1.65–1.40 L, X5 −1.48–−2.08 cmH2O·L−1·s−1, Fres 12.34–15.87 Hz and AX 10.81–17.01 cmH2O·L-1). Changes in FEV1 and Xrs z-scores by COPD grading system are shown in table 1. The changes per year for all parameters appear highest at GOLD stage II; however, this did not reach statistical significance. For the data graded by FEV1/height2, there is a trend for less annualised change in X5, Fres and AX moving from group 1 through to group 4, which is not seen in the GOLD classification. There were no significant changes in Rrs indices, including R5, R20 and R5−R20 over 5 years. There was a significant correlation between change in FEV1 and Xrs (correlation coefficient: X5 0.410, Fres 0.422 and AX 0.434). Concerning the horse-racing effect, there was no correlation between the initial FEV1 level and the rate of change in FEV1, regardless of whether analysed by absolute value or z-score. However, there was a negative correlation between the initial Xrs z-scores and the rate of change in Xrs z-scores (correlation coefficient X5 −0.546, Fres −0.411 and AX −0.591). No correlation was observed between the initial absolute Xrs levels and the rate of change in absolute Xrs.
In this study, Xrs indices changed significantly over 5 years, and there was a significant correlation between changes in FEV1 and Xrs. This is the first study to indicate that the lung function decline in patients with COPD affects not only spirometry but also FOT. This suggests that Xrs indices, including X5, Fres and AX, measured during tidal breathing, are markers of lung function decline in patients with COPD. The lack of significant changes in Rrs indices over 5 years may be explained by the previous finding that Xrs indices were more sensitive to the increased severity of COPD than Rrs indices [8]. The relationship between the FEV1 level and the rate of change in FEV1 has been termed the horse-racing effect, meaning that the lower the level of function, the greater the rate of decline [4]. In this study, we found a negative correlation between the initial Xrs z-scores and the rate of change in Xrs z-scores, suggesting that the measurement of Xrs leads to the early detection of lung function decline in patients with COPD. The lack of significant correlation between the FEV1 level and the rate of change in FEV1 could potentially be explained by the limited sample size. Altogether, the results obtained by FOT correlate with those obtained by spirometry, but they are not identical. This indicates that FOT is not a surrogate test for spirometry, but should be used concomitantly. In older patients who have difficulty in undergoing a spirometry test, FOT would be particularly useful. Additional larger prospective studies are required to confirm whether Xrs is useful as a marker of lung function decline and can be used as a therapeutic target in COPD.
Footnotes
Conflict of interest: None declared.
- Received April 6, 2016.
- Accepted January 20, 2017.
- Copyright ©ERS 2017