Inspiratory resonant frequency of forced oscillation technique as a predictor of the composite physiologic index in interstitial lung disease

doi:10.1016/j.resp.2014.12.009

Respiratory Physiology & Neurobiology

Volume 207, 1 February 2015, Pages 22-27

https://doi.org/10.1016/j.resp.2014.12.009 Get rights and content

Highlights

•
The usefulness of the forced oscillation technique in interstitial lung disease is unclear.
•
The composite physiologic index (CPI) is derived from FEV1, FVC, and diffusing capacity.
•
We assessed the relationship between the CPI and forced oscillatory parameters in interstitial pneumonia.
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Inspiratory resonant frequency of forced oscillation technique was an independent predictor.
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Fibrosis score was also an independent predictor of the CPI.

Abstract

The composite physiologic index (CPI), which is derived from FEV1, FVC, and diffusing capacity, has been developed to predict the extent of fibrosis on high-resolution computed tomography (HRCT). However, the relevance to the forced oscillation technique (FOT) is not fully understood. We hypothesized that FOT would independently predict the CPI in interstitial lung disease (ILD). In this cross-sectional study we assessed the relationship between pulmonary function tests, forced oscillatory parameters, and the degree of fibrosis in ILD. Spirometry, evaluation of diffusing capacity for carbon monoxide, and the broadband frequency FOT were performed in 93 patients with a clinical/HRCT diagnosis of ILD. The CPI was calculated and fibrosis extent was measured by HRCT and scored. Univariate analyses revealed that, of the forced oscillatory parameters, inspiratory resonant frequency best correlated with FVC, FEV1, diffusing capacity, CPI, and fibrosis score. In multiple regression analyses, CPI was independently predicted by inspiratory resonant frequency and fibrosis score (model R² = 0.405, p < 0.0001).

Introduction

Clinical application of the broadband frequency forced oscillation technique (FOT) has progressed recently and an increasing number of reports have examined its usefulness in the evaluation or management of obstructive lung diseases, including COPD or asthma (Paredi et al., 2010, Mori et al., 2011); however, very few investigators have examined respiratory impedance in interstitial lung disease (ILD). Van Noord et al. (1989) measured respiratory system resistance (Rrs) and reactance (Xrs) between 4 and 26 Hz by means of FOT in patients with ILD. They observed higher values of Rrs and decreases in Xrs, which were similar to those in moderate obstructive lung diseases. Mori et al. (2013) found that absolute values of Xrs were smaller in expiratory phases than in inspiratory phases in patients with ILD, which was the reverse change compared with that in patients with COPD. Sugiyama et al. (2013) showed a negative correlation between the differences between inspiratory and expiratory phases of Xrs at 5 Hz (ΔX5) and vital capacity or diffusing capacity.

The composite physiologic index (CPI), which is derived from forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and diffusing capacity for carbon monoxide (DLco), has been developed to predict the extent of fibrosis on high-resolution computed tomography (HRCT), adjusting for emphysema in patients with idiopathic pulmonary fibrosis (IPF) (Wells et al., 2003). A recent large cohort study showed that the CPI was superior to each pulmonary function test and a strong predictor of mortality in IPF (Schmidt et al., 2011). In contrast to spirometry or measurements of DLco, FOT is a method that is easy to perform in elderly patients or those with severe diseases. Forced oscillations are superimposed on tidal breathing, avoiding the need for any special breathing maneuver or noticeable interference with respiration. Furthermore, the relevance of FOT to pulmonary function tests, the CPI, and the degree of fibrosis in ILD is not fully understood. We hypothesized that FOT would predict independently the CPI, thereby becoming a useful biomarker in the management of ILD. In this cross-sectional study, we assessed the relationship between pulmonary function tests, forced oscillatory parameters, and the degree of fibrosis in 93 patients with ILD.

Section snippets

Subjects

Ninety-three patients with ILD who attended outpatient clinics at Shizuoka General Hospital for routine check-ups between August 2011 and July 2013 were enrolled in this study. According to the classification of the ATS/ERS guidelines (Travis et al., 2013), the patients were diagnosed clinically and using HRCT with IPF in 28, non-IPF idiopathic interstitial pneumonias (Non-IPF IIPs) in 31, collagen vascular disease-associated interstitial pneumonia (CVD-IP) in 26, chronic hypersensitivity

Results

The clinical characteristics of the subjects are shown in Table 1. The characteristics of the ILD subgroups (IPF, Non-IPF IIPs, CVD-IP, and others) are also summarized in Supplemental Table 1. The patients with ILD were older and included more smokers and pack-years, lower values of FVC, FEV1, TLC, X5 (whole-breath, inspiratory, and expiratory), and ΔALX, and higher values of R5 (whole-breath, inspiratory, and expiratory), R20 (whole-breath), ΔX5, Fres, and ALX (whole-breath, inspiratory, and

Discussion

We assessed whether forced oscillatory parameters and fibrosis extent contributed independently to the CPI, which was derived from FEV1, FVC, and DLco in 93 patients with ILD. It was found that the CPI was independently predicted by inspiratory Fres, a forced oscillatory parameter, and fibrosis extent as measured by HRCT. These results suggest that FOT may be useful in the management of ILD.

Originally, the CPI was developed to predict the extent of fibrosis on HRCT and improve on previous

Funding

None.

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Cited by (28)

Window of opportunity for respiratory oscillometry: A review of recent research
2023, Respiratory Physiology and Neurobiology
Oscillometry has been around for almost 70 years, but there are still many unknowns. The test is performed during tidal breathing and is therefore free from patient-dependent factors that could influence the results. The Forced Oscillation Technique (FOT), which requires minimal patient cooperation, is gaining ground, particularly with elderly patients and children. In pulmonology, it is a valuable tool for assessing obstructive conditions (with a distinction between central and peripheral obstruction) and restrictive disorders (intrapulmonary and extrapulmonary). Its sensitivity allows the assessment of bronchodilator and bronchoconstrictor responses. Different lung diseases show different patterns of changes in FOT, especially studied in asthma and chronic obstructive pulmonary disease. Because of these differences, many studies have analysed the usefulness of this technique in different areas of medicine. In this paper, the authors would like to present the basics of oscillometry with the areas of its most recent clinical applications.
Respiratory reactance in forced oscillation technique reflects disease stage and predicts lung physiology deterioration in idiopathic pulmonary fibrosis
2020, Respiratory Physiology and Neurobiology
Citation Excerpt :
Conversely, Xrs was believed to be more important for the assessment of ILD pathophysiology, as the current study demonstrated. Fujii et al. (2015) found that Fres in the inspiratory phase correlated with the FVC, FEV1, DLCO, and fibrosis score in ILD. Sugiyama et al. (2013) reported that the presence of ILD was associated with ΔX5 and that ΔX5 was negatively correlated with VC and DLCO.
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease. Although pulmonary function test (PFT) is useful for evaluating the progression of IPF, obtaining adequate results in advanced cases can be challenging. Conversely, the forced oscillation technique (FOT) can be noninvasively performed, even in patients with severely deteriorated lung function. In this study, the usefulness of FOT for the evaluation of IPF disease status was investigated.
We analyzed the PFT and FOT data of 97 patients with IPF.
The respiratory reactance (Xrs) components of FOT, especially in the inspiratory phase, correlated with the PFT values. Patients with advanced disease had significantly lower reactance at 5 Hz (X5), higher resonant frequency (Fres) and low-frequency reactance area (ALX). The longitudinal deterioration of Xrs was also observed. Moreover, X5 in the inspiratory phase predicted subsequent lung capacity deterioration.
The Xrs components of FOT, especially in the inspiratory phase, reflected restrictive ventilatory impairment and disease severity in patients with IPF.
Forced Oscillation Technique and Small Airway Involvement in Chronic Hypersensitivity Pneumonitis
2019, Archivos de Bronconeumologia
Citation Excerpt :
Higher frequencies (>20 Hz) travel shorter distances, such as in the large airways, while lower frequencies (<15 Hz) travel deeper into the lung and reach the small airways.14 FOT has been used for the evaluation of asthma16,17 and chronic obstructive pulmonary disease (COPD)18–20; however, its role in the evaluation of small airway involvement in ILD is relatively incipient.21–26 Increased Rrs values at low frequencies have been found in sarcoidosis,24 silicosis27 and asbestosis,28 while reactance at 5 Hz (X5) values are usually low in patients with ILD.22
Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by the inhalation of specific organic antigens or low-molecular weight substances in genetically susceptible individuals. Although small airway involvement is prominent in patients with chronic HP, conventional pulmonary function tests (PFTs) are relatively insensitive to identify it. Thus, the authors aimed to evaluate resistance (R5) and reactance (X5) values at 5 Hz on inspiration, expiration, and whole breath, as well as small airway resistance (R_5–19) values using a forced oscillation technique (FOT) in patients with chronic HP, and their responses after bronchodilator. In addition, R5 and X5 values according to the presence or absence of mosaic attenuation on computed tomography (CT) were compared.
PFTs with plethysmography, diffusing capacity of the lungs for carbon monoxide (DL_CO) and FOT measurements were performed pre-bronchodilator and post-bronchodilator. High-resolution CT was performed at the same visit, and classified according to the presence or absence of mosaic attenuation. R5 and X5 values were then compared according to the presence or absence of mosaic attenuation on CT.
Twenty-eight patients with chronic HP (57.1% female; mean age, 56 ± 11.5 years; mean forced vital capacity 57 ± 17% predicted) were evaluated. All patients had low X5 values, reflecting lower lung compliance, and only three (8%) demonstrated elevated R5 (whole-breath) values. No patients exhibited bronchodilator response in R5, X5 and R_5–19 values. In patients who exhibited greater extension of mosaic attenuation (n = 11), R5 and X5 values could not discriminate those with a greater presence of these areas on CT.
The results suggest that FOT does not help to additionally characterise concomitant small airway involvement in patients with chronic fibrotic HP who demonstrate restrictive ventilatory pattern in conventional PFTs. Nevertheless, FOT appeared to better characterise decreased lung compliance due to fibrosis through X5. Bronchodilator therapy did not appear to induce an acute response in chronic HP patients with restrictive disease. The precise role of FOT in subacute HP and obstructive chronic HP, therefore, must be evaluated.
La neumonitis por hipersensibilidad (HP) es una enfermedad pulmonar intersticial causada por la inhalación de antígenos orgánicos específicos o sustancias de bajo peso molecular en individuos genéticamente susceptibles. Aunque la implicación de las vías aéreas pequeñas es típica en pacientes con HP crónica, a las pruebas habituales de función pulmonar (PFP) les falta sensibilidad para detectarla. El objetivo fue evaluar los valores de resistencia (R5) y de reactancia (X5) a 5 Hz durante la inspiración, la espiración y el ciclo completo, así como los valores de resistencia de las vías aéreas pequeñas y las respuestas tras broncodilatador. Para ello se utilizó la técnica de oscilación forzada (TOF) en pacientes con HP crónica. Además, se comprobaron los valores R5 y X5, de acuerdo con la presencia o ausencia de patrones de atenuación en mosaico mediante tomografía computarizada (TC).
Se evaluaron las PFP con pletismografía, la capacidad de difusión pulmonar para el monóxido de carbono (DL_CO) y la TOF antes y después de broncodilatador (pre- y posbroncodilatador, respectivamente). La TC de alta resolución se realizó en la misma visita, y los resultados se clasificaron en función de la presencia o ausencia de patrones de atenuación en mosaico.
Se evaluaron 28 pacientes con HP crónica (57,1% mujeres; edad media: 56 ± 11,5 años; capacidad vital forzada media estimada: 57 ± 17%). Todos los pacientes tuvieron valores X5 bajos, indicativo de una distensibilidad pulmonar baja, y solo 3 (8%) presentaron valores elevados de R5 (respiración completa). Ningún paciente exhibió respuesta broncodilatadora en valores R5, X5 y R_5-19. Los valores de R5 y X5 no permitieron discriminar a aquellos pacientes que presentaron patrón de atenuación en mosaico extenso en la TC (n = 11).
Los resultados sugieren que la TOF no proporciona información extra en la caracterización de la implicación concomitante de las vías aéreas pequeñas en pacientes con HP crónica que presentan patrones ventilatorios restrictivos en PFP convencionales. Sin embargo, la TOF parece permitir una mejor caracterización de la disminución de la distensibilidad pulmonar debido a fibrosis a través del valor X5. La terapia broncodilatadora no indujo respuesta aguda en pacientes con HP crónica y enfermedad restrictiva. Por tanto, se debe evaluar el papel específico de la TOF en la HP subaguda y la HP obstructiva crónica.
Longitudinal changes in pulmonary function and respiratory impedance of rheumatoid arthritis
2019, Respiratory Physiology and Neurobiology
Citation Excerpt :
It is expected that FOT will be able to identify respiratory abnormalities that are not detectable by spirometric examinations (Oostveen et al., 2013; da Costa et al., 2014; Ito et al., 2017). Moreover, FOT has been used to characterize respiratory mechanics of interstitial lung disease and RA-related pulmonary diseases (Faria et al., 2012; Sugiyama et al., 2013; Fujii et al., 2015; Sokai et al., 2016). Several studies have investigated the longitudinal changes in pulmonary functions of RA (Linstow et al., 1994; Fuld et al., 2003; Zamora-Legoff et al., 2017), but the parameters of the long-term changes in Zrs of RA are not known.
The aim of this study was to examine long-term changes in pulmonary function and respiratory impedance (Zrs) as assessed by forced oscillation technique (FOT) of rheumatoid arthritis (RA)-related pulmonary disorders. Data of 42 RA patients who underwent pulmonary function tests and Zrs measurements at least twice at a >900-day interval were retrospectively reviewed. Zrs, respiratory resistance (Rrs) and reactance (Xrs), were measured as a function of oscillatory frequency from 4 to 36 Hz. The Rrs and difference between inspiratory and expiratory phases of Xrs were significantly decreased. Annual changes in Xrs parameters significantly correlated with those of spirometric parameters. Zrs parameters were significantly different between the low (the lower 75 percentile of incidence) and high (the top quartile) frequency of adverse respiratory event groups. The Zrs combined with spirometry may be beneficial to evaluate alterations in respiratory functions of RA.
Forced oscillation technique in veterans with preserved spirometry and chronic respiratory symptoms
2019, Respiratory Physiology and Neurobiology
Citation Excerpt :
HRCT patterns of decreased attenuation and ground glass opacities are suggestive of emphysematous and interstitial changes, and these features are commonly associated with reductions in DLCO. In fact, Fujii et al. (2015) found that more negative reactance values were associated with worse DLCO in patients with interstitial lung disease, and no associations were observed with measures of resistance. That reduced DLCO was only observed among those with Abnormal AX in the present study appears to support this earlier work.
To evaluate the utility of the forced oscillation technique (FOT) among military veterans with preserved spirometry and chronic unexplained respiratory symptoms.
178 veterans referred for evaluation of unexplained respiratory symptoms completed pulmonary function testing and FOT. Preserved spirometry was defined as FEV₁/FVC, FEV₁ and FVC ≥ 5th percentile. Frequency dependence of resistance (R4-R20) and reactance area (AX) were assessed via FOT, and R4-R20 ≥ 20% and AX ≥ 95th percentile were considered abnormal.
Spirometry was preserved in 71.3%, of whom 124 had acceptable FOT data. 93 of 124 (75.0%) veterans with preserved spirometry had one or more abnormal findings on FOT. Veterans with abnormal R4-R20 and/or AX had reduced FVC, FEV₁, FEF_25-75, and diffusing capacity (% predicted) in comparison to those with Normal FOT (p = 0.030 to p < 0.001).
In our referral sample, distal airway dysfunction in the presence of preserved spirometry appears common and may represent an at-risk group requiring closer surveillance.
Responsiveness to bronchodilator procaterol in COPD as assessed by forced oscillation technique
2017, Respiratory Physiology and Neurobiology
Citation Excerpt :
Measurement of respiratory system impedance (Zrs), respiratory resistance (Rrs), and reactance (Xrs), has been used to assess respiratory functions of pulmonary diseases, specifically COPD (Dellaca et al., 2004; Ito et al., 2005; Mishima, 2009; Kanda et al., 2010; Paredi et al., 2010; Ohishi et al., 2011; Hasegawa et al., 2015; Akita et al., 2016; Shirai and Kurosawa, 2016). FOT enables measurement of both inspiratory and expiratory parameters during tidal breathing (Cauberghs and Van De Woestijne, 1992; Peslin et al., 1992; Dellaca et al., 2004; Kanda et al., 2010; Paredi et al., 2010; Fujii et al., 2015; Sokai et al., 2016). Spirometry is a standard method to diagnose COPD and evaluate severity and response to medications of this disease (GOLD-2016, 2016).
The aim of this retrospective study was to assess responses to a bronchodilator by forced oscillation technique (FOT) and to relate the results of respiratory impedance (Zrs) to spirometric parameters in patients with chronic obstructive pulmonary disease (COPD). Zrs was measured as a function of frequency from 4 to 36 Hz before and after inhalation of procaterol, a short-acting β₂-agonist (n = 60). Respiratory resistance (Rrs) and reactance (Xrs) were significantly frequency-dependent, and inspiratory and expiratory phases were different both before and after procaterol inhalation. The Rrs at 4 Hz and Xrs at 4–20 Hz during a whole breath were significantly improved after procaterol inhalation. The response to procaterol inhalation varied among patients, and changes in Xrs at 4 Hz significantly correlated with% change in forced expiratory volume in one second and changes in forced vital capacity. Taken together, Zrs, and specifically Xrs parameters, are sensitive to acute physiological responses to a bronchodilator in COPD.

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¹: These authors contributed equally to this work.

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Inspiratory resonant frequency of forced oscillation technique as a predictor of the composite physiologic index in interstitial lung disease

Highlights

Abstract

Introduction

Section snippets

Subjects

Results

Discussion

Funding

Respir. Med.

Respir. Physiol. Neurobiol.

Respir. Physiol. Neurobiol.

Respir. Med.

Standardization of spirometry, 1994 update

Am. J. Respir. Crit. Care Med.

Effect of bronchodilation on expiratory flow limitation and resting lung mechanics in COPD

Eur. Respir. J.

Fleischner Society: glossary of terms for thoracic imaging

Radiology

Nonspecific interstitial pneumonia: prognostic significance of high-resolution computed tomography in 59 patients

J. Comput. Assist. Tomogr.

Guidelines of Respiratory Function Tests: Spirometry, Flow-Volume Curve, and Diffusion Capacity of the Lung