Clinical applications of forced oscillation to assess peripheral airway function

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Abstract

Forced oscillation applies external pressures to the respiratory system to measure respiratory impedance. Impedance of larger central airways may be dissected from that of peripheral airways using multiple oscillation frequencies. Respiratory impedance is calculated by computer-assisted methods that yield separate resistive and reactive components. The reactive component includes respiratory system capacitative and inertive properties, which may be separately visualized for clinical purposes using resonance as a rough dividing line. Low oscillation frequencies comprise those below resonance, and relate most prominently to capacitative properties of peripheral airways. High oscillation frequencies comprise those greater than resonance, which relate most prominently to inertial properties of larger central airways. Measurements of resistance and reactance in patients with peripheral airway disease, before and after therapeutic intervention, manifest characteristic patterns of response in low frequency resistance and reactance measures that appear to be closely correlated with each other. In contrast, changes in large central airways manifest resistance change uniformly over low and high frequencies.

Introduction

This review focuses on clinical utility of the forced oscillation technique (FOT) in assessment of small airways. FOT is implemented by applying oscillations of pressure at either the airway opening (mouth) or at the body surface. The initial description of the FOT method included both types of pressure application (DuBois et al., 1956). While both methods appear useful in clinical research (Lutchen et al., 1998, Skloot et al., 2004), pressure application at the mouth is technically simpler and the present discussion is limited to such measurements. Comprehensive reviews of a broad range of clinical and physiological studies with FOT, since the method first came into use have been previously published (Navajas and Farre’, 1999, Goldman, 2001).

The fundamental assumption of FOT is that respiratory mechanics can be measured from superimposition of external pressure oscillations on the respiratory system during resting breathing. The basic model of the respiratory system upon which FOT analyses are based is a resistance–capacitance–inertance (RIC) model, with the resistance of the airways in series with the inertive/capacitative properties of thoracic gas, large and small airways, and lung tissues. This model clearly oversimplifies even the normal respiratory system, much less that of patients with lung disease; but tentative pressure–flow relationships may be described and compared with known respiratory mechanical features in normal subjects and patients with lung disease. At frequencies an order of magnitude greater than normal respiratory rate, respiratory inertance is a significant mechanical factor and FOT analyses include inertance effects.

FOT was initially applied using multiple single frequencies of sinusoidal oscillations (DuBois et al., 1956) between 2 and 18 cycles per second (Hz). A single frequency sinusoidal oscillation provides very good time resolution with measures of resistance potentially 2–18 times per second. Michaelson et al. (1975) developed a computer-driven loudspeaker output of mixed, multi-frequency waveform, analysis of which provided amplitude and phase of pressure–flow relationships at the cost of less temporal resolution, as the resulting data were analyzed in 16 s blocks. However, mathematical analyses of resistance (in-phase) and reactance (out-of-phase) were accomplished easily using a computer-implemented Fast Fourier Transform (FFT) to provide an extensive description of oscillatory pressure–flow relationships over a range of frequencies between 4 and 32 cycles per second (Hz). Làndsér et al. (1976) utilized pulses of pressure applied at the mouth two times per second, before concluding that a mixed, multi-frequency waveform provided improved signal-to-noise characteristics (Làndsér et al., 1982). Much later, the pulse technique was refined and produced commercially, called impulse oscillometry (IOS) (Klug and Bisgaard, 1998, Nielsen and Bisgaard, 2000, Nielsen and Bisgaard, 2001, Goldman et al., 2002, Marotta et al., 2003, Skloot et al., 2004). The advantages of IOS include good time resolution (five measured pulses per second) and continuous resolution in the frequency domain because the FFT analysis is based on a Fourier integral rather than a Fourier series (Fortney, 1987, Tipler, 1999).

While FOT offers the advantage of a non-invasive, effort-independent and minimally intrusive measure of airflow resistance during spontaneous breathing, some potential disadvantages must be acknowledged. The fact that FOT measures spontaneous breathing permits biological variability from moment to moment in a stable individual. Multiple replicate measurements are required to establish reliable mean values in an individual. Because measurements of transrespiratory pressure and flow are obtained at a single site, the mouth, calculated resistance and reactance include that of the entire respiratory system. Additional measurements of the distribution of mechanical properties between large and small airways are needed to derive peripheral airway mechanics.

Otis et al. (1956) developed a simple model of multiple parallel pathways to separate lung units, each with its own characteristic resistance in series with a compliant airspace. They applied their theory to a mechanical model with two parallel ‘lung’ units, and to normal subjects and patients with asthma and COPD at frequencies of breathing up to about two cycles per second. Grimby et al. (1968) extended the frequency range using FOT in human subjects from three to nine cycles per second, and accordingly included attention to inertance effects. Subsequent investigations are reviewed in this discussion to develop the concept that FOT applied at oscillation frequencies approximately between 5 and 35 Hz can provide useful information to help distinguish between large and small airways.

The thesis presented in this review is that FOT and IOS may be clinically useful to follow changes in small airways disease in patients with airflow obstruction (asthma and COPD) and following lung transplantation. Although the primary topic of this discussion is focused upon peripheral airway function, this review also discusses IOS effects in large airways, to contrast those in peripheral airways. Interpretation of IOS results is discussed in relation to illustrative representative recent FOT data obtained using IOS in clinical settings, while acknowledging that only very few correlations between FOT and clinico-pathological measures of peripheral airway disease have been published.

Section snippets

Partitioning mechanical function within the respiratory system

The anatomical studies of Weibel (1963) provided the infrastructure for modeling the respiratory system as a serial arrangement of conducting airways, progressively decreasing in diameter, with increasing numbers branches to multiple parallel pathways for distribution of flow. Otis et al. (1956) had reasoned that distribution of airflow both temporally and spatially among multiple parallel pathways for lung expansion would be governed by the distribution of time constants (the time constant of

Out-of-phase pressure–flow relationships

To this point, flow resistive components of FOT calculated from the in-phase pressure–flow relationships have been discussed. Spectral analyses also calculate a measure of the out-of-phase pressure–flow relationships known as reactance, simultaneously with calculations of resistance. Reactance is attributable to two out-of-phase mechanical contributions, those related to elastic/capacitative properties and to inertive properties (Peslin and Fredberg, 1986). These properties are both

Artefacts

To interpret IOS data properly, it is necessary to address potential artifacts that might otherwise be misleading. The uniform displacement in R at all frequencies that is characteristic of large airway changes can occur artefactually because IOS and other FOT methods using applied pressures at the mouth include oropharyngeal resistance as well as pulmonary effects. If the tongue position interferes with free airflow through the mouthpiece, a uniform increase in resistance will occur at all

Summary

Factors that may distinguish between small peripheral and large central airway function during FOT measurements have been reviewed. Importantly, it is recognized that very few pathophysiologic correlations of FOT parameters with direct evidence of small airway function have been published to date. Further investigations comparing lung biopsy with FOT in patients undergoing surveillance bronchoscopy after lung transplantation will be helpful. Other investigations comparing FOT changes with

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