Measuring Upper and Lower Airway Resistance During Sleep

with the Forced Oscillation Technique

LISA M. CAMPANA,1,2 R. L. OWENS,2 B. SUKI,1 and A. MALHOTRA2

1Boston University, Boston, MA, USA; and 2Division of Sleep Medicine, Department of Medicine, Brigham and Women’sHospital, 221 Longwood Avenue, Boston, MA 02115, USA

(Received 16 August 2011; accepted 9 November 2011; published online 30 November 2011)

Associate Editor John H. Linehan oversaw the review of this article.

Abstract—The forced oscillation technique (FOT) is a non-invasive technique to monitor airway obstruction in thosewith asthma. The aim of this study was to design and validatea system to use FOT during sleep, both with and withoutbi-level positive airway pressure (BPAP), and to separateupper airway resistance from lower. 8 Hz pressure oscilla-tions were supplied, over which the subject breathed,pressure and flow measurements were then used to calculateimpedance. A phase-shift induced by the pressure transducertubing was characterized, and FOT resistance was comparedto steady flow resistance both with and without BPAP. AMillar catheter was used to measure pressure at the epiglottis,allowing the separation of upper from lower airway resis-tance. A phase shift of 20.010 s was calculated for thepressure transducer tubing, and the average error betweenFOT and steady flow resistance was 20.2 ± 0.2 cmH2O/L/swithout BPAP and 0.4 ± 0.2 cmH2O/L/s with BPAP. Thesystem was tested on three subjects, one healthy, one withobstructive sleep apnea, and one with asthma. The FOT waswell tolerated and resistance was separated into upper andlower airway components. This setup is suitable for moni-toring both upper and lower airway obstruction during sleepin those with and without asthma.

Keywords—Asthma, Lung, Apnea, Airway mechanics,

Impedance.

ABBREVIATIONS

FOT Forced oscillation techniqueBPAP Bi-level positive airway pressurePfar Pressure measured at a distance from the

FOT systemPshort Pressure measured near the FOT system

Pmillar Pressure measured from Millar catheterPm Pressure measured at a nasal mask_V FlowRrs Respiratory system resistanceRup Upper airway resistanceRlow Lower airway resistance

INTRODUCTION

Many people with asthma experience nighttimewheezing and awakenings due to lower airway con-striction. One study found that 64% of those withasthma experience nocturnal symptoms at least threetimes a week.26 Nocturnal symptoms are well knownto be predictive of poor asthma control and thus pooroutcome in these patients.24 However, the typicalmetrics of asthma control [such as the peak expiratoryflow and the forced expiratory volume expelled in 1 s(FEV1)] require cooperation during wakefulness toassess. As such, changes in respiratory function aredifficult to monitor while the subject is asleep. In the-ory, medical therapy could be intensified in thosepatients who are poorly controlled, prior to thedevelopment of overt symptoms or exacerbations. Onthe other hand, the situation is complicated duringsleep since both upper and lower airway resistance canbe considerably impacted by the transition fromwakefulness to sleep. One potential method to monitorairway caliber during sleep is the forced oscillationtechnique (FOT).

The FOT was introduced in 1956 by Dubois et al. asa non-invasive measure of respiratory mechanicalproperties.7 FOT uses small pressure oscillationssuperimposed on top of the subject’s normal breathing,with the resulting pressure and flow signals being used

Address correspondence to Lisa M. Campana, Division of Sleep

Medicine, Department of Medicine, Brigham andWomen’s Hospital,

221 Longwood Avenue, Boston, MA 02115, USA. Electronic mail:

lcampana@bu.edu

Annals of Biomedical Engineering, Vol. 40, No. 4, April 2012 (� 2011) pp. 925–933

DOI: 10.1007/s10439-011-0470-7

0090-6964/12/0400-0925/0 � 2011 Biomedical Engineering Society

925

to calculate impedance of the respiratory system.Although multiple parameters can be assessed, byselecting a single 8 Hz pressure input one can trackairway resistance changes on a breath to breath basis.12

FOT has primarily been used to assess airwayobstruction and disease state in asthma subjects duringthe day; however, FOT can also be used to measurerespiratory system resistance and reactance (Rrs, Xrs)during sleep since the need for patient cooperation isminimal.18 To date, previous studies using FOT duringsleep have only used it to monitor upper airwayobstruction in conjunction with continuous positiveairway pressure (CPAP) in obstructive sleep apneasubjects.8–10,18,23 These studies have not employedbi-level positive airway pressure (BPAP) since CPAP isthe standard therapy for obstructive apnea. One studyhas examined airway resistance in a small cohort ofsubjects with chronic obstructive pulmonary diseasewithout PAP, with CPAP, and with BPAP, but has notassessed sleep.1 The technique may be useful in moni-toring asthma subjects during the night to obtaininformation on both upper and lower airwayobstruction.

Previous studies have successfully used pressuretipped catheters, placed below the base of the tongue,in order to measure airway pressure at the level of theepiglottis.13 Using these catheters in conjunction withFOT could provide the information necessary to sep-arate the relative contributions of upper airway andlower airways to total resistance and reactance mea-sured at the airway opening.

The aim of this study was to develop and validate aforced oscillation system which could be used duringsleep to distinguish between upper airway and lowerairway mechanical properties. Furthermore, we soughtto design a system that could be used both with and

without positive airway pressure so that we couldstudy both those with obstructive sleep apnea andthose without. To this end, we developed and validatedsuch an FOT system as well as performed a feasibilitystudy in human subjects with two different diseases anda healthy control.

MATERIALS AND METHODS

System Design and Validation

A forced oscillation system was designed to supply8 Hz pressure oscillations with ~1 cmH2O peak topeak pressure swings to a subject. The system consistsof a 12 in subwoofer speaker (Image Dynamics D4V.3) housed in a Plexiglas box. The voltage signal tothe speaker is controlled by data acquisition software(Spike V6) which outputs an 8 Hz sinusoidal signal toa power amplifier (JBL CS200.1). The amplifier ispowered by a 12 V power supply and is wired to thefour coils of the subwoofer in a parallel fashion.

Three different setups were used in the system design(Fig. 1). Setup A was used to test the phase response ofthe transducers as well as the accuracy of the resistancecalculations without any positive airway pressure.Setup B was used to test the validity of the resistancecalculations when BPAP was on and setup C was usedwhen attached to a subject. In each setup a disposablebio-filter (nSpire KoKo Moe Filter) is placed at theoutlet of the speaker box. A parallel dead space tube isin place, as well as a one-way exhalation valve, whichallows exhaled gas to exit the system. Two pressuretransducers (Validyne Corp.) measure the pressureoscillations, while flow is measured through a heatedpneumotachometer (model 3700A, Hans Rudolf Inc)and a differential pressure transducer (Validyne Corp).

FIGURE 1. System to generate forced oscillations in a sleeping patient. (A) Setup used to test phase-shift of pressure transducertubing and validate resistance measurements without positive airway pressure. (B) Setup used to validate resistance measure-ments with bi-level positive airway pressure (BPAP). (C) Setup used for overnight studies with patient volunteers.

CAMPANA et al.926

All the setups were based on previously validatedmodels for FOT application.18,19

In setup A, two transducers were used to measurepressure simultaneously, one with long thin tubingconnecting it to the system (Pfar) and the other con-nected directly to the system (Pshort). In a separate trialwe used the Millar catheter (Pmillar) (model MPC-500,Millar, Houston, TX, USA) to confirm that magnitudeand phase angle of the 8 Hz oscillations were preservedas compared to Pshort. Impedance was calculated usingboth Pshort and Pfar as compared to flow _V

� �using the

method described below. We tested the system withlinear resistors made in house with mesh screens. Thesteady flow resistance was determined by measuringmean pressure over a range of flows and calculatingresistance (Fig. 2).

R ¼ Pshort= _V ð1Þ

The root mean square of flow was found when the8 Hz oscillations were on for each resistor and thissignal was used to predict the theoretical value ofresistance through linear regression. We then com-pared the response of the transducers when attachedclosely to the measurement point as opposed to the oneattached far away and the response of the Millarcatheter. Since the transducer must be placed at somedistance away from the patient due to the logistics ofthe sleep study, any phase shift (h) induced by extratubing would be correctable by time shifting theresulting pressure signal. To calculate the time equiv-alent of this phase shift we simply divide the calculatedphase shift by 2pf where f is the frequency of oscilla-tions (8 Hz) (Eq. 2).

Pfar ¼ sinð2pf� tþ hÞ ð2Þ

After determining the correct phase shift of thetransducer and tubing system, the system was config-ured to setup B (Fig. 1) in order to check the accuracyof resistance measurements when BPAP was on. TheBPAP device could not reach the target pressures whenthe system was open to atmosphere, so a 3 L chamberwas added to the setup to simulate a lung. Inspiratorypressure was set to 8 cmH2O while expiratory pressurewas set to 4 cmH2O. Flow _V

� �, and pressures before

and after the resistor were measured. By subtractingthe two pressure recordings the magnitude of theresistors was calculated when BPAP was on andcompared it to the known steady flow resistance values(Fig. 2).

During the feasibility study, the system wasattached to a research subject (setup C) while room airwas bled into the system to prevent rebreathing.Pressure (Pm) and flow _V

� �were measured through a

nasal mask (Philips-Respironics Inc.). A pressure tip-ped catheter (model MCP-500, Millar, 1.67 mmdiameter) was placed through the nostril to 1 cm belowthe base of the tongue in order to measure airwaypressure at the level of the epiglottis (Pepi). Due to thesetup of a sleep study, the transducer for the maskpressure had to be placed at some distance away fromthe patient. Data were sampled at 128 Hz (1401 plus,Cambridge Electronic Design Limited) and outputtedto Matlab. Setup C was been based on a previouslypublished design,18 however with our system we havereplaced the CPAP device with a BPAP device andhave added a epiglottic catheter to allow portioning ofresistance in the upper and lower airways.

Patient Testing

We tested the performance of the system on onehealthy subject, one subject with asthma, and onesubject with obstructive sleep apnea. All studies wereconducted at Brigham and Women’s Hospital inBoston, MA, and all study procedures were approvedby the hospital’s institutional review board. All sub-jects gave informed consent before participation in thestudy. A nasal decongestant (Oxymetazoline) andtopical lidocaine were used to decongest and numb thenose, respectively, before placing the Millar catheter. Anasal mask was placed over the nose and attached tothe FOT system. Pressure and flow were measured atthe airway opening as described above Pmask; _V

� �.

Subjects were monitored with electroencephalography(EEG), electrooculography (EOG), and chin electro-myography (EMG), for accurate sleep staging.11

Exhaled carbon dioxide and oxygen saturation were

FIGURE 2. Resistance of house made resistors calculatedover a range of flows. Resistance was calculated during nopositive airway pressure (black circles) and during BPAP(gray circles) calculated at the root-mean-square of flow whenFOT is on.

Upper and Lower Airway Resistance During Sleep 927

also measured using the established techniques of ourlaboratory.27

Data Analysis

Flow and all pressure signals were sampled at128 Hz. To calculate impedance at 8 Hz, pressure andflow signals were first filtered using a fourth orderButterworth high pass filter with a cutoff frequency of4 Hz and then with a low pass fourth order Butter-worth filter with a cutoff frequency of 12 Hz. To cal-culate the 8 Hz component of resistance we used thecross-power spectrum method.5,15 In this method thefast Fourier transforms of the pressure signals (P) andthe flow through the nose _V

� �were computed over 16

data points (one 8 Hz cycle) and recalculated with asliding window of step size 2. Next, the cross powerspectra of P and the complex conjugate of flow _V�

� �

GP _V

� �and the auto-power spectra of _V G _V _V

� �were

calculated using Eqs. (3)–(4).

GP _V ¼ P� _V� ð3Þ

G _V _V ¼ _V� _V� ð4Þ

The cross power spectra were ensemble averaged overevery eight overlapping spectra (two 8 Hz cycles).Impedance (Z) was then calculated using the averagecross power spectra (Eq. 5), resulting in a resistancemeasurement every 0.25 s (4 Hz). The resistance is thereal (R), or in phase, component of Z, while reactance(X) is the imaginary or out of phase component of Z(Eq. 6).

Z ¼ hGP _VihG _V _Vi

ð5Þ

R ¼ realðZÞX ¼ imagðZÞ

ð6Þ

The coherence function can be calculated to confirmthat noise and non-linearities are only a small portionof the transfer characteristics of the system. Coherence(c) is calculated using Eq. (7).

c ¼hG2

P _Vi

������

hG _V _VihGPPið7Þ

To calculate total respiratory system impedance (Rrs,Xrs) in human subjects, the pressure signal used is Pm

(pressure measured at the nasal mask). To calculateupper airway impedance (Rup, Xup), the pressure signalused was Pm 2 Pepi. Lower airway mechanics(Rlow, Xlow) were found by subtracting upper airwayimpedance from total respiratory system impedance.

Resistance and reactance were also quantified overpoints in the entire breathing cycle, including endinspiration and expiration, and mid inspiration andexpiration points.

RESULTS

The forced oscillation system was first tested againstfour well characterized resistors, ranging from 1.6 to12.1 cmH2O/L/s when no positive airway pressure wasapplied (Fig. 2). The average difference between cal-culated and measured resistance was 20.2 ± 0.2cmH2O/L/s (22.4 ± 2.7% of the steady flow resis-tance) (Fig. 3). The magnitude and phase of imped-ance calculated with Pfar was compared to that ofPshort (Table 1). The magnitude of impedance wassimilar between the two pressure recordings with anaverage difference of 0.09 ± 0.07 cmH2O/L/s. How-ever, there was a measurable phase difference betweenPfar and Pshort that was similar over the range ofimpedances tested (20.51 ± 0.02 rad). The time shiftneeded to be imposed on the Pfar signal to correct forthis phase shift, was calculated to be 20.010 s. Thedifference in magnitude and phase between Pshort andPfar was calculated after time shifting the Pfar signal by20.010 s (Pfar-shifted) (Table 1). When testing the Mil-lar catheter, the magnitude of impedances was similarand a small phase difference of 0.10 ± 0.05 radianswas found (Table 2). Coherence values were >0.99 forall resistors.

Knowing the characteristics of the tubing of the Pfar

transducer, this signal was used for the rest of theanalysis after time shifting by 20.010 s. When BPAPwas on, good agreement was found again between thepredicted resistance value and what was measured with

FIGURE 3. Bland–Altman plot of the difference betweenresistances measured with steady flow and FOT as a functionof the average of the two resistances. Resistance when nopositive airway pressure is applied (squares) and the mean(dashed line), and resistance when BPAP is on (triangles) andthe respective mean (dotted line).

CAMPANA et al.928

FOT (Fig. 3). The average error between calculatedand measured resistance was 0.4 ± 0.2 cmH2O/L/s(9.3 ± 9.5%). The average coherence value was>0.99, the minimum coherence was 0.96. To eliminateartifacts, only resistances that corresponded to coher-ence values greater than 0.95 were used when analyzingdata from the overnight studies.

For the patient testing, the system was applied to ahealthy 31-year-old female subject with no asthma orobstructive sleep apnea (Body Mass Index = 27.7kg/m2) (Fig. 4). The average Rrs across the entirerespiratory cycle over this 30-s period of NREM sleepis 5.1 ± 1.2 cmH2O/L/s. When split into upper andlower airway components, the mean Rup is found to

be 1.5 ± 1.3 cmH2O/L/s and Rlow is 3.6 ±

1.1 cmH2O/L/s.The FOT/BPAP system was next applied to a

46-year-old female subject with obstructive sleepapnea (OSA) (apnea-hypopnea index = 26.1 events/h,BMI = 45.8 kg/m2). During periods of flow limita-tion (Fig. 5), flow decreased despite increasinglynegative downstream pressure, indicating increasingresistance. During these periods of flow limitation,Rrs approaches 20 cmH2O/L/s, with the upper airwayresistance the dominant factor during inspiration.The highest resistances occurred during inspiration,which is consistent with other studies in OSAsubjects.18

TABLE 1. Measured impedance of Pshort, Pfar, and Pfar-shifted.

Z magnitude

(cmH2O/L/s) Z phase (rad)

Magnitude

difference (Pfar 2 Pshort)

(cmH2O/L/s)

Phase difference

(Pfar 2 Pshort) (rad) Time shift (s)

Resistor 1

Pshort 11.84 0.17 0.19 20.54 20.0107

Pfar 12.03 20.37

Pfar-shifted 12.03 0.14

Resistor 2

Pshort 4.90 0.20 0.09 20.53 20.0105

Pfar 4.98 20.33

Pfar-shifted 4.98 0.17

Resistor 3

Pshort 2.67 0.24 0.05 20.50 20.0100

Pfar 2.72 20.27

Pfar-shifted 2.72 0.23

Resistor 4

Pshort 1.65 0.29 0.05 20.48 20.0096

Pfar 1.70 20.20

Pfar-shifted 1.70 0.31

Average 0.09 20.51 20.0102

SD 0.07 0.02 0.0005

TABLE 2. Measured impedance of Pshort and Pmillar.

Magnitude

(cmH2O/L/s) Phase (rad)

Magnitude difference

(cmH2O/L/s) Phase difference (rad) Time shift (s)

Resistor 1

Pshort 11.61 0.14 0.28 0.05 0.0009

Pmillar 11.89 0.19

Resistor 2

Pshort 5.01 0.18 0.25 0.07 0.0013

Pmillar 5.26 0.25

Resistor 3

Pshort 3.08 0.21 0.08 0.12 0.0023

Pmillar 3.16 0.33

Resistor 4

Pshort 1.82 0.25 0.13 0.16 0.0031

Pmillar 1.94 0.41

Average 0.18 0.10 0.0019

SD 0.10 0.05 0.0010

Upper and Lower Airway Resistance During Sleep 929

Next the system was applied to a male subjectwith asthma and no OSA (age = 30 years, BMI =

26.4 kg/m2) (Fig. 6). Two and a half hours of resistancedata are plotted with periods of wakefulness indicatedby arrows. To smooth the data, a moving average filterof 10 breaths is applied before plotting. Total Rrs aver-aged over this time period was 9.3 ± 4.4 cmH2O/L/s,

approximately double the value seen in the healthysubject. Somewhat surprisingly, both the upper andlower airway components were increased compared tothe healthy control subject (Rup: 5.1 ± 4.7 cmH2O/L/sand Rlow: 4.2 ± 2.8 cmH2O/L/s).

When quantifying resistance and reactance over theentire breathing cycle (Fig. 7) in the subject with

FIGURE 4. Example data collected for a healthy subject during Stage 2 sleep. Flow, tidal volume (Vt), pressure at the nasal mask(Pm), pressure at the epiglottis (Pepi), and resistance of the respiratory system (Rrs) separated into upper airway (Rup) and lowerairway (Rlow) resistances.

FIGURE 5. Example of a hypopnea in an OSA subject during Stage 2 sleep. Flow, tidal volume (Vt), pressure at the nasal mask(Pm), pressure at the epiglottis (Pepi), and resistance of the respiratory system (Rrs) separated into upper airway (Rup) and lowerairway (Rlow) resistances.

CAMPANA et al.930

asthma, it was found that local minima of resistancesoccurred at end inspiration and end expiration. Rrs andRup were found to be the largest at mid-inspiration,while Rlow did not vary as much across the breathcycle.

DISCUSSION

The goal of this study was to develop, validate, andtest, the feasibility of an FOT system capable of mea-suring respiratory resistance in patients during sleepwith and without BPAP, as well as partition theresistance into its upper and lower airway components.

This system applied pressure oscillations and calcu-lated resistance accurately both with and without theaddition of positive airway pressure. As shown by theBland–Altman plot the differences between the steadyflow and FOT resistance measurements were negligible(Fig. 3). However, a digital time shift had to be appliedin order to measure accurately the relative phasesbetween pressure and flow when the pressure trans-ducer was located at a distance from the patient. Theepiglottic catheter was capable of recording 8 Hzoscillations with the correct magnitude and phase andcan be used to measure resistance of the upper airway.

Resistance was measured accurately, with only asmall deviation from the steady flow resistance, bothwith and without positive airway pressure. Coherencevalues were high both with and without airway pres-sure, although the minimum coherence was slightlylower with BPAP on. The minima in coherencecorresponded to time periods when BPAP was transi-tioning from one pressure setting to the other. Oursystem is similar to previous system designs which haveemployed forced oscillations over CPAP during sleep.However, with our device we can use FOT with eitherCPAP or BPAP and have added an epiglottic pressurecatheter enabling us to separate upper airway fromlower airway resistance. With this setup we can char-acterize lower airway resistance in those with asthma,which has not been studied during sleep.

The FOT was well tolerated by the subjects makingit feasible to calculate impedance over the course ofthe entire night during stable sleep. By placing the

FIGURE 6. Example of resistance data from asthma subject over a 2–3 h period. Respiratory system resistance (Rrs) is averagedover a moving 10 breath window (top). Rup (gray) and Rlow (black) are plotted below. Arrows indicate drops in resistance that occurwith arousals from sleep.

FIGURE 7. Average of resistance at different points in thebreathing cycle during NREM sleep (~1700 breaths) in theasthma subject (mean 6 SE).

Upper and Lower Airway Resistance During Sleep 931

epiglottic pressure transducer, upper airway resistancecan be separated from the total resistance. Resistancemeasurements during sleep at frequencies of 6–8 Hzhave not been done in large populations. The asthmasubject had an average lower airway resistance of4.2 cmH2O/L/s during sleep, which is in the range ofresistances reported by other FOT studies duringwakefulness.2,20 Upper airway resistance through thenose has also not been characterized using 6–8 Hzfrequencies. Young men and women with no obstruc-tive disease have upper airway resistances of6.6 cmH2O/L/S and 10.2 cmH2O/L/s respectively atthe onset of NREM sleep.25 However, these were notmeasured with FOT, but with pressure differentials atlow flow and high flow conditions. Using this method,resistances cannot be measured over the entirebreathing cycle and are not completely analogous towhat one measures at high frequencies.

As shown in a previous study, total airway resis-tance measured with FOT during sleep is larger duringmid inspiration as compared to mid expiration, evenwhen the airway is open and not flow limited.18 Ourdata confirm this finding, but also show that this effectis driven by the upper airway. This leads one to con-clude that the upper airway is narrowing slightly dur-ing inspiration even when no flow limitation isoccurring. Given that some authors have suggestedthat airway collapse occurs in sleep apnea at end-exhalation,16 our data and technique suggest alterna-tive hypotheses should be pursued.

We propose that FOT can be used to monitorchanges in airway resistance over the breathing cycle,and over the course of the entire night, in asthma andhealthy subjects. FOT can also be used to detectchanges in the caliber of the upper airway in those withcompromised anatomy leading to OSA, and determineat what point in the breathing cycle the upper airwaycollapses. Furthermore, this system would be ideal tostudy the variability of resistance over time, which hasreceived considerable attention recently.6,17,22 Thesystem was also validated for use with a BPAP device.Several previous studies have sought to study the effectof CPAP during sleep in those with both asthma andobstructive sleep apnea. Results have been mixed withone study finding improvements in peak expiratoryflow rates3 and other studies finding no change inpulmonary function tests4,14 after CPAP usage in thosewith asthma. With this FOT system we will be able toinvestigate how positive airway pressure affects bothupper and lower airway obstruction during sleep in apopulation of asthma patients with and withoutobstructive sleep apnea.

One limitation of this technique is that upper air-way resistance makes up a large portion of the total

resistance. Therefore, it would be difficult to drawconclusions about changes in lower airway resistanceduring sleep without an epiglottic pressure catheter inplace to rule out changes in upper airway caliber.Furthermore, during periods of flow limitation, anychanges in lower airway resistance will be masked bylarge increases in upper airway resistance. CPAP orBPAP application would stabilize the upper airwayand possibly allow for a more accurate measurement oflower airway resistance. However, in those withoutOSA the upper airway may narrow slightly but will notcollapse. The magnitude of the 8 Hz oscillationsmeasured on the epiglottic catheter can be used toassess the patency of the upper airway. We only sep-arate upper airway from lower airway resistance whenwe are confident that the pressure oscillations arereaching the epiglottis. We recognize that resistanceestimation in the setting of flow limitation is compli-cated. Another limitation is that respiratory systemresistance contains both chest wall resistance as well asairway resistance. However, it has been shown thatchest wall resistance does not change significantly on abreath to breath basis, except during deep inspirationsto TLC,2 which are rare during sleep.21

In summary, we have developed, validated andtested an FOT system that can partition respiratoryresistance to upper and lower components during sleepwhile subjects were on BPAP. The system can be usedin the future to test various mechanistic hypothesesregarding asthma and OSA. One such hypothesis isthat obesity may increase asthma incidence or severitythrough decreased mechanical stretch on airwaysmooth muscle, which may be reversible with BPAP.Resting lung volumes are low in the obese and tidalvolumes during sleep are limited; this lack of stretch ofthe airway smooth muscle could lead to airway hyper-reactivity in response to provocation. BPAP may beable to reverse these effects through increasing restinglung volumes and through increasing tidal volumesdynamically during sleep, possibly leading to decreasesin airway smooth muscle reactivity. While our systemcould be used to monitor changes in upper and lowerairway resistance throughout the night both on and offBPAP to measure its effect on airway mechanics, alarger prospective study is needed to test the abovehypothesis.

ACKNOWLEDGMENTS

This study was supported by Grants R01-HL-090897-2, F32HL097578, K24 HL093218, K23105542, Ruth L. Kirschstein NRSA T-32.

CAMPANA et al.932

REFERENCES

1Birch, M., D. MacLeod, and M. Levine. An analogueinstrument for the measurement of respiratory impedanceusing the forced oscillation technique. Physiol. Meas.22:323–339, 2001.2Black, L. D., R. Dellaca, K. Jung, H. Atileh, E. Israel,E. P. Ingenito, and K. R. Lutchen. Tracking variations inairway caliber by using total respiratory vs. airway resis-tance in healthy and asthmatic subjects. J. Appl. Physiol.95:511–518, 2003.3Chan, C. S., A. J. Woolcock, and C. E. Sullivan. Nocturnalasthma: role of snoring and obstructive sleep apnea. Am.Rev. Respir. Dis. 137:1502–1504, 1988.4Ciftci, T. U., B. Ciftci, S. F. Guven, O. Kokturk, and H.Turktas. Effect of nasal continuous positive airway pres-sure in uncontrolled nocturnal asthmatic patients withobstructive sleep apnea syndrome. Respir. Med. 99:529–534, 2005.5Daroczy, B., and Z. Hantos. An improved forced oscilla-tory estimation of respiratory impedance. Int. J. Biomed.Comput. 13:221–235, 1982.6Diba, C., C. M. Salome, H. K. Reddel, C. W. Thorpe, B.Toelle, and G. G. King. Short-term variability of airwaycaliber-a marker of asthma? J. Appl. Physiol. 103:296–304,2007.7Dubois, A. B., A. W. Brody, D. H. Lewis, and B. F.Burgess, Jr. Oscillation mechanics of lungs and chest inman. J. Appl. Physiol. 8:587–594, 1956.8Farre, R., J. M. Montserrat, and D. Navajas. Noninvasivemonitoring of respiratory mechanics during sleep. Eur.Respir. J. 24:1052–1060, 2004.9Farre, R., M. Rotger, J. M. Montserrat, and D. Navajas. Asystem to generate simultaneous forced oscillation andcontinuous positive airway pressure. Eur. Respir. J.10:1349–1353, 1997.

10Ficker, J. H., F. S. Fuchs, G. H. Wiest, G. Asshoff, A. H.Schmelzer, and E. G. Hahn. An auto-continuous positiveairway pressure device controlled exclusively by the forcedoscillation technique. Eur. Respir. J. 16:914–920, 2000.

11Iber, C., S. Ancoli-Israel, A. L. Chesson Jr., and S. Quan.The AASM Manual for the Scoring of Sleep and Associ-ated Events. Westchester: American Academy of SleepMedicine, 2007.

12Jensen, A., H. Atileh, B. Suki, E. P. Ingenito, and K. R.Lutchen. Selected contribution: airway caliber in healthyand asthmatic subjects: effects of bronchial challenge anddeep inspirations. J. Appl. Physiol. 91:506–515, 2001;discussion 504–505.

13Jordan, A. S., A. Wellman, J. K. Edwards, K. Schory, L.Dover, M. MacDonald, S. R. Patel, R. B. Fogel, A.Malhotra, and D. P. White. Respiratory control stabilityand upper airway collapsibility in men and women with

obstructive sleep apnea. J. Appl. Physiol. 99:2020–2027,2005.

14Lafond, C., F. Series, and C. Lemiere. Impact of CPAPon asthmatic patients with obstructive sleep apnoea. Eur.Respir. J. 29:307–311, 2007.

15Michaelson, E. D., E. D. Grassman, and W. R. Peters.Pulmonary mechanics by spectral analysis of forced ran-dom noise. J. Clin. Invest. 56:1210–1230, 1975.

16Morrell, M. J., Y. Arabi, B. Zahn, and M. S. Badr.Progressive retropalatal narrowing preceding obstruc-tive apnea. Am. J. Respir. Crit. Care Med. 158:1974–1981,1998.

17Muskulus, M., A. M. Slats, P. J. Sterk, and S. Verduyn-Lunel. Fluctuations and determinism of respiratoryimpedance in asthma and chronic obstructive pulmonarydisease. J. Appl. Physiol. 109:1582–1591, 2010.

18Navajas, D., R. Farre, M. Rotger, R. Badia, M. Puig-de-Morales, and J. M. Montserrat. Assessment of airflowobstruction during CPAP by means of forced oscillation inpatients with sleep apnea. Am. J. Respir. Crit. Care Med.157:1526–1530, 1998.

19Oostveen, E., D. MacLeod, H. Lorino, R. Farre, Z.Hantos, K. Desager, and F. Marchal. The forced oscilla-tion technique in clinical practice: methodology, recom-mendations and future developments. Eur. Respir. J.22:1026–1041, 2003.

20Pasker, H. G., R. Schepers, J. Clement, and K. P. Van deWoestijne. Total respiratory impedance measured bymeans of the forced oscillation technique in subjects withand without respiratory complaints. Eur. Respir. J. 9:131–139, 1996.

21Perez-Padilla, R., P. West, and M. H. Kryger. Sighs duringsleep in adult humans. Sleep 6:234–243, 1983.

22Que, C. L., C. M. Kenyon, R. Olivenstein, P. T. Macklem,and G. N. Maksym. Homeokinesis and short-term vari-ability of human airway caliber. J. Appl. Physiol. 91:1131–1141, 2001.

23Randerath, W., K. Parys, D. Lehmann, B. Sanner, F.Feldmeyer, and K. H. Ruhle. Self-adjusting continuouspositive airway pressure therapy based on the measurementof impedance. A comparison of free pressure variation andindividually fixed higher minimum pressure. Respir. IntRev. Thorac. Dis. 67:272–279, 2000.

24Sutherland, E. R. Nocturnal asthma. J. Allergy Clin.Immunol. 116:1179–1186, 2005; quiz 1187.

25Thurnheer, R., P. K. Wraith, and N. J. Douglas. Influenceof age and gender on upper airway resistance in NREMand REM sleep. J. Appl. Physiol. 90:981–988, 2001.

26Turner-Warwick, M. Epidemiology of nocturnal asthma.Am. J. Med. 85:6–8, 1988.

27Wellman, A., A. Malhotra, A. S. Jordan, K. Schory, S.Gautam, and D. P. White. Chemical control stability in theelderly. J. Physiol. 581:291–298, 2007.

Upper and Lower Airway Resistance During Sleep 933