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Bronchial responsiveness to histamine and methacholine measured with forced expirations and with the forced oscillation technique
Abstract
The objective of this study was to compare bronchial challenge tests with two substances [histamine (H) and methacholine (M)] and two methods of measuring the effect parameter FEV1 and pulmonary impedance [with the forced oscillation technique (FOT)] in order to determine which test is the shortest, and gives the least (drug) load to the patient. Furthermore, it was considered whether the result of one type of challenge test could be transferred to the result of another type of test. It was hypothesized that, since the FOT technique requires no forced manoeuvres of the subjects and therefore does not affect the airway patency, there must be differences in the provocation concentrations for reaching the conventional thresholds of 20% decrease in FEV1 (PC20 FEV1) and 40% increase in airway resistance measured at 8 Hz oscillation frequency (PC40 Rrs8). It was further hypothesized that the interindividual correlations between thresholds for both drugs will be low, because both drugs set off different mechanisms for bronchoconstriction. Bronchial challenge tests were performed in 23 stable asthmatics (15 males and 8 females; mean +/- SD age 30.3 +/- 11.6 years). Their mean control FEV1 was 85.2 +/- 12.6% predicted. For both drugs, PC40 Rrs8 was three-fold lower than PC20 FEV1. The within-drug correlation between log PC20 FEV1 (H,M) and log PC40 Rrs8 (H,M) was quite good [r(H) = 0.73, r(M) = 0.68]. The between-drug correlation of log PC20 FEV1 (H) and log PC20 FEV1 (M) was equally good. However, the 'between-drug' correlation of log PC40 Rrs8 (H) and log PC40 Rrs8 (M) was low (r = 0.36).(ABSTRACT TRUNCATED AT 250 WORDS)
... In addition, although the IOS can detect early stage BHR, it may not be able to identify subjects who are about to develop airway obstruction [1,6,12,13] because IOS parameters depend on the state of the patient. Thus, if a patient has a partial small airway dysfunction before 2 BioMed Research International the test, it is likely that the IOS will yield a low baseline value [10,14,15], and this may underestimate subsequent airway obstruction. ...
... The SD-index and Z-score were calculated at each methacholine dose to determine the extent of deviation to be used for further comparisons [18]. The SD-index was obtained by dividing the change from baseline values by the within-subject SD (SDw), which was calculated by dividing the difference between the mean values of the first and second measurements by the square root of 2 [14]. Zscores were calculated as described by Frei et al. [19]. ...
... Baseline lung function by spirometry [26] and the IOS [27] are the major determinants for measuring BHR. It is well known that the IOS parameters, particularly Rrs, are more sensitive to changes in airway obstruction than other lung function tests [10,14,15,28]. This may lead to higher fluctuations in the baseline values. ...
Objective
To investigate the repeatability and safety of measuring impulse oscillation system (IOS) parameters and the point of wheezing during bronchoprovocation testing of preschool children.
Methods
Two sets of methacholine challenge were conducted in 36 asthma children. The test was discontinued if there was a significant change in reactance (Xrs5) and resistance (Rrs5) at 5 Hz (Condition 1) or respiratory distress due to airway obstruction (Condition 2). The repeatability of PC80_Xrs5, PC30_Rrs5, and wheezing (PCw) was assessed. The changes in Z-scores and SD-indexes from prebaseline (before testing) to postbaseline (after bronchodilator) were determined.
Results
For PC30_Rrs5, PC80_Xrs5, and PCw for subjects, PC80_Xrs5 showed the highest repeatability. Fifteen of 70 tests met Condition 2. The changes from pre- and postbaseline values varied significantly for Rrs5 and Xrs5. Excluding subjects with Z-scores higher than 2SD, we were able to detect 97.1% of bronchial hyperresponsiveness during methacholine challenge based on the change in Rrs5 or Xrs5. A change in IOS parameters was associated with wheezing at all frequencies.
Conclusion
Xrs5 and Rrs5 have repeatability comparable with FEV1, and Xrs5 is more reliable than Rrs5. Clinicians can safely perform a challenge test by measuring the changes in Rrs5, Xrs5, and Z-scores from the prebaseline values.
... The strong association between airway responsiveness measured by FOT and spirometry in the present study is consistent with findings from previous studies in both adults and children. 12,14,16,29,30,33 A similar association was also found in a recent study of impulse oscillometry during mannitol challenge in children. 34 Our study protocol, in which both FOT variables and FEV 1 were measured during the same challenge test, was similar to that used in previous studies that compared FOT and FEV 1 during methacholine or histamine challenge. ...
... 34 Our study protocol, in which both FOT variables and FEV 1 were measured during the same challenge test, was similar to that used in previous studies that compared FOT and FEV 1 during methacholine or histamine challenge. 14,30 The onset of the response to mannitol is very rapid and peaks between 30 and 90 s and declines slowly thereafter, which allows sufficient time to measure both the FOT and FEV 1 variables. Our FOT protocol also included at least two maximal inhalations to measure IC. ...
The forced oscillation technique (FOT) can be used to determine airway hyperresponsiveness, but the cut-points for changes in respiratory system conductance (Grs) and reactance (Xrs) that define a positive mannitol challenge are not known. Furthermore, the effects of changes in lung volume on these cut-points or on the repeatability of the test are unknown.
In 15 non-asthmatic and 52 asthmatic subjects, response to mannitol challenge was measured by Grs and Xrs, using FOT, and by FEV1. The FOT variables were adjusted for inspiratory capacity (IC) at each dose. Dose response slope (DRS) was used in receiver operator characteristic (ROC) analysis to compare the ability of adjusted and unadjusted DRSGrs and DRSXrs to detect a positive challenge, defined as PD15FEV1 ≤635 mg mannitol.
Mannitol challenges were positive in 32 asthmatic and 2 non-asthmatic subjects. Both DRSGrs and DRSXrs detected positive challenges (p < 0.0001 for both), and this was not altered by adjustment for IC for either DRSGrs (p = 0.21) or DRSXrs (p = 0.90). FOT cut-points for a positive challenge were 27% fall in Grs or 0.93 cm H2O/L/s decrease in Xrs at 635 mg. Repeatability of DRSGrs (±2.01 doubling doses) and DRSXrs (±1.95dd) was comparable with DRSFEV1 (±1.67dd) and was not improved by adjustment for IC.
Grs and Xrs, measured by FOT, provide a sensitive, repeatable measure of response to mannitol challenge. Adjusting for lung volume does not alter the ability of these variables to detect a positive response or the repeatability of the measurement.
... A signi cant correlation between the changes in Rrs and FEV1 following bronchoconstriction has been reported by several investigators [50,81,[95][96][97]. SNASHALL et al. [50] compared FEV1 to the modulus of Zrs at 10 Hz (|Zrs10|) in the assessment of BHR in 24 asthmatic patients; the increase in |Zrs10| after challenge was on average 2.7 times as much as the decrease in FEV1. ...
... In all but one patient, PC20FEV1 was larger than PC30|Zrs10|, and in six patients PC20FEV1 was more than two doubling doses of PC30|Zrs10|. In another study, PC20FEV1 was compared with PC40Rrs8 when analysing the response to His and Mch challenge in 23 stable asthmatics [97]. For both agents, PC40Rrs8 was about three times lower than PC20FEV1. ...
The forced oscillation technique (FOT) is a noninvasive method with which to measure respiratory mechanics. FOT employs small-amplitude pressure oscillations superimposed on the normal breathing and therefore has the advantage over conventional lung function techniques that it does not require the performance of respiratory manoeuvres. The present European Respiratory Society Task Force Report describes the basic principle of the technique and gives guidelines for the application and interpretation of FOT as a routine lung function test in the clinical setting, for both adult and paediatric populations. FOT data, especially those measured at the lower frequencies, are sensitive to airway obstruction, but do not discriminate between obstructive and restrictive lung disorders. There is no consensus regarding the sensitivity of FOT for bronchodilation testing in adults. Values of respiratory resistance have proved sensitive to bronchodilation in children, although the reported cutoff levels remain to be confirmed in future studies. Forced oscillation technique is a reliable method in the assessment of bronchial hyperresponsiveness in adults and children. Moreover, in contrast with spirometry where a deep inspiration is needed, forced oscillation technique does not modify the airway smooth muscle tone. Forced oscillation technique has been shown to be as sensitive as spirometry in detecting impairments of lung function due to smoking or exposure to occupational hazards. Together with the minimal requirement for the subject's cooperation, this makes forced oscillation technique an ideal lung function test for epidemiological and field studies. Novel applications of forced oscillation technique in the clinical setting include the monitoring of respiratory mechanics during mechanical ventilation and sleep.
... inflation to total lung capacity (TLC)) during spirometry testing, or with some inhalation agents, potentially affect diagnosis, given both the bronchoprotective and bronchodilator effect of deep inhalation in health and in asthma [67][68][69]. Consequently, oscillometry may be more sensitive than spirometry for detecting AHR in mild asthmatic patients, given their maintained, albeit reduced, response to a deep breath, resulting in a lower provocative dose of methacholine [47,70] and therefore a shorter testing protocol. However, since avoiding deep breaths may result in AHR even in healthy individuals [71], oscillometry may be less sensitive than spirometry in distinguishing healthy from asthmatic individuals. ...
Recently, “Technical standards for respiratory oscillometry” was published, which reviewed the physiological basis of oscillometric measures and detailed the technical factors related to equipment and test performance, quality assurance and reporting of results. Here we present a review of the clinical significance and applications of oscillometry. We briefly review the physiological principles of oscillometry and the basics of oscillometry interpretation, and then describe what is currently known about oscillometry in its role as a sensitive measure of airway resistance, bronchodilator responsiveness and bronchial challenge testing, and response to medical therapy, particularly in asthma and COPD. The technique may have unique advantages in situations where spirometry and other lung function tests are not suitable, such as in infants, neuromuscular disease, sleep apnoea and critical care. Other potential applications include detection of bronchiolitis obliterans, vocal cord dysfunction and the effects of environmental exposures. However, despite great promise as a useful clinical tool, we identify a number of areas in which more evidence of clinical utility is needed before oscillometry becomes routinely used for diagnosing or monitoring respiratory disease.
... Oscillometry has been performed extensively in humans, for example in the study of airway obstruction (Clement et al. 1983, Ducharme und Davis 1997, bronchodilator effects (Zerah et al. 1995), bronchial challenges (Bohadana et al. 1999, Weersink et al. 1995, Wouters et al. 1989), occupational disease manifestations (Pasker et al. 1997), clinical drug efficacy (Pennings und Wouters 1997), infant lung function (Hayden et al. 1998), and the behavior of tissue and airway components of the respiratory system in normal (Hantos et al. 1986) and during bronchoconstriction (Kaczka et al. 1997, Lutchen und Gillis 1997, Lutchen et al. 2001, Lutchen und Suki 1996. The measured resistance of airways is not directly related to those obtained by classical LFT, however, maximal values are not too different (Young und Tesarowski 1994). ...
Respiratory function of donkeys measured by Forced Oscillometry Technique (FOT) has not adequately been characterised. In addition, the respiratory efforts of the thorax and abdominal muscles of donkeys have not adequately been quantified. The aim of this study was to analyse the differences of thoracic and abdominal excursions during breathing by using Respiratory Ultrasound Plethysmography (RUP). Synchronisation, rhythm and relative contribution of the thoracic and abdominal muscles were analysed. Secondly, this study aimed to describe the magnitude of airway impedance (Zrs) and its two components, the airway resistance (Rrs) and the reactance (Xrs) in donkeys. Zrs, Rrs and Xrs were measured at oscillation frequencies (f) ranging from 2 Hz up to 7 Hz. Raw data was cleaned for outliers and statistically analysed. In total 18 donkeys were tested, but data of 2 animals had to be omitted entirely due to bizarre values and patterns. During the measurements, it appeared that some animals were coughing mildly and therefore post hoc the effect of coughing on group means was studied. The group mean differences of Rrs and Xrs were analysed by Mann Whitney-U test for independent
samples.
The RUP system in its current form is too sensitive to signal noise and generated data
are difficult to quantify. Nevertheless, using an alternative algorithm the respiratory strategy of healthy and coughing donkeys appeared different.
Within the oscillation frequency interval from 2 to 7 Hz, donkeys do not appear to show
a clear frequency dependence of Zrs or Rrs unlike horses. However, Zrs and Rrs decreased slightly from 2 to 3 Hz, thereafter both parameters remained relatively stable. The group mean Xrs moved around 0. Not all animals showed the expected positive frequency dependent relation.
It could be shown that the coughing group demonstrated Rrs compared to the healthy group, especially at the lower frequencies (f = 2 to 5 Hz), whereas Xrs was significantly higher in the healthy donkeys at the higher frequencies. These findings suggest that coughing donkeys have increased respiratory resistance of the lower airways and reduced ability of the respiratory tract to store capacitive energy. The latter is associated with stiffness of the lung or with hyperinflation and loss of lung elastic recoil. The coughing was considered to be associated with mild bronchitis caused by lungworms (Dictyocaudus arnefeldii).
The results of this pilot study indicate that subclinical bronchial disease of donkeys can be diagnosed using FOT. However further studies are needed to determine the optimal oscillation spectrum and improvement must be made for measuring procedures including the use of better masks before the method can be used for diagnostic purposes.
Keywords: Donkey pulmonary function, respiratory ultrasound plethysmography, thoracic
abdominal asynchrony, forced oscillation technique, respiratory impedance.
... The 40% increase in IOS parameters was based on previous studies using a threshold of 40% increase in resistance measured with the forced oscillation technique or 40% decrease in specific airway conductance measured with body plethysmography. [9,17,18] FEV 1 and R20 were considered as large airway parameters, FEF 25-75% , R5-R20 and X5 as small airway parameters. ...
Background: Small-particle inhaled corticosteroids (ICS) provide a higher small airway deposition than large-particle ICS. However, we are still not able to identify asthma patients who will profit most from small-particle treatment.
Objective: We aimed to identify these patients by selectively challenging the small and large airways. We hypothesized that the airways could be challenged selectively using small- and large-particle adenosine, both inhaled at a high and a low flow rate.
Design: In this cross-over study 11 asthma subjects performed four dry powder adenosine tests, with either small (MMAD 2.7 µm) or large (MMAD 6.0 µm) particles, inhaled once with a low flow rate (30 l min–1) and once with a high flow rate (60 l min–1). Spirometry and impulse oscillometry were performed after every bronchoprovocation step. We assumed that FEV1 reflects the large airways, and FEF25–75%, R5-R20 and X5 reflect the small airways.
Results: The four adenosine tests were not significantly different with respect to the threshold values of FEV1 (p = 0.12), FEF25–75% (p = 0.37), R5-R20 (p = 0.60) or X5 (p = 0.46). Both small- and large-particle adenosine induced a response in the small airways in the majority of the tests.
Conclusions: In contrast to our hypothesis, all four adenosine tests provoked a response in the small airways and we could not identify different large- or small-airway responders. Interestingly, even the test with large particles and a high flow rate induced a small-airway response, suggesting that selective challenging of the small airways is not necessary. Future studies should investigate the relation between particle deposition and the site of an airway response.
... While forced breathing maneuvers performed during spirometry may independently affect bronchial tone [38,39], IOS provides a highly sensitive index of airway function during resting tidal breathing [19]. IOS offers insight into the location and magnitude of airway resistance and reactance and how these properties may be modified via a single bout of exercise. ...
Background: Responses to a single bout of exercise may provide critical information for maximizing improvements in pulmonary function following exercise training in cystic fibrosis (CF). We sought to determine if acute maximal exercise improves pulmonary function in patients with CF.
Methods: Thirty-three patients with CF completed a comprehensive assessment of pulmonary function to determine forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and lung clearance index (LCI) prior to and immediately following maximal aerobic exercise on a cycle ergometer.
Results: Following exercise, FVC (∆0.08 ± 0.14 L) and FEV1 (∆0.06 ± 0.15 L/min) increased, while LCI decreased (∆-0.71 ± 0.93) (all p < 0.05). Changes in FEV1 (%predicted) were associated with peak work (r = 0.40, p = 0.02) and peak pulmonary ventilation (r = 0.45, p = 0.01).
Conclusions: A single bout of maximal exercise acutely improves pulmonary function in patients with CF and improvements may be related to peak work and peak pulmonary ventilation.
... While forced breathing maneuvers performed during spirometry may independently affect bronchial tone [38,39], IOS provides a highly sensitive index of airway function during resting tidal breathing [19]. IOS offers insight into the location and magnitude of airway resistance and reactance and how these properties may be modified via a single bout of exercise. ...
... In fact, current evidences suggest that FOT parameters correlated well with forced expiratory volume in 1 second (FEV 1 ) and could reflect airway resistance accurately. [7][8][9][10] It was also suggested to be a more sensitive marker for detection of airway hypersensitivity [11][12][13][14] as well as early airway disease. 15,16 Despite these benefits, FOT was not widely applied in the diagnosis and monitoring of patients with geriatric COPD. ...
Introduction:
Performing lung function test in geriatric patients has never been an easy task. With well-established evidence indicating impaired small airway function and air trapping in patients with geriatric COPD, utilizing forced oscillation technique (FOT) as a supplementary tool may aid in the assessment of lung function in this population.
Aims:
To study the use of FOT in the assessment of airflow limitation and air trapping in geriatric COPD patients.
Study design:
A cross-sectional study in a public hospital in Hong Kong. ClinicalTrials.gov ID: NCT01553812.
Methods:
Geriatric patients who had spirometry-diagnosed COPD were recruited, with both FOT and plethysmography performed. "Resistance" and "reactance" FOT parameters were compared to plethysmography for the assessment of air trapping and airflow limitation.
Results:
In total, 158 COPD subjects with a mean age of 71.9±0.7 years and percentage of forced expiratory volume in 1 second of 53.4±1.7 L were recruited. FOT values had a good correlation (r=0.4-0.7) to spirometric data. In general, X values (reactance) were better than R values (resistance), showing a higher correlation with spirometric data in airflow limitation (r=0.07-0.49 vs 0.61-0.67), small airway (r=0.05-0.48 vs 0.56-0.65), and lung volume (r=0.12-0.29 vs 0.43-0.49). In addition, resonance frequency (Fres) and frequency dependence (FDep) could well identify the severe type (percentage of forced expiratory volume in 1 second <50%) of COPD with high sensitivity (0.76, 0.71) and specificity (0.72, 0.64) (area under the curve: 0.8 and 0.77, respectively). Moreover, X values could stratify different severities of air trapping, while R values could not.
Conclusion:
FOT may act as a simple and accurate tool in the assessment of severity of airflow limitation, small and central airway function, and air trapping in patients with geriatric COPD who have difficulties performing conventional lung function test. Moreover, reactance parameters were better than resistance parameters in correlation with air trapping.
... 138 Furthermore, the changes in R rs and FEV 1 after bronchoconstrictor use have been found to be well correlated. [139][140][141] In addition, previous studies found that assessment of AHR by FOT required 3-fold lower concentrations of a contractile agonist than determined using forced expiratory maneuvers, 141 which suggests that the use of FOT may shorten the bronchial challenge test duration. However, there is no agreement yet on which increase in R rs would correspond best to a 20% decrease in FEV 1 . ...
Spirometry is one of the most widely used tests in the assessment and monitoring of asthma. However, spirometry cannot be performed in very young children and some adult patients, and is poorly sensitive to small airways, which are primarily involved in the pathophysiology of asthma. The forced oscillation technique (FOT) has emerged as a powerful alternative technique that instead characterizes respiratory mechanics during normal breathing with no forced maneuver. In this review we highlight the current state of the art of the FOT and its utility in the assessment of lung function in asthma. First we briefly discuss the clinical features and characteristics of asthma. This is followed by a discussion of the assessment of airway obstruction and airway hyperresponsiveness using spirometry. We then review the basics of FOT and its application in respiratory diseases. FOT data are particularly amenable to modeling as an aide to physiological interpretation, and we review several common approaches. This is followed by an in-depth discussion of the assessment of airway variability and heterogeneity using FOT in asthma. Finally, we speculate on the potential clinical utility of FOT in asthma.
... Thus, the bronchial challenge test results are evaluated on the basis of the smallest change of FEV 1 , indicative of AHR, which is defined in most studies as the 20 % decrease of its value after inhalation of a provocative dose (PD 20 FEV 1 ), or concentration (PC 20 FEV 1 ) of the above substances. Many studies have been conducted to assess the efficiency of oscillometry to evaluate AHR, but also the definition of the impedance parameter more strongly correlated with PC 40 R rs 8 [75] and PC 47 R rs 10 [76] were significantly correlated with PC 20 FEV 1 και PD 20 FEV 1 correspondingly, while significant correlation was observed among PD 35 R rs 10 [77], PC 60 R rs 8 [78] and PC 10 FEV 1 . In a study by Van Noord et al. [79], sensitivity of PD 40 G rs 6 (where G rs 6=1/ R rs 6), is proved significantly higher than that of PD15FEV 1 , and the difference is demonstrated more intensively as AHR grade increases. ...
... Comparison of spirometry and FOT responses to bronchial challenge, as well as comparisons between FOT variables, may provide important clues as to the underlying pathophysiology. Lastly, FOT measurements may be capable of detecting differences in the pattern of response between stimuli [39], which may further aid in assigning phenotypes of AHR to distinct clinical populations. ...
Airway hyperresponsiveness (AHR) has long been considered a cardinal feature of asthma. The development of the measurement of AHR forty years ago initiated many important contributions to our understanding of asthma and other airway diseases. However, our understanding of AHR in asthma remains complicated by the multitude of potential underlying mechanisms which in reality are likely to have different contributions amongst individual patients. Therefore the present review will discuss the current state of understanding of the major mechanisms proposed to contribute to AHR and highlight the way in which AHR testing is beginning to highlight distinct abnormalities associated with clinically relevant patient populations. In doing so we aim to provide a foundation by which future research can begin to ascribe certain mechanisms to specific patterns of bronchoconstriction and subsequently match phenotypes of bronchoconstriction with clinical phenotypes. We believe that this approach is not only within our grasp but will lead to improved mechanistic understanding of asthma phenotypes and hopefully better inform the development of phenotype-targeted therapy. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
... As for conventional modeling using the equation of motion, these three forces act in series. Oscillometry has been performed extensively in humans, for example in the study of airway obstruction [83,84], bronchodilator effects [85], bronchial challenges [86][87][88][89], occupational disease manifestations [90], clinical drug efficacy [91], infant lung function [92], and the behavior of tissue and airway components of the respiratory system in normal [93] and during bronchoconstriction [79,[94][95][96]. Among domestic species, the most significant body of work was performed in cattle [97][98][99][100] and dogs [101]. ...
Pulmonary function tests are emerging as an essential tool in equine referral practice. Indications include intermittent cough, excess mucus, abnormal breathing pattern, presence of wheezes or crackles on auscultation, or exercise intolerance. Since non-infectious airway obstruction and inflammation are the most common problems encountered in the lower respiratory tract of horses, tests are largely aimed at describing the severity, anatomical pattern, stability (reactivity) and reversibility of airway constriction. A comprehensive approach often requires multiple tests, since the information gained from each method is different. Four important tests of mechanical function are discussed in this chapter. They include (1) conventional lung mechanics using pleural pressure measurements, (2) forced oscillatory mechanics, (3) flowmetrics ("boxless" plethysmography) and (4) forced expiratory maneuvers. The implementation of bronchoprovocation to assess airway reactivity is reviewed. The flowmetric test can be employed in the field, while the other methods are suitable for specialists and researchers in the pulmonary laboratory. The importance of pulmonary function testing to the early diagnosis of lower airway obstruction is emphasized, since this is the widest application.
... Other studies have reported similar fi ndings, 44,45 whereas Vink et al 46 also demonstrated a correlation between decreased FEV 1 and increased R5 and R10. When used with IOS, lower doses of bronchoprovocative agents are required to induce measurable and signifi cant bronchoconstriction. 47,48 Indeed, Schulze et al 49 showed significant increases in resistance well before a response was seen in FEV 1 at lower doses of methacholine, suggesting that oscillation techniques are more sensitive than spirometry. ...
Simple spirometry and body plethysmography have been routinely used in children aged > 5 years. New techniques based on physiologic concepts that were first described almost 50 years ago are emerging in research and in clinical practice for measuring pulmonary function in children. These techniques have led to an increased understanding of the pediatric lung and respiratory mechanics. Impulse oscillometry (IOS), a simple, noninvasive method using the forced oscillation technique, requires minimal patient cooperation and is suitable for use in both children and adults. This method can be used to assess obstruction in the large and small peripheral airways and has been used to measure bronchodilator response and bronchoprovocation testing. New data suggest that IOS may be useful in predicting loss of asthma control in the pediatric population. This article reviews the clinical applications of IOS, with an emphasis on the pediatric setting, and discusses appropriate coding practices for the clinician.
... Later, the same team found a good correlation between FOT impedance and spirometry in a larger group of asth-matics (n=60) whose PD20 to histamine was #8 mmol [22]. WEERSINK et al. [23] measured FOT impedance and spirometry in stable asthmatics during the inhalation of histamine and methacholine and found that the dose of histamine provoking a 40% increase in FOT resistance measured at 8 Hz was the parameter that gave the lowest burden to the patient: it was reached at a three-fold lower concentration than provocative concentration causing a 20% decrease in FEV1, thus shortening considerably the procedure and lowering the drug load. Recently, SCHMEKEL and SMITH [24], using ROC curves, showed that FOT parameters are more sensitive and more specific than FEV1 at detecting bronchoconstriction occurring in asthmatic patients stimulated with isocapnic hyperventilation of cold air. ...
In population studies, the provocative dose (PD) of bronchoconstrictor causing a significant decrement in lung function cannot be calculated for most subjects. Dose–response curves for carbachol were examined to determine whether this relationship can be summarized by means of a continuous index likely to be calculable for all subjects, namely the two-point dose response slope (DRS) of mean resistance (Rm) and resistance at 10 Hz (R10) measured by the forced oscillation technique (FOT).Five doses of carbachol (320 µg each) were inhaled by 71 patients referred for investigation of asthma (n=16), chronic cough (n=15), nasal polyposis (n=8), chronic rhinitis (n=8), dyspnoea (n=8), urticaria (n=5), post-anaphylactic shock (n=4) and miscellaneous conditions (n=7). FOT resistance and forced expiratory volume in one second (FEV1) were measured in close succession. The PD of carbachol leading to a fall in FEV1 ≥20% (PD20) or a rise in Rm or R10 ≥47% (PD47,Rm and PD47,R10) were calculated by interpolation. DRS for FEV1 (DRSFEV1), Rm (DRSRm) and R10 (DRSR10) were obtained as the percentage change at last dose divided by the total dose of carbachol. The sensitivity (Se) and specificity (Sp) of DRSRm, DRS10 Δ%Rm and Δ%R10 in detecting spirometric bronchial hyperresponsiveness (BHR, fall in FEV1 ≥20%) were assessed by receiver operating characteristic (ROC) curves.There were 23 (32%) “spirometric” reactors. PD20 correlated strongly with DRSFEV1 (r=-0.962; p=0.0001); PD47,Rm correlated significantly with DRSRm (r=-0.648; p=0.0001) and PD47,R10 with DRSR10 (r=-0.552; p=0.0001). DRSFEV1 correlated significantly with both DRSRm (r=0.700; p=0.0001) and DRSR10 (r=0.784; p=0.0001). The Se and Sp of the various FOT indices to correctly detect spirometric BHR were as follows: DRSRm: Se=91.3%, Sp=81.2%; DRSR10: Se=91.3%, Sp=95.8%; Δ%Rm: Se= 86.9%, Sp=52.1%; and Δ%R10: Se=91.3%, Sp=58.3%.Dose–response slopes of indices of forced oscillation technique resistance, especially the dose–response slope of resistance at 10Hz are proposed as simple quantitative indices of bronchial responsiveness which can be calculated for all subjects and that may be useful in occupational epidemiology.
... Accordingly, FOT is a suitable tool in tests aimed at studying the bronchial response to increasing doses of inhaled agent. It has been suggested that FOT is adequate for assessing the increase in airway obstruction induced by bronchial challenges: histamine45464748, methacholine4849505152, hyperventilation with cold air5354555657, carbachol [58], and glutathione [59]. Similarly, FOT has been used to assess the decrease in airway resistance induced by bronchodilatation agents606162636465 . ...
The forced oscillation technique (FOT) allows the noninvasive assessment of the mechanical properties of the respiratory system. Given that the technique does not require patient cooperation, it is suitable for the routine evaluation of respiratory function in a variety of clinical applications. In this paper, the rationale and the most conventional equipment and data processing of the technique are described. A number of clinical applications of FOT are briefly reviewed. One common use of the technique is to assess respiratory function in patients with different pathologies and in epidemiology. One of the most referenced applications of FOT is in tests of airway responsiveness to inhaled agents (bronchoprovocation and bronchodilatation). Finally, two recent promising applications of FOT are described: monitoring respiratory resistance during invasive and noninvasive mechanical ventilation, and detection of upper airway obstruction during sleep.
... The FOT was first described by Dubois et al. (1956) and because of its more widespread use, there is more published data on Rrs and reactance in obstructive lung diseases compared with MBNW. Most studies of FOT are simply comparisons between respiratory system resistance (Rrs) and FEV1 and it has been seen as an attractive alternative to spirometry, especially in children during bronchial challenge tests and for assessing bronchodilator responses (Clement et al., 1983;Solymar et al., 1984;van Noord et al., 1989van Noord et al., , 1994Wesseling et al., 1993;Weersink et al., 1995;Zerah et al., 1995;Rose et al., 2003). The results of these studies show that Rrs is more sensitive to acute changes induced by bronchial challenge or by bronchodilator administration, when compared to spirometry, hitherto considered the gold standard for pulmonary function. ...
The multiple breath nitrogen washout (MBNW) can be analysed to produce the parameters Scond and Sacin as measures of ventilation heterogeneity in conductive and acinar airways, respectively. The derivation of these parameters is based on a model of pulmonary ventilation and results of similar modelling suggest that respiratory system conductance (Grs) measured by forced oscillation technique (FOT) is also sensitive to heterogeneity and to airway closure. Therefore, Scond, the volume of gas trapping at FRC (VtrappedFRC) and Grs may be inter-related parameters. These relationships were examined in 12 normals under baseline and bronchoconstricted states. Specific Grs was measured at 5Hz (sGrs5=Grs5/FRC) and Scond, Sacin and VtrappedFRC by MBNW, before and after methacholine challenge. Scond was independently predicted by VtrappedFRC and FRC in a multivariate model (R2=0.68, p=0.002). Post methacholine challenge, Scond related only to VtrappedFRC (R2=0.79, p<0.0001). The absolute change in Scond induced by methacholine challenge were predicted by the changes in VtrappedFRC and sGrs5 in a multivariate model (R2=0.82, p=0.0002). Sacin was unrelated to VtrappedFRC and sGrs5 before and after methacholine challenge. In conclusion, Scond and sGrs5 are measurements that are sensitive to changes occurring to the function of peripheral conducting airways, in particular heterogeneity and airway closure, while Sacin and presumably heterogeneity in terminal airways, are independent of these. Scond is also related to lung size. We review the current state of knowledge of FOT and MBNW in obstructive lung diseases and discuss future research directions.
... This makes the technique suitable for use in young children who may have difficulty co-operating during a traditional spirometric examination. Another advantage of measurements made during tidal breathing is that the forced breathing manoeuvres performed at conventional spirometry may themselves affect bronchial tone (Weersink et al., 1995;Pellegrino et al., 1996). Furthermore, with FOT, more specific information of the resistive and elastic properties of the respiratory system can be obtained than is possible by spirometric measurements. ...
The forced oscillation technique makes it possible to evaluate the mechanical properties of the respiratory system with a minimum of cooperation. The method is therefore especially useful in children. Impulse oscillometry (IOS) is a commercially available version of this technique. There is, as yet, limited information on reference values for IOS in children. The aim of this study was to extend the reference values for IOS variables and to study their correlation with height, weight and age in healthy children. A sample (n = 360) of children (age 2.1-11.1 years) was measured by using impulse oscillometry (IOS; Jaeger, Würzburg, Germany). The sample was based on children attending kindergarten in Finland and children attending primary school in Sweden. Measurements of respiratory resistance (Rrs) and reactance (Xrs) at 5, 10, 15 and 20 Hz, total respiratory impedance (Zrs) and the resonance frequency (Fr) were made. All variables were related to body height. Most of them were also weakly related to weight. Reference equations for children (height 90-160 cm) are presented.
... chest tightness or dyspnoea). 2 Several studies have reported significant correlations between the changes in FOT measured R rs and FEV 1 following induced bronchoconstriction [25][26][27] while others including this study showed no significant correlation. 22 Broeders et al. compared the FOT measured PC 40 -R 6 with the PC 20 -FEV 1 in stable asthmatics, 10 and showed that PC 40 -R 6 was achieved at a significantly lower methacholine concentration than PC 20 -FEV 1 and in shorter time span. ...
Previous studies showed poor correlation between asthma symptoms and spirometric-based bronchial provocation tests. Use of impulse oscillometry (IOS) in airways resistance measurement may be more sensitive. In 20 individuals with stable asthma, we analysed the relationship between methacholine-induced asthma symptoms scores, IOS and spirometry. Following a screening visit, methacholine challenge testing was performed twice (visits 1 and 2). Dyspnoea, tightness and wheeze were quantified using visual analogue scores. IOS and spirometry were conducted at each incremental dose of methacholine. The Pearson correlation coefficient and linear regression analyses were conducted to explore the relations. A significant correlation was observed between methacholine-induced dyspnoea scores and the change in IOS measures of R((5)) (r=0.62, p=0.004) and X(5) (r=0.51, p=0.022), but not with the spirometric changes in FEV((1)) (r=0.37(,)p=0.11) or MEF(50) (r=0.32, p=0.17). In a multiple linear regression model, R(5) was the only significant variable to explain dyspnoea variability (p=0.003). Results of correlation analyses for chest tightness were similar to those obtained with dyspnoea. However, the symptom of wheeze showed correlation with IOS and spirometry. We conclude that airway resistance measured by IOS during methacholine challenge correlates better with asthma symptoms than traditional spirometric measures implying a higher sensitivity index.
The forced oscillation technique (FOT) is another application of the pressure oscillation method for lung diagnostics. This chapter presents FOT in detail, including working principle, instrumentation, measurement arrangement, and impedance measurement methods. It also describes some clinical applications of FOT. The current applications of FOT can be divided into two main groups based on the frequency range. The first group studies the frequency range outside of spontaneous breathing. The second FOT techniques measuring the respiratory impedance at frequency bands partly or entirely overlap with the frequency band of spontaneous breathing. The impulse oscillation system and MostGraph are two main commercial FOT devices used in clinical practice. FOT is particularly useful in responsiveness tests. The main advantages of FOT are no forced spirometry, no particular breathing maneuver, or noticeable interference with respiration, and it is a noninvasive and versatile method.
Normal tidal breathing is generated by cyclic muscular pressure applied to the chest wall. Mechanical ventilation is produced by cyclic pressure applied to the airway opening. In both situations tidal volume generated by the driving pressure is determined by the mechanical load of the respiratory system. In general, for a given driving pressure, higher mechanical load results in lower ventilatory out put. The mechanical load as computed from the pressure-flow relationship of the respiratory system undergoing sinusoidal oscillation is called respiratory impedance (Zrs), because of the complex structure of the respiratory system Zrs varies markedly with oscillatory frequency. Mechanical properties of the airways and the lung and chest wall tissues can be estimated by fitting suitable physiological models to Zrs measured at different frequencies. Therefore, the study of oscillatory mechanics in a wide range of frequencies is of clinical interest in the assessment of respiratory mechanics in spontaneously breathing and mechanically ventilated patients.
Forced oscillation technique (FOT) is a noninvasive approach for assessing the mechanical properties of the respiratory system. The technique is based on applying a low-amplitude pressure oscillation to the airway opening and computing respiratory impedance defined as the complex ratio of oscillatory pressure and flow. Impedance data are interpreted in terms of mechanical models of the respiratory system. Common clinical applications of FOT include assessment of airflow obstruction in patients with asthma and chronic obstructive pulmonary disease and airway responsiveness. New areas of interest are monitoring of airway patency in sleep and noninvasive mechanical ventilation.
Objectives
This study in healthy adults was conducted to explore the clinical application of capnovolumetric indices as compared to lung function parameters using histamine provocation.Methods
Forty healthy subjects received aerosol histamine or salbutamol in an automatic stimulation system with escalating doses of histamine. Dead space volumes of capnovolumetry and lung function parameters were examined with increased concentrations of histamine at a fixed time interval. The doses of histamine were selected from 0.0562-2.2 mg and 0.1 mg albutamol was inhaled when a maximal dose of histamine was reached. Baseline values in each group were calculated prior to histamine inhalation.ResultsFowler dead space (VDF), Wolff dead space (VDW), threshold dead space (VDT), Bohr dead space (VDB), FEV1 and PEF showed a dose-dependent reduction following histamine provocation, but there were no statistical differences in the measurements at baseline and post S6 provocation. The value of dC3/DV at the maximal dose was significantly increased over its baseline value (P<0.05). VDF, VDT and VDW were significantly increased after bronchodilator use (P<0.05 or <0.01). The changes in capnovolumetry did not correspond with the results of lung function test.Conclusions
The dC3/DV and airway dead spaces of capnovolumetry in healthy adults are significantly increased compared to lung function parameters before or after bronchodilator use, suggesting that capnovolumetry is feasible in diagnostic evaluation of airway reactivity, especially for persons who are unable to undertake lung function test.
Telemedicine seems to offer reliable solutions to health care challenges, but significant contradictory results were recently found. Therefore, it is crucial to carefully select outcomes and target patients who may take advantage of this technology. Continuous positive airway pressure (CPAP) therapy compliance is essential to treat patients with obstructive sleep apnea (OSA). We believe that OSA patients could benefit greatly from a telemedicine approach for CPAP therapy management.
The objective of our study was to evaluate the application of a telemedicine-based approach in the CPAP therapy management, focusing on patients' CPAP follow-up and training.
We performed two studies. First, (study 1) we enrolled 50 consecutive OSA patients who came to our sleep center for the CPAP follow-up visit. Patients performed a teleconsultation with a physician, and once finalized, they were asked to answer anonymously to a questionnaire regarding their opinion about the teleconsultation. In a second randomized controlled trial (RCT) (study 2), we included 40 OSA patients scheduled for CPAP training. There were 20 that received the usual face-to-face training and 20 that received the training via videoconference. After the session, they were blindly evaluated on what they learned about OSA and mask placement.
More than 95% (49/50) of the interviewed patients were satisfied with the teleconsultation, and 66% (33/50) of them answered that the teleconsultation could replace 50%-100% of their CPAP follow-up visits. Regarding the RCT, patients who received the CPAP training via videoconference demonstrated the same knowledge about OSA and CPAP therapy as the face-to-face group (mean 93.6% of correct answers vs mean 92.1%; P=.935). Performance on practical skills (mask and headgear placement, leaks avoidance) was also similar between the two groups.
OSA patients gave a positive feedback about the use of teleconsultation for CPAP follow-up, and the CPAP training based on a telemedicine approach proved to be as effective as face-to-face training. These results support the use of this telemedicine-based approach as a valuable strategy for patients' CPAP training and clinical follow-up.
Objective: To compare the validity of different methods for the assessment of bronchial hyperresponsiveness used by different centers. Methods: Case series of 648 subjects referred to six pulmonary centers, all with a history of shortness of breath without airway obstruction, without use of medication that might influence the tests and without viral infections during the previous two weeks. All subjects answered a questionnaire of recent symptoms and underwent bronchial challenge with a chemical stimulus according to each center's protocol. Analysis was performed by receiver operating characteristic (ROC) plots using the questionnaire's answers as the gold standard. Diagnostic test sensitivities at the cut-offs for bronchial hyperresponsiveness indicated by each center were compared. Results: ROC plots showed poor validity of all tests, i.e. both acceptable sensitivity and specificity were not observed with any test. There was no obvious difference of the slope of the ROC plots between the different centers. However, maximal sensitivity differed considerably: for "wheeze during the previous 12 months", sensitivity at each center's cut-off for the definition of bronchial hyperresponsiveness varied between 0.35 and 0.73. The choice of the question used as the standard had little influence on test validity. Conclusion: Although some of the differences between centers may be explained by subject characteristics, the large differences of the test sensitivities are unacceptable and underscore the need for standardization of these tests, primarily with respect to sufficient sensitivity.
The mechanical impedance of the respiratory system defines the pressure profile required to drive a unit of oscillatory flow into the lungs. Impedance is a function of oscillation frequency, and is measured using the forced oscillation technique. Digital signal processing methods, most notably the Fourier transform, are used to calculate impedance from measured oscillatory pressures and flows. Impedance is a complex function of frequency, having both real and imaginary parts that vary with frequency in ways that can be used empirically to distinguish normal lung function from a variety of different pathologies. The most useful diagnostic information is gained when anatomically based mathematical models are fit to measurements of impedance. The simplest such model consists of a single flow-resistive conduit connecting to a single elastic compartment. Models of greater complexity may have two or more compartments, and provide more accurate fits to impedance measurements over a variety of different frequency ranges. The model that currently enjoys the widest application in studies of animal models of lung disease consists of a single airway serving an alveolar compartment comprising tissue with a constant-phase impedance. This model has been shown to fit very accurately to a wide range of impedance data, yet contains only four free parameters, and as such is highly parsimonious. The measurement of impedance in human patients is also now rapidly gaining acceptance, and promises to provide a more comprehensible assessment of lung function than parameters derived from conventional spirometry. © 2011 American Physiological Society. Compr Physiol 1:1233-1272, 2011.
Pulmonary function testing (PFT) is of great importance in the evaluation and treatment of respiratory diseases. Spirometry is simple, noninvasive, and has been the most commonly used technique in cooperative children, obtaining reliable data in only a few minutes. The development of commercially available equipment as well as the simplification of previous techniques that now require minimal patient cooperation applied during tidal breathing have significantly stimulated the use of PFT in younger children. Tidal breathing techniques such as impulse oscillometry, gas dilution, and plethysmography have permitted previously unobtainable PFT in children 2 to 5 years of age. The purpose of this review is to help clinicians become familiar with available PFT techniques used in young children by discussing their general principles, clinical applications, and limitations.
There are few studies focused on bronchial challenge testing using the oscillation technique, and results from the test in preschool children have been inconsistent.
The aim of this study was to explore which level of provocative concentration (PC) is appropriate for bronchial challenge testing using the impulse oscillometry system (IOS) for assessing asthma. The authors also compared variable diagnostic cutoff values of PC expressed in different ways.
A methacholine challenge test was performed using an IOS and the mean baseline value, resistance (Rrs), reactance (Xrs), resonance frequency (Rf), and area of reactance (AX) of the respiratory system were recorded simultaneously over a frequency spectrum of 5 to 35 Hz in 50 preschool children with asthma and 41 children with chronic cough, serving as controls.
The results of the methacholine challenge test by IOS, expressed as percent changes of the predicted value (Delta%Pred), were significantly different between the two groups, whereas results expressed as actual data or Z-score were not. PC(80)_Xrs5 was a valuable diagnostic cutoff level for asthma with acceptable sensitivity (80.0%) and specificity (82.9%). The areas under the ROC curves of Xrs5 for both actual (0.867; p < .001) and predicted values (0.877; p < .001) were larger than those for Rrs5 (0.746 and 0.730, respectively).
The authors suggest PC(80)_Xrs5 might be a useful parameter for IOS-assessed bronchial challenge testing in preschool children with asthma.
Simple validity controlled forced oscillatory respiratory resistance (Rrsfo) at 8 Hz frequency was compared with flow-volume spirometry in detection of bronchial changes during induced bronchoconstriction. The methacholine provocation test was performed in subjects with mild asthma (n = 18) and in non-asthmatic subjects (n = 61) of which 44 were classified as responders (delta FEV1 > or = 15% in methacholine test). According to the index of maximal response/coefficient of variation for immediately repeated measurements (delta max/Coeffvar), Rrsfo was shown to be at least as sensitive indicator of bronchoconstriction as FEV1, and better than MMEF and FVC. The shape of the dose-response curves were similar for all parameters. In the non-asthmatic group, there were similar plateaux in Rrsfo, FEV1, and FVC at the same methacholine concentrations. In the asthmatic group, the provocative concentrations for Rrsfo and spirometric parameters correlated significantly (PC60-Rrsfo versus PC10-FEV1, P < 0.05; PC60-Rrsfo versus PC25-MMEF, P < 0.01). In the non-asthmatic responsive subjects, the correlations between PC60-Rrsfo and PC25-MMEF were significant (P < 0.05). Thus, Rrsfo at a fixed 8 Hz frequency and built-in validity control was shown to be at least as sensitive an indicator for changes in lung function in asthmatic and non-asthmatic responsive subjects as spirometry. Compared to spirometry, it may give additional information with fewer confounding factors during performance.
Measurements of bronchial hyper-responsiveness rely on sensitive techniques for measurement of bronchoconstriction, ideally based on tidal breathing. A potentially useful technique is measurement of airway dead space (VDaw), which reflects the volume of the conducting airways. The aim of this study was to evaluate measurements of VDaw with the single breath test for CO2 (SBT-CO2), compared to spirometric measurements, as a method of measuring bronchial response to methacholine challenge. Nineteen healthy adults were studied. Dosimetric methacholine challenge tests were performed on two study days. Forced expirations or the SBT-CO2 were used to assess the response. There were dose-dependent reductions in the spirometric measurements, with a 10 +/- 10% reduction from the baseline value of forced expiratory volume at the highest dose of methacholine. There was a dose-dependent reduction from the baseline value of VDaw by 19 +/- 9% at the highest dose. There was also a dose-dependent increase in the slope of the alveolar plateau of the SBT-CO2. This study provides support for measurement of VDaw as a means of evaluating bronchial responsiveness after methacholine challenge. In a group of healthy adults, this method shows a greater response but with similar dispersion as measurement of forced expiratory volume after methacholine challenge.
The Methacholine concentration at which a 20% decrease of the forced expiratory volume in 1s (PC20_FEV1) or a 40% increase in airway resistance (PC40_Rrs6) occur are accepted indicators for airway hyperresponsiveness. We hypothesised that the level of detection of bronchial hyperresponsiveness will differ between the two methods.
The response to Methacholine was assessed by forced oscillation technique (FOT) and spirometry in 20 stable hyperresponsive asthmatics. The effects of repeated lung function measurements on respiratory muscle fatigue were measured from maximal inspiratory mouth pressure (MIP). After each dose, patients scored their perception of dyspnoea on a BORG scale. Differences in patient's burden were measured by comparing the BORG-score at PC40_Rrs6 (BORG-PC40_Rrs6) and at PC20_FEV1 (BORG-PC20_FEV1). Reproducibility was also evaluated.
The PC20_FEV1-values were 2.2 (0.4) doubling dose higher as compared to the PC40_Rrs6 (P<0.001). The mean BORG-score at PC40_Rrs6 was 1.7 points lower as compared to the BORG-score at PC20_FEV1 (P<0.001). The difference (mean(sd)) between the PC20_FEV1 of measurement 1 and 2 was -0.1 (1.4) doubling dose, and -0.3 (2.7) doubling dose for PC40_Rrs6. The MIP after Methacholine provocation was 1.0(0.2) kPa lower as compared to the MIP before the challenge test (P<0.001), suggesting respiratory muscle fatigue.
Measuring PC40_Rrs6 shortens the challenge test and lowers the concentrations of bronchoconstrictor agents as compared to measurements of PC20_FEV1. The FOT-method was less strenuous for patients. In spite of the fact that the reproducibility is two-fold worse than measuring PC20_FEV1, it still remains quite acceptable at a mean of 0.3 doubling dose. The respiratory muscle strength was deteriorated after the challenge test.
The aim of the study was to determine whether the forced oscillation technique (FOT), which does not require active cooperation, may be useful to assess bronchial responsiveness in patients with suspected occupational asthma (OA).
Changes in resistances evaluated by FOT, and DeltaFEV1 measured during methacholine challenge test were compared in 77 adults referred for suspected OA. Spearman correlations and ROC curves were used.
R0 at the final dose of methacholine (R0hmd) and DeltaR0 were strongly correlated with DeltaFEV1 (p < 0.001). The ROC curves showed that R0hmd >or= 240% predicted was the best cut-off value to discriminate subjects with OA from nonasthmatic subjects (sensitivity: 80%, specificity: 76%).
FOT can be proposed as an alternative method for the assessment of bronchial responsiveness in subjects with suspected OA, unable to correctly perform forced expiratory maneuvers.
The efficiency of a standardised inhalation test procedure was studied by examining the reproducibility of responses to histamine and methacholine. In addition, the responses to the two agents were compared. Each set of duplicate tests was carried out on a separate day within one week, and all factors known or presumed to influence responses were carefully controlled. The results were expressed as the provocative concentration of the agent causing a 20% fall in forced expired volume in one second (PC20). Responses to histamine and methacholine were highly reproducible (coefficients of determination [r2] = 0.994 and 0.990 respectively). Responsiveness to histamine correlated closely with responsiveness to methacholine (r2 = 0.85). There was a small but significant cumulative dose effect with methacholine (P less than 0.01) but not with histamine. Side effects of throat irritation, flushing, and headache were more frequent with histamine than methacholine, and were dose-related. The high level of reproducibility indicates the efficiency of the test procedure. The similar severity of effects by agents with different mechanisms of action suggests that the primary cause of non-specific bronchial hyperreactivity lies at the level of bronchial smooth muscle.
Measurement of bronchial reactivity is widely used in epidemiological surveys. Histamine has been compared with methacholine inhalation challenge in two samples of adults from a small town to determine which is the better agent for use in community studies. Increasing doses of histamine and methacholine were given, up to a maximum of 4 and 12 mumol respectively, according to the method of Yan et al, the provocative dose of agonist causing a 20% fall in FEV1 (PD20) being measured. More subjects had a measurable PD20 with methacholine than with histamine, both in a random sample of 108 subjects (25 v 11 subjects, p less than 0.01) and in an additional 95 subjects selected because of wheeze in the last 12 months (67 v 48 subjects, p less than 0.01). Side effects were mild with both agents but histamine caused voice change in more subjects (21% v 11%). Repeatability was assessed in a further group of subjects with wheeze in the last year. The 95% range for a single estimation of PD20 in subjects with a measured PD20 on at least one occasion was +/- 2.5 doubling doses for histamine (n = 25) and +/- 2.1 doubling doses for methacholine (n = 33). Thus methacholine has advantages over histamine for community studies of bronchial reactivity as it is possible to use doses that produce more PD20 measurements with fewer side effects.
An easy and safe dose-response histamine-inhalation test is described, to measure the level of non-specific bronchial reactivity.
The test was performed in 307 subjects. Non-specific bronchial reactivity was increased in 3% of presumed normal subjects, in 100% of active asthmatics and in 69% of asymptomatic asthmatics with previous symptoms only at times of exposure to clinically relevant allergens. It was also increased in 47% of patients with cough and no other chest symptoms, in 40% of patients with rhinitis and vague chest symptoms not by themselves diagnostic of asthma, and in 22% of patients with rhinitis and no chest symptoms.
The patients with asthma were studied when their asthma was well controlled and when their minimum drug requirements had been established. The mean level of bronchial reactivity increased with increasing minimum drug requirements. The level of bronchial reactivity also showed a strong negative correlation with the forced expiratory volume in 1 sec (FEV1). Atopic subjects, with or without asthma, showed a significant positive correlation between the level of bronchial reactivity and atopic status as indicated by the number of positive allergy skin tests.
A technique is described allowing one to determine simultaneously the resistance and reactance of the total respiratory system for various frequencies. During spontaneous breathing, regularly recurring impulses are produced at the mouth by means of a loud speaker. A Fourier analysis of the mouth pressure and flow signals yields mean resistance and reactance values, over 16 s, for all harmonics of 2 Hz up to 30 Hz. The values are in good agreement with those obtained in the absence of breathing and those determined by means of the forced oscillation technique and by body plethysmography. The reproducibility of the measurements is satisfactory (coefficient of variation: 11.6%).
Bronchial hyperresponsiveness is currently defined as an increase in sensitivity to a wide variety of airway narrowing stimuli. Most patients with asthma and chronic obstructive pulmonary disease (COPD) exhibit such an enhanced sensitivity. In asthma, in particular, this hypersensitivity is accompanied by excessive degrees of airway narrowing. This raises the question as to whether measures of sensitivity, e.g. the provocative concentration or dose producing 20% fall in FEV1 (PC20 or PD20), comprise all the relevant information in bronchial hyperresponsiveness. In adjunct to model studies, there is experimental evidence in man that the potential mechanisms of bronchial hyperresponsiveness can be divided into those causing hypersensitivity and those responsible for the increase in the maximal attainable degree of airway narrowing. The recognition and distinction of these components of hyperresponsiveness have clinical implications in the diagnosis and therapy of asthma and COPD. Bronchial hyperresponsiveness is a composite functional disorder, which requires treatment of each of its components.
The potential of the forced oscillation technique to detect the airway response on histamine bronchial challenge tests was compared with that of FEV1 and plethysmographic SGaw. In 53 subjects with a history of episodic wheezing and a normal baseline airway resistance, we carried out bronchial challenges with successively doubling concentrations of histamine until FEV1 had dropped by 15% or more or a concentration of 16 mg/ml histamine was reached. For the baseline values, a mean within-subject coefficient of variation was found of 2.8% for FEV1, 7.4% for SGaw, 8.7% for the oscillatory respiratory conductance at 6 Hz (1/Rrs6), and 7.7% for the mean oscillatory respiratory conductance (between 2 and 26 Hz) (1/Rrs). The latter coefficients allow the calculation of the following threshold values: PD15FEV1, PD40SGaw, PD47 1/Rrs6, and PD42 1/Rrs. The probability of exceeding these levels by chance is virtually zero. Histamine challenge caused significant absolute changes in Rrs at 6 Hz (Rrs6), in mean level of Rrs and of respiratory reactance (Xrs), in slope of Rrs and Xrs versus frequency, and in mean curvature of Rrs-frequency curve. A multivariate analysis of the differences between prechallenge and postchallenge values showed that the parameters with the best sensitivity to detect the effect of histamine were, in decreasing order: the relative change of SGaw, of 1/Rrs6, of 1/Rrs, of FEV1, of FVC, and of 1/Vtg, followed by the absolute change of Xrs and of the average slope of the Rrs-frequency relationship.(ABSTRACT TRUNCATED AT 250 WORDS)
The contribution of impedance measurement of the respiratory system to bronchial challenge tests was studied in 64 asthmatics and 23 control subjects. After histamine challenge, resistance values increased significantly at all frequencies but most markedly at the lower frequencies in the asthmatic group; reactance values significantly decreased at all frequencies. In the control group, resistance significantly increased at 8 and 12 Hz. However, reactance decreased significantly at all frequencies. By multiple logistic model analysis, a simple discriminant score was found with great discriminating power to differentiate asthmatics and nonasthmatics. The discriminating score equals 9 X FEV1 aft - 7 X FEV1 bef. Adding the forced oscillation technique to the equipment for measuring the bronchial response after challenging procedures can give information about the localization of the response to the challenge in the respiratory system.
The forced oscillation technique (FOT) is a lung function method which is applicable from the age of 2.5 years onwards, because only passive co-operation is needed. We used the method as described by Làndsér et al. The aim of this study was to compare indices of bronchial responsiveness obtained by FOT (Rrs6, Rrs, dRrs/df, Xrs), with indices derived from maximal and partial expiratory flow-volume curves (MEFV25, PEFV25, FEV1). Bronchial responsiveness was assessed by methacholine inhalation. Threshold dose (TD), i.e. the dose which caused a 2 SD change from baseline lung function, and provocation dose (PD), i.e. the dose which caused a 20% fall in FEV1, a 40% fall in MEFV25 and PEFV25 and a 40% increase in Rrs and Rrs6, were determined. We found that the indices derived from forced oscillometry compared well to those from maximal and partial flow-volume curves. PD20 FEV1 and PD40 Rrs6 were highly correlated (r = 0.84). TD appeared to be as good as PD to measure bronchial responsiveness and is preferred to PD because of the lower dose needed and limited bronchoconstriction obtained.
With the forced pseudo-random noise oscillation technique (FOT), resistance (Rrs) and reactance (Xrs) of the respiratory system can be measured simultaneously over a frequency spectrum of 2-26 Hz. As only passive cooperation of the child is needed, FOT is suitable for lung function measurements from the age of 2 1/2 years. Hence bronchial responsiveness can be measured in children who are not yet able to perform spirometry or flow-volume curves. We compared bronchial responsiveness to histamine and methacholine obtained with FOT. Threshold dose or provocative dose to histamine and methacholine showed a close correlation in asthmatic children aged 3.6 to 7.8 years. The 24 hour interval within-subject reproducibility of threshold dose and provocative dose to histamine in asthmatic children aged 3.9 to 8.5 years proved to be good. Bronchial responsiveness to histamine or methacholine measured by FOT was not influenced by baseline lung function or by bronchial smooth muscle tone.
A comparison was made of the frequency dependence of total respiratory resistance, (Rrs), and reactance (Xrs), determined by a forced oscillation technique in 442 healthy subjects and in 126 patients with respiratory complaints, with or without slight airways obstruction. The comparison was performed by means of a discriminant analysis. The latter demonstrated that the Rrs and Xrs data, measured between 8 and 24 Hz, of patients differ from those of healthy subjects primarily by a decrease of Rrs with frequency associated with more negative Xrs (and thus with an increase in resonant frequency). This probably also applies to patients with more advanced airways obstruction. The addition of the FEV1 values to the analysis provides only a small amount of independent information. The forced oscillation technique thus appears to be a sensitive tool to separate healthy subjects (smokers and nonsmokers) from patients with respiratory complaints associated or not with a reduced FEV1.
In 407 healthy male subjects, smokers and nonsmokers, the resistance and reactance of the respiratory system were determined between 4 and 24 Hz, using a forced oscillation technique. The values are significantly correlated with age, weight, height, FEV1, and vital capacity. After standardization of the data for the latter variables, there are no differences between smokers and nonsmokers. The technique thus lacks sensitivity for the detection of the effects of smoking.
The measurement of the forced expiratory volume in one second (FEV1) after a maximal inspiration is often used to assess the effect of inhaled bronchoconstrictor agents. In persons with asthma, a deep inspiration transiently alters the bronchial tone in a variable way. This may result in a variable decrease of FEV1 despite a similar degree of pharmacologically induced bronchospasm. In 71 patients with asthma we induced a comparable increase (approximating 200%) in airway resistance (Raw) with aerosolized carbachol. We then measured the change in Raw induced by one deep inspiration; when Raw had returned to the value observed before deep inspiration, the FEV1 was measured. A significant correlation (r = 0.74; p less than 0.001) was found between the transient changes in Raw induced by a deep inspiration (ranging individually from a 33% increase to a 70% decrease) and the decrease in FEV1 (from 0 to 70%). The decrease in FEV1 was greatest in patients in whom a deep inspiration increased Raw and least in those in whom Raw decreased. The initial and post-carbachol Raw values of the 17 patients exhibiting a less than 20% decrease in FEV1 were similar to those of the 54 patients with a decrease in FEV1 of more than 20%. Because a prior deep inspiration prevents changes in FEV1 in some patients with asthma, the use of the FEV1 for bronchial provocation tests can be misleading.
Eight subjects with asthma underwent bronchial challenge with histamine and methacholine. Dose-response curves were drawn on a scale which made the dosage equivalent in molecular weight. The results were analysed in terms of both the slope of the dose-response curve and the dose required to elicit a 20% fall in FEV1. No significant difference between methacholine and histamine was found in either measurement. Because of the similarity of the responses we conclude that the two agents are similar in action and may be used with equal effectiveness in bronchial challenges.
Impedance measurements by the forced pseudo random noise oscillation technique can be used to study the mechanical characteristics of the respiratory system. The objective of this study was to analyse the changes in impedance to a cold air provocation test in patients with asthma, and to correlate these changes with those in the forced expiratory volume in one second (FEV1).
The response to isocapnic hyperventilation with cold air was assessed by respiratory impedance measurements and spirometry in 60 patients with bronchial asthma in whom the provocative dose of histamine resulting in a 20% fall in FEV1 (PD20) was < or = 8 mumol.
Cold air provocation resulted in a mean(SD) fall in FEV1 from 3.75(0.85) litres to 3.10(0.90) litres. The mean(SD) decrease in FEV1 as a percentage of predicted was 15.4(3.8)%. The oscillatory resistance at 8 Hz increased from a mean(SD) of 0.367(0.108) kPa/l/s to 0.613(0.213) kPa/l/s and at 28 Hz the resistance increased from 0.348(0.089) to 0.403(0.099) kPa/l/s. Frequency dependence of resistance became significantly more negative. The reactance at 8 Hz decreased from a mean(SD) of -0.035 (0.041) kPa/l/s to -0.234(0.199) kPa/l/s, and the resonant frequency increased from 12.5(4.9) Hz to 25.7(9.1) Hz. Significant correlations were calculated between the decrease in FEV1 and changes in the various impedance parameters, especially between the decrease in FEV1 and the increase in resistance at 8 Hz (r = -0.66), and the decrease in FEV1 and the increase in the resonant frequency (r = -0.63).
Cold air provocation in asthmatic subjects results in changes in the impedance of the respiratory system that correlate well with the changes in FEV1. These changes in impedance reflect ventilatory inhomogeneities in the peripheral compartment of the bronchial tree. These observations show the value of this technique in the evaluation of induced bronchoconstriction, as both a quantitative and a qualitative analysis of the response is possible.
Oscillatory pulmonary resistance and exercise-induced bronchoconstriction
- Elshout
Bronchial hyperresponsiveness: normal and abnormal control assessment and therapy
- J E Nadel
- R Pauwels
- P D Snasshall