Glottal Aperture and Buccal Airflow Leaks Critically Affect Forced Oscillometry Measurements.

BACKGROUND: The forced oscillation technique (FOT) measures respiratory resistance and reactance; however, the upper airways may affect the results. We quantified the impact of glottal aperture and buccal air leaks. METHODS: In the glottal aperture study (1) 10 healthy subjects (aged 34 ± 2 years) performed a total lung capacity maneuver followed by 10-s breath-hold with and without total glottal closure and (2) the effects of humming (incomplete glottal narrowing) on FOT measurements were studied in six healthy subjects. Glottal narrowing was confirmed by direct rhinolaryngoscopy. In the air leak study, holes of increasing diameter (3.5, 6.0, and 8.5 mm) were made to the breathing filters. Eleven healthy subjects (aged 33 ± 2 years) and five patients with COPD (aged 69 ± 3 years) performed baseline FOT measurements with the three modified filters. RESULTS: Narrow glottal apertures and humming generated whole-breath resistance at 5 Hz (R5) peaks, increased R5 (1.49 ± 0.37 kPa/L/s vs 0.34 ± 0.01 kPa/L/s, P < .001), and decreased whole-breath reactance at 5 Hz (X5) values (-2.10 ± 0.51 kPa/L/s vs -0.09 ± 0.01 kPa/L/s, P < .001). The frequency dependency of resistance was increased. Holes in the breathing filters produced indentations on the breathing trace. Even the smaller holes reduced R5 in healthy subjects (0.33 ± 0.02 to 0.24 ± 0.02 kPa/L/s, P < .01) and patients with COPD (0.50 ± 0.04 to 0.41 ± 0.04 kPa/L/s, P < .05), whereas X5 became less negative (from -0.09 ± 0.01 to -0.05 ± 0.01 in healthy subjects, P < .01; from -0.22 ± 0.06 to -0.11 ± 0.03 kPa/L/s in patients with COPD, P < .05). CONCLUSIONS: Visual inspection of the data is required to exclude glottal narrowing and buccal air leaks identified as R5 peaks and volume indentations, respectively, because these significantly affect FOT measurements.

Analysis of impulse oscillometric measures of lung function and respiratory system model parameters in small airway-impaired and healthy children over a 2-year period.

BACKGROUND: Is Impulse Oscillometry System (IOS) a valuable tool to measure respiratory system function in Children? Asthma (A) is the most prevalent chronic respiratory disease in children. Therefore, early and accurate assessment of respiratory function is of tremendous clinical interest in diagnosis, monitoring and treatment of respiratory conditions in this subpopulation. IOS has been successfully used to measure lung function in children with a high degree of sensitivity and specificity to small airway impairments (SAI) and asthma. IOS measures of airway function and equivalent electrical circuit models of the human respiratory system have been developed to quantify the severity of these conditions. Previously, we have evaluated several known respiratory models based on the Mead's model and more parsimonious versions based on fitting IOS data known as extended RIC (eRIC) and augmented RIC (aRIC) models have emerged, which offer advantages over earlier models. METHODS: IOS data from twenty-six children were collected and compared during pre-bronchodilation (pre-B) and post- bronchodilation (post-B) conditions over a period of 2 years. RESULTS AND DISCUSSION: Are the IOS and model parameters capable of differentiating between healthy children and children with respiratory system distress? Children were classified into two main categories: Healthy (H) and Small Airway-Impaired (SAI). The IOS measures and respiratory model parameters analyzed differed consistently between H and SAI children. SAI children showed smaller trend of "growth" and larger trend of bronchodilator responses than H children.The two model parameters: peripheral compliance (Cp) and peripheral resistance (Rp) tracked IOS indices of small airway function well. Cp was a more sensitive index than Rp. Both eRIC and aRIC Cps and the IOS Reactance Area, AX, (also known as the "Goldman Triangle") showed good correlations. CONCLUSIONS: What are the most useful IOS and model parameters? In this work we demonstrate that IOS parameters such as resistance at 5 Hz (R5), frequency-dependence of resistance (fdR: R5-R20), reactance area (AX), and parameter estimates of respiratory system such as Cp and Rp provide sensitive indicators of lung function and have the capacity to differentiate between obstructed and non-obstructed airway conditions. They are also capable of demonstrating airway growth-related changes over a two-year period. We conclude that the IOS parameters AX and the eRIC model derived parameter Cp are the most reliable parameters to track lung function in children before and after bronchodilator and over a time period (2 years). Which model is more suitable for interpreting IOS data? IOS data are equally well-modelled by eRIC and aRIC models, based on the close correlations of their corresponding parameters - excluding upper airway shunt compliance. The eRIC model is a more parsimonious and equally powerful model in capturing the differences in IOS indices between SAI and H children. Therefore, it may be considered a clinically-preferred model of lung function.

Circuit analysis justifies a reduced Mead's model of the human respiratory impedance for impulse oscillometry data.

Recent attempts at estimating the parameters for respiratory impedance models from data obtained by Impulse Oscillometry (IOS) have come across difficulties when using the well-established Mead's model of human respiratory impedance. Unconstrained optimization of this model often yields values of chest wall compliance (C(W)) and lung compliance (C(l)) too large to be physiologically feasible. We hypothesize that IOS volume displacements are inconsequential to the lung tissue and chest wall due to the small contributions of these displacements relative to lung capacity. In order to explore the validity of this hypothesis we performed a detailed analysis of Mead's impedance model. The IOS input flow signal was approximated by using a combination of typical waveforms, this signal was then used to excite Mead's electrical circuit model of the respiratory impedance with physiologically realistic parameter values estimated using data obtained from one normal adult, ten adult patients with Cystic Fibrosis, ten patients with Asthma and ten normal children, with focus on normal adult data. Pressure waveforms, energy and integrated pressure values were then obtained and compared at different points of interest in the model. This investigation suggests that the pressures "felt" by the lung tissue and chest wall are too small to have a noticeable effect on them therefore making those particular circuit elements unnecessary when the respiratory system is subject to small displacement volumes such as those used in Impulse Oscillometry. Furthermore, we believe that the very large parameter values often obtained with unconstrained optimization of Mead's model are evidence that C(l) and C(w) could be "shorted-out" when modeling IOS data.

Electrical circuit models of the human respiratory system reflect small airway impairment measured by impulse oscillation (IOS).

The use of the forced oscillatory input impedance parameter, frequency-dependence of Resistance (fdR), to assess small airway impairment (SAI) has not been widely accepted due to concern about the effects of "upper airway shunt" on oscillometric resistance and low frequency reactance. On the other hand, recent medical studies suggest that low frequency reactance is a very sensitive index of treatment intervention directed at small airways. The present study was undertaken to analyze and compare Impulse Oscillometry (IOS) resistance and reactance data with model-derived indices of small airway function from two models of the respiratory impedance, one with, and the other without an element for upper airway shunt capacitance. Fifty six patients with stable chronic obstructive lung disease of varying severity due to Cystic Fibrosis (CF) and 21 patients with asthma were evaluated by IOS testing. IOS data were input into the augmented RIC (aRIC) model with an upper airway shunt capacitance, and the extended RIC (eRIC) model, without a shunt capacitance element. Model-derived indices were compared between the two models for CF patients separately from asthma patients. We conclude that IOS indices of SAI are modeled equally well with or without upper airway shunt capacitance, and do not seem to be dependent on upper airway shunt capacitance.

Airway response to emotional stimuli in asthma: the role of the cholinergic pathway.

In asthma, airways constrict in response to emotion and stress, but underlying mechanisms, potential extrathoracic contributions, and associations with airway pathophysiology have not been elucidated. We therefore investigated the role of the cholinergic pathway in emotion-induced airway responses in patients with asthma and the association of these responses with airway pathophysiology. Patients with asthma (n=54) and healthy participants (n=25) received either 40 microg ipratropium bromide or a placebo in a double-blind double-dummy cross-over design in two laboratory sessions with experimental emotion induction. Stimuli were preevaluated films and pictures of pleasant, unpleasant, and neutral quality. Respiratory resistance and reactance at 5 and 20 Hz were measured continuously before and during presentations, together with respiration by impedance plethysmography and end-tidal PCO2 by capnometry. In addition, measures of airway inflammation (fraction of exhaled nitric oxide), airway hyperreactivity (methacholine challenge), and reversibility of obstruction were obtained. Respiratory resistance at 5 and 20 Hz increased during unpleasant stimuli in asthma patients. This response was blocked by ipratropium bromide and was not substantially associated with asthma severity, airway inflammation, hyperreactivity and reversibility, or pattern of ventilation and PCO2. Under the placebo condition, changes in resistance during unpleasant films were positively correlated with patients' reports of psychological asthma triggers. In conclusion, airway constriction to unpleasant stimuli in asthma depends on an intact cholinergic pathway, is largely due to the central airways, and is not substantially associated with other indicators of airway pathology. Its link to the perceived psychological triggers in patients' daily lives suggests a physiological basis for emotion-induced asthma.

Emotional reactivity of the airways in asthma: consistency across emotion-induction techniques and emotional qualities.

Considerable individual differences exist in asthma patients' airway responses to emotional stimuli, but little is known about the generalization of such responses across situations or states of airways constriction. Fifty-four asthma patients and 25 healthy controls viewed in two separate sessions, films and blocks of pictures from each of three emotional qualities, pleasant, unpleasant, and neutral. At the beginning of each session, patients received a placebo or anti-cholinergic bronchodilator (ipratropium bromide), respectively, in a randomized double-blind design. Respiratory resistance, reactance and impedance were recorded throughout stimulus presentations with impulse oscillometry. Resistance increases showed a moderate degree of generalization across unpleasant films and pictures, unpleasant and pleasant pictures, as well as cholinergic blockade and placebo. Thus, the intensity of airway responses to unpleasant emotional stimuli is a moderately stable characteristic of asthma patients. In addition to the central airway, peripheral and extrathoracic airways may also contribute the consistency of such responses.

Viral asthma: implications for clinical practice.

The natural history of asthma appears to be driven primarily by the timing and duration of viral respiratory infections. From the very high rate of infections in childhood, to the more sporadic pattern seen in adults, the cycle of acute injury followed by an inefficient repair process helps explain the clinical patterns of asthma severity currently recognized by asthma guidelines. Why the asthmatic host responds to viral injury in a particular way is largely a mystery and the subject of intense investigation. The role of viruses in asthma extends not just to intermittent but to persistent disease, and to both the atopic as well as nonatopic phenotypes. Future therapeutic strategies should include primary prevention via the development of antiviral innate immunity-enhancing vaccines, as well as secondary prevention via the use of antiviral agents, or immunomodulators designed to boost the antiviral response or interrupt the proinflammatory cascade.

Inert gas washout: theoretical background and clinical utility in respiratory disease.

Inert gas washout was first described more than 60 years ago and 2 principal tests have been developed from it: the single breath and multiple breath washout (MBW) techniques. The invention of fast responding gas analysers almost 60 years ago and small computers 30 years later have facilitated breath-by-breath analysis and the development of sophisticated analysis techniques. It is now possible to detect not only the degree of pulmonary ventilation inhomogeneity, but also to gain important insight into the location of the underlying disease process. While single breath washout requires a full vital capacity effort, tidal breathing during the multiple breath test requires minimal co-operation and co-ordination, and is feasible in subjects of all ages. Available MBW normative data from parameters, such as the lung clearance index, appears to vary minimally with age, making MBW particularly useful to follow children longitudinally. Multiple breath inert gas washout has demonstrated improved sensitivity, in comparison to spirometry, in the early detection of a number of important disease processes, including cystic fibrosis. Despite this, these important techniques remain under-utilised in the clinical setting and there is a lack of commercially available devices currently available. The recent resurgence of research in this area has produced a large number of important studies and a pronounced international interest has developed in these techniques. This review article will provide an overview of the theoretical background of inert gas washout and analysis indices, review important physiological and clinical insights gained from research to date (as well as from our own experience) to illustrate its utility, and outline the challenges that lie ahead in incorporating these techniques into the mainstream clinical setting.

Optimizing performance of respiratory airflow resistance measurements.

In contrast to spirometry, airflow resistance determinations provide an effort independent measure of the airway status and allow measurement in individuals unable or unwilling to provide adequate effort during spirometry. Resistance measurements may be performed using an esophageal balloon, airflow perturbation techniques (including interrupter and oscillatory techniques), or total-body plethysmography. Esophageal balloons are invasive, and airflow perturbation techniques are becoming more widely used. Airflow perturbation methods assess small airway dysfunction using frequency dependence of resistance, a surrogate for frequency dependence of compliance. Body plethysmography remains the "gold standard" for measuring airway resistance and is based on measures of pressure changes and flows with the patient enclosed in a body plethysmograph. While plethysmographic procedures may be completed rapidly, yielding multiple trials within preset repeatability criteria, the equipment is costly and the operator must be highly trained. Plethysmographic specific resistance loops have definite shapes (morphologies) indicative of specific airway disorders, which may be interpreted in a manner analogous to spirometry. Specific resistance and conductance assess the important effects of lung volumes. Reimbursement for resistance measurements varies depending on regional guidelines.

Clinical applications of forced oscillation to assess peripheral airway function.

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

Within- and between-day variability of respiratory impedance, using impulse oscillometry in adolescent asthmatics.

The objectives of the present study were to: 1) assess spirometric indices and respiratory impedance with forced oscillation (FO), using impulse oscillometry (IOS) in clinically stable asthmatic children over 3 consecutive days; 2) assess FO reactance (X), using an integrated index and resistance (R) separately during inspiration and expiration; and 3) assess effects on FO of hand support of cheeks vs. no hand support. Our hypotheses were: 1) because of increased sensitivity, IOS manifests day-to-day variability not demonstrable by spirometry; 2) IOS R during expiration exceeds that during inspiration; and 3) hand support of cheeks affects IOS R and X only minimally. We obtained triplicate twice-daily measures of IOS R and X in asthmatic adolescents at summer camp, in a convenience sample of children willing, with parental permission, to undergo repeated testing on consecutive days. Subjects received all medications between 6:30-7:30 AM, and were bronchodilated at time of testing. Subjects underwent IOS tests without hand support of cheeks, followed by tests with both hands supporting cheeks. ANOVA and regression analyses were used to discern technique differences.Significant differences in IOS inspiratory R5, R5 - R15 (frequency dependence of R), and low frequency reactance area (AX) occurred across 3 days, but spirometric indices were unchanged. Inspiratory R at 5 Hz (R5) was significantly smaller than expiratory R5 (P < 0.0001). ANOVA revealed no significant differences between hand and facial muscle cheek support for IOS R and X below 15 Hz, but significant differences occurred above 15 Hz. In conclusion, inspiratory R5, R5 - R15, and AX are sensitive measures for detecting changes in bronchomotor tone in adolescent asthmatic subjects, while expiratory R5 may be influenced by additional factors. Manual support of cheeks does not appear to affect IOS indices of peripheral airway obstruction in adolescent asthmatics. IOS is a practical method for quantifying respiratory mechanics, and its potential role in disease management warrants further study.

Chronic and acute effects of "crack" cocaine on diffusing capacity, membrane diffusion, and pulmonary capillary blood volume in the lung.

STUDY OBJECTIVES: To evaluate possible alterations in the diffusing capacity of the lung for carbon monoxide (DLCO) or its components, membrane diffusing capacity of the lung for carbon monoxide (DMCO) and pulmonary capillary blood volume (Vc), in habitual smokers of "crack" cocaine (with or without tobacco) and following the short-term administration of inhaled cocaine base or IV cocaine HCl. DESIGN: Cross-sectional and longitudinal evaluation of DLCO and its components in smokers of cocaine alone, tobacco alone, and cocaine plus tobacco, and in nonsmokers and ex-smokers. Measurement of possible acute effects on DLCO and its components after experimental short-term administration of IV and smoked cocaine. SETTING: University and Veterans Affairs hospital research laboratories. PARTICIPANTS: Convenience sample of habitual smokers of crack cocaine with or without tobacco and matched control nonsmokers and ex-smokers, and smokers of tobacco only. MEASUREMENTS: DLCO, DMCO, and Vc. CONCLUSIONS: Neither habitual cocaine smoking in cross-sectional or longitudinal analysis nor the short-term administration of inhaled alkaloidal cocaine significantly affected DLCO or its component parts. In contrast, a clear cross-sectional effect of regular tobacco smoking was demonstrated.