Within-breath changes of airway calibre in patients with airflow obstruction by continuous measurement of respiratory impedance

We bench-tested a commercially available instrument for measuring respiratory impedance (Siregnost FD5: Siemens) and found that resistance (R) and phase changes were accurately recorded in models. In a single human subject, total respiratory resistance (R(l)) was closely comparable to resistance measured by the Mead-Whittenberger technique. The derived continuous variable (R(os)) was similar to R at less than 4 cmH2O . litres-1 . sec, but underestimated R at higher values. Ros was highly correlated with airways resistance by body plethysmography (R(aw)), but with a low slope and high intercept (R(os) = 1.38 + 0.59 R(aw): r = 0.89). Because of turbulence, both in model larynxes and in normal subjects, R(os) tends to rise with increases in flow in either direction. R(os) also tends to fall as lung volume rises, and vice versa, reflecting cyclic changes in airway calibre. We devised indices of expiratory narrowing of airways from the maximum flow-volume loop, and the plethysmographic alveolar pressure-flow loop, and compared them with the slope of the relation between R(os) and lung volume during tidal breathing, in nine normal subjects and 16 patients with airflow obstruction. Twelve of the 16 patients, all with abnormal flow-volume loops, had high R(os)-volume slopes, demonstrating excessive expiratory narrowing even during tidal breathing. We found no patients with normal inspiratory R(os) together with an abnormal R(os)-volume slope. Thus unstressed inspiratory calibre was never dissociated from airways narrowing on expiration.     

Respiratory mechanics during mechanical ventilation: A model study on the effects of leak around a tracheal tube

Air leak around a tracheal tube (TT) during mechanical ventilation is likely to occur during the inspiratory phase because airway pressure is high for a prolonged period. The presence of a leak may introduce errors in measurements of respiratory mechanics made at the airway opening. If so, respiratory mechanics can be measured more accurately when data are collected during the expiratory phase of ventilation. We examined this phenomenon in a lung model. When a leak was introduced into the model, simulating a leak around the TT, the leak occurred predominantly during the inspiratory phase of respiration. As the magnitude of the leak increased, the overestimation of resistance progressively increased, when calculated from pressure and flow measured at the airway opening. A large leak (38%) resulted in an overestimation of respiratory system resistance by 51% and an underestimation of elastance (Ers) by 23% when calculated from the entire ventilatory cycle. However, there was no under- or overestimation in Rrs when calculated from the expiratory phase only, and ERS was overestimated by only 6.1%. Varying peak inspiratory pressure, end-expiratory pressure, and expiratory time did influence the effect of leak, however, respiratory mechanics could still be calculated accurately from the expiratory phase under these conditions. We conclude that measurements of lung mechanics from the expiratory phase is a promising approach to dealing with the problem of measuring respiratory mechanics in mechanically ventilated infants with leaks around the tracheal tube. Pediatr. Pulmonol. 1997; 24:423–428. © 1997 Wiley-Liss, Inc.     

Flow-volume loop changes reflecting respiratory muscle weakness in chronic neuromuscular disorders

In order to identify the changes in pulmonary function and in the flow-volume loop due to respiratory muscle weakness, two groups of 10 nonsmokers with stable, chronic neuromuscular disease but without respiratory symptoms were studied: one without (Group 1) and one with (Group 2) respiratory muscle weakness as assessed by measurement of maximal static inspiratory and expiratory pressures. In Group 1, pulmonary function was normal except for increased ratio of one-second forced expiratory volume to forced vital capacity and forced expiratory flow at 25 to 75 percent forced vital capacity, which may reflect increased elastic lung recoil. Group 2 had mild volume restriction, appropriate for the degree of respiratory muscle weakness, and reduced inspiratory and expiratory flow rates. Pulmonary function was significantly more disturbed in Group 2 than in Group 1, and correlated well with maximal static inspiratory and expiratory pressures. Analysis of the flow-volume loop configuration revealed that four parameters describing effort-dependent portions were significantly related to maximal static inspiratory pressure and maximal static expiratory pressure. These parameters were peak expiratory flow, the slope of the ascending limb of the maximal expiratory curve, a drop of forced expiratory flow near residual volume, and forced inspiratory flow at 50 percent of vital capacity. A flow-volume loop score obtained from these four parameters was significantly higher in Group 2 than in Group 1 (2.8 +/- 1.03 versus 1.1 +/- 1.37; p less than 0.01). A flow-volume loop score of 2 or more had 80 percent specificity and 90 percent sensitivity in predicting respiratory muscle weakness in these patients with chronic neuromuscular disease. These data suggest that sensitive assessment of the flow-volume loop configuration as part of routine pulmonary function testing may help to suspect and identify respiratory muscle weakness.     

Airway dysfunction in patients with Parkinson's disease

To investigate pulmonary function abnormalities in Parkinson's disease (PD), we obtained maximal inspiratory and expiratory flow-volume curves in 63 patients (59 under treatment) with different stages of the disease, not filtered for respiratory symptoms. PD severity was evaluated by the Unified PD Rating Scale, the Webster's scale, and Hoehn and Yahr staging. Patients with more severe PD had lower percentage forced vital capacity (FVC%), and peak inspiratory and expiratory flows. Those with fluctuations and/or dyskinesias had lower FVC% and percentage forced expiratory flow volume in 1 sec (FEV₁%). There were a number of weak but significant correlations between PD scales and spirographic parameters. Thirty one patients (49.2%) had pathological flow-volume curves. The clinical profile and the duration of the disease did not influence the pattern of the curve. Physiologic evidence of upper airway obstruction was observed in 3 cases. A spirometric restrictive ventilatory defect (FEV₁/FVC higher than or equal to 80%) was observed in 54 patients (85%), while generalized airway obstruction was present only in one nonsmoker. We conclude that abnormal flow-volume loop contour is a frequent finding in PD. This probably reflects involvement of the upper airway musculature, that in some patients can produce upper airway obstruction. Generalized airflow limitation is not an important characteristic of PD. By contrast, a restrictive spirometric defect, probably due to incoordinated expiratory effort or abnormally low chest wall compliance, is the main spirometric finding in these patients. Offprint requests to: J. L. Izquierdo-Alonso     

Evaluation of the flow-volume loop as an intra-operative monitor of respiratory mechanics in infants

Airway pressure is currently the primary indicator of respiratory mechanics used by the anesthetist in the operating room. This quantity can signal that the mechanical properties of the respiratory system have changed. However, there is a need for more sophisticated monitors of mechanics, capable of indicating the nature of the change. We have investigated the use of the tidal flow-volume loop in differentiating between an obstruction of the endotracheal tube and changes in the distribution of regional ventilation, using a computer model. Endotracheal obstruction caused the descending limb of flow-volume loop to become convex to the volume axis, whereas ventilation inhomogeneity caused the curve to become concave to the volume axis. In contrast, examination of peak airway pressure did not allow differentiation between the two conditions. We conclude that, while the peak airway pressure is useful in signaling a change in a patient's condition, the combination of airway pressure and the flow-volume loop serves as a more comprehensive monitor of respiratory mechanics.     

A nonlinear regression analysis of nonlinear,passive-deflation flow-volume plots

When studying lung mechanics of intubated premature infants, by the passive-deflation technique we noted that in many flow-volume plots the descending limb was curvilinear with a convexity toward the volume axis. By conventional linear analysis lung mechanics of these patients did not change after the administration of terbutaline, but Mead's tangent-chord slope ratio method for quantifying the amount of curvature showed that the shape of the flow-volume plots did change. Because of the limitations of this method, we developed a microcomputer based, reiterative regression algorithm which optimizes a nonlinear function for the best fit to any given set of data. We then studied six very low birth weight infants with clinical evidence of pulmonary gas trapping (weight at study, 1.22 ± 0.29 kg; age, 26 ± 16 days). We measured respiratory system resistance (R_rs), compliance (C_rs), and expiratory time constants (TC_rs), by the passive deflation technique before and after subcutaneous administration of 0.02 mg/kg of terbutaline. No effect of terbutaline in a dose sufficient to increase heart rate > 25 beatshin was observed. The same data analyzed using the nonlinear regression technique with a function based upon a two compartment model of parallel inhomogeneities revealed one compartment with relatively normal R_rs, C_rs, and TC_rs, values, and a second compartment with a very high R_rs. The latter fell by 50% after terbutaline. These data suggest that abnormalities of airway resistance in ventilated preterm infants are not easily identifiable by classic linear analysis of lung mechanics. We propose that in such patients the two compartment analysis of passive exhalation mechanics measurements can provide better information about R_rs. © 1993 Wiley-Liss, Inc.     

Cough flow-volume relationships in normal and asthmatic children

The flow-volume profile of a maximum voluntary cough resembles that of a maximum expiratory flow-volume (MEFV) curve with superimposed transient peak flows at the onset of each cough effort and portions of zero flow corresponding to periods of glottis closure. A straight line (the cough slope) can be drawn through the transient peak flows, and the ratio of MEFV-equivalent flow to the cough peak flow can be calculated. This cough ratio has been shown to fall during adult life and may be related to changes in airway compliance and cross-sectional area with age. The present study investigated the cough ratio, cough slope, and maximum flows measured from the cough flow-volume curve in a group of normal children aged 7 to 16 years. Maximum flows and the cough slope increased with height, but the cough ratio did not change with growth or age. In a similar group of asthmatic children, baseline measurements of cough showed a reduction in cough peak flow rates, MEFV-equivalent flow, and the cough ratio. These changes are related to alterations in airway compliance and cross-sectional area and are partly reversed following inhalation of a bronchodilator.     

Lung function measurements in awake compared to sleeping newborn infants.

Tidal breathing flow-volume loops were recorded in 19 healthy newborn infants when awake and asleep. This preceded and followed measurements of passive lung mechanics (by single breath occlusion). Our aim was to evaluate possible differences in lung function due to state of arousal or any influence of the occlusion technique. Expiratory volumes and flow rates were larger in awake than in sleeping infants before, but not after occlusion measurements. In sleeping, but not in awake infants, expiratory volumes and flow rates were higher after occlusion than before. Respiratory system compliance was significantly larger in sleeping than awake infants, while differences in respiratory system resistance and airway plateau pressure did not reach a significant level. Our results show that lung function can be measured in awake as well as sleeping infants, but differs significantly according to their arousal state, and whether tidal expiratory flow measurements are performed before or after airway occlusion measurements. Separate reference values for awake and sleeping infants may, therefore, be required. Marked intrasubject variability was found in the occlusion measurements, and criteria for acceptable measurements need to be defined.     

Use of maximal expiratory flows to evaluate central airways obstruction in infants

Partial expiratory flow-volume (PEFV) curves obtained by the rapid compression technique were employed to assess airway function in three infants with three different lesions of the central airways (vascular ring, congenital tracheal stenosis, subglottic polyp). Preoperatively, all three demonstrated severe flow limitation with a relatively constant forced expiratory flow over the tidal volume range. Postoperatively the PEFV curves changed to a normal convex shape, and the maximal expiratory flows at functional residual capacity (VmaxFRC) returned to normal. The PEFV curve adds to our physiologic assessment of the severity of the central airway obstruction in infants and to the efficacy of our therapeutic intervention.     

Passive respiratory mechanics in newborns and children

When the Hering-Breuer reflex is used to relax the respiratory muscles, the passive compliance (Crs), resistance (Rrs), and time constant (Trs) of the respiratory system can be measured from the subsequent expiration. We used this method to assess 22 newborns with respiratory illness. Passive expirations were also recorded in 6 paralyzed, ventilated children. Using a simple slide valve, airway occlusion pressure was measured from a face mask or endotracheal tube, and expiratory flow was measured from a pneumotachygraph. In all subjects, there was a linear function of expiratory flow versus its integral, volume; by extrapolating the linear function to zero flow and zero volume (i.e., initial volume at time zero) Crs, Rrs, and Trs could be calculated; Crs was significantly reduced in mechanically ventilated versus spontaneously breathing infants, and Rrs was significantly higher in intubated versus extubated infants. During passive expiration in newborns, inspiration occurred at a volume above passive functional residual capacity. The passive expiratory flow-volume technique is simple, noninvasive, and appears to provide accurate measurements of respiratory mechanics in the newborn and in paralyzed children.     

Effects of expiratory flow resistance on inspiratory work of breathing

To minimize work of breathing, airway pressure should not fluctuate during spontaneous breathing with continuous positive airway pressure (CPAP). However, flow resistance in the inspiratory limb of the breathing circuit and an inadequate continuous gas flow rate result in airway pressure fluctuation and increased work of breathing. Flow resistance of the expiratory pressure/exhalation valve also directly affects the level of airway pressure during spontaneous inhalation with CPAP (the greater the resistance of the valve, the greater the decrease in airway pressure and work of breathing). We compared this effect with three types of expiratory pressure valves: a threshold resistor with low resistance to flow, an inflatable balloon (mushroom) valve with moderate resistance to flow, and a variable-orifice flow resistor with a high resistance to flow. Work increased up to threefold with the balloon valve and more than tenfold with the flow resistor compared with the threshold resistor. To apply CPAP, expiratory pressure valves with low resistance to flow should be used to minimize fluctuations in airway pressure and, thus, in the work of spontaneous breathing.     

Airway responsiveness in infants following bronchiolitis.

Airway responsiveness to inhaled methacholine was assessed in 18 infants, 4 and 10 months old, following bronchiolitis. Pulmonary function was measured from partial expiratory flow-volume curves generated by the rapid compression technique. Sleeping infants inhaled increasing concentrations of methacholine until maximal expiratory flows at functional residual capacity (VmaxFRC) decreased by 30% or 2.5 mg/mL was inhaled. Airway responsiveness was quantitated by: 1) the threshold concentration (log TC) required to decrease VmaxFRC by 2 standard deviations from baseline; 2) the concentration required to decrease VmaxFRC by 30% (log PC30); and 3) the slope of the dose-response curve between TC and PC30 (log SPC30). At both the first and second evaluation, the bronchiolitic infants had lower baseline VmaxFRC (% pred.) than 24 control infants. In addition, the bronchiolitic infants had heightened airway responsiveness compared to controls, demonstrating lower values for logTC and logPC30 and steeper slopes to their dose-response curves (logSPC30). After accounting for the relationship between airway responsiveness and age, the occurrence of bronchiolitis was found to be a significant independent factor 10 months but not 4 months following bronchiolitis. The bronchiolitic infants did not demonstrate the decline in airway responsiveness with increasing age that occurs in normal infants. We conclude that infants exhibit heightened airway responsiveness following bronchiolitis.     

Alveolar pressure and airway resistance during maximal and submaximal respiratory efforts

A digital computing technique was used to extract continuous calculations of average alveolar pressure and airway resistance from body plethysmographic measurements during forced inspiratory and expiratory vital capacity maneuvers and tidal breathing in human subjects. Derived alveolar pressures were similar to those obtained using an interrupter technique (linear regression slope, 0.99 +/- 0.02; r = 0.98) and by comparison with esophageal pressure measurements. Studies in normal subjects revealed a characteristic pattern of increasing airway resistance throughout the expiratory phases of maximal and submaximal respiratory maneuvers, with maximal resistance of 33 to 110 cm H2O/L/s at low lung volumes during forced vital capacities. In contrast, inspiratory resistance remained low and constant throughout maximal and submaximal inspiratory maneuvers. Patients with COPD showed substantially higher inspiratory and expiratory resistances. In three patients with flow-volume loops suggestive of variable extrathoracic upper airway obstruction, measurements of alveolar pressure and airway resistance made it clear that two of the patients had upper airway obstruction, whereas the other was exerting an inadequate effort. We conclude that this noninvasive technique provides valid estimates of alveolar pressure and airway resistance continuously throughout both phases of the respiratory cycle over a wide range of volumes and flow rates. It may prove to be useful in the assessment of effort and airway obstruction in patients with a variety of pulmonary conditions.     

Dynamic behavior of respiratory system during nasal continuous positive airway pressure in spontaneously breathing premature newborn infants

The end-expiratory lung-volume level of premature newborn infants is maintained above passive resting volume during active breathing, through the combination of reduced time constant and high respiratory rate. To determine whether nasal continuous positive airway pressure (NCPAP) alters this characteristic dynamic breathing pattern, we studied the effects of various NCPAP levels on the dynamic elevation of end-expiratory lung volume level (DeltaEELV) in spontaneously breathing premature newborn infants, using respiratory inductive plethysmography (RIP). Eleven premature newborn infants with moderate respiratory failure were included. NCPAP levels were set in a random order to 0, 2, 4, and 6 cm H2O. Tidal volume (Vt), rib-cage contribution to Vt (%RC), phase angle between abdominal and thoracic motions (theta), respiratory rate (RR), and inspiratory and expiratory times (Ti and Te) were continuously recorded by RIP. The slope of the linear part of the expiratory flow-volume relation was extrapolated up to zero flow level to evaluate the dynamic elevation of the functional residual capacity (FRC) (DeltaEELV). The time-constant of the respiratory system (tauRS) was calculated as the slope of the linear part of the expiratory flow-volume loop. At NCPAP = 6 cm H2O, DeltaEELV reached 0.6 +/- 0.2 times the Vt at NCPAP = 0 cm H2O. An increase in NCPAP level resulted in a significant decrease in DeltaEELV (P < 0.01). A decrease in DeltaEELV during NCPAP was associated with a significant increase in Te from 0.62 +/- 0.13 sec at NCPAP = 0 cm H2O to 0.80 +/- 0.07 sec at NCPAP = 6 cm H2O (P < 0.05), and a decrease in tauRS from 0.4 +/- 0.1 sec at NCPAP = 0 cm H2O to 0.24 +/- 0.04 sec at NCPAP = 6 cm H2O (P < 0.01). These results indicate that the characteristic spontaneous breathing pattern causing a dynamic elevation of FRC is abolished by NCPAP. We speculate that the dynamic volume-preserving mechanisms resulting from expiratory flow braking are no longer required during NCPAP, as the constant pressure may passively elevate FRC.     

容积曲线在诊断OSAS中的应用

目的　探讨仰卧位最大呼气流量-容积(F- V)曲线对睡眠呼吸暂停综合征(OSAS)诊断的可行性。方法　利用德国产JAEGER肺功能仪对37位已确诊的OSAS患者分别进行立位和仰卧位F- V曲线测定,并对比二者的阳性率。结果　立位F- V曲线阳性率67.5 %。而卧位F- V曲线阳性率91 .9% ,两者比较有非常显著性差异。结论　仰卧位测定F -V曲线可作为一种对阻塞性睡眠呼吸暂停综合征的初筛的诊断方法。     

Factors affecting upper airway patency

We studied the following functional factors which affect upper airway patency. First, the effects of inspiratory resistive loading, increased pulmonary resistance, hypercapnic gas or hypoxic gas loading on the upper airway pressure-flow (P-F) relationship were studied. The upper airway P-F curves under these loading conditions shifted upward with load dependency. Secondly, effects of limb muscle contraction on upper airway resistance (Rua) were studied. Rua decreased reflexly during limb muscle contraction. Thirdly, effects of body position on the stability of the upper airway were studied. The upper airway was kept patent in the lateral position. Fourthly, effects of electrical stimulation of the genioglossus muscle on P-F relationship of upper airway were studied. P-F curves of upper airway shifted upward with increase in stimulation frequency. Fifthly, effects of nasal or oropharyngeal lubrication by artificial surfactant on the critical stimulation frequency (CSF) for upper airway opening were studied. Nasal or oropharyngeal lubrication decreased CSF. Based on these fundamental studies, we applied constrained lateral position, submental stimulation due to demand-type stimulator and nasal or oropharyngeal lubrication for treatment of patients with obstructive sleep apnea syndrome (OSAS). We found these three methods were effective in treatment of OSAS patients.     

Consistency of repeated flow-volume parameters in airway challenge studies

A maximal lung inflation is known to alter airway tone in man. Recent investigations, examining how this phenomenon relates to bronchial provocation testing, suggest that a deep inspiration will decrease airway resistance and underestimate the subsequent decrement in lung function following airway challenge. Because the recovery of baseline tone is rapid following a deep inspiration, we evaluated the consistency of three consecutive partial and maximal expiratory flow-volume maneuvers performed at approximately 45- to 60-second intervals. Functional parameters including the forced expiratory volume in 1 s and the maximal expiratory flow at 60% of the vital capacity below total lung capacity on the partial curve (MEF40%P) were constant at each measurement point following induced bronchoconstriction or bronchodilation in both healthy and asthmatic subjects. We suggest that with 45 s between maneuvers, repeatable parameters can be attained from three consecutive flow-volume curves.     

Noninvasive determination of respiratory mechanics during mechanical ventilation of neonates: a review of current and future techniques

Study of the mechanical properties of the respiratory system is needed to help provide a better understanding of the pathogenesis of diseases causing respiratory failure. The nature of neonatal intensive care requires that any technique for monitoring respiratory mechanics be simple, noninvasive, and allow continued free access to the neonate. The peak airway pressure developed during volume cycled ventilation reflects the mechanical properties of the respiratory system but cannot distinguish between changes in the flow-resistive or elastic properties. Similarly, dynamic compliance combines both the flow-resistive and elastic components of the respiratory system in a single number and flow-volume loops also reflect both elements. Extracting a single time-constant from the expiratory limb of the latter assumes a single-compartment model for the respiratory system and, as such, does not provide sufficient information to describe frequency dependence of resistance and compliance. Furthermore, flow-volume loops are markedly distorted by the presence of an endotracheal tube, which must be corrected for, before calculating values of resistance and compliance. To provide the information to understand better the physiologic processes and adaptive mechanisms in diseased states causing acute respiratory failure, it is necessary to use a method that is based on a more detailed and realistic model of the respiratory system. Two such techniques that appear to warrant further investigation in ventilated infants are the interrupter technique and the forced-oscillation technique.     

Pressure-flow curves in infancy

Calibrated pressure-flow (P-V) curves were plotted by computer using data from both the plethysmographic method for measuring airway resistance and the esophageal balloon technique for measuring lung resistance. P-V curves from 100 sick, healthy, and convalescent infants (age range 2 days to 19 months, weight range 0.9-10.4 kg) were classified into five distinctive types according to shape and direction of looping. Two of these patterns, one with a virtually closed, the other with a narrow figure-of-eight loop, reflected the normal physiologic changes in airway caliber that may occur during tidal breathing. The remaining three patterns, with far more marked changes in resistance, were associated with particular pathophysiologic mechanisms of airway obstruction. A wide figure-of-eight configuration, in which the expiratory loop rotated clockwise with marked flow limitation toward end expiration, was found for infants with chronic lung disease. By contrast, a rise in initial expiratory resistance due to dynamic glottic narrowing, with an anticlockwise rotated expiratory P-V loop, occurred in infants with reduced or unstable lung volumes. A clockwise inspiratory loop was observed only for infants intubated during the neonatal period, many of whom had clinical evidence of extrathoracic airway obstruction. Inspection and analysis of P-V curves provides more information about the state of the airways than does a single numerical expression of resistance. However, since normal patterns of P-V curves are not restricted to infants with healthy airways, a combined qualitative and quantitative approach to these measurements is recommended.     

Effects of electrical stimulation of the genioglossus on upper airway resistance in anesthetized dogs

We examined the relationship between the frequency of stimulation of the genioglossus and upper airway resistance in six anesthetized dogs in the supine position. The upper airway was isolated from the lower airway by transecting the cervical trachea, and the pressure flow relationship of the upper airway was obtained by applying constant negative pressure (5, 10, and 20 cm H2O) to the proximal cut end of the trachea. Electrical stimulation of the genioglossus was performed at a constant voltage (10 to 20 V) and at various frequencies (as high as 100 Hz). Upper airway resistance (Rua) during both inspiration and expiration increased with an increase in tracheal negative pressure, and at each tracheal negative pressure Rua was significantly reduced by stimulation of the genioglossus. The effects of genioglossal muscle stimulation were nonlinearly dependent on the stimulating frequency. Below 50 Hz, Rua decreased markedly as the stimulating frequency was increased, but above 50 Hz, Rua plateaued at a minimum value. These findings suggest that at a stimulating frequency of more than 50 Hz, upper airway patency is stably maintained in anesthetized dogs.