Reference value for expiratory time constant calculated from the maximal expiratory flow-volume curve.

BACKGROUND: The expiratory time constant (RCEXP), which is defined as the product of airway resistance and lung compliance, enable us to assess the mechanical properties of the respiratory system in mechanically ventilated patients. Although RCEXP could also be applied to spontaneously breathing patients, little is known about RCEXP calculated from the maximal expiratory flow-volume (MEFV) curve. The aim of our study was to determine the reference value for RCEXP, as well as to investigate the association between RCEXP and other respiratory function parameters, including the forced expiratory volume in 1 s (FEV1)/ forced vital capacity (FVC) ratio, maximal mid-expiratory flow rate (MMF), maximal expiratory flow at 50 and 25% of FVC (MEF50 and MEF25, respectively), ratio of MEF50 to MEF25 (MEF50/MEF25). METHODS: Spirometric parameters were extracted from the records of patients aged 15 years or older who underwent pulmonary function testing as a routine preoperative examination before non-cardiac surgery at the University of Tokyo Hospital. RCEXP was calculated in each patient from the slope of the descending limb of the MEFV curve using two points corresponding to MEF50 and MEF25. Airway obstruction was defined as an FEV1/FVC and FEV1 below the statistically lower limit of normal. RESULTS: We retrospectively analyzed 777 spirometry records, and 62 patients were deemed to have airway obstruction according to Japanese spirometric reference values. The cut-off value for RCEXP was 0.601 s with an area under the receiver operating characteristic curve of 0.934 (95% confidence interval = 0.898-0.970). RCEXP was strongly associated with FEV1/FVC, and was moderately associated with MMF and MEF50. However, RCEXP was less associated with MEF25 and MEF50/MEF25. CONCLUSIONS: Our findings suggest that an RCEXP of longer than approximately 0.6 s can be linked to the presence of airway obstruction. Application of the concept of RCEXP to spontaneously breathing subjects was feasible, using our simple calculation method.

Graphic analysis of flow-volume curves: a pilot study.

BACKGROUND: Conventional spirometric parameters have shown poor correlation with symptoms and health status of chronic obstructive pulmonary disease (COPD). While it is well-known that the pattern of the expiratory flow-volume curve (EFVC) represents ventilatory dysfunction, little attempts have been made to derive quantitative parameters by analyzing the curve. In this study, we aimed to derive useful parameters from EFVC via graphic analysis and tried to validate them in patients with COPD. METHODS: Using Graphical Analysis 3.4 Vernier Software, we derived from the EFVC such parameters as area of obstruction (Ao), area of triangle (AT), area of rectangle (AR) and ratio of volume at 75 and 25% peak expiratory flow (PEF) (0.25/0.75 V). For validation, we reviewed clinical and spirometric data of 61 COPD patients from Seoul National University Airway Registry (SNUAR) and Korean obstructive Lung Disease (KOLD) cohorts. RESULTS: Of all parameters, only RV/TLC significantly correlated with scores from St. George's Respiratory Questionnaire (SGRQ) (r = 0.447, p = 0.037). Six-minute walking distance (6MWD) highly correlated with Ao/AR (r = -0.618, p = 0.005) and Ao/PEF (r = -0.581, p = 0.009) whereas neither FEV1 nor FEV1/FVC had significant correlation with 6MWD. CONCLUSIONS: Ao/AR and Ao/PEF are promising parameters which correlate well with the exercising capacity of COPD patients.

Effect of exercise-induced bronchoconstriction on the configuration of the maximal expiratory flow-volume curve in adults with asthma.

We determined the effect of exercise-induced bronchoconstriction (EIB) on the shape of the maximal expiratory flow-volume (MEFV) curve in asthmatic adults. The slope-ratio index (SR) was used to quantitate the shape of the MEFV curve. We hypothesized that EIB would be accompanied by increases in SR and thus increased curvilinearity of the MEFV curve. Adult asthmatic ( n  = 10) and non-asthmatic control subjects ( n  = 9) cycled for 6-8 min at 85% of peak power. Following exercise, subjects remained on the ergometer and performed a maximal forced exhalation every 2 min for a total 20 min. In each MEFV curve, the slope-ratio index (SR) was calculated in 1% volume increments beginning at peak expiratory flow (PEF) and ending at 20% of forced vital capacity (FVC). Baseline spirometry was lower in asthmatics compared to control subjects (FEV1 % predicted, 89.1 ± 14.3 vs. 96.5 ± 12.2% [SD] in asthma vs. control; p  < 0.05). In asthmatic subjects, post-exercise FEV1 decreased by 29.9 ± 13.2% from baseline (3.48 ± 0.74 and 2.24 ± 0.59 [SD] L for baseline and post-exercise nadir; p  < 0.001). At baseline and at all timepoints after exercise, average SR between 80 and 20% of FVC was larger in asthmatic than control subjects (1.48 ± 0.02 vs. 1.23 ± 0.02 [SD] for asthma vs. control; p < 0.005). This averaged SR did not change after exercise in either subject group. In contrast, post-exercise SR between PEF and 75% of FVC was increased from baseline in subjects with asthma, suggesting that airway caliber heterogeneity increases with EIB. These findings suggest that the SR-index might provide useful information on the physiology of acute airway narrowing that complements traditional spirometric measures.

Effect of carrying a weighted backpack on lung mechanics during treadmill walking in healthy men.

Weighted backpacks are used extensively in recreational and occupational settings, yet their effects on lung mechanics during acute exercise is poorly understood. The purpose of this study was to determine the effects of different backpack weights on lung mechanics and breathing patterns during treadmill walking. Subjects (n = 7, age = 28 ± 6 years), completed two 2.5-min exercise stages for each backpack condition [no backpack (NP), an un-weighted backpack (NW) or a backpack weighing 15, 25 or 35 kg]. A maximal expiratory flow volume curve was generated for each backpack condition and an oesophageal balloon catheter was used to estimate pleural pressure. The 15, 25 and 35 kg backpacks caused a 3, 5 and 8% (P < 0.05) reduction in forced vital capacity compared with the NP condition, respectively. For the same exercise stage, the power of breathing (POB) requirement was higher in the 35 kg backpack compared to NP (32 ± 4.3 vs. 88 ± 9.0 J min(-1), P < 0.05; respectively). Independent of changes in minute ventilation, end-expiratory lung volume decreased as backpack weight increased. As backpack weight increased, there was a concomitant decline in calculated maximal ventilation, a rise in minute ventilation, and a resultant greater utilization of maximal available ventilation. In conclusion, wearing a weighted backpack during an acute bout of exercise altered operational lung volumes; however, adaptive changes in breathing mechanics may have minimized changes in the required POB such that at an iso-ventilation, wearing a backpack weighing up to 35 kg does not increase the POB requirement.

Use of flow-volume curves to predict oral appliance treatment outcome in obstructive sleep apnea: a prospective validation study.

PURPOSE: Flow-volume curves have been shown to relate to upper airway physiology during sleep and may be useful for predicting the response to treatment of obstructive sleep apnea (OSA) with mandibular advancement splints (MAS). The aim of this study was to prospectively assess the potential clinical utility of a previously derived prediction method using flow-volume curves performed during wakefulness. METHODS: Patients with newly diagnosed OSA interested in undertaking treatment with a custom-made MAS were approached to participate in the study. Response to treatment was defined by a 50% or greater reduction in the apnea-hypopnea index. Flow-volume curves were performed in the erect position prior to construction of the MAS. RESULTS: Flow-volume curves were performed in 35 patients. Of these, 25 patients were responders, and 10 patients were non-responders. A combined cut-off of an inspiratory flow rate at 50% of vital capacity (MIF50) less than 6.0 L/s and a ratio of the expiratory flow rate at 50% of vital capacity to MIF50 of greater than 0.7 correctly classified 48.6% of the patients. It had a sensitivity of 36.0%, specificity of 80.0%, positive predictive value of 81.8%, and negative predictive value of 33.3%. CONCLUSIONS: These results suggest that the previously derived prediction model, using flow-volume curves performed during wakefulness, was not sufficient to reliably predict the response to treatment of OSA with MAS. A combination of a functional assessment using flow-volume curves and a structural evaluation of the upper airway with imaging modalities may result in a prediction model with better performance characteristics.

A model-based method for flow limitation analysis in the heterogeneous human lung.

Flow limitation in the airways is a fundamental process constituting the maximal expiratory flow-volume curve. Its location is referred to as the choke point. In this work, expressions enabling the calculation of critical flows in the case of wave-speed, turbulent or viscous limitation were derived. Then a computational model for the forced expiration from the heterogeneous lung was used to analyse the regime and degree of flow limitation as well as movement and arrangement of the choke points. The conclusion is that flow limitation begins at similar time in every branch of the bronchial tree developing a parallel arrangement of the choke points. A serial configuration of flow-limiting sites is possible for short time periods in the case of increased airway heterogeneity. The most probable locations of choke points are the regions of airway junctions. The wave-speed mechanism is responsible for flow choking over most of vital capacity and viscous dissipation of pressure for the last part of the test. Turbulent dissipation, however, may play a significant role as a supporting factor in transition between wave-speed and viscous flow limitation.

Correlation of spirometry and symptom scores in childhood asthma and the usefulness of curvature assessment in expiratory flow-volume curves.

BACKGROUND: Spirometry, and in particular forced expiratory volume in the first second (FEV(1)), are standard tools for objective evaluation of asthma. However, FEV(1) does not correlate with symptom scores, and hence its value in the assessment of childhood asthma may be limited. Therefore, some clinicians subjectively assess the presence of curvature in the maximum expiratory flow-volume (MEFV) curves obtained from spirometry, where concave patterns are observable despite normal FEV(1) values. OBJECTIVE: To evaluate the usefulness of subjective and objective measures of the curvature in the descending phase of the MEFV curve for the assessment of asthma. METHODS: We obtained symptom scores and performed spirometry in 48 patients with asthma (21 females, mean +/- SD age 10.8 +/- 2.4 y). We measured FEV(1), the ratio of FEV(1) to forced vital capacity (FEV(1)/FVC), maximum expiratory flow at one quarter of the way, and at halfway, through the forced expiratory maneuver (MEF(25) and MEF(50), respectively), and maximum expiratory flow in the middle half of the forced expiratory maneuver (MEF(25-75)). Expiratory obstruction was ranked independently by 3 pediatric pulmonologists, by subjective assessment of the MEFV curve. In addition, the curvature of the descending limb of the MEFV curve was quantitatively estimated by introducing an "average curvature index." RESULTS: No significant correlations were found between FEV(1), MEF(50), MEF(25), and MEF(25-75,) respectively, and symptom score (r = -0.22, p = 0.14; r = -0.23, p = 0.11; r = -0.28, p = 0.057; r = -0.27, p = 0.06). A weak correlation was found for FEV(1)/FVC and symptom score (r = -0.33, p = 0.021). However, quantitatively determined average curvature index (ACI) correlated significantly better with measured symptom scores (r = 0.53, p < 0.001) and were in good agreement with the assessment of expiratory obstruction from subjective curvature assessment. CONCLUSIONS: Our general findings show that individual lung function variables do not correlate well with symptoms, whereas subjective curvature assessment is thought to be helpful. With the average curvature index we have illustrated a potential clinical usefulness of quantifying the curvatures of MEFV curves.

Quantifying the shape of maximal expiratory flow-volume curves in healthy humans and asthmatic patients.

Differences in the absolute flow and volume of maximal expiratory flow-volume (MEFV) curves have been studied extensively in health and disease. However, the shapes of MEFV curves have received less attention. We questioned if the MEFV curve shape was associated with (i) expiratory flow limitation (EFL) in health and (ii) changes in bronchial caliber in asthmatics. Using the slope-ratio (SR) index, we quantified MEFV curve shape in 84 healthy subjects and 8 matched asthmatics. Healthy subjects performed a maximal exercise test to assess EFL. Those with EFL during had a greater SR (1.15 ± 0.20 vs. 0.85 ± 0.20, p<0.05) yet, there was no association between maximal oxygen consumption and SR (r=0.14, p>0.05). Asthmatics average SR was greater than the healthy subjects (1.35 ± 0.03 vs. 0.90 ± 0.11, p<0.05), but there were no differences when bronchial caliber was manipulated. In conclusion, a greater SR is related to EFL and this metric could aid in discriminating between groups known to differ in the absolute size of MEFV curves.

The maximum expiratory flow-volume loop in natives of Ladakh and acclimatized lowlanders.

Differences in static and dynamic volumes may exist between high altitude residents of Indian Himalayas and their South American counterparts, as well as with acclimatized lowlander sojourners. Maximum expiratory flow-volume loops were recorded in healthy native highlanders of Ladakh (NH, N = 75) and in healthy acclimatized lowlanders (AL, N = 32) at an altitude of 3450 m in the western Indian Himalayas. The forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1), both corrected for a height of 168 cm, were significantly higher in NH [FVC: 5.02 (0.51) vs. 3.89 (0.45) L, p < 0.0001; FEV1: 4.27 (0.47) vs. 3.44 (0.37) L, p < 0.0001]. The flow rates at larger lung volumes (PEFR, FEF25, and FEF50) were similar in the two groups. The NH showed significantly higher flow rates at low lung volumes, that is, FEF75 and FEF75-85% [FEF75: 2.03 (0.69) vs. 1.70 (0.52) L/s, p = 0.0092; FEF75-85%: 1.42 (0.54) vs. 1.06 (0.35) L/s, p = 0.0001]. The exact mechanisms allowing the higher flow rates at low lung volumes remain to be elucidated, but it is possible that these findings may indicate an inherited adaptive response in the Ladakhi highlander.

[Evaluation of a new method for detection of obstructive disease in children asthma: the negative expiratory pressure (NEP)]. / Intérêt d'une nouvelle méthode de détection du trouble obstructif dans l'asthme de l'enfant: la pression négative expiratoire (NEP).

INTRODUCTION: To take in charge of an asthmatic child it is necessary to evaluate the lung function. METHODS: In this study, the Negative Expiratory Pressure (NEP) has been used for the first time in children with asthma. After lung spirometry by plethysmography, we have used the NEP to assess the prevalence of expiratory flow limitation (FL) during resting breath in 27 asthmatic children (mean age: 11 +/- 2,5 years) 3-4 days after a crisis in both sitting and supine positions. RESULTS: All the children presented an obstructive defect (FEV 1: 63 +/- 13% med) and a dynamic hyperinflation (FRC: 128 +/- 25% med). According to the NEP, 11 children presented an expiratory flow limitation (FL). Asthma was more severe in the FL than in non-FL children (GINA 2002 classification). Among the 11 FL children, 5 were FL in both sitting and supine position and 6 only in supine. Nine of the 27 children were FL with the conventional method. NEP seems a more accurate method to assess the clinical gravity of asthma than FEV 1. The reduction of FRC in the supine position probably explains the greater incidence of FL in supine position. CONCLUSION: Because of its easy execution, NEP seems to be well adapted for children. Links between FL detected by NEP and clinical signs of asthma has to be assessed by furthers studies including more patients.

Reference ranges for shape indices of the flow-volume loop of healthy children.

BACKGROUND: The concavity of the descending limb of the maximum expiratory flow-volume loop (MEFVL) is the earliest change associated with airflow obstruction in small airways (ATS/ERS Task Force). The shape of the MEFVL changes with age but there are no reference values for shape indices for preschool and school children. OBJECTIVES: To define pediatric reference values for spirometric data and 3 shape indices of MEFVL: 2 geometric indices: the ß angle i.e., the angle between the first ½ part and the 2nd part of the MEFVL and the forced expiratory flow after 50% of the forced vital capacity (FVC) has been exhaled/peak expiratory flow (FEF50 /PEF) ratio; and a ratio that describes relative growth between airway and lung parenchyma, the forced expiratory flow between 25 and 75% of FVC/FVC ratio (FEF25-75 /FVC ratio). METHODS: Data were obtained from 446 Caucasian children (2.5 to 15-year-old). The lambda, mu, sigma method was applied. RESULTS: References for spirometric parameters and 3 shape indices. The geometric indices decreased with age from 3 years of age (mean ß angle was 215° and FEF50 /PEF ratio was 0.82) until 8 years of age (mean ß angle was 191° and FEF50 /PEF ratio was 0.60) and then remained constant. The FEF25-75 /FVC ratio also decreased with age. Sex was a significant determinant for FEF25-75 /FVC ratio predicted values. CONCLUSIONS: This study provides standard reference equations for indices of mid-expiratory flows in children and we suggest using the FEF50 /PEF index.

The flow-volume loop in bilateral vocal cord paralysis.

A 38-year-old man with posttraumatic bilateral vocal cord paralysis and a surgically repaired avulsion of the extrathoracic trachea presented with a slight increase of exertional dyspnea (grade 2). Spirometry showed high normal FEV1 for FVC variables, but the F-V loop was characteristic for highly variable UAO with an increased FEV1/PEF ratio of 11 ml/L/min as well as a MEF50/MIF50 of 4.55. Endoscopy during forced respiration showed near total inspiratory obstruction of the larynx due to paradoxical behavior of the vocal cords. In extrathoracic airway obstruction a FEV1/PEF ratio > 10 ml/L/min combined with a MEF50/MIF50 ratio > 4 is suggestive of variable UAO caused by bilateral vocal cord paralysis rather than by a tracheal lesion.

Use of maximum expiratory flow-volume curve parameters in the assessment of exercise-induced bronchospasm.

Exercise-induced bronchospasm (EIB) is often inferred from the reduction after exercise in one arbitrarily selected value derived from the maximum expiratory flow-volume (MEFV) curve (eg, FEV1) on a single test; however, patients with symptoms of EIB not meeting these criteria may risk being undiagnosed. To assess the ability of repeated tests using additional MEFV parameters in identifying EIB-prone patients, we investigated the effects of exercise provocation on the MEFV curve on two separate occasions. Of 95 patients with symptoms of EIB, 61 had reproducible exercise-induced changes (< 10 percent intraresponse variation), falling into four patterns: 27 (44 percent) had significantly reduced VC and airflow throughout the MEFV curve; 18 (30 percent) had unchanged VC but decreased airflow throughout the curve; 11 (18 percent) had reduced airflow above 50 percent VC but not below 50 percent VC; and 5 (8 percent) had significant reductions in airflow only at 50 percent VC or below. Of the other 34 subjects, 18 had no apparent response, and 16 responded on only one occasion, making objective assessment of these patients' EIB equivocal. We conclude that for a given individual, failure to meet arbitrary criteria does not rule out EIB. Additionally, a more subjective approach that integrates, among other factors, all routine MEFV curve parameters taken from multiple tests with clinical symptoms and history provide a more accurate assessment of EIB.

Effects of weight loss on peak flow variability, airways obstruction, and lung volumes in obese patients with asthma.

STUDY OBJECTIVES: To clarify the pathophysiologic features of the relation between asthma and obesity, we measured the effects of weight reduction on peak expiratory flow (PEF) variability and airways obstruction, compared to simultaneous changes in lung volumes and ventilatory mechanics in obese patients with stable asthma. METHODS: Fourteen obese asthma patients (11 women and 3 men; aged 25 to 62 years) were studied before and after a very-low-calorie-diet period of 8 weeks. PEF variability was determined as diurnal and day-to-day variations. FEV(1) and maximal expiratory flow values were measured with a flow-volume spirometer. Lung volumes, airways resistance (Raw), and specific airways conductance were measured using a constant-volume body plethysmograph. Minute ventilation was monitored in patients in supine and standing positions. RESULTS: As patients decreased their body mass index (SD) from 37.2 (3.7) to 32.1(4.2) kg/m(2) (p < 0. 001), diurnal PEF variation declined from 5.5% (2.4) to 4.5% (1.5) (p = 0.01), and day-to-day variation declined from 5.3% (2.6) to 3. 1% (1.3) (p < 0.005). The mean morning PEF, FEV(1), and FVC increased after weight loss (p = 0.001, p < 0.005, and p < 0.05, respectively). Flow rate at the middle part of FVC (FEF(25-75)) increased even when related to lung volumes (FEF(25-75)/FVC; p < 0. 05). Functional residual capacity and expiratory reserve volume were significantly higher after weight loss (p < 0.05 and p < 0.005, respectively). A significant reduction in Raw was found (p < 0.01). Resting minute ventilation decreased after weight loss (p = 0.01). CONCLUSION: Weight loss reduces airways obstruction as well as PEF variability in obese patients with asthma. The results suggest that obese patients benefit from weight loss by improved pulmonary mechanics and a better control of airways obstruction.

A survey of the current use and methods of analysis of bronchoprovocational challenges.

The purpose of this study was to survey the current techniques and methods of analysis in bronchoprovocational challenges currently in use. A questionnaire was sent to 94 investigators who had recently published an article in which a bronchoprovocational technique was used. They were asked to answer questions regarding the techniques used in challenge procedures and to calculate the results of ten histamine challenges which had previously been performed in our laboratory. Forty-four responded; 32 of these gave specific results for the histamine challenge. The most common provocative agent utilized was methacholine (62 percent), and that most used delivery mode was a dosimeter for delivery (55 percent). The most common provocative agent utilized was methacholine (62 percent) and the most used delivery mode was a dosimeter (55 percent).

Obstructive flow-volume loop contours after single lung transplantation.

The development of spirometric airflow obstruction may be a diagnostic dilemma in recipients of single lung allografts. The contribution of bronchial anastomotic stenosis to the observed spirometric obstruction may be clinically difficult to distinguish from that of obliterative bronchiolitis. Similarly, differentiating the "normal" obstructive defect after single lung transplantation for emphysema from obliterative bronchiolitis may be clinically challenging. We retrospectively reviewed the maximum inspiratory and expiratory flow-volume loop contours of lung transplant recipients with either obliterative bronchiolitis (n = 7) or bronchoscopically diagnosed severe bronchial anastomotic stenosis (n = 3). Five patients underwent single lung transplantation for obstructive native lung diseases and underwent observation before and after development of obliterative bronchiolitis. Bronchial anastomotic stenosis-maximum inspiratory and expiratory flow-volume loops were analyzed both before and after correction of stenosis by niobium: yttrium-aluminum-garnet laser photoresection or endobronchial silicone stent placement. Measures of airflow derived from maximum inspiratory and expiratory flow-volume loops, such as peak expiratory flow, peak inspiratory flow, forced expiratory flow at 50% vital capacity, forced inspiratory flow at 50% vital capacity, and forced expiratory volume in 1 second/peak expiratory flow ratio could not differentiate patients with bronchial anastomotic stenosis versus obliterative bronchiolitis. The most clinically useful index was the maximum inspiratory and expiratory flow-volume contour, which was characterized by terminal plateaus during exhalation and inhalation in patients with bronchial anastomotic stenosis. This index was reflected in a lower forced inspiratory flow at 75% vital capacity and forced inspiratory flow at 75% vital capacity/peak inspiratory flow ratio in bronchial anastomotic stenosis that increased after elimination of the anastomotic obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Causes of allograft dysfunction after single lung transplantation for emphysema: extrinsic restriction versus intrinsic obstruction. Brigham and Women's Hospital Lung Transplantation Group.

BACKGROUND: A subset of patients with emphysema who have undergone single lung transplantation (SLT) may subsequently present with dyspnea, worsening airways obstruction, hypoxemia, and progressive chronic native lung hyperinflation. The leading cause of late allograft dysfunction is bronchiolitis obliterans syndrome (BOS). However, extrinsic restriction manifests with a similar clinical presentation and is an additional mechanism to consider. We describe the use of the inspiratory lung resistance (RLi) to distinguish a decline in respiratory status due predominantly to either extrinsic restriction or BOS. METHODS: We studied five patients who underwent SLT for emphysema between 1992 and 1995, in whom the diagnoses of BOS and extrinsic restriction were subsequently entertained. Forced expiratory volume in 1 second (FEV1), RLi, static lung compliance, elastic recoil pressure at total lung capacity (TLC), and the slope of the maximum flow static recoil (MFSR) plot were measured. RESULTS: All patients had severe airflow obstruction, with mean FEV1 0.98 +/- 0.24 liter (26 +/- 5% predicted), elevated static lung compliance, reduced elastic recoil pressure at TLC, and reduced slope of the MFSR plot. Three patients had "low" RLi (9.3-12.8 cm H20/L/sec). Obstruction was attributed predominantly to extrinsic restriction. These patients underwent lung volume reduction surgery (LVRS) on the native lung; improvements in pulmonary mechanics were observed at 6 months. In contrast, two patients had markedly elevated RLi (17.3 and 17.4 cm H2O/L/sec). Obstruction was attributed predominantly to intrinsic airway disease from BOS that was subsequently documented at autopsy. CONCLUSIONS: The RLi appears to be a useful adjunct to the clinical history in distinguishing a decline in respiratory status due predominantly to either BOS or extrinsic restriction in patients who have undergone SLT for emphysema. Determination of the mechanism of allograft dysfunction may allow the selection of an appropriate subset of patients who would benefit from LVRS.

Regulation of ventilatory capacity during exercise in asthmatics.

In asthmatic and control subjects, we examined the changes in ventilatory capacity (VECap), end-expiratory lung volume (EELV), and degree of flow limitation during three types of exercise: 1) incremental, 2) constant load (50% of maximal exercise capacity; 36 min), and 3) interval (alternating between 60 and 40% of maximal exercise capacity; 6-min workloads for 36 min). The VECap and degree of flow limitation at rest and during the various stages of exercise were estimated by aligning the tidal breathing flow-volume (F-V) loops within the maximal expiratory F-V (MEFV) envelope using the measured EELV. In contrast to more usual estimates of VECap (i.e., maximal voluntary ventilation and forced expiratory volume in 1 s x 40), the calculated VECap depended on the existing bronchomotor tone, the lung volume at which the subjects breathed (i.e., EELV), and the tidal volume. During interval and constant-load exercise, asthmatic subjects experienced reduced ventilatory reserve, higher degrees of flow limitation, and had higher EELVs compared with nonasthmatic subjects. During interval exercise, the VECap of the asthmatic subjects increased and decreased with variations in minute ventilation, due in part to alterations in their MEFV curve as exercise intensity varied between 60 and 49% of maximal capacity. In conclusion, asthmatic subjects have a more variable VECap and reduced ventilatory reserve during exercise compared with nonasthmatic subjects. The variations in VECap are due in part to a more labile MEFV curve secondary to changes in bronchomotor tone. Asthmatics defend VECap and minimize flow limitation by increasing EELV.

Simulation of the effects of mechanical nonhomogeneities on expiratory flow from human lungs.

A computational model for expiration from lungs with mechanical nonhomogeneities was used to investigate the effect of such nonhomogeneities on the distribution of expiratory flow and the development of alveolar pressure differences between regions. The nonhomogeneities used were a modest constriction of the peripheral airways and a 50% difference in compliance between regions. The model contains only two mechanically different regions but allows these to be as grossly distributed as left lung-right lung or to be distributed as a set of identical pairs of parallel nonhomogeneous regions with flows from each merging in a specified bronchial generation. The site of flow merging had no effect on the flow-volume curve but had a significant effect on the development of alveolar pressure differences (delta PA). With the peripheral constriction, greater values of delta PA developed when flows were merged peripherally rather than centrally. The opposite was true in the case of a compliance nonhomogeneity. The delta PA values were smaller at submaximal flows. Plots of delta PA vs. lung volume were similar to those obtained experimentally. These results were interpreted in terms of the expression used for the fluid mechanics of the merging flows. delta PA was greater when the viscosity of the expired gas was increased or when its density was reduced. Partial forced expirations were shown to indicate the presence of mechanical nonhomogeneity.

Effort and volume dependence of forced-deflation flow-volume relationships in intubated infants.

The application of negative pressure to the airway opening [called the forced-deflation (FD) technique] allows the examination of maximal expiratory flow-volume curves in intubated infants who are unable to generate a voluntary maximal expiratory maneuver. We explored the questions of effort and volume dependence of flows generated by FD in 18 intubated, sedated, and paralyzed infants [age 10.6 +/- 2.0 (SE) mo; weight 7.2 +/- 0.7 kg] with normal lungs. Effort dependence was assessed by isovolume pressure-flow curves that were constructed in 10 infants from repeated FD maneuvers from total lung capacity (defined as +40 cmH2O) by varying airway opening pressures from 0 (barometric pressure) to -100 cmH2O at intervals of 20 cmH2O. The effect of volume history was assessed by initiating FD maneuvers from different inspiratory volumes delineated by the inspiratory pressures +10, +20, +30, and +40 cmH2O. We compared maximal expiratory flows at isovolume points [50, 25, and 10% forced vital capacity (FVC) of the standard +40/-40 cmH2O FD maneuver] and found that flow limitation consistently occurred in all infants at and below 25% FVC with -40 cmH2O or greater airway opening pressure. We found no significant influence of volume history on maximal flows at and below 25% FVC. Under well-controlled study conditions, we demonstrated excellent reproducibility of maximal expiratory flows at low lung volumes, analogous to those of voluntary forced expiratory maneuvers in adults and older children. This information may be helpful in setting standards for performance and interpretation of FD maneuvers in intubated infants.