The measurement of esophageal pressure allows for the calculation of several important and clinically useful parameters of respiratory mechanics. Esophageal pressure is often measured with balloon-tipped catheters. These catheters may be handmade from natural latex condoms and polyethylene tubing. Given the potential of natural latex to cause allergic reaction, it is important to determine whether esophageal catheter balloons can be fabricated, by hand, using nonlatex condoms as construction materials. To determine the static and dynamic response characteristics of esophageal balloon catheters handmade from latex and nonlatex materials, six esophageal catheter balloons were constructed from each of the following condom materials: natural latex, synthetic polyisoprene, and polyurethane (18 total). Static compliance and working volume range of each balloon catheter was obtained from their pressure-volume characteristics in water. The dynamic response of balloon catheters were measured via a pressure "step" test, from which a third-order underdamped transfer function was modeled. The dynamic ranges of balloon catheters were characterized by the frequencies corresponding to ±5% amplitude- and phase-distortion (fA5% and fφ5%). Balloon catheters handmade from polyurethane condoms displayed the smallest working volume range and lowest static balloon compliance. Despite this lower compliance, fA 5% and fφ5% were remarkably similar between all balloon materials. Our findings suggest that polyisoprene condoms are an ideal nonlatex construction material to use when fabricating esophageal catheter balloons by hand.

SESSION TITLE: Pulmonary Function Testing

BACKGROUND The nonspecific (NS) pulmonary function (PF) pattern refers to a PF test with a normal total lung capacity (TLC), normal FEV₁/FVC ratio, and a low FEV₁, a low FVC, or both. Currently, no information is available regarding the long-term stability of the NS pattern or variables that predict changes in subjects with an initial NS PF pattern. METHODS From 1990 to 2005 we identified 1,284 subjects with an NS pattern on initial PF testing with one or more follow-up PF tests 6 months or more after the initial NS test result. Lung volumes, diffusing capacity, and spirometry data were analyzed. A multivariate, multinomial logistic regression model was used to study the association between different variables and the final PF pattern. RESULTS Overall, 3,674 PF tests were performed in 1,284 subjects over a median follow-up period of 3 years. At last follow-up, 818/1,284 (64%) subjects continued to show the NS pattern, whereas 208/1,284 (16%) showed a restrictive pattern, 191/1,284 (15%) an obstructive pattern, 42/1,284 (3%) a normal pattern, and 25/1,284 (2%) a mixed pattern. The multinomial logistic regression analysis showed that increasing values for specific airway resistance and the difference between TLC and alveolar volume were predictors of a change to an obstructive pattern on follow-up. CONCLUSIONS The NS pattern is a distinct and stable PF test pattern with roughly two-thirds of patients continuing to show this pattern on follow-up testing. Current interpretation guidelines erroneously label the NS pattern as representing obstruction and need to be changed to reflect these data.

Measurements of dynamic force-length behavior of maximally activated strips of smooth muscle during oscillatory length changes show that force decreases well below the isometric force during the shortening phase of the oscillation. The magnitude of the decrease depends on the rate of shortening; for slower shortening, the decrease is smaller and force is larger. Modeling of expiratory flow, based on these data, predicts that vital capacity in constricted lungs depends on the rate of expiration. In maximally constricted lungs, forced vital capacity (FVC) is predicted to be 16% smaller than control, and vital capacity for a very slow expiration (SVC), 31% less than control. These predictions were tested by measuring FVC and SVC in constricted normal subjects. In the first group of 9 subjects, four maneuvers were made following the delivery of two doses of methacholine in the order: SVC, FVC, FVC, SVC. In a second group of 11 subjects, two maneuvers were performed at each dose in the order: FVC, SVC. At the highest dose of methacholine, FVC for both trials in group 1 and for the one trial in group 2 were all approximately 13% less than control, a slightly smaller decrease than predicted. SVC for the 1st trial in group 1 was 27% less than control, also slightly smaller than predicted. The difference between FVC and SVC for this trial, 13%, was close to the predicted difference of 15%. However, SVC for the 2nd trial in group 1 (preceded by 3 vital capacity maneuvers) and for group 2 (preceded by 1) were no different from FVC. We conclude that vital capacity in constricted lungs depends on the dynamic force-length properties of smooth muscle and that the history dependence of the dynamic properties of smooth muscle is more complicated than has been inferred from oscillatory force-length behavior.

Sarcoidosis is a systemic granulomatous disease with predominant manifestation in the lungs, often presenting as interstitial lung disease. Pulmonary function abnormalities in sarcoidosis include restriction of lung volumes, reduction in diffusing capacity of the lung for carbon monoxide (DL,CO), reduced static lung compliance (CL,s) and airway obstruction. The aim of the present study was to assess various lung function indices, including CL,s and DL,CO, as markers of functional abnormality in sarcoidosis patients. Results from 830 consecutive patients referred for lung function tests with a diagnosis of sarcoidosis (223 in stage I, 486 in stage II and 121 in stage III) were retreospectively analysed. The mean±sd age of the patients was 40±11 yrs; 18% were active smokers and 24% were former smokers. Normal total lung capacity was found in 772 (93%) patients. Of these cases, 24.5% had a low CL,s and 21.5% had a low DL,CO. At least one abnormality was observed in 39.3% of these patients, whereas, in restrictive patients, this figure was 88%. Airway obstruction was present in 11.7% of cases. Lung volumes usually remain within the normal range and measurement of either CL,s or DL,CO often reveal impaired lung function in sarcoidosis patients, even when their lung volumes are still in the normal range; these two measurements provide complementary information.

BACKGROUND:Little is known about a fairly frequent abnormal pattern of pulmonary function test results: reduced FEV(1) and FVC with a normal FEV(1)/FVC and normal total lung capacity. We term this a nonspecific pattern (NSP). We sought to identify medical conditions having this pattern and to explore mechanisms producing it.METHODS:From a database of 80,929 test results, the NSP was found in 7,702 subjects from whom was drawn a random sample of 100 subjects. Medical records and all available tests were examined.RESULTS:Airway hyperresponsiveness (AHR) and obesity were common. Two groups of subjects were identified. Group A consisted of 68 subjects with evidence of airway disease, including AHR and chronic lung disease. A volume derecruitment model was proposed to explain their NSP. Group B consisted of 32 subjects with no evidence of airway disease. Restricted expansion of the thorax or lung may explain the NSP in most of these subjects. Forty subjects had repeated tests, and in only 17 were the test results consistently nonspecific.CONCLUSIONS:In a random sample of 100 subjects with the NSP, the probable underlying cause of the pattern in 68 subjects was airway disease. In most of the remaining 32 subjects, restricted expansion of the thorax or lung may be implicated.

We investigated whether obesity is associated with airway hyperresponsiveness in otherwise healthy humans and, if so, whether this correlates with a restrictive lung function pattern or a decreased number of sighs at rest and/or during walking. Lung function was studied before and after inhaling methacholine (MCh) in 41 healthy subjects with body mass index ranging from 20 to 56. Breathing pattern was assessed during a 60-min rest period and a 30-min walk. The dose of MCh that produced a 50% decrease in the maximum expiratory flow measured in a body plethysmograph (PD50MCh) was inversely correlated with body mass index (r2=0.32, P<0.001) and waist circumference (r2=0.25, P<0.001). Significant correlations with body mass index were also found with the maximum changes in respiratory resistance (r2=0.19, P<0.001) and reactance (r2=0.40, P<0.001) measured at 5 Hz. PD50MCh was also positively correlated with functional residual capacity (r2=0.56, P<0.001) and total lung capacity (r2=0.59, P<0.001) in men, but not in women. Neither PD50MCh nor body mass index correlated with number of sighs, average tidal volume, ventilation, or breathing frequency. In this study, airway hyperresponsiveness was significantly associated with obesity in otherwise healthy subjects. In obese men, but not in women, airway hyperresponsiveness was associated with the decreases in lung volumes.

We examined the effects of chest wall strapping (CWS) on the response to inhaled methacholine (MCh) and the effects of deep inspiration (DI). Eight subjects were studied on 1 day with MCh inhaled without CWS (CTRL), 1 day with MCh inhaled during CWS (CWSon/on), and 1 day with MCh inhaled during temporary removal of CWS (CWSoff/on). On the CWSon/on day, MCh caused greater increases in pulmonary resistance, upstream resistance, dynamic elastance, residual volume, and greater decreases in maximal expiratory flow than on the CTRL day. On the CWSoff/on day, the changes in these parameters with MCh were not different from the CTRL day. Six of the subjects were again studied using the same protocol on CTRL and CWSon/on days, except that, on a third day, MCh was given after applying the CWS, but the measurements before and after the inhalation were made without CWS (CWSon/off). The latter sequence was associated with more severe airflow obstruction than during CTRL, but less than with CWSon/on. The bronchodilator effects of a DI were blunted when CWS was applied during measurements (CWSon/on and CWSoff/on) but not after it was removed (CWSon/off). We conclude that CWS is capable of increasing airway responsiveness only when it is applied during the inhalation of the constrictor agent. We speculate that breathing at low lung volumes induced by CWS enhances airway narrowing because the airway smooth muscle is adapted at a length at which the contractile apparatus is able to generate a force greater than normal.

physiology, especially those papers emphasizing adaptive and integrative mechanisms. It is published 12 times a publishes original papers that deal with diverse area of research in applied

Models of the outer epithelia of the human body - namely the skin, the intestine and the lung - have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report.

Preface: vii Acknowledgments: viii List of Abbreviations: ix 1. Introduction 2. Spirometry: Dynamic Lung Volumes 3. Static (Absolute) Lung Volumes 4. Diffusing Capacity of the Lungs 5. Bronchodilators and Bronchial Challenge Testing 6. Arterial Blood Gases 7. Other Tests of Lung Mechanics: Resistance and Compliance 8. Distribution of Ventilation 9. Maximal Respiratory Pressures 10. Preoperative Pulmonary Function Testing 11. Simple Tests of Exercise Capacity 12. Patterns in Various Diseases 13. When to Test and What to Order 14. An Approach to Interpreting Pulmonary Function Tests 15. Illustrative Cases Appendix Subject Inde

This animal model of emphysema exhibits the same abnormalities in respiratory mechanics as those seen in human emphysema. The histologic and radiographic findings also closely resemble changes of panacinar disease. Moreover, the progressive hypoxemia preceding hypercarbia also parallels the clinical course seen in human disease. Drawbacks of this model include the long time period required to develop significant changes and the cost of maintaining the animals for such a time period. Large cystic areas were not noted in our animals and one would have to turn to another model to address the problem of giant bullous emphysema. There is no ideal animal model of pulmonary emphysema, and the usefulness of an experimental model should be judged on how well it answers the specific questions. Significant information has been obtained using various animal models of emphysema in lung transplantation, diaphragmatic function, pulmonary hemodynamics, and in several other areas. The dog appears to be a suitable model for thoracic surgical research on emphysema.

Both interregional and intraregional mechanisms may cause changes in N2 concentration of expired gas during the phases of the single-breath O2 test (SBO2) that follow dead-space washout. To evaluate the possible importance of each mechanism, we performed the SBO2 in excised canine lungs that were first suspended in air and then immersed in stable foams that simulated the vertical gradient of pleural pressure. The lungs were deflated at constant submaximal flows. The slope of phase III diminished with increasing expiratory flow and increased with foam immersion. The onset of phase IV depended on flow, and a terminal decrease in N2 concentration (phase V) was often observed. Simultaneously measured estimates of regional flows and volumes (J. Appl. Physiol. 65: 1764-1774, 1988) were used to further interpret these results. The onset of phase IV at flows greater than quasi-static signified the onset of flow limitation of dependent regions. The onset of phase V corresponded to flow limitation of nondependent regions.

The objective of this investigation was to determine the minimum transpulmonary pressure (PL) at which the forces of interdependence between the airways and the lung parenchyma can prevent airway closure in response to maximal stimulation of the airways in excised canine lobes. We first present an analysis of the relationship between PL and the transmural pressure (Ptm) that airway smooth muscle must generate to close the airways. This analysis predicts that airway closure can occur at PL less than or equal to 10 cmH2O with maximal airway stimulation. We tested this prediction in eight excised canine lobes by nebulizing 50% methacholine into the airways while the lobe was held at constant PL values ranging from 25 to 5 cmH2O. Airway closure was assessed by comparing changes in alveolar pressure (measured by an alveolar capsule technique) and pressure at the airway opening during low-amplitude oscillations in lobar volume. Airway closure occurred in two of the eight lobes at PL = 10 cmH2O; in an additional five it occurred at PL = 7.5 cmH2O. We conclude that the forces of parenchymal interdependence per se are not sufficient to prevent airway closure at PL less than or equal to 7.5 cmH2O in excised canine lobes.