The mechanics of pulmonary ventilation in normal subjects and in patients with emphysema

doi:10.1016/0002-9343(54)90325-3

The American Journal of Medicine

Volume 16, Issue 1, January 1954, Pages 80-97

https://doi.org/10.1016/0002-9343(54)90325-3 Get rights and content

Abstract

1.
1. The intrathoracic pressure exclusive of the pressure required to overcome the retractive force of the lung was measured and shown to be functionally related to the rate of respiratory flow in both normal and emphysematous subjects. This pressure increment at any given level of flow represents the pressure required to overcome both the resistance to air flow through the bronchopulmonary passages and the frictional resistance of the intrathoracic tissues to deformation. The resistance to gas flow is composed of resistance to laminar gas flow and resistance to turbulent gas flow.
2.
2. Pressure-flow curves were obtained from normal subjects and from patients with pulmonary emphysema. Studies were made with subjects breathing air and breathing argon-oxygen. Comparison of the pressure-flow relationships obtained with these two gases demonstrated that tissue friction was negligible both in normal and emphysematous subjects.
3.
3. The resistance to gas flow was evaluated in normal subjects and patients with pulmonary emphysema. The resistance was markedly increased in the patients with emphysema.
4.
4. The resistance to both laminar gas flow and the resistance caused by eddying turbulence are important in normal subjects and patients with emphysema. As the rate of flow is increased, the resistance caused by eddying turbulence becomes progressively greater.
5.
5. A change in the pressure-flow relationship with change in the amount of lung inflation was demonstrated. This was observed particularly during expiration. More pressure was required to produce a given flow at lesser degrees of lung inflation. This was marked in emphysematous subjects. The three variables, pressure, flow and lung inflation, were expressed on a three-dimensional graph.
6.
6. During expiration in emphysematous subjects the pressure-flow curve bends rapidly to approach an asymptote of flow. This accounts for the inability of patients with emphysema to exceed a certain flow regardless of the pressure exerted. In emphysema there is an increase in resistance to air flow in the bronchioles and a decrease in the elastic force of the lung for a given degree of inflation of the lung. As a result, collapse of the unsupported bronchioles tends to occur when the pressure drop between the alveoli and the cartilaginously supported end of the bronchiole exceeds the elastic pressure of the lung.

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This chapter reviews the methodologies of inverse and forward modeling for describing various structural and functional relationships of the mammalian respiratory system. As an organ of gas transport and exchange, the lung relies on mechanical processes to maintain normal function. A large portion of its mechanical behavior can be reduced to relatively simple mathematical descriptions.
Inverse modeling of respiratory mechanics: Inverse modeling relies on physiologic data to infer respiratory structure based on function, using parameters that encapsulate certain physical properties of the system. The arrangement of such parameters defines the topology of the inverse model. A simple single compartment model of the respiratory system can be constructed aswhere the time-varying distending pressure (P) is expressed as a function of gas volume (V) and flow ( $\dot{V}$ ), the coefficients E and R and denote the elastance and resistance of the system, respectively, and P_o denotes the distending pressure at end-expiration. By monitoring volume and pressure at different time points and fitting this equation to the data by regression analysis, we may determine the values of the parameters of E and R. These parameters can be affected by different lung diseases, such as asthma, emphysema, or fibrosis. By determining the ranges of values for normal and diseased lungs, such a model may facilitate disease diagnosis.
Forward modeling of respiratory mechanics: In contrast to inverse modeling, forward modeling may utilize physiologic and anatomic data to predict respiratory function, by explicitly defining mechanical properties and topological arrangement of many different physical elements. Forward modeling is thus useful for testing mechanistic explanations of experimental observations, investigating complicated interactions among elements of complex systems, or generating new hypotheses that can be later tested experimentally. The behaviors predicted by forward models can be compared against observations of the system under similar conditions. By way of example, a simple forward model of pulmonary gas exchange can be constructed by defining the relative amounts of alveolar ventilation ( ${\dot{V}}_{A}$ ) and perfusion ( $\dot{Q}$ ) of involves partitioning the lung distinct compartments, each with different gas exchange capacities: ${[{\dot{V}}_{A} / \dot{Q}]}_{1} = 1$ for the compartment with matched ventilation and perfusion; ${[{\dot{V}}_{A} / \dot{Q}]}_{2} = 0$ for the nonventilated but perfused compartment; and ${[{\dot{V}}_{A} / \dot{Q}]}_{3} \to \infty$ for the ventilated but nonperfused compartment;. Note that ${\dot{V}}_{A}$ and $\dot{Q}$ may be different in each compartment. By definition $\dot{Q}$ is zero in the nonperfused compartment, while ${\dot{V}}_{A}$ is zero in the nonventilated compartment. The net influx of O₂ ( $\dot{V} O_{2}$ ) may be expressed as the product of the alveolar fresh gas ventilation rate ( ${\dot{V}}_{A}$ ) and the difference between inspired oxygen fraction (F_iO₂) and alveolar oxygen fraction (F_AO₂):
This $\dot{V} O_{2}$ can also be expressed as the product of the perfusion rate ( $\dot{Q}$ ) and the difference between mixed venous oxygen content ( $C_{\bar{v}} O_{2}$ ) and end-capillary oxygen content (C_cO₂):
The ventilation-to-perfusion ratio ( ${\dot{V}}_{A} / \dot{Q}$ ) can be expressed as by combining both expressions for $\dot{V} O_{2}$ :
Similarly for the rate of CO₂ removal, we can obtain:where the values of mixed venous blood gas partial pressures are known quantities. Practically, the partial pressures of O₂ and CO₂ are easier to measure than their total contents in the blood. In this regard, we can express the alveolar gas fractions in terms of gas partial pressures:where P_AO₂ denotes the partial pressure of alveolar oxygen, P_ACO₂ the partial pressure of alveolar carbon dioxide, P_atm is atmospheric pressure, and PH₂O is the water vapor pressure. The partial pressures of alveolar gases and end-capillary blood gases are assumed to be equilibrated (i.e., P_cO₂ = P_AO₂ and P_cCO₂ = P_ACO₂). The partial pressures of mixed venous blood may be obtained by sampling the blood in the main pulmonary artery using a Swan-Ganz catheter. The relationship between O₂ and CO₂ partial pressures and their corresponding contents in the blood may then be obtained as:where the subscript x represents the particular blood compartment (e.g., venous, arterial, end-capillary), [Hb] is the concentration of hemoglobin in g dL⁻¹ blood, and S_xO₂ is the corresponding fractional saturation of hemoglobin with O₂. The system of equations relating alveolar gas exchange to perfusion may be solved to obtain the end-capillary blood gas contents. The gas contents of mixed arterial blood may then be determined by a perfusion-weighted average of compartmental blood gas contents:where l indexes the three compartments of the model, ${\dot{Q}}_{l}$ denotes the perfusion to each compartment, and ${\dot{Q}}_{T}$ denotes the total cardiac output. In this way, the forward model can be employed to predict oxygen and carbon dioxide contents of the arterial blood at the entrance to the pulmonary capillary and of the end-capillary oxygenated blood.
Conclusion: In this chapter, we have shown how to employ inverse modeling and forward modeling to characterize respiratory function for assessments of airway and tissue properties in lung disease.
Pulmonary Function Tests in Infants and Children
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Lung function testing in early life can provide information on lung growth and development and can help clinicians in the decision making process. However, the techniques available in infants and preschool-age children are usually not adequately validated for these age groups. Understanding the impact of measurement conditions on the data is essential to achieving valid results. Infant lung function tests are still limited to research settings in highly specialized lung function laboratories and are not suited for the everyday clinical use. In contrast, tests in preschoolers are easy to perform; most of the tests only require minimal subject cooperation and can be undertaken as early as 3 years of age with high feasibility. The main limitations of these techniques are that they are more useful at detecting differences between groups of healthy children and children with lung disease, but they are not specific and sensitive enough to be utilized in individuals in the clinical practice. Interpretation of the results also requires comprehensive understanding of respiratory physiology. There are promising techniques in the focus of pediatric respiratory research in recent years that are likely to improve the clinical utility of lung function measurements during these critical years of lung development.
Expiratory Flow Limitation During Mechanical Ventilation
2018, Chest
Citation Excerpt :
Fry and Hyatt performed seminal studies in normal subjects and patients with emphysema,4-6 measuring isovolumic pressure-flow curves with various expiratory efforts.
Expiratory flow limitation (EFL) is present when the flow cannot rise despite an increase in the expiratory driving pressure. The mechanisms of EFL are debated but are believed to be related to the collapsibility of small airways. In patients who are mechanically ventilated, EFL can exist during tidal ventilation, representing an extreme situation in which lung volume cannot decrease, regardless of the expiratory driving forces. It is a key factor for the generation of auto- or intrinsic positive end-expiratory pressure (PEEP) and requires specific management such as positioning and adjustment of external PEEP. EFL can be responsible for causing dyspnea and patient-ventilator dyssynchrony, and it is influenced by the fluid status of the patient. EFL frequently affects patients with COPD, obesity, and heart failure, as well as patients with ARDS, especially at low PEEP. EFL is, however, most often unrecognized in the clinical setting despite being associated with complications of mechanical ventilation and poor outcomes such as postoperative pulmonary complications, extubation failure, and possibly airway injury in ARDS. Therefore, prompt recognition might help the management of patients being mechanically ventilated who have EFL and could potentially influence outcome. EFL can be suspected by using different means, and this review summarizes the methods to specifically detect EFL during mechanical ventilation.
Intraocular pressure and glaucoma: Is physical exercise beneficial or a risk?
2016, Journal of Optometry
Citation Excerpt :
In association with a VM, IOP was found to elevate to over 40 mmHg for some subjects, especially for those who were myopic.31 Greater intrathoracic pressure was required to produce a given respiratory flow at lesser degrees of lung inflation, especially in emphysematous subjects.32 Reduced lung capacity with age may necessitate deeper respirations during exercise as well as restrict the range of exercise intensity performed.
Intraocular pressure may become elevated with muscle exertion, changes in body position and increased respiratory volumes, especially when Valsalva manoeuver mechanisms are involved. All of these factors may be present during physical exercise, especially if hydration levels are increased. This review examines the evidence for intraocular pressure changes during and after physical exercise. Intraocular pressure elevation may result in a reduction in ocular perfusion pressure with the associated possibility of mechanical and/or ischaemic damage to the optic nerve head. A key consideration is the possibility that, rather than being beneficial for patients who are susceptible to glaucomatous pathology, any intraocular pressure elevation could be detrimental. Lower intraocular pressure after exercise may result from its elevation causing accelerated aqueous outflow during exercise. Also examined is the possibility that people who have lower frailty are more likely to exercise as well as less likely to have or develop glaucoma. Consequently, lower prevalence of glaucoma would be expected among people who exercise. The evidence base for this topic is deficient and would be greatly improved by the availability of tonometry assessment during dynamic exercise, more studies which control for hydration levels, and methods for assessing the potential general health benefits of exercise against any possibility of exacerbated glaucomatous pathology for individual patients who are susceptible to such changes.
La presión intraocular puede elevarse con el exceso de trabajo muscular, los cambios de la posición del cuerpo y el incremento de los volúmenes respiratorios, especialmente cuando los mecanismos de la maniobra de Valsalva se ven implicados. Todos estos factores pueden presentarse durante el ejercicio físico, especialmente cuando se incrementan los niveles de hidratación. Esta revisión examina la evidencia de los cambios en la presión intraocular con anterioridad y posterioridad al ejercicio físico. El incremento de la presión intraocular puede derivar en una reducción de la perfusión ocular, con la posibilidad asociada de daño mecánico y/o isquémico de la cabeza del nervio óptico. Una consideración clave es la posibilidad de que, en lugar de ser beneficioso para los pacientes susceptibles de patología glaucomatosa, cualquier incremento de la presión intraocular podría resultar perjudicial. La disminución de la presión intraocular tras el ejercicio puede ser resultado de su elevación, originando la aceleración de una descarga del acuoso durante el ejercicio. También se ha estudiado la posibilidad de que las personas con menor debilidad sean propensas a realizar ejercicio, y tengan menor probabilidad de padecer o desarrollar glaucoma. Por tanto, cabría esperar una menor prevalencia del glaucoma en aquellas personas que realizan ejercicio. La base de la evidencia para esta cuestión es deficiente, y mejoraría si se dispusiera de pruebas de tonometría realizadas durante el ejercicio dinámico, un mayor número de estudios que controlen los niveles de hidratación, y métodos de evaluación de los beneficios potenciales y generales para la salud al realizar ejercicio, en contraposición a cualquier posibilidad de empeoramiento de la patología glaucomatosa en las personas susceptibles de dichos cambios.
Pulmonary Function Testing in Children
2012, Kendig and Chernick's Disorders of the Respiratory Tract in Children
A model-based method for flow limitation analysis in the heterogeneous human lung
2008, Computer Methods and Programs in Biomedicine
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.

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^☆: This study was supported in part by a grant from the Minnesota Heart Association. Published with approval of Chief Medical Director. The statements and conclusions published by the authors are the result of their own study and do not necessarily reflect the opinion or policy of the Veterans Administration.

¹: From the Department of Medicine, Medical School, University of Minnesota, The Variety Club Heart Hospital, and the Veterans Administration Hospital, Minneapolis, Minn.

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ReviewThe mechanics of pulmonary ventilation in normal subjects and in patients with emphysema☆

Abstract

J. Thoracic Surg.

Lancet

Pulmonary insufficiency; III. A study of 122 cases of chronic pulmonary emphysema

Medicine

Analysis of the ventilatory defect by timed capacity measurements

Am. Rev. Tuberc.

Die Messung der Strömungswiderstände in den Atemwegen des Menschen, insbesondere bei Asthma und Emphysem

Ztschr. f. klin. Med.

The elastic properties of the emphysematous lung and their clinical significance

J. Clin. Investigation

Mechanics of airflow in health and in emphysema

J. Clin. Investigation

The measurement of intraesophageal pressure and its relationship to intrathoracic pressure

J. Lab. & Clin. Med.

The elastic properties of the lung in normal men and in patients with chronic pulmonary emphysema

J. Lab. & Clin. Med.

Der Strömungswiderstand in den menschlichen Atemwegen und der Einfluss der unregelmässigen Verzweigung des Bronchial-systems auf den Atmungsverlauf in verschiedenen Lungenbezirken

Arch. f. d. ges. Physiol.

Applied Hydro- and Aeromechanics

Flowmeter for Recording Respiratory Flow of Human Subjects

Studies of intrapulmonary mixture of gases. IV. The significance of pulmonary emptying rate and a simplified open circuit measurement of residual air

J. Clin. Investigation

Review
The mechanics of pulmonary ventilation in normal subjects and in patients with emphysema☆