A Web-based course of lectures in respiratory physiology

A complete course of respiratory physiology suitable for first-year medical and graduate students has been placed on the Web for our own students and for other educational institutions. There are several reasons for doing this. The first is that the modern-day student uses a variety of options for acquiring knowledge. These include attending lectures, reading texts, iPod downloads, and surfing the internet. This Web-based course is another option that may be preferable for some students. A second reason is that it is becoming increasingly difficult for some medical schools to find faculty members who are willing and able to teach the principles of respiratory physiology. This is a potentially serious problem because a sound knowledge of respiratory physiology will always be necessary for the intelligent practice of medicine. Schools with limited faculty may find it useful to use these Web-based lectures followed by a discussion session with students. Another reason is that some schools have moved away from systematic lectures to case-based discussions, with the possibility that students will not be exposed to some of the principles of respiratory physiology. The hope is that this comprehensive course of lectures will help students to assimilate this important material as the medical school curriculum continues to expand at a rapid rate.     

肺泡表面活性物质（PS）对盐酸吸入性肺损伤的治疗进展

急性肺损伤／急性呼吸窘迫综合征（ALI/ARDS）是临床上常见的危重症,治疗措施包括机械通气及药物综合治疗。肺泡表面活性物质（PS）在维持正常的肺功能起着重要作用,业已证明,PS异常与ALI／ARDS的发病有关,给予外源性PS亦可治疗ALI／ARDS。本文就外源性PS在盐酸吸入性ALI／ARDS的第二时相中的疗效及其可能的作用机制做一综述。     

International Union of Physiological Sciences teaching workshop, April 7-10, 2005, Pali Mountain, California

Fifty-six physiologists from fourteen countries participated in the sixth International Union of Physiological Sciences Teaching Workshop. The four-day program included a poster session, a debate on integrative versus disciplinary curricula, and interactive lectures on evidence-based education, inquiry laboratories, and student preparation for physiology courses. Participants worked in small groups on one of four topics: developing free web-based laboratory resources, information technology, curriculum planning and design, and other issues in classroom teaching.     

FGF/FGFR signaling: From lung development to respiratory diseases

The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling system regulates a variety of biological processes, including embryogenesis, angiogenesis, wound repair, tissue homeostasis, and cancer. It exerts these regulatory functions by controlling proliferation, differentiation, migration, survival, and metabolism of target cells. The morphological structure of the lung is a complex tree-like network for effective oxygen exchange, and the airway terminates in the middle and distal ends of many alveoli. FGF/FGFR signaling plays an important role in the pathophysiology of lung development and pathogenesis of various human respiratory diseases. Here, we mainly review recent advances in FGF/FGFR signaling during human lung development and respiratory diseases, including lung cancer, acute lung injury (ALI), pulmonary arterial hypertension (PAH), chronic obstructive pulmonary disease (COPD), asthma, and pulmonary fibrosis.     

The efficacy of interactive lecturing for students with diverse science backgrounds

Learning is an active process, and, as such, interactive lectures are considered as the educational best practice. This study investigated the efficacy of interactive lecturing in a module of eight respiratory physiology lectures in a second-year Physiology course with two distinct subcohorts: students with strong science backgrounds and those without. The comparison of student performance in the summative examinations of respiratory physiology allowed us to evaluate the efficacy of interactive lecturing for each subcohort. Formal teaching evaluations were used to gauge the students' perception of interactive lectures. To further validate our findings, we repeated the study in the following year. The introduction of interactive lecturing significantly improved learning outcomes, with this improvement being maintained for the period of this study. Furthermore, students with limited prior knowledge, who had typically performed very poorly in this module, achieved a similar learning outcome to those students with a good science background. From these summative results and the students' perceptions, we concluded that students that are alert, motivated and interested in the subject, and engaged in learning activities and that are being encouraged to think and receive constant feedback on their progress will become confident in their learning abilities and have improved learning outcomes.     

Obesity and Pulmonary Function in African Americans

BackgroundObesity prevalence in United States (US) adults exceeds 30% with highest prevalence being among blacks. Obesity is known to have significant effects on respiratory function and obese patients commonly report respiratory complaints requiring pulmonary function tests (PFTs). However, there is no large study showing the relationship between body mass index (BMI) and PFTs in healthy African Americans (AA).ObjectiveTo determine the effect of BMI on PFTs in AA patients who did not have evidence of underlying diseases of the respiratory system.MethodsWe reviewed PFTs of 339 individuals sent for lung function testing who had normal spirometry and lung diffusion capacity for carbon monoxide (DLCO) with wide range of BMI.ResultsFunctional residual capacity (FRC) and expiratory reserve volume (ERV) decreased exponentially with increasing BMI, such that morbid obesity resulted in patients breathing near their residual volume (RV). However, the effects on the extremes of lung volumes, at total lung capacity (TLC) and residual volume (RV) were modest. There was a significant linear inverse relationship between BMI and DLCO, but the group means values remained within the normal ranges even for morbidly obese patients.ConclusionsWe showed that BMI has significant effects on lung function in AA adults and the greatest effects were on FRC and ERV, which occurred at BMI values < 30 kg/m2. These physiological effects of weight gain should be considered when interpreting PFTs and their effects on respiratory symptoms even in the absence of disease and may also exaggerate existing lung diseases.     

Deriving respiratory cell types from stem cells

The reported pluripotential capabilities of many human stem cell types has made them an attractive area of research, given the belief they may hold considerable therapeutic potential for treating a wide range of human diseases and injuries. Although the bulk of stem cell based research has focused on developing procedures for the treatment of pancreatic, neural, cardiovascular and haematopoietic diseases, the potential for deriving respiratory cell types from stem cells for treatment of respiratory specific diseases has also been explored. It is suggested that stem cell derivatives may be used for lung replacement/regeneration therapeutics and high though-put pharmacological screening strategies for a variety of respiratory injuries and diseases including: cystic fibrosis, chronic obstructive pulmonary disease, respiratory distress syndrome, pulmonary fibrosis and pulmonary edema. This review will explore recent progress in characterizing adult respiratory and bone marrow derived stem cells with respiratory potential as well as the endogenous mechanisms directing the homing of these cells to the diseased and injured lung. In addition, the potential for embryonic stem cell based therapies in this domain as well as the histological, anatomical and molecular aspects of respiratory development will be summarized.     

Pulmonary function in children with idiopathic scoliosis

ABSTRACT: Idiopathic scoliosis, a common disorder of lateral displacement and rotation of vertebral bodies during periods of rapid somatic growth, has many effects on respiratory function. Scoliosis results in a restrictive lung disease with a multifactorial decrease in lung volumes, displaces the intrathoracic organs, impedes on the movement of ribs and affects the mechanics of the respiratory muscles. Scoliosis decreases the chest wall as well as the lung compliance and results in increased work of breathing at rest, during exercise and sleep. Pulmonary hypertension and respiratory failure may develop in severe disease. In this review the epidemiological and anatomical aspects of idiopathic scoliosis are noted, the pathophysiology and effects of idiopathic scoliosis on respiratory function are described, the pulmonary function testing including lung volumes, respiratory flow rates and airway resistance, chest wall movements, regional ventilation and perfusion, blood gases, response to exercise and sleep studies are presented. Preoperative pulmonary function testing required, as well as the effects of various surgical approaches on respiratory function are also discussed.     

A classic learning opportunity from Fenn, Rahn, and Otis (1946): the alveolar gas equation

The alveolar gas equation, the focus of a classic paper by Fenn, Rahn, and Otis, provides a framework for understanding the mechanisms involved in pulmonary gas exchange as well as the limits of human performance. The classic 1946 paper by Fehn, Rahn, and Otis gives your students an opportunity to learn about the alveolar gas equation from the physiologists who pioneered it and demonstrates that mathematics and data graphics are fundamental tools with which to learn respiratory physiology. In this essay, I outline avenues of discovery by which your students can explore the alveolar gas equation. Meaningful learning stems from inspiration: to learn, you must be inspired to learn. If anyone can inspire learning in respiratory physiology, it is Wallace Fenn, Hermann Rahn, and Arthur Otis.     

The impact of sex and sex hormones on lung physiology and disease: lessons from animal studies

Numerous animal studies have revealed significant effects of sex and sex hormones on normal lung development, lung physiology, and various lung diseases. The primary goal of this review is to summarize knowledge to date on the effects of sex and sex hormones on lung development, physiology, and disease in animals. Specific emphasis will be placed on fibrosis, allergic airway disease, acute lung injury models, respiratory infection, and lung toxicology studies.     

Noninvasive Intratracheal Intubation to Study the Pathology and Physiology of Mouse Lung

The use of a model that mimics the condition of lung diseases in humans is critical for studying the pathophysiology and/or etiology of a particular disease and for developing therapeutic intervention. With the increasing availability of knockout and transgenic derivatives, together with a vast amount of genetic information, mice provide one of the best models to study the molecular mechanisms underlying the pathology and physiology of lung diseases. Inhalation, intranasal instillation, intratracheal instillation, and intratracheal intubation are the most widely used techniques by a number of investigators to administer materials of interest to mouse lungs. There are pros and cons for each technique depending on the goals of a study. Here a noninvasive intratracheal intubation method that can directly deliver exogenous materials to mouse lungs is presented. This technique was applied to administer bleomycin to mouse lungs as a model to study pulmonary fibrosis.     

Endocrine physiology in a patient-centered learning curriculum

The medical curriculum at the University of North Dakota School of Medicine and Health Sciences has recently been redesigned into a problem-based/traditional hybrid model that utilizes an integrated organ systems-based approach to teach basic and clinical sciences. The number of lecture hours in general has been greatly reduced, and, in particular, lecture hours in physiology have been reduced by 65%. Students learn basic science in small groups led by a faculty facilitator, and students are responsible for a great deal of their own teaching and learning. The curriculum is centered around patient cases and is called patient-centered learning (PCL). The curriculum includes traditional lectures and laboratories supporting faculty-generated learning objectives. Endocrine physiology is taught in year one, utilizing four weeks of patient cases that emphasize normal structure and function of endocrine systems. Endocrine physiology is revisited in year two, which is primarily focused on pathobiology. The PCL curriculum, with emphasis on the endocrine component, is described in detail along with key portions of an endocrine case.     

Use of high resolution algorithm in computerized tomography of disseminated lung diseases]

Lobule of the lung is a principal anatomical structure of the respiratory zone in the lungs. Secondary lobule of the lung consists of about fifty primary lobules and is delineated by fibrous interlobular septa. Each lobule is delineated by interlobular septa and blood is supplied by small arterioles of pulmonary artery system. Its shape is conical and size ranges from 10 to 22 mm. The author used algorithm of high resolution in HR CT to present normal distal generations of respiratory area of the lungs and the same in 32 patients with disseminated lesions to the lungs. It is known, that lobule of the lung may be involved in very important pathologies. The author shown that significant architectural rearrangement takes place in pulmonary lobules and adjacent areas in the course of disseminated pulmonary diseases. The process include thickening of interlobular septa, consolidation of lobular area, changes in the shape of lobuli, and appearance of small cysts. The use of HR CT enables imaging in such pathologies which normally are inaccessible to conventional radiologic examinations.     

A two-component simulation model to teach respiratory mechanics

Interactive learning has been proven instrumental for the understanding of complex systems where the interaction of interdependent components is hard to envision. Due to the mechanical properties and mutual coupling of the lung and thorax, respiratory mechanics represent such a complex system, yet their understanding is essential for the diagnosis, prognosis, and treatment of various respiratory disorders. Here, we present a new mechanical model that allows for the simulation of respiratory pressure and volume changes in different ventilation modes. A bellow reflecting the "lung" is positioned within the inverted glass cylinder of a bell spirometer, which is sealed by a water lock and reflects the "thorax." A counterweight attached to springs representing the elastic properties of the chest wall lifts the glass cylinder, thus creating negative "pleural" pressure inside the cylinder and inflating the bellow. Lung volume changes as well as pleural and intrapulmonary pressures are monitored during simulations of spontaneous ventilation, forced expiration, and mechanical ventilation, allowing for construction of respiratory pressure-volume curves. The mechanical model allows for simulation of respiratory pressure changes during different ventilation modes. Individual relaxation curves constructed for the lung and thorax reflect the basic physiological characteristics of the respiratory system. In self-assessment, 232 medical students passing the physiology laboratory course rated that interactive teaching at the simulation model increased their understanding of respiratory mechanics by 70% despite extensive prior didactic teaching. Hence, the newly developed simulation model fosters students' comprehension of complex mechanical interactions and may advance the understanding of respiratory physiology.     

Glucocorticoids Recruit Tgfbr3 and Smad1 to Shift Transforming Growth Factor-β Signaling from the Tgfbr1/Smad2/3 Axis to the Acvrl1/Smad1 Axis in Lung Fibroblasts

Glucocorticoids represent the mainstay therapy for many lung diseases, providing outstanding management of asthma but performing surprisingly poorly in patients with acute respiratory distress syndrome, chronic obstructive pulmonary disease, lung fibrosis, and blunted lung development associated with bronchopulmonary dysplasia in preterm infants. TGF-β is a pathogenic mediator of all four of these diseases, prompting us to explore glucocorticoid/TGF-β signaling cross-talk. Glucocorticoids, including dexamethasone, methylprednisolone, budesonide, and fluticasone, potentiated TGF-β signaling by the Acvrl1/Smad1/5/8 signaling axis and blunted signaling by the Tgfbr1/Smad2/3 axis in NIH/3T3 cells, as well as primary lung fibroblasts, smooth muscle cells, and endothelial cells. Dexamethasone drove expression of the accessory type III TGF-β receptor Tgfbr3, also called betaglycan. Tgfbr3 was demonstrated to be a “switch” that blunted Tgfbr1/Smad2/3 and potentiated Acvrl1/Smad1 signaling in lung fibroblasts. The Acvrl1/Smad1 axis, which was stimulated by dexamethasone, was active in lung fibroblasts and antagonized Tgfbr1/Smad2/3 signaling. Dexamethasone acted synergistically with TGF-β to drive differentiation of primary lung fibroblasts to myofibroblasts, revealed by acquisition of smooth muscle actin and smooth muscle myosin, which are exclusively Smad1-dependent processes in fibroblasts. Administration of dexamethasone to live mice recapitulated these observations and revealed a lung-specific impact of dexamethasone on lung Tgfbr3 expression and phospho-Smad1 levels in vivo. These data point to an interesting and hitherto unknown impact of glucocorticoids on TGF-β signaling in lung fibroblasts and other constituent cell types of the lung that may be relevant to lung physiology, as well as lung pathophysiology, in terms of drug/disease interactions.     

Proteostasis, an emerging therapeutic paradigm for managing inflammatory airway stress disease

Airways stress diseases (ASDs), including chronic obstructive pulmonary disease (COPD), emphysema and asthma, are predicted to become the third leading cause of morbidity and mortality by 2020. An understanding and the treatment of these diseases will have a high impact on human health and the health system. An emerging area of heathspan impact is the link between ASDs and proteome homeostasis or 'proteostasis', a biological system comprised of > 2000 components that direct the generation, maintenance and removal of proteins to achieve normal function. Alpha-1 antitrypsin deficiency (αA1TD) aggregates activating extracellular folding stress pathways, dysregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and misprocessing by histone acetyltransferase (HAT)/histone deacetylase (HDAC) pathways represent key examples of proteostasis imbalance involved in ASDs. Common to these events in the lung is a chronic inflammatory response in response to nuclear factor-κB (NF-κB) signaling and protein folding stress associated with an excess of mucus secretion, tissue remodeling, peribronchiolar fibrosis, bronchoconstriction and aveolar destruction. All of these emergent properties of disease are a consequence of imbalance in the proteostasis system. Herein, we discuss the role of proteostasis and its consequences on lung pathophysiology in inflammatory ASDs, and suggest how manipulating the proteostasis network through pharmacological intervention of proteostasis pathways could provide multiple routes for the restoration of lung physiology.     

Right Ventricular Systolic Pressure Measurements in Combination with Harvest of Lung and Immune Tissue Samples in Mice

The function of the right heart is to pump blood through the lungs, thus linking right heart physiology and pulmonary vascular physiology. Inflammation is a common modifier of heart and lung function, by elaborating cellular infiltration, production of cytokines and growth factors, and by initiating remodeling processes ¹.Compared to the left ventricle, the right ventricle is a low-pressure pump that operates in a relatively narrow zone of pressure changes. Increased pulmonary artery pressures are associated with increased pressure in the lung vascular bed and pulmonary hypertension ². Pulmonary hypertension is often associated with inflammatory lung diseases, for example chronic obstructive pulmonary disease, or autoimmune diseases ³. Because pulmonary hypertension confers a bad prognosis for quality of life and life expectancy, much research is directed towards understanding the mechanisms that might be targets for pharmaceutical intervention ⁴. The main challenge for the development of effective management tools for pulmonary hypertension remains the complexity of the simultaneous understanding of molecular and cellular changes in the right heart, the lungs and the immune system.Here, we present a procedural workflow for the rapid and precise measurement of pressure changes in the right heart of mice and the simultaneous harvest of samples from heart, lungs and immune tissues. The method is based on the direct catheterization of the right ventricle via the jugular vein in close-chested mice, first developed in the late 1990s as surrogate measure of pressures in the pulmonary artery^5-13. The organized team-approach facilitates a very rapid right heart catheterization technique. This makes it possible to perform the measurements in mice that spontaneously breathe room air. The organization of the work-flow in distinct work-areas reduces time delay and opens the possibility to simultaneously perform physiology experiments and harvest immune, heart and lung tissues.The procedural workflow outlined here can be adapted for a wide variety of laboratory settings and study designs, from small, targeted experiments, to large drug screening assays. The simultaneous acquisition of cardiac physiology data that can be expanded to include echocardiography^5,14-17 and harvest of heart, lung and immune tissues reduces the number of animals needed to obtain data that move the scientific knowledge basis forward. The procedural workflow presented here also provides an ideal basis for gaining knowledge of the networks that link immune, lung and heart function. The same principles outlined here can be adapted to study other or additional organs as needed.     

Alveolus formation: what have we learned from genetic studies?

The respiratory system has two basic functions: air exchange and pathogen clearance. The conducting airway and alveolar parenchyma are the basic structures to fulfill these functions during respiratory cycles. In humans, there are approximately 40 cell types in the lung that coordinately work together through various structural and signaling molecules. These molecules are vital for maintaining normal lung functions in response to environmental changes. Aberrant expression of these molecules can jeopardize human health and cause various pulmonary diseases. In this article, we will review some recent progress made in the pulmonary field, using genetic animal model systems to elucidate molecular mechanisms that are important for alveolar formation and lung diseases.     

Microbiota: A Missing Link in The Pathogenesis of Chronic Lung Inflammatory Diseases

Chronic respiratory diseases account for high morbidity and mortality, with asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) being the most prevalent globally. Even though the diseases increase in prevalence, the exact underlying mechanisms have still not been fully understood. Despite their differences in nature, pathophysiologies, and clinical phenotypes, a growing body of evidence indicates that the presence of lung microbiota can shape the pathogenic processes underlying chronic inflammation, typically observed in the course of the diseases. Therefore, the characterization of the lung microbiota may shed new light on the pathogenesis of these diseases. Specifically, in chronic respiratory tract diseases, the human microbiota may contribute to the disease’s development and severity. The present review explores the role of the microbiota in the area of chronic pulmonary diseases, especially COPD, asthma, and CF.