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Annual Review of Physiology Feb 2020People worldwide are living longer, and it is estimated that by 2050, the proportion of the world's population over 60 years of age will nearly double. Natural lung... (Review)
Review
People worldwide are living longer, and it is estimated that by 2050, the proportion of the world's population over 60 years of age will nearly double. Natural lung aging is associated with molecular and physiological changes that cause alterations in lung function, diminished pulmonary remodeling and regenerative capacity, and increased susceptibility to acute and chronic lung diseases. As the aging population rapidly grows, it is essential to examine how alterations in cellular function and cell-to-cell interactions of pulmonary resident cells and systemic immune cells contribute to a higher risk of increased susceptibility to infection and development of chronic diseases, such as chronic obstructive pulmonary disease and interstitial pulmonary fibrosis. This review provides an overview of physiological, structural, and cellular changes in the aging lung and immune system that facilitate the development and progression of disease.
Topics: Aged; Aging; Cellular Senescence; Humans; Lung; Lung Diseases; Middle Aged
PubMed: 31730381
DOI: 10.1146/annurev-physiol-021119-034610 -
Annual Review of Medicine 2004Tissue injury evokes highly conserved, tightly regulated inflammatory responses and less well-understood host repair responses. Both inflammation and repair involve the... (Review)
Review
Tissue injury evokes highly conserved, tightly regulated inflammatory responses and less well-understood host repair responses. Both inflammation and repair involve the recruitment, activation, apoptosis, and eventual clearance of key effector cells. In this review, we propose the concept of pulmonary fibrosis as a dysregulated repair process that is perpetually "turned on" even though classical inflammatory pathways may be dampened or "switched off." Significant regional heterogeneity, with varied histopathological patterns of inflammation and fibrosis, has been observed in individual patients with idiopathic pulmonary fibrosis. We discuss environmental factors and host response factors, such as genetic susceptibility and age, that may influence these varied manifestations. Better understanding of the mechanisms of lung repair, which include alveolar reepithelialization, myofibroblast differentiation/activation, and apoptosis, should offer more effective therapeutic options for progressive pulmonary fibrosis.
Topics: Humans; Lung; Pulmonary Fibrosis
PubMed: 14746528
DOI: 10.1146/annurev.med.55.091902.103810 -
Cell and Tissue Research Mar 2017The study of the structural basis of gas exchange function in the lung depends on the availability of quantitative information that concerns the structures establishing... (Review)
Review
The study of the structural basis of gas exchange function in the lung depends on the availability of quantitative information that concerns the structures establishing contact between the air in the alveoli and the blood in the alveolar capillaries, which can be entered into physiological equations for predicting oxygen uptake. This information is provided by morphometric studies involving stereological methods and allows estimates of the pulmonary diffusing capacity of the human lung that agree, in experimental studies, with the maximal oxygen consumption. The basis for this "machine lung" structure lies in the complex design of the cells building an extensive air-blood barrier with minimal cell mass.
Topics: Animals; Diffusion; Gases; Humans; Lung
PubMed: 27981379
DOI: 10.1007/s00441-016-2541-4 -
Cell and Tissue Research Mar 2017To fulfill the task of gas exchange, the lung possesses a huge inner surface and a tree-like system of conducting airways ventilating the gas exchange area. During lung... (Review)
Review
To fulfill the task of gas exchange, the lung possesses a huge inner surface and a tree-like system of conducting airways ventilating the gas exchange area. During lung development, the conducting airways are formed first, followed by the formation and enlargement of the gas exchange area. The latter (alveolarization) continues until young adulthood. During organogenesis, the left and right lungs have their own anlage, an outpouching of the foregut. Each lung bud starts a repetitive process of outgrowth and branching (branching morphogenesis) that forms all of the future airways mainly during the pseudoglandular stage. During the canalicular stage, the differentiation of the epithelia becomes visible and the bronchioalveolar duct junction is formed. The location of this junction stays constant throughout life. Towards the end of the canalicular stage, the first gas exchange may take place and survival of prematurely born babies becomes possible. Ninety percent of the gas exchange surface area will be formed by alveolarization, a process where existing airspaces are subdivided by the formation of new walls (septa). This process requires a double-layered capillary network at the basis of the newly forming septum. However, in parallel to alveolarization, the double-layered capillary network of the immature septa fuses to a single-layered network resulting in an optimized setup for gas exchange. Alveolarization still continues, because, at sites where new septa are lifting off preexisting mature septa, the required second capillary layer will be formed instantly by angiogenesis. The latter confirms a lifelong ability of alveolarization, which is important for any kind of lung regeneration.
Topics: Animals; Embryonic Development; Humans; Lung; Organogenesis; Pulmonary Alveoli
PubMed: 28144783
DOI: 10.1007/s00441-016-2545-0 -
Comprehensive Physiology Mar 2016Structural and functional complexities of the mammalian lung evolved to meet a unique set of challenges, namely, the provision of efficient delivery of inspired air to... (Review)
Review
Structural and functional complexities of the mammalian lung evolved to meet a unique set of challenges, namely, the provision of efficient delivery of inspired air to all lung units within a confined thoracic space, to build a large gas exchange surface associated with minimal barrier thickness and a microvascular network to accommodate the entire right ventricular cardiac output while withstanding cyclic mechanical stresses that increase several folds from rest to exercise. Intricate regulatory mechanisms at every level ensure that the dynamic capacities of ventilation, perfusion, diffusion, and chemical binding to hemoglobin are commensurate with usual metabolic demands and periodic extreme needs for activity and survival. This article reviews the structural design of mammalian and human lung, its functional challenges, limitations, and potential for adaptation. We discuss (i) the evolutionary origin of alveolar lungs and its advantages and compromises, (ii) structural determinants of alveolar gas exchange, including architecture of conducting bronchovascular trees that converge in gas exchange units, (iii) the challenges of matching ventilation, perfusion, and diffusion and tissue-erythrocyte and thoracopulmonary interactions. The notion of erythrocytes as an integral component of the gas exchanger is emphasized. We further discuss the signals, sources, and limits of structural plasticity of the lung in alveolar hypoxia and following a loss of lung units, and the promise and caveats of interventions aimed at augmenting endogenous adaptive responses. Our objective is to understand how individual components are matched at multiple levels to optimize organ function in the face of physiological demands or pathological constraints.
Topics: Adaptation, Physiological; Animals; Humans; Lung; Pulmonary Gas Exchange
PubMed: 27065169
DOI: 10.1002/cphy.c150028 -
Comprehensive Physiology Mar 2016The circulation of the lung is unique both in volume and function. For example, it is the only organ with two circulations: the pulmonary circulation, the main function... (Review)
Review
The circulation of the lung is unique both in volume and function. For example, it is the only organ with two circulations: the pulmonary circulation, the main function of which is gas exchange, and the bronchial circulation, a systemic vascular supply that provides oxygenated blood to the walls of the conducting airways, pulmonary arteries and veins. The pulmonary circulation accommodates the entire cardiac output, maintaining high blood flow at low intravascular arterial pressure. As compared with the systemic circulation, pulmonary arteries have thinner walls with much less vascular smooth muscle and a relative lack of basal tone. Factors controlling pulmonary blood flow include vascular structure, gravity, mechanical effects of breathing, and the influence of neural and humoral factors. Pulmonary vascular tone is also altered by hypoxia, which causes pulmonary vasoconstriction. If the hypoxic stimulus persists for a prolonged period, contraction is accompanied by remodeling of the vasculature, resulting in pulmonary hypertension. In addition, genetic and environmental factors can also confer susceptibility to development of pulmonary hypertension. Under normal conditions, the endothelium forms a tight barrier, actively regulating interstitial fluid homeostasis. Infection and inflammation compromise normal barrier homeostasis, resulting in increased permeability and edema formation. This article focuses on reviewing the basics of the lung circulation (pulmonary and bronchial), normal development and transition at birth and vasoregulation. Mechanisms contributing to pathological conditions in the pulmonary circulation, in particular when barrier function is disrupted and during development of pulmonary hypertension, will also be discussed.
Topics: Animals; Humans; Hypertension, Pulmonary; Lung; Morphogenesis; Pulmonary Circulation; Pulmonary Edema
PubMed: 27065170
DOI: 10.1002/cphy.c140049 -
Development (Cambridge, England) Feb 2014The respiratory system, which consists of the lungs, trachea and associated vasculature, is essential for terrestrial life. In recent years, extensive progress has been... (Review)
Review
The respiratory system, which consists of the lungs, trachea and associated vasculature, is essential for terrestrial life. In recent years, extensive progress has been made in defining the temporal progression of lung development, and this has led to exciting discoveries, including the derivation of lung epithelium from pluripotent stem cells and the discovery of developmental pathways that are targets for new therapeutics. These discoveries have also provided new insights into the regenerative capacity of the respiratory system. This Review highlights recent advances in our understanding of lung development and regeneration, which will hopefully lead to better insights into both congenital and acquired lung diseases.
Topics: Animals; Humans; Lung; Models, Biological; Organogenesis; Regeneration
PubMed: 24449833
DOI: 10.1242/dev.098186 -
Clinical Microbiology Reviews Apr 2008A pulmonary cavity is a gas-filled area of the lung in the center of a nodule or area of consolidation and may be clinically observed by use of plain chest radiography... (Review)
Review
A pulmonary cavity is a gas-filled area of the lung in the center of a nodule or area of consolidation and may be clinically observed by use of plain chest radiography or computed tomography. Cavities are present in a wide variety of infectious and noninfectious processes. This review discusses the differential diagnosis of pathological processes associated with lung cavities, focusing on infections associated with lung cavities. The goal is to provide the clinician and clinical microbiologist with an overview of the diseases most commonly associated with lung cavities, with attention to the epidemiology and clinical characteristics of the host.
Topics: Humans; Lung; Lung Diseases; Tomography, X-Ray Computed
PubMed: 18400799
DOI: 10.1128/CMR.00060-07 -
Molecular Microbiology Mar 2022Respiratory infections are a leading cause of mortality worldwide. Most of the research on the underlying disease mechanisms is based on cell culture, organoid, or... (Review)
Review
Respiratory infections are a leading cause of mortality worldwide. Most of the research on the underlying disease mechanisms is based on cell culture, organoid, or surrogate animal models. Although these provide important insights, they have limitations. Cell culture models fail to recapitulate cellular interactions in the lung and animal models often do not permit high-throughput analysis of drugs or pathogen isolates; hence, there is a need for improved, scalable models. Precision-cut lung slices (PCLS), small, uniform tissue slices generated from animal or human lungs are increasingly recognized and employed as an ex vivo organotypic model. PCLS retain remarkable cellular complexity and the architecture of the lung, providing a platform to investigate respiratory pathogens in a near-native environment. Here, we review the generation and features of PCLS, their use to investigate the pathogenesis of viral and bacterial pathogens, and highlight their potential to advance respiratory infection research in the future.
Topics: Animals; Communicable Diseases; Lung
PubMed: 34570407
DOI: 10.1111/mmi.14817 -
Developmental Cell Jan 2022The human lung plays vital roles in respiration, host defense, and basic physiology. Recent technological advancements such as single-cell RNA sequencing and genetic...
The human lung plays vital roles in respiration, host defense, and basic physiology. Recent technological advancements such as single-cell RNA sequencing and genetic lineage tracing have revealed novel cell types and enriched functional properties of existing cell types in lung. The time has come to take a new census. Initiated by members of the NHLBI-funded LungMAP Consortium and aided by experts in the lung biology community, we synthesized current data into a comprehensive and practical cellular census of the lung. Identities of cell types in the normal lung are captured in individual cell cards with delineation of function, markers, developmental lineages, heterogeneity, regenerative potential, disease links, and key experimental tools. This publication will serve as the starting point of a live, up-to-date guide for lung research at https://www.lungmap.net/cell-cards/. We hope that Lung CellCards will promote the community-wide effort to establish, maintain, and restore respiratory health.
Topics: Cell Differentiation; Databases as Topic; Humans; Lung; Regeneration; Single-Cell Analysis
PubMed: 34936882
DOI: 10.1016/j.devcel.2021.11.007