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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 -
BMC Pulmonary Medicine Oct 2018Pulmonary function tests (PFTs) are routinely performed in the upright position due to measurement devices and patient comfort. This systematic review investigated the...
BACKGROUND
Pulmonary function tests (PFTs) are routinely performed in the upright position due to measurement devices and patient comfort. This systematic review investigated the influence of body position on lung function in healthy persons and specific patient groups.
METHODS
A search to identify English-language papers published from 1/1998-12/2017 was conducted using MEDLINE and Google Scholar with key words: body position, lung function, lung mechanics, lung volume, position change, positioning, posture, pulmonary function testing, sitting, standing, supine, ventilation, and ventilatory change. Studies that were quasi-experimental, pre-post intervention; compared ≥2 positions, including sitting or standing; and assessed lung function in non-mechanically ventilated subjects aged ≥18 years were included. Primary outcome measures were forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC, FEV1/FVC), vital capacity (VC), functional residual capacity (FRC), maximal expiratory pressure (PEmax), maximal inspiratory pressure (PImax), peak expiratory flow (PEF), total lung capacity (TLC), residual volume (RV), and diffusing capacity of the lungs for carbon monoxide (DLCO). Standing, sitting, supine, and right- and left-side lying positions were studied.
RESULTS
Forty-three studies met inclusion criteria. The study populations included healthy subjects (29 studies), lung disease (nine), heart disease (four), spinal cord injury (SCI, seven), neuromuscular diseases (three), and obesity (four). In most studies involving healthy subjects or patients with lung, heart, neuromuscular disease, or obesity, FEV1, FVC, FRC, PEmax, PImax, and/or PEF values were higher in more erect positions. For subjects with tetraplegic SCI, FVC and FEV1 were higher in supine vs. sitting. In healthy subjects, DLCO was higher in the supine vs. sitting, and in sitting vs. side-lying positions. In patients with chronic heart failure, the effect of position on DLCO varied.
CONCLUSIONS
Body position influences the results of PFTs, but the optimal position and magnitude of the benefit varies between study populations. PFTs are routinely performed in the sitting position. We recommend the supine position should be considered in addition to sitting for PFTs in patients with SCI and neuromuscular disease. When treating patients with heart, lung, SCI, neuromuscular disease, or obesity, one should take into consideration that pulmonary physiology and function are influenced by body position.
Topics: Humans; Lung; Posture; Respiratory Function Tests
PubMed: 30305051
DOI: 10.1186/s12890-018-0723-4 -
Physiology (Bethesda, Md.) Sep 2017Accurate and comprehensive evaluation of right ventricular (RV)-pulmonary vascular (PV) interactions is critical to the assessment of cardiopulmonary function,... (Review)
Review
Accurate and comprehensive evaluation of right ventricular (RV)-pulmonary vascular (PV) interactions is critical to the assessment of cardiopulmonary function, dysfunction, and failure. Here, we review methods of quantifying RV-PV interactions and experimental results from clinical trials as well as large- and small-animal models based on pressure-volume analysis. We conclude by outlining critical gaps in knowledge that should drive future studies.
Topics: Animals; Heart Ventricles; Humans; Lung; Pulmonary Veins
PubMed: 28814495
DOI: 10.1152/physiol.00040.2016 -
Journal of Digital Imaging Aug 2014This study presents a completely automated method for separating the left and right lungs using free-formed surface fitting on volumetric computed tomography (CT). The...
This study presents a completely automated method for separating the left and right lungs using free-formed surface fitting on volumetric computed tomography (CT). The left and right lungs are roughly divided using iterative 3-dimensional morphological operator and a Hessian matrix analysis. A point set traversing between the initial left and right lungs is then detected with a Euclidean distance transform to determine the optimal separating surface, which is then modeled from the point set using a free-formed surface-fitting algorithm. Subsequently, the left and right lung volumes are smoothly and directly separated using the separating surface. The performance of the proposed method was estimated by comparison with that of a human expert on 44 CT examinations. For all data sets, averages of the root mean square surface distance, maximum surface distance, and volumetric overlap error between the results of the automatic and the manual methods were 0.032 mm, 2.418 mm, and 0.017 %, respectively. Our study showed the feasibility of automatically separating the left and right lungs by identifying the 3D continuous separating surface on volumetric chest CT images.
Topics: Algorithms; Cone-Beam Computed Tomography; Feasibility Studies; Humans; Imaging, Three-Dimensional; Lung; Organ Size; Pattern Recognition, Automated; Pulmonary Disease, Chronic Obstructive; Radiographic Image Interpretation, Computer-Assisted; Reproducibility of Results; Retrospective Studies
PubMed: 24691827
DOI: 10.1007/s10278-014-9680-5 -
Magnetic Resonance in Medicine Jan 2022Lung stiffness alters with many diseases; therefore, several MR elastography (MRE) studies were performed earlier to investigate the stiffness of the right lung during...
PURPOSE
Lung stiffness alters with many diseases; therefore, several MR elastography (MRE) studies were performed earlier to investigate the stiffness of the right lung during breathhold at residual volume and total lung capacity. The aims of this study were 1) to estimate shear stiffness of the lungs using MRE under free breathing and demonstrate the measurements' repeatability and reproducibility, and 2) to compare lung stiffness under free breathing to breathhold and as a function of age and gender.
METHODS
Twenty-five healthy volunteers were scanned on a 1.5 Tesla MRI scanner. Spin-echo dual-density spiral and a spin-echo EPI MRE sequences were used to measure shear stiffness of the lungs during free breathing and breathhold at midpoint of tidal volume, respectively. Concordance correlation coefficient and Bland-Altman analyses were performed to determine the repeatability and reproducibility of the spin-echo dual-density spiral-derived shear stiffness. Repeated measures analyses of variances were used to investigate differences in shear stiffness between spin-echo dual-density spiral and spin-echo EPI, right and left lungs, males and females, and different age groups.
RESULTS
Free-breathing MRE sequence was highly repeatable and reproducible (concordance correlation coefficient > 0.86 for both lungs). Lung stiffness was significantly lower in breathhold than in free breathing (P < .001), which can be attributed to potential stress relaxation of lung parenchyma or breathhold inconsistencies. However, there was no significant difference between different age groups (P = .08). The left lung showed slightly higher stiffness values than the right lung (P = .14). There is no significant difference in lung stiffness between genders.
CONCLUSION
This study demonstrated the feasibility of free-breathing lung MRE with excellent repeatability and reproducibility. Stiffness changes with age and during the respiratory cycle. However, gender does not influence lungs stiffness.
Topics: Echo-Planar Imaging; Elasticity Imaging Techniques; Female; Humans; Lung; Magnetic Resonance Imaging; Male; Reproducibility of Results
PubMed: 34463400
DOI: 10.1002/mrm.28986 -
International Journal of Molecular... Aug 2020The evolutionarily-conserved Notch signaling pathway plays critical roles in cell communication, function and homeostasis equilibrium. The pathway serves as a... (Review)
Review
The evolutionarily-conserved Notch signaling pathway plays critical roles in cell communication, function and homeostasis equilibrium. The pathway serves as a cell-to-cell juxtaposed molecular transducer and is crucial in a number of cell processes including cell fate specification, asymmetric cell division and lateral inhibition. Notch also plays critical roles in organismal development, homeostasis, and regeneration, including somitogenesis, left-right asymmetry, neurogenesis, tissue repair, self-renewal and stemness, and its dysregulation has causative roles in a number of congenital and acquired pathologies, including cancer. In the lung, Notch activity is necessary for cell fate specification and expansion, and its aberrant activity is markedly linked to various defects in club cell formation, alveologenesis, and non-small cell lung cancer (NSCLC) development. In this review, we focus on the role this intercellular signaling device plays during lung development and on its functional relevance in proximo-distal cell fate specification, branching morphogenesis, and alveolar cell determination and maturation, then revise its involvement in NSCLC formation, progression and treatment refractoriness, particularly in the context of various mutational statuses associated with NSCLC, and, lastly, conclude by providing a succinct outlook of the therapeutic perspectives of Notch targeting in NSCLC therapy, including an overview on prospective synthetic lethality approaches.
Topics: Animals; Carcinoma, Non-Small-Cell Lung; Humans; Lung; Lung Neoplasms; Models, Biological; Receptors, Notch; Signal Transduction
PubMed: 32784481
DOI: 10.3390/ijms21165691 -
Korean Journal of Radiology Oct 2021To describe the anatomic locations and imaging features of posterior lung herniation in unilateral pulmonary agenesis and aplasia, focusing on radiograph-CT/MRI...
OBJECTIVE
To describe the anatomic locations and imaging features of posterior lung herniation in unilateral pulmonary agenesis and aplasia, focusing on radiograph-CT/MRI correlation.
MATERIALS AND METHODS
A total of 10 patients (seven with pulmonary agenesis and three with pulmonary aplasia, male: female = 1:9, mean age 7.3 years, age range from 1 month to 20 years) were included. Chest radiographs (n = 9), CT (n = 9), and MRI (n = 1) were reviewed to assess the type of lung underdevelopment, presence of anterior and posterior lung herniation, bronchus origin, supplying artery, and draining vein of the herniated lung.
RESULTS
Pulmonary agenesis/aplasia more commonly affected the left lung (n = 7) than the right lung (n = 3). Anterior lung herniation was observed in nine of the 10 patients. Posterior lung herniation was observed in seven patients with left pulmonary agenesis/aplasia. Two patients showed posterior lung herniation crossing the midline but not beyond the aorta, and five patients showed the posteriorly herniated right lower lobe crossing the midline to extend into the left hemithorax farther beyond the descending thoracic aorta through the space between the esophagus and the aorta. This anatomical configuration resulted in a characteristic radiographic finding of a radiolucent area with a convex lateral border and a vertical medial border in the left lower lung zone, revealing a tongue-like projection on CT and MRI.
CONCLUSION
Posterior lung herniation occurs in unilateral left lung agenesis/aplasia. Approximately 70% of the cases of posterior lung herniation reveal a unique radiolucent tongue-like projection in the left lower lung zone on imaging studies, which is caused by the extension of the posteriorly herniated right lung farther beyond the descending aorta.
Topics: Abnormalities, Multiple; Child; Female; Humans; Infant; Lung; Lung Diseases; Male; Tomography, X-Ray Computed
PubMed: 34269531
DOI: 10.3348/kjr.2021.0155 -
Respirology (Carlton, Vic.) Jul 2009The complex structure of the lung is developed sequentially, initially by epithelial tube branching and later by septation of terminal air sacs with accompanying... (Review)
Review
The complex structure of the lung is developed sequentially, initially by epithelial tube branching and later by septation of terminal air sacs with accompanying coordinated growth of a variety of lung epithelial and mesenchymal cells. Groups of transcriptional factors, peptide growth factors and their intracellular signaling regulators, as well as extracellular matrix proteins are programmed to be expressed at appropriate levels in the right place at the right time to control normal lung formation. Studies of lung development and lung repair/fibrosis to date have discovered that many of the same factors that control normal development are also key players in lung injury repair and fibrosis. Transforming growth factor-beta (TGF-beta) family peptide signaling is a prime example. Lack of TGF-beta signaling results in abnormal lung branching morphogenesis and alveolarization during development, whereas excessive amounts of TGF-beta signaling cause severe hypoplasia in the immature lung and fibrosis in mature lung. This leads us to propose the 'Goldilocks' hypothesis of regulatory signaling in lung development and injury repair that everything must be done just right!
Topics: Extracellular Matrix; Humans; Lung; Lung Injury; Pulmonary Fibrosis; Signal Transduction; Transforming Growth Factor beta
PubMed: 19659647
DOI: 10.1111/j.1440-1843.2009.01565.x -
Current Opinion in Pulmonary Medicine Sep 2016Pulmonary tumour thrombotic microangiopathy (PTTM) describes tumour cell microemboli with occlusive fibrointimal remodelling in small pulmonary arteries, veins and... (Review)
Review
PURPOSE OF REVIEW
Pulmonary tumour thrombotic microangiopathy (PTTM) describes tumour cell microemboli with occlusive fibrointimal remodelling in small pulmonary arteries, veins and lymphatics. Progressive vessel occlusion ultimately results in pulmonary hypertension, which is often severe and rapid in onset. PTTM is associated with carcinomas, notably gastric carcinoma, with vascular endothelial growth factor and platelet-derived growth factor (PDGF) signalling implicated in driving the intimal remodelling. PTTM is a rare cause of pulmonary hypertension, but given that up to a quarter of autopsy specimens from patients dying of carcinoma show evidence for PTTM, it is probably underdiagnosed.
RECENT FINDINGS
Until recently, prognosis in PTTM was universally abysmal from weeks to a few months. Diagnostic utilities include aspiration of tumour cells at wedged right heart catheterization, high-resolution computed tomography (HRCT) findings and computed tomography-positron emission tomography (CT-PET), although definitive diagnosis requires histological analysis. Reports of PTTM treated with a combination of targeted pulmonary vasodilator therapies, anticoagulation, specific chemotherapy and PDGF inhibition, for example using imatinib, suggest that these approaches can prolong survival.
SUMMARY
PTTM is increasingly recognized as an important cause of pulmonary hypertension, often in patients presenting with new-onset pulmonary hypertension and as yet undiagnosed malignancy. Prospects of survival are improving with targeted combination therapy, and early recognition and diagnosis are likely to be the key factors to improve outcome.
Topics: Humans; Lung; Lung Neoplasms; Neoplastic Cells, Circulating; Thrombotic Microangiopathies; Vascular Remodeling
PubMed: 27387102
DOI: 10.1097/MCP.0000000000000297