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1

Farrow, Catherine E., Cheryl M. Salome, Benjamin E. Harris, Dale L. Bailey, Elizabeth Bailey, Norbert Berend, Iven H. Young e Gregory G. King. "Airway closure on imaging relates to airway hyperresponsiveness and peripheral airway disease in asthma". Journal of Applied Physiology 113, n. 6 (15 settembre 2012): 958–66. http://dx.doi.org/10.1152/japplphysiol.01618.2011.

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Abstract (sommario):
The regional pattern and extent of airway closure measured by three-dimensional ventilation imaging may relate to airway hyperresponsiveness (AHR) and peripheral airways disease in asthmatic subjects. We hypothesized that asthmatic airways are predisposed to closure during bronchoconstriction in the presence of ventilation heterogeneity and AHR. Fourteen asthmatic subjects (6 women) underwent combined ventilation single photon emission computed tomography/computed tomography scans before and after methacholine challenge. Regional airway closure was determined by complete loss of ventilation following methacholine challenge. Peripheral airway disease was measured by multiple-breath nitrogen washout from which Scond (index of peripheral conductive airway abnormality) was derived. Relationships between airway closure and lung function were examined by multiple-linear regression. Forced expiratory volume in 1 s was 87.5 ± 15.8% predicted, and seven subjects had AHR. Methacholine challenge decreased forced expiratory volume in 1 s by 23 ± 5% and increased nonventilated volume from 16 ± 4 to 29 ± 13% of computed tomography lung volume. The increase in airway closure measured by nonventilated volume correlated independently with both Scond (partial R2 = 0.22) and with AHR (partial R2 = 0.38). The extent of airway closure induced by methacholine inhalation in asthmatic subjects is greater with increasing peripheral airways disease, as measured by ventilation heterogeneity, and with worse AHR.
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2

Brown, Robert H., Wayne Mitzner, Yonca Bulut e Elizabeth M. Wagner. "Effect of lung inflation in vivo on airways with smooth muscle tone or edema". Journal of Applied Physiology 82, n. 2 (1 febbraio 1997): 491–99. http://dx.doi.org/10.1152/jappl.1997.82.2.491.

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Abstract (sommario):
Brown, Robert H., Wayne Mitzner, Yonca Bulut, and Elizabeth M. Wagner. Effect of lung inflation in vivo on airways with smooth muscle tone or edema. J. Appl. Physiol. 82(2): 491–499, 1997.—Fibrous attachments to the airway wall and a subpleural surrounding pressure can create an external load against which airway smooth muscle must contract. A decrease in this load has been proposed as a possible cause of increased airway narrowing in asthmatic individuals. To study the interaction between the airways and the surrounding lung parenchyma, we investigated the effect of lung inflation on relaxed airways, airways contracted with methacholine, and airways made edematous by infusion of bradykinin into the bronchial artery. Measurements were made in anesthetized sheep by using high-resolution computed tomography to visualize changes in individual airways. During methacholine infusion, airway area was decreased but increased minimally with increases in transpulmonary pressure. Bradykinin infusion caused a 50% increase in airway wall area and a small decrease in airway luminal area. In contrast to airways contracted with methacholine, the luminal area after bradykinin increased substantially with increases in transpulmonary pressure, reaching 99% of the relaxed area at total lung capacity. Thus airway edema by itself did not prevent full distension of the airway at lung volumes approaching total lung capacity. Therefore, we speculate that if a deep inspiration fails to relieve airway narrowing in vivo, this must be a manifestation of airway smooth muscle contraction and not airway wall edema.
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3

Sorkness, Ronald L., Kathryn M. Herricks, Renee J. Szakaly, Robert F. Lemanske e Louis A. Rosenthal. "Altered allergen-induced eosinophil trafficking and physiological dysfunction in airways with preexisting virus-induced injury". American Journal of Physiology-Lung Cellular and Molecular Physiology 292, n. 1 (gennaio 2007): L85—L91. http://dx.doi.org/10.1152/ajplung.00234.2006.

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Abstract (sommario):
Although both asthmatics and allergic rhinitics develop an acute inflammatory response to lower airway allergen challenge, only asthmatics experience airway obstruction resulting from chronic environmental allergen exposure. Hypothesizing that asthmatic airways have an altered response to chronic allergic inflammation, we compared the effects of repeated low-level exposures to inhaled Alternaria extract in sensitized rats with preexisting chronic postbronchiolitis airway dysfunction versus sensitized controls with normal airways. Measurements of air space (bronchoalveolar lavage) inflammatory cells, airway goblet cells, airway wall collagen, airway wall eosinophils, airway alveolar attachments, and pulmonary physiology were conducted after six weekly exposures to aerosolized saline or Alternaria extract. Postbronchiolitis rats, but not those starting with normal airways, had persistent increases in airway wall eosinophils, goblet cell hyperplasia in small airways, and loss of lung elastic recoil after repeated exposure to aerosolized Alternaria extract. Despite having elevated airway wall eosinophils, the postbronchiolitis rats had no eosinophils in bronchoalveolar lavage at 5 days after the last allergen exposure, suggesting altered egression of tissue eosinophils into the air space. In conclusion, rats with preexisting airway pathology had altered eosinophil trafficking and allergen-induced changes in airway epithelium and lung mechanics that were absent in sensitized control rats that had normal airways before the allergen exposures.
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4

Danek, Christopher J., Charles M. Lombard, Donald L. Dungworth, P. Gerard Cox, John D. Miller, Michael J. Biggs, Thomas M. Keast et al. "Reduction in airway hyperresponsiveness to methacholine by the application of RF energy in dogs". Journal of Applied Physiology 97, n. 5 (novembre 2004): 1946–53. http://dx.doi.org/10.1152/japplphysiol.01282.2003.

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Abstract (sommario):
We delivered controlled radio frequency energy to the airways of anesthetized, ventilated dogs to examine the effect of this treatment on reducing airway narrowing caused by a known airway constrictor. The airways of 11 dogs were treated with a specially designed bronchial catheter in three of four lung regions. Treatments in each of the three treated lung regions were controlled to a different temperature (55, 65, and 75°C); the untreated lung region served as a control. We measured airway responsiveness to local methacholine chloride (MCh) challenge before and after treatment and examined posttreatment histology to 3 yr. Treatments controlled to 65°C as well as 75°C persistently and significantly reduced airway responsiveness to local MCh challenge ( P ≤ 0.022). Airway responsiveness (mean percent decrease in airway diameter after MCh challenge) averaged from 6 mo to 3 yr posttreatment was 79 ± 2.2% in control airways vs. 39 ± 2.6% ( P ≤ 0.001) for airways treated at 65°C, and 26 ± 2.7% ( P ≤ 0.001) for airways treated at 75°C. Treatment effects were confined to the airway wall and the immediate peribronchial region on histological examination. Airway responsiveness to local MCh challenge was inversely correlated to the extent of altered airway smooth muscle observed in histology ( r = −0.54, P < 0.001). We conclude that the temperature-controlled application of radio frequency energy to the airways can reduce airway responsiveness to MCh for at least 3 yr in dogs by reducing airway smooth muscle contractility.
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5

Noble, P. B., D. J. Turner e H. W. Mitchell. "Relationship of airway narrowing, compliance, and cartilage in isolated bronchial segments". Journal of Applied Physiology 92, n. 3 (1 marzo 2002): 1119–24. http://dx.doi.org/10.1152/japplphysiol.00662.2001.

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Abstract (sommario):
Structural components of the airway wall may act to load airway smooth muscle and restrict airway narrowing. In this study, the effect of load on airway narrowing was investigated in pig isolated bronchial segments. In some bronchi, pieces of cartilage were removed by careful dissection. Airway narrowing was produced by maximum electrical field stimulation. An endoscope was used to record lumen narrowing. The compliance of the bronchial segments was determined from the cross-sectional area of the lumen and the transmural pressure. Airway narrowing and the velocity of airway narrowing were increased in cartilage-removed airways compared with intact control bronchi. Morphometric assessment of smooth muscle length showed greater muscle shortening to acetylcholine in cartilage-removed airways than in controls. Airway narrowing was positively correlated with airway compliance. Compliance and area of cartilage were negatively correlated. These results show that airway narrowing is increased in compliant airways and that cartilage significantly loads airway smooth muscle in whole bronchi.
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6

Naureckas, E. T., C. A. Dawson, B. S. Gerber, D. P. Gaver, H. L. Gerber, J. H. Linehan, J. Solway e R. W. Samsel. "Airway reopening pressure in isolated rat lungs". Journal of Applied Physiology 76, n. 3 (1 marzo 1994): 1372–77. http://dx.doi.org/10.1152/jappl.1994.76.3.1372.

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Abstract (sommario):
In a previous modeling study, we predicted that the yield pressure for airway reopening (Pyield) should depend on airway fluid surface tension (gamma) and airway radius (R), according to the relationship Pyield = 8.3 gamma/R. To test this prediction, we studied tantalum bronchograms of isolated perfused rat lungs from three rats by using microfocal X-ray imaging. Thirty-two airways with diameters ranging from 300 to 2,400 microns were recorded as the airways were collapsed and reinflated. Airway pressure was reduced transiently to -40 cmH2O to produce airway closure. Airway pressure was then slowly increased from 0 to 25 cmH2O. In each airway, the observed diameter remained constant until a Pyield was reached; at this pressure, airways were seen to “pop” open, allowing clear identification of airway reopening pressure. When Pyield was plotted against diameter at maximum inflation, the experimental data were in approximate agreement with predictions of Pyield made assuming a gamma of 35 dyn/cm. The close correspondence of the measured values with these predictions suggests that surfactant is present in these airways and facilitates airway reopening.
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7

Brown, R. H., e W. Mitzner. "Effect of lung inflation and airway muscle tone on airway diameter in vivo". Journal of Applied Physiology 80, n. 5 (1 maggio 1996): 1581–88. http://dx.doi.org/10.1152/jappl.1996.80.5.1581.

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Abstract (sommario):
How normal airway dimensions change with lung volume is of great importance in determining flow limitation during the normal forced vital capacity maneuver as well as in the manifestation of obstructive lung disease. The literature presents a confusing picture, with some results suggesting that airway diameter increases linearly with the cube root of lung volume and others showing a highly nonlinear relation. The effect of smooth muscle contraction on lung-airway interdependence is even less well understood. Recent morphological work explicitly assumes that airway basement membrane is nondistensible, although the lung volume at which this maximal airway size is reached is unknown. With smooth muscle contraction, folding of the epithelium and basement membrane accounts for the changes in luminal area. In this study, we measured the effect of lung inflation on relaxed and contracted airway areas by using high-resolution computed tomography at different transpulmonary pressures, each held for 2 min. We found that fully relaxed airways are quite distensible up to a pressure of 5-7 cmH2O (P < 0.001), where they reach a maximal size with no further distension up to an airway pressure of 30 cmH2O (P = 0.49). Thus relaxed airways clearly do not expand isotropically with the lung. With smooth muscle tone, the airways in different animals responded differently to lung inflation, with some animals showing minimal airway dilation up to an airway pressure of 20 cmH2O and others showing airways that were more easily dilated with lung expansion. However, maximal diameter of these moderately constricted airways was not usually achieved even up to an airway pressure of 30 cmH2O. Thus a transient deep inspiration in vivo would be expected to have only a small effect on contracted airways.
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8

Fasano, Mary Beth. "Combined airways: impact of upper airway on lower airway". Current Opinion in Otolaryngology & Head and Neck Surgery 18, n. 1 (febbraio 2010): 15–20. http://dx.doi.org/10.1097/moo.0b013e328334aa0e.

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9

Zimmermann, Nives, Marc Rothenberg e Leah Kottyan. "IL-13 is required and sufficient for airway acidification in allergic airway inflammation (141.16)". Journal of Immunology 184, n. 1_Supplement (1 aprile 2010): 141.16. http://dx.doi.org/10.4049/jimmunol.184.supp.141.16.

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Abstract (sommario):
Abstract Clinical studies have shown acidification of airways in asthma. Importantly, studies have suggested that acidification contributes to the pathophysiological process. However, the mechanism of acidification is unclear. We developed a novel method for measuring the acidity of mouse airways and demonstrated that mouse airways are acidified during models of allergic airway inflammation. Our studies determined that airway acidification does not develop in IL-13-deficient mice and that IL-13 delivery alone is sufficient to induce airway acidification. There are multiple ways IL-13 could lead to acidification, including direct effects on epithelial cells or through recruitment of inflammatory cells. We demonstrated a partial role for eosinophils in airway acidification as CCR3 and IL-5-deficient mice had decreased extent of airway acidification in allergen-challenged mice. Furthermore, using dimethyl amiloride, a specific inhibitor of the Na+/H+ exchanger, we demonstrated significant inhibition of airway acidification in allergic airway inflammation, suggesting a role for ion (proton) channels. In summary, our studies demonstrate that mouse airways are acidified during allergic airway inflammation. We also showed that the mechanism of airway acidification in asthma involves IL-13-mediated pathways including eosinophils and proton channels. These results have considerable implications for the development of therapies that target airway acidification.
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10

Brown, Robert H., e Wayne Mitzner. "Airway closure with high PEEP in vivo". Journal of Applied Physiology 89, n. 3 (1 settembre 2000): 956–60. http://dx.doi.org/10.1152/jappl.2000.89.3.956.

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Abstract (sommario):
When airway smooth muscle is contracted in vitro, the airway lumen continues to narrow with increasing concentrations of agonist until complete airway closure occurs. Although there remains some controversy regarding whether airways can close in vivo, recent work has clearly demonstrated that, if the airway is sufficiently stimulated with contractile agonists, complete closure of even large cartilaginous conducting airways can readily occur with the lung at functional residual capacity (Brown RH and Mitzner W. J Appl Physiol 85: 2012–2017, 1998). This result suggests that the tethering of airways in situ by parenchymal attachments is small at functional residual capacity. However, at lung volumes above functional residual capacity, the outward tethering of airways should increase, because both the parenchymal shear modulus and tethering forces increase in proportion to the transpulmonary pressure. In the present study, we tested whether we could prevent airway closure in vivo by increasing lung volume with positive end-expiratory pressure (PEEP). Airway smooth muscle was stimulated with increasing methacholine doses delivered directly to airway smooth muscle at three levels of PEEP (0, 6, and 10 cmH2O). Our results show that increased lung volume shifted the airway methacholine dose-response curve to the right, but, in many airways in most animals, airway closure still occurred even at the highest levels of PEEP.
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11

Gallos, George, Elizabeth Townsend, Peter Yim, Laszlo Virag, Yi Zhang, Dingbang Xu, Matthew Bacchetta e Charles W. Emala. "Airway epithelium is a predominant source of endogenous airway GABA and contributes to relaxation of airway smooth muscle tone". American Journal of Physiology-Lung Cellular and Molecular Physiology 304, n. 3 (1 febbraio 2013): L191—L197. http://dx.doi.org/10.1152/ajplung.00274.2012.

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Abstract (sommario):
Chronic obstructive pulmonary disease and asthma are characterized by hyperreactive airway responses that predispose patients to episodes of acute airway constriction. Recent studies suggest a complex paradigm of GABAergic signaling in airways that involves GABA-mediated relaxation of airway smooth muscle. However, the cellular source of airway GABA and mechanisms regulating its release remain unknown. We questioned whether epithelium is a major source of GABA in the airway and whether the absence of epithelium-derived GABA contributes to greater airway smooth muscle force. Messenger RNA encoding glutamic acid decarboxylase (GAD) 65/67 was quantitatively measured in human airway epithelium and smooth muscle. HPLC quantified GABA levels in guinea pig tracheal ring segments under basal or stimulated conditions with or without epithelium. The role of endogenous GABA in the maintenance of an acetylcholine contraction in human airway and guinea pig airway smooth muscle was assessed in organ baths. A 37.5-fold greater amount of mRNA encoding GAD 67 was detected in human epithelium vs. airway smooth muscle cells. HPLC confirmed that guinea pig airways with intact epithelium have a higher constitutive elution of GABA under basal or KCl-depolarized conditions compared with epithelium-denuded airway rings. Inhibition of GABA transporters significantly suppressed KCl-mediated release of GABA from epithelium-intact airways, but tetrodotoxin was without effect. The presence of intact epithelium had a significant GABAergic-mediated prorelaxant effect on the maintenance of contractile tone. Airway epithelium is a predominant cellular source of endogenous GABA in the airway and contributes significant prorelaxant GABA effects on airway smooth muscle force.
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12

Bai, Yan, e Michael J. Sanderson. "The contribution of Ca2+ signaling and Ca2+ sensitivity to the regulation of airway smooth muscle contraction is different in rats and mice". American Journal of Physiology-Lung Cellular and Molecular Physiology 296, n. 6 (giugno 2009): L947—L958. http://dx.doi.org/10.1152/ajplung.90288.2008.

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Abstract (sommario):
To determine the relative contributions of Ca2+ signaling and Ca2+ sensitivity to the contractility of airway smooth muscle cells (SMCs), we compared the contractile responses of mouse and rat airways with the lung slice technique. Airway contraction was measured by monitoring changes in airway lumen area with phase-contrast microscopy, whereas changes in intracellular calcium concentration ([Ca2+]i) of the SMCs were recorded with laser scanning microscopy. In mice and rats, methacholine (MCh) or serotonin induced concentration-dependent airway contraction and Ca2+ oscillations in the SMCs. However, rat airways demonstrated greater contraction compared with mice, in response to agonist-induced Ca2+ oscillations of a similar frequency. Because this indicates that rat airway SMCs have a higher Ca2+ sensitivity compared with mice, we examined Ca2+ sensitivity with Ca2+-permeabilized airway SMCs in which the [Ca2+]i was experimentally controlled. In the absence of agonists, high [Ca2+]i induced a sustained contraction in rat airways but only a transient contraction in mouse airways. This sustained contraction of rat airways was relaxed by Y-23672, a Rho kinase inhibitor, but not affected by GF-109203X, a PKC inhibitor. The subsequent exposure of Ca2+-permeabilized airway SMCs, with high [Ca2+]i, to MCh elicited a further contraction of rat airways and initiated a sustained contraction of mouse airways, without changing the [Ca2+]i of the SMCs. Collectively, these results indicate that airway SMCs of rats have a substantially higher innate Ca2+ sensitivity than mice and that this strongly influences the transduction of the frequency of Ca2+ oscillations into the contractility of airway SMCs.
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13

Ma, Baoshun, e Jason H. T. Bates. "Mechanical interactions between adjacent airways in the lung". Journal of Applied Physiology 116, n. 6 (15 marzo 2014): 628–34. http://dx.doi.org/10.1152/japplphysiol.01180.2013.

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Abstract (sommario):
The forces of mechanical interdependence between the airways and the parenchyma in the lung are powerful modulators of airways responsiveness. Little is known, however, about the extent to which adjacent airways affect each other's ability to narrow due to distortional forces generated within the intervening parenchyma. We developed a two-dimensional computational model of two airways embedded in parenchyma. The parenchyma itself was modeled in three ways: 1) as a network of hexagonally arranged springs, 2) as a network of triangularly arranged springs, and 3) as an elastic continuum. In all cases, we determined how the narrowing of one airway was affected when the other airway was relaxed vs. when it narrowed to the same extent as the first airway. For the continuum and triangular network models, interactions between airways were negligible unless the airways lay within about two relaxed diameters of each other, but even at this distance the interactions were small. By contrast, the hexagonal spring network model predicted that airway-airway interactions mediated by the parenchyma can be substantial for any degree of airway separation at intermediate values of airway contraction forces. Evidence to date suggests that the parenchyma may be better represented by the continuum model, which suggests that the parenchyma does not mediate significant interactions between narrowing airways.
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14

Tanabe, Naoya, Kaoruko Shimizu, Kunihiko Terada, Susumu Sato, Masaru Suzuki, Hiroshi Shima, Akira Oguma et al. "Central airway and peripheral lung structures in airway disease-dominant COPD". ERJ Open Research 7, n. 1 (gennaio 2021): 00672–2020. http://dx.doi.org/10.1183/23120541.00672-2020.

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Abstract (sommario):
The concept that the small airway is a primary pathological site for all COPD phenotypes has been challenged by recent findings that the disease starts from the central airways in COPD subgroups and that a smaller central airway tree increases COPD risk. This study aimed to examine whether the computed tomography (CT)-based airway disease-dominant (AD) subtype, defined using the central airway dimension, was less associated with small airway dysfunction (SAD) on CT, compared to the emphysema-dominant (ED) subtype.COPD patients were categorised into mild, AD, ED and mixed groups based on wall area per cent (WA%) of the segmental airways and low attenuation volume per cent in the Kyoto–Himeji (n=189) and Hokkaido COPD cohorts (n=93). The volume per cent of SAD regions (SAD%) was obtained by nonrigidly registering inspiratory and expiratory CT.The AD group had a lower SAD% than the ED group and similar SAD% to the mild group. The AD group had a smaller lumen size of airways proximal to the segmental airways and more frequent asthma history before age 40 years than the ED group. In multivariable analyses, while the AD and ED groups were similarly associated with greater airflow limitation, the ED, but not the AD, group was associated with greater SAD%, whereas the AD, but not the ED, group was associated with a smaller central airway size.The CT-based AD COPD subtype might be associated with a smaller central airway tree and asthma history, but not with peripheral lung pathologies including small airway disease, unlike the ED subtype.
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15

Sykes, Peter, Lucy Elliott e Matthew Rowe. "Maintaining the airway". InnovAiT: Education and inspiration for general practice 12, n. 10 (22 luglio 2019): 561–68. http://dx.doi.org/10.1177/1755738019863825.

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Airway-related problems can present in primary care. As first-contact care providers, GPs may encounter a range of airway emergencies that require urgent intervention. Patients may have residual symptoms from procedures such as endotracheal intubation or require specialised airways such as a tracheostomy in the community. This article concentrates on two issues focusing on the adult patient population. First, we discuss emergency airway maintenance in accordance with basic life support. Second, we explore the care of patients living with specialised airways in the community from a physical, psychosocial and emergency perspective.
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16

Okazawa, M., S. Vedal, L. Verburgt, R. K. Lambert e P. D. Pare. "Determinants of airway smooth muscle shortening in excised canine lobes". Journal of Applied Physiology 78, n. 2 (1 febbraio 1995): 608–14. http://dx.doi.org/10.1152/jappl.1995.78.2.608.

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Abstract (sommario):
There is marked heterogeneity of airway narrowing in intraparenchymal airways in response to bronchoconstricting stimuli. We hypothesized that this heterogeneity results from variations in the structure of the airway wall. Freshly excised dog lung lobes were inflated to transpulmonary pressures (PL) of between 5 and 15 cmH2O, and an aerosol containing a high concentration of carbachol was administered. The lobes were fixed and processed for light-microscopic examination and morphometric analysis of membranous airway dimensions. The relationships of smooth muscle shortening to PL and airway dimensions were analyzed using multiple linear regression. The results show that airway smooth muscle shortening was greater at lower PL and in airways with larger internal perimeter and a greater number of folds per internal perimeter and that it was less in airways with greater inner wall area. We conclude that the magnitude and variability of airway smooth muscle shortening and airway narrowing in response to maximal constricting stimuli are influenced by mechanical factors related to airway wall geometry.
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17

Brown, Robert H., Wayne Mitzner e Elizabeth M. Wagner. "Interaction between airway edema and lung inflation on responsiveness of individual airways in vivo". Journal of Applied Physiology 83, n. 2 (1 agosto 1997): 366–70. http://dx.doi.org/10.1152/jappl.1997.83.2.366.

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Abstract (sommario):
Brown, Robert H., Wayne Mitzner, and Elizabeth M. Wagner.Interaction between airway edema and lung inflation on responsiveness of individual airways in vivo. J. Appl. Physiol. 83(2): 366–370, 1997.—Inflammatory changes and airway wall thickening are suggested to cause increased airway responsiveness in patients with asthma. In five sheep, the dose-response relationships of individual airways were measured at different lung volumes to methacholine (MCh) before and after wall thickening caused by the inflammatory mediator bradykinin via the bronchial artery. At 4 cmH2O transpulmonary pressure (Ptp), 5 μg/ml MCh constricted the airways to a maximum of 18 ± 3%. At 30 cmH2O Ptp, MCh resulted in less constriction (to 31 ± 5%). Bradykinin increased airway wall area at 4 and 30 cmH2O Ptp (159 ± 6 and 152 ± 4%, respectively; P < 0.0001). At 4 cmH2O Ptp, bradykinin decreased airway luminal area (13 ± 2%; P< 0.01), and the dose-response curve was significantly lower ( P = 0.02). At 30 cmH2O, postbradykinin, the maximal airway narrowing was not significantly different (26 ± 5%; P = 0.76). Bradykinin produced substantial airway wall thickening and slight potentiation of the MCh-induced airway constriction at low lung volume. At high lung volume, bradykinin increased wall thickness but had no effect on the MCh-induced airway constriction. We conclude that inflammatory fluid leakage in the airways cannot be a primary cause of airway hyperresponsiveness.
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18

Henry, Peter J., Tracy S. Mann, Angela C. D'Aprile, Glenn J. Self e Roy G. Goldie. "An endothelin receptor antagonist, SB-217242, inhibits airway hyperresponsiveness in allergic mice". American Journal of Physiology-Lung Cellular and Molecular Physiology 283, n. 5 (1 novembre 2002): L1072—L1078. http://dx.doi.org/10.1152/ajplung.00076.2002.

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Abstract (sommario):
Within the airways, endothelin-1 (ET-1) can exert a range of prominent effects, including airway smooth muscle contraction, bronchial obstruction, airway wall edema, and airway remodeling. ET-1 also possesses proinflammatory properties and contributes to the late-phase response in allergic airways. However, there is no direct evidence for the contribution of endogenous ET-1 to airway hyperresponsiveness in allergic airways. Allergic inflammation induced in mice by sensitization and challenge with the house dust mite allergen Der P1 was associated with elevated levels of ET-1 within the lung, increased numbers of eosinophils within bronchoalveolar lavage fluid and tissue sections, and development of airway hyperresponsiveness to methacholine ( P < 0.05, n = 6 mice per group). Treatment of allergic mice with an endothelin receptor antagonist, SB-217242 (30 mg · kg−1· day−1), during allergen challenge markedly inhibited airway eosinophilia (bronchoalveolar lavage fluid and tissue) and development of airway hyperresponsiveness. These findings provide direct evidence for a mediator role for ET-1 in development of airway hyperresponsiveness and airway eosinophilia in Der P1-sensitized mice after antigen challenge.
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19

Rosenberg, M. B., J. C. Phero e D. E. Becker. "Essentials of Airway Management, Oxygenation, and Ventilation: Part 2: Advanced Airway Devices: Supraglottic Airways". Anesthesia Progress 61, n. 3 (1 settembre 2014): 113–18. http://dx.doi.org/10.2344/0003-3006-61.3.113.

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Abstract Offices and outpatient dental facilities must be properly equipped with devices for airway management, oxygenation, and ventilation. Part 1 in this series on emergency airway management focused on basic and fundamental considerations for supplying supplemental oxygen to the spontaneously breathing patient and utilizing a bag-valve-mask system including nasopharyngeal and oropharyngeal airways to deliver oxygen under positive pressure to the apneic patient. This article will review the evolution and use of advanced airway devices, specifically supraglottic airways, with the emphasis on the laryngeal mask airway, as the next intervention in difficult airway and ventilation management. The final part of the series (part 3) will address airway evaluation, equipment and devices for tracheal intubation, and invasive airway procedures.
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20

Shahi, Niti, Ryan Phillips, Maxene Meier, Theresa Grover, Henry Galan, Michael Zaretsky, Mariana Meyers, Peggy Kelley e Ahmed I. Marwan. "Outcomes of Airway Management in Micrognathia and Retrognathia Patients Born at Fetal versus Nonfetal Centers". Fetal Diagnosis and Therapy 47, n. 12 (2020): 933–38. http://dx.doi.org/10.1159/000510856.

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Abstract (sommario):
<b><i>Objectives:</i></b> There is a paucity of evidence to guide the perinatal management of difficult airways in fetuses with micrognathia. We aimed to (1) develop a postnatal grading system based on the extent of airway intervention required at birth to assess the severity of micrognathic airways and (2) compare trends in airway management and outcomes by location of birth [nonfetal center (NFC), defined as a hospital with or without an NICU and no fetal team, versus fetal center (FC), defined as a hospital with an NICU and fetal team]. <b><i>Methods:</i></b> We retrospectively reviewed the prenatal and postnatal records of all neonates diagnosed with micrognathia from January 2010 to April 2018 at a quaternary children’s hospital. We developed a novel grading scale, the Micrognathia Grading Scale (MGS), to grade the extent of airway intervention at birth from 0 (no airway intervention) to 4 (requirement of EXIT or advanced airway instrumentation for airway securement). <b><i>Results:</i></b> We identified 118 patients with micrognathia. Eighty-nine percent (105/118) were eligible for grading using the MGS. When the MGS was applied, the airway grades were as follows: grade 0 (30%), grade 1 (10%), grade 2 (9%), grade 3 (48%), and grade 4 (4%). A quarter of micrognathic patients with grade 0–2 airways had postnatal hospital readmissions for airway obstruction after birth, of which all were born at NFC. Over 40% of patients with grade 3–4 micrognathic airways required airway intervention within 24 h of birth. Overall, NFC patients had a readmission rate of (27%) for airway obstruction after birth compared to FC patients (17%). <b><i>Conclusions:</i></b> Due to the high incidence of grade 3–4 airways on the MGS in micrognathic patients, fetuses with prenatal findings suggestive of micrognathia should be referred to a comprehensive fetal care center capable of handling complex neonatal airways. For grade 0–2 airways, infants frequently had postnatal complications necessitating airway intervention; early referral to a multidisciplinary team for both prenatal and postnatal airway management is recommended.
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21

Dubsky, S., G. R. Zosky, K. Perks, C. R. Samarage, Y. Henon, S. B. Hooper e A. Fouras. "Assessment of airway response distribution and paradoxical airway dilation in mice during methacholine challenge". Journal of Applied Physiology 122, n. 3 (1 marzo 2017): 503–10. http://dx.doi.org/10.1152/japplphysiol.00476.2016.

Testo completo
Abstract (sommario):
Detailed information on the distribution of airway diameters during bronchoconstriction in situ is required to understand the regional response of the lungs. Imaging studies using computed tomography (CT) have previously measured airway diameters and changes in response to bronchoconstricting agents, but the manual measurements used have severely limited the number of airways measured per subject. Hence, the detailed distribution and heterogeneity of airway responses are unknown. We have developed and applied dynamic imaging and advanced image-processing methods to quantify and compare hundreds of airways in vivo. The method, based on CT, was applied to house dust-mite-sensitized and control mice during intravenous methacholine (MCh) infusion. Airway diameters were measured pre- and post-MCh challenge, and the results compared demonstrate the distribution of airway response throughout the lungs during mechanical ventilation. Forced oscillation testing was used to measure the global response in lung mechanics. We found marked heterogeneity in the response, with paradoxical dilation of airways present at all airway sizes. The probability of paradoxical dilation decreased with decreasing baseline airway diameter and was not affected by pre-existing inflammation. The results confirm the importance of considering the lung as an entire interconnected system rather than a collection of independent units. It is hoped that the response distribution measurements can help to elucidate the mechanisms that lead to heterogeneous airway response in vivo. NEW & NOTEWORTHY Information on the distribution of airway diameters during bronchoconstriction in situ is critical for understanding the regional response of the lungs. We have developed an imaging method to quantify and compare the size of hundreds of airways in vivo during bronchoconstriction in mice. The results demonstrate large heterogeneity with both constriction and paradoxical dilation of airways, confirming the importance of considering the lung as an interconnected system rather than a collection of independent units.
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22

Shifren, Adrian, Chad Witt, Chandrika Christie e Mario Castro. "Mechanisms of Remodeling in Asthmatic Airways". Journal of Allergy 2012 (19 gennaio 2012): 1–12. http://dx.doi.org/10.1155/2012/316049.

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Abstract (sommario):
Asthma is a chronic inflammatory airway disorder characterized by airway hyperresponsiveness and reversible airflow obstruction. Subgroups of asthma patients develop airflow obstruction that is irreversible or only partially reversible and experience an accelerated rate of lung function decline. The structural changes in the airways of these patients are referred to as airway remodeling. All elements of the airway wall are involved, and remodeled airway wall thickness is substantially increased compared to normal control airways. Airway remodeling is thought to contribute to the subphenotypes of irreversible airflow obstruction and airway hyperresponsiveness, and it has been associated with increased disease severity. Reversal of remodeling is therefore of paramount therapeutic importance, and mechanisms responsible for airway remodeling are feasible therapeutic targets for asthma treatment. This paper will focus on our current understanding of the mechanisms of airway remodeling in asthma and potential targets for future intervention.
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23

Royce, Simon G., Anna M. Tominaga, Matthew Shen, Krupesh P. Patel, Brooke M. Huuskes, Rebecca Lim, Sharon D. Ricardo e Chrishan S. Samuel. "Serelaxin improves the therapeutic efficacy of RXFP1-expressing human amnion epithelial cells in experimental allergic airway disease". Clinical Science 130, n. 23 (20 ottobre 2016): 2151–65. http://dx.doi.org/10.1042/cs20160328.

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Abstract (sommario):
We have identified combination cell-based therapies that effectively treat the airway inflammation and airway remodelling (structural changes) that contribute to airway obstruction and related airway hyperresponsiveness in murine chronic allergic airways.
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24

Cailleau, Loic, Thomas Geeraerts, Vincent Minville, Olivier Fourcade, Thomas Fernandez, Jean Etienne Bazin, Linden Baxter et al. "Is there a benefit for anesthesiologists of adding difficult airway scenarios for learning fiberoptic intubation skills using virtual reality training? A randomized controlled study". PLOS ONE 18, n. 1 (27 gennaio 2023): e0281016. http://dx.doi.org/10.1371/journal.pone.0281016.

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Abstract (sommario):
Fiberoptic intubation for a difficult airway requires significant experience. Traditionally only normal airways were available for high fidelity bronchoscopy simulators. It is not clear if training on difficult airways offers an advantage over training on normal airways. This study investigates the added value of difficult airway scenarios during virtual reality fiberoptic intubation training. A prospective multicentric randomized study was conducted 2019 to 2020, among 86 inexperienced anesthesia residents, fellows and staff. Two groups were compared: Group N (control, n = 43) first trained on a normal airway and Group D (n = 43) first trained on a normal, followed by three difficult airways. All were then tested by comparing their ORSIM® scores on 5 scenarios (1 normal and 4 difficult airways). The final evaluation ORSIM® score for the normal airway testing scenario was significantly higher for group N than group D: median score 76% (IQR 56.5–90) versus 58% (IQR 51.5–69, p = 0.0039), but there was no difference in ORSIM® scores for the difficult intubation testing scenarios. A single exposure to each of 3 different difficult airway scenarios did not lead to better fiberoptic intubation skills on previously unseen difficult airways, when compared to multiple exposures to a normal airway scenario. This finding may be due to the learning curve of approximately 5–10 exposures to a specific airway scenario required to reach proficiency.
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25

Kott, Kayleen S., Kent E. Pinkerton, John M. Bric, Charles G. Plopper, Krishna P. Avadhanam e Jesse P. Joad. "Methacholine responsiveness of proximal and distal airways of monkeys and rats using videomicrometry". Journal of Applied Physiology 92, n. 3 (1 marzo 2002): 989–96. http://dx.doi.org/10.1152/japplphysiol.00415.2001.

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Abstract (sommario):
Rat and monkey are species that are used in models of human airway hyperresponsiveness. However, the wall structures of rat and monkey airways are different from each other, with that of the monkey more closely resembling that of humans. We hypothesized that differences in wall structure would explain differences in airway responsiveness. Using videomicrometry, we measured airway luminal area in lung slices to compare proximal and distal airway responsiveness to methacholine in the rat and monkey. The airway type was then histologically identified. Proximal airways of the young rat and monkey were equally responsive to methacholine. In contrast, respiratory bronchioles of monkeys were less responsive than were their proximal bronchi, whereas the distal bronchioles of rats were more responsive than their proximal bronchioles. Both proximal and distal airways of younger monkeys were more responsive than those of older monkeys. Airway heterogeneity in young monkeys was greatest with regard to degree of airway closure of respiratory bronchioles. We conclude that responsiveness to methacholine varies with airway wall structure and location.
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26

Kirchner, K. K., e J. T. McBride. "Changes in airway length after unilateral pneumonectomy in weanling ferrets". Journal of Applied Physiology 68, n. 1 (1 gennaio 1990): 187–92. http://dx.doi.org/10.1152/jappl.1990.68.1.187.

Testo completo
Abstract (sommario):
We have previously shown that airway cross-sectional area increases 15-20% after pneumonectomy in weanling ferrets by measuring bronchial casts. We have now reanalyzed these same casts to quantitate changes in airway length after pneumonectomy. In each cast the distance from each of 120 airways to the terminal bronchiole along its axial pathway was measured. The relationship between the logarithm of this distance and that of the fraction of the lobe subtended by an airway could be described by a quadratic equation with a correlation coefficient greater than 0.85. Subsegmental and more distal airways of postpneumonectomy animals were 33-47% longer than those of controls. Overall the main axial pathway of airways in the left lower lobes was 12% longer in operated animals, but this increase was primarily accounted for by an increase in the length of the more peripheral airways. Central airways were little if any longer in operated animals. After pneumonectomy in weanling ferrets, subsegmental and peripheral airway lengths increase to a greater degree than lung volume and airway cross-sectional area, whereas central airway lengths increase to a lesser extent if at all. The mechanisms responsible for this difference between central and intralobar compensatory airway growth are unknown.
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27

Gunst, S. J., D. O. Warner, T. A. Wilson e R. E. Hyatt. "Parenchymal interdependence and airway response to methacholine in excised dog lobes". Journal of Applied Physiology 65, n. 6 (1 dicembre 1988): 2490–97. http://dx.doi.org/10.1152/jappl.1988.65.6.2490.

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Abstract (sommario):
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.
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28

Sheel, A. William, Jordan A. Guenette, Ren Yuan, Lukas Holy, John R. Mayo, Annette M. McWilliams, Stephen Lam e Harvey O. Coxson. "Evidence for dysanapsis using computed tomographic imaging of the airways in older ex-smokers". Journal of Applied Physiology 107, n. 5 (novembre 2009): 1622–28. http://dx.doi.org/10.1152/japplphysiol.00562.2009.

Testo completo
Abstract (sommario):
We sought to determine the relationship between lung size and airway size in men and women of varying stature. We also asked if men and women matched for lung size would still have differences in airway size and if so where along the pulmonary airway tree would these differences exist. We used computed tomography to measure airway luminal areas of the large and central airways. We determined airway luminal areas in men ( n = 25) and women ( n = 25) who were matched for age, body mass index, smoking history, and pulmonary function and in a separate set of men ( n = 10) and women ( n = 11) who were matched for lung size. Men had greater values for the larger airways and many of the central airways. When male and female subjects were pooled there were significant associations between lung size and airway size. Within the male and female groups the magnitudes of these associations were decreased or nonsignificant. In males and females matched for lung size women had significantly smaller airway luminal areas. The larger conducting airways in females are significantly smaller than those of males even after controlling for lung size.
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29

Martin, J. G., A. Opazo-Saez, T. Du, R. Tepper e D. H. Eidelman. "In vivo airway reactivity: predictive value of morphological estimates of airway smooth muscle". Canadian Journal of Physiology and Pharmacology 70, n. 4 (1 aprile 1992): 597–601. http://dx.doi.org/10.1139/y92-076.

Testo completo
Abstract (sommario):
Airway responsiveness to methacholine and other bronchoconstrictors is highly variable within and among species. The aim of the experiments in this report was to evaluate the importance of the quantity of airway smooth muscle as a determinant of intra- and inter-species variability in airway responsiveness. To do this we established concentration–response curves to methacholine in a sample of normal guinea pigs as well as in rat, rabbit, and dog. After challenge we excised the lungs for the quantitation of smooth muscle by morphometry. Animals were anesthetized with pentobarbital and mechanically ventilated using a Harvard ventilator. Aerosols of methacholine were administered in progressively doubling concentrations from 0.0625 to 256 mg/mL for a period of 30 s for each concentration. The maximal response, determined from pulmonary resistance (RL), and the concentration of methacholine required to effect 50% of the maximal RL were determined. After provocation testing the lungs were removed and fixed with 10% Formalin. Midsagittal sections and parahilar sections were stained with hematoxylin–phloxine–saffron for microscopic examination of smooth muscle. The images of all airways in the sections were traced using a camera lucida side-arm attachment and digitized using commercial software. The area of the airway wall occupied by smooth muscle was determined and standardized for airway size by dividing it by the square of the epithelial basement membrane length. The variability in airway smooth muscle in the intraparenchymal airways was significantly greater between than within individual guinea pigs (n = 13). This was not true of extraparenchymal airways. There was a significant relationship between the quantity of airway smooth muscle in the intraparenchymal cartilaginous airways and the EC50 but not the maximal value of resistance (Rmax). In contrast there was a statistically significant positive correlation between Rmax and airway smooth muscle for all species. There was also a significant inverse correlation between EC50 and airway smooth muscle for all species. We conclude that airway smooth muscle appears to be an important determinant of inter-animal differences in sensitivity of guinea pigs to aerosolized methacholine. Smooth muscle also appears to be a determinant of interspecies differences in both sensitivity and maximal responses to methacholine.Key words: airways responsiveness, mechanical determinants, limited bronchoconstriction, methacholine, morphometry.
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30

Royce, Simon G., Yu R. Miao, Melissa Lee, Chrishan S. Samuel, Geoffrey W. Tregear e Mimi L. K. Tang. "Relaxin Reverses Airway Remodeling and Airway Dysfunction in Allergic Airways Disease". Endocrinology 150, n. 6 (12 febbraio 2009): 2692–99. http://dx.doi.org/10.1210/en.2008-1457.

Testo completo
Abstract (sommario):
Mice deficient in the antifibrotic hormone relaxin develop structural changes in the airway that resemble airway remodeling, and demonstrate exaggerated remodeling changes in models of allergic airways disease (AAD). Relaxin expression in asthma has not been previously studied. We evaluated the efficacy of relaxin in the treatment of established airway remodeling in a mouse model of AAD. Relaxin expression in mouse AAD was also examined by immunohistochemistry and real-time PCR. BALB/c mice with established AAD were treated with relaxin or vehicle control (sc for 14 d), and effects on airway remodeling, airway inflammation, and airway hyperresponsiveness (AHR) were assessed. Relaxin expression was significantly reduced in the airways of mice with AAD compared with controls. Recombinant relaxin treatment in a mouse model of AAD reversed collagen deposition and epithelial thickening, and significantly improved AHR (all P &lt; 0.05 vs. vehicle control), but did not influence airway inflammation or goblet cell hyperplasia. Relaxin treatment was associated with increased matrix metalloproteinase-2 levels, suggesting a possible mechanism for its antifibrotic effects. Endogenous relaxin expression is decreased in murine AAD, whereas exogenous relaxin represents a novel treatment capable of reversing established airway remodeling and AHR.
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31

Noble, Peter B., Robyn L. Jones, Alvenia Cairncross, John G. Elliot, Howard W. Mitchell, Alan L. James e Peter K. McFawn. "Airway narrowing and bronchodilation to deep inspiration in bronchial segments from subjects with and without reported asthma". Journal of Applied Physiology 114, n. 10 (15 maggio 2013): 1460–71. http://dx.doi.org/10.1152/japplphysiol.01489.2012.

Testo completo
Abstract (sommario):
The present study presents preliminary findings on how structural/functional abnormalities of the airway wall relate to excessive airway narrowing and reduced bronchodilatory response to deep inspiration (DI) in subjects with a history of asthma. Bronchial segments were acquired from subjects undergoing surgery, mostly to remove pulmonary neoplasms. Subjects reported prior doctor-diagnosed asthma ( n = 5) or had no history of asthma ( n = 8). In vitro airway narrowing in response to acetylcholine was assessed to determine maximal bronchoconstriction and sensitivity, under static conditions and during simulated tidal and DI maneuvers. Fixed airway segments were sectioned for measurement of airway wall dimensions, particularly the airway smooth muscle (ASM) layer. Airways from subjects with a history of asthma had increased ASM ( P = 0.014), greater maximal airway narrowing under static conditions ( P = 0.003), but no change in sensitivity. Maximal airway narrowing was positively correlated with the area of the ASM layer ( r = 0.58, P = 0.039). In tidally oscillating airways, DI produced bronchodilation in airways from the control group ( P = 0.0001) and the group with a history of asthma ( P = 0.001). While bronchodilation to DI was reduced with increased airway narrowing ( P = 0.02; r = −0.64)), when the level of airway narrowing was matched, there was no difference in magnitude of bronchodilation to DI between groups. Results suggest that greater ASM mass in asthma contributes to exaggerated airway narrowing in vivo. In comparison, the airway wall in asthma may have a normal response to mechanical stretch during DI. We propose that increased maximal airway narrowing and the reduced bronchodilatory response to DI in asthma are independent.
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32

Li, Xiaopeng, Xiao Xiao Tang, Luis G. Vargas Buonfiglio, Alejandro P. Comellas, Ian M. Thornell, Shyam Ramachandran, Philip H. Karp et al. "Electrolyte transport properties in distal small airways from cystic fibrosis pigs with implications for host defense". American Journal of Physiology-Lung Cellular and Molecular Physiology 310, n. 7 (1 aprile 2016): L670—L679. http://dx.doi.org/10.1152/ajplung.00422.2015.

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Abstract (sommario):
While pathological and clinical data suggest that small airways are involved in early cystic fibrosis (CF) lung disease development, little is known about how the lack of cystic fibrosis transmembrane conductance regulator (CFTR) function contributes to disease pathogenesis in these small airways. Large and small airway epithelia are exposed to different airflow velocities, temperatures, humidity, and CO2 concentrations. The cellular composition of these two regions is different, and small airways lack submucosal glands. To better understand the ion transport properties and impacts of lack of CFTR function on host defense function in small airways, we adapted a novel protocol to isolate small airway epithelial cells from CF and non-CF pigs and established an organotypic culture model. Compared with non-CF large airways, non-CF small airway epithelia cultures had higher Cl− and bicarbonate (HCO3−) short-circuit currents and higher airway surface liquid (ASL) pH under 5% CO2 conditions. CF small airway epithelia were characterized by minimal Cl− and HCO3− transport and decreased ASL pH, and had impaired bacterial killing compared with non-CF small airways. In addition, CF small airway epithelia had a higher ASL viscosity than non-CF small airways. Thus, the activity of CFTR is higher in the small airways, where it plays a role in alkalinization of ASL, enhancement of antimicrobial activity, and lowering of mucus viscosity. These data provide insight to explain why the small airways are a susceptible site for the bacterial colonization.
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33

Mahjour, Seyed B., Kazunori Gomi, Busub Lee, Olivier Elemento, Scott Randell e Renat Shaykhiev. "2566 Personalized models of distal airway epithelial-stromal unit in COPD". Journal of Clinical and Translational Science 2, S1 (giugno 2018): 23. http://dx.doi.org/10.1017/cts.2018.106.

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Abstract (sommario):
OBJECTIVES/SPECIFIC AIMS: The objective of this study is to develop patient-derived “personalized” organotypic models of human distal airways, in which basal stem cells (BCs) isolated from the pre-/terminal conducting airway region are co-cultured with autologous stromal cells from the same region to reproduce patient-specific distal airway epithelial-stromal units and their remodeling in COPD. METHODS/STUDY POPULATION: We established a protocol to isolate and propagate epithelial BCs, fibroblasts, and endothelial cells from the distal airways of normal and COPD lung donors. Heterogeneous cellular and molecular phenotypes in the human distal airways were characterized using immunofluorescence and single-cell RNA sequencing. Patient-specific distal airway epithelial-stromal units were reconstructed by co-culturing BCs and autologous stromal cells using an air-liquid interface-based airway wall model and a bronchosphere-based 3D distal airway organoid assay. RESULTS/ANTICIPATED RESULTS: Histologic analysis of derived epithelial-stromal units revealed heterogeneous patient-specific phenotypes characterized by hypo-/hyper-/metaplastic lesions (hypo-regenerative phenotype, mucous cell hyperplasia, squamous metaplasia, distal-to-proximal repatterning) in the epithelial compartment, accompanied, in some samples, by stromal remodeling. Candidate epithelial-stromal cross-talk mechanisms were identified using quantitative real-time RT-PCR analysis of autologous epithelial and stromal compartments of established patient-specific distal airway unit models. DISCUSSION/SIGNIFICANCE OF IMPACT: Epithelial and stromal cells isolated from distal airways of subjects with and without COPD can be assembled into functional, organ-level tissue which mimics the architecture of human distal airways and, in patients with COPD, reproduces several distal airway remodeling phenotypes. Patient-specific models of distal airway epithelial-stromal cross-talk established in this study can be used to identify candidate pathways that mediate disease-relevant airway remodeling and potentially utilized as pre-clinical platforms for developing personalized therapeutic approaches to suppress the progression of distal airway remodeling in chronic lung diseases, including COPD.
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34

Barnes, P. J. "Muscarinic receptors in airways: recent developments". Journal of Applied Physiology 68, n. 5 (1 maggio 1990): 1777–85. http://dx.doi.org/10.1152/jappl.1990.68.5.1777.

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Abstract (sommario):
Recently there have been important advances in our understanding of muscarinic receptors in airways that have important implications for understanding airway control and for future therapy of airway diseases. The transduction mechanisms involved in muscarinic receptor activation are now better understood. Receptor-linked phosphoinositide hydrolysis leads to release of calcium ions from intracellular stores, resulting in contraction of airway smooth muscle. At least five subtypes of muscarinic receptor have now been cloned, although only three subtypes can be distinguished pharmacologically. M1 receptors are facilitatory to neurotransmission in airway parasympathetic ganglion cells and have also been identified in airway submucosal glands and on the alveolar walls of human lung. M2 receptors are located on postganglionic nerves and function as powerful feedback inhibitory receptors (autoreceptors) that are likely to be involved in modulation of reflex bronchoconstriction. These receptors may be dysfunctional in asthmatic airways. M3 receptors are present on airway smooth muscle and submucosal glands and mediate the classical muscarinic effects in airways. Molecular biology techniques should now allow further study of the factors that regulate transcription and expression of muscarinic receptors in airways.
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35

Phung, Thien-Khoi N., Scott E. Sinclair, Patrudu Makena, Robert C. Molthen e Christopher M. Waters. "Dynamic airway constriction in rats: heterogeneity and response to deep inspiration". American Journal of Physiology-Lung Cellular and Molecular Physiology 317, n. 1 (1 luglio 2019): L39—L48. http://dx.doi.org/10.1152/ajplung.00050.2019.

Testo completo
Abstract (sommario):
Airway narrowing due to hyperresponsiveness severely limits gas exchange in patients with asthma. Imaging studies in humans and animals have shown that bronchoconstriction causes patchy patterns of ventilation defects throughout the lungs, and several computational models have predicted that these regions are due to constriction of smaller airways. However, these imaging approaches are often limited in their ability to capture dynamic changes in small airways, and the patterns of constriction are heterogeneous. To directly investigate regional variations in airway narrowing and the response to deep inspirations (DIs), we utilized tantalum dust and microfocal X-ray imaging of rat lungs to obtain dynamic images of airways in an intact animal model. Airway resistance was simultaneously measured using the flexiVent system. Custom-developed software was used to track changes in airway diameters up to generation 19 (~0.3–3 mm). Changes in diameter during bronchoconstriction were then measured in response to methacholine (MCh) challenge. In contrast with the model predictions, we observed significantly greater percent constriction in larger airways in response to MCh challenge. Although there was a dose-dependent increase in total respiratory resistance with MCh, the percent change in airway diameters was similar for increasing doses. A single DI following MCh caused a significant reduction in resistance but did not cause a significant increase in airway diameters. Multiple DIs did, however, cause significant increases in airway diameters. These measurements allowed us to directly quantify dynamic changes in airways during bronchoconstriction and demonstrated greater constriction in larger airways.
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36

Ramchandani, R., X. Shen, C. L. Elmsley, W. T. Ambrosius, S. J. Gunst e R. S. Tepper. "Differences in airway structure in immature and mature rabbits". Journal of Applied Physiology 89, n. 4 (1 ottobre 2000): 1310–16. http://dx.doi.org/10.1152/jappl.2000.89.4.1310.

Testo completo
Abstract (sommario):
Our laboratory has previously demonstrated that maximal bronchoconstriction produces a greater degree of airway narrowing in immature than in mature rabbit lungs (33). To determine whether these maturational differences could be related to airway structure, we compared the fraction of the airway wall occupied by airway smooth muscle (ASM) and cartilage, the proportion of wall area internal to ASM, and the number of alveolar attachments to the airways, from mature and immature (6-mo- and 4-wk-old, respectively) rabbit lungs that were formalin fixed at total lung capacity. The results demonstrate that the airway walls of immature rabbits had a greater percentage of smooth muscle, a lower percentage of cartilage, and fewer alveolar attachments compared with mature rabbit airways; however, we did not find maturational differences in the airway wall thickness relative to airway size. We conclude that structural differences in the airway wall may contribute to the greater airway narrowing observed in immature rabbits during bronchoconstriction.
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37

Pascoe, C. D., L. Wang, H. T. Syyong e P. D. Paré. "A Brief History of Airway Smooth Muscle’s Role in Airway Hyperresponsiveness". Journal of Allergy 2012 (18 ottobre 2012): 1–8. http://dx.doi.org/10.1155/2012/768982.

Testo completo
Abstract (sommario):
A link between airway smooth muscle (ASM) and airway hyperresponsiveness (AHR) in asthma was first postulated in the midnineteenth century, and the suspected link has garnered ever increasing interest over the years. AHR is characterized by excessive narrowing of airways in response to nonspecific stimuli, and it is the ASM that drives this narrowing. The stimuli that can be used to demonstrate AHR vary widely, as do the potential mechanisms by which phenotypic changes in ASM or nonmuscle factors can contribute to AHR. In this paper, we review the history of research on airway smooth muscle’s role in airway hyperresponsiveness. This research has ranged from analyzing the quantity of ASM in the airways to testing for alterations in the plastic behavior of smooth muscle, which distinguishes it from skeletal and cardiac muscles. This long history of research and the continued interest in this topic mean that the precise role of ASM in airway responsiveness remains elusive, which makes it a pertinent topic for this collection of articles.
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38

Noble, Peter B., Adrian R. West, Robert A. McLaughlin, Julian J. Armstrong, Sven Becker, Peter K. McFawn, Jonathan P. Williamson et al. "Airway narrowing assessed by anatomical optical coherence tomography in vitro: dynamic airway wall morphology and function". Journal of Applied Physiology 108, n. 2 (febbraio 2010): 401–11. http://dx.doi.org/10.1152/japplphysiol.00511.2009.

Testo completo
Abstract (sommario):
Regulation of airway caliber by lung volume or bronchoconstrictor stimulation is dependent on physiological, structural, and mechanical events within the airway wall, including airway smooth muscle (ASM) contraction, deformation of the mucosa and cartilage, and tensioning of elastic matrices linking wall components. Despite close association between events in the airway wall and the resulting airway caliber, these have typically been studied separately: the former primarily using histological approaches, the latter with a range of imaging modalities. We describe a new optical technique, anatomical optical coherence tomography ( aOCT), which allows changes at the luminal surface (airway caliber) to be temporally related to corresponding dynamic movements within the airway wall. A fiber-optic aOCT probe was inserted into the lumen of isolated, liquid-filled porcine airways. It was used to image the response to ASM contraction induced by neural stimulation and to airway inflation and deflation. Comparisons with histology indicated that aOCT provided high-resolution images of the airway lumen including mucosal folds, the entire inner wall (mucosa and ASM), and partially the cartilaginous outer wall. Airway responses assessed by aOCT revealed several phenomena in “live” airways (i.e., not fixed) previously identified by histological investigations of fixed tissue, including a geometric relationship between ASM shortening and luminal narrowing, and sliding and bending of cartilage plates. It also provided direct evidence for distensibility of the epithelial membrane and anisotropic behavior of the airway wall. Findings suggest that aOCT can be used to relate changes in airway caliber to dynamic events in the wall of airways.
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39

Riley, R. H., T. Strang e S. Rao. "Survey of Airway Skills of Surgeons in Western Australia". Anaesthesia and Intensive Care 37, n. 4 (luglio 2009): 630–33. http://dx.doi.org/10.1177/0310057x0903700406.

Testo completo
Abstract (sommario):
Our objective was to survey all consultant surgeons, including obstetricians/gynaecologists, in the State of Western Australia to assess their experience with, and readiness to assist anaesthetists with a difficult or failed airway. Survey questionnaires were mailed to all surgeons registered in Western Australia (n=445). A total of 238 responses (53%) were received, mostly from general surgeons, obstetrician/gynaecologists and orthopaedic surgeons. Forty percent had provided non-surgical assistance with a difficult airway and 60% had assisted with a surgical airway. All ear, nose and throat surgeons who responded to the survey had assisted with an emergency surgical airway and 47 surgeons reported having performed six or more surgical airways. However, 26% of respondents had never performed a surgical airway and 37% did not feel confident in performing an urgent surgical airway. Seven percent of respondents reported witnessing a failed airway that resulted in death or neurological damage. Seventy percent of respondents had undergone formal training in tracheostomy and 26% had advanced trauma life support or early management of severe trauma training. These findings indicate that surgeons in Western Australia perform surgical airways infrequently and only occasionally assist anaesthetists with difficult airway management. However, some surgeons lack confidence and training in surgical airway management. Because anaesthetists cannot always rely on their surgical colleagues to provide a surgical airway during a crisis, we recommend that anaesthetists discuss airway management with their surgical colleagues for all patients with identified difficult airways and that anaesthesia training should include surgical airway management.
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40

Titze, Ingo R., Anil Palaparthi, Karin Cox, Amanda Stark, Lynn Maxfield e Brian Manternach. "Vocalization with semi-occluded airways is favorable for optimizing sound production". PLOS Computational Biology 17, n. 3 (29 marzo 2021): e1008744. http://dx.doi.org/10.1371/journal.pcbi.1008744.

Testo completo
Abstract (sommario):
Vocalization in mammals, birds, reptiles, and amphibians occurs with airways that have wide openings to free-space for efficient sound radiation, but sound is also produced with occluded or semi-occluded airways that have small openings to free-space. It is hypothesized that pressures produced inside the airway with semi-occluded vocalizations have an overall widening effect on the airway. This overall widening then provides more opportunity to produce wide-narrow contrasts along the airway for variation in sound quality and loudness. For human vocalization described here, special emphasis is placed on the epilaryngeal airway, which can be adjusted for optimal aerodynamic power transfer and for optimal acoustic source-airway interaction. The methodology is three-fold, (1) geometric measurement of airway dimensions from CT scans, (2) aerodynamic and acoustic impedance calculation of the airways, and (3) simulation of acoustic signals with a self-oscillating computational model of the sound source and wave propagation.
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41

Lambert, R. K., R. Ramchandani, X. Shen, S. J. Gunst e R. S. Tepper. "Computational model of airway narrowing: mature vs. immature rabbit". Journal of Applied Physiology 93, n. 2 (1 agosto 2002): 611–19. http://dx.doi.org/10.1152/japplphysiol.00063.2002.

Testo completo
Abstract (sommario):
Immature rabbits have greater maximal airway narrowing and greater maximal fold increases in airway resistance during bronchoconstriction than mature animals. We have previously demonstrated that excised immature rabbit lungs have more distensible airways, a lower shear modulus, and structural differences in the relative composition and thickness of anatomically similar airways. In the present study, we incorporated anatomic and physiological data for mature and immature rabbits into a computational model of airway narrowing. We then investigated the relative importance of maturational differences in these factors as determinants of the greater airway narrowing that occurs in the immature animal. The immature model demonstrated greater sensitivity to agonist, as well as a greater maximal fold increase in airway resistance. Exchanging values for airway compliance between the mature and immature models resulted in the mature model exhibiting a greater maximal airway response than the immature model. In contrast, exchanging the shear moduli or the composition of the airway wall relative to the airway size produced relatively small changes in airway reactivity. Our results strongly suggest that the mechanical properties of the airway, i.e., greater compliance of the immature airway, can be an important factor contributing to the greater airway narrowing of the immature animal.
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42

Chapman, David G., Norbert Berend, Gregory G. King e Cheryl M. Salome. "Effect of deep inspiration avoidance on ventilation heterogeneity and airway responsiveness in healthy adults". Journal of Applied Physiology 110, n. 5 (maggio 2011): 1400–1405. http://dx.doi.org/10.1152/japplphysiol.00855.2010.

Testo completo
Abstract (sommario):
The mechanisms by which deep inspiration (DI) avoidance increases airway responsiveness in healthy subjects are not known. DI avoidance does not alter respiratory mechanics directly; however, computational modeling has predicted that DI avoidance would increase baseline ventilation heterogeneity. The aim was to determine if DI avoidance increased baseline ventilation heterogeneity and whether this correlated with the increase in airway responsiveness. Twelve healthy subjects had ventilation heterogeneity measured by multiple-breath nitrogen washout (MBNW) before and after 20 min of DI avoidance. This was followed by another 20-min period of DI avoidance before the inhalation of a single methacholine dose. The protocol was repeated on a separate day with the addition of five DIs at the end of each of the two periods of DI avoidance. Baseline ventilation heterogeneity in convection-dependent and diffusion-convection-dependent airways was calculated from MBNW. The response to methacholine was measured by the percent fall in forced expiratory volume in 1 s/forced vital capacity (FVC) (airway narrowing) and percent fall in FVC (airway closure). DI avoidance increased baseline diffusion-convection-dependent airways ( P = 0.02) but did not affect convection-dependent airways ( P = 0.9). DI avoidance increased both airway closure ( P = 0.002) and airway narrowing ( P = 0.02) during bronchial challenge. The increase in diffusion-convection-dependent airways due to DI avoidance did not correlate with the increase in either airway narrowing ( rs = 0.14) or airway closure ( rs = 0.12). These findings suggest that DI avoidance increases diffusion-convection-dependent ventilation heterogeneity that is not associated with the increase in airway responsiveness. We speculate that DI avoidance reduces surfactant release, which increases peripheral ventilation heterogeneity and also predisposes to peripheral airway closure.
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43

Olson, L. E. "Small airway pressure-diameter relationships during nonhomogeneous lung lobe inflation". Journal of Applied Physiology 62, n. 6 (1 giugno 1987): 2377–82. http://dx.doi.org/10.1152/jappl.1987.62.6.2377.

Testo completo
Abstract (sommario):
The pressure-diameter behavior of airways within a collaterally ventilating segment of lung was evaluated radiographically in 12 excised dog lung lobes. The results were compared with the pressure-diameter behavior of airways in a lung region adjacent to the collaterally ventilating segment. Airways in each lung region were dusted with powdered tantalum, and airway diameters were measured during homogeneous and nonhomogeneous lobe inflation. Intrasegmental and extrasegmental airways behaved similarly during homogeneous lobe inflation; airway diameter increased as alveolar pressure increased. The lobe was inflated nonhomogeneously by raising pressure in the collaterally ventilating segment (Ps) while maintaining pressure at the lobar bronchus (Pao) constant at 5, 10, or 15 cmH2O. Increasing Ps at constant Pao reciprocally affected intrasegmental and extrasegmental airways. When Pao was low, intrasegmental airways were expanded, and extrasegmental airways were compressed when Ps was raised. When Pao was high, airway diameter was unaffected by increasing Ps presumably because the airways were already maximally expanded. A comparison of diameters during homogenous and nonhomogenous lobe inflation suggests a very small interdependence effect from the parenchyma surrounding the collaterally ventilating segment. These results demonstrate the combined effects of parenchymal properties and airway pressure-diameter relationships in determining the effect of local lung distortion on airway function.
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44

Ramchandani, R., X. Shen, S. J. Gunst e R. S. Tepper. "Comparison of elastic properties and contractile responses of isolated airway segments from mature and immature rabbits". Journal of Applied Physiology 95, n. 1 (luglio 2003): 265–71. http://dx.doi.org/10.1152/japplphysiol.00362.2002.

Testo completo
Abstract (sommario):
Immature rabbits have greater maximal airway narrowing with bronchoconstriction in vivo compared with mature animals. As isolated immature lungs have a lower shear modulus, it is unclear whether the greater airway narrowing in the immature lung is secondary to less tethering between the airways and the lung parenchyma or to differences in the mechanical properties of the mature and immature airways. In the present study, we compared the mechanical properties of fluid-filled, isolated, intraparenchymal airway segments of the same generation from mature and immature rabbits. Stimulation with ACh resulted in greater airway narrowing in immature than mature bronchi. The immature bronchi were more compliant, had a lower resting airway volume, and were more collapsible compared with the mature bronchi. When the airways were contracted with ACh under isovolume conditions, the immature bronchi generated greater active pressure, and they were more sensitive to ACh than were mature bronchi. Our results suggest that maturational differences in the structure and function of the airways in the absence of the lung parenchyma can account for the greater maximal narrowing of immature than mature airways in vivo.
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45

Kaczka, David W., Robert H. Brown e Wayne Mitzner. "Assessment of heterogeneous airway constriction in dogs: a structure-function analysis". Journal of Applied Physiology 106, n. 2 (febbraio 2009): 520–30. http://dx.doi.org/10.1152/japplphysiol.90576.2008.

Testo completo
Abstract (sommario):
Obstructive lung diseases are often characterized by heterogeneous patterns of bronchoconstriction, although specific relationships between structural heterogeneity and lung function have yet to be established. We measured respiratory input impedance (Zrs) in eight anesthetized dogs using broadband forced oscillations at baseline and during intravenous methacholine (MCh) infusion. We also obtained high-resolution computed tomographic (HRCT) scans in 4 dogs and identified 20–30 individual airway segments in each animal. The Zrs spectra and HRCT images were obtained before and 5 min following a deep inspiration (DI) to 35 cmH2O. Each Zrs spectrum was fitted with two different models of the respiratory system: 1) a lumped airways model consisting of a single airway compartment, and 2) a distributed airways model incorporating a continuous distribution of airway resistances. For the latter, we found that the mean level and spread of airway resistances increased with MCh dose. Whereas a DI had no effect on average airway resistance during MCh infusion, it did increase the level of airway heterogeneity. At baseline and low-to-moderate doses of MCh, the lumped airways model was statistically more appropriate to describe Zrs in the majority of dogs. At the highest doses of MCh, the distributed airways model provided a superior fit in half of the dogs. There was a significant correlation between heterogeneity assessed with inverse modeling and the standard deviation of airway diameters obtained from HRCT. These data demonstrate that increases in airway heterogeneity as assessed with forced oscillations and inverse modeling can be linked to specific structural alterations in airway diameters.
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46

Stewart, Peter S., e Oliver E. Jensen. "Patterns of recruitment and injury in a heterogeneous airway network model". Journal of The Royal Society Interface 12, n. 111 (ottobre 2015): 20150523. http://dx.doi.org/10.1098/rsif.2015.0523.

Testo completo
Abstract (sommario):
In respiratory distress, lung airways become flooded with liquid and may collapse due to surface-tension forces acting on air–liquid interfaces, inhibiting gas exchange. This paper proposes a mathematical multiscale model for the mechanical ventilation of a network of occluded airways, where air is forced into the network at a fixed tidal volume, allowing investigation of optimal recruitment strategies. The temporal response is derived from mechanistic models of individual airway reopening, incorporating feedback on the airway pressure due to recruitment. The model accounts for stochastic variability in airway diameter and stiffness across and between generations. For weak heterogeneity, the network is completely ventilated via one or more avalanches of recruitment (with airways recruited in quick succession), each characterized by a transient decrease in the airway pressure; avalanches become more erratic for airways that are initially more flooded. However, the time taken for complete ventilation of the network increases significantly as the network becomes more heterogeneous, leading to increased stresses on airway walls. The model predicts that the most peripheral airways are most at risk of ventilation-induced damage. A positive-end-expiratory pressure reduces the total recruitment time but at the cost of larger stresses exerted on airway walls.
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47

Harvey, Brian C., Harikrishnan Parameswaran e Kenneth R. Lutchen. "Can breathing-like pressure oscillations reverse or prevent narrowing of small intact airways?" Journal of Applied Physiology 119, n. 1 (1 luglio 2015): 47–54. http://dx.doi.org/10.1152/japplphysiol.01100.2014.

Testo completo
Abstract (sommario):
Periodic length fluctuations of airway smooth muscle during breathing are thought to modulate airway responsiveness in vivo. Recent animal and human intact airway studies have shown that pressure fluctuations simulating breathing can only marginally reverse airway narrowing and are ineffective at protecting against future narrowing. However, these previous studies were performed on relatively large (>5 mm diameter) airways, which are inherently stiffer than smaller airways for which a preponderance of airway constriction in asthma likely occurs. The goal of this study was to determine the effectiveness of breathing-like transmural pressure oscillations to reverse induced narrowing and/or protect against future narrowing of smaller, more compliant intact airways. We constricted smaller (luminal diameter = 2.92 ± 0.29 mm) intact airway segments twice with ACh (10−6 M), once while applying tidal-like pressure oscillations (5–15 cmH2O) before, during, and after inducing constriction (Pre + Post) and again while only imposing the tidal-like pressure oscillation after induced constriction (Post Only). Smaller airways were 128% more compliant than previously studied larger airways. This increased compliance translated into 196% more strain and 76% greater recovery (41 vs. 23%) because of tidal-like pressure oscillations. Larger pressure oscillations (5–25 cmH2O) caused more recovery (77.5 ± 16.5%). However, pressure oscillations applied before and during constriction resulted in the same steady-state diameter as when pressure oscillations were only applied after constriction. These data show that reduced straining of the airways before a challenge likely does not contribute to the emergence of airway hyperreactivity observed in asthma but may serve to sustain a given level of constriction.
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48

McKay, Karen O., Barry R. Wiggs, Peter D. Paré e Roger D. Kamm. "Zero-stress state of intra- and extraparenchymal airways from human, pig, rabbit, and sheep lung". Journal of Applied Physiology 92, n. 3 (1 marzo 2002): 1261–66. http://dx.doi.org/10.1152/japplphysiol.00131.2001.

Testo completo
Abstract (sommario):
Alterations in airway wall anatomic properties and the consequential effects on airway narrowing have been assessed by use of computational models. In these models, it is generally assumed that at zero transmural pressure the airway wall exists in a zero-stress state. Many studies have shown that this is often not the case, as evidenced by a nonzero opening angle. In this study, we measured the opening angle of airway rings at zero transmural pressure to test this assumption. The airway tree was dissected from human, pig, sheep, and rabbit lungs. Airways were excised from the tree, and the opening angle was measured. There were obvious species and regional differences in opening angle. Rabbit airways from both extraparenchymal and intraparenchymal sites exhibited marked opening angles (7–82°). Extraparenchymal airways from sheep had large opening angles (up to 50°), but ovine intraparenchymal airways had small opening angles. Measurable opening angles were rarely observed in human and porcine airways of any size. The assumption of a stable zero-stress state at zero transmural pressure is therefore valid for human and porcine, but not rabbit and sheep, airways.
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49

Reihill, James A., Lisa E. J. Douglas e S. Lorraine Martin. "Modulation of Ion Transport to Restore Airway Hydration in Cystic Fibrosis". Genes 12, n. 3 (22 marzo 2021): 453. http://dx.doi.org/10.3390/genes12030453.

Testo completo
Abstract (sommario):
Cystic fibrosis (CF) is a life-limiting genetic disorder caused by loss-of-function mutations in the gene which codes for the CF transmembrane conductance regulator (CFTR) Cl− channel. Loss of Cl− secretion across the apical membrane of airway lining epithelial cells results in dehydration of the airway surface liquid (ASL) layer which impairs mucociliary clearance (MCC), and as a consequence promotes bacterial infection and inflammation of the airways. Interventions that restore airway hydration are known to improve MCC. Here we review the ion channels present at the luminal surface of airway epithelial cells that may be targeted to improve airway hydration and MCC in CF airways.
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50

Klučka, Jozef, Petr Štourač, Roman Štoudek, Michaela Ťoukálková, Hana Harazim e Martina Kosinová. "Controversies in Pediatric Perioperative Airways". BioMed Research International 2015 (2015): 1–11. http://dx.doi.org/10.1155/2015/368761.

Testo completo
Abstract (sommario):
Pediatric airway management is a challenge in routine anesthesia practice. Any airway-related complication due to improper procedure can have catastrophic consequences in pediatric patients. The authors reviewed the current relevant literature using the following data bases: Google Scholar, PubMed, Medline (OVID SP), and Dynamed, and the following keywords: Airway/s, Children, Pediatric, Difficult Airways, and Controversies. From a summary of the data, we identified several controversies: difficult airway prediction, difficult airway management, cuffed versus uncuffed endotracheal tubes for securing pediatric airways, rapid sequence induction (RSI), laryngeal mask versus endotracheal tube, and extubation timing. The data show that pediatric anesthesia practice in perioperative airway management is currently lacking the strong evidence-based medicine (EBM) data that is available for adult subpopulations. A number of procedural steps in airway management are derived only from adult populations. However, the objective is the same irrespective of patient age: proper securing of the airway and oxygenation of the patient.
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