Exercise- and Cold-Induced Asthma

1995 ◽  
Vol 20 (3) ◽  
pp. 300-314 ◽  
Author(s):  
Gordon G. Giesbrecht ◽  
Magdy Younes
Keyword(s):  
Inflammatory Responses ◽  
Late Phase ◽  
Smooth Muscle Contraction ◽  
Phase Response ◽  
Epithelial Damage ◽  
Airway Narrowing ◽  
Respiratory Heat Loss ◽  
Vascular Congestion ◽  
Prostaglandin Release ◽  
Temperature Receptors

Exercise- and cold-induced asthma are commonly recognized respiratory disorders. The asthmatic response includes several factors contributing to airway narrowing, and thus increased airway resistance. These include airway smooth muscle contraction, mucus accumulation, and bronchial vascular congestion as well as epithelial damage and vascular leakage. The etiology for these disorders is nonantigenic. The primary stimulus is probably a combination of airway cooling and drying (leading to hypertonicity of airway lining fluid). Symptoms generally do not occur during the stimulus period (e.g., exercise) itself. This protection may in part be due to increased catecholamine levels during exercise. The early phase response, which occurs 5 to 15 min poststimulus, may be mediated through a combination of (a) direct influences, (b) vagal reflexes triggered by airway sensory receptors, or (c) responses to mediator release. Spontaneous recovery occurs within 30 min to 2 hrs. There is usually a refractory period of about 1 to 2 hrs during which responses to further stimuli are attenuated. This may be due to depletion of histamine and other mediators. As well, prostaglandin release (mediated via LTD4 which is released during exercise) inhibits further airway narrowing. A late phase response has been reported 4 to 10 hrs poststimulus in some patients. These reactions are accompanied by a second release of histamine and other mediators that cause inflammatory responses and epithelial damage. However, the exercise dependence of this response is debated. Key words: respiratory heat loss, hyper osmolarity, pulmonary receptors, temperature receptors, inflammation, epithelial damage

scholarly journals Protective perioperative strategy using a third generation hydroxyethyl starch during surgery in a murine model of liver reperfusion injury

2011 ◽  
Vol 26 (6) ◽  
pp. 456-462
Author(s):  
Dora Catré ◽  
Maria Francelina Lopes ◽  
Celeste Bento ◽  
António Silvério Cabrita
Keyword(s):  
Reperfusion Injury ◽  
Hydroxyethyl Starch ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Histological Study ◽  
Late Phase ◽  
Phase Response ◽  
Volume Control ◽  
Third Generation ◽  
Hepatic Ischemia

PURPOSE: To investigate whether a third generation colloid, hydroxyethyl starch (HES 130/0.4), used for perioperative fluid therapy, protects the rat liver against the late-phase response of ischemia/reperfusion injury (IRI) and if inhibition of neutrophil hepatic infiltration plays a part in this mechanism. METHODS: Wistar rats were used (8 in each group). Three groups had IRI induced by lobar vascular occlusion (60 minutes) and reperfusion (24 hours) and received HES (13 mL/kg iv), 7.5% saline (HS) (13 mL/kg iv) or no fluid. Three other groups were sham-operated and received the same fluid as the test groups. After 24 hours of reperfusion, blood was drawn for alanine aminotransferase (ALT) quantification and ischemic liver samples were taken for histological study (hematoxylin and eosin and chloroacetate staining of neutrophils). RESULTS: HES treatment attenuated the elevation in serum ALT (P=0.001) and reduced the extent of hepatocellular necrosis (P<0.01) compared with the IRI controls. HES-mediated cytoprotection was associated with a decrease of infiltration of neutrophils in the necrotic areas (P<0.05) compared with the untreated IRI rats, but not with the volume control IRI rats (P>0.05). CONCLUSION: Hydroxyethyl starch suppresses inflammatory response and ameliorates the late-phase response of hepatic ischemia/reperfusion injury.

Preconditioning with ethanol prevents postischemic leukocyte-endothelial cell adhesive interactions

2002 ◽  
Vol 283 (3) ◽  
pp. H1019-H1030 ◽  
Author(s):  
Taiji Yamaguchi ◽  
Catherine Dayton ◽  
T. Shigematsu ◽  
Patsy Carter ◽  
Toshikazu Yoshikawa ◽  
...  
Keyword(s):  
Temporal Pattern ◽  
Receptor Agonist ◽  
Inflammatory Responses ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Late Phase ◽  
Ethanol Exposure ◽  
Ethanol Ingestion ◽  
Adhesive Interactions ◽  
Ethanol Ethanol

Long-term ethanol consumption at low to moderate levels exerts cardioprotective effects in the setting of ischemia and reperfusion (I/R). The aims of this study were to determine whether 1) a single orally administered dose of ethanol [ethanol preconditioning (EtOH-PC)] would induce a biphasic temporal pattern of protection (early and late phases) against the inflammatory responses to I/R and 2) adenosine and nitric oxide (NO) act as initiators of the late phase of protection. Ethanol was administered as a bolus to C57BL/6 mice at a dose that achieved a peak plasma concentration of ∼45 mg/dl 30 min after gavage and returned to control levels within 60 min of alcohol ingestion. The superior mesenteric artery was occluded for 45 min followed by 60 min of reperfusion beginning 10 min or 1, 2, 3, 4, or 24 h after ethanol ingestion, and the numbers of fluorescently labeled rolling and firmly adherent (stationary) leukocytes in single postcapillary venules of the small intestine were quantified using intravital microscopic approaches. I/R induced marked increases in leukocyte rolling and adhesion, effects that were attenuated by EtOH-PC 2–3 h before I/R (early phase), absent when assessed after 10 min, 1 h, and 4 h of ethanol ingestion, with an even more powerful late phase of protection reemerging when I/R was induced 24 h later. The anti-inflammatory effects of late EtOH-PC were abolished by treatment with adenosine deaminase, an adenosine A2 (but not A1) receptor antagonist, or a NO synthase (NOS) inhibitor during the period of EtOH-PC. Preconditioning with an adenosine A2 (but not an A1) receptor agonist in lieu of ethanol 24 h before I/R mimicked the protective actions of late phase EtOH-PC. Like EtOH-PC, the effect of preconditioning with an adenosine A2 receptor agonist was abrogated by coincident NOS inhibition. These findings suggest that EtOH-PC induces a biphasic temporal pattern of protection against the proinflammatory effects of I/R. In addition, our observations are consistent with the hypothesis that the late phase of EtOH-PC is triggered by NO formed secondary to adenosine A2 receptor-dependent activation of NOS during the period of ethanol exposure.

scholarly journals Decreased airway narrowing and smooth muscle contraction in hyperresponsive pigs

2002 ◽  
Vol 93 (4) ◽  
pp. 1296-1300 ◽  
Author(s):  
Debra J. Turner ◽  
Peter B. Noble ◽  
Matthew P. Lucas ◽  
Howard W. Mitchell
Keyword(s):  
Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Porcine Model ◽  
Smooth Muscle Contraction ◽  
Airway Wall ◽  
Muscle Contractility ◽  
Smooth Muscle Contractility ◽  
Airway Narrowing

Increased smooth muscle contractility or reduced smooth muscle mechanical loads could account for the excessive airway narrowing and hyperresponsiveness seen in asthma. These mechanisms were investigated by using an allergen-induced porcine model of airway hyperresponsiveness. Airway narrowing to electric field stimulation was measured in isolated bronchial segments, over a range of transmural pressures (0–20 cmH2O). Contractile responses to ACh were measured in bronchial segments and in isolated tracheal smooth muscle strips isolated from control and test (ovalbumin sensitized and challenged) pigs. Test airways narrowed less than controls ( P < 0.0001). Test pigs showed reduced contractility to ACh, both in isolated bronchi ( P < 0.01) and smooth muscle strips ( P < 0.01). Thus isolated airways from pigs exhibiting airway hyperresponsiveness in vivo are hyporesponsive in vitro. The decreased narrowing in bronchi from hyperresponsive pigs may be related to decreased smooth muscle contractility. These data suggest that mechanisms external to the airway wall may be important to the hyperresponsive nature of sensitized lungs.

Nitric Oxide is a Mediator of the Late-Phase Response in an Animal Model of Nasal Allergy

2000 ◽  
Vol 122 (5) ◽  
pp. 706-711 ◽  
Author(s):  
William F. Durland ◽  
Andrew P. Lane ◽  
Kimberly W. Durland ◽  
Timothy L. Smith ◽  
Kenneth L. Johnson ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Inflammatory Cell ◽  
Late Phase ◽  
Phase Response ◽  
Brown Norway ◽  
Nasal Allergy ◽  
Synthase Inhibitor ◽  
Histamine Challenge

The presence of nitric oxide (NO) in the nose is well documented; however, the role of this molecule in nasal physiology is still poorly understood. Our laboratory has previously demonstrated that NO is a mediator of the immediate secretory response to an intranasal histamine challenge in a rat model of nasal allergy. Histamine challenge, however, does not elicit a late-phase response (LPR). To study the role of NO in the LPR, we developed a model of nasal allergy in which brown Norway rats are actively sensitized to the allergen ovalbumin and later challenged intranasally with either phosphate-buffered saline solution (vehicle), ovalbumin in vehicle, or ovalbumin and the NO synthase inhibitor N-nitro-L-arginine methyl ester. In each experiment, nasal lavage samples were collected 30, 120, 240, and 360 minutes after challenge. Lavage samples were analyzed for albumin content by ELISA, inflammatory cell concentration with a hemocytometer, and evidence of inflammation by light microscopy. Blocking NO synthesis with N-nitro-L-arginine methyl ester significantly inhibited both albumin exudation and inflammatory cell influx into the nasal cavity during the LPR. These data suggest that NO plays a role in the LPR of nasal allergy.

Modeling the acute- and late-phase responses to peripheral airway cooling and desiccation

2002 ◽  
Vol 93 (1) ◽  
pp. 195-200 ◽  
Author(s):  
Michael S. Davis ◽  
Chris M. Royer ◽  
Mark Payton ◽  
Brian Buttress
Keyword(s):  
Acute Phase ◽  
Bronchoalveolar Lavage Fluid ◽  
Polynomial Function ◽  
Late Phase ◽  
Lavage Fluid ◽  
Canine Model ◽  
Phase Response ◽  
Linear Relationships ◽  
Peripheral Airway ◽  
Isocapnic Hyperpnea

Acute bronchoconstriction after isocapnic hyperpnea can be produced in most asthmatic individuals. However, the existence of a late-phase response is less certain. We used a canine model of isocapnic hyperpnea to test the hypothesis that this discrepancy is due to differences in the challenge threshold for the responses. Acute-phase and late-phase bronchoconstriction was measured in nine dogs after peripheral airway exposure to unconditioned air. Additionally, bronchoalveolar lavage fluid (BALF) was obtained during the late-phase response. The acute-phase response was a polynomial function with a decreasing slope at higher challenges, whereas the late-phase response suggested that a minimum threshold of challenge severity was needed to produce late-phase bronchoconstriction. BALF leukocyte and eicosanoid concentrations had linear relationships with challenge severity. Our data support the hypothesis that acute- and late-phase posthyperpnea responses have different dose-response relationships, a fact that may explain the frequent lack of a late-phase response. However, our data suggest that mild inflammation can be induced with relatively lower challenge severity.

scholarly journals The colonic macrophage transcription factor RBP-J orchestrates intestinal immunity against bacterial pathogens

2020 ◽  
Vol 217 (4) ◽  
Author(s):  
Lan Kang ◽  
Xiang Zhang ◽  
Liangliang Ji ◽  
Tiantian Kou ◽  
Sinead M. Smith ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Immune Responses ◽  
Inflammatory Responses ◽  
Late Phase ◽  
Intestinal Immunity ◽  
Adaptive Immune Responses ◽  
Cell Lineages ◽  
Adaptive Immune ◽  
Intestinal Macrophage ◽  
Pathogen Clearance

Macrophages play pleiotropic roles in maintaining the balance between immune tolerance and inflammatory responses in the gut. Here, we identified transcription factor RBP-J as a crucial regulator of colonic macrophage–mediated immune responses against the enteric pathogen Citrobacter rodentium. In the immune response phase, RBP-J promoted pathogen clearance by enhancing intestinal macrophage-elicited Th17 cell immune responses, which was achieved by maintenance of C/EBPβ-dependent IL-6 production by overcoming miRNA-17∼92–mediated suppressive effects. RBP-J deficiency–associated phenotypes could be genetically corrected by further deleting miRNA-17∼92 in macrophages. In the late phase, noneradicated pathogens in RBP-J KO mice recruited abundant IL-1β–expressing CD64+Ly6C+ colonic macrophages and thereby promoted persistence of ILC3-derived IL-22 to compensate for the impaired innate and adaptive immune responses, leading to ultimate clearance of pathogens. These results demonstrated that colonic macrophage–intrinsic RBP-J dynamically orchestrates intestinal immunity against pathogen infections by interfacing with key immune cells of T and innate lymphoid cell lineages.

Sign in / Sign up

Export Citation Format

Share Document