Acid aspiration-induced airways hyperresponsiveness in mice (original) (raw)
Related papers
Airway acidification and gastroesophageal reflux
Current Allergy and Asthma Reports, 2008
Although challenging to study, researchers recently recognized the relevance of airway pH to the pathophysiology of several respiratory diseases, ranging from asthma and cystic fibrosis to pneumonia. The airway epithelium is extraordinarily sensitive to acid. Gastroesophageal reflux can and does cause respiratory symptoms, through both neurally mediated pathways and direct aspiration. Direct aspiration has a variety of immunologic, biochemical, and physiologic effects that aggravate asthma and other respiratory diseases, yet strategies to diagnose and treat gastroesophageal refluxrelated respiratory symptoms remain imprecise.
The American Journal of Medicine, 2001
Although a strong association exists between gastroesophageal reflux (GER) and asthma, results of studies designed to maximize the likelihood of identifying that GER worsens pulmonary function in patients with asthma have been negative or inconclusive. Asthma symptoms worsen during symptomatic reflux episodes, and asthma symptom severity correlates with the severity of symptomatic reflux. Various reasons have been proposed to explain these findings. Discomfort associated with GER can cause reflux-associated respiratory symptoms even when pulmonary function is normal. New findings suggest that increases in minute ventilation rather than inhibition of diaphragm activity are responsible for the changes in respiratory sensation during acid perfusion of the esophagus in nonasthmatic subjects. These results may also pertain to asthmatic patients, because increasing minute ventilation can cause dyspnea and bronchospasm in this population. Treating GER, either medically or surgically, may improve asthma symptoms by preventing GER-induced changes in minute ventilation.
Respiratory Research, 2010
Background: Pulmonary function has been reported in mice using negative pressure-driven forced expiratory manoeuvres (NPFE) and the forced oscillation technique (FOT). However, both techniques have always been studied using separate cohorts of animals or systems. The objective of this study was to obtain NPFE and FOT measurements at baseline and following bronchoconstriction from a single cohort of mice using a combined system in order to assess both techniques through a refined approach.
Pulmonary responses to tracheal or esophageal acidification in guinea pigs with airway inflammation
Journal of applied physiology (Bethesda, Md. : 1985), 2002
The association between asthma and gastroesophageal reflux has been attributed to microaspiration of gastric contents and/or vagally mediated reflex bronchoconstriction. In previous experimental studies concerning the pulmonary effects of tracheal or esophageal acid infusion, only animals without airway inflammation have been studied. We assessed the effects of esophageal and tracheal administration of hydrochloric acid (HCl) on normal guinea pigs (GP) and GP with airway inflammation induced by repeated ovalbumin exposures. These GP were anesthetized (pentobarbital sodium) and received 1) 20 microl of either 0.2 N HCl or saline into the trachea, or 2) 1 ml of either 1 N HCl or saline into the esophagus. Intratracheal HCl resulted in a significant increase in both respiratory system elastance and resistance (P < 0.001). There were no significant changes in respiratory mechanics when HCl was infused into the esophagus. In conclusion, we observed that infusion of large volumes of HC...
Issues determining direct airways hyperresponsiveness in mice
Frontiers in physiology, 2012
Airways hyperresponsiveness (AHR) is frequently a primary outcome in mouse models of asthma. There are, however, a number of variables that may affect the outcome of such measurements and the interpretation of the results. This article highlights issues that should be kept in mind when designing experiments using AHR as an outcome by reviewing techniques commonly used to assess AHR (unrestrained plethysmography and respiratory input impedance using forced oscillations), discussing the relationship between structure and function and, then exploring how the localization of AHR evolves over time, how the airway epithelium may affect the kinetics of methacholine induced AHR and finally how lung volume and positive end expiratory pressure (PEEP) can be used as tools assessing respiratory mechanics.
Toxicology, 2009
Background: To assess the importance of the route of challenge in an existing mouse model of chemicalinduced asthma, we replaced intranasal instillation by oropharyngeal aspiration. To our knowledge, oropharyngeal aspiration as a challenge route has not yet been investigated in a mouse model of chemicalinduced asthma. Methods: On days 1 and 8, mice were dermally sensitized with toluene diisocyanate (TDI) (0.3%) [or vehicle (acetone/olive oil)] and on day 15 they received a single challenge, via oropharyngeal aspiration, with TDI (0.01%) or vehicle. One day after challenge, airway reactivity to methacholine was measured by a forced oscillation technique (FlexiVent) and total and differential cell counts, as well as levels of KC, IL-5, IL-17 and TNF-␣, were assessed in the bronchoalveolar lavage (BAL) fluid. Lymphocytes from the auricular and mediastinal lymph nodes were cultured to determine the concanavaline A-induced secretion of IL-2, IL-4, IL-10, IL-13, IL-17 and IFN-␥. Total serum IgE was measured. Results: In TDI-sensitized mice, a significant increase in airway reactivity was found after a single oropharyngeal challenge with TDI. BAL neutrophils and eosinophils were increased 7-and 5-fold, respectively. An upregulation of Th1 (IFN-␥), Th2 (IL-4, IL-10, IL-13) and Th17 (IL-17) cytokines was found in the auricular lymph nodes, in the mediastinal lymph nodes only IL-4 was upregulated. The total serum IgE level in TDI-sensitized mice was significantly increased when compared to control mice. Conclusion: We conclude that challenging mice via oropharyngeal aspiration mimics the characteristics of human asthma well, without the possible drawbacks of other techniques. .be (V. De Vooght), jeroen.vanoirbeek@med.kuleuven.be (J.A.J. Vanoirbeek), steven.haenen@med.kuleuven.be (S. Haenen), erik.verbeken@med.kuleuven.be (E. Verbeken), ben.nemery@med.kuleuven.be (B. Nemery), peter.hoet@med.kuleuven.be (P.H.M. Hoet).
CHEST Journal, 1999
To identify and critically review the published peer-reviewed, English-language studies of the effects of both spontaneous and simulated gastroesophageal reflux (GER) on pulmonary function in asthmatic adults. Design: Using the 1966 to 1997 MEDLINE database, the terms asthma and lung disease were combined with GER to identify studies of the effects of GER and acid perfusion (AP) of the esophagus on pulmonary function. The bibliographies were also reviewed. Studies of asthmatics with and without symptomatic GER were analyzed both together and separately. Results: A total of 254 citations, including 180 published in English, were identified. Among these were 18 studies of GER and AP in asthmatic adults. These reports, which contain data on 312 asthmatics, found that the FEV 1 and the midexpiratory rate did not change during AP and GER in the studies containing 97% and 94% of the asthmatics, respectively. Flow volume loop indexes, including the flow at 50% of the vital capacity (V 50), flow at 25% of the vital capacity, and the peak expiratory flow rate, did not change during AP or GER in the studies with 77%, 60%, and 65% of the asthmatics, respectively. Small changes in the resistance were reported in the studies containing 42% of the asthmatics. Among asthmatics without symptomatic GER, no changes in spirometry, resistance, and flow volume indexes were found, except for a 10% decline in V 50 in one study with seven subjects. Conclusions: In asthmatics with GER, the effects of AP on pulmonary function are minimal, and only a minority are affected. The literature does not support the conclusion that asymptomatic reflux contributes to worsening lung function.
Effect of high dose inhaled acetic acid on airway responsiveness in Fischer rats
Canadian respiratory journal : journal of the Canadian Thoracic Society
Sudden, severe airway injury has been associated with an acute, and at times persisting, airway hyper-responsiveness with clinical features of asthma, termed reactive airways dysfunction syndrome (RADS). An attempt was made to develop a rat model of RADS by exposing inbred Fischer rats to inhaled 8 N acetic acid for 2 mins (13 N inhalation was lethal). Lung resistance (RL) and lung elastance (EL) were measured in 14 eight- to 10-week old male rats. Baseline responsiveness to methacholine was quantified by calculating the dose required for doubling of RL. The next day, the study group (n=11) was exposed to aerosolized acetic acid. Control animals (n=3) were similarly exposed to buffered saline solution. Acetic acid exposure resulted in a significant (P<0.02) increase in RL (by 80%) and EL (by 67%), lasting less than 10 mins postexposure, but no significant change in methacholine responsiveness at one day and seven days postexposure. Failure to induce persistent airway hyper-respon...
Airway hyperresponsiveness in asthma: lessons from in vitro model systems and animal models
European Respiratory Journal, 2008
Airway hyperresponsiveness (AHR) is a hallmark clinical symptom of asthma. At least two components of AHR have been identified: 1) baseline AHR, which is persistent and presumably caused by airway remodelling due to chronic recurrent airway inflammation; and 2) acute and variable AHR, which is associated with an episodic increase in airway inflammation due to environmental factors such as allergen exposure. Despite intensive research, the mechanisms underlying acute and chronic AHR are poorly understood. Owing to the complex variety of interactive processes that may be involved, in vitro model systems and animal models are indispensable to the unravelling of these mechanisms at the cellular and molecular level. The present paper focuses on a number of translational studies addressing the emerging central role of the airway smooth muscle cell, as a multicompetent cell involved in acute airway constriction as well as structural changes in the airways, in the pathophysiology of airway hyperresponsiveness.