The effects of inhaled house dust mite on airway barrier function and sensitivity to inhaled methacholine in mice

Turi, G. J.; Ellis, Russ; Wattie, Jennifer; Labiris, N. R.; Inman, Mark D.

doi:10.1152/ajplung.00271.2010

Cited by 25 publications

(17 citation statements)

References 24 publications

(35 reference statements)

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“…Single high dose OVA increased Rrs comparable to that seen for low dose MCh (see section “Results”). This exposure is likely to be far greater than the dosage of OVA delivered through inhalation, where upper airway impaction, large airway branch-point deposition and the presence of a robust airway epithelial barrier (Hogg, 1982; Turi et al, 2011) all conspire to reduce the dosage of agonist delivered to submucosal airway smooth muscle sites. Thus, it is possible that the final inhaled OVA exposure may not have significantly altered R RS or induced bronchoconstriction.…”

Section: Discussionmentioning

confidence: 99%

OVA-induced airway hyperresponsiveness alters murine heart rate variability and body temperature

et al. 2012

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Altered autonomic (ANS) tone in chronic respiratory disease is implicated as a factor in cardiovascular co-morbidities, yet no studies address its impact on cardiovascular function in the presence of murine allergic airway (AW) hyperresponsiveness (AHR). Since antigen (Ag)-induced AHR is used to model allergic asthma (in which ANS alterations have been reported), we performed a pilot study to assess measurement feasibility of, as well as the impact of allergic sensitization to ovalbumin (OVA) on, heart rate variability (HRV) in a murine model. Heart rate (HR), body temperature (TB), and time- and frequency-domain HRV analyses, a reflection of ANS control, were obtained in chronically instrumented mice (telemetry) before, during and for 22 h after OVA or saline aerosolization in sensitized (OVA) or Alum adjuvant control exposed animals. OVA mice diverged significantly from Alum mice with respect to change in HR during aerosol challenge (P < 0.001, Two-Way ANOVA; HR max change Ctrl = +80 ± 10 bpm vs. OVA = +1 ± 23 bpm, mean ± SEM), and displayed elevated HR during the subsequent dark cycle (P = 0.006). Sensitization decreased the TB during aerosol challenge (P < 0.001). Sensitized mice had decreased HRV prior to challenge (SDNN: P = 0.038; Low frequency (LF) power: P = 0.021; Low/high Frequency (HF) power: P = 0.042), and increased HRV during Ag challenge (RMSSD: P = 0.047; pNN6: P = 0.039). Sensitized mice displayed decreased HRV subsequent to OVA challenge, primarily in the dark cycle (RMSSD: P = 0.018; pNN6: P ≤ 0.001; LF: P ≤ 0.001; HF: P = 0.040; LF/HF: P ≤ 0.001). We conclude that implanted telemetry technology is an effective method to assess the ANS impact of allergic sensitization. Preliminary results show mild sensitization is associated with reduced HRV and a suppression of the acute TB-response to OVA challenge. This approach to assess altered ANS control in the acute OVA model may also be beneficial in chronic AHR models.

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Section: Discussionmentioning

confidence: 99%

OVA-induced airway hyperresponsiveness alters murine heart rate variability and body temperature

et al. 2012

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“…For decades, the primary assumption is that allergy is caused by overactive immunological responses against allergens, driven by activated Th2 cells and due to aberrant T-regulatory cells [18, 19]. Recently, Turi et al postulated that the impaired epithelial barrier function that allows aeroallergens to trigger the overactive immunological responses could be a direct result of proteolytic activities of aeroallergens, including HDM [20]. The current hypothesis is that Der p1 m, the major allergen in HDM, causes injury to the epithelium and enters the tissue to induce inflammation via Toll-like receptor 4 [21, 22].…”

Section: Discussionmentioning

confidence: 99%

House dust mite sensitization in toddlers predict persistent wheeze in children between eight to fourteen years old

et al. 2012

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BackgroundIdentifying toddlers at increased risk of developing persistent wheeze provides an opportunity for risk-reducing interventions. House dust mite (HDM) allergen sensitization might identify this group of high-risk children.ObjectiveWe examined whether a positive skin prick test (SPT) to at least 1 of the 3 HDMs in wheezing toddlers, would serve as a predictor for persistent wheeze at age 8 to 14 years old.MethodsA cohort of 78 children, who had wheezing episodes, and underwent SPT to 3 HDMs between the ages of 2 to 5 years old, were enrolled. SPT results were obtained from the National University Hospital database. Four to 9 years later, the children, currently between 8 to 14 years old, were re-assessed for persistence of asthma symptoms and other atopic disorders via a telephone interview. A validated questionnaire on current wheezing and asthma, developed by the International Study of Asthma and Allergies in Childhood, was used. Fisher's exact test was used to evaluate the association between persistence of asthma and a positive SPT.ResultsOf the 78 children who participated in the study, 42 (53.8%) had a positive SPT and 36 (46.2%) had a negative SPT. Of these, 18 (42.9%) of SPT positive and 7 (19.4%) of SPT negative children had persistence of asthma symptoms. There is a significant association between a positive SPT during the preschool years, and persistence of asthma (p = 0.0314 [<0.05]).ConclusionHDM sensitization at ages 2 to 5 years old in wheezing children predicts persistence of asthma after 4 to 9 years. This in turn may have benefits for management of asthma in this high-risk group.

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“…The pups (n ϭ 7 for Ctrl and PNE) were placed in a double-chambered plethysmograph (Buxco Electronics, Wilmington, NC). After stabilization, they were exposed to aerosolized vehicle and then methacholine (Sigma, St. Louis, MO) solutions in a dose-increasing manner (3.125, 6.250, 12.500, and 25.000 mg/ml) as previously reported (51).…”

Section: Experimental Protocolsmentioning

confidence: 99%

Prenatal nicotinic exposure augments cardiorespiratory responses to activation of bronchopulmonary C-fibers

Zhuang

Zhao

Zang

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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Rat pups prenatally exposed to nicotine (PNE) present apneic (lethal ventilatory arrest) responses during severe hypoxia. To clarify whether these responses are of central origin, we tested PNE effects on ventilation and diaphragm electromyography (EMGdi) during hypoxia in conscious rat pups. PNE produced apnea (lethal ventilatory arrest) identical to EMGdi silencing during hypoxia, indicating a central origin of this apneic response. We further asked whether PNE would sensitize bronchopulmonary C-fibers (PCFs), a key player in generating central apnea, with increase of the density and transient receptor potential cation channel subfamily V member 1 (TRPV1) expression of C-fibers/neurons in the nodose/jugular (N/J) ganglia and neurotrophic factors in the airways and lungs. We compared 1) ventilatory and pulmonary C-neural responses to right atrial bolus injection of capsaicin (CAP, 0.5 μg/kg), 2) bronchial substance P-immunoreactive (SP-IR) fiber density, 3) gene and protein expressions of TRPV1 in the ganglia, and 4) nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) protein in bronchoalveolar lavage fluid (BALF) and TrkA and TrkB genes in the ganglia between control and PNE pups. PNE markedly strengthened the PCF-mediated apneic response to CAP via increasing pulmonary C-neural sensitivity. PNE also enhanced bronchial SP-IR fiber density and N/J ganglia neural TRPV1 expression associated with increased gene expression of TrkA in the N/G ganglia and decreased NGF and BDNF in BALF. Our results suggest that PNE enhances PCF sensitivity likely through increasing PCF density and TRPV1 expression via upregulation of neural TrkA and downregulation of pulmonary BDNF, which may contribute to the PNE-promoted central apnea (lethal ventilatory arrest) during hypoxia.

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The effects of inhaled house dust mite on airway barrier function and sensitivity to inhaled methacholine in mice

Abstract: Turi GJ, Ellis R, Wattie JN, Labiris NR, Inman MD. The effects of inhaled house dust mite on airway barrier function and sensitivity to inhaled methacholine in mice.

Cited by 25 publications

References 24 publications

OVA-induced airway hyperresponsiveness alters murine heart rate variability and body temperature

OVA-induced airway hyperresponsiveness alters murine heart rate variability and body temperature

House dust mite sensitization in toddlers predict persistent wheeze in children between eight to fourteen years old

Prenatal nicotinic exposure augments cardiorespiratory responses to activation of bronchopulmonary C-fibers

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