Endotracheal nebulization of N-acetylcysteine increases airway resistance in cats with experimental asthma

Reinero, Carol R.; Lee‐Fowler, Tekla; Dodam, John R.; Cohn, Leah A.; DeClue, Amy E.; Guntur, Vamsi P.

doi:10.1016/j.jfms.2010.09.010

Cited by 24 publications

(24 citation statements)

References 17 publications

(12 reference statements)

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“…We also observed that intratracheal administration of NAC together with BPEx, unexpectedly, was toxic or pro-inflammatory to the animals. Delivery of NAC into the airways has been reported to have the potential to induce bronchospasm and irritant effects (43,44) and i.p. administration is far more common.…”

Section: Discussionmentioning

confidence: 99%

Inhaled Birch Pollen Extract Induces Airway Hyperresponsiveness via Oxidative Stress but Independently of Pollen-Intrinsic NADPH Oxidase Activity, or the TLR4–TRIF Pathway

Shalaby

Allard-Coutu

O’Sullivan

et al. 2013

The Journal of Immunology

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Oxidative stress in allergic asthma may result from oxidase activity or pro-inflammatory molecules in pollens. Signaling via TLR4 and its adaptor TRIF has been implicated in reactive oxygen species (ROS)-mediated acute lung injury and in T helper 2 immune responses. We investigated the contributions of oxidative stress and TLR4/TRIF signaling to experimental asthma induced by birch pollen exposure exclusively via the airways. Mice were exposed to native or heat-inactivated white birch pollen extract (BPEx) intratracheally and injected with the antioxidants, N-acetyl-L-cysteine (NAC) or dimethylthiourea (DMTU) prior to sensitization, challenge, or all allergen exposures, to assess the role of oxidative stress and pollen-intrinsic NADPH oxidase activity in allergic sensitization, inflammation and airway hyperresponsiveness (AHR). Additionally, TLR4 signaling was antagonized concomitantly with allergen exposure, or the development of allergic airway disease was evaluated in TLR4 or TRIF knockout mice. NAC inhibited BPEx-induced eosinophilic airway inflammation and AHR except when given exclusively during sensitization, whereas DMTU was inhibitory even when administered with the sensitization alone. Heat-inactivation of BPEx had no effect on the development of allergic airway disease. Oxidative stress-mediated AHR was also TLR4- and TRIF-independent, however, TLR4 deficiency decreased, while TRIF deficiency increased BPEx-induced airway inflammation. In conclusion, oxidative stress plays a significant role in allergic sensitization to pollen via the airway mucosa, but the pollen-intrinsic NADPH oxidase activity and TLR4 or TRIF signaling are unnecessary for the induction of allergic airway disease and AHR. Pollen extract does, however, activate TLR4, thereby enhancing airway inflammation which is restrained by the TRIF-dependent pathway.

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Section: Discussionmentioning

confidence: 99%

Inhaled Birch Pollen Extract Induces Airway Hyperresponsiveness via Oxidative Stress but Independently of Pollen-Intrinsic NADPH Oxidase Activity, or the TLR4–TRIF Pathway

Shalaby

Allard-Coutu

O’Sullivan

et al. 2013

The Journal of Immunology

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“…Although systemic absorption of heparin could lead to bleeding as a complication, no hemorrhage was reported with nebulized heparin with doses ranging from 50,000 to 400,000 IU of unfractionated heparin in people . An irritating effect of NAC on airway mucosa, presumably associated with acidity (pKa of 2.2) and the foul sulfur odor of the compound, has been suspected in humans and cats, but no data are available in dogs to the authors' knowledge …”

mentioning

confidence: 95%

Recurrent Obstructive Fibrinous Tracheal Pseudomembranes in a Young English Bulldog

Robin

Guieu

Boedec

2017

Veterinary Internal Medicne

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Endotracheal intubation is a common procedure, rarely associated with life‐threatening complications (e.g., tracheal rupture, necrosis, foreign body). A 1.5‐year‐old English Bulldog was presented for respiratory distress, with increased respiratory efforts and stridor, 2 days after endotracheal intubation. Cervical and thoracic radiographs disclosed a severe narrowing of the tracheal lumen associated with an intraluminal soft‐tissue structure at the thoracic inlet. Tracheoscopy confirmed the presence of an obstructive fibrinous tracheal pseudomembrane (OFTP) creating a 1‐way valve obstruction. Removal of the OFTP dramatically improved the dog's respiratory function, but the lesion reformed twice despite corticosteroid and antibiotic therapy PO, warranting repeated endoscopic removal of the OFTP. No additional recurrences were observed after treatment with inhaled heparin and N‐acetylcysteine q4h. No respiratory signs were reported 9 months after discharge. Postintubation OFTP has been reported rarely in humans and never described in dogs. Unexplained signs of upper airway obstruction shortly after endotracheal intubation should prompt consideration of OFTP in dogs, even if intubation was uneventful. Unlike its counterpart in humans, OFTP in dogs can reoccur after endoscopic removal, warranting repeated endoscopic extraction. A combination of corticosteroid therapy PO and heparin and N‐acetylcysteine inhalation q4h may be attempted if recurrence is observed.

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“…Cats treated with oral masitinib demonstrated lower P plat and a lower P plat -PEEP; measurement techniques in cats were previously characterized in our feline asthma model utilizing the Engström Carestation ventilator [25]. P plat -PEEP reflects lung resistive pressure, an inverse parameter of respiratory system compliance, which often improves with small airway dilation [28] and reduction in small airway edema or inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…Cats were ventilated for a minimum of 5 min prior to data collection. Airway reactivity was evaluated by obtaining ventilator-calculated airway resistance (R aw ) measurements in response to methacholine (MCh) challenge as previously described [25]. …”

Section: Methodsmentioning

confidence: 99%

The Tyrosine Kinase Inhibitor Masitinib Blunts Airway Inflammation and Improves Associated Lung Mechanics in a Feline Model of Chronic Allergic Asthma

Lee‐Fowler¹,

Guntur

Dodam³

et al. 2012

Int Arch Allergy Immunol

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Background: Blockade of tyrosine kinase signaling by masitinib, a c-kit/PDGF receptor tyrosine kinase inhibitor, can modulate allergic airway inflammation, but effects on lung mechanics have not been well characterized. We hypothesized masitinib would decrease airway eosinophilia and consequently improve pulmonary mechanics in a feline allergic asthma model. Methods: Asthma was induced in 12 cats using Bermuda grass allergen (BGA). Cats received 50 mg/day oral masitinib or placebo. Bronchoalveolar lavage fluid (BALF) was analyzed for eosinophils, total protein (TP) and BGA-specific IgE. Ventilator-acquired mechanics after methacholine (MCh) challenge determined MCh concentration needed to increase baseline airway resistance by 200% (EC₂₀₀R_aw), positive end expiratory occlusion pressure (PEEP) and end inspiratory breath hold pressure (P_plat). An inverse correlate of respiratory system compliance P_plat-PEEP was also calculated. Data were analyzed using the Wilcoxon test, with one-tailed significance set at p < 0.1. Results: After 4 weeks, percent eosinophils in BALF was lower in masitinib-treated cats (7 ± 9%) versus controls (30 ± 27%, p = 0.023). BALF TP significantly differed (p = 0.047) between groups, decreasing with masitinib and increasing with placebo. BALF BGA-specific IgE was unaffected by masitinib. Both groups showed an improvement in EC₂₀₀R_aw (masitinib, p = 0.015; control, p = 0.078) but no significant change in PEEP after 4 weeks. Masitinib-treated cats demonstrated decreased P_plat (p = 0.033) and P_plat-PEEP (p = 0.075) at week 4, suggesting an improvement in respiratory compliance. Conclusions: Masitinib reduced BALF eosinophilia and TP, indicating improved airway inflammation and edema, and improved P_plat and P_plat-PEEP, suggesting benefit to respiratory compliance influenced by airway inflammation/edema. Masitinib deserves further study in humans with chronic allergic asthma.

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Endotracheal nebulization of N-acetylcysteine increases airway resistance in cats with experimental asthma

Cited by 24 publications

References 17 publications

Inhaled Birch Pollen Extract Induces Airway Hyperresponsiveness via Oxidative Stress but Independently of Pollen-Intrinsic NADPH Oxidase Activity, or the TLR4–TRIF Pathway

Inhaled Birch Pollen Extract Induces Airway Hyperresponsiveness via Oxidative Stress but Independently of Pollen-Intrinsic NADPH Oxidase Activity, or the TLR4–TRIF Pathway

Recurrent Obstructive Fibrinous Tracheal Pseudomembranes in a Young English Bulldog

The Tyrosine Kinase Inhibitor Masitinib Blunts Airway Inflammation and Improves Associated Lung Mechanics in a Feline Model of Chronic Allergic Asthma

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