Recurrent Airway Obstruction Research Articles

Cause, Treatment and Prevention of Recurrent Airway Obstruction (ORVA) in Equino

Cause, Treatment and Prevention of Recurrent Airway Obstruction (ORVA) in Equino

Aortic remodelling induced by obstructive apneas is normalized with mesenchymal stem cells infusion

Obstructive sleep apnea syndrome (OSA) promotes aortic dilatation, increased stiffness and accelerated atherosclerosis, but the mechanisms of vascular remodelling are not known. We aimed to assess vascular remodelling, its mechanisms, and the effect of mesenchymal stem cells (MSC) infusions in a clinically relevant rat model of chronic OSA involving recurrent airway obstructions leading thoracic pressure swings and intermittent hypoxia/hypercapnia (OSA-rats). Another group of rats were placed in the same setup without air obstructions (Sham-rats) and were considered controls. Our study demonstrates that chronic, non-invasive repetitive airway obstructions mimicking OSA promote remarkable structural changes of the descending thoracic aorta such as eccentric aortic hypertrophy due to an increased wall thickness and lumen diameter, an increase in the number of elastin fibers which, in contrast, get ruptured, but no changes in tunica media fibrosis. As putative molecular mechanisms of the OSA-induced vascular changes we identified an increase in reactive oxygen species and renin-angiotensin system markers and an imbalance in oxide nitric synthesis. Our results also indicate that MSC infusion blunts the OSA-related vascular changes, most probably due to their anti-inflammatory properties.

Beyond steroids and bronchodilators – investigating additional therapies for horses with severe equine asthma

Chronic inflammatory airway disease in horses has been known by many names over the past few decades, including heaves, chronic obstructive pulmonary disease (COPD), inflammatory airway disease (IAD) and recurrent...

S7B-04 SESSION 7B: HFM ROBIN - PART II RATE AND RISK FACTORS FOR REPEATED MANDIBULAR DISTRACTION OSTEOGENESIS IN INFANT PATIENTS WITH TONGUE BASED AIRWAY OBSTRUCTION

Introduction: Mandibular distraction osteogenesis (MDO) has demonstrated efficacy for tongue-based airway obstruction in infant Pierre Robin Sequence (PRS). The purpose of this study is to identify risk factors for patients who require repeat distraction after MDO in early infancy for PRS. Methods: Consecutive patients who underwent MDO from 2004 to 2018 at a single institution were retrospectively reviewed. Patient characteristics including age at initial MDO, comorbidities, polysomnographic parameters, and distraction data were collected. Patients whose initial surgery was before 2 months of age were identified and divided into cohorts: single versus repeat distraction. Results: 103 patients were identified during the study period - 95 had a single distraction procedure and 8 required repeat distraction. Indications for repeat distraction were recurrent airway obstruction (6), failure to extubate (1), and persistent micrognathia (1). There was no difference in age or weight at initial distraction, duration of distraction, or distraction length between single and repeat distraction groups. Overall, average AHI was 39.9 pre-operatively and 10.1 post-operatively; neither varied between groups. Genetic anomalies and syndromic diagnoses were more common in the repeat distraction group (75.0% vs. 40.0% single distraction, p=0.06). More patients had laryngomalacia in the repeat distraction group (75.0% vs. 33.7% single distraction, p=0.02). Conclusion: MDO has been accepted as efficacious in PRS but the rate of repeat distraction has not been described. In this study 7.8% of infants required redistraction and the identified risk factors were genetic anomaly or syndromic diagnosis, pre-operative laryngomalacia, or recurrent airway obstruction.

The Results of Surgical Treatment of Hypertension in Mild and Moderate Obstructive Sleep Apnea Syndrome

Background: Obstructive sleep apnea syndrome (OSAS) is the most common respiratory disorder related to sleep. It is characterized by recurrent upper airway obstruction episodes and a decrease in arterial oxygen saturation during sleep. The most important complications of OSAS are related to the cardiovascular system. Hypertension (30% - 60%) is the leading cause of these complications. Objectives: This study aimed to investigate the removal of upper airway obstruction through surgical operations in the tension treatment of OSAS patients with hypertension. Methods: This retrospective study included 42 patients with hypertension from 2008 to 2017 who were diagnosed with OSAS based on the result of polysomnogram (PSG) test. All the patients were examined in detail in otorhinolaryngology and cardiology clinics, their endoscopic and imaging evaluations were carried out and their blood pressure was followed-up. Preoperative and postoperative arterial blood pressure values for upper airway obstruction were statistically analyzed. Results: The mean preoperative systolic and diastolic arterial blood pressure values of the patients with hypertension were 152.3 ± 21.2 and 97.2 ± 12.3 mmHg, respectively. Their postoperative systolic and diastolic arterial blood pressure levels were found to be 124.5 ± 19.3 and 86.4 ± 12.1 mmHg, respectively (P < 0.05). This decrease in the arterial blood pressure was significant. Conclusions: Removal of upper airway obstruction through a surgical operation was found to play an important role in the blood pressure treatment of OSAS patients with hypertension.

Cardiovascular Complications in Obstructive Sleep Apnea Syndrome

: Obstructive sleep apnea syndrome (OSAS) is the most common respiratory disorder related to sleep. It is characterized by recurrent upper airway obstruction episodes and hypoxemia attacks during sleep. Cardiovascular complications are rather frequent in OSAS. This compilation study aimed to show cardiovascular pathologies occurring during OSAS in detail and emphasize the need of treating OSAS during the treatment of these pathologies

Equine asthma: managing the environment

Equine asthma is an umbrella term defined by nonseptic lower airway inflammation. Currently there are two broad categories, namely mild to moderate equine asthma (formerly known as inflammatory airway disease) and severe equine asthma (formerly known as recurrent airway obstruction or heaves). Environmental challenge is involved in the aetiopathogenesis of both these subcategories. Much of this challenge, and the part that we can control, is provided by the organic dust associated with the stabling of horses. This article reviews the available evidence relating to the environmental management of equine asthma and tries to relate this to practical options for providing a low-dust environment.

Investigation of smell and taste function in patients with obstructive sleep apnoea syndrome

This study investigated the relationship between disease severity and taste and smell functions in patients with obstructive sleep apnoea syndrome. A total of 65 patients with recurrent upper airway obstruction during sleep were included. Participants were divided into four groups according to apnoea-hypopnoea index, obtained on polysomnography. Smell and taste tests were performed on these patients. A significant difference was observed between the smell thresholds of the groups for the identification test (p = 0.016). In the taste test, significant differences were observed between the groups in terms of sweet, sour, salty and bitter taste test thresholds (p = 0.029, p = 0.0005, p = 0.001 and p = 0.017, respectively). As sleep apnoea severity increased (according to the apnoea-hypopnoea index) in obstructive sleep apnoea syndrome patients, the taste and smell thresholds decreased due to the effect of neuropathy and inflammation in the upper respiratory tract.

Assessment of serum allergen-specific IgE levels in horses with seasonal allergic dermatitis and recurrent airway obstruction in Spain.

Allergic conditions are prevalent equine diseases that can be diagnosed by clinical examination alone, but definitive diagnosis is more likely with laboratory testing. The ELISA Allercept© test was used to analyse the serum samples of 73 horses with allergic diseases. Sixty-one horses (83.5%) had allergen-specific IgE levels ≥ 150 ELISA Units (EU), the cut-off defined by the assay. Fifty-four horses had allergic dermatitis (AD) with high IgE levels to Tyrophagus putrescentiae (51.9%), Rumex crispus (48.1%), Tabanus (46.3%) and Dermatophagoides farinae/ D. pteronyssinus (40.7%). Seven horses with recurrent airway obstruction (RAO) had a high prevalence of T. putrescentiae (85.7%), followed by that of Acarus siro (57.1%) and D. farinae/D. pteronyssinus (57.1%). Horses affected with RAO had more positive reactions to mites (2.22 ± 0.84) than did horses with AD (1.51 ± 0.61, P < 0.05). A strong correlation of serum allergen-specific IgE level was found between Culex tarsalis and Stomoxys (r = 0.943) and between Dactylis glomerata and both Secale cereale (r = 0.79) and R. crispus (r = 0.696). These results indicate that among horses with allergic diseases in Spain, ELISA tests demonstrated a high prevalence of serum allergen-specific IgE in response to mites. Our study emphasises the importance of laboratory testing and updating allergy panels to improve the likelihood of a definitive diagnosis and the identification of allergens that should be included in allergic disease treatment.

Respiratory and volumetric changes of the upper airways in craniofacial synostosis patients

To assess postoperative changes of the upper airway in a pediatric syndromic cranial-synostosis (SCS) population who underwent Le Fort III (LFIII) or frontofacial advancement by distraction osteogenesis (DO).Charts' review of 25 SCS infants presented at our tertiary-care children's hospital between January 2005 and December 2016 was performed. Preoperative (T0) and postoperative (T1) three-dimensional computed tomography (3D-CT) and polysomnography (PSG) were recorded. Differences between T0 and T1 airway volumes and changes in PSG data were analyzed.18 patients were included. The mean T0 and T1 volumes were calculated as 15.963 mm3 ± 7.181 SD and 24.550 mm3 ± 12.946 SD, respectively. Airway areas increased significantly (p < 0.05) in the total study-group by a median value of 8.004 mm3, together with a global 72.22% improvement in respiratory parameters.A statistically significant gain of the upper airway after LF III and DO in SCS patients has been demonstrated. Given the absence of a direct relationship between post-operative upper airway volume increase and OSAS degree improvement, further insights should consider performing T0 and T1 sleep endoscopy analysis to complete the diagnostic workup and to better assess the level of residual or recurrent upper airway obstruction in patients who experience unsuccessful surgical treatment.

The Endothelin-A Receptor Antagonist Zibotentan Induces Damage to the Nasal Olfactory Epithelium Possibly Mediated in Part through Type 2 Innate Lymphoid Cells.

Zibotentan, an endothelin-A receptor antagonist, has been used in the treatment of various cardiovascular disorders and neoplasia. Castrated athymic nude mice receiving zibotentan for a preclinical xenograft efficacy study experienced weight loss, gastrointestinal bloat, and the presence of an audible respiratory click. Human side effects have been reported in the nasal cavity, so we hypothesized that the nasal cavity is a target for toxicity in mice receiving zibotentan. Lesions in the nasal cavity predominantly targeted olfactory epithelium in treated mice and were more pronounced in castrated animals. Minimal lesions were present in vehicle control animals, which suggested possible gavage-related reflux injury. The incidence, distribution, and morphology of lesions suggested direct exposure to the nasal mucosa and a possible systemic effect targeting the olfactory epithelium, driven by a type 2 immune response, with group 2 innate lymphoid cell involvement. Severe nasal lesions may have resulted in recurrent upper airway obstruction, leading to aerophagia and associated clinical morbidity. These data show the nasal cavity is a target of zibotentan when given by gavage in athymic nude mice, and such unanticipated and off-target effects could impact interpretation of research results and animal health in preclinical studies.

Treatment of horses with asthma syndrome

Treatment of horses with asthma syndrome

Fungi in respiratory samples of horses with inflammatory airway disease.

BackgroundFungi contribute to the inflammatory response of lungs in horses with recurrent airway obstruction and in some forms of asthma in humans. The role of fungi in inflammatory airway disease (IAD) has not been assessed.ObjectivesEvaluate the prevalence of fungi in the respiratory samples of horses diagnosed with IAD, describe clinical signs associated with the presence of fungi in respiratory samples, and assess the risk factors associated with IAD and with the presence of fungi in the airways.AnimalsSeven‐hundred thirty‐one active horses referred to a specialized ambulatory practice for signs of respiratory disease or poor performance.MethodsA prospective observational study was performed, collecting clinical data, environmental conditions, and results of a tracheal wash (TW; cytology, fungal culture, and bacterial culture), and bronchoalveolar lavage (cytology).ResultsA positive fungal culture was obtained in 55% (402/731) of horses. Horses with fungal elements observed on the TW cytology had 2 times greater chance of having IAD than horses without fungi (odds ratio [OR] = 2.1; 95% CI 1.08‐3.33; P = .0003). Risks of being diagnosed with IAD and likelihood of fungi in TW were higher when horses were bedded on straw (OR = 2.0; 95% CI 1.2‐3.2 and OR = 1.9; 95% CI 1.3‐2.6, respectively) or fed dry hay (OR = 2.7; 95% CI 1.7‐4.4 and OR = 2.6; 95% CI 1.6‐3.4, respectively).Conclusions and Clinical ImportanceHorses inhaling aerosolized fungal particles are at a significantly higher risk of developing IAD. The type of bedding and forage represent significant risk factors for IAD and fungal contamination of equine airways.

Lung lesions of slaughtered horses in southern Brazil

ABSTRACT: Respiratory diseases cause significant veterinary costs, reduce performance and require withdrawal of horses. Yet, studies of the causes of pneumonia in horses are scant. This study aimed to describe the pathological and microbiological features of lung lesions in slaughtered horses in southern Brazil. In this study, 84 samples of lungs were examined, and a conclusive diagnosis was obtained in 74 cases. These were composed of bronchopneumonia in 50 cases, followed by granulomatous eosinophilic pneumonia (9/74), recurrent airway obstruction (7/74), lung fibrosis (4/74), lung hemorrhage (3/74) and pulmonary pythiosis (1/74). Bronchopneumonia had grossly firm focally extensive yellow to dark-red areas, which consisted microscopically of multifocal to coalescing infiltrate of degenerate neutrophils. Streptococcus equi subsp. zooepidemicus was identified in 21 of the 50 cases. Granulomatous eosinophilic pneumonia had multifocal pinpoint firm-hard yellow areas, which microscopically were composed of granulomas with a mineralized center surrounded by collagen fibers and severe infiltrate of eosinophils. Recurrent airway obstruction had mild multifocal pinpoint firm white areas that consisted microscopically of large amounts of mucus inside bronchi and bronchiole. Lung fibrosis had two patterns: focally extensive areas of consolidation and firm nodular areas. Microscopically, the first pattern had interstitial to peribronchial fibrosis, while the second had, in addition to the interstitial fibrosis, a severe pneumocyte hyperplasia and an alveolar infiltrate of neutrophils and macrophages with rare intranuclear inclusion bodies (equine herpesvirus 5, EHV-5). Pulmonary pythiosis presented a focal firm nodular area, with multiple kunkers observed in the cut surface, which corresponded microscopically to areas of necrosis surrounded by a mixed inflammatory infiltrate. At the periphery of the necrotic areas, multiple negatively stained hyphae were observed, which were evidenced through Grocott’s stain and immunohistochemistry anti-Pythium insidiosum.

Equine asthma: Integrative biologic relevance of a recently proposed nomenclature.

The term “equine asthma” has been proposed as a unifying descriptor of inflammatory airway disease (IAD), recurrent airway obstruction (RAO), and summer pasture‐associated obstructive airway disease. Whilst the term will increase comprehensibility for both the lay and scientific communities, its biologic relevance must be compared and contrasted to asthma in human medicine, recognizing the limited availability of peer‐reviewed equine‐derived data, which are largely restricted to clinical signs, measures of airway obstruction and inflammation and response to therapy. Such limitations constrain meaningful comparisons with human asthma phenotypes. Suggested minimum inclusion criteria supporting the term asthma, as well as similarities and differences between IAD, RAO, and multiple human asthma phenotypes are discussed. Furthermore, differences between phenotype and severity are described, and typical features for equine asthma subcategories are proposed. Based on shared features, we conclude that mild/moderate (IAD) and severe (RAO) equine asthma are biologically appropriate models for both allergic and non‐allergic human asthma, with RAO (severe equine asthma) also being an appropriate model for late‐onset asthma. With the development of new biologic treatments in humans and the application of more targeted therapeutic approaches in the horse, it would appear appropriate to further investigate the allergic (Th‐2) and non‐allergic (non‐Th‐2) phenotypes of equine asthma. Further research is required to more fully determine the potential clinical utility of phenotype classification.

EQTL discovery and their association with severe equine asthma in European Warmblood horses

BackgroundSevere equine asthma, also known as recurrent airway obstruction (RAO), is a debilitating, performance limiting, obstructive respiratory condition in horses that is phenotypically similar to human asthma. Past genome wide association studies (GWAS) have not discovered coding variants associated with RAO, leading to the hypothesis that causative variant(s) underlying the signals are likely non-coding, regulatory variant(s). Regions of the genome containing variants that influence the number of expressed RNA molecules are expression quantitative trait loci (eQTLs). Variation associated with RAO that also regulates a gene’s expression in a disease relevant tissue could help identify candidate genes that influence RAO if that gene’s expression is also associated with RAO disease status.ResultsWe searched for eQTLs by analyzing peripheral blood mononuclear cells (PBMCs) from two half-sib families and one unrelated cohort of 82 European Warmblood horses that were previously treated in vitro with: no stimulation (MCK), lipopolysaccharides (LPS), recombinant cyathostomin antigen (RCA), and hay-dust extract (HDE). We identified high confidence eQTLs that did not violate linear modeling assumptions and were not significant due to single outlier individuals. We identified a mean of 4347 high confidence eQTLs in four treatments of PBMCs, and discovered two trans regulatory hotspots regulating genes involved in related biological pathways. We corroborated previous RAO associated single nucleotide polymorphisms (SNPs), and increased the resolution of past GWAS by analyzing 1,056,195 SNPs in 361 individuals. We identified four RAO-associated SNPs that only regulate gene expression of dexamethasone-induced protein (DEXI), however we found no significant association between DEXI gene expression and presence of RAO.ConclusionsThousands of genetic variants regulate gene expression in PBMCs of European Warmblood horses in cis and trans. Most high confidence eSNPs are significantly enriched near the transcription start sites of their target genes. Two trans regulatory hotspots on chromosome 11 and 13 regulate many genes involved in transmembrane cell signaling and neurological development respectively when PBMCs are treated with HDE. None of the top fifteen RAO associated SNPs strongly influence disease status through gene expression regulation.

Effect of antigen challenge on dynamics of CD62P and CD41/61 expression on platelets in horses with recurrent airway obstruction (RAO)

Recurrent airway obstruction (RAO), also known as heaves, is an allergic respiratory condition that develops in horses following an exposure to aeroallergens in hay and straw. This is manifested by airway hyperreactivity, inflammation, bronchoconstriction, as well as a leukocyte and platelet infiltration into the airways. Platelet activation and an increase in circulating platelet-leukocyte aggregates may lead to airway remodeling. The aim of this study was to explore the effect of seven-day antigen challenge on dynamics of platelet indices and CD41/61 and CD62 P expression on platelets in horses with RAO. Ten RAO-affected horses and ten healthy horses were included in this study. All horses were exposed to 7 days hay and straw challenge. Blood samples were collected prior to the challenge (Pre-challenge) and 1, 2, 3, 7 and 14 days after the initiating the antigen challenge. Blood samples were obtained to determine the platelet count (PLT), mean platelet volume (MPV) and platelet large cell ratio (P-LCR). Expression of CD62 P and CD41/61 was detected by flow cytometry on activated platelets. Antigen challenge resulted in a significant gradual decrease of PLT in RAO horses, but not in controls. MPV and P-LCR in control and RAO-affected horses remained unchanged after antigen challenge. The expression of CD62 P and CD41/61 in RAO horses was significantly higher compared to control horses. The antigen challenge resulted in an increase expression of CD62 P and CD41/61 on the platelets of RAO-affected horses, while did not lead to significant changes in the control group. An increased expression of CD62 P and CD41/61 indicates platelet activation what may contribute to the formation of platelet aggregates in their respiratory system.

Sleep-disordered breathing in C57BL/6J mice with diet-induced obesity.

Obesity leads to sleep-disordered breathing (SDB) manifested by recurrent upper airway obstructions termed obstructive sleep apnea (OSA) and carbon dioxide retention due to hypoventilation. The objective of this work was to characterize breathing during sleep in C57BL6/J mice with diet-induced obesity (DIO). Arterial blood gas was measured in nine obese and nine lean mice during wakefulness. Nine male mice with DIO and six lean male C57BL/6J mice were head mounted with electroencephalogram (EEG) and electromyogram (EMG) electrodes. Sleep recordings were performed in the whole body plethysmography chamber; upper airway obstruction was characterized by the presence of inspiratory flow limitation in which airflow plateaus with increases in inspiratory effort. Obese mice showed significantly lower pH and higher partial pressure of arterial CO2 (PaCO2) in arterial blood gas compared to lean mice, 7.35 ± 0.04 versus 7.46 ± 0.06 (p < 0.001) and 38 ± 8 mm Hg versus 30 ± 5 mm Hg (p < 0.001). Obese mice had similar levels of minute ventilation to lean mice during sleep and wakefulness, despite higher body weight and temperature, indicating an increase in the metabolic rate and hypoventilation. Obese mice also showed baseline hypoxemia with decreased mean oxyhemoglobin saturation across sleep/wake states. Obese mice had a higher prevalence of flow-limited breathing compared to lean mice during sleep. However, the oxygen desaturation index in lean and obese mice did not differ. We conclude that DIO in mice leads to hypoventilation. Obesity also increases the frequency of inspiratory limited breaths, but it does not translate into progression of OSA.

0534 Balanced Co-activation of Protrudors and Rectractors is Required to Prevent Pharyngeal Obstruction During Sleep

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction caused by a loss of upper airway muscle tone during sleep. Reductions in Genioglossus (GG) muscle tone, the main upper airway (UA) dilator, during sleep is thought to play a critical role in the pathogenesis of UA obstruction. Nevertheless, recent evidence suggests that lingual retractors also stabilize UA patency during sleep, leading us to hypothesize that co-activating lingual muscles can augment responses in UA patency during sleep 14 apneic patients implanted with a multi-channel hypoglossal nerve stimulating system (Imthera aura 6000) underwent mid-sagittal ultrasound tongue imaging during wakefulness. Changes in tongue shape and position were characterized by measuring its vertical height and the polar dimensions between the tongue surface and genioglossus origin in the mandible (mental spine). Changes in airway patency were characterized by comparing airflow responses between stimulated and adjacent unstimulated breaths during NREM sleep. Two distinct morphologic responses to stimulation were observed. Anterior tongue base and hyoid bone movement (5.3 ± 0.2 to 4.2 ± 0.5 cm) with concomitant increases in tongue height (4.7 ± 0.4 to 5.3 ± 0.7 cm) resulting in only modest changes in airway patency. In contrast, when stimulation generated forward movement (5.7 ± 0.3 to 4.5 ± 0.7 cm) without any increase in height (4.6 ± 0.5 to 4.6 ± 0.9 cm), marked increases in airway patency were observed. Lingual muscles that protrude the tongue while preserving tongue shape and prevent the tongue from bulging upward were associated with greater increases in pharyngeal patency during sleep. These morphologic differences suggest that co-stimulating lingual muscles stiffen the tongue, and prevent it from prolapsing into the pharynx during sleep. Our findings further suggest that dilating and stiffening actions of lingual protrudors and retractors can maintain UA patency during sleep. Imthera Medical AHA: 16post31000017.

In an Adult Horse With Severe Asthma (Previously Recurrent Airway Obstruction) Does Using Inhaled Corticosteroids Result in an Equal Improvement in Clinical Signs When Compared to Systemic Corticosteroids?

&lt;strong&gt;PICO question&lt;/strong&gt;&lt;br /&gt;&lt;p&gt;In an adult horse with severe asthma (previously recurrent airway obstruction (RAO)) does using inhaled corticosteroids result in an equal improvement in clinical signs when compared to systemic corticosteroids?&lt;/p&gt;&lt;strong&gt;Clinical bottom line&lt;/strong&gt;&lt;br /&gt;&lt;p&gt;The level of confidence in the outcomes from the body of evidence in the 4 papers identified is high. This suggests inhaled corticosteroids (fluticasone and beclomethasone) when used at an appropriate dose can have equivalent effects on severe equine asthma as systemic intravenous dexamethasone. Inhaled corticosteroids can take longer to have the desired effects. &lt;/p&gt;&lt;br /&gt; &lt;img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="Open Access" /&gt; &lt;img src="https://www.veterinaryevidence.org/rcvskmod/icons/pr-icon.jpg" alt="Peer Reviewed" /&gt;