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V Gerber - One of the best experts on this subject based on the ideXlab platform.
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relationship of horse owner assessed respiratory signs index to characteristics of Recurrent Airway Obstruction in two warmblood families
Equine Veterinary Journal, 2010Co-Authors: E Laumen, Marcus G Doherr, V GerberAbstract:Summary Reasons for performing study: The horse owner assessed respiratory signs index (HOARSI-1–4, healthy, mildly, moderately and severely affected, respectively) is based on owner-reported clinical history and has been used for the investigation of Recurrent Airway Obstruction (RAO) genetics utilising large sample sizes. Reliable phenotype identification is of paramount importance in genetic studies. Owner reports of respiratory signs have shown good repeatability, but the agreement of HOARSI with an in-depth examination of the lower respiratory tract has not been investigated. Objectives: To determine the correlation of HOARSI grades 3/4 with the characteristics of RAO and of HOARSI-2 with the characteristics of inflammatory Airway disease. Further, to test whether there are phenotypic differences in the manifestation of lung disease between families. Methods: Seventy-one direct offspring of 2 RAO-affected Warmblood stallions (33 from the first family, 38 from the second) were graded as HOARSI-1–4 and underwent a clinical examination of the respiratory system, arterial blood gas analysis, endoscopic mucus scoring, cytology of tracheobronchial secretion (TBS) and bronchoalveolar lavage fluid (BALF), and clinical assessment of Airway reactivity to methacholine chloride. Results: HOARSI-3/4 animals in clinical exacerbation showed signs consistent with RAO: coughing, nasal discharge, abnormal lung sounds and breathing pattern as well as increased numbers of neutrophils in TBS and BALF, excessive mucus accumulation and Airway hyper-responsiveness to methacholine. HOARSI-3/4 horses in remission only had increased amounts of tracheal mucus and TBS neutrophil percentages. Clinical phenotypes were not significantly different between the 2 families. Conclusions and clinical relevance: HOARSI reliably identifies RAO-affected horses in our population.
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increased parasite resistance and Recurrent Airway Obstruction in horses of a high prevalence family
Journal of Veterinary Internal Medicine, 2010Co-Authors: S Neuhaus, Caroline F Frey, Bruno Gottstein, P Bruendler, Marcus G Doherr, V GerberAbstract:Background: Equine Recurrent Airway Obstruction (RAO) shares many characteristics with human asthma. In humans, an inverse relationship between susceptibility to asthma and resistance to parasites is suspected. Hypothesis/Objectives: Members of a high-incidence RAO half-sibling family (F) shed fewer strongylid eggs compared with RAO-unaffected pasture mates (PM) and that RAO-affected horses shed fewer eggs than RAO-unaffected half-siblings. Animals: Seventy-three F and 73 unrelated, age matched PM. Methods: Cases and controls kept under the same management and deworming regime were examined. Each individual was classified as RAO affected or RAO unaffected and fecal samples were collected before and 1–3 weeks and 3 months after deworming. Samples were analyzed by combined sedimentation-flotation and modified McMaster methods and classified into 3 categories of 0 eggs per gram of feces (EpG), 1–100 EpG, and >100 EpG, respectively. Results: PM compared with RAO-affected F had a 16.7 (95% confidence interval [CI]: 2.0–136.3) times higher risk for shedding > 100 EpG compared with 0 EpG and a 5.3 (95% CI: 1.0–27.4) times higher risk for shedding >100 EpG compared with 0 EpG. There was no significant effect when RAO-unaffected F were compared with their PM. RAO-unaffected compared with RAO-affected offspring had a 5.8 (95% CI: 0.0–1.0) times higher risk for shedding 1–100 EpG. Age, sex, breed, and sharing pastures with other species had no significant confounding effects. Conclusion and Clinical Importance: RAO is associated with resistance against strongylid parasites in a high-prevalence family.
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tracheobronchial mucus viscoelasticity during environmental challenge in horses with Recurrent Airway Obstruction
Equine Veterinary Journal, 2010Co-Authors: V Gerber, D A Schneider, Malcolm King, N E RobinsonAbstract:: The goal of this study was to compare the rheological properties of mucus from horses with Recurrent Airway Obstruction (RAO) to that from healthy controls during environmental challenge by stabling in stalls with straw as bedding and hay as feed. We determined viscoelasticity (log G* dyn/cm2, at 10 radian/s) and calculated mucociliary clearability index (MCI) and cough clearability index (CCI), which are derivative parameters of G* and the ratio of viscosity and elasticity measured at 1 and 100 radian/s, respectively. We also investigated the solids content of mucus, and cytology of bronchoalveolar lavage fluid (BALF). Samples were obtained before (0 h) and 6, 24 and 48 h after environmental challenge. The central findings were rheological changes in Airway mucus, which occurred over time in RAO-affected animals, but not in controls. Mucus rheology was similar in both groups at 0 and 6 h. In RAO-affected horses, mucus viscoelasticity, as measured by log G*, increased from 2.49 +/- 0.18 dyn/cm2 (mean +/- s.e.) at 0 h to 3.05 +/- 0.13 dyn/cm2 at 24 h after environmental challenge, and was accompanied by significant decreases in MCI and CCI. Percent solids of mucus did not differ significantly between the 2 groups, nor over time. Rheological values did not correlate with BALF cytology. We conclude that viscoelastic properties of tracheal mucus samples from RAO horses in remission do not differ from those of normal horses. However, environmental challenge causes clinical signs of small Airway disease and a concurrent increase in mucus viscoelasticity only in RAO horses. Therefore, we infer that unfavourable changes in mucus rheology may contribute to stasis and accumulation of mucus in RAO horses in exacerbation, but not in clinical remission.
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mucin genes in horse Airways muc5ac but not muc2 may play a role in Recurrent Airway Obstruction
Equine Veterinary Journal, 2010Co-Authors: V Gerber, N E Robinson, A M Jefcoat, Patrick J Venta, J Rawson, Jon A HotchkissAbstract:REASONS FOR PERFORMING STUDY: Increased mucin gene expression may be an important cause of mucus accumulation observed in Recurrent Airway Obstruction (RAO)-affected horses. To date, however, no mucin gene sequences are available for the horse. OBJECTIVES: To identify equine homologues of gel-forming mucins and investigate their expression at different Airway generations of healthy and RAO-affected horses. METHODS: Two equine homologues were identified by cloning and sequencing fragments of equine (eq)MUC5AC and eqMUC2. RESULTS: Semiquantitative RT-PCR on RNA from Airways (generations 1, 5, 10, 15; small Airways and parenchyma), stomach (glandular), and colon revealed that eqMUC5AC is expressed in equine stomach and in all of the Airway samples. In contrast, eqMUC2 steady-state mRNA levels were detected in colon and very faintly in stomach, but not in Airway tissue. EqMUC5AC expression was also compared to that of ZO-1, a tight junction protein, and eqMUC5AC/ZO-1 ratios were higher in RAO-affected compared to control horses at all Airway generations. CONCLUSIONS: That eqMUC5AC is expressed in horse Airways, but any expression of MUC2 is undetectable and unlikely to be of physiological consequence. POTENTIAL RELEVANCE: EqMUC5AC up-regulation may be a primary mechanism responsible for mucus hypersecretion and accumulation in RAO.
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a whole genome scan for Recurrent Airway Obstruction in warmblood sport horses indicates two positional candidate regions
Mammalian Genome, 2009Co-Authors: J E Swinburne, Gaudenz Dolf, Tosso Leeb, Jolanta Klukowskarotzler, Helen Bogle, Michaela Drogemuller, Elizabeth Temperton, V GerberAbstract:Recurrent Airway Obstruction (RAO), or heaves, is a naturally occurring asthma-like disease that is related to sensitisation and exposure to mouldy hay and has a familial basis with a complex mode of inheritance. A genome-wide scanning approach using two half-sibling families was taken in order to locate the chromosome regions that contribute to the inherited component of this condition in these families. Initially, a panel of 250 microsatellite markers, which were chosen as a well-spaced, polymorphic selection covering the 31 equine autosomes, was used to genotype the two half-sibling families, which comprised in total 239 Warmblood horses. Subsequently, supplementary markers were added for a total of 315 genotyped markers. Each half-sibling family is focused around a severely RAO-affected stallion, and the phenotype of each individual was assessed for RAO and related signs, namely, breathing effort at rest, breathing effort at work, coughing, and nasal discharge, using an owner-based questionnaire. Analysis using a regression method for half-sibling family structures was performed using RAO and each of the composite clinical signs separately; two chromosome regions (on ECA13 and ECA15) showed a genome-wide significant association with RAO at P < 0.05. An additional 11 chromosome regions showed a more modest association. This is the first publication that describes the mapping of genetic loci involved in RAO. Several candidate genes are located in these regions, a number of which are interleukins. These are important signalling molecules that are intricately involved in the control of the immune response and are therefore good positional candidates.
Vinzenz Gerber - One of the best experts on this subject based on the ideXlab platform.
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a genome wide association study for equine Recurrent Airway Obstruction in european warmblood horses reveals a suggestive new quantitative trait locus on chromosome 13
Animal Genetics, 2017Co-Authors: Debora Schnider, Tosso Leeb, Vinzenz Gerber, S Rieder, Markus NeuditschkoAbstract:Recurrent Airway Obstruction (RAO), also known as heaves, is an asthma-like respiratory disease. Its development is strongly influenced by environmental risk factors such as sensitization and exposure to moldy hay, straw bedding and stabling indoors. A hereditary component has been documented in previous studies; however, so far no causative genetic variant that influences the risk of developing RAO has been identified. In this study, we revised an existing dataset and selected 384 horses for genotyping on the Affymetrix high-density equine SNP array. We performed an allelic case-control genome-wide association study, which revealed a suggestively significant association on equine chromosome 13 at 32 843 309 bp. This SNP is located in the protein-coding gene TXNDC11, which is possibly involved in the folding process of the multiprotein complexes DUOX1 and DUOX2. In humans, these proteins are known to take part in regulating the production of H2 O2 in the respiratory tract epithelium as well as in MUC5AC mucin expression. Therefore, TXNDC11 may be considered a functional candidate gene, and further research is needed to explore its potential role in RAO-affected horses.
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analysis of genomic copy number variation in equine Recurrent Airway Obstruction heaves
Animal Genetics, 2016Co-Authors: Sharmila Ghosh, Vinzenz Gerber, Jeanpierre Lavoie, P J Das, C M Mcqueen, C E Swiderski, B P Chowdhary, Terje RaudseppAbstract:Summary We explored the involvement of genomic copy number variants (CNVs) in susceptibility to Recurrent Airway Obstruction (RAO), or heaves—an asthmalike inflammatory disease in horses. Analysis of 16 RAO-susceptible (cases) and six RAO-resistant (control) horses on a custom-made whole-genome 400K equine tiling array identified 245 CNV regions (CNVRs), 197 previously known and 48 new, distributed on all horse autosomes and the X chromosome. Among the new CNVRs, 30 were exclusively found in RAO cases and were further analyzed by quantitative PCR, including additional cases and controls. Suggestive association (P = 0.03; corrected P = 0.06) was found between RAO and a loss on chromosome 5 involving NME7, a gene necessary for ciliary functions in lungs and involved in primary ciliary dyskinesia in humans. The CNVR could be a potential marker for RAO susceptibility but needs further study in additional RAO cohorts. Other CNVRs were not associated with RAO, although several involved genes of interest, such as SPI2/SERPINA1 from the serpin gene family, which are associated with chronic obstructive pulmonary disease and asthma in humans. The SPI2/SERPINA1 CNVR showed striking variation among horses, but it was not significantly different between RAO cases and controls. The findings provide baseline information on the relationship between CNVs and RAO susceptibility. Discovery of new CNVs and the use of a larger population of RAO-affected and control horses are needed to shed more light on their significance in modulating this complex and heterogeneous disease.
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multiple hypersensitivities including Recurrent Airway Obstruction insect bite hypersensitivity and urticaria in 2 warmblood horse populations
Journal of Veterinary Internal Medicine, 2015Co-Authors: Dounia Kehrli, Vendula Jandova, Kerstin Fey, P Jahn, Vinzenz GerberAbstract:Background Multiple hypersensitivities (MHS) have been described in humans, cats, and dogs, but not horses. Hypotheses Horses suffering from Recurrent Airway Obstruction (RAO), insect bite hypersensitivity (IBH), or urticaria (URT) will have an increased risk of also being affected by another one of these hypersensitivities. This predisposition for MHS also will be associated with decreased shedding of strongylid eggs in feces and with a single nucleotide polymorphism (SNP BIEC2-224511), previously shown to be associated with RAO. Animals The first population (P1) included 119 randomly sampled horses representative of the Swiss sporthorse population; the replication population (P2) included 210 RAO-affected Warmblood horses and 264 RAO-unaffected controls. All horses were Warmbloods, 14 years or older. Methods Associations between disease phenotypes (RAO, IBH, URT, MHS) fecal egg counts, the SNP BIEC2-224511 as well as management and environmental factors were investigated. Results In P1, RAO-affected horses had a 13.1 times higher odds ratio (OR) of also suffering from IBH (P = .004). In P2, the respective OR was 7.4 (P = .002) and IBH-affected horses also showed a 7.1 times increased OR of concomitantly suffering from URT (P < .001). IBH, URT, and MHS phenotypes were significantly associated with the absence of nematode eggs in the feces. Conclusions and Clinical Importance This is the first report of MHS in horses. Specifically, an increased risk for IBH should be expected in RAO-affected horses.
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evaluation of coughing and nasal discharge as early indicators for an increased risk to develop equine Recurrent Airway Obstruction rao
Journal of Veterinary Internal Medicine, 2014Co-Authors: S Bosshard, Vinzenz GerberAbstract:Background It is often assumed that horses with mild respiratory clinical signs, such as mucous nasal discharge and occasional coughing, have an increased risk of developing Recurrent Airway Obstruction (RAO). Hypothesis Compared to horses without any clinical signs of respiratory disease, those with occasional coughing, mucous nasal discharge, or both have an increased risk of developing signs of RAO (frequent coughing, increased breathing effort, exercise intolerance, or a combination of these) as characterized by the Horse Owner Assessed Respiratory Signs Index (HOARSI 1–4). Animals Two half-sibling families descending from 2 RAO-affected stallions (n = 65 and n = 47) and an independent replication population of unrelated horses (n = 88). Methods In a retrospective cohort study, standardized information on occurrence and frequency of coughing, mucous nasal discharge, poor performance, and abnormal breathing effort—and these factors combined in the HOARSI—as well as management factors were collected at intervals of 1.3–5 years. Results Compared to horses without clinical signs of respiratory disease (half-siblings 7%; unrelated horses 3%), those with mild respiratory signs developed clinical signs of RAO more frequently: half-siblings with mucous nasal discharge 35% (P < .001, OR: 7.0, sensitivity: 62%, specificity: 81%), with mucous nasal discharge and occasional coughing 43% (P < .001, OR: 9.9, sensitivity: 55%, specificity: 89%); unrelated horses with occasional coughing: 25% (P = .006, OR = 9.7, sensitivity: 75%, specificity: 76%). Conclusions and Clinical importance Occasional coughing and mucous nasal discharge might represent an increased risk of developing RAO.
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replication and fine mapping of a qtl for Recurrent Airway Obstruction in european warmblood horses
Animal Genetics, 2012Co-Authors: Mostafa Shakhsiniaei, Cord Drögemüller, Gaudenz Dolf, Vinzenz Gerber, J E Swinburne, Jolanta Klukowskarotzler, Alessandra Ramseyer, C Ehrmann, Dounia Saftic, Tosso LeebAbstract:Recurrent Airway Obstruction (RAO), or 'heaves', is a common performance-limiting allergic respiratory disease of mature horses. It is related to sensitization and exposure to mouldy hay and has a familial basis with a complex mode of inheritance. In a previous study, we detected a QTL for RAO on ECA 13 in a half-sib family of European Warmblood horses. In this study, we genotyped additional markers in the family and narrowed the QTL down to about 1.5 Mb (23.7-25.2 Mb). We detected the strongest association with SNP BIEC2-224511 (24,309,405 bp). We also obtained SNP genotypes in an independent cohort of 646 unrelated Warmblood horses. There was no genome-wide significant association with RAO in these unrelated horses. However, we performed a genotypic association study of the SNPs on ECA 13 in these unrelated horses, and the SNP BIEC2-224511 also showed the strongest association with RAO in the unrelated horses (p(raw) = 0.00037). The T allele at this SNP was associated with RAO both in the family and the unrelated horses. Thus, the association study in the unrelated animals provides independent support for the previously detected QTL. The association study allows further narrowing of the QTL interval to about 0.5 Mb (24.0-24.5 Mb). We sequenced the coding regions of the genes in the critical region but did not find any associated coding variants. Therefore, the causative variant underlying this QTL is likely to be a regulatory mutation.
N E Robinson - One of the best experts on this subject based on the ideXlab platform.
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the effect of intravenous lidocaine infusion on bronchoalveolar lavage cytology in equine Recurrent Airway Obstruction
Journal of Veterinary Internal Medicine, 2012Co-Authors: M E Wilson, A L Behan, C Berney, N E RobinsonAbstract:Background Lidocaine decreases neutrophilic inflammation in models of acute lung injury and decreases inflammation in asthmatic patients. Neutrophilic bronchiolitis develops in Recurrent Airway Obstruction (RAO), but it remains unknown if lidocaine infusion decreases neutrophil migration into the Airways. Hypothesis Lidocaine decreases neutrophilic inflammation as measured in BALF in RAO-affected horses. Animals Six RAO-susceptible horses in remission. Methods In a randomized cross-over design, horses received lactated Ringer's solution (LRS) IV or lidocaine hydrochloride IV with a minimum of 4 weeks at pasture between treatments. Treatments were delivered as continuous infusions beginning 4 hours before and for 68 hours during exposure to hay and straw challenge. Clinical score (CS, grade 0–8), maximal change in pleural pressure (∆Pplmax), and bronchoalveolar lavage fluid (BALF) cytology were measured at baseline and the end of challenge (day 4). Plasma lidocaine concentrations were monitored daily. Results At baseline, there were no significant differences in variables between treatments. Plasma lidocaine concentration was consistently > 1100 ng/mL. After challenge, CS increased significantly [baseline: 2/8 (2–3), [median (interquartile range)]; day 4: 4/8 (4–5) P = .0006] as did ∆Pplmax [baseline: 3.6 (2.63–4.95) cmH20; day 4: 9.62 (6.5–16) P = .0036], but there was no difference between treatments. Percentage of neutrophils was not different between treatments, but lidocaine infusion significantly increased BALF total cells [baseline: LRS 2.18 ± 0.82 × 105 cells/mL (mean ± SD), lidocaine 1.6 ± 0.3 × 105, day 4: LRS 2.0 ± 0.88 × 105, lidocaine 4.4 ± 2 × 105 (P = .0045)]. Conclusions and Clinical Importance Lidocaine does not decrease neutrophilic inflammation in RAO.
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relationship between clinical signs and lung function in horses with Recurrent Airway Obstruction heaves during a bronchodilator trial
Equine Veterinary Journal, 2010Co-Authors: N E Robinson, Michal A Olszewski, D Boehler, C Matson, Jani Hakala, Cédric Berney, Frederik J. DerksenAbstract:Summary During a trial to determine the dose response to the β2-adrenergic agonist pirbuterol, we judged the severity of Airway Obstruction by use of a clinical scoring system and compared this to objective data obtained by quantitative measures of lung function. Six horses affected by Recurrent Airway Obstruction were used in this trial. Four hundred and sixty-eight measurements of lung function and clinical scores were obtained from 13 measurement periods when horses received each of 6 doses of pirbuterol. Scores of 1–4 were assigned to degree of nasal flaring and abdominal effort and summed for a total score. The veterinarian scoring the signs did not know the dose of pirbuterol received by the horse and was unaware of the lung function data. Nasal, abdominal and total scores were significantly related to changes in lung function and changes in breathing pattern. There were significant differences between total scores greater than 5 in indices that reflected changes in breathing strategy (peak inspiratory and expiratory flow), peripheral Airway Obstruction (dynamic elastance), and effort of breathing (maximal change in pleural pressure). Below a total score of 5, there were fewer significant differences in lung function even though measurements of pulmonary resistance and dynamic elastance indicated considerable Airway Obstruction. Failure of clinical score to reflect this low-grade Airway Obstruction suggests that Airway disease is underdiagnosed and its detection would be helped by the availability of a convenient lung function test.
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tracheobronchial mucus viscoelasticity during environmental challenge in horses with Recurrent Airway Obstruction
Equine Veterinary Journal, 2010Co-Authors: V Gerber, D A Schneider, Malcolm King, N E RobinsonAbstract:: The goal of this study was to compare the rheological properties of mucus from horses with Recurrent Airway Obstruction (RAO) to that from healthy controls during environmental challenge by stabling in stalls with straw as bedding and hay as feed. We determined viscoelasticity (log G* dyn/cm2, at 10 radian/s) and calculated mucociliary clearability index (MCI) and cough clearability index (CCI), which are derivative parameters of G* and the ratio of viscosity and elasticity measured at 1 and 100 radian/s, respectively. We also investigated the solids content of mucus, and cytology of bronchoalveolar lavage fluid (BALF). Samples were obtained before (0 h) and 6, 24 and 48 h after environmental challenge. The central findings were rheological changes in Airway mucus, which occurred over time in RAO-affected animals, but not in controls. Mucus rheology was similar in both groups at 0 and 6 h. In RAO-affected horses, mucus viscoelasticity, as measured by log G*, increased from 2.49 +/- 0.18 dyn/cm2 (mean +/- s.e.) at 0 h to 3.05 +/- 0.13 dyn/cm2 at 24 h after environmental challenge, and was accompanied by significant decreases in MCI and CCI. Percent solids of mucus did not differ significantly between the 2 groups, nor over time. Rheological values did not correlate with BALF cytology. We conclude that viscoelastic properties of tracheal mucus samples from RAO horses in remission do not differ from those of normal horses. However, environmental challenge causes clinical signs of small Airway disease and a concurrent increase in mucus viscoelasticity only in RAO horses. Therefore, we infer that unfavourable changes in mucus rheology may contribute to stasis and accumulation of mucus in RAO horses in exacerbation, but not in clinical remission.
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mucin genes in horse Airways muc5ac but not muc2 may play a role in Recurrent Airway Obstruction
Equine Veterinary Journal, 2010Co-Authors: V Gerber, N E Robinson, A M Jefcoat, Patrick J Venta, J Rawson, Jon A HotchkissAbstract:REASONS FOR PERFORMING STUDY: Increased mucin gene expression may be an important cause of mucus accumulation observed in Recurrent Airway Obstruction (RAO)-affected horses. To date, however, no mucin gene sequences are available for the horse. OBJECTIVES: To identify equine homologues of gel-forming mucins and investigate their expression at different Airway generations of healthy and RAO-affected horses. METHODS: Two equine homologues were identified by cloning and sequencing fragments of equine (eq)MUC5AC and eqMUC2. RESULTS: Semiquantitative RT-PCR on RNA from Airways (generations 1, 5, 10, 15; small Airways and parenchyma), stomach (glandular), and colon revealed that eqMUC5AC is expressed in equine stomach and in all of the Airway samples. In contrast, eqMUC2 steady-state mRNA levels were detected in colon and very faintly in stomach, but not in Airway tissue. EqMUC5AC expression was also compared to that of ZO-1, a tight junction protein, and eqMUC5AC/ZO-1 ratios were higher in RAO-affected compared to control horses at all Airway generations. CONCLUSIONS: That eqMUC5AC is expressed in horse Airways, but any expression of MUC2 is undetectable and unlikely to be of physiological consequence. POTENTIAL RELEVANCE: EqMUC5AC up-regulation may be a primary mechanism responsible for mucus hypersecretion and accumulation in RAO.
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environment and prednisone interactions in the treatment of Recurrent Airway Obstruction heaves
Equine Veterinary Journal, 2010Co-Authors: C Jackson, C Berney, A M Jefcoat, N E RobinsonAbstract:Summary Recurrent Airway Obstruction (RAO) or heaves is a manifestation of a hypersensitivity to dust, moulds, and spores in the environment of a susceptible horse. Although in the majority of RAO-affected horses, clinical remission can be achieved by keeping horses at pasture to reduce their allergen exposure, this often is not practicable. For this reason, we investigated if changing the environment of a single stall in a 4 stall stable was sufficient to improve lung function and reduce inflammation in RAO-affected horses. In addition, we determined if addition of oral prednisone provided additional benefit. Twelve RAO-susceptible horses were stabled, fed hay, and bedded on straw until they developed Airway Obstruction. At this point, bedding was changed to wood shavings and they were fed a pelleted diet for 2 weeks. Lung function was measured and bronchoalveolar lavage was performed before and 3, 7, and 14 days after environmental modification. In a crossover design, horses were treated for the 14 days with prednisone tablets (2.2 mg/kg bwt, q. 24 h). Horses then returned to pasture for 30 days. Airway Obstruction was greatest before environmental modification. Significant improvement in lung function occurred within 3 days of the change in environment and continued to Day 7. Airway function was best after 30 days at pasture. The clinical response achieved by environmental modification was not significantly improved by addition of oral prednisone. The total number of cells, total neutrophils, and percent neutrophils was greatest before environmental modification. In the absence of prednisone, total and percent neutrophils did not decrease until Day 14 and total cell number until 30 days at pasture. In the presence of prednisone, total cells and total and percent neutrophils decreased by Day 3 and again at pasture. The fact that lung function can be improved within 3 days by environmental management alone emphasises the need for allergen reduction as the cornerstone of treatment of RAO. Although prednisone induced a more rapid reduction in Airway inflammation, this was not associated with a more rapid improvement in Airway function.
J E Swinburne - One of the best experts on this subject based on the ideXlab platform.
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replication and fine mapping of a qtl for Recurrent Airway Obstruction in european warmblood horses
Animal Genetics, 2012Co-Authors: Mostafa Shakhsiniaei, Cord Drögemüller, Gaudenz Dolf, Vinzenz Gerber, J E Swinburne, Jolanta Klukowskarotzler, Alessandra Ramseyer, C Ehrmann, Dounia Saftic, Tosso LeebAbstract:Recurrent Airway Obstruction (RAO), or 'heaves', is a common performance-limiting allergic respiratory disease of mature horses. It is related to sensitization and exposure to mouldy hay and has a familial basis with a complex mode of inheritance. In a previous study, we detected a QTL for RAO on ECA 13 in a half-sib family of European Warmblood horses. In this study, we genotyped additional markers in the family and narrowed the QTL down to about 1.5 Mb (23.7-25.2 Mb). We detected the strongest association with SNP BIEC2-224511 (24,309,405 bp). We also obtained SNP genotypes in an independent cohort of 646 unrelated Warmblood horses. There was no genome-wide significant association with RAO in these unrelated horses. However, we performed a genotypic association study of the SNPs on ECA 13 in these unrelated horses, and the SNP BIEC2-224511 also showed the strongest association with RAO in the unrelated horses (p(raw) = 0.00037). The T allele at this SNP was associated with RAO both in the family and the unrelated horses. Thus, the association study in the unrelated animals provides independent support for the previously detected QTL. The association study allows further narrowing of the QTL interval to about 0.5 Mb (24.0-24.5 Mb). We sequenced the coding regions of the genes in the critical region but did not find any associated coding variants. Therefore, the causative variant underlying this QTL is likely to be a regulatory mutation.
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comparison of genomic and proteomic data in Recurrent Airway Obstruction affected horses using ingenuity pathway analysis
BMC Veterinary Research, 2011Co-Authors: Julien Racine, Vinzenz Gerber, J E Swinburne, Miskovic M Feutz, Paige C Riley, Jiri Adamec, Laurent L CouetilAbstract:Recurrent Airway Obstruction (RAO) is a severe chronic respiratory disease affecting horses worldwide, though mostly in the Northern hemisphere. Environmental as well as genetic factors strongly influence the course and prognosis of the disease. Research has been focused on characterization of immunologic factors contributing to inflammatory responses, on genetic linkage analysis, and, more recently, on proteomic analysis of Airway secretions from affected horses. The goal of this study was to investigate the interactions between eight candidate genes previously identified in a genetic linkage study and proteins expressed in bronchoalveolar lavage fluid (BALF) collected from healthy and RAO-affected horses. The analysis was carried out with Ingenuity Pathway Analysis® bioinformatics software. The gene with the greatest number of indirect interactions with the set of proteins identified is Interleukin 4 Receptor (IL-4R), whose protein has also been detected in BALF. Interleukin 21 receptor and chemokine (C-C motif) ligand 24 also showed a large number of interactions with the group of detected proteins. Protein products of other genes like that of SOCS5, revealed direct interactions with the IL-4R protein. The interacting proteins NOD2, RPS6KA5 and FOXP3 found in several pathways are reported regulators of the NFκB pathway. The pathways generated with IL-4R highlight possible important intracellular signaling cascades implicating, for instance, NFκB. Furthermore, the proposed interaction between SOCS5 and IL-4R could explain how different genes can lead to identical clinical RAO phenotypes, as observed in two Swiss Warmblood half sibling families because these proteins interact upstream of an important cascade where they may act as a functional unit.
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ige igga iggb and igg t serum antibody levels in offspring of two sires affected with equine Recurrent Airway Obstruction
Animal Genetics, 2010Co-Authors: A Scharrenberg, Vinzenz Gerber, J E Swinburne, A D Wilson, Jolanta Klukowskarotzler, E Laumen, E MartiAbstract:Equine Recurrent Airway Obstruction (RAO) is a chronic lower Airway disease of the horse caused by hypersensitivity reactions to inhaled stable dust, including mould spores such as Aspergillus fumigatus. The goals of this study were to investigate whether total serum IgE levels and allergen-specific IgE and IgG subclasses are influenced by genetic factors and/or RAO and whether quantitative trait loci (QTL) could be identified for these parameters. The offspring of two RAO-affected sires (S1: n=56 and S2: n=65) were grouped by stallion and disease status, and total serum IgE levels and specific IgE, IgGa, IgGb and IgG(T) levels against recombinant Aspergillus fumigatus 7 (rAspf7) were measured by ELISA. A panel of 315 microsatellite markers covering the 31 equine autosomes were used to genotype the stallions and their offspring. A whole-genome scan using half-sib regression interval mapping was performed for each of the IgG and IgE subclasses. There was no significant effect of disease status or sire on total IgE levels, but there was a significant effect of gender and age. rAspf7-specific IgGa levels were significantly higher in RAO-affected than in healthy horses. The offspring of S1 had significantly higher rAspf7-specific IgGa and IgE levels than those of S2. Five QTLs were significant chromosome-wide (P<0.01). QTLs for rAspf7-specific IgGa and IgE were identified on ECA 1, for rAspf7-specific IgGa and IgGb on ECA 24 and for rAspf7 IgGa on ECA 26. These results provide evidence for effects of disease status and genetics on allergen-specific IgGa and IgE.
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a whole genome scan for Recurrent Airway Obstruction in warmblood sport horses indicates two positional candidate regions
Mammalian Genome, 2009Co-Authors: J E Swinburne, Gaudenz Dolf, Tosso Leeb, Jolanta Klukowskarotzler, Helen Bogle, Michaela Drogemuller, Elizabeth Temperton, V GerberAbstract:Recurrent Airway Obstruction (RAO), or heaves, is a naturally occurring asthma-like disease that is related to sensitisation and exposure to mouldy hay and has a familial basis with a complex mode of inheritance. A genome-wide scanning approach using two half-sibling families was taken in order to locate the chromosome regions that contribute to the inherited component of this condition in these families. Initially, a panel of 250 microsatellite markers, which were chosen as a well-spaced, polymorphic selection covering the 31 equine autosomes, was used to genotype the two half-sibling families, which comprised in total 239 Warmblood horses. Subsequently, supplementary markers were added for a total of 315 genotyped markers. Each half-sibling family is focused around a severely RAO-affected stallion, and the phenotype of each individual was assessed for RAO and related signs, namely, breathing effort at rest, breathing effort at work, coughing, and nasal discharge, using an owner-based questionnaire. Analysis using a regression method for half-sibling family structures was performed using RAO and each of the composite clinical signs separately; two chromosome regions (on ECA13 and ECA15) showed a genome-wide significant association with RAO at P < 0.05. An additional 11 chromosome regions showed a more modest association. This is the first publication that describes the mapping of genetic loci involved in RAO. Several candidate genes are located in these regions, a number of which are interleukins. These are important signalling molecules that are intricately involved in the control of the immune response and are therefore good positional candidates.
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mixed inheritance of equine Recurrent Airway Obstruction
Journal of Veterinary Internal Medicine, 2009Co-Authors: V Gerber, J E Swinburne, Jolanta Klukowskarotzler, D Baleri, Gaudenz DolfAbstract:BACKGROUND: Mode of inheritance of equine Recurrent Airway Obstruction (RAO) is unknown. HYPOTHESIS: Major genes are responsible for RAO. ANIMALS: Direct offspring of 2 RAO-affected Warmblood stallions (n = 197; n = 163) and a representative sample of Swiss Warmbloods (n = 401). METHODS: One environmental and 4 genetic models (general, mixed inheritance, major gene, and polygene) were tested for Horse Owner Assessed Respiratory Signs Index (1-4, unaffected to severely affected) by segregation analyses of the 2 half-sib sire families, both combined and separately, using prevalences estimated in a representative sample. RESULTS: In all data sets the mixed inheritance model was most likely to explain the pattern of inheritance. In all 3 datasets the mixed inheritance model did not differ significantly from the general model (P= .62, P= 1.00, and P= .27) but was always better than the major gene model (P < .01) and the polygene model (P < .01). The frequency of the deleterious allele differed considerably between the 2 sire families (P= .23 and P= .06). In both sire families the displacement was large (t= 17.52 and t= 12.24) and the heritability extremely large (h(2)= 1). CONCLUSIONS AND CLINICAL RELEVANCE: Segregation analyses clearly reveal the presence of a major gene playing a role in RAO. In 1 family, the mode of inheritance was autosomal dominant, whereas in the other family it was autosomal recessive. Although the expression of RAO is influenced by exposure to hay, these findings suggest a strong, complex genetic background for RAO.
Tosso Leeb - One of the best experts on this subject based on the ideXlab platform.
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a genome wide association study for equine Recurrent Airway Obstruction in european warmblood horses reveals a suggestive new quantitative trait locus on chromosome 13
Animal Genetics, 2017Co-Authors: Debora Schnider, Tosso Leeb, Vinzenz Gerber, S Rieder, Markus NeuditschkoAbstract:Recurrent Airway Obstruction (RAO), also known as heaves, is an asthma-like respiratory disease. Its development is strongly influenced by environmental risk factors such as sensitization and exposure to moldy hay, straw bedding and stabling indoors. A hereditary component has been documented in previous studies; however, so far no causative genetic variant that influences the risk of developing RAO has been identified. In this study, we revised an existing dataset and selected 384 horses for genotyping on the Affymetrix high-density equine SNP array. We performed an allelic case-control genome-wide association study, which revealed a suggestively significant association on equine chromosome 13 at 32 843 309 bp. This SNP is located in the protein-coding gene TXNDC11, which is possibly involved in the folding process of the multiprotein complexes DUOX1 and DUOX2. In humans, these proteins are known to take part in regulating the production of H2 O2 in the respiratory tract epithelium as well as in MUC5AC mucin expression. Therefore, TXNDC11 may be considered a functional candidate gene, and further research is needed to explore its potential role in RAO-affected horses.
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replication and fine mapping of a qtl for Recurrent Airway Obstruction in european warmblood horses
Animal Genetics, 2012Co-Authors: Mostafa Shakhsiniaei, Cord Drögemüller, Gaudenz Dolf, Vinzenz Gerber, J E Swinburne, Jolanta Klukowskarotzler, Alessandra Ramseyer, C Ehrmann, Dounia Saftic, Tosso LeebAbstract:Recurrent Airway Obstruction (RAO), or 'heaves', is a common performance-limiting allergic respiratory disease of mature horses. It is related to sensitization and exposure to mouldy hay and has a familial basis with a complex mode of inheritance. In a previous study, we detected a QTL for RAO on ECA 13 in a half-sib family of European Warmblood horses. In this study, we genotyped additional markers in the family and narrowed the QTL down to about 1.5 Mb (23.7-25.2 Mb). We detected the strongest association with SNP BIEC2-224511 (24,309,405 bp). We also obtained SNP genotypes in an independent cohort of 646 unrelated Warmblood horses. There was no genome-wide significant association with RAO in these unrelated horses. However, we performed a genotypic association study of the SNPs on ECA 13 in these unrelated horses, and the SNP BIEC2-224511 also showed the strongest association with RAO in the unrelated horses (p(raw) = 0.00037). The T allele at this SNP was associated with RAO both in the family and the unrelated horses. Thus, the association study in the unrelated animals provides independent support for the previously detected QTL. The association study allows further narrowing of the QTL interval to about 0.5 Mb (24.0-24.5 Mb). We sequenced the coding regions of the genes in the critical region but did not find any associated coding variants. Therefore, the causative variant underlying this QTL is likely to be a regulatory mutation.
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The interleukin 4 receptor gene and its role in Recurrent Airway Obstruction in Swiss Warmblood horses.
Animal genetics, 2011Co-Authors: Jolanta Klukowska-rötzler, June E Swinburne, Cord Drögemüller, Gaudenz Dolf, Jozef Janda, Tosso Leeb, Vinzenz GerberAbstract:Recurrent Airway Obstruction (RAO) in horses is the result of an interaction of genetic and environmental factors and shares many characteristics with human asthma. Many studies have suggested that the interleukin-4 receptor gene (IL4R) is associated with this disease, and a QTL region on chromosome 13 containing IL4R was previously detected in one of the two Swiss Warmblood families. We sequenced the entire IL4R gene in this family and detected 93 variants including five non-synonymous protein-coding variants. The allele distribution at these SNPs supported the previously detected QTL signal. Subsequently, we investigated IL4R mRNA expression in bronchoalveolar lavage fluid cells. During exacerbation, IL4R expression was increased in RAO-affected offspring in the implicated family, but not in the other family. These findings support that IL4R plays a role in some cases of RAO.
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a whole genome scan for Recurrent Airway Obstruction in warmblood sport horses indicates two positional candidate regions
Mammalian Genome, 2009Co-Authors: J E Swinburne, Gaudenz Dolf, Tosso Leeb, Jolanta Klukowskarotzler, Helen Bogle, Michaela Drogemuller, Elizabeth Temperton, V GerberAbstract:Recurrent Airway Obstruction (RAO), or heaves, is a naturally occurring asthma-like disease that is related to sensitisation and exposure to mouldy hay and has a familial basis with a complex mode of inheritance. A genome-wide scanning approach using two half-sibling families was taken in order to locate the chromosome regions that contribute to the inherited component of this condition in these families. Initially, a panel of 250 microsatellite markers, which were chosen as a well-spaced, polymorphic selection covering the 31 equine autosomes, was used to genotype the two half-sibling families, which comprised in total 239 Warmblood horses. Subsequently, supplementary markers were added for a total of 315 genotyped markers. Each half-sibling family is focused around a severely RAO-affected stallion, and the phenotype of each individual was assessed for RAO and related signs, namely, breathing effort at rest, breathing effort at work, coughing, and nasal discharge, using an owner-based questionnaire. Analysis using a regression method for half-sibling family structures was performed using RAO and each of the composite clinical signs separately; two chromosome regions (on ECA13 and ECA15) showed a genome-wide significant association with RAO at P < 0.05. An additional 11 chromosome regions showed a more modest association. This is the first publication that describes the mapping of genetic loci involved in RAO. Several candidate genes are located in these regions, a number of which are interleukins. These are important signalling molecules that are intricately involved in the control of the immune response and are therefore good positional candidates.
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genetics of Recurrent Airway Obstruction rao
Deutsche Tierarztliche Wochenschrift, 2008Co-Authors: Vinzenz Gerber, Gaudenz Dolf, J E Swinburne, Jolanta Klukowskarotzler, E Marti, Sarah C Blott, Paivi Nussbaumer, Alessandra Ramseyer, Dominik Burger, Tosso LeebAbstract:Recurrent Airway Obstruction (RAO) is a multifactorial and polygenic disease. Affected horses are typically 7 years of age or older and show exercise intolerance, increased breathing effort, coughing, Airway neutrophilia, mucus accumulation and hyperreactivity as well as cholinergic bronchospasm. The environmental factors responsible are predominantly allergens and irritants in haydust, but the immunological mechanisms underlying RAO are still unclear. Several studies have demonstrated a familiar predisposition for RAO and it is now proven that the disease has a genetic basis. In offspring, the risk of developing RAO is 3-fold increased when one parent is affected and increases to almost 5-fold when both parents have RAO. Segregation analysis in two high-prevalence families demonstrated a high heritability and a complex inheritance with several major genes. A whole genomescan showed chromosome-wide significant linkage of seven chromosomal regions with RAO. Of the microsatellites, which were located near atopy candidate genes, those in a region of chromosome 13 harboring the IL4R gene were strongly associated with the RAO phenotype in the offspring of one RAO-affected stallion. Furthermore, IgE-levels are influenced by hereditary factors in the horse, and we have evidence that RAO-affected offspring of the same stallion have increased levels of specific IgE against moldspore allergens. The identification of genetic markers and ultimately of the responsible genes will not only allow for an improved prophylaxis, i.e. early identification of susceptible individuals and avoidance of high-risk matings, but also improve our ability to find new therapeutic targets and to optimize existing treatments.