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Article ; Online: The equine asthma model of airway remodeling: from a veterinary to a human perspective.

Bullone, Michela / Lavoie, Jean-Pierre

2019 Volume 380, Issue 2, Page(s) 223–236

Abstract: Human asthma is a complex and heterogeneous disorder characterized by chronic inflammation, bronchospasm and airway remodeling. The latter is a major determinant of the structure-function relationship of the respiratory system and likely contributes to ... ...

Abstract	Human asthma is a complex and heterogeneous disorder characterized by chronic inflammation, bronchospasm and airway remodeling. The latter is a major determinant of the structure-function relationship of the respiratory system and likely contributes to the progressive and accelerated decline in lung function observed in patients over time. Corticosteroids are the cornerstone of asthma treatment. While their action on inflammation and lung function is well characterized, their effect on remodeling remains largely unknown. An important hindrance to the study of airway remodeling as a major focus in asthma research is the lack of reliable non-invasive biomarkers. In consequence, the physiologic and clinical consequences of airway wall thickening and altered composition are not well understood. In this perspective, equine asthma provides a unique and ethical (non-terminal) preclinical model for hypothesis testing and generation. Severe equine asthma is a spontaneous disease affecting adult horses characterized by recurrent and reversible episodes of disease exacerbations. It is associated with bronchoalveolar neutrophilic inflammation, bronchospasm, and excessive mucus secretion. Severe equine asthma is also characterized by bronchial remodeling, which is only partially improved by prolonged period of disease remission induced by therapy or antigen avoidance strategies. This review will focus on the similarities and differences of airway remodeling in equine and human asthma, on the strengths and limitations of the equine model, and on the challenges the model has to face to keep up with human asthma research.
MeSH term(s)	Animals ; Asthma/physiopathology ; Disease Models, Animal ; Horse Diseases/physiopathology ; Horses ; Humans ; Veterinary Medicine/methods
Language	English
Publishing date	2019-11-12
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	125067-x
ISSN	1432-0878 ; 0302-766X
ISSN (online)	1432-0878
ISSN	0302-766X
DOI	10.1007/s00441-019-03117-4
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Article ; Online: MicroRNAs as Biomarkers in Corticosteroid-Resistant/Neutrophilic Asthma: Still a Long Way to Go!

Ricciardolo, Fabio L M / Carriero, Vitina / Bullone, Michela

American journal of respiratory and critical care medicine

2020 Volume 202, Issue 1, Page(s) 4–6

MeSH term(s)	Adrenal Cortex Hormones ; Asthma ; Biomarkers ; Humans ; Inflammation ; MicroRNAs ; Sputum
Chemical Substances	Adrenal Cortex Hormones ; Biomarkers ; MicroRNAs
Keywords	covid19
Language	English
Publishing date	2020-05-14
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202004-1216ED
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Article ; Online: The Contribution of Oxidative Stress and Inflamm-Aging in Human and Equine Asthma.

Bullone, Michela / Lavoie, Jean-Pierre

International journal of molecular sciences

2017 Volume 18, Issue 12

Abstract: Aging is associated with a dysregulation of the immune system, leading to a general pro-inflammatory state of the organism, a process that has been named inflamm-aging. Oxidative stress has an important role in aging and in the regulation of immune ... ...

Abstract	Aging is associated with a dysregulation of the immune system, leading to a general pro-inflammatory state of the organism, a process that has been named inflamm-aging. Oxidative stress has an important role in aging and in the regulation of immune responses, probably playing a role in the development of age-related diseases. The respiratory system function physiologically declines with the advancement of age. In elderly asthmatic patients, this may contribute to disease expression. In this review, we will focus on age-related changes affecting the immune system and in respiratory structure and function that could contribute to asthma occurrence, and/or clinical presentation in the elderly. Also, naturally occurring equine asthma will be discussed as a possible model for studying the importance of oxidative stress and immun-aging/inflamm-aging in humans.
MeSH term(s)	Aging/genetics ; Aging/immunology ; Aging/physiology ; Animals ; Asthma/immunology ; Asthma/metabolism ; Horses ; Humans ; Inflammation/immunology ; Inflammation/metabolism ; Neutrophils/metabolism ; Oxidative Stress/genetics ; Oxidative Stress/immunology ; Oxidative Stress/physiology
Language	English
Publishing date	2017-12-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms18122612
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Article: Within-Breath Oscillatory Mechanics in Horses Affected by Severe Equine Asthma in Exacerbation and in Remission of the Disease

Stucchi, Luca / Ferrucci, Francesco / Bullone, Michela / Dellacà, Raffaele L. / Lavoie, Jean Pierre

Animals. 2021 Dec. 21, v. 12, no. 1

2021

Abstract: Oscillometry is a technique that measures the resistance (R) and the reactance (X) of the respiratory system. In humans, analysis of inspiratory and expiratory R and X allows to identify the presence of tidal expiratory flow limitation (EFLt). The aim of ...

Abstract	Oscillometry is a technique that measures the resistance (R) and the reactance (X) of the respiratory system. In humans, analysis of inspiratory and expiratory R and X allows to identify the presence of tidal expiratory flow limitation (EFLt). The aim of this study was to describe inspiratory and expiratory R and X measured by impulse oscillometry system (IOS) in horses with severe asthma (SEA) when in clinical remission (n = 7) or in exacerbation (n = 7) of the condition. Seven healthy, age-matched control horses were also studied. Data at 3, 5, and 7 Hz with coherence > 0.85 at 3 Hz and >0.9 at 5 and 7 Hz were considered. The mean, inspiratory and expiratory R and X and the difference between inspiratory and expiratory X (ΔX) were calculated at each frequency. The data from the three groups were statistically compared. Results indicated that in horses during exacerbation of severe asthma, X during expiratory phase is more negative than during inspiration, such as in humans in presence of EFLt. The evaluation of X during inspiration is promising in discriminating between horses with SEA in remission and control horses.
Keywords	asthma ; horses ; mechanics ; remission ; respiratory system
Language	English
Dates of publication	2021-1221
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2606558-7
ISSN	2076-2615
ISSN	2076-2615
DOI	10.3390/ani12010004
Database	NAL-Catalogue (AGRICOLA)

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Article: Within-Breath Oscillatory Mechanics in Horses Affected by Severe Equine Asthma in Exacerbation and in Remission of the Disease.

Stucchi, Luca / Ferrucci, Francesco / Bullone, Michela / Dellacà, Raffaele L / Lavoie, Jean Pierre

Animals : an open access journal from MDPI

2021 Volume 12, Issue 1

Abstract	Oscillometry is a technique that measures the resistance (R) and the reactance (X) of the respiratory system. In humans, analysis of inspiratory and expiratory R and X allows to identify the presence of tidal expiratory flow limitation (EFLt). The aim of this study was to describe inspiratory and expiratory R and X measured by impulse oscillometry system (IOS) in horses with severe asthma (SEA) when in clinical remission (
Language	English
Publishing date	2021-12-21
Publishing country	Switzerland
Document type	Journal Article
ISSN	2076-2615
ISSN	2076-2615
DOI	10.3390/ani12010004
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Article ; Online: Effect of intravenous tiludronate disodium administration on the radiographic progression of osteoarthritis of the fetlock joint in Standardbred racehorses.

Bertuglia, Andrea / Basano, Ilaria / Pagliara, Eleonora / Bottegaro, Nika Brkljaca / Spinella, Giuseppe / Bullone, Michela

Journal of the American Veterinary Medical Association

2021 Volume 259, Issue 6, Page(s) 651–661

Abstract: Objective: To compare the effects of tiludronate disodium and 3 other medical treatments on clinical and radiographic findings and biomarkers of disease progression in horses with osteoarthritis of the fetlock joint.: Animals: 100 Standardbred ... ...

Abstract	Objective: To compare the effects of tiludronate disodium and 3 other medical treatments on clinical and radiographic findings and biomarkers of disease progression in horses with osteoarthritis of the fetlock joint. Animals: 100 Standardbred racehorses with spontaneous traumatic injury of the fetlock joint. Procedures: Horses were retrospectively grouped by whether they received tiludronate IV or triamcinolone acetonide and hyaluronan, polysulfated glycosaminoglycan, or interleukin-1 receptor antagonist protein intra-articularly. Data were collected on clinical, radiographic, and ultrasonographic findings and results for serum and synovial samples obtained before and 6 months after treatment. Lameness score, joint flexion test response, radiographic score, serum concentrations of tumor necrosis factor-α and carboxy-terminal telopeptides of collagen types I and II (CTX-I and II, respectively), and synovial fluid concentrations of interleukin-1β, prostaglandin E Results: All treatments resulted in a significant improvement in lameness score and joint flexion test response at 6 months. In horses that received triamcinolone acetonide and hyaluronan, synovial fluid interleukin-1β, prostaglandin E Conclusions and clinical relevance: Tiludronate appeared to inhibit the radiographic progression of osteoarthritis in high-motion joints of racehorses at 6 months after treatment by inhibiting subchondral bone remodeling. Whether this effect was associated with a worsening of progressive cartilage damage remains to be ascertained.
MeSH term(s)	Animals ; Diphosphonates/therapeutic use ; Horse Diseases/diagnostic imaging ; Horse Diseases/drug therapy ; Horses ; Osteoarthritis/diagnostic imaging ; Osteoarthritis/drug therapy ; Osteoarthritis/veterinary ; Retrospective Studies ; Synovial Fluid
Chemical Substances	Diphosphonates ; tiludronic acid (6PNS59HP4Y)
Language	English
Publishing date	2021-08-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	390811-2
ISSN	1943-569X ; 0003-1488
ISSN (online)	1943-569X
ISSN	0003-1488
DOI	10.2460/javma.259.6.651
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Article ; Online: Fetlock Joint Angle Pattern and Range of Motion Quantification Using Two Synchronized Wearable Inertial Sensors per Limb in Sound Horses and Horses with Single Limb Naturally Occurring Lameness.

Pagliara, Eleonora / Marenchino, Maddalena / Antenucci, Laura / Costantini, Mario / Zoppi, Giacomo / Giacobini, Mario Dante Lucio / Bullone, Michela / Riccio, Barbara / Bertuglia, Andrea

Veterinary sciences

2022 Volume 9, Issue 9

Abstract: Fetlock joint angle (FJA) pattern is a sensitive indicator of lameness. The first aim of this study is to describe a network of inertial measurement units system (IMUs) for quantifying FJA simultaneously in all limbs. The second aim is to evaluate the ... ...

Abstract	Fetlock joint angle (FJA) pattern is a sensitive indicator of lameness. The first aim of this study is to describe a network of inertial measurement units system (IMUs) for quantifying FJA simultaneously in all limbs. The second aim is to evaluate the accuracy of IMUs for quantifying the sagittal plane FJA overground in comparison to bi-dimensional (2-D) optical motion capture (OMC). 14 horses (7 free from lameness and 7 lame) were enrolled and analyzed with both systems at walk and trot on a firm surface. All enrolled horses were instrumented with 8 IMUs (a pair for each limb) positioned at the dorsal aspect of the metacarpal/metatarsal bone and pastern and acquiring data at 200 Hz. Passive markers were glued on the center of rotation of carpus/tarsus, fetlock, and distal interphalangeal joint, and video footages were captured at 60 Hz and digitalized for OMC acquisition. The IMU system accuracy was reported as Root Mean Square Error (RMSE) and Pearson Correlation Coefficient (PCC). The Granger Causality Test (GCT) and the Bland−Altman analysis were computed between the IMUs and OMC patterns to determine the agreement between the two systems. The proposed IMU system was able to provide FJAs in all limbs using a patented method for sensor calibration and related algorithms. Fetlock joint range of motion (FJROM) variability of three consecutive strides was analyzed in the population through 3-way ANOVA. FJA patterns quantified by IMUs demonstrated high accuracy at the walk (RMSE 8.23° ± 3.74°; PCC 0.95 ± 0.03) and trot (RMSE 9.44° ± 3.96°; PCC 0.96 ± 0.02) on both sound (RMSE 7.91° ± 3.19°; PCC 0.97 ± 0.03) and lame horses (RMSE 9.78° ± 4.33°; PCC 0.95 ± 0.03). The two systems’ measurements agreed (mean bias around 0) and produced patterns that were in temporal agreement in 97.33% of the cases (p < 0.01). The main source of variability between left and right FJROM in the population was the presence of lameness (p < 0.0001) and accounted for 28.46% of this total variation. IMUs system accurately quantified sagittal plane FJA at walk and trot in both sound and lame horses.
Language	English
Publishing date	2022-08-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2768971-2
ISSN	2306-7381 ; 2306-7381
ISSN (online)	2306-7381
ISSN	2306-7381
DOI	10.3390/vetsci9090456
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Article: Giant Multinucleated Cells Are Associated with Mastocytic Inflammatory Signature Equine Asthma.

Basano, Ilaria / Romolo, Alessandra / Iamone, Giulia / Memoli, Giulia / Riccio, Barbara / Lavoie, Jean-Pierre / Miniscalco, Barbara / Bullone, Michela

Animals : an open access journal from MDPI

2022 Volume 12, Issue 9

Abstract: Equine asthma is currently diagnosed by the presence of increased neutrophil (>5%), mast cell (>2%), and/or eosinophil (>1%) differential cell count. Macrophages are normal resident cells within the alveoli. Their presence in BALF is considered normal, ... ...

Abstract	Equine asthma is currently diagnosed by the presence of increased neutrophil (>5%), mast cell (>2%), and/or eosinophil (>1%) differential cell count. Macrophages are normal resident cells within the alveoli. Their presence in BALF is considered normal, but the clinical implication of the presence of activated or fused macrophages (giant multinucleated cells, GMC) is currently overlooked. We aimed to assess the prevalence, cytological determinants, and clinical significance of increased GMC counts in BALF of 34 asthmatic horses compared to 10 controls. Counts were performed on 15 randomly selected high magnification fields per cytospin slide (40×), and expressed as GMC:single macrophage (GMC:M) ratio. Regression models were used for statistical analysis. GMC was frequently observed in both asthmatic and control horses, with an increased prevalence of equine asthma (p = 0.01). GMC:M ratio was significantly higher in severe vs. mild to moderate equine asthmatic and control horses. In asthmatic horses, an increased GMC:M ratio was significantly associated with BALF mastocytosis (p = 0.01), once adjusting for age and the presence and severity of clinical signs of the horses. Tachypnea was the only clinical sign that tended to be positively associated with GMC:M ratio after adjustment (p = 0.08). In conclusion, our data suggest that a relationship might exist between molecular mechanisms regulating GMC formation and mast cell recruitment in the equine lung. The same mechanisms could lead to tachypnea even in the absence of respiratory effort at rest. We suggest including GMC count in the basic cytological assessment of BALF samples to gain more insights into their role in equine asthma.
Language	English
Publishing date	2022-04-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606558-7
ISSN	2076-2615
ISSN	2076-2615
DOI	10.3390/ani12091070
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Article ; Online: Asthma "of horses and men"--how can equine heaves help us better understand human asthma immunopathology and its functional consequences?

Bullone, Michela / Lavoie, Jean-Pierre

Molecular immunology

2015 Volume 66, Issue 1, Page(s) 97–105

Abstract: Animal models have been studied to unravel etiological, immunopathological, and genetic attributes leading to asthma. However, while experiments in which the disease is artificially induced have helped discovering biological and molecular pathways ... ...

Abstract	Animal models have been studied to unravel etiological, immunopathological, and genetic attributes leading to asthma. However, while experiments in which the disease is artificially induced have helped discovering biological and molecular pathways leading to allergic airway inflammation, their contribution to the understanding of the causality of the disease has been more limited. Horses naturally suffer from an asthma-like condition called "heaves" which presents sticking similarities with human asthma. It is characterized by reversible airway obstruction, airway neutrophilic inflammation, and a predominant Th2 immune response. This model allows one to investigate the role of neutrophils in asthma, which remains contentious, the regulation of chronic neutrophilic inflammation, and their possible implication in pulmonary allergic responses. Furthermore, the pulmonary remodeling features in heaves closely resemble those of human asthma, which makes this model unique to investigate the kinetics, reversibility, as well as the physiological consequences of tissue remodeling. In conclusion, heaves and asthma share common clinical presentation and also important immunological and tissue remodeling features. This makes heaves an ideal model for the discovery of novel pathways implicated in the asthmatic inflammation and associated tissue remodeling.
MeSH term(s)	Animals ; Asthma/immunology ; Asthma/pathology ; Horse Diseases/immunology ; Horse Diseases/pathology ; Horses ; Humans ; Inflammation/immunology ; Inflammation/pathology ; Lung/immunology ; Lung/pathology ; Neutrophil Infiltration ; Neutrophils/immunology ; Neutrophils/pathology
Language	English
Publishing date	2015-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	424427-8
ISSN	1872-9142 ; 0161-5890
ISSN (online)	1872-9142
ISSN	0161-5890
DOI	10.1016/j.molimm.2014.12.005
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Article: Use of a biopolymer delivery system to investigate the influence of interleukin-4 on recruitment of neutrophils in equids

Godbout, Mireille / Vargas, Amandine / Helie, Pierre / Bullone, Michela / Lavoie, Jean-Pierre

American journal of veterinary research. 2020 Apr., v. 81, no. 4

2020

Abstract: OBJECTIVE To use a biopolymer delivery system to investigate the ability of interleukin (IL)-4 to recruit neutrophils into subcutaneous tissues of equids. ANIMALS 16 horses and 2 ponies. PROCEDURES Animals were assigned to 3 experiments (6/experiment). ... ...

Abstract	OBJECTIVE To use a biopolymer delivery system to investigate the ability of interleukin (IL)-4 to recruit neutrophils into subcutaneous tissues of equids. ANIMALS 16 horses and 2 ponies. PROCEDURES Animals were assigned to 3 experiments (6/experiment). Effects of recombinant equine (Req) IL-4 (100, 250, or 500 ng/site) versus a positive control (ReqIL-8; 100 ng, 250 ng, or 1 μg/site) and a negative control (Dulbecco PBSS or culture medium) on neutrophil chemotaxis were assessed after SC injection into the neck with an injectable biopolymer used as the vehicle. Tissue samples including the biopolymer plug were collected by biopsy at various time points from 3 hours to 7 days after injection. Neutrophil infiltration was evaluated by histologic scoring (experiments 1, 2, and 3) or flow cytometry (experiment 3). RESULTS Histologic neutrophil infiltration scores did not differ significantly among treatments at most evaluated time points. On flow cytometric analysis, log-transformed neutrophil counts in biopsy specimens were significantly greater for the ReqIL-8 treatment (1 μg/site) than the negative control treatment at 3 but not 6 hours after injection; results did not differ between ReqIL-4 and control treatments at either time point. Negative control treatments induced an inflammatory response in most equids in all experiments. CONCLUSIONS AND CLINICAL RELEVANCE Flow cytometry was a more reliable method to estimate neutrophil migration than histologic score analysis. The ReqIL-4 treatment did not induce a detectable neutrophil response, compared with the negative control treatment in this study. Evidence of inflammation in negative control samples suggested the biopolymer is not a suitable vehicle for use in equids.
Keywords	Equidae ; biopolymers ; biopsy ; chemotaxis ; culture media ; flow cytometry ; histology ; horses ; inflammation ; interleukin-4 ; neck ; neutrophils ; veterinary medicine
Language	English
Dates of publication	2020-04
Size	p. 344-354.
Publishing place	American Veterinary Medical Association
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	390796-x
ISSN	1943-5681 ; 0002-9645
ISSN (online)	1943-5681
ISSN	0002-9645
DOI	10.2460/ajvr.81.4.344
Database	NAL-Catalogue (AGRICOLA)

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