BackgroundSevere neutrophilic asthma is poorly responsive to glucocorticosteroids (GC). Neutrophil extracellular traps (NETs) within the lungs have been associated with the severity of airway obstruction and inflammation in asthma, and were found to be unaffected by GC in vitro. As IL-17 is overexpressed in neutrophilic asthma and contributes to steroid insensitivity in different cell types, we hypothesized that NETs formation in asthmatic airways would be resistant to GC through an IL-17 mediated pathway.MethodsSix neutrophilic severe asthmatic horses and six healthy controls were studied while being treated with dexamethasone. Lung function, bronchoalveolar lavage fluid (BALF) cytology and NETs formation, as well as the expression of CD11b and CD13 by blood and airway neutrophils were evaluated. The expression of IL-17 and its role in NETs formation were also studied.ResultsAirway neutrophils from asthmatic horses, as opposed to blood neutrophils, enhanced NETs formation, which was then decreased by GC. GC also tended to decrease the expression of CD11b in blood neutrophils, but not in airway neutrophils. IL-17 mRNA was increased in BALF cells of asthmatic horses and was unaffected by GC. However, both GC and IL-17 inhibited NETs formation in vitro.ConclusionGC decreased NETs formation in vitro and also in vivo in the lungs of asthmatic horses. However, airway neutrophil activation during asthmatic inflammation was otherwise relatively insensitive to GC. The contribution of IL-17 to these responses requires further study.Electronic supplementary materialThe online version of this article (10.1186/s12931-017-0689-4) contains supplementary material, which is available to authorized users.

Pulmonary, oral and nasal microbiome are influenced by environmental conditions, but only the pulmonary microbiome differs between horses with and without asthma. This difference, mainly present when airway inflammation was present in horses with asthma but not in controls, suggests that the altered lung microbiome in asthma might not be inherent but coincident with inflammation.

Rationale Overexpression of the (+)insert smooth muscle myosin heavy chain (SMMHC) isoform could contribute to airway bronchospasm by increasing the velocity of contraction. Whether the (+)insert isoform is present in the small airways and its expression is reversible in asthma are unknown. Objectives To determine the anatomical location and the expression kinetics of the (+)insert SMMHC isoform in airways of horses with heaves and to evaluate its modulation in response to disease status. Methods We evaluated the (+)insert SMMHC isoform in the airways of horses with heaves during disease exacerbation and remission, and in controls. The expression kinetics of the SMMHC (+)insert was then assessed at multiple time points in two studies: first, in horses with heaves treated for a 1-year period with antigen avoidance alone, inhaled corticosteroids alone or both; second, in horses with heaves before and after a 30-day natural antigen exposure. Gene expression analysis was assessed by quantitative PCR and protein expression was confirmed by targeted mass spectrometry. Measurements and main results The (+)insert SMMHC isoform was significantly increased in central and peripheral airways, but not in the trachea of heavesaffected horses in clinical exacerbation when compared horses with heaves in remission and controls. Both corticosteroid administration and antigen avoidance led to a significant reduction of the (+)insert expression in the airways. The (+)insert SMMHC isoform was not significantly increased in airways after 1 month of antigenic re-exposure. Conclusions The (+)insert SMMHC expression is increased throughout the bronchial tree in horses with heaves and reversible by corticosteroids administration and antigen avoidance.

Summary — In ruminants, the forestomachs, and especially the reticulorumen, have walls with anatomical and histological properties that permit the exchanges of various metabolites, water and minerals between the rumen contents and the blood. The development of papillae on the walls and the local blood circulation favour these exchanges. They depend to varying degrees on the food supply and the concentrations of volatile fatty acids (VFA) produced by the microbial catabolism of polysaccharides. The absorption of VFA and ammonia occurs essentially by a process of passive diffusion of their nonionised form through the epithelial cell membranes. For each of these substances, the existence of a transport system for the ionised forms is also suspected, but its relative importance is unknown. Shortterm modifications in the absorption of these two substances are thus primarily determined by variations in their intraruminal concentrations and pH. Other factors may also be implicated, and it is known in particular that the absorption of ammonia is enhanced when the intraruminal concentration of VFA or the carbon dioxide (C0 2 ) level increases. The movement of urea through the wall occurs from the blood towards the rumen content according to the concentration gradient. The main factors liable to influence the transepithelial flux of urea seem to be the blood urea levels and factors that act on the contact surface between the blood compartment and the epithelium (C0 2 , VFA). Ruminal ammonia concentration also affects the net urea transfer across the rumen wall but the mechanisms involved in this regulation are not clearly understood. The absorption of water through the rumen wall results from an osmotic pressure gradient between the rumen and the plasma. This is modified not only by factors that modify the blood flow rates at the wall, but also by electrolyte concentrations. The absorption of minerals from the rumen has also been demonstrated (Mg, Ca, Na, Cl, K,

Background There are limited data on potential dysbiosis of the airway microbiota in horses with asthma. Hypothesis/Objectives We hypothesized that the respiratory microbiota of horses with moderate asthma is altered. Our objectives were (a) to quantify tracheal bacterial populations using culture and qPCR, (2) to compare aerobic culture and qPCR, and (c) to correlate bacterial populations with bronchoalveolar lavage fluid (BALF) cytology. Animals Eighteen horses with moderate asthma from a hospital population and 10 controls. Methods Prospective case‐control study. Aerobic culture was performed on tracheal aspirates, and streptococci, Pasteurella multocida, Chlamydophila spp., Mycoplasma spp., as well as 16S (bacterial) and 18S (fungal) rRNA subunits were quantified by qPCR. Results Potential pathogens such as Streptococcus spp., Actinobacillus spp., and Pasteurellaceae were isolated from 8, 5, and 6 horses with asthma and 3, 0, and 2 controls, respectively. There was a positive correlation between Streptococcus spp. DNA and 16S rRNA gene (r ≥ 0.7, P ≤ 0.02 in both groups), but the overall bacterial load (16S) was lower in asthma (1.5 ± 1.3 versus 2.5 ± 0.8 × 104 copy/μL, P < 0.05). There was no association between microbial populations and clinical signs, tracheal mucus or BALF inflammation. Conclusions and Clinical Importance This study does not support that bacterial overgrowth is a common feature of chronic moderate asthma in horses. Lower bacterial load could suggest dysbiosis of the lower airways, either as a consequence of chronic inflammation or previous treatments, or as a perpetuating factor of inflammation.