Effect of Dexamethasone and Fluticasone on Airway Hyperresponsiveness in Horses With Inflammatory Airway Disease.

BACKGROUND: Airway hyperresponsiveness (AWHR), expressed as hypersensitivity (PC75 RL ) or hyperreactivity (slope of the histamine dose-response curve), is a feature of inflammatory airway disease (IAD) or mild equine asthma in horses. Glucocorticoids are used empirically to treat IAD. OBJECTIVES: To determine whether dexamethasone (DEX) (0.05 mg/kg IM q24h) and inhaled fluticasone (FLUT) (3,000 µg q12h) administered by inhalation are effective in decreasing AWHR, lung inflammation, and clinical signs in horses with IAD. METHODS: A randomized crossover study design was used. Eight horses with IAD were assigned to a treatment group with either DEX or FLUT. Measured outcomes included lung mechanics during bronchoprovocative challenges, bronchoalveolar lavage fluid (BALF) cytology, and scoring of clinical signs during exercise. RESULTS: Dexamethasone and FLUT abolished the increase in RL by 75% at any histamine bronchoprovocative dose in all horses after the first week of treatment. However, after 2 weeks of FLUT treatment, 1 horse redeveloped hypersensitivity. There was a significant decrease in the number of lymphocytes after treatment with both DEX and FLUT (P = .039 for both) but no significant differences in other BALF cell types or total cell counts (P > .05). There was no difference in the scoring of the clinical signs during each treatment and washout period (P > .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Both DEX and FLUT treatments significantly inhibit airway hypersensitivity and hyperreactivity in horses with IAD. There are no significant effects on the clinical signs or the number of inflammatory cells (except lymphocytes) in BALF. The treatments have no residual effect 3 weeks after discontinuation.

The TRPV1 receptor agonist capsaicin is an ineffective bronchoprovocant in an experimental model of feline asthma.

OBJECTIVES: Airway hyper-responsiveness (AHR), a key feature of feline asthma, can be measured using bronchoprovocation testing. Limitations of both direct and indirect bronchoprovocants evaluated to date in experimental feline asthma have led to a search for a more specific indirect bronchoprovocant (ie, one which relies on existing inflammatory cells or activated neural pathways in diseased but not healthy airways). We hypothesized that capsaicin, a transient receptor potential cation channel subfamily V member 1 agonist, would lead to dose-responsive increases in airway resistance as measured by ventilator-acquired pulmonary mechanics in experimentally asthmatic cats. METHODS: Five cats induced to have asthma using Bermuda grass allergen (BGA) were studied. Twenty-four hours after aerosol challenge of BGA, cats were anesthetized and underwent neuromuscular blockade for ventilator-acquired pulmonary mechanics. Cats were monitored with pulse oximetry for hemoglobin desaturation. Parameters recorded on a breath-by-breath basis on the ventilator included airway resistance (Raw) and compliance. Saline at baseline and 10-fold increasing concentrations of capsaicin (0.4-4000.0 µM) were aerosolized for 30 s and data collected for 4 mins between doses. The intended endpoint of the study was a doubling in baseline airway resistance, halving of compliance or oxygen desaturation <75%. RESULTS: All cats completed the trial, reaching the highest dose of capsaicin without reaching any of the aforementioned endpoints. No biologically significant alteration in any other pulmonary mechanics parameter was noted. CONCLUSIONS AND RELEVANCE: Capsaicin does not appear to be an effective bronchoprovocant in a feline asthma model.

Comparison of direct and indirect bronchoprovocation testing using ventilator-acquired pulmonary mechanics in healthy cats and cats with experimental allergic asthma.

Airway hyperresponsiveness (AHR) is a key feature of asthma and can be measured using bronchoprovocation. Direct (methacholine, MCh) or indirect (adenosine-5-monophosphate, AMP; or mannitol) bronchoprovocants are used in human patients, the latter inducing AHR only with pre-existing airway inflammation. The present study compared the responses to direct (MCh) and indirect (mannitol, AMP) bronchoprovocation in healthy and asthmatic cats (n=6/group). The order of bronchoprovocant was randomized using a published table of random numbers and there was a 1-month washout before crossover to the next treatment. Pulmonary mechanics were measured in anesthetized and mechanically ventilated cats using a critical care ventilator. Saline at baseline and increasing doses of each bronchoprovocant were aerosolized for 30 s, followed by 4 min of data collection between doses. The endpoint for each bronchoprovocant was reached when airway resistance exceeded 200% of baseline values (EC200Raw). There was a significant difference (P<0.001) in the airway response of asthmatic vs. healthy cats over the range of MCh concentrations, despite there being no significant difference in the EC200Raw between the groups. Response to MCh was significantly greater (P<0.05) in asthmatic than in healthy cats at MCh concentrations as low as 0.0625 mg/mL. For AMP, a small subset of asthmatics (n=2/6) responded at low concentrations; four asthmatic cats and all healthy cats failed to respond even to the highest concentrations of AMP. One asthmatic cat but no healthy cats responded to mannitol. In conclusion, MCh discriminated asthmatic from healthy cats but neither AMP nor mannitol was an effective bronchoprovocant in this model.

A bovine model of respiratory Chlamydia psittaci infection: challenge dose titration.

This study aimed to establish and evaluate a bovine respiratory model of experimentally induced acute C. psittaci infection. Calves are natural hosts and pathogenesis may resemble the situation in humans. Intrabronchial inoculation of C. psittaci strain DC15 was performed in calves aged 2-3 months via bronchoscope at four different challenge doses from 10(6) to 10(9) inclusion-forming units (ifu) per animal. Control groups received either UV-inactivated C. psittaci or cell culture medium. While 10(6) ifu/calf resulted in a mild respiratory infection only, the doses of 10(7) and 10(8) induced fever, tachypnea, dry cough, and tachycardia that became apparent 2-3 days post inoculation (dpi) and lasted for about one week. In calves exposed to 10(9) ifu C. psittaci, the respiratory disease was accompanied by severe systemic illness (apathy, tremor, markedly reduced appetite). At the time point of most pronounced clinical signs (3 dpi) the extent of lung lesions was below 10% of pulmonary tissue in calves inoculated with 10(6) and 10(7) ifu, about 15% in calves inoculated with 10(8) and more than 30% in calves inoculated with 10(9) ifu C. psittaci. Beside clinical signs and pathologic lesions, the bacterial load of lung tissue and markers of pulmonary inflammation (i.e., cell counts, concentration of proteins and eicosanoids in broncho-alveolar lavage fluid) were positively associated with ifu of viable C. psittaci. While any effect of endotoxin has been ruled out, all effects could be attributed to infection by the replicating bacteria. In conclusion, the calf represents a suitable model of respiratory chlamydial infection. Dose titration revealed that both clinically latent and clinically manifest infection can be reproduced experimentally by either 10(6) or 10(8) ifu/calf of C. psittaci DC15 while doses above 10(8) ifu C. psittaci cannot be recommended for further studies for ethical reasons. This defined model of different clinical expressions of chlamydial infection allows studying host-pathogen interactions.

Effects of obesity on lung function and airway reactivity in healthy dogs.

The present study investigated the effects of bodyweight (BW) gain on respiratory function and airway responsiveness in healthy Beagles using barometric whole body plethysmography (BWBP). Six adult dogs were examined before and after a fattening diet. The high-energy diet induced a mean increase in BW of 41±6%. BWBP basal parameters were recorded prior to airway reactivity testing (using increasing concentrations of histamine nebulisations). An airway responsiveness index (H-Penh300) was calculated as the histamine concentration necessary to reach 300% of basal enhanced pause (Penh, bronchoconstriction index). The same dogs underwent a doxapram hydrochloride (Dxp) stimulation testing 2 weeks later. Basal measurements showed that obese dogs had tidal volume per kg (TV/BW) that was significantly decreased whilst respiratory rate (RR) increased significantly. H-Penh300 decreased significantly in obese Beagles, indicating increased bronchoreactivity. Dxp administration induced a significant increase in TV/BW, minute volume per kg (MV/BW), peak inspiratory and expiratory flows per kg (PIF/BW and PEF/BW) in both normal and obese dogs although the TV/BW increase was significantly less marked in the obese group. In conclusion, obesity induced changes in basal respiratory parameters, increased bronchoreactivity and a blunted response to Dxp-induced respiratory stimulation. This combination of basal respiratory parameters, bronchoreactivity testing and pharmacological stimulation testing using non-invasive BWBP can help characterize pulmonary function and airway responsiveness in obese dogs.

Lactobacillus rhamnosus HN001 attenuates allergy development in a pig model.

BACKGROUND: Probiotics have been studied as immunomodulatory agents of allergy. Several human probiotic trials tracking the development of eczema and other forms of allergy have yielded inconsistent results. A recent infant study demonstrated that pre and postnatal Lactobacillus rhamnosus HN001 (HN001) supplementation decreased the prevalence of eczema and IgE associated eczema. However, the influence of HN001 on the incidence of wheeze, asthma, and/or other allergic manifestations has yet to be reported. OBJECTIVE: This study was conducted to determine the effects of the probiotic HN001 on the development of allergic lung disease in a pig model. METHODS: Allergy was induced by a series of subcutaneous and intratracheal sensitizations with Ascaris suum allergen (ASA) during a six week time frame in post-weanling pigs supplemented daily with HN001, or without supplementation. One week following final sensitization intradermal skin tests and respiratory challenges were conducted. RESULTS: In response to intradermal and respiratory challenges, ASA-sensitized pigs fed HN001 had less severe skin flare reactions, smaller increases in pleural pressure, and trends towards lower changes in arterial oxygen and carbon dioxide partial pressure levels compared to control pigs. The frequency of ASA-specific IFN-γ-secreting peripheral blood mononuclear cells, as well as the amount of IL-10 produced by ASA-specific cells, was of greater magnitude in probiotic-fed pigs compared to control animals. These observations suggest that differences in clinical responses to the allergen challenges may be related to probiotic-induced modulation of Th1 (IFN-γ) and regulatory (IL-10) cytokine expression. CONCLUSIONS: Probiotic supplementation decreased the severity of allergic skin and lung responses in allergen-sensitized pigs with a corresponding increase in IFN-γ expression. A similar correlation between certain allergic responses and increased IFN-γ expression has been reported in human clinical studies of allergy; this pig model of allergy may be indicative of potential probiotic modulation of allergic lung disease in humans.

Assessing the effectiveness of intubation as a challenge model in contagious bovine pleuropneumonia vaccine experiments.

A study was carried out to assess the effectiveness of a bronchoscope in administering a pathogenic field strain of Mycoplasma mycoides subsp. mycoides (MmmSC) in cattle challenge experiments. Out of 16 animals inoculated using the bronchoscope, 10 (62.2%) showed clinical disease as evidenced by fever and 15 (93.8%) displayed typical lesions of CBPP from which MmmSC was isolated. Serum samples collected weekly were tested by Complement Fixation Test (CFT) and competitive enzyme-linked immunosorbent assay (c-ELISA). Antibodies to MmmSC were detected in 10 out of the 16 animals by the CFT and 11 out of the 16 animals by c-ELISA. The onset of clinical disease was as early as 2 days post-inoculation, and most of the animals developed clinical disease 2 to 3 weeks post-infection. These results clearly demonstrate that nasotracheal inoculation of pathogenic strain of MmmSC with the aid of a bronchoscope can lead to early onset of clinical disease; similar to previous studies but with higher numbers of animals showing clinical disease. This is in contrast with previous studies where early clinical disease was observed in as little as 15% of inoculated animals. This nasotracheal inoculation method using a bronchoscope can, therefore, be adopted for use in experimental challenge infections of cattle. This method is found to be a better replacement to the contact transmission method whose drawback includes extra cost of donor animals and unpredictable rate and timing of transmission from intubated to challenge animals.

Differential rates of apoptosis and recruitment limit eosinophil accumulation in the lungs of asthma-resistant CBA/Ca mice.

The accumulation of eosinophils is a common feature of allergic airway inflammation and correlates with disease severity. In an ovalbumin (OVA)-induced murine model of allergic lung disease, CBA/Ca mice develop much lower levels of lung eosinophilia, lung oedema, mucus hypersecretion and airways obstruction than BALB/c and C57BL/6 strains. In this study these strains have been examined to identify mechanisms that control the recruitment and survival of eosinophils in the allergic lung. Following immunization with OVA, CBA/Ca mice developed a robust systemic allergic response, with high levels of total and OVA-specific IgE and increases in peripheral blood eosinophils. Lung eotaxin-1 levels and expression of CD18 on eosinophils recovered by bronchoalveolar lavage (BAL) were least pronounced in CBA/Ca mice, whereas mRNA for L-selectin was highest in eosinophils from C57BL/6 mice. Apoptosis of BAL eosinophils ex vivo was most pronounced in the CBA/Ca strain. BALB/c mice expressed the highest levels of the eosinophil growth and survival factor interleukin (IL)-5 in the lungs and BAL eosinophils from these animals expressed more of the anti-apoptotic proteins Bcl-xL and Bcl-2 than cells from the other strains. A combination of lower levels of recruitment and rapid apoptosis may therefore limit the accumulation of eosinophils and pathology in the lungs of CBA/Ca mice. In addition, although the level of pathology that developed in C57BL/6 and BALB/c mice was similar, some of the underlying mechanisms are likely to differ.

Comparison of barometric whole body plethysmography and its derived parameter enhanced pause (PENH) with conventional respiratory mechanics in healthy Beagle dogs.

The purpose of the study was to compare barometric whole body plethysmography (BWBP) and its derived parameter, enhanced pause (PENH), with conventional respiratory mechanics measurements. Resistance (RL), dynamic compliance (Cdyn) and pleural pressure changes were measured in six healthy anaesthetised Beagle dogs using a pneumotachograph and oesophageal balloon technique consecutive to BWBP-derived variables. Upper airway airflow limitation was established (1) by a filter or (2) by insertion of a narrow endotracheal tube. Bronchoconstriction was induced by nebulisation of carbachol at increasing concentrations until PENH exceeded 300% baseline. Upper airway narrowing significantly increased resistance (baseline RL 2.0+/-0.3, RL filter 11.8+/-3.2, RL luminal narrowing 21.1+/-2.3cm H(2)O/L/s; P <0.03), whereas PENH did not change significantly (baseline PENH 0.55+/-0.17, PENH filter 0.49+/-0.10; PENH luminal narrowing 0.50+/-0.18; P >0.05). Carbachol-induced bronchoconstriction caused a significant increase in PENH (baseline PENH 0.43+/-0.14, PENH carbachol 2.62+/-2.14; P <0.02) and resistance (baseline RL 2.1+/-0.3, RL carbachol 28.8+/-13.0 cm H2O/L/s; P <0.01), and a pronounced drop in compliance (baseline Cdyn 163.3+/-73.9, Cdyn carbachol 9.7+/-2.9mL/cmH2O; P <0.02). It was concluded that BWBP detects airflow limitation due to bronchoconstriction but not due to upper airway obstruction in healthy dogs. BWBP represents a valid, although not very sensitive screening tool for respiratory function testing.

Early onset airway obstruction in response to organic dust in the horse.

Equine recurrent airway obstruction (RAO) has been used as a naturally occurring model of human asthma. However, it is unknown whether there is an early-phase response in RAO. The aim of this study was to determine whether exposure to organic dust induces immediate changes in lung function in RAO-affected horses, which could be mediated by airway mast cells. Six RAO-affected horses in remission and six control horses were challenged with hay-straw dust suspension by nebulization. Total respiratory resistance at 1 Hz, measured by forced oscillation, was increased from 0.62 +/- 0.09 cmH(2)O.l(-1).s (mean +/- SE) to 1.23 +/- 0.20 cmH(2)O.l(-1).s 15 min after nebulization in control horses (P = 0.023) but did not change significantly in the RAO group. Total respiratory reactance at 1 Hz (P = 0.005) was significantly lower in the control horses (-0.77 +/- 0.07 cmH(2)O.l(-1).s) than in the RAO group (-0.49 +/- 0.04 cmH(2)O.l(-1).s) 15 min after nebulization. Bronchoalveolar lavage fluid (BALF) histamine concentration was significantly elevated 10 and 20 min postnebulization in control horses but not in RAO horses. Minimum reactance at 1 Hz in the early postnebulization period significantly correlated with both prechallenge BALF mast cell numbers (r = -0.65, P = 0.02) and peak BALF histamine concentration postnebulization (r = -0.61, P = 0.04). In conclusion, RAO horses, unlike human asthmatic patients, do not exhibit an early-phase response. However, healthy control horses do demonstrate a mild but significant early (<20 min) phase response to inhaled organic dust. This response may serve to decrease the subsequent dose of dust inhaled and as such provide a protective mechanism, which may be compromised in RAO horses.

Altered airway responsiveness in adult sheep born prematurely: effects of allergen exposure.

The aim of this study was to determine the effects of preterm birth per se on airway function in adult sheep. Preterm birth was induced at approximately 0.89 of term. At approximately 1 year of age the authors measured pulmonary resistance (RL) and airway responsiveness before and after house dust mite (HDM) challenge. Mature preterm sheep tended to have greater baseline RL than controls (P = .12): the smaller preterm sheep showed significantly greater RL than controls following bronchoconstrictor challenge. Preterm animals tended to have greater baseline total blood leukocyte count (P = .06). It was concluded that preterm sheep, especially with low postnatal growth, have greater airway responsiveness to bronchoconstrictor and higher baseline RL.

Qualitative and quantitative evaluation of equine respiratory mechanics by impulse oscillometry.

REASONS FOR PERFORMING STUDY: The long-established conventional reference technique (CRT) for measuring respiratory mechanics in horses lacks sensitivity and there is a need for further refinement in new technology, such as the impulse oscillometry system (IOS). OBJECTIVES: To evaluate the potential use of the IOS as a clinical respiratory function test and compare it to the current CRT in horses suffering from common upper and lower airway dysfunctions. METHODS: Six healthy horses were tested before and after induction of a unilateral nasal obstruction (UNO) or transient left laryngeal hemiplegia (LLH). Six heaves-affected horses were tested in clinical remission and during a heaves crisis, before and after nebulisation of cumulative doses of a bronchodilator therapy (ipratropium bromide; IPB). RESULTS: As opposed to the CRT, the IOS was able to detect partial upper airway obstruction (UAO) caused by UNO or LLH in resting horses, without differentiating both conditions. Upper airway obstruction caused an upward shift of resistance (R(rs)) from 5 to 35 Hz without altering reactance (X(rs)). As for the CRT, IOS respiratory parameters measured in heaves-affected horses in crisis differed significantly from values measured during remission. The difference in frequency-dependent behaviour of R(rs) and X(rs) allowed discrimination between upper and lower airway obstructions. Bronchodilator treatment induced significant dose-dependent changes in X(rs) at 5 and 10 Hz, from the first dose. Total pulmonary resistance (RL) and R(rs) at 5 Hz were affected from the second dose and displayed similar sensitivity. Although post treatment RL values were comparable to remission, R(rs) and X(rs) remained significantly different, characterising persistent peripheral obstruction. CONCLUSIONS: The IOS was more sensitive than the CRT in detecting partial UAO in resting horses and persistent post treatment peripheral dysfunction in heaves-affected horses. The IOS is a sensitive test that provides graded quantitative and qualitative information on disease-induced respiratory dysfunctions as well as on treatment efficiency in horses. POTENTIAL RELEVANCE: The IOS could represent a practical and sensitive alternative respiratory function test for routine clinical investigations of common airway obstructive diseases and therapy in horses.

Evaluation of respiratory function by barometric whole-body plethysmography in healthy dogs.

The objective of the present study was to assess the validity of barometric whole-body plethysmography (BWBP), to establish reference values, and to standardise a bronchoprovocative test to investigate airway responsiveness using BWBP in healthy dogs. BWBP measurements were obtained from six healthy beagle dogs using different protocols: (1) during three consecutive periods (3.5min each) in two morning and two evening sessions; (2) before and after administration of two protocols of sedation; (3) before and after nebulisation of saline and increasing concentrations of carbachol and histamine both in conscious dogs and in dogs under both protocols of sedation. Enhanced pause (PENH) was used as index of bronchoconstriction. Basal BWBP measurements were also obtained in 22 healthy dogs of different breeds, age and weight. No significant influence of either time spent in the chamber or daytime was found for most respiratory variables but a significant dog effect was detected for most variables. A significant body weight effect was found on tidal volume and peak flow values (P<0.05). Response to carbachol was not reproducible and always associated with side effects. Nebulisation of histamine induced a significant increase in respiratory rate, peak expiratory flow, peak expiratory flow/peak inspiratory flow ratio and PENH (P<0.05). The response was reproduced in each dog at different concentrations of histamine. Sedation with acepromazine+buprenorphine had little influence on basal measurements and did not change the results of histamine challenge. It was concluded that BWBP is a safe, non invasive and reliable technique of investigation of lung function in dogs which provides new opportunities to characterise respiratory status, to evaluate airway hyperresponsiveness and to assess therapeutic interventions.

Whole body barometric plethysmography: a screening method to investigate airway reactivity and acute lung injuries in freely moving pigs.

The aim of this work was to investigate whether the Penh index, measured using whole body barometric plethysmography, can be used as a screening parameter to evaluate the airway reactivity and the intensity of the pulmonary response to endotoxins. Penh was firstly recorded in non-sedated freely moving piglets exposed (1) to a nebulized acetylcholine (Ach) pre-treated or not with clenbuterol, or (2) to endotoxin challenge. To measure Penh simultaneously with total pulmonary resistance (R(L)), dynamic compliance (C(dyn)) and intrapleural pressure changes (Max Delta Ppl), an oesophageal balloon catheter technique was used and the piglets were anaesthetised. The recordings were performed during (1) an intravenous metacholine (Mch) challenge and (2) in endotoxin-exposed animals. In freely moving animals, Ach induced a significant dose-dependent increase in Penh, which was significantly blocked by clenbuterol. Endotoxin instillation also resulted in a significant rise in Penh while the corresponding response measured under anaesthesia was significantly and positively correlated with R(L) and Max Delta Ppl. Similar results were obtained during Mch challenge but the Penh was negatively correlated with C(dyn). We conclude that Penh could be used in freely moving piglets as a screening index for airway reactivity and pulmonary functional changes in cholinergic and endotoxin challenges.

Allergen challenge alters lymphocyte phosphodiesterase activity in horses with heaves.

Heaves is an allergic airway disease in horses characterised by reversible airway obstruction, bronchial hyperresponsiveness and airway inflammation associated with a Th(2) response. Cyclic nucleotide-dependent signalling pathways can regulate lymphocyte function. In this study, we examined lymphocyte PDE activity comparing horses with heaves to healthy control animals. Total PDE activity and the effects of isoenzyme selective inhibitors were measured before, 5 and 24 h after the start of a 7 h allergen challenge. Allergen challenge had no effect on either total cAMP PDE activity or its inhibition by the PDE4 selective inhibitor, rolipram, and the non-selective PDE inhibitor, theophylline. In contrast, the PDE3 selective inhibitor, quazinone, caused significantly greater inhibition of cAMP PDE activity before challenge in the heaves susceptible group. Additionally, total cGMP PDE activity was significantly lower 24 h after the start of challenge in the heaves affected group (11+/-2 and 21+/-3 pmol/min/mg for heaves and control animals, respectively) and the PDE5 selective inhibitor, zaprinast, caused significantly less inhibition in the heaves group at this time point. The functional significance of these findings was explored by examining the effect of PDE3, PDE4 and PDE5 selective inhibitors on mitogen-induced mononuclear cell proliferation before and 24 h after the start of allergen challenge. Proliferation decreased after challenge in the heaves group (stimulation index=328+/-110 and 200+/-72 before and after challenge, respectively) whilst remaining constant in the control group (stimulation index=161+/-13 and 183+/-45 before and after challenge, respectively). However, all three PDE inhibitors caused a similar amount of inhibition at each time point and the effect of a combination of a PDE3 and a PDE5 inhibitor was simply additive in both groups. These results suggest differences in the control of lymphocyte PDE activity in horses with heaves.

Use of the impulse oscillometry system for testing pulmonary function during methacholine bronchoprovocation in horses.

OBJECTIVE: To compare sensitivity of the impulse oscillometry system (IOS) with that of the conventional reference technique (CRT; ie, esophageal balloon method) for pulmonary function testing in horses. ANIMALS: 10 horses (4 healthy; 6 with recurrent airway obstruction [heaves] in remission). PROCEDURE: Healthy horses (group-A horses) and heaves-affected horses (group-B horses) were housed in a controlled environment. At each step of a methacholine bronchoprovocation test, threshold concentration (TC(2SD); results in a 2-fold increase in SD of a value) and sensitivity index (SI) were determined for respiratory tract system resistance (R(rs)) and respiratory tract system reactance (X(rs)) at 5 to 20 Hz by use of IOS and for total pulmonary resistance (RL) and dynamic lung compliance (C(dyn)), by use of CRT. RESULTS: Bronchoconstriction resulted in an increase in R(rs) at 5 Hz (R(5Hz)) and a decrease in X(rs) at all frequencies. Most sensitive parameters were X(rs) at 5 Hz (X(5Hz)), R(5Hz), and R(5Hz):R(10Hz) ratio; RL and the provocation concentration of methacholine resulting in a 35% decrease in dynamic compliance (PC(35)C(dyn)) were significantly less sensitive than these IOS parameters. The TC(2SD) for X(rs) at 5 and 10 Hz was significantly lower in group-B horses, compared with group-A horses. The lowest TC(2SD) was obtained for X(5Hz) in group-B horses and R(5Hz) in group-A horses. CONCLUSIONS AND CLINICAL RELEVANCE: In contrast to CRT parameters, IOS parameters were significantly more sensitive for testing pulmonary function. The IOS provides a practical and noninvasive pulmonary function test that may be useful in assessing subclinical changes in horses.

Allergen-specific IgG and IgA in serum and bronchoalveolar lavage fluid in a model of experimental feline asthma.

Allergic asthma, a Th2 cell driven response to inhaled allergens, has classically been thought of as predominantly mediated by IgE antibodies. To investigate the role of other immunoglobulin classes (e.g., IgG and IgA) in the immunopathogenesis of allergic asthma, levels of these allergen-specific immunoglobulins were measured in serum and mucosal fluids. Bermuda grass allergen (BGA)-specific IgG and IgA ELISAs in serum and bronchoalveolar lavage fluid (BALF) were developed and optimized in an experimental model of BGA-induced feline asthma. Levels of BGA-specific IgG and IgA significantly increased over time in serum and BALF after allergen sensitization. Additionally, these elevated levels of BGA-specific IgG and IgA were seen in conjunction with the development of an asthmatic phenotype indicated by positive intradermal skin tests, enhanced airways hyperreactivity, and increased eosinophil percentages in the BALF.

Airway responsiveness of rabbits after exposure to 2-octyl dodecanol.

Cooling lubricants are used in the metal industry during drilling or turning. Vapors and aerosols of these lubricants are suspected to induce airway hyperresponsiveness (AHR) in exposed workers. In a previous study the authors demonstrated that water-soluble lubricants induce AHR after acute exposure of rabbits to concentrations near the German MAK value (10 mg/m(3)). In the present investigation the influence of a fatty alcohol as special non-water-soluble cooling lubricant was examined to determine its influence on airway responsiveness (AR). The effects of an aerosolized non-water-soluble lubricant (40, 90, and 220 mg/m(3)) on AR to acetylcholine in a rabbit model were studied. Lubricant atmosphere analysis was performed with infrared spectroscopy. Before exposure, after 2 and 4 hours of application, AR to aerosols from 0.2 and 2% acetylcholine was tested. Basal airway and cardiovascular parameters as well as blood gases did not change during exposure. Lubricant aerosol concentration of 40 and 220 mg/m(3) for 4 hours did not significantly alter AR. Inhalation of 90 mg/m(3) lubricant increased contractile response to ACH significantly. In contrast to formerly investigated water-soluble cooling lubricants, the examined non-water-soluble lubricant did not increase AR in concentrations near the MAK; however, in higher concentrations a significant (p<.05) increase was obtained.

Effect of instillation into lung of autologous blood on pulmonary function and tracheobronchial wash cytology.

This study aimed at measuring the functional consequences and the pulmonary cytology changes following a simulation of pulmonary haemorrhage. Pulmonary function tests including lobeline-induced hyperventilation, cytology of tracheo-bronchial wash (TBW) and thoracic radiographs were performed before, as well as 1, 7, 14 and 28 days after, the instillation of 300 ml of blood into the lungs of 4 horses deemed free of exercise-induced pulmonary haemorrhage (Group 1). Control data (Group 2) were obtained by instilling the same volume of saline into the lungs of the same horses in a crossover design (control). The instillation of blood or saline resulted in an increase in the number of neutrophils in the TBW. Thoracic radiographs showed increased opacity in the caudodorsal region of the lungs in 4/4 (Day 1) and 2/4 horses (Day 7), in Group 1, and in 2/4 (Day 1) and 0/4 horses (Day 7) in the control group. These changes were attributed to the instillation procedure rather than the nature of the instilled material. Breathing mechanics and arterial blood gases at rest were not affected in either Groups 1 or 2. However, the maximal expiratory peak flow recorded during lobeline-induced hyperventilation was significantly lower (P<0.05) and the total pulmonary resistance significantly higher (P<0.05) on Day 1 in Group 1, but not Group 2. These observations suggest that expiratory flows might be partly limited in bleeders when breathing at high airflow.

Comparison of forced oscillation with the conventional method for histamine bronchoprovocation testing in horses.

OBJECTIVE: To compare response of horses to histamine bronchoprovocation (HBP), using total respiratory resistance (Rrs) measured by forced oscillatory mechanics (FOM) with dynamic compliance (Cdyn) and pulmonary resistance (RL) measured by the esophageal balloon method. ANIMALS: 10 horses with various degrees of airway reactivity. PROCEDURE: The 2 methods for measuring airway responses to HBP were performed on separate days. Endpoints compared were increase of 150 or 200% of baseline Rrs (PC150Rrs, PC200Rrs) and to 150% of baseline RL (PC150RL) or decrease to 65% of baseline Cdyn (PC65Cdyn). Frequency dependence of respiratory mechanics, using FOM, was evaluated, using the slope of Rrs over 1 to 3 Hz and the ratios of Rrs at 1 Hz to Rrs at 2 and 3 Hz (Rrs1Hz/Rrs2Hz, Rrs1Hz/Rrs3Hz) and of Rrs at 2 Hz to Rrs at 3 Hz (Rrs2Hz/Rrs3Hz). Effect of histamine on frequency dependence was assessed. RESULTS: Correlation with PC65Cdyn was high for PC150Rrs (rs = 0.93) and PC200Rrs (rs = 0.96). Correlation between PC65Cdyn and PC150RL was weakly positive (rs = 0.61). The slope of Rrs over 1 to 3 Hz changed significantly between baseline (-0.07+/-0.09 cm H2O/L/s/Hz) and final histamine dose (-0.28+/-0.10 cm H2O/L/s/Hz). The Rrs1Hz/Rrs3Hz and Rrs2Hz/Rrs3Hz differed significantly (P < 0.05 between baseline [1.27+/-0.36 and 0.96+/-0.11, respectively] and final histamine dose [1.62+/-0.37 and 1.09+/-0.14, respectively]). CONCLUSIONS: Correlation between histamine-induced changes in respiratory mechanics, as measured by FOM and the pneumotachograph-esophageal balloon method, was good. The FOM results indicated frequency dependence of respiratory mechanics during HBP. CLINICAL RELEVANCE: A noninvasive method of measuring airway reactivity will facilitate routine evaluation of horses with suspected small airway disease and may be suitable for field studies.