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.     

In vitro responses of distal airways in horses with recurrent airway obstruction

Distal airway segments (ID, 3 to 4 mm; length, 5 mm) from 2 groups of horses were isolated and suspended in tissue baths filled with Krebs solution, aerated with 5% CO2 in oxygen and maintained at 37 degrees C. Responses to exogenous acetylcholine, isoproterenol, or electrical field stimulation were compared. Control horses (n = 30) had no history of recurrent airway obstruction, whereas principal horses (n = 15) had recurrent airway obstruction and were studied during an acute episode of airway obstruction. Although the distal airways contracted in response to the cumulative half-logarithmic addition of acetylcholine (10(-10) M to 10(-3) M) in both groups, bronchi obtained from principals were less sensitive to acetylcholine than were bronchi obtained from controls. Tetdrodotoxin-sensitive electrical field stimulation-induced contractions were observed in both groups of airways, but the tension achieved in principal bronchi was less than in controls. All electrical field stimulation-induced contractions were abolished by atropine, indicating that the only excitatory innervation of equine distal airway is through the parasympathetic system. To examine the effect of isoproterenol and determine inhibitory innervation, bronchi were precontracted with histamine. Electrical field stimulation did not cause relaxation of precontracted bronchi in either group, thus indicating that distal airways lack inhibitory innervation. Isoproterenol caused similar, dose-dependent relaxation in both groups.     

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.     

Reproducibility of Airway Responsiveness in Horses Using Flowmetric Plethysmography and Histamine Bronchoprovocation

Background: Inflammatory airway disease has a high prevalence in horses, but is often a diagnostic challenge. Flowmetric plethysmography and histamine bronchoprovocation (FP/HBP) is a simple and effective tool for diagnosis, but reproducibility of these measurements made over time has not been established.
Hypothesis: We hypothesize that the measurement of airway responsiveness in horses using FP/HBP is consistent over both short and long periods of time.
Animals: Twenty-nine healthy adult horses from 2 university herds.
Methods: In this prospective experimental study, airway responsiveness was determined in each horse at day 0 (baseline [BL]) with FP/ HBP, using PC35 (provocative concentration of histamine needed to increase Δ_flow by 35%) as a measure of airway responsiveness. Each horse was re-tested 1–4 weeks after BL (short-term [ST]) and again at 3–12 months after BL (long-term [LT]).
Results: In the ST period, 23/27 (85%) of the horses had a PC35 that was within 1 doubling concentration of histamine of their BL value, with a mean change of 0.52 doubling concentrations (95% CI 0.26–0.79, range 0–2.06). For the LT data, 19/26 (73%) of horses were within 1 doubling concentration of their BL value, with a mean change of 0.81 doubling concentrations (95% CI 0.45–1.17, range 0.14–3.10). There was no significant difference in reproducibility between the 2 groups of subjects.
Conclusions and Clinical Importance: Repeated measurements of airway responsiveness obtained with FP/HBP show acceptable reproducibility over time periods up to a year. However, caution must be used when testing horses when ambient air temperature is low.     

Reflex activities of the upper airway muscles during experimental nasal occlusion in anesthetized dogs

Reflex responses of the upper airway muscles during experimental nasal and tracheal occlusions were studied in 21 anesthetized dogs breathing through the nose or a tracheostomy (tracheal cannula). Out of them, five animals were examined for maintained negative and positive pressures applied to the isolated upper airway. When the nose was occluded at end-expiration during three consecutive breathings, the electromyographic (EMG) activity of alae nasi (AN) and posterior cricoarytenoid (PCA) muscle markedly increased. The upper airway was subjected to negative pressure, -2.41 approximately -3.04 kPa (n = 34) by these nasal occlusions. The activity of upper airway muscles was also increased by tracheal occlusions. However, such augmentation of PCA activity was much less in tracheal occlusions than nasal occlusions, whereas there was the smaller difference in AN activity between both occlusions. During nasal occlusions, a prolongation of the inspiratory time (TI) was observed. Furthermore, maintained negative pressure applied to the isolated upper airway provoked an augmentation of PCA activity. Such an augmented EMG activity of PCA and the prolongation of TI were largely diminished by sectioning the superior laryngeal nerves. These results proves that the upper airway muscles play an important role to protect the upper airway from collapsing by nasal occlusions. In addition, it is suggested that a lack of lung volume feedback is substantially concerned with the activation of AN, while negative pressure in the upper airway is essential to stimulate PCA.     

A guinea pig model of bovine pneumonic pasteurellosis.

The induction of pneumonic pasteurellosis in guinea pigs (Cavia porcellus) was examined. Specific pathogen free male guinea pigs were anesthetized and a tracheostomy performed to introduce 10(5), 10(4) or 10(3) Pasteurella haemolytica-A1 into the left principal bronchus. The surgical site was closed with tissue adhesive and staples and the animals were monitored for signs of respiratory tract infection. Within 24 hours after inoculation they became depressed, anorectic, pyretic and dyspneic. Fibrinous pleuropneumonia with prominent areas of necrosis and hemorrhage was present. Pericardial effusion was a frequent finding. There was infiltration of the pleura and alveoli with degenerate heterophils and macrophages, a hyperplastic mesothelium and fibrin exudation on the pleura and within alveoli. Hemorrhage, congestion, consolidation, edema and fibrin exudation were prominent in the hilar region of the lungs. Bacterial colonies were evident in all airways. More bacteria were recovered from infected lungs than were inoculated (p less than 0.05) indicating P. haemolytica was actively multiplying in the lungs. Hematological and clinical chemistry data were consistent with fibrinous pneumonia, however, blood cultures were positive for P. haemolytica in 61% (11/18) of animals sampled. Examination of pneumonic pasteurellosis in guinea pigs may be useful in studying pathogenetic and pathological features applicable to bovine pneumonic pasteurellosis (shipping fever pneumonia).     

Effect of short-term oral and inhaled corticosteroids on airway inflammation and responsiveness in a feline acute asthma model

The objective of this study was to investigate whether high-dose inhaled fluticasone propionate (FP), alone or in combination with salmeterol (SAL), is as effective as oral prednisolone in reducing airway inflammation and obstruction in cats with experimentally-induced acute asthma. Six cats sensitised to Ascaris suum (AS) were enrolled in a prospective controlled therapeutic trial and underwent four aerosol challenges, at 1-month intervals with AS allergen. The allergen - stimulated animals received four consecutive days treatment with either oral prednisolone at 1mg/kg twice daily, 500 μg of FP inhaled twice daily, or a combination of FP/SAL at 500 μg/50 μg inhaled twice daily, respectively, according to a randomised cross-over design. Treatment-related changes in lung function, airway responsiveness (AR) and bronchoalveolar lavage fluid (BALF) cytology were assessed. Barometric whole-body plethysmography (BWBP) was used for the assessment of respiratory variables and AR. No significant differences in respiratory rate or Penh (an estimate of airflow limitation measured by BWBP) were detected among treatment groups. Allergen-induced airway hyper-responsiveness was significantly inhibited by all three steroid treatments (P<0.05). The mean BALF eosinophil percentage (±SEM) was lower after oral and inhaled corticosteroid treatment and these changes were significant for groups receiving prednisolone and the FP/SAL combination. Findings suggest high-dose FP, particularly in combination with SAL, is effective in ameliorating airway inflammation and hyper-responsiveness in this model of acute feline asthma, and highlight the potential use of these drugs in cats experiencing acute exacerbations of the naturally occurring disease.     

Vagal afferent activities and respiratory reflexes during drug-induced bronchoconstriction in the guinea pig.

Vagal afferent activities and respiratory reflexes during drug-induced bronchoconstriction were studied in 31 anesthetized, spontaneously breathing or artificially ventilated guinea pigs. Histamine (5, 10, 20 micrograms/kg), ACh (10, 20, 40 micrograms/kg) and endothelin-1 (2 micrograms/kg) were intravenously injected to the animals in order to induce the bronchoconstriction. In spontaneously breathing and vagi intact animals, a considerable respiratory change characterized by rapid-shallow breathing was elicited by histamine. Such respiratory change was abolished by bilateral vagotomy, indicating that the vagal pathway fairly participated in the respiratory change during bronchoconstriction. Indeed, recordings of electrical activities of single vagal afferent nerve fibers from pulmonary stretch and irritant receptors elucidated that the bronchoconstriction by the three drugs markedly influenced these receptor activities. The response of stretch receptors to bronchoconstriction was grouped into four types: two of those types showed a marked increase in their activities and the other two a decrease or no change. Such uneven response was assumed to be derived from heterogenous contraction and aeration among the intrapulmonary small airway. On the other hand, irritant receptors were invariably stimulated by increased transmural pressure during bronchoconstriction. Administration of isoproterenol (20 micrograms/kg) which inhibited the smooth muscle contraction abolished stimulatory effect of the drugs to irritant receptors, suggesting that the effect was due to indirect action through the muscle contraction rather than their direct action to the nerve endings.     

Non-invasive assessment of airway responsiveness in healthy and allergen-sensitised cats by use of barometric whole body plethysmography

This study aimed at determining whether airway responsiveness (AR) tests performed by use of barometric whole body plethysmography (BWBP) were repeatable in cats and to what extent AR was affected by the nebulization protocol used, the age of the animals, the inflammatory status of the airways and prior bronchodilator treatment. Repeatability of AR was tested on two occasions in 30 healthy cats. The concentration of carbachol inducing a 300% increase of the enhanced pause (Penh)--an estimator of airflow limitation--was calculated (C-Penh300) and did not differ significantly between the two tests (0.035+/-0.017% compared to 0.034+/-0.016%) and was significantly and positively correlated. The comparison between rapidly and slowly increasing carbachol concentrations was performed in ten healthy cats and showed a significantly lower C-Penh300 (%) when slowly increasing concentrations were used (0.037+/-0.013% compared to 0.039+/-0.015%, P<0.05). A significant age-related increase of C-Penh300 was evidenced by performing AR tests in 15 healthy cats at 12, 18, 24 and 30 months (12 months: 0.026+/-0.008%, 18 months: 0.031+/-0.009%, 24 months: 0.038+/-0.01%, 30 months: 0.043+/-0.014%, P<0.05). C-Penh300 significantly decreased in 12 Ascaris suum-sensitised cats after allergen exposure (0.026+/-0.016% compared to 0.033+/-0.016%, P<0.05) and was negatively correlated with the granulocyte percentage of bronchoalveolar lavage fluid (r=-0.36, P<0.01). Compared with a placebo inhalation, pre-treatment with inhaled salbutamol significantly increased C-Penh300 in four healthy cats (0.093+/-0.021% compared to 0.036+/-0.004%, P<0.05). This study provides evidence that AR determination by use of BWBP is promising as non-invasive indicator of lower airway inflammation or for monitoring response to bronchodilator treatment.     

Investigations on the conjunctival goblet cells and on the characteristics of glands associated with the eye in the guinea pig

Objective To investigate the distribution and density of conjunctival goblet cells (GC) and to study the anatomy and microscopic characteristics of glands associated with the eye in the guinea pig. Procedures Twenty‐five guinea pigs were used. Meibomian gland openings were counted using biomicroscopy. Conjunctiva, eyelids and glands were embedded in glycol methacrylate and paraffin. Sections were stained with hematoxylin and eosin (H&E), periodic acid Schiff’s reaction (PAS) and Alcian blue (AB). Results Highest GC densities were found in the bulbar and palpebral region of the nasal conjunctiva (GC index: 13.7–16.4%). Lowest GC densities (GC index: 0.0–1.0%) were found in 3/4 limbal regions (nasal and temporal upper eyelid, temporal lower eyelid). Guinea pigs have 27.1 ± 3.0 (mean ± SD) meibomian gland openings in the upper lid and 25.7 ± 2.3 in the lower lid. Difference between upper and lower lid was significant (P = 0.037). Two subconjunctival sebaceous glands occur temporal to each eye. The Harderian gland is very large. In the lacrimal gland three different cell types were distinguished both according to the cell structure and histochemical staining. Conclusions Goblet cell densities are lower in guinea pigs than in dogs and horses. Positive staining with PAS and AB could be an indication that mucins are produced in the lacrimal gland. If so, they may contribute to the mucin layer of the tear film. Both the extraordinarily large Harderian gland and the subconjunctival sebaceous glands produce lipids and may contribute to the lipid layer of the tear film.     

Effect of topical anesthesia of the laryngeal mucosa on upper airway mechanics in exercising horses.

OBJECTIVE: To determine the effect of desensitization of the laryngeal mucosal mechanoreceptors on upper airway mechanics in exercising horses. ANIMALS: 6 Standardbreds. PROCEDURE: In study 1, videoendoscopic examinations were performed while horses ran on a treadmill with and without topical anesthesia of the laryngeal mucosa. In study 2, peak tracheal and nasopharyngeal pressures and airflows were obtained from horses during incremental treadmill exercise tests, with and without topical anesthesia of the laryngeal mucosa. A nasal occlusion test was performed on each horse while standing during an endoscopic examination for both trials. RESULTS: In study 1, horses had nasopharyngeal collapse while running on the treadmill when the laryngeal mucosa was anesthetized. In study 2, inspiratory upper airway and nasopharyngeal impedance were significantly higher, and peak tracheal inspiratory pressure, respiratory frequency, and minute ventilation were significantly lower in horses when the laryngeal mucosa was anesthetized, compared with values obtained when horses exercised without topical anesthesia. Peak inspiratory and expiratory airflows were lower in horses when the laryngeal mucosa was anesthetized, although differences did not quite reach significance (P = 0.06 and 0.09, respectively). During a nasal occlusion test, horses had episodes of nasopharyngeal collapse and dorsal displacement of the soft palate when the laryngeal mucosa was anesthetized. Upper airway function was normal in these horses without laryngeal mucosal anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: Receptors within the laryngeal mucosa may be important in maintaining upper airway patency in exercising horses.     

Effect of histamine on blood flow to the adrenal glands of pigs

Blood flow to the adrenal glands was measured with radioactive microspheres labeled with⁸⁵Sr in 25–37 kg pigs following the intravenous infusion of physiological saline solution or histamine solution (2 ug/kg/min) for 60 minutes. Total blood flow averaged 2.28 ml/min/gland for control pigs and 4.38 ml/min/gland for histamine-treated pigs (P<.0005). Mean blood flow to the adrenal glands of histamine-treated pigs (3.15 ml/min/g) was 82% higher than that of control pigs (1.73 ml/min/g); the difference was highly significant (P<.0005). The result of this study showed that histamine caused an increased blood flow to the porcine adrenal glands.     

Measurement of total respiratory impedance in dogs by the forced oscillation technique

The resistance (R _rs) and reactance (X _rs) of the total respiratory system were determined at various frequencies in 14 healthy conscious beagle dogs. A pseudorandom noise pressure wave was produced at the nostrils of the animals by means of a loudspeaker adapted to the nose by a tightly fitting mask. A Fourier analysis of the pressure and flow signals yielded meanR _rs andX _rs, over 16 s, at frequencies from 2 to 26 Hz. The influence of the posture of the dog, the position of its head, the linearity of the respiratory system, the reproducibility of the method and the effects of upper and lower airway obstructions were studied. In sitting and standing healthy dogs with the head in the extended position,R _rs values increased progressively with frequency from 5.4±0.4 (SEM) cmH₂O L^–1 s at 6 Hz up to 8.8±0.7 cmH₂O L^–1 s at 26 Hz, the mean resonant frequency being 6.1±0.5 Hz. No significant differences were observed between measurements performed with the head in the normal or the extended position. In a recumbent posture, allR _rs values were increased butR _rs was still dependent on the frequency in the same way (7.1±0.7 cmH₂O L^–1 s at 6Hz up to 10.0±0.5 cmH₂O L^–1 s at 26 Hz). Tracheal compression also induced higherR _rs values without changes in the frequency dependence or in the resonant frequency.In anaesthetized dogs, airway obstruction was induced by inhalation of histamine (4 mg/ml for 5 min; theR _rs values tended to decrease with increasing frequency, and the resonant frequency was markedly increased.Abbreviations FOT forced oscillation technique - IV intravenous(ly)     

Comparative responses of bronchial rings to mediators of airway hyperreactivity in healthy horses and those affected with summer pasture-associated obstructive pulmonary disease

OBJECTIVE: To compare responses of bronchial rings obtained from healthy horses and horses affected with summer pasture-associated obstructive pulmonary disease (SPAOPD) to selected mediators of airway hyperreactivity in vitro. SAMPLE POPULATION: Bronchial rings from 6 healthy horses and 6 horses affected with SPAOPD. PROCEDURE: Bronchial rings obtained from each group of horses were mounted in organ baths and attached to force transducers interfaced with a polygraph. After applying 2g of tension, each ring was allowed to equilibrate for 45 minutes in Tyrode's solution at 37 C. Cumulative concentration-response relationships to graded concentrations of selected mediators (10(-8) to 10(-4) M) were determined and analyzed for significance at each concentration. RESULTS: Acetylcholine, histamine, 5-hydroxytryptamine, and leukotriene D4 induced concentration-dependent contractile responses in bronchial rings. Prostaglandin F2alpha induced weak and inconsistent contractile responses. The other 2 agents, norepinephrine and substance P, did not induce concentration-dependent responses. Considering the overall group-drug effect, acetylcholine, histamine, 5-hydroxytryptamine, and leukotriene D4 were effective in inducing consistent concentration-dependent contractile responses in both groups. Only 5-hydroxytryptamine and histamine induced significant responses in contractility between groups. The response of bronchial rings from horses with SPAOPD to 5-hydroxytryptamine was significantly greater than those from control horses, whereas the response to histamine was significantly lower. Significant responses were evident at concentrations ranging from 10(-6) to 10(-4) M for both drugs. CONCLUSIONS AND CLINICAL RELEVANCE: Because the airways of horses with SPAOPD had increased responsiveness to 5-hydroxytryptamine in vitro, treatment modalities using 5-hydroxytryptamine antagonists should be investigated to address this phenomenon.     

Functional, inflammatory and morphological characterisation of a cat model of allergic airway inflammation

The aims of this study were to characterise a model of feline allergic airway inflammation and to test through a longitudinal investigation whether five repeated allergen exposures would lead to signs of airway remodelling that would be detectable in vivo. Eight healthy control cats and eight cats sensitised with Ascaris suum allergens were investigated. Barometric whole body plethysmography (BWBP) was used for the assessment of respiratory variables and airway responsiveness (AR). Bronchoalveolar lavage fluid (BALF) was sampled for cytology and determination of F(2)-isoprostane concentration and matrix metalloproteinase type 9 (MMP-9) activity. Thoracic radiography and bronchoscopy scores were also established. Cats were investigated prior to sensitisation and after inhalation of placebo or allergen challenge 1. BWBP measurements revealed a significant increase of enhanced pause (Penh), an index of bronchoconstriction, and AR in sensitised cats in response to allergen challenge 1. A significant increase in BALF neutrophil and eosinophil %, F(2)-isoprostane concentration and MMP-9 activity, and increased radiography and bronchoscopy scores were recorded. After a recovery period of 6 weeks, all variables except BALF MMP-9 returned to baseline values. Four further allergen challenges induced similar changes to those seen in challenge 1 and no signs of persistent changes suggestive of bronchial remodelling were detectable. The model provides an in vivo approach to functional, inflammatory and morphological changes occurring in response to single and repeated allergen exposure.     

The neurophysiology of dyspnea

Objective – To review the human and veterinary literature regarding the neurophysiology of dyspnea and to provide evidence for the beneficial effects of several novel therapies aimed at the alleviation of dyspneic sensations. Data Sources – Data sources included scientific reviews, case reports, original research publications, and recent research conference proceedings. Human Data Synthesis – The use of blood oxygenation level‐dependent functional magnetic resonance imaging technology has revealed that the brain regions activated by air hunger in humans are also those activated by fear, pain, and thirst perception. In human subjects, it has been found that agents known to enhance the firing of pulmonary slowly adapting receptors (SARs) can alleviate the sensation of dyspnea without altering central respiratory drive. Several small studies have also shown that nebulized opioids can reduce the sensation of dyspnea apparently via activation of peripheral opioid receptors in the lung. Veterinary Data Synthesis – There are several animal models relevant to both small and large animal clinical patient populations. Treatment of rats with a nebulized SAR sensitizing agent (furosemide) enhances SAR firing in response to lung inflation. Behavioral escape responses to airway occlusion are reduced in lightly anesthetized cats when treated with nebulized furosemide. Opioid agonists have been shown to inhibit the release of acetylcholine and other mediators from the airways of dogs and guinea pigs. Studies using a goat model with bilateral destruction of the pre‐Bötzinger Complex do not support current paradigms of air hunger origination. Conclusions – Veterinary patients may benefit from an approach to dyspnea that incorporates an understanding of the origins of the unpleasant sensations associated with the condition. Several novel therapies have shown promise in alleviating dyspneic sensations without altering respiratory drive. Further study is needed to determine the safety and efficacy of these therapies in veterinary patients.     

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.     

Airway hyperresponsiveness to adenosine 5’-monophosphate in feline chronic inflammatory lower airway disease

Airway hyperresponsiveness is a key feature of human asthma and chronic bronchitis and response to the indirectly acting agonist adenosine 5′-monophosphate (AMP) is thought to reflect underlying airway inflammation. To examine whether airway responsiveness testing (ART) with AMP may be used to differentiate healthy cats from those with asthma (FA) and chronic bronchitis (CB), 24 cats (9 FA, 6 CB, 9 controls) underwent ART with AMP at concentrations of 0.1, 1, 10, 100 and 500 mg/mL using barometric whole body plethysmography.The defined endpoint of ART, an increase in enhanced pause (Penh) exceeding 300% of the post-saline value (baseline), was reached in 9/15 patients (7 FA, 2 CB), but in none of the controls. Mean Penh (±SD) at baseline (BL) was 0.49 ± 0.16 for cases, and 0.54 ± 0.16 for controls, and was significantly increased after AMP challenge in clinical cases (2.62 ± 2.20), but not in controls (0.63 ± 0.30, P < 0.05). After separating responder (R) and non-responder (NR) cases, a more pronounced difference after challenge was found (R: 3.96 ± 1.84, NR: 0.6 ± 0.21, P < 0.001). The provocative concentration of the agonist that increased Penh to 300% of BL (PC Penh 300) in R cases was 52.98 ± 48.04 mg/mL AMP. Age had no influence on the responder status or PC Penh 300. It was concluded that AMP challenge may offer a new method for the identification of cats with lower inflammatory airway disease, and possibly for monitoring disease progression or response to therapy.     

Inhaled fluticasone reduces bronchial responsiveness and airway inflammation in cats with mild chronic bronchitis

This study investigated the effect of inhaled fluticasone on lower airway inflammation and bronchial responsiveness (BR) to inhaled carbachol in cats with very mild, chronic bronchitis (n = 5) that were compared with healthy cats serving as controls (n = 6). Chest radiographs, BR tests performed non-invasively by barometric whole body plethysmography (BWBP) and bronchoalveolar lavage (BAL) were performed before and after treatment. BR was quantified by calculating the concentration of carbachol inducing bronchoconstriction (C-Penh300%), defined as a 300% increase of baseline Penh, an index of bronchoconstriction obtained by BWBP. BAL fluid was analyzed cytologically and the oxidant marker 8-iso-PGF2alpha was determined. At test 1, healthy cats and cats with bronchitis were untreated, whereas for test 2 inhalant fluticasone (250 microg once daily) was administrated for 2 consecutive weeks to cats with bronchitis. Control cats remained untreated. Inhaled fluticasone induced a significant increase in C-Penh300% and a significant decrease of BAL fluid total cells, macrophages, neutrophils and 8-iso-PGF2alpha in cats with bronchitis, whilst untreated control cats did not show significant changes over time. This study shows that a 2-week fluticasone treatment significantly reduced lower airway inflammation in very mild bronchitis. BR could be successfully monitored in cats using BWPB and decreased significantly in response to inhaled fluticasone. 8-Iso-PGF2alpha in BAL fluid was responsive to treatment and appeared as a sensitive biomarker of lower airway inflammation in cats.