Jérôme Leemans

Description of original endoscopic findings and respiratory functional assessment using barometric whole-body plethysmography in dogs suffering from brachycephalic airway obstruction syndrome

The clinical features of brachycephalic airway obstructive disease in 11 brachycephalic dogs are described in this study. The respiratory strategy was assessed before (n=11) and after (n=6) surgery using barometric whole-body plethysmography (BWBP), with the relationship between BWBP variables and the severity of the clinical signs assessed by the use of a respiratory score based on clinical, radiographic and endoscopic findings. Partial collapse of the left main bronchus was a common finding not previously described as part of the brachycephalic airway obstructive disease syndrome. Epiglottic cysts, laryngeal granulomas and nasopharyngeal turbinates in English Bulldogs were other previously unreported findings. No significant correlation between the respiratory score and any of the BWBP variables was detected. Compared to healthy dogs, brachycephalic dogs had a significantly lower Te/Ti ratio (expiratory time over inspiratory time), peak inspiratory flow (PIF) per kg bodyweight (BW), significantly higher peak expiratory flow (PEF) per kgBW, PEF/PIF, and enhanced pause. These variations are compatible with upper airway obstructions primarily in the extrathoracic airways. Following surgery, a significant decrease in PEF/PIF was detected. The study showed that BWBP could be used to characterise the respiratory strategy in brachycephalic dogs before and after surgery.

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-PGF2α was determined. At test 1, healthy cats and cats with bronchitis were untreated, whereas for test 2 inhalant fluticasone (250 μg 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-PGF2α 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-PGF2α in BAL fluid was responsive to treatment and appeared as a sensitive biomarker of lower airway inflammation in cats.

Bronchodilators in bronchoscopy-induced airflow limitation in allergen-sensitized cats.

This study investigated the effect of bronchoscopy and bronchoalveolar lavage (BAL) on respiratory function, determined by barometric whole-body plethysmography (BWBP), of healthy and allergen-sensitized cats. Furthermore, the efficacy of inhaled bronchodilators in preventing changes in respiratory function was determined. For test 1, 18 healthy experimental cats were investigated on day 1 by BWBP. On day 2, the cats underwent BWBP after sedation (medetomidine), after anesthesia induction (propofol), and after bronchoscopy and BAL. Enhanced pause (Penh) was significantly increased after bronchoscopy and BAL (1.64 +/- 0.17 versus 1.23 +/- 0.07, P < .05). For test 2, 6 cats were sensitized to ovalbumin (OVA), 6 cats were sensitized to Ascaris suum (AS), and 6 cats served as controls. On day 0, OVA- and AS-sensitized cats underwent an inhaled allergen challenge, whereas controls were exposed to saline. On days 1 and 2, the same protocol as described for test 1 was repeated. Post-BAL Penh of the AS-sensitized cats was significantly higher than at test 1 (2.28 +/- 0.22 versus 1.69 +/- 0.33, P < .05) and was correlated with BAL fluid neutrophil count (r = 0.55, P < .05). During tests 3, 4, and 5, the same protocol as used for test 2 was applied to each cat group, with the animals being randomly treated before sedation with inhaled salbutamol (200 microg), ipratropium bromide (40 microg), or a combination of both (200 + 40 microg). Post-BAL Penh of the AS-sensitized group was significantly decreased after the salbutamol + ipratropium bromide treatment (1.56 +/- 0.18 versus 2.28 +/- 0.22, P < .05). This study suggests that bronchoscopy and BAL induce airflow limitation in cats, which is more severe in the presence of lower airway inflammation. Inhaled salbutamol + ipratropium bromide reduce BAL-induced bronchoconstriction in AS-challenged cats and might be recommended as preventive treatment of asthmatic cats undergoing bronchoscopy.

A pilot study comparing the antispasmodic effects of inhaled salmeterol, salbutamol and ipratropium bromide using different aerosol devices on muscarinic bronchoconstriction in healthy cats.

This study compared the duration and magnitude of the antispasmodic effects of salmeterol (SLM), salbutamol (SAL), ipratropium bromide (IB) and the combination of SAL and IB (SAL/IB) against carbachol-induced bronchoconstriction in healthy cats, and investigated the gain in efficacy using a two or fourfold increase in drug dosages. The drug regimens used were: (1) SLM 25 microg, SAL 100 microg, IB 20 microg and SAL/IB 100 microg/20 microg for bronchodilators delivered by a metered-dose inhaler (MDI); (2) SAL 3.75 mg and IB 62.5 microg for nebulised (NEB) medications. To monitor the bronchodilator effect, airway responsiveness was assessed at different time points using barometric whole-body plethysmography and calculation of the concentration of inhaled carbachol inducing a 300% increase of baseline Penh (enhanced pause), an estimator of airflow limitation. Maximum C-Penh300 was recorded 15 min after NEB SAL, IB MDI, NEB IB and 1h after SAL MDI and 4h after SLM MDI, respectively. C-Penh300 was significantly different from control values (without treatment) up to 24h for SLM MDI, 8h for IB MDI and 4h for other drugs. In terms of efficacy, SAL/IB MDI showed a synergistic antispasmodic effect at 15 min, 4h and 8h after administration. A fourfold increase of the initial dose of IB MDI and NEB IB significantly increased C-Penh300. Despite a fourfold dose increase, SLM displayed the weakest degree of bronchoprotection compared to other bronchodilators. The study provides evidence that inhaled bronchodilators are efficient at preventing muscarinic-induced bronchospasm in healthy cats and that SAL and IB appear to be short-acting bronchodilators in contrast to SLM.

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.

Prophylactic effects of omega-3 polyunsaturated fatty acids and luteolin on airway hyperresponsiveness and inflammation in cats with experimentally-induced asthma.

The aim of this study was to assess the preventive effects of omega-3 polyunsaturated fatty acids (omega3 PUFA) and luteolin supplementation on allergen-induced inflammation in eight Ascaris suum (AS)-sensitised cats. Airway responsiveness (AR) tests were performed and venous blood and bronchoalveolar lavage fluid (BALF) collected before and following a single (AS-stimulated) allergen exposure, as well as at the end of a 4-week treatment period, which was followed by a second AS-challenge. The omega6/omega3 fatty acid ratio in erythrocyte membranes, BALF cytology, AR to carbachol, and BALF lipoxin A(4) (LXA(4)), an endogenous inhibitor of inflammation, were assessed at each time point. Compared to respective unstimulated values, AS-challenged cats exhibited a significant rise in BALF eosinophil percentage and there was a trend to increased BALF total cell counts, increased AR and reduced BALF LXA(4) concentrations. The significant decrease in the blood omega6/omega3 ratio seen after supplementation demonstrated that omega3 PUFA were efficiently absorbed. No changes in BALF cytology were found between untreated and treated AS-stimulated cats, but BALF LXA(4) levels were significantly elevated and AR significantly decreased following supplement intake. The study suggests that omega3-luteolin supplementation may have some beneficial effects on AR through a LXA(4)-dependent pathway in cats with experimentally-induced asthma.

Salmeterol or doxycycline do not inhibit acute bronchospasm and airway inflammation in cats with experimentally-induced asthma

The objective of this study was to determine if inhaled salmeterol, a long-acting β(2)-adrenergic agonist, and oral doxycycline, a tetracycline antibiotic displaying matrix metalloproteinase (MMP) inhibitory activity, reduce airway inflammation and obstruction in cats with experimentally-induced asthma. Eight Ascaris suum (AS)-sensitised cats were enrolled in a prospective study in which they underwent four AS-challenges at 1 month intervals. The challenged animals were given no treatment or were treated on 4 consecutive days with either: (1) oral prednisolone (1mg/kg twice daily), (2) inhaled salmeterol (50 μg twice daily), or (3) oral doxycycline (5mg/kg twice daily), according to a randomised cross-over design. Inhibition of allergen-induced early (EAR) and late (LAR) asthmatic reactions were assessed by barometric whole-body plethysmography. Cytology and measurement of MMP-2 and -9 activities were carried out on bronchoalveolar lavage fluid (BALF). Although none of the treatments prevented the EAR, prednisolone treatment inhibited the LAR. Relative to untreated cats, the eosinophil percentage and MMP-2 activity in BALF were significantly reduced following prednisolone treatment (P<0.05). Short-term therapy with either salmeterol or doxycycline had no effect on the EAR or LAR or on airway inflammation. Given the chronic nature of this disease in cats, long-term therapy may be required to produce more favourable functional and clinical outcomes.

Correlation of bronchoalveolar eosinophilic percentage with airway responsiveness in cats with chronic bronchial disease.

OBJECTIVES To retrospectively assess the relationship between bronchoalveolar lavage fluid analysis and lung function parameters as assessed by means of barometric whole body plethysmography and airway responsiveness testing in cats with chronic bronchial disease and to evaluate the potential application of barometric whole body plethysmography and airway responsiveness testing to distinguish between eosinophilic and non-eosinophilic bronchitis. METHODS Twelve cats presented for chronic bronchial disease with complete bronchoalveolar lavage fluid and barometric whole body plethysmography data were identified. Cats were retrospectively assigned to eosinophilic bronchitis or non-eosinophilic bronchitis groups on the basis of bronchoalveolar lavage fluid eosinophil percentage (threshold 17%). Airway responsiveness was quantified by calculating the concentration of carbachol-inducing bronchoconstriction (C-Penh-300), defined as a 300% increase of basal enhanced pause (Penh). RESULTS Log Penh was significantly higher and C-Penh-300 significantly lower in eosinophilic bronchitis cats compared to non-eosinophilic bronchitis cats (P=0·031 and P=0·032, respectively). Bronchoalveolar lavage fluid eosinophil percentage was moderately correlated with log Penh (P=0·012, r=0·70) and showed a weak inverse correlation with C-Penh-300 (P=0·047, r=-0·58). CLINICAL SIGNIFICANCE This study provides supportive evidence of a correlation between airway eosinophilic inflammation and plethysmographic measures of bronchoconstriction and airway responsiveness. Further investigation of the use of barometric whole body plethysmography to differentiate between forms of chronic bronchial disease in cats is indicated.

A comparison of in vitro relaxant responses to ipratropium bromide, β-adrenoceptor agonists and theophylline in feline bronchial smooth muscle.

This study compares the potency and efficacy of different relaxant drugs including anticholinergic, β-adrenergic and methylxanthine agents on acetylcholine-contracted feline bronchi, and investigates the influence of the initial muscarinic-induced tone on bronchodilator response. Feline bronchi were removed from euthanased client-owned cats and were contracted with acetylcholine to cause either 40% or 80% of the acetylcholine maximal contraction. The efficacy and potency of bronchodilating drugs were obtained from cumulative dose-response curves with efficacy (E(max)) as the maximal relaxant response and potency (-logEC(50)) as the logarithm of the concentration of drug inducing 50% of maximal relaxation. Under low contractile tone (40%), all bronchodilators relaxed feline bronchi in a concentration-dependent manner with the following rank order of potency: formoterol>ipratropium bromide>fenoterol>isoprenaline>salbutamol≥salmeterol>theophylline. E(max) values ranged from 80% to 100% depending on the tested drug. Constriction of feline bronchi with high-dose acetylcholine (80%) caused a rightward and downward shift of the β(2)-mimetic dose-response curves. Significant decreases in -logEC(50) and E(max) values were reported for salbutamol, formoterol and salmeterol. This study provides evidence that existing classes of bronchodilators produce effective relaxation of acetylcholine-contracted feline bronchi and that airway responsiveness to β(2)-stimulants is dependent on the magnitude of the initial muscarinic-induced tone. The clinical relevance of these in vitro findings has yet to be explored in clinical trials.