<p>In a prospective randomised double-blind study eighty patients with MRI verified lumbar disc herniation and corresponding clinical findings underwent microscopic disc removal. The patients were peroperatively given systemic and local corticosteroids or placebo, and followed for 2 years. The hospital stay and time to return to full-time work was significantly shorter in the treatment group. Pain measured as worst pain during the last week was also lower in the corticosteroid group. The results indicate that peroperative treatment with corticosteroids reduces pain and improves the functional outcome in patients operated for lumbar disc herniations.</p><p>To evaluate whether thermal quantitative sensory testing (QST) is applicable in the study of sensory dysfunction in lumbar disc herniations 66 patients with disc herniations underwent thermal QST. We found that thermal QST reflects sensory dysfunction in patients with lumbar disc herniations. However, thermal QST seems to have a poor predictive value for identifying the anatomic location of a herniated lumbar disc.</p><p>Quantitative sensory testing (QST) was used to detect damage to the myelinated A-delta fibres (cold sense) and the unmyelinated C-fibres (warmth sense). Corticosteroids combined with surgery in lumbar disc surgery improved the normalisation for the warmth disturbance compared to the control group. </p><p>A prospective analysis was performed on the predictive value of preoperatively determined lumbar lordosis and flexion for pain and disability in patients treated by microscopic lumbar disc surgery. Preoperative hyperlordosis correlated to more pain postoperatively (p=0.004). In patients with hypoflexion there was an association between hyperlordosis and moderate or severe pain postoperatively (p<0.001). The same outcomes were found for DRI. The stiff and straight back indicates a good outcome of lumbar disc surgery concerning pain and disability. </p>

<p>Ormarsdóttir, S. 2001. Osteoporosis in Chronic Liver Disease. Acta Universitatis Upsaliensis. <i>Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine</i> 1037. 60 pp. Uppsala. ISBN 91-554-5021-0. </p><p>Osteoporosis is a well-known and frequently reported complication of chronic liver disease (CLD) with a high fracture rate contributing to significant morbidity after liver transplantation. The pathogenesis is unknown and controversy exists about many risk factors for osteoporosis in CLD. </p><p>In the present thesis, bone mineral density (BMD) was found to be significantly lower at the lumbar spine (<i>p</i><0.01) in a cohort of patients with CLD compared with age- and gender -matched individuals. Osteoporosis was found in 30% of the patients and 15% of the controls, respectively. Low body mass index (BMI), corticosteroid treatment, prothrombin time, age and female gender were independent risk factors for osteoporosis in the patients. </p><p>In a follow-up study, 43 of 72 patients were available for a second BMD measurement 25 months (median) after the first. Bone loss at the femoral neck was 1.5 ± 2.4% in females and 2.9 ± 2.0% in males with a significant decrease in BMD Z-score over time (<i>p</i>=0.005 and <i>p</i>=0.02 for females and males, respectively), indicating increased bone loss at this site. Hyperbilirubinaemia and low circulating levels of 25-hydroxy vitamin D₃ predicted increased bone loss at the femoral neck. These findings suggest that cortical bone, in addition to trabecular bone, may be affected in CLD and bilirubin and vitamin D₃ may be involved in the pathophysiology of osteoporosis in CLD. </p><p>In order to elucidate the suggested role of insulin-like growth factors (IGFs) and leptin in the pathophysiology of osteoporosis in CLD, we studied the relationship between these factors and BMD. Levels of IGFs were extremely low (<i>p</i><0.0001 compared with the controls) and related to liver function but no correlation was found between the IGFs and BMD. Serum leptin adjusted for BMI correlated negatively with BMD in female patients (<i>p</i>=0.003 and <i>p</i>=0.04 at the lumbar spine and the femoral neck, respectively) and in male patients at the femoral neck (<i>p</i>=0.04). Thus, the IGFs appear not to be involved in the pathophysiology of osteoporosis in CLD but a role of circulating leptin is possible. </p>

<p>Ultrastructural studies of airway epithelium in airway disease are important for diagnosis and understanding the underlying pathology which helps clinicians to improve the patients' treatment.</p><p>Airway biopsies from a 5-month old boy with respiratory problems and gastro-oesophageal reflux were studied by transmission electron microscopy (TEM). The tracheal columnar cells showed accumulation of lamellar bodies, indicative of lysosomal storage disease. The patient was diagnosed with Gaucher disease type 2.</p><p>Shedding of airway epithelial cells is commonly found in asthma. The attachment of these cells to the basal lamina was investigated by TEM of biopsies from patients with asthma and healthy controls. The contact area between columnar cells and basal lamina in asthmatics was significantly less than in controls. Attachment of columnar cells to the basal lamina occurs mainly indirectly, via desmosomal attachment to basal cells. </p><p>Primary ciliary dyskinesia (PCD) is a congenital disease. It is important to differentiate PCD from acquired (secondary) ciliary dyskinesia (SCD). The number of dynein arms determined by TEM was 1.5 and 1.4 for outer and inner dynein arms, respectively in PCD, versus 7.9 and 5.2 for controls and 8.1 and 5.9 in SCD. Compared to PCD patients, SCD patients have more structurally abnormal cilia. A significant difference was found in orientation of the central microtubule pair between PCD and SCD, but also overlap. </p><p>Leukotriene receptor antagonists are a new treatment for asthma. Both corticosteroids and montelukast caused apoptosis and necrosis of airway epithelial cells, and reduced the expression of intercellular adhesion molecule-1. Treatment of cells with tumor necrosis factor-α or interferon-γ reduced the fraction of the lateral cell membrane occupied by desmosomes and this effect was counteracted by corticosteroids. </p>

Le chat est la seule espèce animale qui développe spontanément une entité clinique similaire à bien des égards à lasthme allergique humain. Communément appelée « asthme félin » par homologie à la maladie humaine, cette entité pathologique est le résultat dune inflammation persistante des voies respiratoires, associée à des phases aiguës de bronchospasme, une hyperréactivité bronchique à des stimuli divers et dans les stades avancés à des remaniements tissulaires de la paroi bronchique (e.g., érosions épithéliales, hypertrophie de la musculature lisse, hyperplasie glandulaire). Des modèles dasthme félin, obtenus par sensibilisation expérimentale à un allergène, reproduisent la majorité des caractéristiques cliniques, fonctionnelles et lésionnelles de la maladie naturelle et sont au premier plan de la découverte de nouvelles stratégies thérapeutiques (i.e., cyclosporine A, corticostéroïdes oraux et inhalés, immunothérapie spécifique). De la pathogénie de lasthme, ressort toute limportance de dominer lobstruction récurrente des voies respiratoires. Même si les bronchodilatateurs inhalés sont recommandés dans la prise en charge des crises dasthme chez le chat, leur efficacité clinique reste incertaine et peu étayée. Ainsi, les principes actifs, les posologies et les protocoles thérapeutiques actuellement préconisés sont dans une large mesure empiriques et/ou extrapolés de la médecine humaine, et nécessitent dêtre validés dans des conditions expérimentales contrôlées. Nos travaux sinscrivent donc dans cette optique et visent à définir une approche thérapeutique tant préventive que symptomatique des crises de bronchospasme chez le chat, ainsi quune utilisation rationnelle des bronchodilatateurs à longue durée daction pour un contrôle optimal de linflammation asthmatique. Lors dune première étude, nous avons investigué lactivité in vitro, vis-à-vis du muscle lisse bronchique félin, de différentes agents bronchodilatateurs parmi lesquels des agonistes β2-adrénergiques (isoprotérénol, salbutamol [SAL], fénotérol, formotérol, salmétérol [SLM]), un anticholinergique (ipratropium bromide [IB]) et une méthylxanthine (théophylline). Tous ont produit une relaxation dose-dépendante de la musculature lisse bronchique, avec des spécificités propres en termes de puissance, defficacité ou dactivité intrinsèque. Sur une base comparative, le formotérol est le ß2-mimétique le plus puissant, et lisoprotérénol le plus efficace avec le fénotérol. Le fénotérol et le formotérol sont des agonistes complets des récepteurs ß2-adrénergiques, le SAL et le SLM des agonistes partiels. Tenant compte des résultats des essais in vitro et de la disponibilité de formulations administrables par aérosols dans lespèce féline, les effets bronchoprotecteurs (intensité, durée daction) de six médications inhalées ont été caractérisés chez le chat sain, en préambule à leur utilisation dans des conditions pathologiques. Un modèle de bronchoconstriction induite par le carbachol a été retenu dans le cadre de cette deuxième étude. Il ressort de cette étude que le SLM en aérosol-doseur (25µg) présente un effet bronchoprotecteur soutenu persistant 24 heures mais est aussi la médication la moins efficace. Le SAL et lIB (nébulisation ou aérosol-doseur) sont des bronchodilatateurs à courte durée daction (48 heures) dont lutilisation combinée en aérosol-doseur (SAL IB : 100µg/20µg) met en exergue une synergie daction. Les conditions naturelles étant souvent incompatibles avec une approche anticipative de la crise dasthme, les traitements instaurés sont davantage à visée curative que prophylactique. Dans une troisième étude, nous avons exploré les effets bronchorelaxants du SAL (100µg) et de lIB (20µg), administrés seuls ou en traitement combiné, sur une bronchoconstriction induite par un aéroallergène (Ascaris suum) chez des chats rendus expérimentalement asthmatiques. La technique dinhalation par aérosol-doseur a été privilégiée vu les effets synergiques de la combinaison « SAL IB » et lintérêt de cette voie dadministration dans la gestion à domicile des crises dasthme. Aux doses testées, les bronchodilatateurs inhalés nont exercé aucun effet notable, naffectant en rien la résolution du bronchospasme induit. Chez lhomme, les crises et les épisodes dexacerbation de lasthme sont fréquents dans le cours évolutif de la maladie. Aucune étude chez le chat asthmatique en crise aiguë (induite ou spontanée) natteste de lefficacité des corticostéroïdes inhalés ni ne mentionne dans ce contexte lintérêt scientifique dune association aux ß2-mimétiques à longue durée daction. Nous avons donc comparé les effets de la prednisolone orale (1mg/kg q12h) à ceux dune dose élevée de fluticasone inhalée, seule (500µg q12h aérosol-doseur) ou en traitement combiné avec du SLM (500µg/50µg q12h aérosol-doseur), sur la fonction et linflammation pulmonaires dans un modèle félin dasthme aigu. Cette quatrième étude a montré quune courte cure orale de prednisolone diminue significativement linflammation bronchique à éosinophiles. De fortes doses de fluticasone inhalée se sont avérées bénéfiques dans le contrôle de lhyperréactivité bronchique non spécifique, sans toutefois exercer des effets marqués sur linflammation bronchique sous-jacente. Combiner cette corticothérapie inhalée au SLM a permis dobtenir des effets anti-éosinophiliques accrus et comparables à ceux de la prednisolone orale. Aucune des médications testées na modifié significativement la réponse clinique et fonctionnelle consécutive à linhalation de lallergène. Létude précédente permet de supposer que le SLM potentialise lactivité anti-inflammatoire des corticostéroïdes inhalés et/ou est doté de propriétés anti-inflammatoires intrinsèques. Dans une cinquième étude, nous avons donc investigué les effets du SLM en monothérapie (50µg q12h aérosol-doseur) sur la fonction et linflammation pulmonaires. Il ressort de cette étude, conduite sur un modèle félin dasthme aigu, que le SLM en monothérapie nexerce pas deffet protecteur sur la survenue dun bronchospasme allergique et est dépourvu de tout effet anti-inflammatoire propre. Les résultats obtenus, dans les conditions expérimentales de nos essais, conduisent aux conclusions suivantes : 1) les bronchodilatateurs inhalés (SAL, IB, SLM) sont dune efficacité thérapeutique limitée dans la prévention et le traitement symptomatique du bronchospasme allergique chez le chat sensibilisé à Ascaris suum 2) en revanche, recourir au SLM comme thérapie adjuvante aux corticostéroïdes inhalés ouvre de nouvelles perspectives thérapeutiques dans le contrôle de linflammation et de lhyperréactivité bronchiques chez le chat asthmatique./The cat is the only animal species that spontaneously develops a clinical entity closely similar to human allergic asthma and commonly referred to as feline asthma. Feline asthma is a chronic inflammatory disease of the lower airways characterised by intermittent respiratory distress due to bronchoconstriction, non-specific bronchial hyperresponsiveness and airway remodeling at latter stages (e.g., epithelial erosions, smooth muscle hypertrophy, glandular hyperplasia). Based on experimental sensitisation to allergens, models of feline asthma mimic many clinical, functional and lesional features of the naturally developing condition. Moreover, development and implementation of feline asthma models have greatly facilitated the search for novel therapies (i.e., cyclosporin A, oral and inhaled corticosteroids, specific immunotherapy). In considering the pathogenesis of asthma, it is of major importance to control recurrent airway obstruction. Although inhaled bronchodilators are recommended for the management of acute asthmatic exacerbations in cats, their clinical efficacy remains uncertain and poorly documented. Most currently recommended drugs, dosages and therapeutic schemes are largely empirical and extrapolated from human medicine, and need to be further validated under controlled experimental conditions. Hence, our work was aimed at determining the potential of inhaled bronchodilators for preventive and curative treatment of acute bronchospasms in asthmatic cats as well as at exploring the benefit of using long-acting bronchodilators to optimally control the airway inflammation. In the first study, we investigated in vitro effects on isolated feline bronchi of different bronchodilating agents including β2-adrenergic agonists (isoproterenol, salbutamol [SAL], fenoterol, formoterol, salmeterol [SLM]), an anticholinergic (ipratropium bromide [IB]) and a methylxanthin derivative (theophylline). All compounds caused a dose-related relaxation of bronchial smooth muscle, each exhibiting specificities in terms of potency, efficacy and intrinsic activity. On a comparative basis, isoproterenol and fenoterol are the most efficacious β2-mimetics while formoterol is the most potent one. Fenoterol and formoterol act as full agonists of β2-adrenoceptors, SAL and SLM as partial agonists. Taking into account results from in vitro testing procedures and availability of aerosol formulations suitable for lung delivery in cats, we compared the antispasmodic effects (magnitude, duration of action) of six inhaled medications against carbachol-induced bronchoconstriction in healthy cats. This second study showed that SLM by metered-dose inhaler (25µg) has a sustained activity for as long as 24 hours but is also the least efficacious medication. SAL and IB (nebulisation or metered-dose inhaler) are short-acting bronchodilators (4-8 hours) whose combination delivered with a metered-dose inhaler (SAL IB: 100µg/20µg) exhibits a synergistic antispasmodic effect. In the natural disease, asthmatic crisis are difficult to predict in terms of occurrence. Therefore, therapeutic interventions are more curative than preventive. In a third study, we explored the bronchodilating effects of SAL (100µg) and IB (20µg), delivered either alone or as a combined therapy, on allergen-induced bronchospasms in Ascaris suum-sensitised cats. The inhalation technique using a metered-dose inhaler was retained given the synergistic effects of the combination SAL IB with this method and its therapeutic interest for at-home management of asthmatic crisis. At the tested doses, these bronchodilators failed to reverse allergen-induced bronchospasms in cats with experimental asthma. In human beings, crisis and exacerbations of asthma are frequent events in the natural course of the disease. Efficacy of inhaled corticosteroids in cats with acute asthmatic exacerbations (induced or spontaneous) has not yet been determined, nor the potential benefit of adding long-acting β2-agonists in this context. Thus, the fourth study was aimed at comparing the effects of oral prednisolone (1mg/kg q12h) with those of inhaled fluticasone at high doses, alone (500µg q12h metered-dose inhaler) or combined with salmeterol (500µg/50µg q12h metered-dose inhaler), on lung function and airway inflammation in a feline model of acute asthma. This study showed that a short course of oral prednisolone significantly reduced allergen-induced bronchial eosinophilic inflammation. High doses of inhaled fluticasone proved to be efficient for decreasing non specific airway hyperresponsiveness but failed to markedly reduce the underlying airway inflammation. Adding salmeterol to inhaled fluticasone led to anti-eosinophilic effects of the same magnitude as those found for oral prednisolone. None of these treatments improved clinical and functional responses to allergen exposure. According to the previous study, it may be that SLM has an anti-inflammatory effect on its own and/or functions as a steroid-potentiating agent. In a fifth study, we investigated the effects of salmeterol as monotherapy (50 µg q12h metered-dose inhaler) on lung function and airway inflammation in our feline model of acute asthma. This inhaled medication did not prevent occurrence of allergic bronchospasm in Ascaris suum-sensitised and challenged cats, nor did it possess intrinsic anti-inflammatory activity. Under our experimental conditions, the main results achieved led to the following conclusions: 1) the inhaled bronchodilators (SAL, IB, SLM) are of limited efficacy for the prevention and symptomatic treatment of allergic bronchospasm in cats sensitised to Ascaris suum; 2) in contrast, using salmeterol as adjuvant therapy to inhaled corticosteroids opens up new perspectives for the treatment of bronchial inflammation and hyperresponsiveness in asthmatic cats.

Ormarsdóttir, S. 2001. Osteoporosis in Chronic Liver Disease. Acta Universitatis Upsaliensis. Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1037. 60 pp. Uppsala. ISBN 91-554-5021-0. Osteoporosis is a well-known and frequently reported complication of chronic liver disease (CLD) with a high fracture rate contributing to significant morbidity after liver transplantation. The pathogenesis is unknown and controversy exists about many risk factors for osteoporosis in CLD. In the present thesis, bone mineral density (BMD) was found to be significantly lower at the lumbar spine (p&lt;0.01) in a cohort of patients with CLD compared with age- and gender -matched individuals. Osteoporosis was found in 30% of the patients and 15% of the controls, respectively. Low body mass index (BMI), corticosteroid treatment, prothrombin time, age and female gender were independent risk factors for osteoporosis in the patients. In a follow-up study, 43 of 72 patients were available for a second BMD measurement 25 months (median) after the first. Bone loss at the femoral neck was 1.5 ± 2.4% in females and 2.9 ± 2.0% in males with a significant decrease in BMD Z-score over time (p=0.005 and p=0.02 for females and males, respectively), indicating increased bone loss at this site. Hyperbilirubinaemia and low circulating levels of 25-hydroxy vitamin D3 predicted increased bone loss at the femoral neck. These findings suggest that cortical bone, in addition to trabecular bone, may be affected in CLD and bilirubin and vitamin D3 may be involved in the pathophysiology of osteoporosis in CLD. In order to elucidate the suggested role of insulin-like growth factors (IGFs) and leptin in the pathophysiology of osteoporosis in CLD, we studied the relationship between these factors and BMD. Levels of IGFs were extremely low (p&lt;0.0001 compared with the controls) and related to liver function but no correlation was found between the IGFs and BMD. Serum leptin adjusted for BMI correlated negatively with BMD in female patients (p=0.003 and p=0.04 at the lumbar spine and the femoral neck, respectively) and in male patients at the femoral neck (p=0.04). Thus, the IGFs appear not to be involved in the pathophysiology of osteoporosis in CLD but a role of circulating leptin is possible.

In a prospective randomised double-blind study eighty patients with MRI verified lumbar disc herniation and corresponding clinical findings underwent microscopic disc removal. The patients were peroperatively given systemic and local corticosteroids or placebo, and followed for 2 years. The hospital stay and time to return to full-time work was significantly shorter in the treatment group. Pain measured as worst pain during the last week was also lower in the corticosteroid group. The results indicate that peroperative treatment with corticosteroids reduces pain and improves the functional outcome in patients operated for lumbar disc herniations. To evaluate whether thermal quantitative sensory testing (QST) is applicable in the study of sensory dysfunction in lumbar disc herniations 66 patients with disc herniations underwent thermal QST. We found that thermal QST reflects sensory dysfunction in patients with lumbar disc herniations. However, thermal QST seems to have a poor predictive value for identifying the anatomic location of a herniated lumbar disc. Quantitative sensory testing (QST) was used to detect damage to the myelinated A-delta fibres (cold sense) and the unmyelinated C-fibres (warmth sense). Corticosteroids combined with surgery in lumbar disc surgery improved the normalisation for the warmth disturbance compared to the control group. A prospective analysis was performed on the predictive value of preoperatively determined lumbar lordosis and flexion for pain and disability in patients treated by microscopic lumbar disc surgery. Preoperative hyperlordosis correlated to more pain postoperatively (p=0.004). In patients with hypoflexion there was an association between hyperlordosis and moderate or severe pain postoperatively (p&lt;0.001). The same outcomes were found for DRI. The stiff and straight back indicates a good outcome of lumbar disc surgery concerning pain and disability.

Ultrastructural studies of airway epithelium in airway disease are important for diagnosis and understanding the underlying pathology which helps clinicians to improve the patients' treatment. Airway biopsies from a 5-month old boy with respiratory problems and gastro-oesophageal reflux were studied by transmission electron microscopy (TEM). The tracheal columnar cells showed accumulation of lamellar bodies, indicative of lysosomal storage disease. The patient was diagnosed with Gaucher disease type 2. Shedding of airway epithelial cells is commonly found in asthma. The attachment of these cells to the basal lamina was investigated by TEM of biopsies from patients with asthma and healthy controls. The contact area between columnar cells and basal lamina in asthmatics was significantly less than in controls. Attachment of columnar cells to the basal lamina occurs mainly indirectly, via desmosomal attachment to basal cells. Primary ciliary dyskinesia (PCD) is a congenital disease. It is important to differentiate PCD from acquired (secondary) ciliary dyskinesia (SCD). The number of dynein arms determined by TEM was 1.5 and 1.4 for outer and inner dynein arms, respectively in PCD, versus 7.9 and 5.2 for controls and 8.1 and 5.9 in SCD. Compared to PCD patients, SCD patients have more structurally abnormal cilia. A significant difference was found in orientation of the central microtubule pair between PCD and SCD, but also overlap. Leukotriene receptor antagonists are a new treatment for asthma. Both corticosteroids and montelukast caused apoptosis and necrosis of airway epithelial cells, and reduced the expression of intercellular adhesion molecule-1. Treatment of cells with tumor necrosis factor-α or interferon-γ reduced the fraction of the lateral cell membrane occupied by desmosomes and this effect was counteracted by corticosteroids.

Asthma affects nearly two and a half million people in Canada. In Saskatchewan, the prevalence of asthma has increased across all age groups since 1981. Current literature indicates that the purchase of all asthma medications increased in the last 20 years both province and nationwide. Since the early 1990s, the Canadian Consensus Guidelines (CCG) for the treatment of asthma recommended increasing the use of inhaled corticosteroids as a mainstay for controlling asthma symptoms. The CCG have also encouraged decreasing the use of short-acting, inhaled beta2-agonist medication. <p>The objective of this descriptive epidemiological study was to investigate asthma medication prescribing at the individual level among physician-diagnosed asthma patients, aged 0 to 64 years, in Saskatchewan from January 1, 1991 to December 31, 2000. Saskatchewan residents covered under the provincial health insurance plan who received a physicians diagnosis of asthma, identified each calendar year, were included in the study (296,430 asthma patients in total). <p> Nearly 80.0% of this asthma population purchased at least one asthma medication in each calendar year. From 1991 to 2000, users and the mean number of prescriptions of short-acting beta2-agonists decreased slightly. The proportion of users and mean number prescriptions per year of inhaled corticosteroids increased. The highest mean numbers of prescriptions and users of inhaled corticosteroids were among the 0-4 year olds. <p>Short-acting beta2-agonists, inhaled corticosteroids, and oral corticosteroids were the most popular medications. Users of theophyllines and cromoglycates decreased. The 15-34 year old males showed the greatest "inappropriate" use as high users of short-acting beta2-agonists and low users of inhaled corticosteroids. <p>There was increasing compliance with the CCG over the ten years. The combination of beta2-agonists with inhaled corticosteroids usurped beta2-agonist monotherapy as the most popular form of asthma therapy by the year 2000. Users of combination therapy increased from 19% to 38.7%, while users of beta2-agonists alone decreased from 34.5% to 23.1%. <p>From 1996 to 2000, the monthly number of both short-acting beta2-agonists and inhaled corticosteroids prescriptions decreased for all users in July and August. Peak increases in the number of short-acting beta2-agonist prescriptions, for children under 15, occurred in September. For adults, peak increases occurred in December for both medications. <p>These study results will enhance the understanding of asthma medication use among children and adults and will help healthcare professionals develop new treatment programs for the management of asthma.

Asthma affects nearly two and a half million people in Canada. In Saskatchewan, the prevalence of asthma has increased across all age groups since 1981. Current literature indicates that the purchase of all asthma medications increased in the last 20 years both province and nationwide. Since the early 1990s, the Canadian Consensus Guidelines (CCG) for the treatment of asthma recommended increasing the use of inhaled corticosteroids as a mainstay for controlling asthma symptoms. The CCG have also encouraged decreasing the use of short-acting, inhaled beta2-agonist medication. <p>The objective of this descriptive epidemiological study was to investigate asthma medication prescribing at the individual level among physician-diagnosed asthma patients, aged 0 to 64 years, in Saskatchewan from January 1, 1991 to December 31, 2000. Saskatchewan residents covered under the provincial health insurance plan who received a physicians diagnosis of asthma, identified each calendar year, were included in the study (296,430 asthma patients in total). <p> Nearly 80.0% of this asthma population purchased at least one asthma medication in each calendar year. From 1991 to 2000, users and the mean number of prescriptions of short-acting beta2-agonists decreased slightly. The proportion of users and mean number prescriptions per year of inhaled corticosteroids increased. The highest mean numbers of prescriptions and users of inhaled corticosteroids were among the 0-4 year olds. <p>Short-acting beta2-agonists, inhaled corticosteroids, and oral corticosteroids were the most popular medications. Users of theophyllines and cromoglycates decreased. The 15-34 year old males showed the greatest "inappropriate" use as high users of short-acting beta2-agonists and low users of inhaled corticosteroids. <p>There was increasing compliance with the CCG over the ten years. The combination of beta2-agonists with inhaled corticosteroids usurped beta2-agonist monotherapy as the most popular form of asthma therapy by the year 2000. Users of combination therapy increased from 19% to 38.7%, while users of beta2-agonists alone decreased from 34.5% to 23.1%. <p>From 1996 to 2000, the monthly number of both short-acting beta2-agonists and inhaled corticosteroids prescriptions decreased for all users in July and August. Peak increases in the number of short-acting beta2-agonist prescriptions, for children under 15, occurred in September. For adults, peak increases occurred in December for both medications. <p>These study results will enhance the understanding of asthma medication use among children and adults and will help healthcare professionals develop new treatment programs for the management of asthma.

Le souffle chez les chevaux et l’asthme chez l’humain sont des maladies respiratoires qui partagent plusieurs caractéristiques, notamment des épisodes de bronchospasme et de détresse respiratoire dus à une inflammation pulmonaire inappropriée en réponse à une inhalation de substances antigéniques. Les manifestations cliniques incluent des efforts respiratoires augmentés, des sifflements et de la toux. Au niveau des voies respiratoires, on observe une augmentation du muscle lisse péribronchique, une fibrose sous épithéliale, une métaplasie/hyperplasie épithéliale et du mucus en quantité augmentée. L’augmentation du muscle lisse est particulièrement importante car elle n’affecte pas seulement le calibre basal des voies respiratoires, mais elle accentue l’obstruction respiratoire lors de bronchoconstriction. Ces changements sont regroupés sous le terme de « remodelage » et sont associés à un déclin accéléré de la fonction respiratoire chez les patients asthmatiques. Alors que les traitements actuels contrôlent efficacement le bronchospasme et relativement bien l’inflammation, leurs effets sur le remodelage sont mal connus. Dans le cadre de thèse, la réversibilité du remodelage musculaire péribronchique a été investiguée chez des chevaux atteints du souffle dans deux études longitudinales. Ces études, faites principalement sur du tissu pulmonaire prélevé par thoracoscopie, sont difficilement réalisables chez l’humain pour des raisons éthiques, ou chez d’autres animaux, car ceux-ci présentent rarement une inflammation de type asthmatique de façon spontanée. Les résultats démontrent que les chevaux atteints du souffle ont approximativement deux fois plus de muscle péribronchique que les chevaux sains d’âge similaire gardés dans les mêmes conditions, et que la prolifération des myocytes contribue à cette augmentation. Ils démontrent aussi qu’une stimulation antigénique relativement brève chez des chevaux atteints du souffle depuis plusieurs années n’accentue pas le remodelage, ce qui suggère que l’augmentation du muscle lisse atteint un plateau. Nous avons également montré que le remodelage du muscle lisse chez des chevaux adultes est partiellement réversible et que cette réversibilité peut être accélérée par l’administration de corticostéroïdes par inhalation. Il semble toutefois qu’une portion du remodelage chronique est irréversible puisque les corticostéroïdes ont accéléré la diminution du muscle mais sans toutefois mener à une amélioration plus marquée au terme de l’étude qu’avec une modification environnementale stricte. La diminution de trente pourcent observée sur un an paraît modeste mais elle démontre clairement, et pour une première fois, que le remodelage du muscle lisse présent chez des chevaux adultes malades depuis plusieurs années est au moins partiellement réversible. / Equine heaves and asthma in people are two respiratory diseases that share many characteristics, including episodes of bronchospasm and respiratory distress due to an inappropriate airway inflammation in response to inhaled antigens. In both diseases, the main clinical manifestations are increased breathing efforts, wheezing and coughing. Changes in the airway wall include increased airway smooth muscle, subepithelial fibrosis, epithelial changes, and increased mucus. The increase in smooth muscle is of particular importance as it not only affects baseline airway caliber, but also accentuates the effect of bronchoconstriction on airflow limitation. These structural changes are grouped under the term “remodeling” and are associated with the accelerated decline of respiratory function in asthmatics. While current treatments offer adequate control of bronchospasm and inflammation, their effects on remodeling are unknown. In this thesis, airway smooth muscle remodeling reversibility was investigated in heaves-affected horses. The longitudinal studies conducted here, mostly made on peripheral pulmonary tissue harvested under thoracoscopic guidance, can not be easily done in people for ethical reasons, or in other animal species, few of them having spontaneous asthma-like disease like horses. Results have shown that heaves-affected horses have twice as much airway smooth muscle than age-matched controls kept in the same environment, and that myocyte proliferation contributes to this increase. It was also shown that a relatively brief antigenic exposure in chronically affected horses does not further increase smooth muscle mass, which suggests that it may reach a plateau over time. It was also shown that airway smooth muscle is partially reversible and that this reversibility can be accelerated with inhaled corticosteroids. On the other hand, corticosteroids only accelerated the decrease in mass compared to strict environmental control, without affecting the total improvement observed at the end of the study, which suggests that some of this chronic remodeling is irreversible. The thirty percent decrease seems relatively modest but it is nevertheless the first demonstration that airway smooth muscle remodeling of adult horses affected by heaves for years is at least in part reversible.