Godard P

Eosinophilic inflammation in sputum of poorly controlled asthmatics

Despite full effective treatment, asthmatic patients often present with poorly controlled asthma. Airway eosinophilia is associated with asthma, but its relationship with asthma control is still undetermined. To investigate the relationship between airway eosinophilia and asthma control, cellular and biochemical markers of airway inflammation were measured in 19 subjects with poorly controlled asthma, 16 subjects with asthma under control and eight normal volunteers. The severity of asthma was mild-to-moderate persistent in 23 patients (14 poorly controlled) and severe prednisone-dependent in 12 subjects (five poorly controlled). Induced sputum was analysed for total and differential cell counts, leukotriene E4 (LTE4), eosinophil cationic protein (ECP), regulated on activation, normal T-cell expressed and secreted (RANTES), and interleukin (IL)-8. Sputum eosinophils, LTE4, ECP and RANTES levels (but not IL-8) were significantly higher in patients with poorly controlled asthma as compared to patients with controlled asthma. By contrast, sputum cells and sputum inflammatory markers were not different among groups of patients with different severity of asthma. These results suggest that sputum eosinophilia is associated with poorly controlled asthma rather than with the severity of asthma.

Inflammatory features of nasal mucosa in smokers with and without COPD

Background: To investigate whether nasal and bronchial inflammation coexists in chronic obstructive pulmonary disease (COPD), nasal and bronchial biopsy specimens from seven control subjects, seven smokers without COPD, and 14 smokers with COPD were studied. Methods: Nasal and bronchial biopsy specimens were taken from the same patients during bronchoscopy and squamous cell metaplasia and the thickness of the epithelium and basement membrane were measured. The numbers of eosinophils (EG2), neutrophils (elastase), macrophages (CD68), and CD8 T lymphocytes (CD8/144B) were assessed by immunohistochemistry. Results: Smokers with and without COPD had squamous metaplasia in the nasal and bronchial epithelium. In all groups the thickness of the nasal epithelium was greater than that of the bronchial epithelium. The thickness of the basement membrane was similar in nasal and bronchial biopsy specimens from smokers with and without COPD, but was greater in the bronchi than in the nasal epithelium of controls. Eosinophil number was higher in the nasal and bronchial mucosa of smokers without COPD than in smokers with COPD or controls. Neutrophil number was higher in the nasal and bronchial mucosa of smokers with COPD than in smokers without COPD or controls. CD8 T lymphocyte numbers were similar in smokers with and without COPD and higher than in controls. There were fewer macrophages in nasal and bronchial biopsy specimens from smokers without COPD than in those with COPD. Conclusion: Nasal and bronchial inflammation coexists in smokers and is characterised by infiltration of CD8 T lymphocytes. In smokers without COPD this feature is associated with an increased number of eosinophils, while in those with COPD it is linked to an increased number of neutrophils in both nasal and bronchial biopsy specimens.

Can endobronchial biopsy analysis be recommended to discriminate between asthma and COPD in routine practice

Background: International guidelines stress the importance of accurately discriminating between asthma and chronic obstructive pulmonary disease (COPD). Although characteristic pathological features have been described for both conditions, their discriminatory power has never been systematically assessed. Methods: Endobronchial biopsy (EBB) specimens from patients with a clear clinical diagnosis of asthma and COPD (50 per group) were examined by three pathologists in a double blind manner. They were asked to propose a pathological diagnosis of either asthma or COPD and to analyse qualitatively the most frequent abnormalities reported in the literature. Results: The sensitivity and specificity of EBB ranged from 36% to 48% and from 56% to 79%, respectively. Eosinophils strongly biased the pathological diagnoses in favour of asthma, whereas their estimated prevalence was similar (11–37% in asthma and 13–41% in COPD). Metaplasia (11–39% in COPD, 1–18% in asthma) and epithelial inflammation (28–61% in COPD, 11–38% in asthma) tended to be specific to COPD, whereas epithelial desquamation (80–98% in asthma, 61–88% in COPD) and basement membrane thickening (71–94% in asthma, 53–88% in COPD) tended to be associated with asthma. There was acceptable intra- and inter-observer agreement only for metaplasia and epithelial eosinophils. Conclusions: Specific histopathological features of asthma and COPD probably exist, but current routine analysis procedures to assess EBB specimens are not sufficiently discriminatory. This might be rectified by improving pathological definitions.

Regulation of E-cadherin expression by dexamethasone and tumour necrosis factor-α in nasal epithelium

Asthma and rhinitis often coexist and share many clinical features. The extent of epithelial alteration in nasal inflammation is controversial. Cell-cell adhesion plays an important role in tissue morphogenesis and homeostasis and is mediated by the cadherin family. In human bronchial epithelial cells the authors have shown that tumour necrosis factor (TNF)-α induced a significant decrease of E-cadherin and β-catenin expression. The addition of dexamethasone inhibited this decrease. The aim of the present study was to investigate the effect of TNF-α and dexamethasone on the regulation of E-cadherin, γ-catenin and β-catenin in human nasal epithelial cells (HNEC). A primary culture of HNEC, obtained from human nasal turbinates after surgery, was used. The quantitative and qualitative modulation of E-cadherin, γ-catenin and β-catenin expression was assessed by Western blot and immunofluorescence analysis. In order to assess the TNF-α-induced activation of HNEC, interleukin-8 and RANTES (regulated on activation, normal T-cell expressed and secreted) release was assessed by enzyme-linked immunosorbent assay. The results showed that TNF-α induced, a decrease in γ-catenin and β-catenin expression, but had no effect on E-cadherin expression. Immunofluorescence showed that TNF-α induced cytoplasmic localisation of E-cadherin, γ-catenin and β-catenin. Dexamethasone inhibited the effect of TNF-α and induced a three-fold increase in E-cadherin expression. These results suggest that the difference in nasal and bronchial epithelial cohesion may be due to the differential effect of tumour necrosis factor-α and dexamethasone on E-cadherin expression.

Lipoxins and other arachidonate derived mediators in bronchial asthma

Leukotrienes and lipoxins, arachidonate derived mediators from the lipoxygenase (LO) pathways, are associated with bronchial asthma.1-3 They have been detected in vivo in bronchoalveolar lavage (BAL) fluid4-6 and are biosynthesised in vitro by human alveolar macrophages (AM) and polymorphonuclear cells (PMN) after non-specific stimulation.7 Lipoxins were first isolated by Serhan et al 8 9 who incubated granulocytes with 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE). Lipoxin synthesis was also achieved by the addition of other exogenous substrates to cell cultures.8 10 11 In contrast, lipoxin synthesis by co-cultures of two different cell types does not require the addition of any exogenous substrates.11-13 The biosynthesis of lipoxins was shown to be the result of a cellular cooperation mechanism between two different cell types. The enzymatic mechanism of transcellular metabolism involves the action of at least two different lipoxygenases (fig 1). Thus, lipoxins may be generated following receptor mediated activation of either co-incubated PMN and platelets,13 or ionophore stimulation of PMN alone after exposure to exogenous 15(S)-HETE.14 Figure 1 Transcellular metabolism. As shown previously,15 AM from asthmatic patients display high levels of 5-LO activity. 15(S)-HETE is considered to be specific to human epithelium airways and endothelial cells.16-18Human epithelial and endothelial cells are unable to produce lipoxins from endogenous 15(S)-HETE16 19 but they are surrounded by several cell types which show 5-LO activity. Moreover, lipoxins have been identified in the BAL fluid of patients with lung disease20 and in stimulated whole blood.21Because of these observations, and assuming that peripheral blood cells were activated before trafficking to the airways, we have investigated whether AM and peripheral blood cells display sufficient LO activity to transform 15(S)-HETE and have determined whether the generation of lipoxins and their precursors is related to the severity of asthma and can be …

Évaluation de la qualité des soins dans l'asthme

Resume Introduction L’asthme est une maladie bronchique chronique, variable et reversible. C’est une maladie prevalente et couteuse, qui fait l’objet d’une attention particuliere de la part des pouvoirs publics (un Plan asthme a ete publie ; elle est inscrite dans la loi de sante publique). Etat des connaissances Pour juger de la pertinence des soins dispenses, les parametres a prendre en compte sont multiples : la mortalite, la gestion des urgences, des hospitalisations, le cout et des indices tels que le DALY. L’evaluation de l’asthme professionnel merite une place toute particuliere. Tous les adjectifs (variable, reversible, chronique) qui definissent l’asthme permettent de comprendre la difficulte d’une bonne prise en charge et donc d’une bonne qualite des soins. Perspectives Les pouvoirs publics doivent faire en sorte que les outils de prise en charge soient disponibles. Les medecins et tous les personnels de sante doivent s’adapter aux malades et a leur maladie. Les malades enfin doivent s’impliquer dans leur prise en charge. Seule leur participation active permettra d’ameliorer a terme et de maniere sensible la qualite des soins. Conclusion Au cours des 20 dernieres annees, des progres substantiels ont ete accomplis mais la recherche fondamentale et clinique doit etre poursuivie pour les rendre encore plus perceptibles.

Évaluation des pratiques professionnelles pour la prise en charge de la BPCO au CHU de Montpellier

INTRODUCTION Chronic obstructive pulmonary disease (COPD), because of its severity and prevalence, is an important target for the evaluation of professional practices. We present the results of an evaluation at Montpellier University Hospital in 2006 (number of admissions 4800/yr). RESULTS One hundred and twenty-one observations were retrieved, 8% of the total where COPD was recorded as the principal diagnosis (Median age: 66 years; male: 67%). Eighty-eight per cent of the patients had undergone thoracic radiography and 50.8% had had lung function testing. Body mass index was recorded for 89.9% of the patients and the annual number of exacerbations in 14.9%. Information on smoking cessation was given to only 41.9% of the patients, pulmonary rehabilitation was considered in 14.5% and bronchodilators and/or inhaled corticoids were prescribed for 47.8%. Patients admitted under the care of a respiratory team were significantly more likely to have received information on the means of smoking cessation: 75% vs. 35% (p: 0.0004), lung function testing: 73% vs. 38% (p: 0.0005) and been offered pulmonary rehabilitaion: 35% vs. 5% (p<0.0001). CONCLUSION There is considerable room for improvement in the care of COPD within the hospital in order for it to conform to national and international guidelines. Specialist respiratory care is more adherent with guidelines than non-specialist care.

Article originalÉvaluation des pratiques professionnelles pour la prise en charge de la BPCO au CHU de MontpellierEvaluation of professional practice in the management of COPD at Montpellier University Hospital

INTRODUCTION Chronic obstructive pulmonary disease (COPD), because of its severity and prevalence, is an important target for the evaluation of professional practices. We present the results of an evaluation at Montpellier University Hospital in 2006 (number of admissions 4800/yr). RESULTS One hundred and twenty-one observations were retrieved, 8% of the total where COPD was recorded as the principal diagnosis (Median age: 66 years; male: 67%). Eighty-eight per cent of the patients had undergone thoracic radiography and 50.8% had had lung function testing. Body mass index was recorded for 89.9% of the patients and the annual number of exacerbations in 14.9%. Information on smoking cessation was given to only 41.9% of the patients, pulmonary rehabilitation was considered in 14.5% and bronchodilators and/or inhaled corticoids were prescribed for 47.8%. Patients admitted under the care of a respiratory team were significantly more likely to have received information on the means of smoking cessation: 75% vs. 35% (p: 0.0004), lung function testing: 73% vs. 38% (p: 0.0005) and been offered pulmonary rehabilitaion: 35% vs. 5% (p<0.0001). CONCLUSION There is considerable room for improvement in the care of COPD within the hospital in order for it to conform to national and international guidelines. Specialist respiratory care is more adherent with guidelines than non-specialist care.

Un diagnostic par l'imagerie seule est-il possible dans les pneumopathies interstitielles pulmonaires?

L’imagerie, depuis l’utilisation du scanner X ou Tomodensitométrie Haute Résolution (TDM HR), tient une place essentielle dans le diagnostic des pneumopathies interstitielles diffuses (PID) [2, 3]. Les apports de la TDM HR ont d’ailleurs participé avec les données cliniques, paracliniques et anatomopathologiques à la classification et la nosologie de ces affections qui littéralement intéressent l’interstitium pulmonaire, mais atteignent aussi l’arbre aérien périphérique (bronchioles) les vaisseaux distaux (artéres, veines et lymphatiques) ainsi que les espaces aériens destinés à l’hématose (bronchioles respiratoires, acini et alvéoles). Ainsi, les PID constituent un vaste groupe d’affections aux frontières encore mal précisées et résumées dans les Tableaux Ia, Ib, Ic et Id. Il faut souligner que les pneumopathies interstitielles diffuses idiopathiques (PIDI) ont bénéficié d’une classification nouvelle par Katzenstein, faisant apparaître de nouvelles entités comme la pneumopathie interstitielle non spécifique (PINS) (tableau II). Chaque chapitre pathologique comporte des éléments étiologiques et physiopathologiques originaux, un profil clinique et paraclinique parfois évocateur mais pas toujours, et une imagerie qui est le reflet in vivo des anomalies anatomopathologiques constitutionnelles de la maladie. Imagerie et anatomopathologie sont évidemment complémentaires. Par rapport à l’anatomopathologie, l’imagerie a l’inconvénient de ne donner qu’une vision macroscopique des lésions. À ce sujet, il faut savoir que la résolution spatiale TDM HR a été fortement améliorée sur les nouveaux appareils en particulier sur la TDM HR multi-barrettes. Sur les appareils classiques, spiralés ou non, la résolution spatiale TDM HR avoisinait les 500 μ. Aujourd’hui, la résolution spatiale de la TDM HR multi-barrettes atteint les 300 μ avec un pixel isotropique, ce qui permet la réalisation instantanée de reconstructions spatiales (coupes coronales, sagittales et Session pathologies interstitielles