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ABSTRACT: According to the Global Initiative for Asthma (GINA) classification, mild asthma includes intermittent and mild persistent asthma. It represents more than 75% of asthmatic children. The symptoms and functional impact are well described. Mild asthma can lead to severe exacerbations. Progression to more severe disease may occur. Consequently, it is important to diagnose mild asthma, to initiate the appropriate treatment early, and to identify the risk factors for aggravation. Nevertheless, mild asthma is under-diagnosed and under-treated. Bronchial inflammation and remodeling are observed in mild asthma. A daily low-dose of inhaled corticosteroids is the reference treatment for mild persistent asthma. Intermittent inhaled corticosteroids cannot be recommended in children with mild persistent asthma.
Revue des Maladies Respiratoires 02/2013; 30(2):115-24. · 0.59 Impact Factor
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ABSTRACT: The association of inflammatory involvement of the distal airways or bronchiolitis and systemic diseases is essentially observed in Sjögren's syndrome, rheumatoid arthritis and chronic inflammatory bowel disease. Bronchiolitis may be mainly cellular in nature, often involving lympho-monocytic cells, and sometimes associated with lymphoid follicles, as in Sjögren's syndrome. It may also, particularly in rheumatoid arthritis, be constrictive, with peribronchiolar fibrosis. This type is associated with a worse prognosis, with possible progression to chronic respiratory insufficiency. The diagnosis of bronchiolitis should be suspected in any atypical form of asthma, or recurrent "bronchitis", and it is essential to look for extrarespiratory symptoms and auto-antibodies to establish the diagnose of systemic disease. The CT appearances coupled with the evaluation of pulmonary function parameters usually lead to the diagnosis. In severe and/or rapidly progressive cases treatment-combining corticosteroids with immunosuppressive drugs may be prescribed, but often with disappointing results. In these cases, lung transplantation should be considered in young patients.
Revue des Maladies Respiratoires 12/2012; 29(10):1254-63. · 0.59 Impact Factor
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ABSTRACT: Exacerbations remain, in both adults and children, a common reason for emergency consultation. The management of the asthmatic patient with an acute exacerbation is well defined.
The initial evaluation, based on the background risk factors and the clinical examination, will determine the choice of treatment and management. Treatment is based on bronchodilators and corticosteroids in the majority of cases.
An episode of exacerbation may be the opportunity to establish contact with the patient (an educational approach) to improve the adherence to long-term treatment with inhaled corticosteroids, which remain the best way of preventing future exacerbations.
Early and appropriate management of exacerbations of asthma should reduce asthma morbidity and mortality. It could also reduce the socioeconomic costs of these episodes and the number and duration of hospital admissions.
Revue des Maladies Respiratoires 02/2012; 29(2):245-53. · 0.59 Impact Factor
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European Respiratory Journal 12/2011; 38(6):1487-9. · 5.89 Impact Factor
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ABSTRACT: Chronic obstructive pulmonary disease (COPD) is characterized by poorly reversible airflow limitation associated with airway remodelling and inflammation of both large and small airways. The site of airflow obstruction in COPD is located in the small airways, justifying a focus on this compartment. The structural abnormalities that are found in bronchioles with a diameter less than 2mm are characterized by increased airway wall thickness with peribronchial fibrosis, and by luminal obstruction by mucous exudates. Destruction of alveolar walls, the hallmark of emphysema, may be related to protease-antiprotease imbalance, and to mechanisms involving apoptosis, senescence, and autoimmunity. Cigarette smoke inhalation triggers the recruitment of innate immune cells (neutrophils and macrophages) and putatively adaptive immunity mediated via T and B lymphocytes and lymphoid follicles in the small airways. These data suggest a potential role for therapies that can target remodelling and inflammation in the small airways of patients with COPD.
Revue des Maladies Respiratoires 06/2011; 28(6):749-60. · 0.59 Impact Factor
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ABSTRACT: Prevention of exacerbations and effective treatment is essential in pregnant asthmatic women. The management is well documented. Misunderstanding of the recommendations leads to unsuitable, insufficient treatment and is responsible for more frequent recurrences in the pregnant woman compared with the non pregnant. Above all, good control of the disease and the prevention of exacerbations, based on inhaled corticosteroid therapy and smoking cessation, reduces complications, in particular prematurity and low birth weight.
Revue des Maladies Respiratoires 06/2011; 28(6):834-8. · 0.59 Impact Factor
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Allergy 04/2011; 66(9):1254-6. · 6.27 Impact Factor
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P-R Burgel,
A Bourdin,
P Chanez,
F Chabot,
A Chaouat,
T Chinet,
J de Blic,
P Devillier,
A Deschildre,
A Didier,
G Garcia,
G Jebrak,
F Laurent,
H Morel,
T Perez,
C Pilette,
N Roche, I Tillie-Leblond,
S Verbanck,
D Dusser
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ABSTRACT: This review is the summary of a workshop on the role of distal airways in chronic obstructive pulmonary disease (COPD), which took place in 2009 in Vence, France. The evidence showing inflammation and remodelling in distal airways and the possible involvement of these in the pathobiology, physiology, clinical manifestations and natural history of COPD were examined. The usefulness and limitations of physiological tests and imaging techniques for assessing distal airways abnormalities were evaluated. Ex vivo studies in isolated lungs and invasive measurements of airway resistance in living individuals have revealed that distal airways represent the main site of airflow limitation in COPD. Structural changes in small conducting airways, including increased wall thickness and obstruction by muco-inflammatory exudates, and emphysema (resulting in premature airway closure), were important determinants of airflow limitation. Infiltration of small conducting airways by phagocytes (macrophages and neutrophils), dendritic cells and T and B lymphocytes increased with airflow limitation. Distal airways abnormalities were associated with patient-related outcomes (e.g. dyspnoea and reduced health-related quality of life) and with the natural history of the disease, as reflected by lung function decline and mortality. These data provide a clear rationale for targeting distal airways in COPD.
European Respiratory Review 03/2011; 20(119):7-22.
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D Montani,
A Cavailles,
L Bertoletti,
A Botelho,
A Cortot,
C Taillé,
S Marchand-Adam,
D Pinot,
C Chouaid,
B Crestani,
G Garcia,
M Humbert,
J-P L'huillier,
A Magnan, I Tillie-Leblond,
P Chanez
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ABSTRACT: In this article a French working party critically review the international literature to revise the definition, pathophysiology, treatment and cost of exacerbations of adult asthma. The various guidelines do not always provide a consistent definition of exacerbations of asthma. An exacerbation can be defined as deterioration of clinical and/or functional parameters lasting more than 24 hours, without return to baseline, requiring a change of treatment. No single clinical or functional criterion can be used as an early marker of an exacerbation. Innate and acquired immune mechanisms, modified by contact with infectious, irritant or allergenic agents, participate in the pathogenesis of exacerbations, which are accompanied by bronchial inflammation. In 2010, mortality is related to progression of exacerbations, often occurring before the patient seeks medical attention. The objective of treatment is to control asthma and prevent exacerbations. However, many factors can trigger exacerbations and often cannot be controlled. The efficacy of inhaled corticosteroids has been demonstrated on reduction of the number of exacerbations and the number of asthma-related deaths. This treatment is cost-effective, especially in terms of reduction of exacerbations.
Revue des Maladies Respiratoires 12/2010; 27(10):1175-94. · 0.59 Impact Factor
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ABSTRACT: Classification of chronic obstructive pulmonary disease (COPD) is usually based on the severity of airflow limitation, which may not reflect phenotypic heterogeneity. Here, we sought to identify COPD phenotypes using multiple clinical variables. COPD subjects recruited in a French multicentre cohort were characterised using a standardised process. Principal component analysis (PCA) was performed using eight variables selected for their relevance to COPD: age, cumulative smoking, forced expiratory volume in 1 s (FEV(1)) (% predicted), body mass index, exacerbations, dyspnoea (modified Medical Research Council scale), health status (St George's Respiratory Questionnaire) and depressive symptoms (hospital anxiety and depression scale). Patient classification was performed using cluster analysis based on PCA-transformed data. 322 COPD subjects were analysed: 77% were male; median (interquartile range) age was 65.0 (58.0-73.0) yrs; FEV(1) was 48.9 (34.1-66.3)% pred; and 21, 135, 107 and 59 subjects were classified in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1, 2, 3 and 4, respectively. PCA showed that three independent components accounted for 61% of variance. PCA-based cluster analysis resulted in the classification of subjects into four clinical phenotypes that could not be identified using GOLD classification. Importantly, subjects with comparable airflow limitation (FEV(1)) belonged to different phenotypes and had marked differences in age, symptoms, comorbidities and predicted mortality. These analyses underscore the need for novel multidimensional COPD classification for improving patient care and quality of clinical trials.
European Respiratory Journal 09/2010; 36(3):531-9. · 5.89 Impact Factor
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ABSTRACT: INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) is a disorder resulting from an interaction between a genetic predisposition, still poorly understood, and the impact of environmental factors including tobacco smoke or professional or domestic air contaminants. BACKGROUND: The prevalence of COPD in the world concerns women as much as men, but it remains under diagnosed among women smokers. The mortality data show an increase in mortality among women compared to men. It thus seems that COPD in women presents more often a particular phenotype, characterized more by bronchial attacks than by emphysema, and by more marked functional effects on the quality of life. Anxiety and depression seem more marked with further repercussions on the quality of life. The effectiveness of treatment may be different, in particular with regard to nicotine weaning and respiratory rehabilitation. VIEWPOINT AND CONCLUSIONS: In the evaluation of chronic diseases in women little is known about COPD. Further studies, focusing specifically on these differences, are needed in order to improve the diagnosis and management of COPD in women.
Revue des Maladies Respiratoires 06/2010; 27(6):611-24. · 0.59 Impact Factor
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Revue des Maladies Respiratoires 02/2010; 27(2):106-7. · 0.59 Impact Factor
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ABSTRACT: Inflammation and remodelling are constant features of asthma. They are present throughout the whole bronchial tree, even in the small airways (less than 2 mm). The inflammatory cell infiltrate and structural changes are, in most cases, identical. However, in severe asthma, nocturnal asthma and fatal asthma, the cellular infiltrate in the distal airways is more intense and the number of activated cells is increased. In fatal asthma there are major alterations in the distal airways involving the smooth muscle and the bronchial epithelium, and mucus hypersecretion leading to distal airway plugging. Thus the histopathological changes in the distal airways contribute to the most severe stages of asthma and should be targeted by treatment. Currently the non-invasive tools that reflect inflammation are unable to assess these changes in the distal airways.
Revue des Maladies Respiratoires 10/2009; 26(8):851-8. · 0.59 Impact Factor
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P-R Burgel,
J de Blic,
P Chanez,
C Delacourt,
P Devillier,
A Didier,
J-C Dubus,
I Frachon,
G Garcia,
M Humbert,
F Laurent,
R Louis,
A Magnan,
B Mahut,
T Perez,
N Roche, I Tillie-Leblond,
M Tunon de Lara,
D Dusser
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ABSTRACT: The present review is the summary of an expert workshop that took place in Vence (France) in 2007 on the role of distal airways in asthma. The evidence showing inflammation and remodelling in distal airways, and their possible involvement in asthma control and natural history, was reviewed. The usefulness and limitations of various techniques used for assessing distal airways were also evaluated, including pulmonary function tests and imaging. Finally, the available data studying the benefit of treatment better targeting distal airways in asthma was examined. It was concluded that both proximal and distal airways were involved in asthma and that distal airways were the major determinant of airflow obstruction. Inflammation in distal airways appeared more intense in severe and uncontrolled asthma. Distal airways were poorly attained by conventional aerosol of asthma medications owing to their granulometry, being composed of 3-5 μm particles. Both proximal and distal airways might be targeted either by delivering medications systemically or by aerosol of extra-fine particles. Extra-fine aerosols of long-acting β-agonists, inhaled corticosteroids or inhaled corticosteroid/long-acting β-agonist combinations have been shown in short-term studies to be not inferior to non-extra-fine aerosols of comparators. However, available studies have not yet demonstrated that extra-fine inhaled medications offer increased benefit compared with usual aerosols in asthmatic patients.
European Respiratory Review 06/2009; 18(112):80-95.
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ABSTRACT: Asthma symptoms are the main reason for healthcare utilization and are a fundamental parameter for the evaluation of asthma control. Currently, asthma is defined as a chronic inflammatory disease. A French expert group studied the association between inflammation and asthma symptoms by carrying out a critical review of the international literature. Uncontrolled asthmatics have an increased number of polynuclear eosinophils in the induced sputum and an increased production of exhaled NO. Control by anti-inflammatory treatment is accompanied by a reduction in bronchial eosinophilia and exhaled NO. Asthma symptoms are the result of complex mechanisms and many factors modify their perception. Experimental data suggest that there is a relationship between the perception of symptoms and eosinophilic inflammation and that inhaled corticoid therapy improves this perception. Although they are still not applicable in routine practice, follow-up strategies based on the evaluation of inflammation are thought to be more effective in reducing exacerbations than those usually recommended based on symptoms and sequential analysis of respiratory function. Inhaled corticosteroid therapy is the reference disease-modifying therapy for persistent asthma. Recent studies demonstrated that adjustment of anti-inflammatory treatment based on symptoms is an effective strategy to prevent exacerbations and reduce the total number of doses of inhaled corticosteroids.
Allergy 03/2009; 64(3):354-67. · 6.27 Impact Factor
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ABSTRACT: In asthma, symptoms are the main reason for recourse to healthcare and are a fundamental parameter for the evaluation of asthma control. Currently, asthma is defined as a chronic inflammatory disease. Uncontrolled asthmatics have an increased number of eosinophils in induced sputum and an increased production of exhaled NO. Control by anti-inflammatory treatment is accompanied by a reduction in bronchial eosinophilia and exhaled NO. Asthma symptoms are the result of complex mechanisms and many factors modify their perception. Experimental data suggests that there is a relationship between the perception of symptoms and eosinophilic inflammation, and that inhaled corticoid therapy improves this perception. Although they are still not applicable in routine practice, follow-up strategies based on the evaluation of inflammation are thought to be more effective in reducing exacerbations than those usually recommended based on retrospective evaluation of symptoms and sequential analysis of respiratory function. Inhaled corticosteroid therapy is the reference maintenance therapy for persistent asthma and adjustment of anti-inflammatory treatment based on symptoms is an effective strategy to prevent exacerbations and reduce the total dose of inhaled corticosteroids. A French expert group has undertaken a study of the association between inflammation and asthma symptoms by carrying out a critical review of the international literature.
Revue des Maladies Respiratoires 11/2008; 25(8):933-51. · 0.59 Impact Factor
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ABSTRACT: Severe asthma may involve an irreversible obstructive pattern, and structural changes in bronchial airways are believed to play a key role in this context. The aim of the present study was to compare airway remodeling in severe asthmatic children with or without obstructive pattern.
Two groups of children with severe asthma and persistent symptoms, 5-14 years old were included, 15 with persistent obstructive pattern (group O) and 10 without obstructive pattern (group N). Persistent obstructive pattern was defined as a forced expiratory volume in 1 s (FEV(1)) less than 80% of the predicted value after a course of systemic corticosteroids and no significant improvement after bronchodilator. We examined bronchial biopsies by pathological and immunochemical methods and quantified airway smooth muscle (ASM) and mucus gland areas, reticular basement membrane (RBM) thickening, distance between ASM and RBM, muscle light chain kinase (MLCK) expression and number of vessels (CD31 expression).
Surface area of ASM (P = 0.009), MLCK expression (P = 0.03) and number of vessels (P = 0.0008) were increased in group O compared with group N. Distance of RBM-ASM was shorter in group O (P = 0.007). FEV(1) negatively correlated with ASM area (r = -0.6; P = 0.002), MLCK expression (r = -0.45; P = 0.02) and CD31 expression (r = -0.7; P = 0.0003), and positively correlated with the distance of RBM-ASM (r = 0.5; P = 0.007).
Structural abnormalities of airway remodeling are present in children with severe asthma. Only an increase in surface area of ASM and the density of the vascular network are more pronounced in children with persistent obstructive pattern, while RBM thickening is similar. These results are concordant with longitudinal studies which emphasize the precocity of bronchial obstruction.
Allergy 06/2008; 63(5):533-41. · 6.27 Impact Factor
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ABSTRACT: Respiratory muscle involvement is a rarely reported manifestation of inflammatory myopathies. We report the case of a 38-year-old woman with antisynthetase syndrome who presented with inflammatory myopathy and acute pulmonary interstitial involvement that initially improved with corticosteroids and immunoglobulins. A few months later dyspnoea resumed despite the absence of evidence of interstitial deterioration or other common diagnosis including vascular or infectious disorders. Isolated respiratory muscular involvement was evidenced by functional testing. Disease course was favourable with corticosteroids and immunoglobulins. Inflammatory myopathy of the antisynthetases syndrome could be limited or mainly expressed to respiratory muscles. Unexplained dyspnoea should call in mind a muscular respiratory myositis.
La Revue de Médecine Interne 05/2008; 29(4):325-7. · 0.61 Impact Factor
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ABSTRACT: A multicentre retrospective study was undertaken to examine patients with interstitial lung disease (ILD) with the initial clinical manifestation of an anti-synthetase syndrome (anti-Jo-1 antibodies), and to analyse the characteristics and long-term outcome of these patients according to their clinical presentation (acute or gradual onset), treatment and adverse events related to treatment.
32 patients, 15 (47%) presenting with acute onset and associated respiratory insufficiency (group A) and 17 (53%) with gradual onset (group G) were examined. Myositis was diagnosed at admission in only 31% of cases and was observed during follow-up in 56% of cases, but the prevalence did not differ between the two groups.
Fever and radiological patterns including diffuse patchy ground-glass opacities, basal irregular lines and consolidation on high-resolution CT scan were more frequent in group A than in group G. More patients in group G had neutrophils in the bronchoalveolar lavage fluid and autoantibodies other than anti-Jo-1 (rheumatoid factor, anti SSa/SSb) than in group A. The percentage of patients in whom the ILD improved at 3 months was significantly higher in group A than in group G (13/15 vs 9/17; p = 0.006). In contrast, after 12 months, most patients with ILD progression were in group A and were treated with corticosteroids alone. A combination of corticosteroids and an immunosuppressive drug was required in most cases (84%) at the end of the follow-up period. Severe adverse effects of treatment were observed and varicella zoster virus infection was frequent.
Early testing for anti-synthetase antibodies, particularly anti-Jo-1, and creatine kinase determination are useful procedures in patients presenting with ILD. Treatment with corticosteroids and immunosuppressive drugs is required in most patients. At the end of the study, around two-thirds of patients had stable ILD while the other third had disease progression with respiratory insufficiency.
Thorax 02/2008; 63(1):53-9. · 6.84 Impact Factor
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ABSTRACT: We report a case of occupational hypersensitivity pneumonitis in a patient handling chicory leaves.
The diagnosis was based symptoms of broncho-alveolitis with pyrexia, positive precipitins to moulds present on chicory, especially Fusarium, and the disappearance of the clinical and radiological manifestations following cessation of exposure to chicory.
"Chicory worker's lung" is an occupational disease which should be considered in cases of respiratory symptoms suggestive of hypersensitivity pneumonitis and chronic exposure to chicory leaves.
Revue des Maladies Respiratoires 12/2007; 24(9):1139-42. · 0.59 Impact Factor
