[Features of asthma in women: what is the relationship with hormonal status?]. / Particularités de l'asthme de la femme: quelle relation avec le statut hormonal?

INTRODUCTION: The prevalence and control of asthma are modulated by hormonal changes in women, suggesting an influence of sex hormones on the airways. BACKGROUND: The blood levels of both oestrogens and progesterone can modulate airway tone and inflammation. Asthma prevalence changes at puberty and the menopause, events also associated with modifications of adipose tissue and behaviour. Changes in lung function and asthma control are well documented during the menstrual cycle. However, an effect of hormone therapy on asthma control has not been demonstrated. PERSPECTIVE: The effect of a targeted hormonal therapeutic intervention in menopausal asthma, a phenotype, which is frequently particularly severe, or in premenstrual asthma, should be evaluated by randomized trials. CONCLUSION: Involvement of sex hormones and their cyclical variations in the characteristics of asthma in women is probable, despite lack of convincing data. However, no definitive protective or deleterious effect can be assigned. Complex interactions with adipose tissue, airways anatomy and the domestic or working environment must be taken into account to explain these differences.

[Lung is also involved in juvenile dermatomyositis]. / Le poumon est une cible de la dermatomyosite de l'enfant.

Juvenile dermatomyositis is the leading cause of chronic idiopathic inflammatory myopathy of auto-immune origin in children. Lung involvement in inflammatory myopathies is well described in adults, involving mostly interstitial lung disease, aspiration pneumonia and alveolar hypoventilation. We propose to describe its specificities in children. Pulmonary involvement may be asymptomatic and therefore must be systematically screened for. In case of clinical or functional respiratory abnormality, a chest computed tomographic (CT) scan is necessary. In children, a decrease of respiratory muscle strength seems common and should be systematically and specifically searched for by non-invasive and reproducible tests (sniff test). Interstitial lung disease usually associates restrictive functional defect, impairment of carbon monoxide diffusion and interstitial lung disease on CT scan. As in adults, the first-line treatment of juvenile dermatomyositis is based on corticosteroids. Corticosteroid resistant forms require corticosteroid bolus or adjuvant immunosuppressive drugs (methotrexate or cyclosporine). There is no consensus in pediatrics for the treatment of diffuse interstitial lung disease. Complications of treatment, including prolonged steroid therapy, are frequent and therefore a careful assessment of the treatments risk-benefit ratio is necessary, especially in growing children.

Oxidative stress-mediated iNKT-cell activation is involved in COPD pathogenesis.

Chronic obstructive pulmonary disease (COPD) is a major clinical challenge mostly due to cigarette smoke (CS) exposure. Invariant natural killer T (iNKT) cells are potent immunoregulatory cells that have a crucial role in inflammation. In the current study, we investigate the role of iNKT cells in COPD pathogenesis. The frequency of activated NKT cells was found to be increased in peripheral blood of COPD patients relative to controls. In mice chronically exposed to CS, activated iNKT cells accumulated in the lungs and strongly contributed to the pathogenesis. The detrimental role of iNKT cells was confirmed in an acute model of oxidative stress, an effect that depended on interleukin (IL)-17. CS extracts directly activated mouse and human dendritic cells (DC) and airway epithelial cells (AECs) to trigger interferonγ and/or IL-17 production by iNKT cells, an effect ablated by the anti-oxidant N-acetylcystein. In mice, this treatment abrogates iNKT-cell accumulation in the lung and abolished the development of COPD. Together, activation of iNKT cells by oxidative stress in DC and AECs participates in the development of experimental COPD, a finding that might be exploited at a therapeutic level.

[Mild asthma in children: new data and a revival of interest]. / Asthme léger de l'enfant : données nouvelles et regain d'intérêt.

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.

[The distal airways in systemic disease]. / Voies aériennes distales et maladies de système.

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.

[Asthma: treatment of exacerbations]. / Asthme: traitement des exacerbations.

INTRODUCTION: 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. BACKGROUND: 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. VIEWPOINTS: 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. CONCLUSION: 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.

[Structural abnormalities and inflammation in COPD: a focus on small airways]. / Modifications structurales et inflammation dans la BPCO : importance des voies aériennes distales.

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.

[Exacerbations of asthma in pregnant women]. / Exacerbations de l'asthme chez la femme enceinte.

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.

Update on the roles of distal airways in COPD.

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.

Hypersensitivity pneumonitis and metalworking fluids contaminated by mycobacteria.

Metalworking fluids (MWF) are responsible for hypersensitivity pneumonitis (HP). The aim of the present study was to identify the antigen (Ag) responsible for MWF-associated HP, and to optimise serological diagnosis by definition of a threshold allowing discrimination between HP patients and asymptomatic exposed workers. 13 patients, who were workers at a car engine manufacturing plant, were suspected of MWF-associated HP. Microbial analysis of 83 used MWFs was carried out. Sera from 13 MWF-associated HP patients, 12 asymptomatic exposed workers and 18 healthy unexposed controls were tested to determine their immunological responses to three Ags, including Mycobacterium immunogenum. M. immunogenum was identified in 40% of used fluids by culture and confirmed by DNA sequencing. The threshold for differentiating MWF-associated HP patients from asymptomatic exposed workers was five arcs of precipitation (sensitivity 77% and specificity 92%), as determined by electrosyneresis (ES). Using ELISA methods with protein extract from M. immunogenum, a threshold leading to 92% sensitivity and 100% specificity was established. The detection of specific antibodies against M. immunogenum Ag at high levels in case sera suggests that M. immunogenum-contaminated MWF is responsible for MWF-associated HP. To discriminate MWF-associated HP patients from asymptomatic exposed workers, we suggest a five-arc threshold for ES and a 1.6-AU threshold for ELISA methods.

[Adult asthma exacerbations in questions]. / Les exacerbations de l'asthme de l'adulte en questions.

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.

[Are there specific characteristics of COPD in women?]. / Existe-t-il des spécificités chez les femmes atteintes de BPCO ?

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.

Clinical COPD phenotypes: a novel approach using principal component and cluster analyses.

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.

[Asthma: a disease of the whole bronchial tree]. / L'asthme: une maladie de tout l'arbre aérien.

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.

Relation between inflammation and symptoms in asthma.

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.