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.
Subject(s)
Status Asthmaticus/physiopathology , Adrenal Cortex Hormones/economics , Adrenal Cortex Hormones/therapeutic use , Adrenergic beta-2 Receptor Agonists/therapeutic use , Adult , Air Pollution/adverse effects , Anti-Asthmatic Agents/economics , Anti-Asthmatic Agents/therapeutic use , Anti-Bacterial Agents/therapeutic use , Antibodies, Anti-Idiotypic , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Bronchitis/complications , Bronchitis/physiopathology , Bronchodilator Agents/therapeutic use , Case Management , Comorbidity , Cost-Benefit Analysis , Humans , Leukocytes/pathology , Leukotriene Antagonists/therapeutic use , Omalizumab , Oxygen Inhalation Therapy , Respiratory Tract Infections/complications , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/physiopathology , Respiratory Tract Infections/virology , Status Asthmaticus/complications , Status Asthmaticus/drug therapy , Status Asthmaticus/economics , Status Asthmaticus/mortality , Status Asthmaticus/psychology , Status Asthmaticus/therapySubject(s)
Diverticulum/diagnosis , Hemoptysis/diagnosis , Tracheal Diseases/diagnosis , Adult , Bronchoscopy , Diagnosis, Differential , Diverticulum/diagnostic imaging , Hemoptysis/diagnostic imaging , Hemoptysis/etiology , Humans , Incidental Findings , Male , Radiography, Thoracic , Substance-Related Disorders/complications , Tomography, X-Ray Computed , Tracheal Diseases/diagnostic imagingABSTRACT
BACKGROUND: Asthma exacerbations represent the main source of costs and morbidity in asthma care, and drugs specifically designed to prevent exacerbations are needed. A prerequisite is to dispose of a precise knowledge of inflammatory events leading to exacerbations. OBJECTIVE: To study T-cell activation during exacerbations from severe refractory asthmatics. METHODS: Proportions of blood T-cell interleukin (IL)-13, interferon-gamma, IL-4, IL-5, IL-10 production and of CD4+CD25+(high)CD62L+CD45RO+ [T regulatory (Treg)] cells were determined by flow cytometry. Blood cytokine mRNA was studied by reverse transcription-polymerase chain reaction and the respective protein levels were determined by cytokine beads array. Depletion of Treg cells was performed to study their activation. T-cell cytokines were detected in parallel in induced sputum. RESULTS: At baseline, T helper 2 (Th2) cells were increased in asthmatics, whereas T helper 1 (Th1) and Treg T cells were decreased. T helper 2 cells increased before exacerbations, followed by Th1 cells, in blood and induced sputum, albeit Treg cells decreased in parallel with IL-10-producing T cells. Concordant results were found at the mRNA level. The suppressive activity of Treg cells was impaired during exacerbations compared to baseline. CONCLUSIONS: New insights are given into pathophysiology of asthma exacerbations: Although at baseline T-cell activation is Th2-biased, a mixed Th1/Th2 activation occurs during exacerbations. The Treg cell deficiency found at baseline in SRA increases during exacerbations.
Subject(s)
Asthma/blood , Asthma/physiopathology , T-Lymphocytes/metabolism , Adult , Aged , Female , Humans , Interleukin-10/blood , Interleukin-13/blood , Interleukin-4/blood , Interleukin-5/blood , Male , Middle Aged , Severity of Illness Index , T-Lymphocytes, Regulatory/metabolismABSTRACT
This study investigated the relation between positive thyroid transcription factor 1 (TTF1) staining and survival of patients affected by primary adenocarcinoma (ADC) of the lung. Pathological tissue from consecutive ADC patients was collected from 2002 to 2004. The anti-TTF1 antibody (8G7G3/1, dilution of 1/200) was used. Thyroid transcription factor 1 staining was assessed for each tumour as positive or negative. Probability of survival was estimated by Kaplan-Meier and difference tested by log-rank test. A Cox's regression multivariate analysis was carried out. In all, 106 patients were studied (66% male, 69% PS0-1, 83% with stage III or IV). Tumours expressed positive TTF1 staining in 66% of cases. Multivariate analysis demonstrated an independent lower risk of death for patients whose tumour expresses positive TTF1 staining (HR = 0.51, 95% CI 0.30-0.85; P = 0.01) and higher grade of differentiation (HR = 0.40, 95% CI 0.24-0.68; P = 0.001). In conclusion, positive TTF1 staining strongly and independently correlates with survival of patients with primary ADC of the lung.
