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.

[Assessment of imaging techniques in the evaluation of small airways disease in asthma]. / Apport de l'imagerie dans l'évaluation de l'atteinte des petites voies aériennes dans l'asthme.

The imaging techniques that have been used in the exploration and evaluation of treatment in asthma include computed tomography (CT), helium-magnetic resonance imaging (MRI), single photon emission computerized tomoscintigraphy (SPECT) and positron emission tomography (PET). Only MRI does not involve radiation. However, in the case of CT, technical improvements and the advantages of the air-filled lung have resulted in a decreased radiation burden. High resolution examinations, using a low dose of about one-year of natural background irradiation, are possible even in infancy. CT is the best evaluated so far, the simplest to perform and the least expensive. In asthma several morphological changes related to small airway disease can be visualised on CT images: cylindrical bronchiolectasis, thickening of the bronchial walls and air trapping, an indirect marker of bronchiolar obstruction. Today there is a robust body of evidence that valid indices of small airways disease can be deduced from quantitative analysis of lung density, indices that correlate well with clinical severity and functional measurements. In addition, the sensitivity of the method is sufficient to demonstrate therapeutic effects.

[The relationship between inflammation and symptoms in asthma]. / Relation entre inflammation et symptômes dans l'asthme.

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.

[Cutaneous, pulmonary and bone aspergillosis in a patient presumed immunocompetent presenting subacute cutaneous lupus erythematosus]. / Aspergillose cutanée, pulmonaire et osseuse chez un malade ayant un lupus érythémateux cutané subaigu sans déficit immunitaire associé.

INTRODUCTION: We report a case of cutaneous, pulmonary and bone aspergillosis successfully treated after many years of progression in a patient presumed immunocompetent presenting subacute cutaneous lupus erythematosus. CASE-REPORT: A 43-year-old man, treated with thalidomide for subacute cutaneous lupus erythematosus, presented chest pain with haemoptysis and dyspnea. A pulmonary nodule was detected but the microbiological investigation was negative. The histological examination showed granuloma with round structures. No cause was found. Three years later, skin lesions appeared on the patient's face concomitantly with a pulmonary relapse. Histopathological examination of these lesions demonstrated septate hyphae. Aspergillus fumigatus was isolated in skin and lung. Disseminated aspergillosis was then diagnosed as spondylodiscitis developed. Treatment with combined voriconazole and caspofungin produced significant and rapid improvement of lesions. DISCUSSION: While aspergillosis is commonly seen in immunocompetent patients, angiotropic dissemination points to cellular immunodepression. Our patient, however, was not presenting immunodepression. We discuss the possible contributory role of thalidomide in dissemination of aspergillosis given that the literature to date contains only one reported case of cutaneous aspergillosis secondary to A. fumigatus in an immunocompetent patient. We would also point out the specific histopathological pattern of this disseminated aspergillosis with both septate hyphae and round structures. Invasive aspergillosis is highly lethal but the chances of recovery are now greater thanks to new antifungal agents.

[Characteristics of mild asthma: clinical signs and medication use. Position statement of the Mild Asthma Working Group (174)]. / Caractéristiques de l'asthme léger: signes cliniques et traitements médicamenteux. Le point de vue du Groupe de Travail sur l'Asthme Léger.

OBJECTIVE: To update on the state of knowledge in mild asthma (intermittent and persistent mild asthma, according to the GINA classification) review the literature, and the position statement of the French Mild Asthma Working Group. METHODS: The French Mild Asthma Working Group (11 lung specialists, 4 paediatricians, 1 pharmacologist, and 1 general practitioner) selected, analysed, and summarised the literature on the descriptive epidemiology, physiopathology, clinical signs, and management of mild asthma. The position of the working group on the descriptive epidemiology (causal factors excluded) and the nature of the bronchial inflammation has been presented in a previous article. The present article focuses on the clinical features of mild asthma and the use of medication for it. RESULTS: Mild asthma was more frequent, more symptomatic, and less well controlled in children than in adults. Its generally benign evolution may in some (<10%) cases be complicated by severe episodes. Patients with mild persistent asthma require controller medication every day: permanent low-dose inhaled corticosteroid monotherapy is the reference foundation treatment for persistent mild asthma. CONCLUSIONS: The present findings should help clinicians and guide them in their approach to managing this condition.

[Characteristics of mild asthma: descriptive epidemiology and nature of bronchial inflammation. Position of the Mild Asthma Working Group]. / Caractéristiques de l'asthme léger: épidémiologie descriptive et nature de l'inflammation bronchique.

INTRODUCTION: Update on the state of knowledge in the mild asthma (intermittent and persistent mild asthma, according to the GINA classification) literature, and position of a French Mild Asthma Working Group. STATE OF THE ART: The French Mild Asthma Working Group (11 lung specialists, 4 paediatricians, 1 pharmacologist, and 1 general practitioner) selected, analysed, and summarised the literature on the epidemiology, physiopathology, clinical signs, and management of mild asthma. The present article shows the position of the working group on mild asthma descriptive epidemiology (causal factors excluded) and the nature of the bronchial inflammation. Clinical signs and medicinal treatments will be presented in a second article. PERSPECTIVES: Between 50% and 75% of asthma patients, depending on the study, present mild asthma. Childhood-to-adulthood cohort monitoring found severity to be unchanged over developmental time. Its generally benign evolution may in some (<10%) cases be complicated by severe episodes. Inflammation and airway-wall remodelling were always found, although of variable intensity, and non-specific (except for absence of infiltration by polymorphonuclear neutrophils). Corticosteroid therapy by inhalation reduces bronchial inflammation, but with little impact on airway-wall remodelling. CONCLUSION: The present findings should help clinicians in identifying and understanding mild asthma.

Quality of life in lung cancer: does disclosure of the diagnosis have an impact?

BACKGROUND: Quality of life (QOL) is an important component of evaluation in oncology. Usually, QOL is used in phase III studies to compare two treatments. The aim of this trial was to evaluate the impact of the disclosure of the diagnosis of cancer on QOL by using the European Organisation for Research and Treatment of Cancer core Quality of Life Questionnaire (EORTC QLQ)-C30 questionnaire and the supplemental lung cancer-specific module QLQ-LC13. PATIENTS AND METHODS: Patients hospitalised for exploration of an abnormal chest X-ray, with no previous history of cancer, a performance status < or =2, and able to fulfil the questionnaire were eligible. The patients answered the questionnaire two times: before (Q1) and after (Q2) the disclosure of the diagnosis. RESULTS: Seventy patients answered at Q1 and Q2. After the disclosure, some scores deteriorated: arm pain (P=0.009), physical functioning (P=0.01), role functioning (P=0.008), emotional functioning (P=0.0001) and social functioning (P=0.012), whereas the patients' own assessment of global QOL (item global QOL in functioning scales) did not show the same evolution. CONCLUSION: Disclosure of the diagnosis had an impact on social and emotional QOL. Patients with lung cancer need psychological support at the beginning of their disease.

[Exposure to asbestos. Role of thoracic imagery in screening and follow-up]. / Exposition à l'amiante. La place de l'imagerie thoracique dans le dépistage et le suivi.

Chest radiograph and computed tomography are the most appropriate imaging tools for detecting asbestos-related pleural and parenchymal disease due to their availability and performances. The cost and irradiation delivery of conventional chest X-rays are limited. Technical parameters and reading should be standardized. Digital chest radiograph will progressively replace conventional techniques but technical standards and performance data are lacking. Computed tomography, using spiral or conventional mode, explores the whole lung and pleura. High resolution computed tomography samples both lung and pleura but its sensitivity for parenchymal fibrosis detection is greater. Several methods can be employed and should be recommended to reduce radiation dose in spiral and high resolution computed tomography. Computed tomography is more sensitive and specific than chest radiograph in early detection of pleural plaques and parenchymal fibrosis but is not infallible. The error reading rate of chest radiograph for early detection of bronchial carcinoma is high. Computed tomography is more sensitive but lacks specificity and leads to detect a high rate of lesions the relation to asbestos exposure of which are difficult to establish. No scientific data are available to assess the contribution of imaging in early detection of mesothelioma.

Assessment of imaging techniques for evaluating small-airway disease in asthma.

The imaging techniques used to investigate patients with asthma and to assess the effects of asthma treatments include computed tomography (CT), helium magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), and positron-emission tomography (PET). Only MRI does not involve radiation exposure. Technical improvements in CT, together with the imaging advantages inherent in the presence of air in the lung, have diminished the radiation exposure required for lung CT. High-resolution low-dose lung CT protocols deliver a dose roughly equal to 1 year of natural radiation exposure and can be used even in paediatric patients. To date, CT is the most extensively studied lung imaging method, the simplest to perform, and the least expensive. In patients with asthma, CT may show several structural changes related to small-airway disease including cylindrical bronchiolectasis, bronchial wall thickening, and air trapping; an indirect marker for bronchiolar obstruction. A robust body of evidence indicates that valid CT markers for small-airway disease can be derived from quantitative lung density measurements and that these markers correlate with clinical severity and lung function test results. In addition, these CT markers are sufficiently sensitive to demonstrate therapeutic effects.

Update on the roles of distal airways in asthma.

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 ß-agonists, inhaled corticosteroids or inhaled corticosteroid/long-acting ß-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.

Mild asthma: an expert review on epidemiology, clinical characteristics and treatment recommendations.

This review is the synthesis of a working group on mild asthma. Mild asthma includes intermittent and persistent mild asthma according to the Global Initiative for Asthma (GINA) classification, and affects between 50% and 75% of asthmatic patients. Mild asthma is more frequent, more symptomatic, and less well controlled in children than in adults. Cohort studies from childhood to adulthood show that asthma severity usually remains stable over time. Nevertheless, mild asthma can lead to severe exacerbations, with a frequency ranging from 0.12 to 0.77 per patient-year. Severe exacerbations in mild asthma represent 30-40% of asthma exacerbations requiring emergency consultation. In mild asthma, inflammation and structural remodelling are constant, of varying intensity, but nonspecific. Therapy with inhaled corticosteroids (ICS) decreases bronchial inflammation, but has only a slight effect on structural remodelling, and, when stopped, inflammation immediately recurs. Permanent low-dose ICS therapy is the reference treatment for persistent mild asthma. Effectiveness is to be reassessed at 3 months, and if it is insufficient the patient is no longer considered mildly asthmatic, and treatment has to be stepped up. As mild asthma is the most frequent form of the disease, diagnosis and management require physicians' particular attention.

IgE-dependent expression of mRNA for IL-4 and IL-5 in human lung mast cells.

By using the reverse transcriptase (RT)-PCR and in situ hybridization we have studied the expression of mRNA for IL-5 and IL-4 in human lung mast cells induced by cross-linkage of high affinity Fc epsilon Rs. Lung mast cells were purified using affinity magnetic selection with mAb YB5.B8 against c-kit to achieve a final mast cell purity > 93%. Purified mast cells were precultured with stem cell factor (SCF) (10 ng/ml) and myeloma IgE (3 micrograms/ml) for 16 h before challenge with anti-IgE (1 or 10 micrograms/ml). IgE-dependent activation of lung mast cells caused expression of IL-5 mRNA, which was evident by 2 h and persisted for up to 48-72 h in all of 12 experiments, whereas IL-4 mRNA expression was of a shorter duration and was demonstrable in 6 of 13 experiments. We confirmed that mast cells, and not T cells, were the source of these cytokine messages by using reverse transcriptase-PCR in cell preparations containing known numbers of mast cells and T cells, in situ hybridization in enriched mast cell preparations, and double in situ hybridization-immunocytochemical staining. IL-5 mRNA expression did not require the pretreatment of cells with SCF, whereas expression of IL-4 mRNA seemed to require both anti-IgE and SCF. The strength of IL-5 mRNA signal was related to anti-IgE concentration. Immunoreactive IL-5 was detectable 8 h after anti-IgE challenge, and 10(6) mast cells generated a mean of 731 +/- 400 pg of IL-5 into the supernatant during 48-h culture, but no IL-4 product was detectable. These findings demonstrate the capacity of human lung mast cells to transcribe IL-4 and IL-5 after IgE-dependent activation and to synthesize and release immunoreactive IL-5.

Pneumothoraces and chest tube placement after CT-guided transthoracic lung biopsy using a coaxial technique: incidence and risk factors.

OBJECTIVE: This study investigates factors influencing the risk of pneumothorax and chest tube placement in patients undergoing CT-guided transthoracic lung biopsy for pulmonary lesions using a coaxial technique. SUBJECTS AND METHODS: The study included 307 patients with pulmonary lesions biopsied under CT guidance. Patient-related parameters considered were age, sex, presence of emphysema or bullae, and lung function data. Lesion-related variables were size, location, cavitary appearance on CT, pleural contact, and depth of the lesion. Procedure variables were duration, type of needle, and experience of the operator. All variables were analyzed as single and multiple dependent variables for occurrence of pneumothorax. RESULTS: Pneumothorax occurred in 61 (19.9%) of the 307 patients, and chest tube placement was required in six patients (2.0%). Univariate analysis showed that lesion size, lesion location, lesion depth, and difficulty of the procedure were significantly associated with a higher rate of pneumothorax. Using multivariate logistic regression analysis, we found that lesion depth from the pleural entry point was the sole variable that was significantly associated with an increased risk of pneumothorax. This risk increased with the depth of the lesion. Chest tube placement was required more frequently in patients with severe emphysema, obstructive lung disease, or hyperinflation. CONCLUSION: Lesion depth is the predominant risk factor for pneumothorax in patients undergoing CT-guided transthoracic lung biopsy. Chest tube placement is necessary more frequently in patients with severe emphysema, obstructive lung disease, or hyperinflation.

Increased prevalence of asthma and allied diseases among active adolescent tobacco smokers after controlling for passive smoking exposure. A cause for concern?

BACKGROUND: Whereas effects on allergic and respiratory health have been established for passive tobacco smoking, contradictory results still exist for active tobacco smoking. OBJECTIVE: Whether adolescents with asthma and allied diseases have higher rates of active smoking compared with adolescents without asthma was assessed after controlling for environmental tobacco smoking exposure. METHODS: A population-based sample of 14,578 adolescents was enrolled in an epidemiological survey on allergies in France. RESULTS: After controlling for age, sex, geographic region, familial allergy and passive smoking, current (in the past year) wheezing (12.4%), current asthma (5.6%), lifetime asthma (12.3%), current rhinoconjunctivitis (13.9%), lifetime hayfever (14.4%) and current eczema (9.3%) but not lifetime eczema (22.5%) were all significantly related to active smoking (>1 cigarette/day) (9.3%). A higher risk of current wheezing, current and lifetime asthma or current eczema was seen in smokers exposed to passive smoking compared with smokers not exposed to it using a polychotomous logistic regression model, in which the different modalities of exposure to active and passive smoking constituted the response variable. Passive smoking was significantly associated only with current diseases. Active smoking was also highly related to both severe asthma (OR=4.02; 95% confidence interval: 1.37, 11.79) and severe rhinoconjunctivitis (OR=2.95; 1.58, 5.49). The highest rate of adolescents suffering from the co-morbidity of lifetime asthma and hayfever (3.6%) was also seen in active smokers compared with passive and non-smokers (5.5% vs. 3.6% and 3.1%, respectively; P=0.001). CONCLUSIONS: Being asthmatic or allergic does not seem to act as a deterrent towards starting active smoking or continuing to smoke in adolescence. Results suggest the need for considering individual allergic status in programming health educational activities aimed at reducing smoking among adolescents.