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.

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.

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.

[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.

Interstitial lung disease and anti-Jo-1 antibodies: difference between acute and gradual onset.

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Airway remodeling is correlated with obstruction in children with severe asthma.

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Effects of oxygen on exercise-induced increase of pulmonary arterial pressure in idiopathic pulmonary fibrosis.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a severe disease with no known effective therapy. Patients with IPF may develop severe increase of pulmonary arterial pressure (PAP) on exercise, the mechanisms of which is not clearly identified. OBJECTIVES: To determine whether oxygen may correct the increase of PAP developed during exercise in patients with IPF. PATIENTS AND METHODS: We performed a prospective study on patients with IPF and no hypoxaemia at rest. The absence of pulmonary hypertension (PH) at rest was confirmed by echocardiography (systolic PAP <35 mmHg). Eight patients underwent echocardiography during exercise in air and with oxygen (to maintain saturation of at least 94%). Right ventricle-right atrium gradient and cardiac output were measured at rest, after each increment and at peak. We then compared the echocardiographic results obtained for air and oxygen. RESULTS: All patients developed significant increase of SPAP on exercise (73 +/- 14 mmHg in air). Oxygen did not significantly improve SPAP on exercise (SPAP: 76 +/- 15 mmHg). Echocardiographic characteristics were similar between air and oxygen except for exercise tolerance in term of workload (p=0.045) and endurance (p=0.017). Resting pulmonary function tests did not predict the occurrence of increase of PAP on exercise. CONCLUSION: Our results demonstrate that oxygen does not improve exercise-induced increase of PAP in patients with IPF and support the hypothesis that hypoxic vaso-constriction is not the main mechanism of acute increase of PAP during exercise.

[Inspiratory muscle myopathy and antisynthetase syndrome]. / Myopathie des muscles inspiratoires au cours du syndrome des antisynthétases.

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.

[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.

[Catamenial hemoptysis during hormone replacement treatment]. / Hémoptysie cataméniale sous traitement hormonal substitutif.

INTRODUCTION: Catamenial haemoptysis is a rare clinical entity resulting from the presence of ectopic intra pulmonary endometrial tissue, either parenchymatous or endobronchial. The main diagnostic criterion is the periodic character of the haemoptysis which is synchronous with menstruation. CASE REPORT: The authors report a case of catamenial haemoptysis due to endobronchial endometriosis in a 46 year old menopausal woman receiving hormone replacement treatment (HRT). She presented with 3 episodes of haemoptysis synchronous with the first days of her menstrual cycle. A thoracic CT scan showed ground glass lesions with micronodulation. Bronchoscopy showed violacious lesions bleeding on contact. The endobronchial and CT abnormalities had disappeared by day 5. After withdrawal of the HRT the haemoptysis did not recur during a follow-up of 2 years. CONCLUSION: Endobronchial endometrioisis remains a rare occurrence. This is the first case reported in a menopausal woman with artificial cycles receiving hormone replacement therapy.

[Hypersensitivity pneumonitis in a chicory worker]. / Pneumopathie d'hypersensibilité chez une endivière.

INTRODUCTION: We report a case of occupational hypersensitivity pneumonitis in a patient handling chicory leaves. CASE REPORT: 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. CONCLUSION: "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.

["EXACO": four year follow-up of exacerbations in a cohort of patients with COPD]. / "EXACO": suivi sur 4 ans des exacerbations d'une cohorte de patients atteints de bronchopneumopathie chronique obstructive.

EXACO is a French prospective observational epidemiological study. Chest physicians will enrol 1200 patients who will be followed up for 4 years. The aims of the study are to describe the exacerbations in COPD patients at different levels of severity and to confirm the existence of a sub-group of patients defined as frequent exacerbators. The clinical characteristics associated with this profile and the decline of FEV1 will be evaluated. A validation of the VSRQ scale will be performed. The data will be collected from chest physicians and by phone calls to the patients every three months.

[Pulmonary involvement in polymyositis and dermatomyositis]. / Atteintes pulmonaires des polymyosites et dermatopolymyosites.

Polymyositis is characterised by an inflammatory reaction in skeletal muscle with a variable degree of muscular weakness and associated with skin lesions in the case of dermatomyositis. Involvement of the muscles of deglutition and the diaphragm may lead to inhalation pneumonia and acute or chronic respiratory failure, often hypercapnic. The other respiratory manifestations are diffuse interstitial pneumonitis (DIP), usually non-specific, and very occasionally pulmonary arterial hypertension. The development of DIP during polymyositis is a grave prognostic factor, respiratory involvement being one of the main causes of morbidity and mortality. The onset of DIP is acute in between 30 and 47% of cases. Anti-synthetase antibodies (particularly anti-JO-1) are positive in about 75% of cases. Treatment is usually with a combination of immunosuppressants and corticosteroids without any immunosuppressants therapy having shown a superiority.

[Acute invasive pulmonary aspergillosis in chronic lung disease--a review]. / Aspergillose pulmonaire aiguë invasive et pathologies pulmonaires chroniques.

INTRODUCTION: Apart from malignancies and solid organ transplant, chronic lung disease, in particular chronic obstructive pulmonary disease (COPD), is a third important predisposing factor for acute invasive pulmonary aspergillosis. STATE OF THE ART: COPD is present in 2% of patients dying from invasive aspergillosis. This opportunistic infection occurs because of an immunodeficiency linked both to altered local immunity and to systemic factors such as long term steroid treatment and malnutrition. In patients whose sputum and/or endotracheal aspirate specimens contain hyphal forms of filamentous Aspergillus, half will have a clinically significant aspergillus infection. Diagnostic tests include serum galactomannan antigen test, serum antibody titre, thoracic CT scan and bronchoalveolar lavage (BAL). The identification of fungal hyphae in BAL fluid by microscopy and/or on culture is critical for a positive diagnosis. The mortality rate for acute invasive pulmonary aspergillosis in chronic lung diseases reaches almost 100%. Antifungal monotherapy is still recommended as a first line treatment. Combined treatment can be used in refractory aspergillosis as a salvage therapy. The question of maintaining, decreasing or interrupting steroid treatment must be considered. PERSPECTIVES: Prospective studies are needed to evaluate a standardised diagnostic strategy such as exists for patients with haematological disease. Whether this will improve prognosis remains to be seen. CONCLUSION: Acute invasive pulmonary aspergillosis complicating chronic lung disease is not rare. Improved diagnosis procedures and recent therapeutic advances may have a positive impact on patient prognosis.

[Pulmonary disease in dental laboratory technicians]. / Manifestations pulmonaires des prothésistes dentaires.

INTRODUCTION: The manufacture of dental prostheses exposes the technician to inhalation of various potentially dangerous dusts (silica, hard metals, dental alloys and acrylic resins). BACKGROUND AND VIEWPOINT: Inhalation of dusts produced by the technician in the work place may lead to several respiratory disorders (pneumoconiosis, hypersensitivity pneumonitis, asthma, lung cancer). The continuous development of new materials leads to further manifestations of these disorders and justifies their notification, even in the absence of an accepted occupational disease. This step is taken inconsistently as many dental technicians are not salaried or insured. CONCLUSION: The seriousness of some of these disorders and the absence of effective treatment makes it important to develop effective methods of prevention for the protection of individuals and groups, and for early detection.

[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.

Invasive pulmonary aspergillosis in chronic obstructive pulmonary disease: an emerging fungal pathogen.

Acute invasive pulmonary aspergillosis occurs predominantly in immunocompromised hosts, with increasing numbers of cases of invasive aspergillosis among patients with chronic obstructive pulmonary disease (COPD) being reported. Among 13 cases of invasive aspergillosis diagnosed in COPD patients admitted to the intensive care unit with acute respiratory distress, the only risk factor for invasive fungal infection was corticosteroid treatment. Invasive aspergillosis should be suspected in COPD patients receiving steroid treatment who have extensive pulmonary infiltrates. Survival depends on rapid diagnosis and early appropriate treatment. A decrease or interruption of steroid treatment should be considered as part of the overall therapeutic strategy.