Isabelle Tillie-Leblond

Pulmonary manifestations of Sjögren's syndrome.

Sjögrens syndrome is a chronic inflammatory disorder characterized by lymphocytic infiltration of exocrine glands, mainly the lacrimal and salivary glands. However, extraglandular organ systems may frequently be involved, including the lungs. Although subclinical pulmonary inflammation exists in more than 50% of patients, clinically significant pulmonary involvement affects approximately 10% of patients and may be the first manifestation of the disease. The entire respiratory tract may be involved, with a wide spectrum of manifestations including xerotrachea and bronchial sicca, obstructive small airway disease, various patterns of interstitial lung disease, lymphoinfiltrative or lymphoproliferative lung disease, such as lymphoma (usually of MALT type), pulmonary hypertension, pleural involvement, lung cysts, and pulmonary amyloidosis.

Immuno-reactive proteins from Mycobacterium immunogenum useful for serodiagnosis of metalworking fluid hypersensitivity pneumonitis

Metalworking fluid-associated hypersensitivity pneumonitis (MWF-HP) is a pulmonary disease caused by inhaling microorganisms present in the metalworking fluids used in the industrial sector. Mycobacterium immunogenum is the main etiological agent. Among the clinical, radiological and biological tools used for diagnosis, serological tests are important. The aim of this study was to identify immunogenic proteins in M. immunogenum and to use recombinant antigens for serological diagnosis of MWF-HP. Immunogenic proteins were detected by two-dimensional Western blot and candidate proteins were identified by mass spectrometry. Recombinant antigens were expressed in Escherichia coli and tested by enzyme-linked immunosorbent assay (ELISA) with the sera of 14 subjects with MWF-HP and 12 asymptomatic controls exposed to M. immunogenum. From the 350 spots visualized by two-dimensional gel electrophoresis with M. immunogenum extract, 6 immunogenic proteins were selected to be expressed as recombinant antigens. Acyl-CoA dehydrogenase antigen allowed for the best discrimination of MWF-HP cases against controls with an area under the receiver operating characteristics (ROC) curve of 0.930 (95% CI=0.820-1), a sensitivity of 100% and a specificity of 83% for the optimum threshold. Other recombinant antigens correspond to acyl-CoA dehydrogenase FadE, cytosol aminopeptidase, dihydrolipoyl dehydrogenase, serine hydroxymethyltransferase and superoxide dismutase. This is the first time that recombinant antigens have been used for the serodiagnosis of hypersensitivity pneumonitis. The availability of recombinant antigens makes it possible to develop standardized serological tests which in turn could simplify diagnosis, thus making it less invasive.

Cryptogenic hemoptysis in chronic obstructive pulmonary disease: characteristics and outcome.

Background: Hemoptysis is a common presenting symptom and cause of hospitalization in the department of respiratory diseases. In a number of patients with chronic obstructive pulmonary disease (COPD) presenting with this symptom, investigations fail to reveal a precise etiology. Little data are available regarding characteristics and outcome of COPD patients presenting with cryptogenic hemoptysis (CH). Objectives: Our study goal was to assess the functional characteristics of these subjects, the risk factors for CH and the severity of hemoptysis, as well as long-term outcome. Methods: For more than 1 year, we enrolled and followed a group of 39 consecutive COPD patients admitted to our center with CH. Results: Between 1988 and 2003, 39 patients with COPD were admitted for CH in which investigation failed to reveal an etiology. The mean age was 51.3 years. All subjects were active smokers. Twenty-one patients (54%) had at least 1 risk factor for prolonged bleeding. Patients with more severe airflow obstruction tended to have more severe bleeding. Bronchoscopy appeared as useful as a computed tomography in locating the bleeding site. Arterial embolization succeeded in controlling bleeding in all patients who underwent angiography. One patient experienced a relapse in bleeding at 2 months. One developed lung cancer after 1 year. Thirty-four patients were followed for an average of 5 years. Only 2 subjects experienced recurrent hemoptysis. None died. Conclusions: CH in patients with COPD is associated with a favorable short- and long-term outcome when managed with timely angiographic embolization. Long-term incidence of lung cancer was uncommon after an episode of CH, and recurrences of hemoptysis were rare.

Defining the “Frequent Exacerbator” Phenotype in COPD: A Hypothesis-Free Approach

Background The COPD “frequent exacerbator” phenotype is usually defined by at least two treated exacerbations per year and is associated with a huge impact on patient health. However, existence of this phenotype and corresponding thresholds still need to be formally confirmed by statistical methods analyzing exacerbation profiles with no specific a priori hypothesis. The aim of this study was to confirm the existence of the frequent exacerbator phenotype with an innovative unbiased statistical analysis of prospectively recorded exacerbations. Methods Data from patients with COPD from the French cohort in Exacerbations of COPD Patients (EXACO) were analyzed using the KmL method designed to cluster longitudinal data and receiver operating characteristic (ROC) curve analysis to determine the best threshold to allocate patients to identified clusters. Univariate and multivariate analyses were performed to study characteristics associated with different clusters. Results Two clusters of patients were identified based on exacerbation frequency over time, with 2.89 exacerbations per year on average in the first cluster (n = 348) and 0.71 on average in the second cluster (n = 116). The best threshold to distinguish these clusters was two moderate to severe exacerbations per year. Frequent exacerbators had more airflow limitation, symptoms, and health‐related quality of life impairment. A simple clinical score was derived to help identify patients at risk of exacerbations. Conclusions These analyses confirmed the existence and clinical relevance of a frequent exacerbator subgroup of patients with COPD and the currently used threshold to define this phenotype.

Allergic Bronchopulmonary Mycosis

Allergic bronchopulmonary aspergillosis (ABPA) is a common manifestation in chronic allergic asthma and cystic fibrosis (CF) patients. The role of epithelial cell dysfunctions and of the Th2 immune response (“Interleukin-4 (IL-4) hypersensitivity”), seems to be essential for developing an ABPA. Genetic factors associated with the occurrence of ABPA are identified. Different phenotypes of ABPA are described: the sero-positive ABPA, and the bronchiectasis ABPA. Sero-positive ABPA and bronchiectasis ABPA may be the illustration of two stages of the disease, time leading to an inevitable bronchial destruction. It may also be illustrate different expression of the disease. Genetic factors may favor one or the other of these two phenotypes. When clinical, radiological and biological criteria for ABPA appear in combination and the diagnosis is made, then the treatment would need to include both systemic corticosteroids and the antifungal agent itraconazole. However, treatment regimens for this antifungal therapy have yet to be definitively established, although many experts report the benefit of prolonged antifungal treatment.