[Anti-IL-5 in severe asthma associated with eosinophilic granulomatosis with polyangiitis. Real-life study]. / Anti-IL-5 dans l'asthme sévère associé à une granulomatose éosinophilique avec polyangéite. Étude en vie réelle.

INTRODUCTION: Eosinophilic granulomatosis with polyangiitis (EGPA) is a form of necrotizing vasculitis affecting small vessels and typically characterized by severe glucocorticoid (GC)-dependent eosinophilic asthma. While mepolizumab, which is indicated at a dose of 100mg/4weeks in severe eosinophilic asthma, has been shown to be an effective treatment for EGPA-related asthma at a dose of 300mg/4weeks, it was only recently approved at this dose. METHODS: This retrospective, single-center, observational study was conducted to investigate over a 5-year period (2014-2019) the effect of mepolizumab 100mg/4weeks at 12months in patients with EGPA and glucocorticoid-dependant severe asthma. Response to treatment was defined as reduction in daily dose of oral corticosteroids to at most 5mg/day or reduction in annual exacerbation by at least 50%. RESULTS: Thirty patients were included, of whom twenty-three were treated (two were not fully evaluable). Among the 21 evaluable treated patients, 13 (62%) had responded at 12months. At baseline, non-responders had lower FEV1 levels and lower blood eosinophil levels than responders. CONCLUSIONS: Mepolizumab at a "severe asthma" dose (100mg/4weeks) is effective in treatment of GC-dependent severe asthma in most patients with EGPA.

[The effects of inhaled steroids withdrawal in COPD]. / Impact du sevrage des corticostéroïdes inhalés dans la BPCO.

The key pathophysiological feature of chronic obstructive pulmonary disease (COPD) is an abnormal inflammatory bronchial reaction after inhalation of toxic substances. The priority is the avoidance of such toxic inhalations, but the use of anti-inflammatory drugs also seems appropriate, especially corticosteroids that are the sole anti-inflammatory drug available for this purpose in France. The risks associated with the prolonged use of these parenteral drugs are well known. Inhalation is therefore the optimal route, but inhaled drugs may also lead to adverse consequences. In COPD, there is an inhaled corticosteroids overuse, and a non-satisfactory respect of the guidelines. Consequently, their withdrawal should be considered. We reviewed seven clinical studies dealing with inhaled corticosteroids withdrawal in patients with COPD and found that included populations were heterogenous with different concomitant treatments. In non-frequent exacerbators receiving inhaled corticosteroids outside the recommendations, withdrawal appears to be safe under a well-managed bronchodilator treatment. In patients with severe COPD and frequent exacerbations, the risk of acute respiratory event is low when they receive concomitant optimal inhaled bronchodilators. However, other risks may be observed (declining lung function, quality of life) and a discussion of each case should be performed, especially in case of COPD and asthma overlap.

[The place of inhaled corticosteroids in COPD]. / Place des corticostéroïdes inhalés dans la BPCO.

INTRODUCTION: Clinical trials have provided some evidence of a favorable effect of inhaled corticosteroids on the frequency of exacerbations and on the quality of life of patients with chronic obstructive pulmonary disease (COPD). In contrast, ICS have little or no impact on lung function decline and on mortality. STATE OF THE ART: Inhaled corticosteroids are recommended only in a minority of COPD patients, those with severe disease and repeated exacerbations and probably those with the COPD and asthma overlap syndrome. However, surveys indicate that these drugs are inappropriately prescribed in a large population of patients with COPD. Overtreatment with inhaled corticosteroids exposes these patients to an increased risk of potentially severe side-effects such as pneumonia, osteoporosis, and oropharyngeal candidiasis. Moreover, it represents a major waste of health-care spending. CONCLUSION: Primary care physicians as well as pulmonologists should be better aware of the benefits as well as the side-effects and costs of inhaled corticosteroids.

Primary ciliary dyskinesia in adults.

INTRODUCTION: Primary ciliary dyskinesia is an autosomal recessive genetic disorder leading to structural and/or functional abnormalities of motor cilia. Impaired mucociliary clearance is responsible for the development of a multi-organ disease, which particularly affects the upper and lower airways. STATE OF THE ART: In adults, primary ciliary dyskinesia is mainly characterized by bronchiectasis and chronic ear and sinus disorders. Situs inversus is found in half of patients and fertility disorders are commonly associated. Diagnosis is based on specialized tests: reduced level of nasal nitric oxide concentrations is suggestive of primary ciliary dyskinesia, but only a nasal or bronchial biopsy/brushing with analysis of beat pattern by videomicroscopy and/or analysis of cilia morphology by electronic microscopy can confirm the diagnosis. However, the diagnosis is difficult to achieve due to the limited access to these specialized tests and to difficulties in interpreting them. Genetic tests are under development and may provide new diagnostic tools. Treatment is symptomatic, based on airway clearance techniques (e.g., physiotherapy) and systemic and/or inhaled antibiotics. Prognosis is related to the severity of the respiratory impairment, which can be moderate or severe. PERSPECTIVES AND CONCLUSIONS: Diagnosis and management of primary ciliary dyskinesia remain poorly defined and should be supported by specialized centers to standardize the diagnosis, improve the treatment and promote research.

[Pleuropneumonia due to Mycobacterium chelonae]. / Pleuropneumonie à Mycobacterium chelonae.

Mycobacterium chelonae (M. chelonae) is rarely responsible for respiratory infection. This report concerns the case of an 81-year-old man with previously asymptomatic bronchiectasis, colonised by M. chelonae for 3 years. He was hospitalised for acute dyspnoea and fever due to a right hydro-pneumothorax with cavitated alveolar opacities of the right lung. Pleural fluid and bronchial aspiration were positive for M. chelonae and no other microorganisms were detected. The effusion was drained and the patient treated with clarythromycin and amikacin. The radiological abnormalities improved but the patient's general condition remained poor. Treatment was continued for 11 months. Because of the absence of any other bacteria, clinical deterioration following broad-spectrum antibiotics and stabilisation of the lesions after anti-mycobacterial treatment, our diagnosis was severe M. chelonae pleuro-pneumonia in an immunocompetent patient.

Nasal airway ion transport is linked to the cystic fibrosis phenotype in adult patients.

BACKGROUND: This study was conducted to determine whether the major nasal airway ion transport abnormalities in cystic fibrosis (that is, defective cAMP regulated chloride secretion and basal sodium hyperabsorption) are related to the clinical expression of cystic fibrosis and/or to the genotype. METHODS: Nasal potential difference was measured in 79 adult patients with cystic fibrosis for whom clinical status, respiratory function, and CFTR genotype were determined. RESULTS: In univariate and multivariate analysis, patients with pancreatic insufficiency were more likely to have low responses to low chloride (odds ratio (OR) 8.6 (95% CI 1.3 to 58.5), p = 0.03) and isoproterenol (OR 11.2 (95% CI 1.3 to 93.9), p = 0.03) solutions. Similarly, in univariate and multivariate analysis, patients with poor respiratory function (forced expiratory volume in 1 second <50% of predicted value) were more likely to have an enhanced response to amiloride solution (OR 3.7 (95% CI 1.3 to 11.0), p = 0.02). However, there was no significant relationship between nasal potential difference and the severity of the genotype. CONCLUSIONS: Nasal epithelial ion transport in cystic fibrosis is linked to the clinical expression of the disease. The pancreatic status appears to be mostly related to the defect in epithelial chloride secretion whereas the respiratory status is mostly related to abnormal sodium transport and the regulatory function of the CFTR protein.

Impact of highly active antiretroviral therapy on the occurrence of bacteraemia in HIV-infected patients and their epidemiologic characteristics.

OBJECTIVE: 1. to assess the impact of highly active antiretroviral therapy (HAART) on the occurrence of bacteraemia in HIV-infected patients and their clinical and microbiological characteristics. 2. to identify risk factors for bacteraemia in this setting. METHODS: The files of all HIV-infected patients hospitalized for an episode of bacteraemia in a 28-bed infectious diseases unit between January 1995 and December 1998 were reviewed. Cases occurring during HAART were compared to cases occurring in patients not receiving HAART. Furthermore, in a case-control study, patients with bacteraemia occurring during HAART were compared with other patients receiving HAART. RESULTS: There were 74 episodes of bacteraemia in patients not receiving HAART and 31 episodes in patients receiving HAART. The occurrence of bacteraemia fell from 10.5/100 hospitalizations in 1995 to 5.5/100 in 1998 (P = 0.02 trend test). The occurence of P. aeruginosa bacteraemia fell sharply (9/398 vs 1/273, P = 0.05). A significant fall in catheter-related infections was observed between 1995 and 1998 (5.5% vs 1.8%). The two-thirds/one-third distribution of hospital-acquired and community-acquired infections remained stable throughout the period study. In patients receiving HAART, the case-control study showed by multivariate analysis, that a CD4 cell count of less than 100/ micro L [OR = 7.3 (1.9-49.7)], and the use of exogenous devices [OR = 13.3 (2.5-71)] were significantly associated with the risk of bacteraemia. CONCLUSION: The introduction of HAART has been associated with a significant fall in the occurrence of bacteraemia. However, patients with a low CD4 cell count remain at risk of bacteraemia with similar microbiological and epidemiological characteristics than in the pre-HAART era.