Long-term adherence to ambulatory initiated continuous positive airway pressure in non-syndromic OSA children.

PURPOSE: In children, the usual indications for continuous positive airway pressure (CPAP) are residual OSA after adenotonsillectomy and/or persistent OSA due to obesity. Data concerning adherence (hours/night) following ambulatory CPAP initiation are scarce. METHODS: An observational cohort of 78 children was followed over 2 years. All exhibited sleep-disordered breathing (SDB) symptoms, were assessed by polysomnography, and prescribed CPAP. CPAP was initiated at hospital for 10 children. RESULTS: OSA children, mean age 10.4 ± 3.2 years, were mostly males (75.6%), with a mean body mass index of 21.2 ± 7.3 kg/m2, and mean apnea+hypopnea index of 12.2 ± 10.6 events/hour. Seventy-two children were still on CPAP at 3 months, 63 at 6 months, 55 at 1 year, and 34 at 2 years. CPAP was discontinued thanks to rehabilitation programs, dento-facial orthopedics, and/or weight loss. Mean CPAP adherence at 1, 3, 6, 12, and 24 months was respectively 6.1 ± 2.8, 6.2 ± 2.6, 6.2 ± 2.8, 6.3 ± 2.8, and 7.0 ± 2.7 h/night. There was a trend towards higher CPAP adherence and younger age, primary versus middle/high school attendance, higher baseline apnea+hypopnea index, and neurocognitive disorders. CONCLUSION: In our population, mean CPAP adherence defined in hours per night was high and did not decrease during the 24-month follow-up. These findings support the feasibility of ambulatory CPAP initiation in non-syndromic OSA. The high CPAP adherence is expected to be associated with improvements in neurocognition, and in metabolic and cardiovascular parameters.

[Factors predicting mortality during an outbreak of Legionnaire's disease in the north of France]. / Epidémie de légionellose dans le Pas-de-Calais (2003--2004): analyse descriptive et facteurs prédictifs d'une évolution défavorable.

Between November 2003 and January 2004 in the North of France a large outbreak of legionnaire's disease affected 85 patients. The clinical, biological and radiological characteristics of the patients were investigated to determine factors associated with mortality. Two populations were defined and compared: patients who died within 28 days and those who survived. Eighty-five patients were included in this study. The median age was 75 years. The median fever was 39.3 +/- 0.1 degrees. Fifteen patients (17.6%) had at least 3 underlying co-morbidities. Cough, dyspnoea, confusion and diarrhoea were found in respectively 46, 68, 47, and 15% of the patients. The median of urea was 0.7 +/- 0.05 g/L, creatinine 16 +/- 1.5 mg/L, CRP 332 +/- 15 mg/L. On the chest X-ray, lung infiltrates were present in 64% and multilobar in 40%. The overall mortality rate was 21%. In univariate analysis, diabetes mellitus, dyspnoea, urea>0.90 g/l and CRP>350 mg/l were predictive factors of mortality. In multivariate analysis, diabetes mellitus, urea>0.90 g/l, and bilateral infiltrates on chest X ray were retained as independent risk factors for death.

[Hereditary multiple exostosis complicated by spontaneous haemothorax]. / Hémothorax spontané compliquant une maladie des exostoses multiples.

Spontaneous haemothorax is a rare event in the general population. However some diseases, including hereditary multiple exostosis, have an increased incidence of this complication. We report the case of a 22 year old patient with hereditary multiple exostosis who presented with a right sided haemothorax due to an exostosis of the seventh rib. The pathophysiology of spontaneous haemothorax in the setting of hereditary multiple exostosis is discussed together with surgical treatment and long term follow up.

[Severe varicella zoster pneumonia during the course of treatment with azathioprine for Crohn's disease]. / Pneumopathie varicelleuse sévère au cours d'un traitement par azathioprine pour une maladie de Cröhn.

INTRODUCTION: Disseminated varicella zoster infection has only rarely been reported in patients with inflammatory bowel disease, despite the frequent use of azathioprine for this disorder. CASE REPORT: We report the case of an 18-year-old woman who developed severe varicella zoster pneumonia 9 months after starting azathioprine for Crohn's disease. The patient recovered after prompt treatment with acyclovir and discontinuation of the azathioprine. CONCLUSIONS: Strategies concerning the treatment and the prevention of varicella infection in the immunocompromised patient are discussed.

[The anti-synthetase syndrome]. / Le syndrome des anti-synthétases.

The anti-synthetase syndrome comprises the association of an inflammatory myopathy (polymyositis, dermatomyositis), interstitial pneumonitis, skin lesions characteristic of "mechanics hands", Raynaud's phenomena, inflammatory polyarthritis and, at the biological level, antinuclear antibodies known as anti-synthetases. We report our observations of two patients, one with a typical anti-synthetase syndrome and one with an incomplete form. Two men aged 49 and 47 presented with increasing dyspnoea upon effort, muscular weakness, arthralgia, bilateral pulmonary crackles and, in the first case, typical hairless skin lesions. In both cases the chest x-rays and CT scans confirmed the presence of interstitial lesions, predominantly in the lower lobes. Lung function tests showed a restrictive pattern with reduced gas transfer. At the biological level both patients presented an inflammatory picture with elevated muscle enzymes and anti-Jo-1 antibodies. Immuno-suppressive treatment with cortico-steroids and cyclophosphamide lead to a symptomatic improvement, regression of the radiological changes and improvement in the measurements of pulmonary function.

Airway neutrophil inflammation in nonasthmatic patients with food allergy.

BACKGROUND: Patients with food allergy (FA) have been recently shown to develop bronchial hyperresponsiveness (BHR), despite the absence of any concomitant asthmatic manifestation. In order to explain this observation, we sought to examine the presence of a bronchial inflammation in induced sputum of nonasthmatic patients with FA. METHODS: Twelve nonasthmatic patients with FA (urticaria, digestive symptoms, anaphylaxis) were included in the study. Results were compared to these obtained from eight asthmatic patients without food allergy and eight healthy controls. Diagnosis of FA was based on double-blind placebo-controlled challenge. Sputum cells and fluid-phase eosinophil cationic protein (ECP), myeloperoxidase (MPO) and interleukin-8 (IL-8) were measured in induced sputum. BHR was evaluated using methacholine inhalation. RESULTS: Sputum from asthmatics, in comparison with the sputum of healthy subjects and patients with FA contained a higher proportion of eosinophils and higher levels of ECP (< 0.001). In marked contrast, patients with FA exhibited an increased proportion of neutrophils and IL-8 in comparison with asthmatics and controls (P < 0.05 for neutrophils and P < 0.001 for IL-8). There was a significant correlation between sputum neutrophils and IL-8 (r = 0.68, P < 0.001). MPO levels were not different between the groups. There was a trend toward higher levels of IL-8 and ECP in food allergic patients with BHR in comparison with patients with FA without BHR. CONCLUSION: Our results demonstrate that a subclinical neutrophil airway inflammation is present in patients with food allergy free of clinical respiratory symptoms and that IL-8 may be an important mediator of this neutrophilia.

[Respiratory bronchiolitis with diffuse interstitial lung disease]. / Bronchiolite respiratoire avec pneumopathie interstitielle diffuse.

Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) is a disease that exclusively affects cigarette smokers. Long-term prognosis is good with cessation of smoking, in combination or not with corticosteroid therapy. We report here the case of a 50-year-old patient with RB-IL diagnosed on lung biopsy. Despite corticosteroid and cyclophosphamide therapy, no functional or radiological improvement was obtained. In contrast, cessation of smoking was associated with the disappearance of the infiltrative opacities. Clinical and radiological parameters remained stable during follow-up (13 years) while a moderate obstructive pattern appeared.

Bronchial interleukin-5 and eotaxin expression in nasal polyposis. Relationship with (a)symptomatic bronchial hyperresponsiveness.

An eosinophilic bronchial inflammation was previously demonstrated in patients with nasal polyposis (NP) and asymptomatic bronchial hyperresponsiveness (BHR) similar to that observed in asthmatic patients with NP, whereas patients with NP without BHR did not. The aim of the study was to investigate the contribution of interleukin 5 (IL-5) and eotaxin to the pathogenesis of BHR associated with NP. Eleven patients with NP without BHR (Group A), 8 patients with NP and asymptomatic BHR (Group B), and 9 patients with NP and asthma (Group C) were included. Bronchial biopsies were studied for IL-5 and eotaxin immunoreactivity and IL-5 mRNA expression. IL-5 levels were determined in bronchial lavage (BL). Compared with Groups A and B, Group C patients exhibited higher numbers of IL-5 protein(+) cells, IL-5 mRNA(+) cells, and eotaxin(+) cells in bronchial submucosa. Compared with Group A, Group B patients showed an increased number of IL-5 protein(+) cells, whereas the number of IL-5 mRNA(+) cells and eotaxin(+) cells was similar. IL-5 levels in BL were increased only in Group C. Our study provides evidence of IL-5 involvement in bronchial eosinophilia and in the pathogenesis of asymptomatic BHR associated with NP, whereas both IL-5 and eotaxin are involved in asthma associated with NP.

Cell and cytokine profiles in nasal secretions from patients with nasal polyposis: effects of topical steroids and surgical treatment.

BACKGROUND: Nasal polyposis (NP), a chronic inflammatory disease of the paranasal sinus mucosa, is frequently associated with asthma. Previous reports showed that surgical treatment for nasal polyps may influence asthma evolution. We hypothesized that sinus surgery may alter the cytokine network in nasal secretions. METHODS: We evaluated the characteristics (cells and mediators) of nasal lavages in nine patients with untreated NP (group A), 17 patients treated with topical steroids (group B), 21 patients treated by nasal surgery endonasal ethmoidectomy associated with topical steroids (group C), and 12 healthy subjects (controls). RESULTS: Percentages of both eosinophils and neutrophils were higher in NP patients than in controls. Percentages of eosinophils and interleukin-5 (IL-5) level were higher in group A than in group C and controls. There was a positive correlation between IL-5 and eosinophils. In marked contrast, IL-8, IL-10, and IL-1beta levels were significantly higher in group C than in groups A and B and controls; TNF-alpha concentration was significantly lower in group C than in groups A and B and controls; and there was a negative correlation between IL-10 and TNF-alpha. The percentage of eosinophils was higher in asthmatic patients with NP than in nonasthmatic patients. In addition, in group C, asthmatic patients also had a significantly higher level of IL-10 than nonasthmatic patients. CONCLUSIONS: Our study demonstrates that percentages of eosinophils and neutrophils, and IL-5 level were increased in nasal secretions from untreated patients with NP. Topical steroid treatment is associated with a decrease of inflammatory cells and mediators. In marked contrast, nasal surgery is associated with marked changes, in cytokine profile in nasal secretions, that are clearly different from those of controls and topical steroid-treated NP patients.

Overexpression of IL-10 mRNA in gut mucosa of patients with allergic asthma.

Because an airway-like inflammation has been reported in the gut of asthmatic patients, we sought to examine the expression of immunoregulatory cytokines like IL-4, IL-10, and IL-13 by gut mucosa. To establish this, we initiated this study to examine mRNA expressions of IL-4, IL-10, and IL-13 in duodenal mucosa from patients with asthma. Duodenal biopsy specimens were obtained from 20 asthmatic patients (10 allergic, 10 nonallergic) and 8 healthy controls. Cytokine mRNA was quantified with reverse transcriptase-competitive PCR, and results were expressed in proportion to the number of beta-actin mRNA in the same sample. IL-10 and IL-4 mRNA were detectable in all patients, whereas no IL-13 mRNA was detected. IL-10 mRNA concentrations were significantly higher in allergic subjects with asthma than in control subjects and nonallergic subjects with asthma. No significant difference was observed for IL-4. IL-10 mRNA expression was not related to asthma severity, FEV(1), blood eosinophilia, or IgE levels. Our results support the hypothesis that IL-10 overexpression may counterbalance the effects of proinflammatory cytokines and mitigate the inflammatory reaction found in gut mucosa of subjects with asthma.

[Biological manifestations of sarcoidosis]. / Manifestations biologiques au cours de la sarcoïdose.

Sarcoidosis is a multisystem granulomatous disease of unknown origin. No single biological marker allows definitive diagnosis of sarcoidosis or may accurately predict the disease prognosis. However, some biological markers are helpful tools as diagnostic aids and disease activity markers. At the blood level, lymphopenia with CD4 depletion, elevated levels of serum-angiotensin converting enzyme, lyzozyme, beta 2 microglobulin and disturbed calcium metabolism resulting in hypercalcemia and hypercalciuria can help guide diagnosis. Lymphocytic alveolitis with a high CD4/CD8 ratio in bronchoalveolar lavage fluid is highly suggestive of the disease. A wide range of new biological markers are proposed but their pronostic significance is still controversial. In clinical practice, biological markers may help in monitoring treated patients with sarcoidisis.

Interstitial lung diseases in collagen vascular diseases.

In this review, a clinical update is presented of the most important collagen vascular diseases (CVDs) and the different types of interstitial lung disease (ILD) encountered in these CVDs. These CVDs represent a heterogenous group of immunologically mediated inflammatory disorders with a large variety of affected organs besides the lungs. The frequency, clinical presentation, prognosis and response to therapy vary depending on the histological pattern (usual interstitial pneumonia, desquamative interstitial pneumonia, organising pneumonia, diffuse alveolar damage, nodular lesions, etc.), as well as on the underlying CVD (scleroderma, rheumatoid arthritis, systemic lupus erythematosus, dermatopolymyositis, Sjogren's syndrome or mixed connective tissue disease). The diagnosis of most of these CVDs is based on a number of criteria; in several of these, however, lung involvement is not part of the diagnostic criteria. In addition, there may be overlaps between several of these CVDs. Optimal treatment varies depending on the type of collagen vascular disease and the presence of interstitial lung disease, although in many cases, a combination of corticosteroids and cytostatic drugs are given.

[The common mucosal immune system in respiratory disease]. / Le système immunitaire muqueux commun en pathologie respiratoire.

The principal function of the mucosal immune system is to protect the mucosa from exogenous aggression. It also involves a lymphocyte recirculation phenomenon allowing activated lymphocytes to migrate to the aggressed site, for example the bronchi, and to recirculate and colonize other sites of the mucosal immune system. In asthma, analysis of the other sites of the common mucosal immune system demonstrates asthma-like inflammatory reactions in the accessory salivary glands and the gut: lymphocyte infiltrate, mast cell activation, thickening of the basal membrane, accumulation and activation of eosinophils (gut), activation of endothelial cells expressing ICAM-1. Lymphocyte, eosinophil and mast cell infiltration is observed in the digestive tract as well as increased expression of IL-3, IL-5 and GM-CSF. The similarity of the anomalies observed in BALT and GALT tissues would suggest the entire mucosal immune system is implicated in asthma.

Cytokine profile in minor salivary glands from patients with bronchial asthma.

BACKGROUND: T lymphocytes are important components of the bronchial inflammatory cell infiltrate in asthma. Because lymphocytes activated in the respiratory tract recirculate to remote glandular and mucosal sites, we previously studied the histologic features of minor salivary glands (MSGs) in bronchial asthma and found an airway-like inflammation with T-lymphocyte infiltration, the presence of mast cells that were often degranulated, and basement membrane thickening but no eosinophil infiltration. OBJECTIVE: We sought to investigate the cellular infiltration and cytokine profile in MSGs from untreated asthmatic subjects, steroid-treated asthmatic subjects, and control subjects and to compare these values with those found in bronchial biopsy specimens. METHODS: The cellular infiltration was studied by using immunohistochemistry. Cytokine messenger (m)RNA expression for IL-4, IL-5, and IFN-gamma was determined by using in situ hybridization and cytokine immunoreactivity with immunohistochemistry. RESULTS: A significant increase in CD4 and IL-4 mRNA(+) cells was observed in MSGs from asthmatic patients (both untreated and steroid-treated subjects) when compared with control subjects, which correlated with the clinical severity of asthma (FEV(1) and Aas score). In contrast to the bronchi, no IL-5 mRNA expression was observed in MSGs, and no difference was observed for MSG IFN-gamma mRNA between the groups. At the level of MSG protein expression, the 3 cytokines were seen, with a significant increase in IL-4 protein expression in steroid-treated asthmatic subjects compared with untreated asthmatic subjects and control subjects, but there were no differences between the groups in IL-5 and IFN-gamma protein expression. CONCLUSION: The cytokine mRNA expression pattern observed in the MSGs of asthmatic subjects was different from that found in the bronchi, suggesting a different local immune regulation.

[Allergic bronchopulmonary aspergillosis]. / Aspergillose bronchopulmonaire allergique.

Allergic bronchopulmonary aspergillosis (ABPA) is an immunologic bronchopulmonary inflammation due to an immune response of the lower respiratory tract against Aspergillus fumigatus. The major clinical features of ABPA include asthma, recurrent pulmonary infiltrates, immediate wheal and flare skin reactivity to A. fumigatus, elevated total serum IgE levels, detectable serum precipitating antibodies to A. fumigatus, peripheral blood eosinophilia, elevated levels of Aspergillus-specific serum IgE and central bronchiectasis with normal distal structures. The diagnosis of ABPA should be considered in asthmatics of all ages. Evolution of the disease comprises five stages from the acute to the fibrotic stage including pulmonary fibrosis and respiratory insufficiency. The goals of ABPA treatment are to control patient's asthma and prevent exacerbations of ABPA. During the acute stage, prednisone should be administered. Antifungals agents (itraconazole) may be useful to prevent exacerbations of the disease.

Long-term follow-up of pulmonary function in patients with nasal polyposis.

The outcome of asthma and/or nonspecific bronchial hyperresponsiveness (BHR) associated with nasal polyposis (NP) is uncertain. Over a 4-yr period, we investigated the long-term changes of pulmonary function and BHR in 46 patients with NP. Each subject was assessed for nasal symptoms and tested for allergy skin prick tests, serum total IgE, spirometry, and carbachol challenge at baseline before initiating any treatment (T0). Nasal symptoms evaluation, spirometric measurements, and carbachol challenge were repeated at T1 and at T2 (respectively, 12.7 +/- 0.9 and 47.9 +/- 2. 2 mo after T0). In addition, bronchodilator response was measured at T2. At T0, 25 patients exhibited BHR and 16 of 25 were asthmatic. All patients were treated first with topical steroids for 6 wk (beclomethasone 600 microg/d). Eighteen patients were successfully treated with topical steroids (topical steroids responders). Intranasal ethmoidectomy was performed in 28 patients who did not improve with topical steroids alone (topical steroids nonresponders). Nasal score improved at T1 and remained improved at T2 as compared with T0 in both groups (p < 0.005). Topical steroids nonresponders demonstrated a significant decrease of FEV(1), FEV(1)/FVC ratio, and FEF(25-75) at T1 (p < 0.05) and at T2 (p < 0.0005), whereas no significant change was observed in FEV(1) and FEV(1)/FVC ratio in responders. DeltaFEV(1) (%) between T2 and T0 was not related to the presence of asthma, BHR, or atopy. Bronchodilator response at T2 was similar in the two groups. BHR did not significantly change over the 4-yr follow-up period in the two groups. No change in pulmonary symptoms and/or asthma severity occurred. Our results show that nonreversible airflow obstruction appears over a 4-yr follow-up period in topical steroids nonresponders patients with NP requiring nasal surgery. The long-term contribution of these changes to the development of respiratory symptoms in patients with NP remains to be documented.

[Idiopathic pulmonary fibrosis: from biopathology to treatment]. / Fibrose pulmonaire idiopathique: de la biopathologie au traitement.

Alveolitis, accumulation of immune and inflammatory cells within the lower respiratory tract, is the key to the development of pulmonary fibrosis. Alveolitis is responsible for lung injury (due to release of oxidant and proteolytic enzymes) and exaggerated lung repair (due to proliferation of mesenchymal cells and imbalance of collagen synthesis). Rationale for the treatment of pulmonary fibrosis implies the knowledge of pathophysiology of the different steps of the fibrotic process.