The use of exhaled air analysis in discriminating interstitial lung diseases: a pilot study.

BACKGROUND: Fibrotic Interstitial lung diseases (ILD) are a heterogeneous group of chronic lung diseases characterized by diverse degrees of lung inflammation and remodeling. They include idiopathic ILD such as idiopathic pulmonary fibrosis (IPF), and ILD secondary to chronic inflammatory diseases such as connective tissue disease (CTD). Precise differential diagnosis of ILD is critical since anti-inflammatory and immunosuppressive drugs, which are beneficial in inflammatory ILD, are detrimental in IPF. However, differential diagnosis of ILD is still difficult and often requires an invasive lung biopsy. The primary aim of this study is to identify volatile organic compounds (VOCs) patterns in exhaled air to non-invasively discriminate IPF and CTD-ILD. As secondary aim, the association between the IPF and CTD-ILD discriminating VOC patterns and functional impairment is investigated. METHODS: Fifty-three IPF patients, 53 CTD-ILD patients and 51 controls donated exhaled air, which was analyzed for its VOC content using gas chromatograph- time of flight- mass spectrometry. RESULTS: By applying multivariate analysis, a discriminative profile of 34 VOCs was observed to discriminate between IPF patients and healthy controls whereas 11 VOCs were able to distinguish between CTD-ILD patients and healthy controls. The separation between IPF and CTD-ILD could be made using 16 discriminating VOCs, that also displayed a significant correlation with total lung capacity and the 6 min' walk distance. CONCLUSIONS: This study reports for the first time that specific VOC profiles can be found to differentiate IPF and CTD-ILD from both healthy controls and each other. Moreover, an ILD-specific VOC profile was strongly correlated with functional parameters. Future research applying larger cohorts of patients suffering from a larger variety of ILDs should confirm the potential use of breathomics to facilitate fast, non-invasive and proper differential diagnosis of specific ILDs in the future as first step towards personalized medicine for these complex diseases.

Early activation of the cardiac CX3CL1/CX3CR1 axis delays ß-adrenergic-induced heart failure.

We recently highlighted a novel potential protective paracrine role of cardiac myeloid CD11b/c cells improving resistance of adult hypertrophied cardiomyocytes to oxidative stress and potentially delaying evolution towards heart failure (HF) in response to early ß-adrenergic stimulation. Here we characterized macrophages (Mφ) in hearts early infused with isoproterenol as compared to control and failing hearts and evaluated the role of upregulated CX3CL1 in cardiac remodeling. Flow cytometry, immunohistology and Mφ-depletion experiments evidenced a transient increase in Mφ number in isoproterenol-infused hearts, proportional to early concentric hypertrophy (ECH) remodeling and limiting HF. Combining transcriptomic and secretomic approaches we characterized Mφ-enriched CD45+ cells from ECH hearts as CX3CL1- and TNFα-secreting cells. In-vivo experiments, using intramyocardial injection in ECH hearts of either Cx3cl1 or Cx3cr1 siRNA, or Cx3cr1-/- knockout mice, identified the CX3CL1/CX3CR1 axis as a protective pathway delaying transition to HF. In-vitro results showed that CX3CL1 not only enhanced ECH Mφ proliferation and expansion but also supported adult cardiomyocyte hypertrophy via a synergistic action with TNFα. Our data underscore the in-vivo transient protective role of the CX3CL1/CX3CR1 axis in ECH remodeling and suggest the participation of CX3CL1-secreting Mφ and their crosstalk with CX3CR1-expressing cardiomyocytes to delay HF.

[Infliximab-induced hepatitis during treatment of vulvar Crohn's disease]. / Hépatite induite par l'infliximab lors du traitement d'une maladie de Crohn vulvaire.

BACKGROUND: We report a case of acute cytolytic hepatitis induced by infliximab in a patient with severe vulvar Crohn's disease. PATIENTS AND METHODS: A 29-year-old Congolese woman presented with severe vulvar Crohn's disease active for 7 years. In view of resistance to standard medication (corticosteroids and metronidazole), treatment with infliximab 5mg/kg per injection was initiated. The patient developed acute cytolytic hepatitis 10 days after the first injection and the disease was asymptomatic. The various investigations confirmed the direct cytotoxicity of infliximab. A favourable outcome was gradually achieved after increasing the dosage of corticosteroids. At the same time, an improvement in the vulvar lesions was noted after this sole injection. DISCUSSION: Infliximab-induced is rare, with only 20 reported cases. The physiopathological mechanism is unknown and a number of aetiologies have been suggested. CONCLUSION: This new case raises the issue of the need for routine liver function testing during infliximab therapy given the asymptomatic nature of this effect.

Tumour necrosis factor antagonists and inflammatory bowel diseases: a national practice survey.

BACKGROUND: Although the use of tumour necrosis factor (TNF) antagonists is increasingly codified, several unresolved issues remain. AIM: To conduct a French national survey on TNF antagonists use in inflammatory bowel disease (IBD). METHODS: A postal questionnaire was sent to all French gastroenterologists among whom 450 prescribe TNF antagonists for IBD. Only anti-TNF prescribers were invited to respond. RESULTS: A total of 333 questionnaires could be analysed, which represented a rate of survey completeness of 74%. Scheduled maintenance infliximab treatment was prescribed by 92% of gastroenterologists. In Crohn's disease in remission after 1 year of TNF antagonists, 77.4% of physicians continued treatment. In luminal Crohn's disease, 97% of hospital practitioners introduced infliximab as first-line anti-TNF therapy vs. 78% of physicians with nonhospital activity (P = 0.002); only 22.5% of gastroenterologists opted for adalimumab as first-line therapy. In Crohn's disease in remission after 6 months of azathioprine in combination with infliximab, 63.8% of practitioners discontinued azathioprine. In case of pregnancy during anti-TNF treatment, 35.1% of physicians discontinued therapy at the time of conception and did not administer anti-TNF therapy during pregnancy. CONCLUSIONS: The attitudes of French gastroenterologists generally reflect the recommendations regarding the use of anti-TNF and concomitant immunosuppressive therapy in IBD.

Wireless capsule in inflammatory bowel disease.

Capsule endoscopy (CE) is a safe, non-invasive diagnostic tool to evaluate small bowel lesions. CE, like conventional endoscopy, can detect focal and small-ulcerated lesions along the entire length of the small bowel, which are not identified by other imaging techniques. Meta-analysis has shown that CE is better than any other radiological technique to detect small bowel lesions in patients with suspected or known Crohn's disease (CD). In unclassified colitis, CE is also useful in distinguishing CD and ulcerative colitis (UC). In established CD, CE may be used to detect post-operative recurrence, determine the extent of small bowel lesions and link ulcerated lesions with clinical symptoms. Although CE is well tolerated there is a theoretical risk of capsule impaction in general and in CD in particular. To avoid capsule impaction, a new option called the "patency capsule" is available especially in patients with symptoms suggesting small bowel obstruction. However, few data are available about this new device and its use in clinical practice needs to be clarified.

[Acinar cell carcinoma of the pancreas: a rare tumor with particular clinical and paraclinical presentation]. / Carcinome à cellules acineuses du pancréas : une tumeur rare avec des caractéristiques cliniques et paracliniques particulières.

Acinar cell carcinoma of the pancreas is a rare tumour with specific clinical and paraclinical presentation. Its management is not well codified resulting from its low frequency.

[Biologic therapies in inflammatory bowel disease: anti-TNF and new therapeutic targets]. / Biothérapies et MICI: anti-TNF et nouvelles cibles thérapeutiques.

PURPOSE: Advances in the understanding of inflammatory bowel disease (IBD) pathophysiological mechanisms in the last few years have allowed the development of novel therapies such as biologic therapies. Theoretically, biologic therapies represent a more specific management of IBD with fewer effects. CURRENT KNOWLEDGE AND KEY POINTS: Currently, infliximab is the only effective and widely accepted biologic therapy for the treatment of Crohn disease after the conventional therapies. Others anti-TNF therapies such as adalimumab or certolizumab will be soon an alternative treatment notably for patients with allergic reactions to infliximab and for those with lost of response because of anti-infliximab antibody development. Anti-integrin alpha4 therapies have been delayed by three progressive multifocal leukoencephalopathy cases. Immunostimulating therapy may be highly relevant in the future with granulocyte-monocyte colony-stimulating factor. PERSPECTIVES: Efficacy of these new therapies will modify therapeutics of Crohn's disease and ulcerative colitis and in particular decrease the use of corticosteroids, which are not well tolerated by the patients.

[Lactic acidosis and hepatic mitochondrial changes during a treatment with zidovudine]. / Acidose lactique et altérations mitochondriales hépatiques au cours d'un traitement par zidovudine.

Adverse effects of zidovudine, which mainly result in myopathies and hematological disorders, could be due to multitissular mitochondrial toxicity of the drug. During zidovudine treatment, most cases of lactic acidosis have been attributed to mitochondrial myopathy. We report a case of hepatocellular failure with lactic acidosis in a 33 year-old patient with the human immunodeficiency virus infection and treated with zidovudine for 8 months. Liver biopsy showed massive macrovacuolar steatosis and ultrastructural mitochondrial abnormalities similar to those previously described in the skeletal muscle. This is the second reported case of lactic acidosis and hepatocellular failure which is probably related to hepatic mitochondrial dysfunction caused by zidovudine.