[Sarcoidosis following tuberculosis. Is there a link between these granulomatous diseases?] / Une sarcoïdose dans le décours d'une tuberculose. Existe-t-il un lien étiologique entre ces deux maladies granulomateuses ?

We report the case of a 38-year old non-smoking female who initially presented to the hospital with frequent cough and sputum for several weeks. The investigations confirmed the diagnosis of tuberculosis and a triple therapy was introduced with clinical improvement. Two years later, the patient reported recurrence of respiratory symptoms. The new investigations concluded initially to a recurrence of tuberculosis and a quadriple therapy was introduced. The treatment was poorly tolerated and rapidly stopped. It was then decided to perform a biopsy through mediastinoscopy in the hilar ganglia, which confirmed the diagnosis of sarcoidosis. The etiology of sarcoidosis is not yet clearly established, one of the hypothesis would be the direct involvement of an infectious agent that would induce an excessive immune response. The clinical case below supports a possible role of Mycobacterium tuberculosis in the pathogenesis of sarcoidosis.

Nous rapportons le cas d'une patiente âgée de 38 ans, non fumeuse, qui s'est présentée à l'hôpital pour une symptomatologie de toux et d'expectorations depuis plusieurs semaines. Les différentes investigations ont permis d'établir un diagnostic de tuberculose et une trithérapie a été introduite avec une évolution favorable de la patiente. Deux ans plus tard, la patiente rapporte une récidive des plaintes respiratoires. Les nouveaux examens menés concluent, dans un premier temps, à une récidive de tuberculose et une quadrithérapie est instaurée. Le traitement fut mal toléré et stoppé rapidement. Il est alors décidé de réaliser une biopsie par médiastinoscopie au niveau des ganglions hilaires qui permettra de confirmer le diagnostic de sarcoïdose. L'étiologie de la sarcoïdose n'étant pas encore clairement établie, une des hypothèses est l'implication directe d'un agent infectieux qui induirait une réaction immunitaire excessive. Le cas clinique ci-dessous étaye la théorie selon laquelle le Mycobacterium tuberculosis pourrait être un des agents étiologiques de la sarcoïdose.

Multimodal chemometric approach for the analysis of human exhaled breath in lung cancer patients by TD-GC × GC-TOFMS.

Lung cancer is the deadliest cancer in developed countries. To reduce its mortality rate, it is important to enhance our capability to detect it at earlier stages by developing early diagnostic methods. In that context, the analysis of exhaled breath is an interesting approach because of the simplicity of the medical act and its non-invasiveness. Thermal desorption comprehensive two-dimensional gas chromatography time of flight mass spectrometry (TD-GC × GC-TOFMS) has been used to characterize and compare the volatile content of human breath of lung cancer patients and healthy volunteers. On the sampling side, the contaminations induced by the bags membrane and further environmental migration of VOCs during and after the sampling have also been investigated. Over a realistic period of 6 h, the concentration of contaminants inside the bag can increase from 2 to 3 folds based on simulated breath samples. On the data processing side, Fisher ratio (FR) and random forest (RF) approaches were applied and compared in regards to their ability to reduce the data dimensionality and to extract the significant information. Both approaches allow to efficiently smooth the background signal and extract significant features (27 for FR and 17 for RF). Principal component analysis (PCA) was used to evaluate the clustering capacity of the different models. For both approaches, a separation along PC-1 was obtained with a variance score around 35%. The combined model provides a partial separation with a PC-1 score of 52%. This proof-of-concept study further confirms the potential of breath analysis for cancer detection but also underlines the importance of quality control over the full analytical procedure, including the processing of the data.

[Bronchial thermoplasty in the management of severe asthma : retrospective analysis of 10 cases treated at academic hospital of Liège]. / Thermoplastie bronchique dans le traitement de l'asthme sévère. Analyse rétrospective de 10 cas traités au CHU de Liège.

As treating severe forms of asthma represents a medical and economical challenge, research for new therapies in this area is extensive and expansive. Recently, bronchial thermoplasty (BT) - ie. bronchoscopic procedure delivering a thermic form of energy through radiofrequency to the bronchi, in order to interfere with the components of the smooth muscle layer - arose as a promising technique. Our study followed the path of 10 patients from CHU Liège (University Hospital), who underwent this procedure in a context of severe asthma. We compared clinical and spirometric and treatment data in patients at 0 - 6 and 12 months post-procedural intervals, in order to determine whether thermoplasty had been improving asthma. Overall, we observed a stabilization and possibly a clinical improvement while reducing the total amount of exacerbation rate, and the burden of maintenance oral corticoids.

En raison du défi médico-économique que représente le traitement des formes sévères d'asthme, les recherches concernant de nouvelles thérapies dans ce domaine sont multiples et variées. Récemment, la thermoplastie bronchique - correspondant à un acte bronchoscopique permettant de délivrer une énergie par radiofréquence au niveau des bronches, afin d'interférer avec les composants de la couche musculaire lisse - s'annonçait comme une procédure prometteuse. Nous avons étudié 10 patients, suivis au CHU de Liège dans un contexte d'asthme sévère, et ayant bénéficié de cette technique. Nous avons comparé des données cliniques, spirométriques et thérapeutiques aux intervalles de 6 et 12 mois après procédure, afin de de déterminer si celle-ci avait été bénéfique sur leur pathologie asthmatique. Globalement, nous observons une stabilisation, voire une amélioration clinique, avec, notamment, une diminution des exacerbations, tout en réduisant la charge en corticoïdes systémiques.

Heterogeneity of phenotypes in severe asthmatics. The Belgian Severe Asthma Registry (BSAR).

UNLABELLED: The Belgian severe asthma registry is a web-based registry encompassing demographic, clinical, functional and inflammatory data of severe asthmatics (SA), aiming at improving awareness, knowledge on its natural history and subphenotypes, and offering tools to optimize care of this asthma population. METHODS: The cross-sectional analyses of this registry included 350 SA as defined by the ATS (2000) from 9 Belgian centres, with at least one year follow up. RESULTS: Mean age was 55 ± 14 yrs. SA were more frequently female (57%) and atopic (70%). Late-onset asthma (≥40 yr) was observed in 31% of SA. Current smokers represented 12% while 31% were ex-smokers. In addition to high doses ICS + LABA, 65% of patients were receiving LTRA, 27% anti-IgE and 24% maintenance oral corticosteroids (8 mg (Interquartile range-IQR:4-8) methylprednisolone). Despite impaired airflow (median FEV1:67%; IQR: 52-81) only 65% had a post-bronchodilator FEV1/FVC ratio <70%. The median blood eosinophil count was 240/mm³. The median FENO was 26 ppb (IQR: 15-43) and 22% of SA had FENO ≥ 50 ppb. Induced sputum was successful in 86 patients. Eosinophilic asthma (sputum Eos ≥ 3%) was the predominant phenotype (55%) while neutrophilic (sputum Neu ≥ 76%) and paucigranulocytic asthma accounted for 22% and 17% respectively. Comorbidities included rhinitis and chronic rhinosinusitis (49%), nasal polyposis (19%), oesophageal reflux (36%), overweight and obesity (47%) and depression (19%). In addition, 8% had aspirin-induced asthma and 3% ABPA. Asthma was not well-controlled in 83% according to ACT < 20 and 77% with ACQ > 1.5. CONCLUSION: In this cohort of patients with severe asthma, the majority displayed indices of persistent airflow limitation and eosinophilic inflammation despite high-dose corticosteroids, suggesting potential for eosinophil-targeted biotherapies.

[Asthma: a complex disease determined by genetic and environmental factors]. / L'asthme: une maladie complexe mettant en jeu facteurs environnementaux et terrain génétique.

Asthma is a complex disease highly dependent of environmental exposure and genetic background. Through linkage analysis, positional cloning and genome wide association studies, novel asthma genes have come out such as ADAM-33 or ORMLD3. Important environmental factors include allergenic exposure, pollutants and especially particulate matters, tobacco, aerosol exposure, viral infections and level of exposure to endotoxin. The effects of environmental factors are modulated by the genetic sequence and numerous single nucleotide polymorphisms (SNPs). Recently, it has also become clear that environmental factors may alter gene expression by DNA methylation or histone methylation/acetylation without changing the gene sequence and thereby changing asthmatic phenotype.

[Targeted asthma therapies: confirmations, hopes, and disappointments]. / Les traitements ciblés dans l'asthme: confirmations, espoirs et déceptions.

Asthma is a chronic inflammatory disease of the airways. The inflammatory process is driven by different pathways involving cytokines and other protein mediators. Patients with severe asthma are at high risk of severe exacerbations and death and have few therapeutic options available. Therefore, biological agents have been developed to help patients with refractory asthma by interfering with several compounds of the asthma inflammatory cascade. In addition to decreasing exacerbations, some of those treatments have a steroid sparing role and many beneficial effects in asthmatics.

Is FENO50 useful diagnostic tool in suspected asthma?

BACKGROUND: Asthma diagnosis is based on the presence of symptoms and the demonstration of airflow variability. Airway inflammation measured by fractional exhaled nitric oxide, measured at a flow rate of 50 ml/s (FE(NO50)) remains a controversial diagnostic tool. AIM: To assess the ability of FE(NO50) to identify bronchial hyperresponsiveness (BHR) to methacholine (provocative concentration of methacholine causing a 20% fall in FEV(1); PC20M ≤ 16 mg/ml) and to establish whether or not symptoms relate to FE(NO50) and PC20M in patients with no demonstrated reversibility to ß(2) -agonist. METHODS: We conducted a prospective study on 174 steroid naive patients with respiratory symptoms, forced expiratory volume in 1 s (FEV(1) ) ≥ 70% predicted and no demonstrated reversibility to ß(2) -agonist. Patients answered to a standardised symptom questionnaire and underwent FE(NO50) and methacholine challenge. Receiver-operating characteristic (ROC) curve and logistic regression analysis assessed the relationship between PC20M and FE(NO50) , taking into account covariates (smoking, atopy, age, gender and FEV(1)). RESULTS: A total of 82 patients had a PC20M ≤ 16 mg/ml and had significantly higher FE(NO50) (19 ppb vs. 15 ppb; p < 0.05). By constructing ROC curve, we found that FE(NO50) cut-off value of 34 ppb was able to identify not only BHR with high specificity (95%) and positive predictive value (88%) but low sensitivity (35%) and negative predictive value (62%). When combining all variables into the logistic model, FE(NO50) (p = 0.0011) and FEV(1) (p < 0.0001) were independent predictors of BHR whereas age, gender, smoking and atopy had no influence. The presence of diurnal and nocturnal wheezing was associated with raised FE(NO50) (p < 0.001 and p < 0.05, respectively). CONCLUSION: The value of FE(NO50) > 34 ppb has high predictive value of PC20M < 16 in patients with suspected asthma in whom bronchodilating test failed to demonstrate reversibility or was not indicated. However, FE(NO50) ≤ 34 ppb does not rule out BHR and should prompt the clinician to ask for a methacholine challenge.

Disturbed cytokine production at the systemic level in difficult-to-control atopic asthma: evidence for raised interleukin-4 and decreased interferon-γ release following lipopolysaccharide stimulation.

BACKGROUND: Disturbed cytokine production is thought to govern inflammation in asthma, which, in its turn, may lead to uncontrolled disease. The aim of this study was to assess the relationship between cytokine production from blood leucocytes and the level of asthma control. METHODS: We compared the production of interleukin (IL)-4, IL-6, IL-10, interferon (IFN)-γ and tumour necrosis factor-α from peripheral blood leucocytes in non-atopic healthy subjects (n = 22), atopic non-asthmatics (n = 10), well-controlled asthmatics [Juniper asthma control questionnaire (ACQ) score <1.5; n = 20] and patients with uncontrolled asthma despite inhaled or oral corticoids (ACQ score ≥1.5; n = 20). Fifty microlitres of peripheral blood was incubated for 24 h with RPMIc, lipopolysaccharide (LPS; 1 ng/ml) or phytohaemagglutinin (1 µg/ml), and cytokines were measured by immunotrapping (ELISA). RESULTS: Both controlled and uncontrolled asthmatics as well as atopic non-asthmatics spontaneously produced more IL-4 than non-atopic healthy subjects (p < 0.001). IL-4 production induced by LPS was significantly greater (p < 0.05) in both asthma groups compared to atopic non-asthmatics and non-atopic healthy subjects. By contrast, IFN-γ release induced by LPS was lower in uncontrolled asthmatics than in non-atopic healthy subjects (p < 0.05) and controlled asthmatics (p < 0.05). IL-10 release after LPS was greater in uncontrolled asthmatics than in atopic non-asthmatics (p < 0.05). No difference was observed regarding other cytokines. CONCLUSION: Blood cells from patients with difficult-to-control atopic asthma display highly skewed Th2 cytokine release following LPS stimulation.

Cytokine production from sputum cells and blood leukocytes in asthmatics according to disease severity.

BACKGROUND: Although mild to moderate asthma is known to be Th2 driven, cytokines produced in refractory asthma might not fit the classical Th2 pattern. METHODS: The aim of our study was to assess the cytokine production by sputum and blood cells from 15 refractory asthmatics (American Thoracic Society Criteria) compared to 15 mild untreated and 17 moderate treated asthmatics and 22 healthy subjects. Spontaneous production of interleukin (IL)-4, IL-6, IL-10, interferon-gamma, and tumor necrosis factor alpha was measured by immunotrapping after 24 h sputum or blood cell culture. RESULTS: Moderate and refractory asthmatics were both characterized by a lower production of IL-6 from their airway cells compared to healthy subjects. However, the difference was no longer significant when expressing the results per gram of sputum. No significant difference between the three groups was found regarding other cytokines. As for cytokine production from blood, the three groups of asthmatics exhibited raised production of IL-4 when compared to healthy subjects, and this was true when results were expressed per blood volume or after normalization for total leukocyte cell count. Moderate asthmatics exhibited greater production of IL-10 when compared to refractory asthmatics and healthy subjects when results were normalized for total leukocyte cell count. CONCLUSIONS: Sputum cells from moderate and refractory asthmatics release less IL-6. While the systemic overproduction of IL-4 was observed through the all spectrum of asthma severity, moderate asthmatics exhibited greater systemic IL-10 production compared to refractory asthmatics.

[Radiation recall dermatitis after oral cyclophosphamide]. / Le cas clinique du mois. Réaction de rappel d'irradiation induite par l'administration de cyclophosphamide.

Radiation recall dermatitis is an inflammatory skin reaction occurring in a previously irradiated field following the delivery of a promoting agent. It has been described after a number of antineoplastic agents such as gemcitabine, taxanes, anthracyclines. We report the case of a 50-year-old man with metastatic prostate cancer who developed two consecutive radiation recall dermatitis episodes triggered by oral cyclophosphamide. They occurred 4 to 5 weeks after palliative radiotherapy on bone metastasis. Spontaneous resolution was observed within 6 weeks after discontinuation of cyclophosphamide and with local supportive care. To our knowledge this is the first reported case of radiation recall dermatitis after oral cyclophosphamide.

[Clinical case of the month. Lower limb revascularization from descending thoracic aorta in occluded axillobifemoral bypass]. / Le cas clinique du mois. Revascularisation des artères fémorales à partir de l'aorte thoracique descendante après thrombose d'un pontage axillo-bifémoral.

We report the case of a patient who had lower limb revascularization by a bypass graft originating from the decending thoracic aorta, after total thrombosis of an axillobifemoral bypass graft. The latter had been performed for surgical repair of a secondary aorto-enteric fistula. We successively discuss the three particular apects of this observation: the secondary aortodigestive fistula, the axillobifemoral bypass and the bypass between the descending thoracic aorta and the femoral arteries.

[How to explore... insipidus polyuropolydipsia syndrome]. / Comment j'explore... un syndrome polyuropolydipsique insipide.

The finding of a polyuropolydispsic syndrome should prompt a complete biological investigation of its etiology. If polyuria can be a minor sign as in psychiatric disorder, it can also be the first manifestation of diabetes mellitus but also central diabetes insipidus, the latter linked to cerebral tumors, metastases in the hypothalamus, granulomatous disease, but also nephrogenic diabetes insipidus such as chronic renal disease or autoimmune disease. Intracellular dehydration is the major risk in case of a polyuropolydipsic syndrome. Prognosis depends on the capacity to maintain water balance through an intact thirst mechanism. After a brief review of the majority of causes of diabetes insipidus, we propose a diagnosis algorithm to easily make the diagnosis.