Intérêt de la mesure de l'inflammation en clinique dans l'asthme.

in EMC Pneumologie (2012)

L'asthme: une maladie complexe mettant en jeu facteurs environnementaux et terrain genetique.

in Revue Médicale de Liège (2012), 67(5-6), 286-91

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 ... [more ▼]

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. [less ▲]

Is FE(NO50) useful diagnostic tool in suspected asthma?

in International Journal of Clinical Practice (2012), 66(2), 158-65

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 ... [more ▼]

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 beta(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 beta(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. [less ▲]

Induced sputum in asthma: from bench to bedside.

in Current medicinal chemistry (2011), 18(10), 1415-22

During recent years there has been a growing interest in using non-invasive biomarkers to understand and monitor the airway inflammation in subjects with respiratory tract disorders and mainly asthma and ... [more ▼]

During recent years there has been a growing interest in using non-invasive biomarkers to understand and monitor the airway inflammation in subjects with respiratory tract disorders and mainly asthma and chronic obstructive pulmonary disease (COPD). Sputum induction is generally a well-tolerated and safe procedure and a European Respiratory Society Task Force has published a comprehensive review on sputum methodology. Induced sputum cell count and, to a lesser extent, mediator measurements have been particularly well validated. In asthma, the sputum and the cell culture supernatant can be used for the measurement of a variety of soluble mediators, including eosinophil-derived proteins, nitric oxide (NO) derivatives, cytokines and remodelling-associated proteins. Sputum eosinophilia (> 3%) is a classic feature of asthma although half of the patients seems to be non eosinophilic. Measuring the percentage of sputum eosinophils has proved to be useful in the clinical arena in helping to predict short term response to inhaled corticosteroids (ICS) and tailor the dose of ICS in the severe patients but there is scope for the application of other induced sputum markers potentially useful in clinical practice. The widespread application of induced sputum in asthma across the spectrum of disease severity has given insight into the relationship between airway function and airway inflammation, proposed new disease phenotypes and defined which of these phenotypes respond to current therapy, and perhaps most importantly provided an additional tool to guide the clinical management of asthmatic patients. To date sputum induction is the only non-invasive measure of airway inflammation that has a clearly proven role in asthma management. [less ▲]

Exhaled nitric oxide thresholds associated with a sputum eosinophil count >=3% in a cohort of unselected patients with asthma.

in Thorax (2010), 65(12), 1039-1044

Background It has been claimed that exhaled nitric oxide (FeNO) could be regarded as a surrogate marker for sputum eosinophil count in patients with asthma. However, the FeNO threshold value that ... [more ▼]

Background It has been claimed that exhaled nitric oxide (FeNO) could be regarded as a surrogate marker for sputum eosinophil count in patients with asthma. However, the FeNO threshold value that identifies a sputum eosinophil count >/=3% in an unselected population of patients with asthma has been poorly studied. Methods This retrospective study was conducted in 295 patients with asthma aged 15-84 years recruited from the asthma clinic of University Hospital of Liege. Receiver-operating characteristic (ROC) curve and logistic regression analysis were used to assess the relationship between sputum eosinophil count and FeNO, taking into account covariates such as inhaled corticosteroids (ICS), smoking, atopy, age and sex. Results Derived from the ROC curve, FeNO >/=41 ppb gave 65% sensitivity and 79% specificity (AUC=0.777, p=0.0001) for identifying a sputum eosinophil count >/=3%. Using logistic regression analysis, a threshold of 42 ppb was found to discriminate between eosinophilic and non-eosinophilic asthma (p<0.0001). Patients receiving high doses of ICS (>/=1000 mug beclometasone) had a significantly lower FeNO threshold (27 ppb) than the rest of the group (48 ppb, p<0.05). Atopy also significantly altered the threshold (49 ppb for atopic vs 30 ppb for non-atopic patients, p<0.05) and there was a trend for a lower threshold in smokers (27 ppb) compared with non-smokers (46 ppb, p=0.066). Age and sex did not affect the relationship between FeNO and sputum eosinophilia. When combining all variables into the logistic model, FeNO (p<0.0001), high-dose ICS (p<0.05) and smoking (p<0.05) were independent predictors of sputum eosinophilia, while there was a trend for atopy (p=0.086). Conclusion FeNO is able to identify a sputum eosinophil count >/=3% with reasonable accuracy and thresholds which vary according to dose of ICS, smoking and atopy. [less ▲]

Le cas clinique du mois. Reaction de rappel d'irradiation induite par l'administration de cyclophosphamide.

in Revue Médicale de Liège (2009), 64(4), 179-81

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 ... [more ▼]

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. [less ▲]

L'omalizumab (Xolair) dans le traitement de l'asthme allergique persistant severe.

in Revue Médicale de Liège (2009), 64(5-6), 313-7

L’asthme est une maladie chronique des voies aériennes. La plupart des asthmatiques ont une inflammation bronchique liée à un processus immunologique faisant intervenir les immunoglobulines E (IgE). En ... [more ▼]

L’asthme est une maladie chronique des voies aériennes. La plupart des asthmatiques ont une inflammation bronchique liée à un processus immunologique faisant intervenir les immunoglobulines E (IgE). En dépit des thérapeutiques existantes, les patients atteints d’asthme sévère ont une qualité de vie sérieusement altérée et présentent un risque élevé d’exacerbations graves pouvant parfois être fatales. L’omalizumab est un anticorps (Ac) monoclonal humanisé dirigé contre les IgE circulantes, interférant ainsi avec une des cascades moléculaires importantes dans la pathogénie de l’asthme. L’omalizumab a montré qu’il était capable d’améliorer la qualité de vie et de réduire la fréquence des exacerbations ainsi que le recours aux corticoïdes inhalés et systémiques. Selon les nouvelles recommandations de l’asthme du GINA 2006, cet agent biologique est indiqué dans l’asthme allergique persistant sévère. [less ▲]

Diabete insipide dans le cadre d'un carcinome pulmonaire a petites cellules: un paradoxe?

in Annales d'Endocrinologie (2005), 66(4), 355-60

We observed oat-cell lung carcinoma in a man who presented with diabetes insipidus. The chest radiograph showed a suspect nodule within a context of major nicotine addiction. Histopathological examination ... [more ▼]

We observed oat-cell lung carcinoma in a man who presented with diabetes insipidus. The chest radiograph showed a suspect nodule within a context of major nicotine addiction. Histopathological examination of the transbronchial biopsy confirmed the diagnosis of oat-cell carcinoma. Brain CT revealed metastasis to the pituitary gland and the pituitary stalk. Vasopressin was undetectable. This case illustrates an uncommon clinical presentation of small-cell lung carcinoma. Oat-cell carcinoma can modify osmoregulation in two different ways. Only sporadic cases of neurogenic diabetes insipidus due to the primary involvement of small-cell lung carcinoma have been reported. More often, this type of lung tumor is associated with inappropriate antidiuretic hormone secretion. [less ▲]

Comment j'explore... un syndrome polyuropolydipsique insipide

in Revue Médicale de Liège (2004), 59(11), 664-668

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 ... [more ▼]

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. [less ▲]