[Asthma in clinical practice: from inflammatory phenotypes to personalized treatment]. / L'asthme bronchique en pratique clinique : des phénotypes inflammatoires au traitement personnalisé.

Asthma is a chronic inflammatory disease of the airways. Classification of asthma in different phenotypes has therapeutic implications and may lead to personalized medicine. Induced sputum is the gold standard for asthma phenotyping but is complex, time-consuming and not widely available. The combination of different biomarkers such as exhaled nitric oxide, blood eosinophils and total serum IgE levels allows the prediction of inflammatory phenotype in 58% of asthmatic patients when sputum is not available. We recently demonstrated the interest of measuring volatile organic compounds in exhaled breath to phenotype asthma. These compounds could play an important role in the future to predict the response to expensive biologicals available in severe asthma to reduce exacerbations and the use of systemic corticosteroids.

: L'asthme est une pathologie inflammatoire chronique des voies respiratoires. Classer l'asthme en différents phénotypes inflammatoires a des implications thérapeutiques importantes et peut conduire à un traitement personnalisé. Le gold standard pour l'établissement du phénotype inflammatoire est l'analyse de l'expectoration induite qui est une technique complexe, difficilement accessible en routine. La combinaison de plusieurs biomarqueurs d'intérêt tels le monoxyde d'azote dans l'air exhalé, l'éosinophilie systémique et le taux d'IgE sérique permet de prédire correctement le phénotype inflammatoire dans 58% des cas. Récemment, nous avons également mis en évidence l'intérêt de la détection de molécules dans l'haleine. Ces composés organiques volatiles pourraient représenter des biomarqueurs futurs de la réponse au traitement, spécialement dans l'asthme sévère, pour lequel des traitements ciblés coûteux sont actuellement disponibles en vue de réduire les exacerbations et le recours aux corticostéroïdes oraux.

Step-down of inhaled corticosteroids in non-eosinophilic asthma: A prospective trial in real life.

BACKGROUND: While non-eosinophilic asthmatics are usually considered poorly responsive to inhaled corticosteroids (ICSs), studies assessing a step-down of ICS in this specific population are currently lacking. OBJECTIVES: To assess the proportion of non-eosinophilic asthmatics in whom ICS may be withdrawn without any clinical degradation and to determine the predictive markers of a failure to stop treatment with ICS. METHODS: This prospective study was completed by 36 non-eosinophilic asthmatics, defined by sputum eosinophils <3% and blood eosinophils <400/µL. In these patients, whichever the baseline asthma control level, the dose of ICS was gradually reduced every 3 months until they met the failure criteria or successfully discontinued ICS for 6 months. The failure criteria were an ACQ score ≥1.5 with an increase from baseline >0.5 or a number of severe exacerbations during the study which was greater than the number during the year prior to the baseline visit. Receiver-operating characteristic (ROC) curves were constructed to assess predictors of a failure to stop ICS. This study is registered with ClinicalTrials.gov, number NCT02169323. RESULTS: In 14 patients (39%), ICSs were completely withdrawn, and in 10 further patients (28%), ICS were stepped-down to a reduced ICS dose without any deterioration of asthma control and exacerbation rate. Baseline predictors of a failure to stop ICS were a greater age (area under ROC curve [ROC AUC] and [95% CI]: 0.77 [0.62-0.93]) and elevated blood eosinophils (ROC AUC [95% CI]: 0.77 [0.61-0.93]). After the first step-down of ICS, the best predictor was an elevated blood eosinophil count (ROC AUC [95% CI]: 0.85 [0.72-0.99]). CONCLUSIONS & CLINICAL RELEVANCE: Withdrawing or reducing the dose of ICS is feasible in two-thirds of non-eosinophilic asthmatics irrespective of baseline asthma control. An elevated blood eosinophil count may predict the failure to stop ICS.

[Asthma and obesity]. / Asthme et obésité.

Asthma and obesity are both common diseases in western world. According to the data from our asthma clinic 20 % of our patients are obese and this rate increases up to 25 % in severe asthmatics included in the Belgian Severe Asthma national Registry. Alteration of thoracic mechanics contributes to greater symptom burden and poor asthma control in obese asthmatics. In particular the response to inhaled corticoids is attenuated. Weight loss results in a dramatic improvement in asthma control and should be a major goal in the asthma management of these patients.

Asthme et obésité sont deux pathologies courantes dans les pays occidentaux. Selon les données de notre clinique de l'asthme, 20 % des patients asthmatiques sont obèses, mais ce taux monte à 25 % lorsqu'on considère les patients sévères inclus dans le Registre national belge de l'Asthme sévère. L'altération de la mécanique ventilatoire consécutive à l'excès pondéral rend l'asthme plus symptomatique et plus difficilement contrôlable chez le patient obèse. En particulier, il existe une réponse atténuée à la corticothérapie inhalée. La perte pondérale s'accompagne d'une amélioration spectaculaire de la symptomatologie et doit constituer un objectif thérapeutique primordial chez les patients asthmatiques obèses.

[Medication screening by the community pharmacist in Belgium]. / Revue de la medication par le pharmacien d'officine en Belgique: pourquoi, comment et situation actuelle.

About 20% of the European population is older than 65 years. Because of multimorbidity (i.e. multiple chronic condition within a patient), older patients are often prescribed multiple drugs [i.e. polypharmacy). Both older age and polypharmacy significantly increase the risk for adverse drug events. International research showed that more or less 5% of all unplanned hospital admissions is related to the use of medication. About 70% of these drug related admissions happened in patients older than 65 years. Moreover, about half of the admissions could have been avoided. These preventable hospital admissions were caused by the intake of medication without an indication, problems with medication adherence, interactions and/or insufficient monitoring. We define this as (potential Drug Related Problems [DRPI. DRPs can occur on multiple occasions during the medication management process: prescribing, dispensing, intake and monitoring. When DRPs can be detected in an early stage, significant consequences can be avoided. To accomplish this, multiple strategies are possible. One of the possibilities is performing a periodic medication screening by the community pharmacist in patient groups at risk. During such a medication screening, the pharmacotherapy is critically evaluated in a systematic and structured way. The implementation of medication screening in first-line health care is currently limited. The community pharmacist is nevertheless ideally placed to perform this task. There is an important relation of trust between him and the patient and the community pharmacist has access to a full medication history. Furthermore, as an expert in drug-related issues, he possesses all necessary knowledge to perform the pharmacotherapeutic analysis.

[PERSONALIZED TREATMENT OF ASTHMA: THE ISSUE OF ANTI-INTERLEUKIN-5 ANTIBODIES]. / TRAITEMENT PERSONNALISÉ DANS L'ASTHME: le cas des anticorps monoclonaux dirigés contre l'interleukine-5.

Asthma is a chronic inflammatory disease that often features eosinophilia, especially in its most severe forms. Monoclonal antibodies directed towards interleukin-5, such as mepolizumab or reslizumab, were shown to be very effective at reducing blood and airways eosinophilia. When administered monthly by intravenous or subcutaneous injection in severe eosinophilic asthmatic patients, they reduce severe exacerbation rate by 50 %, improve asthma control and quality of life, and have an oral glucocorticoids sparing effect in those requiring oral corticoids as maintenance therapy.

Comparison of the quantitative performances and measurement uncertainty estimates obtained during method validation versus routine applications of a novel hydrophilic interaction chromatography method for the determination of cidofovir in human plasma.

Method validation is essential to ensure that an analytical method is fit for its intended purpose. Additionally, it is advisable to estimate measurement uncertainty in order to allow a correct interpretation of the results generated by analytical methods. Measurement uncertainty can be efficiently estimated during method validation as a top-down approach. However, method validation predictions of the quantitative performances of the assay and estimations of measurement uncertainty may be far away from the real performances obtained during the routine application of this assay. In this work, the predictions of the quantitative performances and measurement uncertainty estimations obtained from a method validation are compared to those obtained during routine applications of a bioanalytical method. For that purpose, a new hydrophilic interaction chromatography (HILIC) method was used. This method was developed for the determination of cidofovir, an antiviral drug, in human plasma. Cidofovir (CDV) is a highly polar molecule presenting three ionizable functions. Therefore, it is an interesting candidate for determination by HILIC mode. CDV is an acyclic cytidine monophosphate analog that has a broad antiviral spectrum and is currently undergoing evaluation in clinical trials as a topical agent for treatment of papillomavirus infections. The analytical conditions were optimized by means of design of experiments approach in order to obtain robust analytical conditions. These ones were absolutely necessary to enable the comparisons mentioned above. After a sample clean-up by means of solid phase extraction, the chromatographic analysis was performed on bare silica stationary phase using a mixture of acetonitrile-ammonium hydrogen carbonate (pH 7.0; 20mM) (72:28, v/v) as mobile phase. This newly developed bioanalytical method was then fully validated according to FDA (Food and Drug Administration) requirements using a total error approach that guaranteed that each future result will fall within acceptance limits of ±30% with a probability of 95% over a concentration range of 92.7-1020ng/mL. A routine application of the cidofovir determination in two pre-clinical trials demonstrated that the prediction made during the pre-study validation was consistent by retrospective analysis of the quality control (QC) samples. Finally, comparison of the measurement uncertainty estimations calculated from the method validation with those obtained from the routine application of the method was performed, stressing that the estimations obtained during method validation underestimated those obtained from routine applications and that the magnitude of this underestimation was function of the cidofovir concentration. Finally, this new HILIC method is reliable, easily applicable to routine analysis and transposable at low cost in other laboratories.

Integration and recording of a reconstituted voltage-gated sodium channel in planar lipid bilayers.

Functional assays for membrane proteins become increasingly important in biosciences. We demonstrate the integration of reconstituted bacterial voltage-gated sodium channels (NaChBac) into preformed free-standing lipid bilayers by using the nystatin-ergosterol method to promote proteoliposome fusion. Vesicle delivery and subsequent NaChBac activity were monitored, the orientation of the transferred ion channels was assessed measuring at both, positive and negative holding potentials and the channel specificity was demonstrated by adding the blocker nimodipine. A conductance of 120 pS per channel and an opening time in the range of seconds have been observed. Interestingly, we found that fusion of proteoliposomes into preformed free-standing bilayers is limited, if hydrophobically silanized silicon nitride membranes are used as the supporting material. In this case the diameter of the liposome had to be at least 20 times smaller compared to that of the pore to render fusion possible.