Targeted asthma therapies: confirmations, hopes, and disappointments

peer reviewedAsthma 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

Corticosteroids: still at the frontline in asthma treatment?

Inhaled corticosteroids (ICS) have led to improved asthma control and reduced asthma mortality in the Western world. ICS are effective in combating T-helper type 2-driven inflammation featuring mast cell and eosinophilic airway infiltration. Their effect on innate immunity-driven neutrophilic inflammation is poor and their ability to prevent airway remodeling and accelerated lung decline is controversial. Although ICS remain pivotal drugs in asthma management, research is needed to find drugs complementary to the combination ICS/long-acting beta2-agonist in refractory asthma and perhaps a new class of drugs as a first-line treatment in mild to moderate noneosinophilic asthma.Peer reviewe

Blood eosinophil count to predict bronchial eosinophilic inflammation in COPD.

No abstract available

How I treat ... by optimizing the blockade of renin-angiotensin-aldosterone system

peer reviewedThe blockade of the renin-angiotensin-aldosterone system (RAAS) has been shown to be useful, or even mandatory, in the management of arterial hypertension, congestive heart failure, post-myocardial infarction and nephropathy with albuminuria, due to diabetes or not. Such blockade can be obtained with an angiotensin converting enzyme inhibitor, a specific antagonist of angiotensin II AT1 receptors and/or recently a direct inhibitor of renin such as aliskiren. Various studies have demonstrated the advantage of optimising RAAS blockade in order to benefit of the best cardiorenal protection. The present article describes the various modalities to optimize the RAAS blockade, either by using a maximal dosage of a monotherapy, or by choosing a double inhibition of RAAS. New prospects for the RAAS blockade will be also briefly considered.Le blocage du système rénine-angiotensine-aldostérone (SRAA) s'est avéré très utile, voire incontournable, dans le traitement de l'hypertension artérielle, de la décompensation cardiaque, du post-infarctus et de la néphropathie albuminurique, diabétique ou non. Ce blocage peut être réalisé par un inhibiteur de l'enzyme de conversion de l'angiotensine, un antagoniste des récepteurs AT1 de l'angiotensine II et/ou, récemment, un inhibiteur direct de la rénine, comme l'aliskiren. Diverses études ont montré l'intérêt d'optimiser le blocage du SRAA pour bénéficier des meilleurs effets de protection cardio-rénale. Cet article décrit les modalités pour obtenir un blocage optimal du SRAA, soit en recourant à un dosage maximal d'une monothérapie, soit en faisant appel à une double inhibition pharmacologique du SRAA. De nouvelles perspectives concernant le blocage du SRAA seront également évoquées

Granulocytic Airway Inflammation and Clinical Asthma Outcomes.

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Sputum IgE and Cytokines in Asthma: Relationship with Sputum Cellular Profile.

peer reviewedBACKGROUND: Local IgE production may play a role in asthma pathogenesis. The aim of the study was to assess sputum total IgE and cytokines in asthmatics according to sputum cellular phenotype. METHODS: We studied 122 subjects including 22 non atopic healthy subjects, 41 eosinophilic (sputum eosinophils >/=3%), 16 neutrophilic (sputum neutrophils >76%) and 43 pauci-granulocytic asthmatics (sputum eosinophils /=0.1 kU/l) when compared to "IgE low" asthmatics (IgE<0.1 kU/l). CONCLUSION: The eosinophilic asthma phenotype was associated with raised sputum IgE and a Th2 cytokine profile. Raised sputum IgE was associated with a heterogeneous cytokine overproduction

Radiation recall dermatitis after oral cyclophosphamide

peer reviewedRadiation 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

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

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 /= 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 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

Risk Factors associated with frequent exacerbations in asthma

peer reviewedBackground: Asthma is a chronic airway inflammatory disease with various degrees of severity. Exacerbations are commonly seen in uncontrolled asthma and their treatment involves oral corticosteroids use with a lot of side effects. Objective: The aim of the study was to identify easily available predictors for future exacerbations in patients with asthma. Methods: This is a prospective study on 250 consecutive patients with asthma with a successful sputum induction. Exacerbation rate in the following year was assessed by telephone interview. Logistic regression was used to test the relationship between the binary outcomes (<1 or ≥1 exacerbation, <2 or ≥2 exacerbations) and a set of covariates including demographic, clinical, functional and inflammatory characteristics such as FeNO, sputum and blood cell counts. The results were then applied and validated in a new cohort of 1450 patients. Results: Sputum and blood eosinophils were able to identify patients presenting ≥1 or ≥2 exacerbations with the same discriminative power (AUC:0.65 and 0.64 respectively). The multiple regression analysis identified that exacerbations in the previous year (OR = 9.3), treatment with high doses ICS (OR = 27.1), blood eosinophils (cells/mm3, OR = 1.8) and FEV1/FVC (OR = 0.93) were independent predictors of exacerbations in the year following the visit with an AUC of 0.93 for this model. Frequent exacerbations (≥2) were also predicted by exacerbations in the previous year (OR = 10.5), treatment with high doses ICS (OR = 39.2) and blood eosinophils (OR = 3.5) with an AUC of 0.95 for the model. Conclusion: Blood and sputum eosinophils have similar predictive value for future exacerbations. Prediction could be improved by combining this information with lung function, ICS dose and history of previous exacerbations