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Anti-IL5 therapy for asthma and beyond.

ABSTRACT: Airway inflammation is considered to be the primary component contributing to the heterogeneity and severity of airway disorders. Therapeutic efficacies of diverse novel biologics targeting the inflammatory pathways are under investigation. One such target is IL-5, a type-1 cytokine that is central to the initiation and sustenance of eosinophilic airway inflammation. Over the past decade, anti-IL5 molecules have been documented to have mixed therapeutic benefits in asthmatics. Post hoc analyses of the trials reiterate the importance of identifying the IL-5-responsive patient endotypes. In fact, the currently available anti-IL5 treatments are being considered beyond asthma management; especially in clinical complications with an underlying eosinophilic pathobiology such as hypereosinophilic syndrome (HES) and eosinophilic granulomatosis and polyangitis (EGPA). In addition, closer analyses of the available data indicate alternative mechanisms of tissue eosinophilia that remain uncurbed with the current dosage and delivery platform of the anti-IL5 molecules.

SUBMITTER: Mukherjee M

PROVIDER: S-EPMC4326373 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Anti-IL5 therapy for asthma and beyond.

Mukherjee Manali M Sehmi Roma R Nair Parameswaran P

The World Allergy Organization journal 20141204 1

Airway inflammation is considered to be the primary component contributing to the heterogeneity and severity of airway disorders. Therapeutic efficacies of diverse novel biologics targeting the inflammatory pathways are under investigation. One such target is IL-5, a type-1 cytokine that is central to the initiation and sustenance of eosinophilic airway inflammation. Over the past decade, anti-IL5 molecules have been documented to have mixed therapeutic benefits in asthmatics. Post hoc analyses ...[more]

PMID: 25709744

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Project description:Background Eosinophilic inflammatory phenotype was thought to be the most common phenotype of cough variant asthma (CVA), nevertheless other phenotypes were also reported. Purpose The study aimed to analyze the inflammatory phenotypes of CVA in relation to treatment response to the stepwise anti-asthmatic treatment. Patients and Methods The study included 45 patients with chronic cough (CC) and suspicion of CVA (normal chest X-ray, presence of bronchial hyperresponsiveness and no history of wheezing or dyspnea) in whom induced sputum was successfully collected. Based on the cellular composition of the sputum, patients were divided into major inflammatory phenotypes: eosinophilic, neutrophilic, paucigranulocytic or mixed granulocytic. A stepwise treatment, including inhaled corticosteroids with long-acting β2-agonist, montelukast and short-term therapy with prednisone was initiated. Good treatment response was defined as the reduction in cough severity at least 20 mm from the baseline in visual analogue scale and improvement in cough-related quality of life assessed by the Leicester cough questionnaire at least 1.3 points after any of three steps. Results Finally, 40/45 (88.9%) patients improved after therapy. Eosinophilic asthma was found in 13/40 (32.5%) patients, neutrophilic in 6/40 (15.0%) and paucigranulocytic pattern in 21/40 (52.5%) patients. No one demonstrated a mixed granulocytic phenotype. The response to the treatment was similar in all groups. However, the reduction in cough severity was inversely related to the percentage of sputum neutrophils (r = −0.44, P = 0.003). We showed that the percentage of neutrophils in sputum >46% may be considered as a predictor of poor response to anti-asthmatic therapy. Conclusion The diversity of inflammatory phenotypes with paucigranulocytic preponderance was found in subjects with CVA. The response to anti-asthmatic treatment in patients with CVA was not related to the inflammatory phenotype. High neutrophil count in sputum may predict poor response to anti-asthmatic therapy in patients with CC and bronchial hyperresponsiveness.

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Anti-IL5 therapy for asthma and beyond.

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Anti-IL5 therapy for asthma and beyond.

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