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Evaluation of New Drugs for Asthma and COPD: Endpoints, Biomarkers and Clinical Trial Design.

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Evaluation of New Drugs for Asthma and COPD: Endpoints, Biomarkers and Clinical Trial Design.

Handb Exp Pharmacol. 2016 Nov 13;

Authors: Singh D

Abstract
There remains a considerable need to develop novel therapies for patients with asthma and chronic obstructive pulmonary disease (COPD). The greatest challenge at the moment is measuring the effects of novel anti-inflammatory drugs, as these drugs often cause only small effects on lung function. Measurements that demonstrate the pharmacological and clinical effects of these drugs are needed. Furthermore, we now recognise that only subgroups of patients are likely to respond to these novel drugs, so using biomarkers to determine the clinical phenotype most suitable for such therapies is important. An endotype is a subtype of a (clinical) condition defined by a distinct pathophysiological mechanism. An endotype-driven approach may be more helpful in drug development, enabling drugs to be targeted specifically towards specific biological mechanisms rather than clinical characteristics. This requires the development of biomarkers to define endotypes and/or to measure drug effects. This newer approach should continue alongside efforts to optimise the measurement of clinical endpoints, including patient-reported outcome measurements, required by drug regulatory authorities.

PMID: 27838852 [PubMed – as supplied by publisher]

View full post on pubmed: asthma

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New guidelines: Introduce peanuts to infants early to prevent allergies

By Rob Goodier (Reuters Health) – Parents may be able to reduce the chance that their children will develop peanut allergies by introducing the food early on, as young as four to six months of age, experts now say. The timing and method should depend on the infant’s risk of a peanut allergy, according to doctors who presented a preview of updated guidelines today in San Francisco at the annual meeting of the American College of Allergy, Asthma and Immunology. “Guidance regarding when to introduce peanut into the diet of an infant is changing, based on new research that shows that early introduction around 4-6 months of life, after a few other foods have been introduced into the infant’s diet, is associated with a significantly reduced risk of such infants developing peanut allergy,” said Dr. Matthew Greenhawt, a pediatrician and co-director of the Food Challenge and Research Unit at Children’s Hospital Colorado in Aurora, Colorado, who coauthored the update.

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[Medical Diagnostics for Mold Exposure Indoors].

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[Medical Diagnostics for Mold Exposure Indoors].

Pneumologie. 2016 Nov;70(11):699-741

Authors: Wiesmüller GA, Heinzow B, Aurbach U, Bergmann KC, Bufe A, Buzina W, Cornely OA, Engelhart S, Fischer G, Gabrio T, Heinz W, Herr CE, Kleine-Tebbe J, Klimek L, Köberle M, Lichtnecker H, Lob-Corzilius T, Merget R, Mülleneisen N, Nowak D, Rabe U, Raulf M, Seidl HP, Steiß JO, Szewszyk R, Thomas P, Valtanen K, Hurraß J

PMID: 27829254 [PubMed – in process]

View full post on pubmed: asthma

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The soluble guanylyl cyclase activator BAY 60-2770 inhibits murine allergic airways inflammation and human eosinophil chemotaxis.

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The soluble guanylyl cyclase activator BAY 60-2770 inhibits murine allergic airways inflammation and human eosinophil chemotaxis.

Pulm Pharmacol Ther. 2016 Nov 2;:

Authors: Baldissera L, Squebola-Cola DM, Calixto MC, Lima-Barbosa AP, Rennó AL, Anhê GF, Condino-Neto A, De Nucci G, Antunes E

Abstract
OBJECTIVES: Activators of soluble guanylyl cyclase (sGC) act preferentially in conditions of enzyme oxidation or haem group removal. This study was designed to investigate the effects of the sGC activator BAY 60-2770 in murine airways inflammation and human eosinophil chemotaxis.
METHODS: C57Bl/6 mice treated or not with BAY 60-2770 (1 mg/kg/day, 14 days) were intranasally challenged with ovalbumin (OVA). At 48 h, bronchoalveolar lavage fluid (BALF) was performed, and circulating blood, bone marrow and lungs were obtained. Human eosinophils purified from peripheral blood were used to evaluate the cell chemotaxis.
RESULTS: OVA-challenge promoted marked increases in eosinophil number in BAL, lung tissue, circulating blood and bone marrow, all of which were significantly reduced by BAY 60-2770. The IL-4 and IL-5 levels in BALF were significantly reduced by BAY 60-2770. Increased protein expression of iNOS, along with decreases of expression of sGC (?1 and ?1 subunits) and cGMP levels were detected in lung tissue of OVA-challenged mice. BAY 60-2770 fully restored to baseline the iNOS and sGC subunit expressions, and cGMP levels. In human isolated eosinophils, BAY 60-2770 (1-5 ?M) had no effects on the cGMP levels and eotaxin-induced chemotaxis; however, prior incubation with ODQ (10 ?M) markedly elevated the BAY 60-2770-induced cyclic GMP production, further inhibiting the eosinophil chemotaxis.
CONCLUSIONS: BAY 60-2770 reduces airway eosinophilic inflammation and rescue the sGC levels. In human eosinophils under oxidized conditions, BAY 60-2770 elevates the cGMP levels causing cell chemotaxis inhibition. BAY 60-2770 may reveal a novel therapeutic target for asthma treatment.

PMID: 27816773 [PubMed – as supplied by publisher]

View full post on pubmed: asthma