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Hyaluronan May Be Marker of Airway Remodeling

SAN FRANCISCO – Increase in sputum hyaluronan may serve as a noninvasive biomarker of airway remodeling in patients with severe asthma, results from a small novel study demonstrated.

While previous studies have shown that hyaluronan and versican are increased in the extracellular matrix of patients with obstructive lung disease, researchers led by Dr. Andrew G. Ayars, a fellow in allergy and immunology at the University of Washington, Seattle, set out to evaluate levels of hyaluronan and versican in sputum supernatants of 17 prednisone-dependent asthmatics who were randomized to either an anti-interleukin-5 antibody (mepolizumab) or placebo for 16 weeks.

In their abstract, which was unveiled during a poster session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, the researchers stated that hyaluronan is a glycosaminoglycan, which "acts as a vital structural component in connective tissues and is important in cell migration, immune cell adhesion, activation, and intracellular signaling." They described versican as "a large extracellular matrix proteoglycan that is present in a variety of human tissues," noting that it binds to hyaluronan.

Seven patients were treated with mepolizumab (at a dose of 750 mg) and 10 were treated with placebo administered intravenously over a 30-minute period at weeks 2, 6, 10, 14, and 18. Patients underwent a predefined prednisone tapering schedule if they remained exacerbation free at follow-up visits. The researchers performed spirometry and used enzyme-linked immunosorbent assay (ELISA) to measure levels of sputum hyaluronan and versican before and after treatment.

Study participants had a mean age of 56 years in the mepolizumab group and 58 years in the placebo group, and men made up 44% of the mepolizumab group and 73% of the placebo group.

Dr. Ayars and his associates observed a significant increase in sputum hyaluronan in the placebo group following prednisone taper (P = .003). They also observed a significantly lower level of sputum hyaluronan after treatment with mepolizumab vs. treatment with placebo (P = .01).

A numerical, nonsignificant increase in sputum versican was seen in the placebo group, while a numerical, nonsignificant decrease was seen in the mepolizumab group.

Dr. Ayars acknowledged that the findings are preliminary, and said that a current study is underway to test the association in patients with mild asthma treated with 2-4 weeks of inhaled corticosteroids.

Dr. Ayars said that he had no relevant financial conflicts to disclose.

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SAN FRANCISCO – Increase in sputum hyaluronan may serve as a noninvasive biomarker of airway remodeling in patients with severe asthma, results from a small novel study demonstrated.

While previous studies have shown that hyaluronan and versican are increased in the extracellular matrix of patients with obstructive lung disease, researchers led by Dr. Andrew G. Ayars, a fellow in allergy and immunology at the University of Washington, Seattle, set out to evaluate levels of hyaluronan and versican in sputum supernatants of 17 prednisone-dependent asthmatics who were randomized to either an anti-interleukin-5 antibody (mepolizumab) or placebo for 16 weeks.

In their abstract, which was unveiled during a poster session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, the researchers stated that hyaluronan is a glycosaminoglycan, which "acts as a vital structural component in connective tissues and is important in cell migration, immune cell adhesion, activation, and intracellular signaling." They described versican as "a large extracellular matrix proteoglycan that is present in a variety of human tissues," noting that it binds to hyaluronan.

Seven patients were treated with mepolizumab (at a dose of 750 mg) and 10 were treated with placebo administered intravenously over a 30-minute period at weeks 2, 6, 10, 14, and 18. Patients underwent a predefined prednisone tapering schedule if they remained exacerbation free at follow-up visits. The researchers performed spirometry and used enzyme-linked immunosorbent assay (ELISA) to measure levels of sputum hyaluronan and versican before and after treatment.

Study participants had a mean age of 56 years in the mepolizumab group and 58 years in the placebo group, and men made up 44% of the mepolizumab group and 73% of the placebo group.

Dr. Ayars and his associates observed a significant increase in sputum hyaluronan in the placebo group following prednisone taper (P = .003). They also observed a significantly lower level of sputum hyaluronan after treatment with mepolizumab vs. treatment with placebo (P = .01).

A numerical, nonsignificant increase in sputum versican was seen in the placebo group, while a numerical, nonsignificant decrease was seen in the mepolizumab group.

Dr. Ayars acknowledged that the findings are preliminary, and said that a current study is underway to test the association in patients with mild asthma treated with 2-4 weeks of inhaled corticosteroids.

Dr. Ayars said that he had no relevant financial conflicts to disclose.

SAN FRANCISCO – Increase in sputum hyaluronan may serve as a noninvasive biomarker of airway remodeling in patients with severe asthma, results from a small novel study demonstrated.

While previous studies have shown that hyaluronan and versican are increased in the extracellular matrix of patients with obstructive lung disease, researchers led by Dr. Andrew G. Ayars, a fellow in allergy and immunology at the University of Washington, Seattle, set out to evaluate levels of hyaluronan and versican in sputum supernatants of 17 prednisone-dependent asthmatics who were randomized to either an anti-interleukin-5 antibody (mepolizumab) or placebo for 16 weeks.

In their abstract, which was unveiled during a poster session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, the researchers stated that hyaluronan is a glycosaminoglycan, which "acts as a vital structural component in connective tissues and is important in cell migration, immune cell adhesion, activation, and intracellular signaling." They described versican as "a large extracellular matrix proteoglycan that is present in a variety of human tissues," noting that it binds to hyaluronan.

Seven patients were treated with mepolizumab (at a dose of 750 mg) and 10 were treated with placebo administered intravenously over a 30-minute period at weeks 2, 6, 10, 14, and 18. Patients underwent a predefined prednisone tapering schedule if they remained exacerbation free at follow-up visits. The researchers performed spirometry and used enzyme-linked immunosorbent assay (ELISA) to measure levels of sputum hyaluronan and versican before and after treatment.

Study participants had a mean age of 56 years in the mepolizumab group and 58 years in the placebo group, and men made up 44% of the mepolizumab group and 73% of the placebo group.

Dr. Ayars and his associates observed a significant increase in sputum hyaluronan in the placebo group following prednisone taper (P = .003). They also observed a significantly lower level of sputum hyaluronan after treatment with mepolizumab vs. treatment with placebo (P = .01).

A numerical, nonsignificant increase in sputum versican was seen in the placebo group, while a numerical, nonsignificant decrease was seen in the mepolizumab group.

Dr. Ayars acknowledged that the findings are preliminary, and said that a current study is underway to test the association in patients with mild asthma treated with 2-4 weeks of inhaled corticosteroids.

Dr. Ayars said that he had no relevant financial conflicts to disclose.

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Hyaluronan May Be Marker of Airway Remodeling
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Hyaluronan May Be Marker of Airway Remodeling
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FROM THE ANNUAL MEETING OF THE AMERICAN ACADEMY OF ALLERGY, ASTHMA, AND IMMUNOLOGY

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Major Finding: In patients with severe asthma who were randomized to either mepolizumab or placebo for 16 weeks, researchers observed a significant increase in sputum hyaluronan in the placebo group following prednisone taper (P = .003). They also observed a significantly lower level of sputum hyaluronan after treatment with mepolizumab vs. treatment with placebo (P = .01).

Data Source: A novel study of 17 prednisone-dependent asthmatics.

Disclosures: Dr. Ayars said that he had no relevant financial conflicts to disclose.