Pulmonary Health Hub

Major Finding: In this sample, 47% of children with allergies also were deficient in vitamin D.

Data Source: Researchers assess vitamin D levels in 99 children who had asthma, atopic dermatitis, and/or a food allergy.

Disclosures: Researchers had no financial conflicts to disclosure. The study was supported in part by a grant from the National Institutes of Health.

NEW ORLEANS — Approximately half of children with asthma were deficient in vitamin D in a study of 99 children aged 18 and younger.

Previous published studies in the literature have suggested that vitamin D insufficiency contributes to the pathophysiology of allergic disease.

However, data on vitamin D's impact on children with allergies and asthma are limited, Dr. Daniel Searing said in a poster presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In his investigation, Dr. Searing and colleagues at National Jewish Health in Denver, Colo., identified 99 children who had asthma, atopic dermatitis, and/or a food allergy.

The researchers assessed vitamin D by measuring serum 25-hydroxyvitamin D levels.

Overall, 47% of the patients had insufficient levels of vitamin D (less than 30 ng/mL). The median vitamin D level was 31 ng/mL.

To assess the impact of vitamin D on inflammation, the researchers cultured peripheral blood mononuclear cells (PBMC) from 11 patients using either 10 nM vitamin D or a placebo medium for 24 hours, and supplemented them with either 10 or 100 nM of dexamethasone for the last 3 hours of culturing.

Next, they measured mitogen-activated protein kinase phosphatase-1 (MKP-1) and interleukin-10 (IL-10).

“Vitamin D enhances glucocorticoid induction of MKP-1 and IL-10 in asthmatic PBMC in vitro,” the researchers explained.

In turn, the addition of supplemental vitamin D can enhance the activity of dexa-methasone more than 10-fold, they added.

However, “the relationship between vitamin D and corticosteroid pathways, as well as its effect on the inflammatory response, is not fully understood,” the researchers emphasized.

But the results suggest that vitamin D supplementation may enhance the anti-inflammatory function of corticosteroids in asthma patients, they noted.

Median vitamin D levels were significantly lower in children taking inhaled corticosteroids (29 ng/mL), oral corticosteroids (25 ng/mL), and long-acting beta-agonists (25 ng/mL), compared with children who were not taking inhaled corticosteroids, oral corticosteroids, or long-acting beta-agonists (35 ng/mL, 32 ng/mL, and 34 ng/mL, respectively).

In addition, median vitamin D levels were significantly lower in children with positive vs. negative aeroallergen sensitivity to dog dander (29 ng/mL vs. 35 ng/mL) and house dust mites (27 ng/mL vs. 31 ng/mL).

To watch an interview of Dr. Searing, go to www.youtube.com/user/ElsGlobalMedicalNews

Major Finding: In this sample, 47% of children with allergies also were deficient in vitamin D.

Data Source: Researchers assess vitamin D levels in 99 children who had asthma, atopic dermatitis, and/or a food allergy.

Disclosures: Researchers had no financial conflicts to disclosure. The study was supported in part by a grant from the National Institutes of Health.

NEW ORLEANS — Approximately half of children with asthma were deficient in vitamin D in a study of 99 children aged 18 and younger.

Previous published studies in the literature have suggested that vitamin D insufficiency contributes to the pathophysiology of allergic disease.

However, data on vitamin D's impact on children with allergies and asthma are limited, Dr. Daniel Searing said in a poster presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In his investigation, Dr. Searing and colleagues at National Jewish Health in Denver, Colo., identified 99 children who had asthma, atopic dermatitis, and/or a food allergy.

The researchers assessed vitamin D by measuring serum 25-hydroxyvitamin D levels.

Overall, 47% of the patients had insufficient levels of vitamin D (less than 30 ng/mL). The median vitamin D level was 31 ng/mL.

To assess the impact of vitamin D on inflammation, the researchers cultured peripheral blood mononuclear cells (PBMC) from 11 patients using either 10 nM vitamin D or a placebo medium for 24 hours, and supplemented them with either 10 or 100 nM of dexamethasone for the last 3 hours of culturing.

Next, they measured mitogen-activated protein kinase phosphatase-1 (MKP-1) and interleukin-10 (IL-10).

“Vitamin D enhances glucocorticoid induction of MKP-1 and IL-10 in asthmatic PBMC in vitro,” the researchers explained.

In turn, the addition of supplemental vitamin D can enhance the activity of dexa-methasone more than 10-fold, they added.

However, “the relationship between vitamin D and corticosteroid pathways, as well as its effect on the inflammatory response, is not fully understood,” the researchers emphasized.

But the results suggest that vitamin D supplementation may enhance the anti-inflammatory function of corticosteroids in asthma patients, they noted.

Median vitamin D levels were significantly lower in children taking inhaled corticosteroids (29 ng/mL), oral corticosteroids (25 ng/mL), and long-acting beta-agonists (25 ng/mL), compared with children who were not taking inhaled corticosteroids, oral corticosteroids, or long-acting beta-agonists (35 ng/mL, 32 ng/mL, and 34 ng/mL, respectively).

In addition, median vitamin D levels were significantly lower in children with positive vs. negative aeroallergen sensitivity to dog dander (29 ng/mL vs. 35 ng/mL) and house dust mites (27 ng/mL vs. 31 ng/mL).

To watch an interview of Dr. Searing, go to www.youtube.com/user/ElsGlobalMedicalNews

Major Finding: In this sample, 47% of children with allergies also were deficient in vitamin D.

Data Source: Researchers assess vitamin D levels in 99 children who had asthma, atopic dermatitis, and/or a food allergy.

Disclosures: Researchers had no financial conflicts to disclosure. The study was supported in part by a grant from the National Institutes of Health.

NEW ORLEANS — Approximately half of children with asthma were deficient in vitamin D in a study of 99 children aged 18 and younger.

Previous published studies in the literature have suggested that vitamin D insufficiency contributes to the pathophysiology of allergic disease.

However, data on vitamin D's impact on children with allergies and asthma are limited, Dr. Daniel Searing said in a poster presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In his investigation, Dr. Searing and colleagues at National Jewish Health in Denver, Colo., identified 99 children who had asthma, atopic dermatitis, and/or a food allergy.

The researchers assessed vitamin D by measuring serum 25-hydroxyvitamin D levels.

Overall, 47% of the patients had insufficient levels of vitamin D (less than 30 ng/mL). The median vitamin D level was 31 ng/mL.

To assess the impact of vitamin D on inflammation, the researchers cultured peripheral blood mononuclear cells (PBMC) from 11 patients using either 10 nM vitamin D or a placebo medium for 24 hours, and supplemented them with either 10 or 100 nM of dexamethasone for the last 3 hours of culturing.

Next, they measured mitogen-activated protein kinase phosphatase-1 (MKP-1) and interleukin-10 (IL-10).

“Vitamin D enhances glucocorticoid induction of MKP-1 and IL-10 in asthmatic PBMC in vitro,” the researchers explained.

In turn, the addition of supplemental vitamin D can enhance the activity of dexa-methasone more than 10-fold, they added.

However, “the relationship between vitamin D and corticosteroid pathways, as well as its effect on the inflammatory response, is not fully understood,” the researchers emphasized.

But the results suggest that vitamin D supplementation may enhance the anti-inflammatory function of corticosteroids in asthma patients, they noted.

Median vitamin D levels were significantly lower in children taking inhaled corticosteroids (29 ng/mL), oral corticosteroids (25 ng/mL), and long-acting beta-agonists (25 ng/mL), compared with children who were not taking inhaled corticosteroids, oral corticosteroids, or long-acting beta-agonists (35 ng/mL, 32 ng/mL, and 34 ng/mL, respectively).

In addition, median vitamin D levels were significantly lower in children with positive vs. negative aeroallergen sensitivity to dog dander (29 ng/mL vs. 35 ng/mL) and house dust mites (27 ng/mL vs. 31 ng/mL).

To watch an interview of Dr. Searing, go to www.youtube.com/user/ElsGlobalMedicalNews

Major Finding: There was a 22.7-mL increase in forced expiratory volume in 1 second (FEV₁) for each 1 ng/mL increase in serum vitamin D. In subjects with reduced vitamin D levels below 30 ng/mL, 1.03-mg/mL provocative concentration of methacholine was required to induce a 20% fall in FEV₁, whereas 1.92 mg/mL was required in those with a serum vitamin D level of 30 ng/mL or more.

Data Source: A cross-sectional study included 54 nonsmoking adults with persistent asthma.

Disclosures: The current study was supported by the National Institutes of Health. Dr. Sutherland disclosed that he serves on advisory boards for Dey and GlaxoSmithKline and as a consultant to Schering-Plough.

KEYSTONE, COLO. — Low vitamin D levels in adults with asthma are associated with impaired lung function, increased airway hyperresponsiveness, and diminished in vitro response to glucocorticoids, according to a cross-sectional study.

The inference from this study is that vitamin D deficiency—a common finding in adults with asthma—may be one of the mechanisms underlying suboptimal clinical response to inhaled corticosteroids. This raises the testable hypothesis that vitamin D supplementation may improve asthma severity and treatment response, Dr. E. Rand Sutherland said at a meeting on allergy and respiratory diseases.

A multicenter prospective clinical trial of vitamin D supplementation in asthma is forthcoming to see whether it improves asthma control. Results are probably 4 years away, said Dr. Sutherland, who is chief of the division of pulmonary and critical care medicine at National Jewish Health, Denver.

“I don't know that we have actionable data here in terms of what to do with asthmatics, but there is probably very little harm in giving 1,000-4,000 IU/day of cholecalciferol. If you're up against the wall in terms of what to do with a patient, this is one thing that's cheap, relatively easy, and may not be harmful,” he said in response to an audience question.

The cross-sectional study included 54 nonsmoking adults with persistent asthma. Their mean serum vitamin D concentration was 28 ng/mL; most experts consider levels below 30 ng/mL insufficient, he noted at the meeting, sponsored by the National Jewish Medical and Research Center.

The higher a study participant's serum vitamin D concentration, the greater the lung function. In a multivariate regression analysis, there was a 22.7-mL increase in forced expiratory volume in 1 second (FEV₁) for each 1 ng/mL increase in vitamin D (Am. J. Respir. Crit. Care Med. 2010;181:699-704).

Airway hyperresponsiveness was also more pronounced in subjects with reduced vitamin D levels. They had a 1.03-mg/mL provocative concentration of methacholine to induce a 20% fall in FEV₁, whereas 1.92 mg/mL was required in those with a serum vitamin D level of 30 ng/mL or more.

Among the 30 subjects not on inhaled corticosteroid therapy, higher serum vitamin D concentrations were associated with greater dexamethasone-induced expression of mitogen-activated protein kinase phosphatase-1 by peripheral blood mononuclear cells.

“We feel pretty good about these data as a potential biologic underpinning to some of the population data that suggested higher vitamin D concentrations are a biomarker of steroid responsiveness.” he said. He cited a study of 616 school-age children with asthma, in which higher vitamin D concentrations were associated with decreased need for inhaled corticosteroids (Am. J. Respir. Crit. Care Med. 2009;179:765-71).

Major Finding: There was a 22.7-mL increase in forced expiratory volume in 1 second (FEV₁) for each 1 ng/mL increase in serum vitamin D. In subjects with reduced vitamin D levels below 30 ng/mL, 1.03-mg/mL provocative concentration of methacholine was required to induce a 20% fall in FEV₁, whereas 1.92 mg/mL was required in those with a serum vitamin D level of 30 ng/mL or more.

Data Source: A cross-sectional study included 54 nonsmoking adults with persistent asthma.

Disclosures: The current study was supported by the National Institutes of Health. Dr. Sutherland disclosed that he serves on advisory boards for Dey and GlaxoSmithKline and as a consultant to Schering-Plough.

KEYSTONE, COLO. — Low vitamin D levels in adults with asthma are associated with impaired lung function, increased airway hyperresponsiveness, and diminished in vitro response to glucocorticoids, according to a cross-sectional study.

The inference from this study is that vitamin D deficiency—a common finding in adults with asthma—may be one of the mechanisms underlying suboptimal clinical response to inhaled corticosteroids. This raises the testable hypothesis that vitamin D supplementation may improve asthma severity and treatment response, Dr. E. Rand Sutherland said at a meeting on allergy and respiratory diseases.

A multicenter prospective clinical trial of vitamin D supplementation in asthma is forthcoming to see whether it improves asthma control. Results are probably 4 years away, said Dr. Sutherland, who is chief of the division of pulmonary and critical care medicine at National Jewish Health, Denver.

“I don't know that we have actionable data here in terms of what to do with asthmatics, but there is probably very little harm in giving 1,000-4,000 IU/day of cholecalciferol. If you're up against the wall in terms of what to do with a patient, this is one thing that's cheap, relatively easy, and may not be harmful,” he said in response to an audience question.

The cross-sectional study included 54 nonsmoking adults with persistent asthma. Their mean serum vitamin D concentration was 28 ng/mL; most experts consider levels below 30 ng/mL insufficient, he noted at the meeting, sponsored by the National Jewish Medical and Research Center.

The higher a study participant's serum vitamin D concentration, the greater the lung function. In a multivariate regression analysis, there was a 22.7-mL increase in forced expiratory volume in 1 second (FEV₁) for each 1 ng/mL increase in vitamin D (Am. J. Respir. Crit. Care Med. 2010;181:699-704).

Airway hyperresponsiveness was also more pronounced in subjects with reduced vitamin D levels. They had a 1.03-mg/mL provocative concentration of methacholine to induce a 20% fall in FEV₁, whereas 1.92 mg/mL was required in those with a serum vitamin D level of 30 ng/mL or more.

Among the 30 subjects not on inhaled corticosteroid therapy, higher serum vitamin D concentrations were associated with greater dexamethasone-induced expression of mitogen-activated protein kinase phosphatase-1 by peripheral blood mononuclear cells.

“We feel pretty good about these data as a potential biologic underpinning to some of the population data that suggested higher vitamin D concentrations are a biomarker of steroid responsiveness.” he said. He cited a study of 616 school-age children with asthma, in which higher vitamin D concentrations were associated with decreased need for inhaled corticosteroids (Am. J. Respir. Crit. Care Med. 2009;179:765-71).

Major Finding: There was a 22.7-mL increase in forced expiratory volume in 1 second (FEV₁) for each 1 ng/mL increase in serum vitamin D. In subjects with reduced vitamin D levels below 30 ng/mL, 1.03-mg/mL provocative concentration of methacholine was required to induce a 20% fall in FEV₁, whereas 1.92 mg/mL was required in those with a serum vitamin D level of 30 ng/mL or more.

Data Source: A cross-sectional study included 54 nonsmoking adults with persistent asthma.

Disclosures: The current study was supported by the National Institutes of Health. Dr. Sutherland disclosed that he serves on advisory boards for Dey and GlaxoSmithKline and as a consultant to Schering-Plough.

KEYSTONE, COLO. — Low vitamin D levels in adults with asthma are associated with impaired lung function, increased airway hyperresponsiveness, and diminished in vitro response to glucocorticoids, according to a cross-sectional study.

The inference from this study is that vitamin D deficiency—a common finding in adults with asthma—may be one of the mechanisms underlying suboptimal clinical response to inhaled corticosteroids. This raises the testable hypothesis that vitamin D supplementation may improve asthma severity and treatment response, Dr. E. Rand Sutherland said at a meeting on allergy and respiratory diseases.

A multicenter prospective clinical trial of vitamin D supplementation in asthma is forthcoming to see whether it improves asthma control. Results are probably 4 years away, said Dr. Sutherland, who is chief of the division of pulmonary and critical care medicine at National Jewish Health, Denver.

“I don't know that we have actionable data here in terms of what to do with asthmatics, but there is probably very little harm in giving 1,000-4,000 IU/day of cholecalciferol. If you're up against the wall in terms of what to do with a patient, this is one thing that's cheap, relatively easy, and may not be harmful,” he said in response to an audience question.

The cross-sectional study included 54 nonsmoking adults with persistent asthma. Their mean serum vitamin D concentration was 28 ng/mL; most experts consider levels below 30 ng/mL insufficient, he noted at the meeting, sponsored by the National Jewish Medical and Research Center.

The higher a study participant's serum vitamin D concentration, the greater the lung function. In a multivariate regression analysis, there was a 22.7-mL increase in forced expiratory volume in 1 second (FEV₁) for each 1 ng/mL increase in vitamin D (Am. J. Respir. Crit. Care Med. 2010;181:699-704).

Airway hyperresponsiveness was also more pronounced in subjects with reduced vitamin D levels. They had a 1.03-mg/mL provocative concentration of methacholine to induce a 20% fall in FEV₁, whereas 1.92 mg/mL was required in those with a serum vitamin D level of 30 ng/mL or more.

Among the 30 subjects not on inhaled corticosteroid therapy, higher serum vitamin D concentrations were associated with greater dexamethasone-induced expression of mitogen-activated protein kinase phosphatase-1 by peripheral blood mononuclear cells.

“We feel pretty good about these data as a potential biologic underpinning to some of the population data that suggested higher vitamin D concentrations are a biomarker of steroid responsiveness.” he said. He cited a study of 616 school-age children with asthma, in which higher vitamin D concentrations were associated with decreased need for inhaled corticosteroids (Am. J. Respir. Crit. Care Med. 2009;179:765-71).

KEYSTONE, COLO. — The top diagnostic priorities when a lung problem is detected in a patient with underlying rheumatoid arthritis or another autoimmune disease are to rule out infection and drug reactions.

“The first 50 things on my list are infection and drug-induced disease. Almost all the drugs used to treat the autoimmune diseases put you at increased risk for infection—usually atypical infection. And all of the drugs used in treating autoimmune diseases have clearly been associated with the development of drug-induced lung disease, although some more than others,” Dr. Kevin K. Brown observed at a meeting on allergy and respiratory diseases.

Excluding infection up front is a high priority because it's the one type of interstitial lung disease (ILD) that's readily treatable. Also, a missed pulmonary infection spells trouble because efforts to treat nearly all other forms of ILD entail immunosuppression, which will make an infection worse, noted Dr. Brown, vice chairman of the department of medicine at National Jewish Health.

Lung problems are extremely common in patients with autoimmune diseases. Chest abnormalities are present on high-resolution CT in 70%-90% of patients with systemic lupus erythematosus, rheumatoid arthritis, scleroderma, or other collagen vascular diseases, although the abnormalities often don't show up on a chest x-ray. Although many of these patients report having no respiratory complaints, a careful history not uncommonly indicates that these patients have made lifestyle changes because of exertional shortness of breath or other symptoms.

“It used to be that patients with rheumatoid arthritis were not very active because if they were active they paid for it that night when their synovitis acted up. Now it's a rare patient whose synovitis can't be effectively managed. So we're seeing patients get off the couch, being very active, but having trouble getting up and down the stairs, not because of their arthritis but because of their lung disease,” he said at the meeting, which was sponsored by the National Jewish Medical and Research Center.

One of the biggest offenders in terms of drug-induced ILD in patients with autoimmune disease is methotrexate. Probably 5%-7% of patients on methotrexate have drug-induced ILD. There are so many options available today for the treatment of collagen vascular diseases that, when Dr. Brown identifies ILD in a patient being treated for an autoimmune disease, he simply asks that the drug—whatever it is—be stopped and the patient be put on something else rather than trying to prove cause and effect.

An ILD in the setting of autoimmune disease is associated with lower quality of life, more impaired functional status, greater health care costs, and markedly reduced survival over the next 4-5 years compared with the same autoimmune disease without ILD.

Dr. Brown and others have shown that the specific autoimmune disease doesn't really matter: The prognosis for patients with an ILD and an autoimmune disease is significantly worse than for those with that autoimmune disease alone.

Clinical symptoms suggestive of autoimmune disease in a patient with an ILD include weight loss, fever, onset of Raynaud's after about age 40 years, gastroesophageal reflux, rash, keratoconjunctivitis sicca, arthralgias, and myalgias. A laboratory red flag that the ILD may be the first manifestation of an underlying autoimmune disease is the presence of nucleolar-staining antinuclear antibodies. Specific patterns of abnormal findings on CT and pathology also suggest rheumatologic disease, noted Dr. Brown, who reported having no conflicts of interest.

KEYSTONE, COLO. — The top diagnostic priorities when a lung problem is detected in a patient with underlying rheumatoid arthritis or another autoimmune disease are to rule out infection and drug reactions.

“The first 50 things on my list are infection and drug-induced disease. Almost all the drugs used to treat the autoimmune diseases put you at increased risk for infection—usually atypical infection. And all of the drugs used in treating autoimmune diseases have clearly been associated with the development of drug-induced lung disease, although some more than others,” Dr. Kevin K. Brown observed at a meeting on allergy and respiratory diseases.

Excluding infection up front is a high priority because it's the one type of interstitial lung disease (ILD) that's readily treatable. Also, a missed pulmonary infection spells trouble because efforts to treat nearly all other forms of ILD entail immunosuppression, which will make an infection worse, noted Dr. Brown, vice chairman of the department of medicine at National Jewish Health.

Lung problems are extremely common in patients with autoimmune diseases. Chest abnormalities are present on high-resolution CT in 70%-90% of patients with systemic lupus erythematosus, rheumatoid arthritis, scleroderma, or other collagen vascular diseases, although the abnormalities often don't show up on a chest x-ray. Although many of these patients report having no respiratory complaints, a careful history not uncommonly indicates that these patients have made lifestyle changes because of exertional shortness of breath or other symptoms.

“It used to be that patients with rheumatoid arthritis were not very active because if they were active they paid for it that night when their synovitis acted up. Now it's a rare patient whose synovitis can't be effectively managed. So we're seeing patients get off the couch, being very active, but having trouble getting up and down the stairs, not because of their arthritis but because of their lung disease,” he said at the meeting, which was sponsored by the National Jewish Medical and Research Center.

One of the biggest offenders in terms of drug-induced ILD in patients with autoimmune disease is methotrexate. Probably 5%-7% of patients on methotrexate have drug-induced ILD. There are so many options available today for the treatment of collagen vascular diseases that, when Dr. Brown identifies ILD in a patient being treated for an autoimmune disease, he simply asks that the drug—whatever it is—be stopped and the patient be put on something else rather than trying to prove cause and effect.

An ILD in the setting of autoimmune disease is associated with lower quality of life, more impaired functional status, greater health care costs, and markedly reduced survival over the next 4-5 years compared with the same autoimmune disease without ILD.

Dr. Brown and others have shown that the specific autoimmune disease doesn't really matter: The prognosis for patients with an ILD and an autoimmune disease is significantly worse than for those with that autoimmune disease alone.

Clinical symptoms suggestive of autoimmune disease in a patient with an ILD include weight loss, fever, onset of Raynaud's after about age 40 years, gastroesophageal reflux, rash, keratoconjunctivitis sicca, arthralgias, and myalgias. A laboratory red flag that the ILD may be the first manifestation of an underlying autoimmune disease is the presence of nucleolar-staining antinuclear antibodies. Specific patterns of abnormal findings on CT and pathology also suggest rheumatologic disease, noted Dr. Brown, who reported having no conflicts of interest.

KEYSTONE, COLO. — The top diagnostic priorities when a lung problem is detected in a patient with underlying rheumatoid arthritis or another autoimmune disease are to rule out infection and drug reactions.

“The first 50 things on my list are infection and drug-induced disease. Almost all the drugs used to treat the autoimmune diseases put you at increased risk for infection—usually atypical infection. And all of the drugs used in treating autoimmune diseases have clearly been associated with the development of drug-induced lung disease, although some more than others,” Dr. Kevin K. Brown observed at a meeting on allergy and respiratory diseases.

Excluding infection up front is a high priority because it's the one type of interstitial lung disease (ILD) that's readily treatable. Also, a missed pulmonary infection spells trouble because efforts to treat nearly all other forms of ILD entail immunosuppression, which will make an infection worse, noted Dr. Brown, vice chairman of the department of medicine at National Jewish Health.

Lung problems are extremely common in patients with autoimmune diseases. Chest abnormalities are present on high-resolution CT in 70%-90% of patients with systemic lupus erythematosus, rheumatoid arthritis, scleroderma, or other collagen vascular diseases, although the abnormalities often don't show up on a chest x-ray. Although many of these patients report having no respiratory complaints, a careful history not uncommonly indicates that these patients have made lifestyle changes because of exertional shortness of breath or other symptoms.

“It used to be that patients with rheumatoid arthritis were not very active because if they were active they paid for it that night when their synovitis acted up. Now it's a rare patient whose synovitis can't be effectively managed. So we're seeing patients get off the couch, being very active, but having trouble getting up and down the stairs, not because of their arthritis but because of their lung disease,” he said at the meeting, which was sponsored by the National Jewish Medical and Research Center.

One of the biggest offenders in terms of drug-induced ILD in patients with autoimmune disease is methotrexate. Probably 5%-7% of patients on methotrexate have drug-induced ILD. There are so many options available today for the treatment of collagen vascular diseases that, when Dr. Brown identifies ILD in a patient being treated for an autoimmune disease, he simply asks that the drug—whatever it is—be stopped and the patient be put on something else rather than trying to prove cause and effect.

An ILD in the setting of autoimmune disease is associated with lower quality of life, more impaired functional status, greater health care costs, and markedly reduced survival over the next 4-5 years compared with the same autoimmune disease without ILD.

Dr. Brown and others have shown that the specific autoimmune disease doesn't really matter: The prognosis for patients with an ILD and an autoimmune disease is significantly worse than for those with that autoimmune disease alone.

Clinical symptoms suggestive of autoimmune disease in a patient with an ILD include weight loss, fever, onset of Raynaud's after about age 40 years, gastroesophageal reflux, rash, keratoconjunctivitis sicca, arthralgias, and myalgias. A laboratory red flag that the ILD may be the first manifestation of an underlying autoimmune disease is the presence of nucleolar-staining antinuclear antibodies. Specific patterns of abnormal findings on CT and pathology also suggest rheumatologic disease, noted Dr. Brown, who reported having no conflicts of interest.

KEYSTONE, COLO. — Acute exacerbations of chronic obstructive pulmonary disease are a far more important driver of mortality than is generally appreciated.

Physicians often shrug off acute exacerbations of COPD as part of the natural course of the disease. Not so. There are several preventive therapies of proven efficacy, but to apply them most efficiently it's useful to turn to several large published studies that are instructive in identifying the high-risk subgroups, Dr. Barry Make said at a meeting on allergy and respiratory diseases.

“It's all about knowing how to prevent COPD exacerbations in the right COPD patient at the right time,” emphasized Dr. Make, director of pulmonary rehabilitation at National Jewish Health and professor of medicine at the University of Colorado, Denver.

He was senior author of a large Veterans Affairs study that brought to light the serious consequences of acute exacerbations. The retrospective study involved 51,353 COPD patients discharged after a severe exacerbation, defined as one entailing hospitalization (Chest 2007;132: 1748-55).

The key finding was that these patients had impressively high all-cause mortality: 21% over the subsequent year and 55% at 5 years. They also had COPD rehospitalization rates of 25% and 44% at 1 and 5 years, respectively. The greater the number of prior COPD hospitalizations, the higher the subsequent all-cause mortality.

Median survival after the index hospitalization was 4.2 years. The median length of stay during rehospitalization was 6.5 days. These hospitalizations are expensive; indeed, acute exacerbations account for the bulk of health care expenditures for COPD, which is arguably the costliest of all the respiratory diseases, Dr. Make said at the meeting, which was sponsored by the National Jewish Medical and Research Center.

Frequent COPD exacerbations also are an enormous burden on patients' health-related quality of life. This was underscored in a classic study in which patients with three or more exacerbations over the course of a year had a mean 14.8-point worse score on the St. George's Respiratory Questionnaire than those with 0–2 exacerbations (Am. J. Respir. Crit. Care Med. 1998;157:1418-22).

“There's nothing else that comes close to having that big an effect on quality of life,” said the pulmonologist, who noted that medications typically improve St. George's scores by only about 3.5 points.

The VA study showed that patients who have had a COPD exacerbation are at increased risk for another. In another study, British investigators showed that these recurrent exacerbations are not random events over time, but rather they cluster in such a way that the first 8 weeks after an initial exacerbation is a particularly high-risk period.

During 904 patient-years of follow-up in the British study, 27% of first exacerbations were followed by a discrete recurrent exacerbation within 8 weeks, despite what the investigators thought was full recovery from the first event (Am. J. Respir. Crit. Care Med. 2009;179:369-74).

The implication is that the first few weeks after an initial exacerbation are a particularly important time for monitoring, initiation of preventive therapy, and educating patients about early recognition of acutely worsening cough, dyspnea, and/or sputum in order to catch acute exacerbations early, Dr. Make said.

Another group at increased risk for acute exacerbations is patients with more severe COPD by the GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria.

Preliminary data from the National Heart, Lung, and Blood Institute's ongoing genetic epidemiology of COPD project show that roughly half of GOLD stage 3 patients have had an exacerbation within the past year, as have nearly 60% of those with stage 4 disease.

“If you want to target selected patients in your practice about information on what exacerbations are and how to prevent and treat them, the more severely diseased patients are the ones. But even among those with GOLD stage 1 COPD, 15% had an exacerbation within the previous year,” he said.

Diclosures: Dr. Make disclosed serving on advisory boards for Boehringer-Ingelheim, GlaxoSmithKline, AstraZeneca, Dey, Forest, Novartis, Nycomed, and Schering-Plough.

KEYSTONE, COLO. — Acute exacerbations of chronic obstructive pulmonary disease are a far more important driver of mortality than is generally appreciated.

Physicians often shrug off acute exacerbations of COPD as part of the natural course of the disease. Not so. There are several preventive therapies of proven efficacy, but to apply them most efficiently it's useful to turn to several large published studies that are instructive in identifying the high-risk subgroups, Dr. Barry Make said at a meeting on allergy and respiratory diseases.

“It's all about knowing how to prevent COPD exacerbations in the right COPD patient at the right time,” emphasized Dr. Make, director of pulmonary rehabilitation at National Jewish Health and professor of medicine at the University of Colorado, Denver.

He was senior author of a large Veterans Affairs study that brought to light the serious consequences of acute exacerbations. The retrospective study involved 51,353 COPD patients discharged after a severe exacerbation, defined as one entailing hospitalization (Chest 2007;132: 1748-55).

The key finding was that these patients had impressively high all-cause mortality: 21% over the subsequent year and 55% at 5 years. They also had COPD rehospitalization rates of 25% and 44% at 1 and 5 years, respectively. The greater the number of prior COPD hospitalizations, the higher the subsequent all-cause mortality.

Median survival after the index hospitalization was 4.2 years. The median length of stay during rehospitalization was 6.5 days. These hospitalizations are expensive; indeed, acute exacerbations account for the bulk of health care expenditures for COPD, which is arguably the costliest of all the respiratory diseases, Dr. Make said at the meeting, which was sponsored by the National Jewish Medical and Research Center.

Frequent COPD exacerbations also are an enormous burden on patients' health-related quality of life. This was underscored in a classic study in which patients with three or more exacerbations over the course of a year had a mean 14.8-point worse score on the St. George's Respiratory Questionnaire than those with 0–2 exacerbations (Am. J. Respir. Crit. Care Med. 1998;157:1418-22).

“There's nothing else that comes close to having that big an effect on quality of life,” said the pulmonologist, who noted that medications typically improve St. George's scores by only about 3.5 points.

The VA study showed that patients who have had a COPD exacerbation are at increased risk for another. In another study, British investigators showed that these recurrent exacerbations are not random events over time, but rather they cluster in such a way that the first 8 weeks after an initial exacerbation is a particularly high-risk period.

During 904 patient-years of follow-up in the British study, 27% of first exacerbations were followed by a discrete recurrent exacerbation within 8 weeks, despite what the investigators thought was full recovery from the first event (Am. J. Respir. Crit. Care Med. 2009;179:369-74).

The implication is that the first few weeks after an initial exacerbation are a particularly important time for monitoring, initiation of preventive therapy, and educating patients about early recognition of acutely worsening cough, dyspnea, and/or sputum in order to catch acute exacerbations early, Dr. Make said.

Another group at increased risk for acute exacerbations is patients with more severe COPD by the GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria.

Preliminary data from the National Heart, Lung, and Blood Institute's ongoing genetic epidemiology of COPD project show that roughly half of GOLD stage 3 patients have had an exacerbation within the past year, as have nearly 60% of those with stage 4 disease.

“If you want to target selected patients in your practice about information on what exacerbations are and how to prevent and treat them, the more severely diseased patients are the ones. But even among those with GOLD stage 1 COPD, 15% had an exacerbation within the previous year,” he said.

Diclosures: Dr. Make disclosed serving on advisory boards for Boehringer-Ingelheim, GlaxoSmithKline, AstraZeneca, Dey, Forest, Novartis, Nycomed, and Schering-Plough.

KEYSTONE, COLO. — Acute exacerbations of chronic obstructive pulmonary disease are a far more important driver of mortality than is generally appreciated.

Physicians often shrug off acute exacerbations of COPD as part of the natural course of the disease. Not so. There are several preventive therapies of proven efficacy, but to apply them most efficiently it's useful to turn to several large published studies that are instructive in identifying the high-risk subgroups, Dr. Barry Make said at a meeting on allergy and respiratory diseases.

“It's all about knowing how to prevent COPD exacerbations in the right COPD patient at the right time,” emphasized Dr. Make, director of pulmonary rehabilitation at National Jewish Health and professor of medicine at the University of Colorado, Denver.

He was senior author of a large Veterans Affairs study that brought to light the serious consequences of acute exacerbations. The retrospective study involved 51,353 COPD patients discharged after a severe exacerbation, defined as one entailing hospitalization (Chest 2007;132: 1748-55).

The key finding was that these patients had impressively high all-cause mortality: 21% over the subsequent year and 55% at 5 years. They also had COPD rehospitalization rates of 25% and 44% at 1 and 5 years, respectively. The greater the number of prior COPD hospitalizations, the higher the subsequent all-cause mortality.

Median survival after the index hospitalization was 4.2 years. The median length of stay during rehospitalization was 6.5 days. These hospitalizations are expensive; indeed, acute exacerbations account for the bulk of health care expenditures for COPD, which is arguably the costliest of all the respiratory diseases, Dr. Make said at the meeting, which was sponsored by the National Jewish Medical and Research Center.

Frequent COPD exacerbations also are an enormous burden on patients' health-related quality of life. This was underscored in a classic study in which patients with three or more exacerbations over the course of a year had a mean 14.8-point worse score on the St. George's Respiratory Questionnaire than those with 0–2 exacerbations (Am. J. Respir. Crit. Care Med. 1998;157:1418-22).

“There's nothing else that comes close to having that big an effect on quality of life,” said the pulmonologist, who noted that medications typically improve St. George's scores by only about 3.5 points.

The VA study showed that patients who have had a COPD exacerbation are at increased risk for another. In another study, British investigators showed that these recurrent exacerbations are not random events over time, but rather they cluster in such a way that the first 8 weeks after an initial exacerbation is a particularly high-risk period.

During 904 patient-years of follow-up in the British study, 27% of first exacerbations were followed by a discrete recurrent exacerbation within 8 weeks, despite what the investigators thought was full recovery from the first event (Am. J. Respir. Crit. Care Med. 2009;179:369-74).

The implication is that the first few weeks after an initial exacerbation are a particularly important time for monitoring, initiation of preventive therapy, and educating patients about early recognition of acutely worsening cough, dyspnea, and/or sputum in order to catch acute exacerbations early, Dr. Make said.

Another group at increased risk for acute exacerbations is patients with more severe COPD by the GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria.

Preliminary data from the National Heart, Lung, and Blood Institute's ongoing genetic epidemiology of COPD project show that roughly half of GOLD stage 3 patients have had an exacerbation within the past year, as have nearly 60% of those with stage 4 disease.

“If you want to target selected patients in your practice about information on what exacerbations are and how to prevent and treat them, the more severely diseased patients are the ones. But even among those with GOLD stage 1 COPD, 15% had an exacerbation within the previous year,” he said.

Diclosures: Dr. Make disclosed serving on advisory boards for Boehringer-Ingelheim, GlaxoSmithKline, AstraZeneca, Dey, Forest, Novartis, Nycomed, and Schering-Plough.

KEYSTONE, COLO. — Management of a solitary pulmonary nodule 1 cm or less in size in a patient at intermediate risk for lung cancer remains an enormous challenge and considerable burden on the health care system.

“This is where all the money is,” Dr. Ali I. Musani observed at a meeting on allergy and respiratory diseases.

More than 150,000 patients per year in the United States present to physicians with a solitary pulmonary nodule (SPN). It's an incidental finding on 1 in 500 chest x-rays. The prevalence of an SPN on a screening CT in individuals at increased risk for lung cancer because of smoking history or occupational exposure is 13%.

In deciding what to do about these lesions, size matters.

“If a nodule is more than 1 cm and up to 2 cm, that's the ideal size for me, because that's where all my sampling technologies come into play. If a nodule is 1 cm or less, we still don't have very good technologies to biopsy them. If you start taking all these out, even in the high-risk population, the vast majority are going to be benign. So if they're worried, take it out; otherwise, follow by CT scan,” said Dr. Musani, director of interventional pulmonology at National Jewish Health.

The standard recommendation for follow-up is 2 years of watchful waiting with CT every 6 months, looking for the lesion growth that would trigger a biopsy. When Dr. Musani is concerned about the possibility of bronchoalveolar carcinoma, however, that recommendation goes out the window.

“In recent years bronchoalveolar carcinoma has become very, very common. These cancers grow very slowly; 2 years of stability really means nothing. So if I see features of bronchoalveolar carcinoma on the CT, I don't care about the American College of Chest Physicians or American Thoracic Society recommendations, I keep doing CTs for 4 or 5 years,” he said at the meeting, which was sponsored by the National Jewish Medical and Research Center.

A key problem is the lack of an established screening tool for lung cancer, despite the readily identifiable risk factors for the malignancy. More than three-quarters of lung cancers are diagnosed at stage III or IV, with a 5-year survival rate of only 15%. In contrast, lung cancers diagnosed at stage I have an 88% 10-year survival rate, so early diagnosis with the help of screening CT offers great hope.

CT is reliable for localizing and characterizing a lung lesion, but a biopsy is still essential for diagnosis. A variety of tools is available for this purpose, including transthoracic needle aspiration (TTNA), standard bronchoscopy, sputum cytology, and surgical biopsy. Each has its disadvantages.

The most exciting diagnostic development of late is electromagnetic navigation bronchoscopy.

This proprietary technology, marketed by superDimension Inc., utilizes a $20,000 software package to convert a high-resolution CT into a three-dimensional road map for real-time navigation using a steerable endoscopic catheter guided by GPS-like technology while the patient lies in an electromagnetic field. This provides minimally invasive access to SPNs located deep in the lungs, well beyond the reach of standard bronchoscopy. Once at the target, biopsy needles and forceps are passed through the catheter channel.

Dr. Musani's personal experience with the superDimension i-Logic electronic navigation bronchoscopy system has been quite favorable.

“I want to see data on 1- to 2-cm lesions. That's the real challenge,” the pulmonologist noted.

Dr. Musani disclosed serving on the speakers bureaus for Cardinal Health, Olympus, and superDimension.

iLogic provides a three-dimensional road map for real-time navigation using a steerable endoscopic catheter guided by GPS-like technology.

Source Images courtesy superDimension, Inc

KEYSTONE, COLO. — Management of a solitary pulmonary nodule 1 cm or less in size in a patient at intermediate risk for lung cancer remains an enormous challenge and considerable burden on the health care system.

“This is where all the money is,” Dr. Ali I. Musani observed at a meeting on allergy and respiratory diseases.

More than 150,000 patients per year in the United States present to physicians with a solitary pulmonary nodule (SPN). It's an incidental finding on 1 in 500 chest x-rays. The prevalence of an SPN on a screening CT in individuals at increased risk for lung cancer because of smoking history or occupational exposure is 13%.

In deciding what to do about these lesions, size matters.

“If a nodule is more than 1 cm and up to 2 cm, that's the ideal size for me, because that's where all my sampling technologies come into play. If a nodule is 1 cm or less, we still don't have very good technologies to biopsy them. If you start taking all these out, even in the high-risk population, the vast majority are going to be benign. So if they're worried, take it out; otherwise, follow by CT scan,” said Dr. Musani, director of interventional pulmonology at National Jewish Health.

The standard recommendation for follow-up is 2 years of watchful waiting with CT every 6 months, looking for the lesion growth that would trigger a biopsy. When Dr. Musani is concerned about the possibility of bronchoalveolar carcinoma, however, that recommendation goes out the window.

“In recent years bronchoalveolar carcinoma has become very, very common. These cancers grow very slowly; 2 years of stability really means nothing. So if I see features of bronchoalveolar carcinoma on the CT, I don't care about the American College of Chest Physicians or American Thoracic Society recommendations, I keep doing CTs for 4 or 5 years,” he said at the meeting, which was sponsored by the National Jewish Medical and Research Center.

A key problem is the lack of an established screening tool for lung cancer, despite the readily identifiable risk factors for the malignancy. More than three-quarters of lung cancers are diagnosed at stage III or IV, with a 5-year survival rate of only 15%. In contrast, lung cancers diagnosed at stage I have an 88% 10-year survival rate, so early diagnosis with the help of screening CT offers great hope.

CT is reliable for localizing and characterizing a lung lesion, but a biopsy is still essential for diagnosis. A variety of tools is available for this purpose, including transthoracic needle aspiration (TTNA), standard bronchoscopy, sputum cytology, and surgical biopsy. Each has its disadvantages.

The most exciting diagnostic development of late is electromagnetic navigation bronchoscopy.

This proprietary technology, marketed by superDimension Inc., utilizes a $20,000 software package to convert a high-resolution CT into a three-dimensional road map for real-time navigation using a steerable endoscopic catheter guided by GPS-like technology while the patient lies in an electromagnetic field. This provides minimally invasive access to SPNs located deep in the lungs, well beyond the reach of standard bronchoscopy. Once at the target, biopsy needles and forceps are passed through the catheter channel.

Dr. Musani's personal experience with the superDimension i-Logic electronic navigation bronchoscopy system has been quite favorable.

“I want to see data on 1- to 2-cm lesions. That's the real challenge,” the pulmonologist noted.

Dr. Musani disclosed serving on the speakers bureaus for Cardinal Health, Olympus, and superDimension.

iLogic provides a three-dimensional road map for real-time navigation using a steerable endoscopic catheter guided by GPS-like technology.

Source Images courtesy superDimension, Inc

KEYSTONE, COLO. — Management of a solitary pulmonary nodule 1 cm or less in size in a patient at intermediate risk for lung cancer remains an enormous challenge and considerable burden on the health care system.

“This is where all the money is,” Dr. Ali I. Musani observed at a meeting on allergy and respiratory diseases.

More than 150,000 patients per year in the United States present to physicians with a solitary pulmonary nodule (SPN). It's an incidental finding on 1 in 500 chest x-rays. The prevalence of an SPN on a screening CT in individuals at increased risk for lung cancer because of smoking history or occupational exposure is 13%.

In deciding what to do about these lesions, size matters.

“If a nodule is more than 1 cm and up to 2 cm, that's the ideal size for me, because that's where all my sampling technologies come into play. If a nodule is 1 cm or less, we still don't have very good technologies to biopsy them. If you start taking all these out, even in the high-risk population, the vast majority are going to be benign. So if they're worried, take it out; otherwise, follow by CT scan,” said Dr. Musani, director of interventional pulmonology at National Jewish Health.

The standard recommendation for follow-up is 2 years of watchful waiting with CT every 6 months, looking for the lesion growth that would trigger a biopsy. When Dr. Musani is concerned about the possibility of bronchoalveolar carcinoma, however, that recommendation goes out the window.

“In recent years bronchoalveolar carcinoma has become very, very common. These cancers grow very slowly; 2 years of stability really means nothing. So if I see features of bronchoalveolar carcinoma on the CT, I don't care about the American College of Chest Physicians or American Thoracic Society recommendations, I keep doing CTs for 4 or 5 years,” he said at the meeting, which was sponsored by the National Jewish Medical and Research Center.

A key problem is the lack of an established screening tool for lung cancer, despite the readily identifiable risk factors for the malignancy. More than three-quarters of lung cancers are diagnosed at stage III or IV, with a 5-year survival rate of only 15%. In contrast, lung cancers diagnosed at stage I have an 88% 10-year survival rate, so early diagnosis with the help of screening CT offers great hope.

CT is reliable for localizing and characterizing a lung lesion, but a biopsy is still essential for diagnosis. A variety of tools is available for this purpose, including transthoracic needle aspiration (TTNA), standard bronchoscopy, sputum cytology, and surgical biopsy. Each has its disadvantages.

The most exciting diagnostic development of late is electromagnetic navigation bronchoscopy.

This proprietary technology, marketed by superDimension Inc., utilizes a $20,000 software package to convert a high-resolution CT into a three-dimensional road map for real-time navigation using a steerable endoscopic catheter guided by GPS-like technology while the patient lies in an electromagnetic field. This provides minimally invasive access to SPNs located deep in the lungs, well beyond the reach of standard bronchoscopy. Once at the target, biopsy needles and forceps are passed through the catheter channel.

Dr. Musani's personal experience with the superDimension i-Logic electronic navigation bronchoscopy system has been quite favorable.

“I want to see data on 1- to 2-cm lesions. That's the real challenge,” the pulmonologist noted.

Dr. Musani disclosed serving on the speakers bureaus for Cardinal Health, Olympus, and superDimension.

iLogic provides a three-dimensional road map for real-time navigation using a steerable endoscopic catheter guided by GPS-like technology.

Source Images courtesy superDimension, Inc

KEYSTONE, COLO. — Acute exacerbations of chronic obstructive pulmonary disease are a far more important driver of mortality than is generally appreciated.

Physicians often shrug off acute exacerbations of COPD as part of the natural course of the disease. Not so. There are several preventive therapies of proven efficacy, but to apply them most efficiently it's useful to turn to several large published studies that are instructive in identifying the high-risk subgroups, Dr. Barry Make said at a meeting on allergy and respiratory diseases.

“It's all about knowing how to prevent COPD exacerbations in the right COPD patient at the right time,” emphasized Dr. Make, director of pulmonary rehabilitation at National Jewish Health and professor of medicine at the University of Colorado, Denver.

He was senior author of a large Veterans Affairs study that brought to light the serious consequences of acute exacerbations. The retrospective study involved 51,353 COPD patients discharged after a severe exacerbation, defined as one entailing hospitalization (Chest 2007;132:1748–55).

The key finding was that these patients had impressively high all-cause mortality: 21% over the subsequent year and 55% at 5 years. They also had COPD rehospitalization rates of 25% and 44% at 1 and 5 years, respectively. The greater the number of prior COPD hospitalizations, the higher the subsequent all-cause mortality.

Median survival after index hospitalization was 4.2 years. Median length of stay during rehospitalization was 6.5 days. These hospitalizations are expensive. Acute exacerbations account for the bulk of health care expenditures for COPD, arguably the costliest of all the respiratory diseases, Dr. Make said at the meeting, which was sponsored by the National Jewish Medical and Research Center.

Frequent COPD exacerbations also are an enormous burden on patients' health-related quality of life. This was underscored in a classic study in which patients with three or more exacerbations over the course of a year had a mean 14.8-point worse score on the St. George's Respiratory Questionnaire than those with 0–2 exacerbations (Am. J. Respir. Crit. Care Med. 1998;157:1418–22).

The VA study demonstrated that patients who've had a COPD exacerbation are at increased risk for another. In another study, British investigators showed that these recurrent exacerbations are not random events over time, but rather they cluster such that the first 8 weeks after an initial exacerbation is a particularly high-risk period (Am. J. Respir. Crit. Care Med. 2009;179:369–74).

Dr. Make disclosed serving on advisory boards for Boehringer-Ingelheim, GlaxoSmithKline, AstraZeneca, Dey, Forest, Novartis, Nycomed, and Schering-Plough.

How to Keep COPD Under Check

Preventing acute exacerbations is a top priority in patients with chronic obstructive pulmonary disease, and physicians can draw on three types of medication and one nonpharmacologic therapy of proven benefit for this purpose.

Each of the two drugs with Food and Drug Administration approval for the prevention of acute exacerbations is supported by a multiyear randomized trial of roughly 6,000 patients, which is unusually large for the field of COPD, Dr. Make noted.

Tiotropium (Spiriva, Boehringer-Ingelheim), a long-acting anticholinergic bronchodilator, received FDA approval for this indication last December.

In the massive 4-year Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial, use of tiotropium resulted in a 14% reduction in the annual rate of moderate to severe exacerbations, compared with usual care (N. Engl. J. Med. 2008; 359:1543–54).

The other approved medication, fluticasone/salmeterol (Advair Diskus, GlaxoSmithKline), reduced moderate to severe exacerbations by 25% over 3 years in the Towards a Revolution in COPD Health (TORCH) trial (N. Engl. J. Med. 2007;356:775–89).

Long-acting beta-agonists are also of proven efficacy in preventing acute exacerbations, as shown in a large meta-analysis that demonstrated a 21% reduction in relative risk (JAMA 2003;290:2301–12), but they are not FDA approved for this purpose, he said.

Pulmonary rehabilitation—a comprehensive program of education and physical exercise—is also of proven benefit in reducing acute exacerbations. A meta-analysis of six trials involving 230 patients demonstrated that pulmonary rehab reduced by 74% the relative risk of severe exacerbations entailing hospital admission (Respir. Res. 2005;6:54).

“For those patients who refuse to take medications, this is something else they can do.” Pulmonary rehab, he stressed, is of value across the broad spectrum of COPD severity.

“I don't wait for patients to reach GOLD [Global Initiative for Chronic Obstructive Lung Disease] stage 3 or 4 to turn to pulmonary rehabilitation. … I use this therapy in most of my patients,” he said.

KEYSTONE, COLO. — Acute exacerbations of chronic obstructive pulmonary disease are a far more important driver of mortality than is generally appreciated.

Physicians often shrug off acute exacerbations of COPD as part of the natural course of the disease. Not so. There are several preventive therapies of proven efficacy, but to apply them most efficiently it's useful to turn to several large published studies that are instructive in identifying the high-risk subgroups, Dr. Barry Make said at a meeting on allergy and respiratory diseases.

“It's all about knowing how to prevent COPD exacerbations in the right COPD patient at the right time,” emphasized Dr. Make, director of pulmonary rehabilitation at National Jewish Health and professor of medicine at the University of Colorado, Denver.

He was senior author of a large Veterans Affairs study that brought to light the serious consequences of acute exacerbations. The retrospective study involved 51,353 COPD patients discharged after a severe exacerbation, defined as one entailing hospitalization (Chest 2007;132:1748–55).

The key finding was that these patients had impressively high all-cause mortality: 21% over the subsequent year and 55% at 5 years. They also had COPD rehospitalization rates of 25% and 44% at 1 and 5 years, respectively. The greater the number of prior COPD hospitalizations, the higher the subsequent all-cause mortality.

Median survival after index hospitalization was 4.2 years. Median length of stay during rehospitalization was 6.5 days. These hospitalizations are expensive. Acute exacerbations account for the bulk of health care expenditures for COPD, arguably the costliest of all the respiratory diseases, Dr. Make said at the meeting, which was sponsored by the National Jewish Medical and Research Center.

Frequent COPD exacerbations also are an enormous burden on patients' health-related quality of life. This was underscored in a classic study in which patients with three or more exacerbations over the course of a year had a mean 14.8-point worse score on the St. George's Respiratory Questionnaire than those with 0–2 exacerbations (Am. J. Respir. Crit. Care Med. 1998;157:1418–22).

The VA study demonstrated that patients who've had a COPD exacerbation are at increased risk for another. In another study, British investigators showed that these recurrent exacerbations are not random events over time, but rather they cluster such that the first 8 weeks after an initial exacerbation is a particularly high-risk period (Am. J. Respir. Crit. Care Med. 2009;179:369–74).

Dr. Make disclosed serving on advisory boards for Boehringer-Ingelheim, GlaxoSmithKline, AstraZeneca, Dey, Forest, Novartis, Nycomed, and Schering-Plough.

How to Keep COPD Under Check

Preventing acute exacerbations is a top priority in patients with chronic obstructive pulmonary disease, and physicians can draw on three types of medication and one nonpharmacologic therapy of proven benefit for this purpose.

Each of the two drugs with Food and Drug Administration approval for the prevention of acute exacerbations is supported by a multiyear randomized trial of roughly 6,000 patients, which is unusually large for the field of COPD, Dr. Make noted.

Tiotropium (Spiriva, Boehringer-Ingelheim), a long-acting anticholinergic bronchodilator, received FDA approval for this indication last December.

In the massive 4-year Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial, use of tiotropium resulted in a 14% reduction in the annual rate of moderate to severe exacerbations, compared with usual care (N. Engl. J. Med. 2008; 359:1543–54).

The other approved medication, fluticasone/salmeterol (Advair Diskus, GlaxoSmithKline), reduced moderate to severe exacerbations by 25% over 3 years in the Towards a Revolution in COPD Health (TORCH) trial (N. Engl. J. Med. 2007;356:775–89).

Long-acting beta-agonists are also of proven efficacy in preventing acute exacerbations, as shown in a large meta-analysis that demonstrated a 21% reduction in relative risk (JAMA 2003;290:2301–12), but they are not FDA approved for this purpose, he said.

Pulmonary rehabilitation—a comprehensive program of education and physical exercise—is also of proven benefit in reducing acute exacerbations. A meta-analysis of six trials involving 230 patients demonstrated that pulmonary rehab reduced by 74% the relative risk of severe exacerbations entailing hospital admission (Respir. Res. 2005;6:54).

“For those patients who refuse to take medications, this is something else they can do.” Pulmonary rehab, he stressed, is of value across the broad spectrum of COPD severity.

“I don't wait for patients to reach GOLD [Global Initiative for Chronic Obstructive Lung Disease] stage 3 or 4 to turn to pulmonary rehabilitation. … I use this therapy in most of my patients,” he said.

KEYSTONE, COLO. — Acute exacerbations of chronic obstructive pulmonary disease are a far more important driver of mortality than is generally appreciated.

Physicians often shrug off acute exacerbations of COPD as part of the natural course of the disease. Not so. There are several preventive therapies of proven efficacy, but to apply them most efficiently it's useful to turn to several large published studies that are instructive in identifying the high-risk subgroups, Dr. Barry Make said at a meeting on allergy and respiratory diseases.

“It's all about knowing how to prevent COPD exacerbations in the right COPD patient at the right time,” emphasized Dr. Make, director of pulmonary rehabilitation at National Jewish Health and professor of medicine at the University of Colorado, Denver.

He was senior author of a large Veterans Affairs study that brought to light the serious consequences of acute exacerbations. The retrospective study involved 51,353 COPD patients discharged after a severe exacerbation, defined as one entailing hospitalization (Chest 2007;132:1748–55).

The key finding was that these patients had impressively high all-cause mortality: 21% over the subsequent year and 55% at 5 years. They also had COPD rehospitalization rates of 25% and 44% at 1 and 5 years, respectively. The greater the number of prior COPD hospitalizations, the higher the subsequent all-cause mortality.

Median survival after index hospitalization was 4.2 years. Median length of stay during rehospitalization was 6.5 days. These hospitalizations are expensive. Acute exacerbations account for the bulk of health care expenditures for COPD, arguably the costliest of all the respiratory diseases, Dr. Make said at the meeting, which was sponsored by the National Jewish Medical and Research Center.

Frequent COPD exacerbations also are an enormous burden on patients' health-related quality of life. This was underscored in a classic study in which patients with three or more exacerbations over the course of a year had a mean 14.8-point worse score on the St. George's Respiratory Questionnaire than those with 0–2 exacerbations (Am. J. Respir. Crit. Care Med. 1998;157:1418–22).

The VA study demonstrated that patients who've had a COPD exacerbation are at increased risk for another. In another study, British investigators showed that these recurrent exacerbations are not random events over time, but rather they cluster such that the first 8 weeks after an initial exacerbation is a particularly high-risk period (Am. J. Respir. Crit. Care Med. 2009;179:369–74).

Dr. Make disclosed serving on advisory boards for Boehringer-Ingelheim, GlaxoSmithKline, AstraZeneca, Dey, Forest, Novartis, Nycomed, and Schering-Plough.

How to Keep COPD Under Check

Preventing acute exacerbations is a top priority in patients with chronic obstructive pulmonary disease, and physicians can draw on three types of medication and one nonpharmacologic therapy of proven benefit for this purpose.

Each of the two drugs with Food and Drug Administration approval for the prevention of acute exacerbations is supported by a multiyear randomized trial of roughly 6,000 patients, which is unusually large for the field of COPD, Dr. Make noted.

Tiotropium (Spiriva, Boehringer-Ingelheim), a long-acting anticholinergic bronchodilator, received FDA approval for this indication last December.

In the massive 4-year Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial, use of tiotropium resulted in a 14% reduction in the annual rate of moderate to severe exacerbations, compared with usual care (N. Engl. J. Med. 2008; 359:1543–54).

The other approved medication, fluticasone/salmeterol (Advair Diskus, GlaxoSmithKline), reduced moderate to severe exacerbations by 25% over 3 years in the Towards a Revolution in COPD Health (TORCH) trial (N. Engl. J. Med. 2007;356:775–89).

Long-acting beta-agonists are also of proven efficacy in preventing acute exacerbations, as shown in a large meta-analysis that demonstrated a 21% reduction in relative risk (JAMA 2003;290:2301–12), but they are not FDA approved for this purpose, he said.

Pulmonary rehabilitation—a comprehensive program of education and physical exercise—is also of proven benefit in reducing acute exacerbations. A meta-analysis of six trials involving 230 patients demonstrated that pulmonary rehab reduced by 74% the relative risk of severe exacerbations entailing hospital admission (Respir. Res. 2005;6:54).

“For those patients who refuse to take medications, this is something else they can do.” Pulmonary rehab, he stressed, is of value across the broad spectrum of COPD severity.

“I don't wait for patients to reach GOLD [Global Initiative for Chronic Obstructive Lung Disease] stage 3 or 4 to turn to pulmonary rehabilitation. … I use this therapy in most of my patients,” he said.

Nonmotor symptoms of Parkinson's disease remain underdiagnosed despite their widespread occurrence, which is the impetus behind new treatment guidelines from the American Academy of Neurology.

“Nonmotor symptoms are an integral part of this syndrome. These symptoms can be as troublesome as motor symptoms and impact activities of daily living, though they are often underrecognized by health care professionals,” wrote Dr. Theresa A. Zesiewicz, lead author of the guidelines and professor of neurology at the University of South Florida, Tampa (Neurology 2010;74:924–31).

Treatment of depression, dementia, and psychosis in Parkinson's disease (PD) has been addressed in a previous guideline (Neurology 2006;66:996–1002), as has treatment of PD-related sialorrhea with botulinum toxin (Neurology 2008;70:1707–14).

However, there are many other nonmotor symptoms for which there is a paucity of research concerning treatment, wrote Dr. Zesiewicz and her colleagues wrote.

“The disease process of PD certainly contributes to many nonmotor symptoms, including autonomic dysfunction (orthostatic hypotension, gastrointestinal symptoms), depression, sexual dysfunction, and sleep dysfunction,” said Dr. Zesiewicz in an interview. “However, medications used to treat PD can contribute to other nonmotor symptoms. For example, the use of some PD medications can contribute to excessive daytime sleepiness, while others can cause insomnia.”

In general, the treatment of most nonmotor PD symptoms should mirror treatments given to non-PD patients, because “research is not currently available to support or refute their use specifically in PD patients,” she said. The new guidelines provide evidence-based recommendations for the treatment of only four conditions: erectile dysfunction, constipation, restless legs syndrome, and fatigue.

A wide range of nonmotor symptoms were reviewed for the guidelines, including autonomic dysfunction such as gastrointestinal disorders, orthostatic hypotension, sexual dysfunction, and urinary incontinence; sleep disorders, such as restless legs syndrome, periodic limb movements of sleep, excessive daytime somnolence, insomnia, REM sleep behavior disorder; fatigue; and anxiety.

After a literature search to capture articles on these symptoms published in 1966–2008, a panel review deemed 46 papers relevant for the development of evidence-based recommendations, concluding that there was insufficient evidence to make recommendations on the treatment of urinary incontinence, orthostatic hypotension, insomnia, REM sleep behavior disorder, and anxiety.

For the treatment of erectile dysfunction in PD, the authors recommend that sildenafil citrate (50 mg) “is possibly efficacious.” Sexual dysfunction is common in both men and women with PD, they wrote. “Dysautonomia manifests as erectile dysfunction (ED) but also as reduced genital sensitivity and lubrication and difficulties reaching orgasm.” Only one controlled clinical trial for the treatment of ED was available for review, however.

For constipation, they concluded that isosmotic macrogol (polyethylene glycol) “possibly improves constipation in PD.” Four studies evaluating the efficacy of pharmacologic agents for PD-related constipation were reviewed, and the recommendation is based on one class II study.

Regarding PD-related sleep dysfunction, the authors found sufficient evidence to make treatment recommendations for excessive daytime somnolence (EDS), and restless leg syndrome or periodic limb movements of sleep.

Based on the results of two class I studies, they recommend modafinil to improve patients' perceptions of wakefulness, although “it is ineffective in objectively improving EDS as measured by objective tests,” they added.

In addition, they said, levodopa/carbidopa “probably decreases the frequency of spontaneous nighttime leg movements,” based on one class I study and should therefore be considered to treat periodic limb movements of sleep in Parkinson's disease.

And finally, “methylphenidate is possibly useful in treating fatigue in PD,” they concluded, based on one class II study.

However, there is potential for abuse, they warn. “Although there is no current evidence to suggest such a risk in PD, patients with PD do have a risk for dopamine dysregulation syndrome and impulse control disorders that share many clinical and functional imaging features with addiction,” they cautioned.

“The same rules for treating PD patients with these medications would apply as when treating any patients, including careful monitoring of drug interactions and taking comorbid conditions into consideration,” Dr. Zesiewicz noted.

“Of course, it is important to recognize that the treatments recommended are not the only available treatments,” commented Dr. Ronald B. Postuma, a PD researcher and assistant professor of neurology at the Montreal General Hospital. “The guidelines focus only on therapies that have good randomized controlled trial evidence. All experienced clinicians will recognize several useful treatments that are not in the recommendations because of incomplete evidence,” he said in an interview.

Disclosures: Dr. Zesiewicz reported receiving funding for travel and for serving on speakers bureaus from Boehringer Ingelheim and Teva Pharmaceutical Industries Ltd. She also reported receiving research support from various pharmaceutical companies.

Nonmotor symptoms of Parkinson's disease remain underdiagnosed despite their widespread occurrence, which is the impetus behind new treatment guidelines from the American Academy of Neurology.

“Nonmotor symptoms are an integral part of this syndrome. These symptoms can be as troublesome as motor symptoms and impact activities of daily living, though they are often underrecognized by health care professionals,” wrote Dr. Theresa A. Zesiewicz, lead author of the guidelines and professor of neurology at the University of South Florida, Tampa (Neurology 2010;74:924–31).

Treatment of depression, dementia, and psychosis in Parkinson's disease (PD) has been addressed in a previous guideline (Neurology 2006;66:996–1002), as has treatment of PD-related sialorrhea with botulinum toxin (Neurology 2008;70:1707–14).

However, there are many other nonmotor symptoms for which there is a paucity of research concerning treatment, wrote Dr. Zesiewicz and her colleagues wrote.

“The disease process of PD certainly contributes to many nonmotor symptoms, including autonomic dysfunction (orthostatic hypotension, gastrointestinal symptoms), depression, sexual dysfunction, and sleep dysfunction,” said Dr. Zesiewicz in an interview. “However, medications used to treat PD can contribute to other nonmotor symptoms. For example, the use of some PD medications can contribute to excessive daytime sleepiness, while others can cause insomnia.”

In general, the treatment of most nonmotor PD symptoms should mirror treatments given to non-PD patients, because “research is not currently available to support or refute their use specifically in PD patients,” she said. The new guidelines provide evidence-based recommendations for the treatment of only four conditions: erectile dysfunction, constipation, restless legs syndrome, and fatigue.

A wide range of nonmotor symptoms were reviewed for the guidelines, including autonomic dysfunction such as gastrointestinal disorders, orthostatic hypotension, sexual dysfunction, and urinary incontinence; sleep disorders, such as restless legs syndrome, periodic limb movements of sleep, excessive daytime somnolence, insomnia, REM sleep behavior disorder; fatigue; and anxiety.

After a literature search to capture articles on these symptoms published in 1966–2008, a panel review deemed 46 papers relevant for the development of evidence-based recommendations, concluding that there was insufficient evidence to make recommendations on the treatment of urinary incontinence, orthostatic hypotension, insomnia, REM sleep behavior disorder, and anxiety.

For the treatment of erectile dysfunction in PD, the authors recommend that sildenafil citrate (50 mg) “is possibly efficacious.” Sexual dysfunction is common in both men and women with PD, they wrote. “Dysautonomia manifests as erectile dysfunction (ED) but also as reduced genital sensitivity and lubrication and difficulties reaching orgasm.” Only one controlled clinical trial for the treatment of ED was available for review, however.

For constipation, they concluded that isosmotic macrogol (polyethylene glycol) “possibly improves constipation in PD.” Four studies evaluating the efficacy of pharmacologic agents for PD-related constipation were reviewed, and the recommendation is based on one class II study.

Regarding PD-related sleep dysfunction, the authors found sufficient evidence to make treatment recommendations for excessive daytime somnolence (EDS), and restless leg syndrome or periodic limb movements of sleep.

Based on the results of two class I studies, they recommend modafinil to improve patients' perceptions of wakefulness, although “it is ineffective in objectively improving EDS as measured by objective tests,” they added.

In addition, they said, levodopa/carbidopa “probably decreases the frequency of spontaneous nighttime leg movements,” based on one class I study and should therefore be considered to treat periodic limb movements of sleep in Parkinson's disease.

And finally, “methylphenidate is possibly useful in treating fatigue in PD,” they concluded, based on one class II study.

However, there is potential for abuse, they warn. “Although there is no current evidence to suggest such a risk in PD, patients with PD do have a risk for dopamine dysregulation syndrome and impulse control disorders that share many clinical and functional imaging features with addiction,” they cautioned.

“The same rules for treating PD patients with these medications would apply as when treating any patients, including careful monitoring of drug interactions and taking comorbid conditions into consideration,” Dr. Zesiewicz noted.

“Of course, it is important to recognize that the treatments recommended are not the only available treatments,” commented Dr. Ronald B. Postuma, a PD researcher and assistant professor of neurology at the Montreal General Hospital. “The guidelines focus only on therapies that have good randomized controlled trial evidence. All experienced clinicians will recognize several useful treatments that are not in the recommendations because of incomplete evidence,” he said in an interview.

Disclosures: Dr. Zesiewicz reported receiving funding for travel and for serving on speakers bureaus from Boehringer Ingelheim and Teva Pharmaceutical Industries Ltd. She also reported receiving research support from various pharmaceutical companies.

Nonmotor symptoms of Parkinson's disease remain underdiagnosed despite their widespread occurrence, which is the impetus behind new treatment guidelines from the American Academy of Neurology.

“Nonmotor symptoms are an integral part of this syndrome. These symptoms can be as troublesome as motor symptoms and impact activities of daily living, though they are often underrecognized by health care professionals,” wrote Dr. Theresa A. Zesiewicz, lead author of the guidelines and professor of neurology at the University of South Florida, Tampa (Neurology 2010;74:924–31).

Treatment of depression, dementia, and psychosis in Parkinson's disease (PD) has been addressed in a previous guideline (Neurology 2006;66:996–1002), as has treatment of PD-related sialorrhea with botulinum toxin (Neurology 2008;70:1707–14).

However, there are many other nonmotor symptoms for which there is a paucity of research concerning treatment, wrote Dr. Zesiewicz and her colleagues wrote.

“The disease process of PD certainly contributes to many nonmotor symptoms, including autonomic dysfunction (orthostatic hypotension, gastrointestinal symptoms), depression, sexual dysfunction, and sleep dysfunction,” said Dr. Zesiewicz in an interview. “However, medications used to treat PD can contribute to other nonmotor symptoms. For example, the use of some PD medications can contribute to excessive daytime sleepiness, while others can cause insomnia.”

In general, the treatment of most nonmotor PD symptoms should mirror treatments given to non-PD patients, because “research is not currently available to support or refute their use specifically in PD patients,” she said. The new guidelines provide evidence-based recommendations for the treatment of only four conditions: erectile dysfunction, constipation, restless legs syndrome, and fatigue.

A wide range of nonmotor symptoms were reviewed for the guidelines, including autonomic dysfunction such as gastrointestinal disorders, orthostatic hypotension, sexual dysfunction, and urinary incontinence; sleep disorders, such as restless legs syndrome, periodic limb movements of sleep, excessive daytime somnolence, insomnia, REM sleep behavior disorder; fatigue; and anxiety.

After a literature search to capture articles on these symptoms published in 1966–2008, a panel review deemed 46 papers relevant for the development of evidence-based recommendations, concluding that there was insufficient evidence to make recommendations on the treatment of urinary incontinence, orthostatic hypotension, insomnia, REM sleep behavior disorder, and anxiety.

For the treatment of erectile dysfunction in PD, the authors recommend that sildenafil citrate (50 mg) “is possibly efficacious.” Sexual dysfunction is common in both men and women with PD, they wrote. “Dysautonomia manifests as erectile dysfunction (ED) but also as reduced genital sensitivity and lubrication and difficulties reaching orgasm.” Only one controlled clinical trial for the treatment of ED was available for review, however.

For constipation, they concluded that isosmotic macrogol (polyethylene glycol) “possibly improves constipation in PD.” Four studies evaluating the efficacy of pharmacologic agents for PD-related constipation were reviewed, and the recommendation is based on one class II study.

Regarding PD-related sleep dysfunction, the authors found sufficient evidence to make treatment recommendations for excessive daytime somnolence (EDS), and restless leg syndrome or periodic limb movements of sleep.

Based on the results of two class I studies, they recommend modafinil to improve patients' perceptions of wakefulness, although “it is ineffective in objectively improving EDS as measured by objective tests,” they added.

In addition, they said, levodopa/carbidopa “probably decreases the frequency of spontaneous nighttime leg movements,” based on one class I study and should therefore be considered to treat periodic limb movements of sleep in Parkinson's disease.

And finally, “methylphenidate is possibly useful in treating fatigue in PD,” they concluded, based on one class II study.

However, there is potential for abuse, they warn. “Although there is no current evidence to suggest such a risk in PD, patients with PD do have a risk for dopamine dysregulation syndrome and impulse control disorders that share many clinical and functional imaging features with addiction,” they cautioned.

“The same rules for treating PD patients with these medications would apply as when treating any patients, including careful monitoring of drug interactions and taking comorbid conditions into consideration,” Dr. Zesiewicz noted.

“Of course, it is important to recognize that the treatments recommended are not the only available treatments,” commented Dr. Ronald B. Postuma, a PD researcher and assistant professor of neurology at the Montreal General Hospital. “The guidelines focus only on therapies that have good randomized controlled trial evidence. All experienced clinicians will recognize several useful treatments that are not in the recommendations because of incomplete evidence,” he said in an interview.

Disclosures: Dr. Zesiewicz reported receiving funding for travel and for serving on speakers bureaus from Boehringer Ingelheim and Teva Pharmaceutical Industries Ltd. She also reported receiving research support from various pharmaceutical companies.

Major Finding: Symptom scores related to sleep and sexual function improved significantly after adults with CRS underwent surgery.

Data Source: A prospective study of 113 adults with CRS who presented to a single tertiary care center.

Disclosures: Dr. Benninger is a consultant and has received research funding from ArthroCare Corp., and coauthor Dr. Timothy Smith is a consultant for Sinexus.

ORLANDO — Surgical treatment of chronic rhinosinusitis can improve sleep and sexual function in adult patients who failed medical therapy, based on a study of 113 patients.

“It has been shown that rhinosinusitis has a significant quality of life impact even in comparison to chronic debilitating diseases such as diabetes and congestive heart failure,” said Dr. Michael Benninger of the Cleveland Clinic, who presented the study findings at the annual meeting of the Triological Society.

Previous studies have examined how treatment of chronic rhinosinusitis (CRS) affects quality of life, but the impact of CRS treatment on patients' sleep and sexual function has not been well studied, Dr. Benninger said.

In this study, Dr. Benninger and his colleagues prospectively enrolled English-speaking adults aged 18 years and older who presented to a tertiary care center with chronic rhinosinusitis. Prior to endoscopic sinus surgery, each patient completed the Rhinosinusitis Disability Index to show how they perceived the impact of CRS on their quality of life. Responses were measured using a 5-point Likert scale, with 0 being “never” and 5 being “always.” The patients were followed for at least 9 months.

Before surgery, 41% of the patients said that their CRS “sometimes,” “almost always,” or “always” affected their sexual function, compared with a significantly lower 19% of patients following surgery.

The percentage of patients who reported that their CRS “never” or “almost never” affected their sleep improved significantly, from 15% before surgery to more than 50% after.

Many specific symptoms of CRS may have a negative impact both on sleep quality and sexual activity, Dr. Benninger said at the meeting. For example, CRS sufferers may not feel like kissing when they have a chronically runny nose and congestion.

The study results suggest that the surgery is effective in improving sleep and sexual function, although a longer follow-up period is needed to show whether the improvements persist. In addition, a more detailed analysis may be needed to better evaluate the relationships among particular CRS symptoms, such as nasal drainage or facial pain, on patients' overall perception of their sexual function, the researchers noted.

Major Finding: Symptom scores related to sleep and sexual function improved significantly after adults with CRS underwent surgery.

Data Source: A prospective study of 113 adults with CRS who presented to a single tertiary care center.

Disclosures: Dr. Benninger is a consultant and has received research funding from ArthroCare Corp., and coauthor Dr. Timothy Smith is a consultant for Sinexus.

ORLANDO — Surgical treatment of chronic rhinosinusitis can improve sleep and sexual function in adult patients who failed medical therapy, based on a study of 113 patients.

“It has been shown that rhinosinusitis has a significant quality of life impact even in comparison to chronic debilitating diseases such as diabetes and congestive heart failure,” said Dr. Michael Benninger of the Cleveland Clinic, who presented the study findings at the annual meeting of the Triological Society.

Previous studies have examined how treatment of chronic rhinosinusitis (CRS) affects quality of life, but the impact of CRS treatment on patients' sleep and sexual function has not been well studied, Dr. Benninger said.

In this study, Dr. Benninger and his colleagues prospectively enrolled English-speaking adults aged 18 years and older who presented to a tertiary care center with chronic rhinosinusitis. Prior to endoscopic sinus surgery, each patient completed the Rhinosinusitis Disability Index to show how they perceived the impact of CRS on their quality of life. Responses were measured using a 5-point Likert scale, with 0 being “never” and 5 being “always.” The patients were followed for at least 9 months.

Before surgery, 41% of the patients said that their CRS “sometimes,” “almost always,” or “always” affected their sexual function, compared with a significantly lower 19% of patients following surgery.

The percentage of patients who reported that their CRS “never” or “almost never” affected their sleep improved significantly, from 15% before surgery to more than 50% after.

Many specific symptoms of CRS may have a negative impact both on sleep quality and sexual activity, Dr. Benninger said at the meeting. For example, CRS sufferers may not feel like kissing when they have a chronically runny nose and congestion.

The study results suggest that the surgery is effective in improving sleep and sexual function, although a longer follow-up period is needed to show whether the improvements persist. In addition, a more detailed analysis may be needed to better evaluate the relationships among particular CRS symptoms, such as nasal drainage or facial pain, on patients' overall perception of their sexual function, the researchers noted.

Major Finding: Symptom scores related to sleep and sexual function improved significantly after adults with CRS underwent surgery.

Data Source: A prospective study of 113 adults with CRS who presented to a single tertiary care center.

Disclosures: Dr. Benninger is a consultant and has received research funding from ArthroCare Corp., and coauthor Dr. Timothy Smith is a consultant for Sinexus.

ORLANDO — Surgical treatment of chronic rhinosinusitis can improve sleep and sexual function in adult patients who failed medical therapy, based on a study of 113 patients.

“It has been shown that rhinosinusitis has a significant quality of life impact even in comparison to chronic debilitating diseases such as diabetes and congestive heart failure,” said Dr. Michael Benninger of the Cleveland Clinic, who presented the study findings at the annual meeting of the Triological Society.

Previous studies have examined how treatment of chronic rhinosinusitis (CRS) affects quality of life, but the impact of CRS treatment on patients' sleep and sexual function has not been well studied, Dr. Benninger said.

In this study, Dr. Benninger and his colleagues prospectively enrolled English-speaking adults aged 18 years and older who presented to a tertiary care center with chronic rhinosinusitis. Prior to endoscopic sinus surgery, each patient completed the Rhinosinusitis Disability Index to show how they perceived the impact of CRS on their quality of life. Responses were measured using a 5-point Likert scale, with 0 being “never” and 5 being “always.” The patients were followed for at least 9 months.

Before surgery, 41% of the patients said that their CRS “sometimes,” “almost always,” or “always” affected their sexual function, compared with a significantly lower 19% of patients following surgery.

The percentage of patients who reported that their CRS “never” or “almost never” affected their sleep improved significantly, from 15% before surgery to more than 50% after.

Many specific symptoms of CRS may have a negative impact both on sleep quality and sexual activity, Dr. Benninger said at the meeting. For example, CRS sufferers may not feel like kissing when they have a chronically runny nose and congestion.

The study results suggest that the surgery is effective in improving sleep and sexual function, although a longer follow-up period is needed to show whether the improvements persist. In addition, a more detailed analysis may be needed to better evaluate the relationships among particular CRS symptoms, such as nasal drainage or facial pain, on patients' overall perception of their sexual function, the researchers noted.

SAN DIEGO — Patients whose chronic obstructive pulmonary disease was treated with tiotropium monotherapy had significantly fewer disease-related hospitalizations during a 12-month window than those on other long-acting bronchodilator regimens, a large national study showed.

The retrospective study looked at COPD-related inpatient admissions in Thomson MarketScan, a large U.S. administrative claims database. The analysis involved 52,274 commercially insured patients with COPD who had one or more prescription claims for a long-acting bronchodilator (LABD) in 2004-2006, Emily D. Durden, Ph.D., reported at the annual meeting of the American College of Chest Physicians.

The COPD patients were categorized into five LABD regimens. Those on monotherapy with tiotropium (Spiriva) had significantly lower rates of disease-related hospital admissions during 12 months of follow-up than those on salmeterol (Serevent), formoterol fumarate (Foradil), salmeterol/fluticasone propionate (Advair), or combination therapy with two or more LABDs, said Dr. Durden of Thomson Reuters. (See box.)

Patients in the tiotropium monotherapy group had significantly more comorbidities than those in the other study arms. They also were more likely to have been vaccinated against influenza. Mean health care costs in the 6-month prestudy period were lowest in the salmeterol group at $12,885 and highest in patients on combination LABD therapy, at nearly $17,100.

Dr. Durden noted that the retrospective, nonrandomized nature of her study means that it can't provide proof that tiotropium was the actual cause of the significantly lower hospitalization rate.

However, Dr. Donald P. Tashkin described a new meta-analysis he and his coworkers have conducted that incorporated data from 30 placebo-controlled clinical trials of tiotropium for COPD, including the massive 4-year Understanding Potential Long-Term Impacts on Function With Tiotropium (UPLIFT) trial (Chest 2010;137:20-30).

The results of this meta-analysis indicate that tiotropium provided a 12% reduction in the risk of all-cause mortality relative to placebo and a 17% reduction in the risk of composite cardiovascular events, including stroke as well as MI, said Dr. Tashkin, professor emeritus of medicine at the University of California, Los Angeles.

The relative risks of acute MI and of heart failure were reduced by 23% and 17%, respectively, in this analysis based upon more than 13,000 patient-years of exposure to the LABD.

Disclosures: Dr. Tashkin's meta-analysis and Dr. Durden's study were both funded by Boehringer Ingelheim and Pfizer, which comarket tiotropium. Dr. Tashkin is a consultant to both companies. Dr. Durden reported having no financial conflicts.

Source Elsevier Global Medical News

SAN DIEGO — Patients whose chronic obstructive pulmonary disease was treated with tiotropium monotherapy had significantly fewer disease-related hospitalizations during a 12-month window than those on other long-acting bronchodilator regimens, a large national study showed.

The retrospective study looked at COPD-related inpatient admissions in Thomson MarketScan, a large U.S. administrative claims database. The analysis involved 52,274 commercially insured patients with COPD who had one or more prescription claims for a long-acting bronchodilator (LABD) in 2004-2006, Emily D. Durden, Ph.D., reported at the annual meeting of the American College of Chest Physicians.

The COPD patients were categorized into five LABD regimens. Those on monotherapy with tiotropium (Spiriva) had significantly lower rates of disease-related hospital admissions during 12 months of follow-up than those on salmeterol (Serevent), formoterol fumarate (Foradil), salmeterol/fluticasone propionate (Advair), or combination therapy with two or more LABDs, said Dr. Durden of Thomson Reuters. (See box.)

Patients in the tiotropium monotherapy group had significantly more comorbidities than those in the other study arms. They also were more likely to have been vaccinated against influenza. Mean health care costs in the 6-month prestudy period were lowest in the salmeterol group at $12,885 and highest in patients on combination LABD therapy, at nearly $17,100.

Dr. Durden noted that the retrospective, nonrandomized nature of her study means that it can't provide proof that tiotropium was the actual cause of the significantly lower hospitalization rate.

However, Dr. Donald P. Tashkin described a new meta-analysis he and his coworkers have conducted that incorporated data from 30 placebo-controlled clinical trials of tiotropium for COPD, including the massive 4-year Understanding Potential Long-Term Impacts on Function With Tiotropium (UPLIFT) trial (Chest 2010;137:20-30).

The results of this meta-analysis indicate that tiotropium provided a 12% reduction in the risk of all-cause mortality relative to placebo and a 17% reduction in the risk of composite cardiovascular events, including stroke as well as MI, said Dr. Tashkin, professor emeritus of medicine at the University of California, Los Angeles.

The relative risks of acute MI and of heart failure were reduced by 23% and 17%, respectively, in this analysis based upon more than 13,000 patient-years of exposure to the LABD.

Disclosures: Dr. Tashkin's meta-analysis and Dr. Durden's study were both funded by Boehringer Ingelheim and Pfizer, which comarket tiotropium. Dr. Tashkin is a consultant to both companies. Dr. Durden reported having no financial conflicts.

Source Elsevier Global Medical News

SAN DIEGO — Patients whose chronic obstructive pulmonary disease was treated with tiotropium monotherapy had significantly fewer disease-related hospitalizations during a 12-month window than those on other long-acting bronchodilator regimens, a large national study showed.

The retrospective study looked at COPD-related inpatient admissions in Thomson MarketScan, a large U.S. administrative claims database. The analysis involved 52,274 commercially insured patients with COPD who had one or more prescription claims for a long-acting bronchodilator (LABD) in 2004-2006, Emily D. Durden, Ph.D., reported at the annual meeting of the American College of Chest Physicians.

The COPD patients were categorized into five LABD regimens. Those on monotherapy with tiotropium (Spiriva) had significantly lower rates of disease-related hospital admissions during 12 months of follow-up than those on salmeterol (Serevent), formoterol fumarate (Foradil), salmeterol/fluticasone propionate (Advair), or combination therapy with two or more LABDs, said Dr. Durden of Thomson Reuters. (See box.)

Patients in the tiotropium monotherapy group had significantly more comorbidities than those in the other study arms. They also were more likely to have been vaccinated against influenza. Mean health care costs in the 6-month prestudy period were lowest in the salmeterol group at $12,885 and highest in patients on combination LABD therapy, at nearly $17,100.

Dr. Durden noted that the retrospective, nonrandomized nature of her study means that it can't provide proof that tiotropium was the actual cause of the significantly lower hospitalization rate.

However, Dr. Donald P. Tashkin described a new meta-analysis he and his coworkers have conducted that incorporated data from 30 placebo-controlled clinical trials of tiotropium for COPD, including the massive 4-year Understanding Potential Long-Term Impacts on Function With Tiotropium (UPLIFT) trial (Chest 2010;137:20-30).

The results of this meta-analysis indicate that tiotropium provided a 12% reduction in the risk of all-cause mortality relative to placebo and a 17% reduction in the risk of composite cardiovascular events, including stroke as well as MI, said Dr. Tashkin, professor emeritus of medicine at the University of California, Los Angeles.

The relative risks of acute MI and of heart failure were reduced by 23% and 17%, respectively, in this analysis based upon more than 13,000 patient-years of exposure to the LABD.

Disclosures: Dr. Tashkin's meta-analysis and Dr. Durden's study were both funded by Boehringer Ingelheim and Pfizer, which comarket tiotropium. Dr. Tashkin is a consultant to both companies. Dr. Durden reported having no financial conflicts.

Source Elsevier Global Medical News

KEYSTONE, COLO. — Low vitamin D levels in adults with asthma are associated with impaired lung function, increased airway hyperresponsiveness, and diminished in vitro response to glucocorticoids, according to a cross-sectional study.

The inference from this study is that vitamin D deficiency—a common finding in adults with asthma—may be one of the mechanisms underlying suboptimal clinical response to inhaled corticosteroids. This raises the testable hypothesis that vitamin D supplementation may improve asthma severity and treatment response, Dr. E. Rand Sutherland said at a meeting on allergy and respiratory diseases.

In light of the intriguing findings, a multicenter prospective clinical trial of vitamin D supplementation in asthma is being organized to see whether it improves asthma control. Results are probably 4 years away, said Dr. Sutherland, who is chief of the division of pulmonary and critical care medicine at National Jewish Health, Denver.

“I don't know that we have actionable data here in terms of what to do with asthmatics, but there is probably very little harm in giving 1,000-4,000 IU/day of cholecalciferol. If you're up against the wall in terms of what to do with a patient, this is one thing that's cheap, relatively easy, and may not be harmful,” he said in response to an audience question.

The cross-sectional study included 54 nonsmoking adults with persistent asthma. Their mean serum vitamin D concentration was 28 ng/mL; most experts consider levels below 30 ng/mL insufficient, he noted at the meeting, sponsored by the National Jewish Medical and Research Center.

The higher a participant's serum vitamin D concentration, the greater the lung function. In a multivariate regression analysis, there was a 22.7-mL increase in forced expiratory volume in 1 second (FEV₁) for each 1-ng/mL increase in vitamin D (Am. J. Respir. Crit. Care Med. 2010;181:699-704).

Airway hyperresponsiveness was also more pronounced in participants with reduced vitamin D levels. These patients required a 1.03-mg/mL provocative concentration of methacholine to induce a 20% fall in FEV₁, whereas 1.92 mg/mL was required in participants who had a serum vitamin D level of 30 ng/mL or more.

“We feel pretty good about these data as a potential biologic underpinning to some of the population data that suggested higher vitamin D concentrations are a biomarker of steroid responsiveness,” the pulmonologist observed.

Disclosures: The study was supported by the National Institutes of Health. Dr. Sutherland disclosed that he serves on advisory boards for Dey and GlaxoSmithKline and as a consultant to Schering-Plough.

There was a 22.7-mL increase in FEV₁ for each 1-ng/mL increase in vitamin D.

Source DR. SUTHERLAND

KEYSTONE, COLO. — Low vitamin D levels in adults with asthma are associated with impaired lung function, increased airway hyperresponsiveness, and diminished in vitro response to glucocorticoids, according to a cross-sectional study.

The inference from this study is that vitamin D deficiency—a common finding in adults with asthma—may be one of the mechanisms underlying suboptimal clinical response to inhaled corticosteroids. This raises the testable hypothesis that vitamin D supplementation may improve asthma severity and treatment response, Dr. E. Rand Sutherland said at a meeting on allergy and respiratory diseases.

In light of the intriguing findings, a multicenter prospective clinical trial of vitamin D supplementation in asthma is being organized to see whether it improves asthma control. Results are probably 4 years away, said Dr. Sutherland, who is chief of the division of pulmonary and critical care medicine at National Jewish Health, Denver.

“I don't know that we have actionable data here in terms of what to do with asthmatics, but there is probably very little harm in giving 1,000-4,000 IU/day of cholecalciferol. If you're up against the wall in terms of what to do with a patient, this is one thing that's cheap, relatively easy, and may not be harmful,” he said in response to an audience question.

The cross-sectional study included 54 nonsmoking adults with persistent asthma. Their mean serum vitamin D concentration was 28 ng/mL; most experts consider levels below 30 ng/mL insufficient, he noted at the meeting, sponsored by the National Jewish Medical and Research Center.

The higher a participant's serum vitamin D concentration, the greater the lung function. In a multivariate regression analysis, there was a 22.7-mL increase in forced expiratory volume in 1 second (FEV₁) for each 1-ng/mL increase in vitamin D (Am. J. Respir. Crit. Care Med. 2010;181:699-704).

Airway hyperresponsiveness was also more pronounced in participants with reduced vitamin D levels. These patients required a 1.03-mg/mL provocative concentration of methacholine to induce a 20% fall in FEV₁, whereas 1.92 mg/mL was required in participants who had a serum vitamin D level of 30 ng/mL or more.

“We feel pretty good about these data as a potential biologic underpinning to some of the population data that suggested higher vitamin D concentrations are a biomarker of steroid responsiveness,” the pulmonologist observed.

Disclosures: The study was supported by the National Institutes of Health. Dr. Sutherland disclosed that he serves on advisory boards for Dey and GlaxoSmithKline and as a consultant to Schering-Plough.

There was a 22.7-mL increase in FEV₁ for each 1-ng/mL increase in vitamin D.

Source DR. SUTHERLAND

KEYSTONE, COLO. — Low vitamin D levels in adults with asthma are associated with impaired lung function, increased airway hyperresponsiveness, and diminished in vitro response to glucocorticoids, according to a cross-sectional study.

The inference from this study is that vitamin D deficiency—a common finding in adults with asthma—may be one of the mechanisms underlying suboptimal clinical response to inhaled corticosteroids. This raises the testable hypothesis that vitamin D supplementation may improve asthma severity and treatment response, Dr. E. Rand Sutherland said at a meeting on allergy and respiratory diseases.

In light of the intriguing findings, a multicenter prospective clinical trial of vitamin D supplementation in asthma is being organized to see whether it improves asthma control. Results are probably 4 years away, said Dr. Sutherland, who is chief of the division of pulmonary and critical care medicine at National Jewish Health, Denver.

“I don't know that we have actionable data here in terms of what to do with asthmatics, but there is probably very little harm in giving 1,000-4,000 IU/day of cholecalciferol. If you're up against the wall in terms of what to do with a patient, this is one thing that's cheap, relatively easy, and may not be harmful,” he said in response to an audience question.

The cross-sectional study included 54 nonsmoking adults with persistent asthma. Their mean serum vitamin D concentration was 28 ng/mL; most experts consider levels below 30 ng/mL insufficient, he noted at the meeting, sponsored by the National Jewish Medical and Research Center.

The higher a participant's serum vitamin D concentration, the greater the lung function. In a multivariate regression analysis, there was a 22.7-mL increase in forced expiratory volume in 1 second (FEV₁) for each 1-ng/mL increase in vitamin D (Am. J. Respir. Crit. Care Med. 2010;181:699-704).

Airway hyperresponsiveness was also more pronounced in participants with reduced vitamin D levels. These patients required a 1.03-mg/mL provocative concentration of methacholine to induce a 20% fall in FEV₁, whereas 1.92 mg/mL was required in participants who had a serum vitamin D level of 30 ng/mL or more.

“We feel pretty good about these data as a potential biologic underpinning to some of the population data that suggested higher vitamin D concentrations are a biomarker of steroid responsiveness,” the pulmonologist observed.

Disclosures: The study was supported by the National Institutes of Health. Dr. Sutherland disclosed that he serves on advisory boards for Dey and GlaxoSmithKline and as a consultant to Schering-Plough.

There was a 22.7-mL increase in FEV₁ for each 1-ng/mL increase in vitamin D.

Source DR. SUTHERLAND