Pulmonary Health Hub

ORLANDO – Unselected people from the general population without clinically apparent lung disease but with low lung function had significantly increased mortality during follow-up that was independent of cardiac function, in results from more than 13,000 middle-aged Germans.

“Subtle, subclinical pulmonary impairment is a risk indicator for increased mortality independent of cardiac performance,” Dr. Christina Baum said at the American Heart Association scientific sessions.

The researchers used spirometry to measure each subject’s forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC). The results showed that “spirometry is a good screening tool that is not very expensive,” making spirometry an effective risk assessment tool for use in the general adult population, said Dr. Baum of the department of general and interventional cardiology at the University Heart Center in Hamburg, Germany.

She and her associates used data collected in the Gutenberg Health Study, which enrolled more than 15,000 German women and men aged 35-74 years during 2007-2012. The investigators excluded people with a history of pulmonary disease, resulting in a study cohort of 13,191, who averaged 55 years old, with 51% men.

At enrollment into the study, all people underwent screening spirometry and echocardiography. Their average baseline FEV₁ was 2.9 L and their average FVC was 3.7 L, and 4% had heart failure based on assessments of left ventricular size and function by echocardiography. The first 5,000 enrollees also had measurements taken of their serum levels of N-terminal probrain natriuretic peptide and cardiac troponin I through use of a high-sensitivity assay. The researchers used data from patients followed for a median of 5.5 years.

During follow-up, people in the lowest tertile for FEV₁ and those in the lowest tertile for FVC had higher rates of all-cause mortality, compared with those in the highest tertile for each of these two parameters.

In a multivariate analysis that adjusted for age, sex, body mass index, smoking status, hypertension, dyslipidemia, heart failure status, serum levels of N-terminal probrain natriuretic peptide and cardiac troponin I, and other parameters, people with lower FEV₁ and FVC readings had significantly worse survival, Dr. Baum said. Every 1–standard deviation increase in FEV₁ was linked with a statistically significant, 38% reduced mortality rate; furthermore, a similar significant inverse association existed between FVC and mortality, she reported.

[email protected]

On Twitter@mitchelzoler

ORLANDO – Unselected people from the general population without clinically apparent lung disease but with low lung function had significantly increased mortality during follow-up that was independent of cardiac function, in results from more than 13,000 middle-aged Germans.

“Subtle, subclinical pulmonary impairment is a risk indicator for increased mortality independent of cardiac performance,” Dr. Christina Baum said at the American Heart Association scientific sessions.

The researchers used spirometry to measure each subject’s forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC). The results showed that “spirometry is a good screening tool that is not very expensive,” making spirometry an effective risk assessment tool for use in the general adult population, said Dr. Baum of the department of general and interventional cardiology at the University Heart Center in Hamburg, Germany.

She and her associates used data collected in the Gutenberg Health Study, which enrolled more than 15,000 German women and men aged 35-74 years during 2007-2012. The investigators excluded people with a history of pulmonary disease, resulting in a study cohort of 13,191, who averaged 55 years old, with 51% men.

At enrollment into the study, all people underwent screening spirometry and echocardiography. Their average baseline FEV₁ was 2.9 L and their average FVC was 3.7 L, and 4% had heart failure based on assessments of left ventricular size and function by echocardiography. The first 5,000 enrollees also had measurements taken of their serum levels of N-terminal probrain natriuretic peptide and cardiac troponin I through use of a high-sensitivity assay. The researchers used data from patients followed for a median of 5.5 years.

During follow-up, people in the lowest tertile for FEV₁ and those in the lowest tertile for FVC had higher rates of all-cause mortality, compared with those in the highest tertile for each of these two parameters.

In a multivariate analysis that adjusted for age, sex, body mass index, smoking status, hypertension, dyslipidemia, heart failure status, serum levels of N-terminal probrain natriuretic peptide and cardiac troponin I, and other parameters, people with lower FEV₁ and FVC readings had significantly worse survival, Dr. Baum said. Every 1–standard deviation increase in FEV₁ was linked with a statistically significant, 38% reduced mortality rate; furthermore, a similar significant inverse association existed between FVC and mortality, she reported.

[email protected]

On Twitter@mitchelzoler

ORLANDO – Unselected people from the general population without clinically apparent lung disease but with low lung function had significantly increased mortality during follow-up that was independent of cardiac function, in results from more than 13,000 middle-aged Germans.

“Subtle, subclinical pulmonary impairment is a risk indicator for increased mortality independent of cardiac performance,” Dr. Christina Baum said at the American Heart Association scientific sessions.

The researchers used spirometry to measure each subject’s forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC). The results showed that “spirometry is a good screening tool that is not very expensive,” making spirometry an effective risk assessment tool for use in the general adult population, said Dr. Baum of the department of general and interventional cardiology at the University Heart Center in Hamburg, Germany.

She and her associates used data collected in the Gutenberg Health Study, which enrolled more than 15,000 German women and men aged 35-74 years during 2007-2012. The investigators excluded people with a history of pulmonary disease, resulting in a study cohort of 13,191, who averaged 55 years old, with 51% men.

At enrollment into the study, all people underwent screening spirometry and echocardiography. Their average baseline FEV₁ was 2.9 L and their average FVC was 3.7 L, and 4% had heart failure based on assessments of left ventricular size and function by echocardiography. The first 5,000 enrollees also had measurements taken of their serum levels of N-terminal probrain natriuretic peptide and cardiac troponin I through use of a high-sensitivity assay. The researchers used data from patients followed for a median of 5.5 years.

During follow-up, people in the lowest tertile for FEV₁ and those in the lowest tertile for FVC had higher rates of all-cause mortality, compared with those in the highest tertile for each of these two parameters.

In a multivariate analysis that adjusted for age, sex, body mass index, smoking status, hypertension, dyslipidemia, heart failure status, serum levels of N-terminal probrain natriuretic peptide and cardiac troponin I, and other parameters, people with lower FEV₁ and FVC readings had significantly worse survival, Dr. Baum said. Every 1–standard deviation increase in FEV₁ was linked with a statistically significant, 38% reduced mortality rate; furthermore, a similar significant inverse association existed between FVC and mortality, she reported.

[email protected]

On Twitter@mitchelzoler

Children with a history of atopic disease (AD) are at a significantly higher risk for an anemia diagnosis than are children without AD, according to an analysis of two large U.S. population-based studies.

In addition, the risk of anemia increased with the number of caregiver-reported atopic disorders, reported the investigators, Dr. Jonathan I. Silverberg and his associates in the department of dermatology, Northwestern University, Chicago. A current diagnosis of eczema or asthma was associated with a significantly increased risk of anemia, particularly microcytic anemia, in the study, published online on Nov. 30 in JAMA Pediatrics (doi: 10.1001/jamapediatrics.2015.3065).

The authors evaluated data from the U.S. National Health Interview Survey (NHIS) on about 207,000 children and adolescents collected between 1997 and 2013, and from the National Health and Nutrition Examination Survey (NHANES) on nearly 31,000 children and adolescents between 1999 and 2012.

Data from the NHIS cohort found a significantly elevated anemia risk among children with a caregiver-reported history of hay fever, eczema, asthma, and food allergy (P less than .001 for all 4 disorders). After adjustments for age, sex, ethnicity and socioeconomic factors, the anemia risk for a child with any single atopic disorder was modestly elevated (adjusted odds ratio, 1.84; 95% confidence interval, 1.60-2.11; P less than .001). The adjusted risk among those with all four disorders was markedly elevated (adjusted OR, 7.87; 95% CI, 5.17-12.00; P less than .001).

In the NHANES cohort, the investigators found a current asthma or eczema diagnosis associated with anemia, as defined by laboratory assessment (adjusted OR, 1.33; 95% CI, 1.04-1.70; P = .02 for asthma; and an adjusted OR 1.93; 95% CI, 1.04-3.59; P = .04 for eczema).

©roobcio/thinkstockphotos.com

In the NHANES cohort, asthma was associated with an increased risk for microcytic anemia (adjusted OR, 1.61; 95% CI 1.09-2.38 P = .02). In the 2005-2006 NHANES cohort, a history of eczema was associated with an increased risk of microcytic anemia (adjusted OR, 2.03; 95% CI, 1.20-3.46; P = .009). But no significant associations for hay fever and any type of anemia were noted.

While the reasons for the observed association between atopic disease and anemia remain unknown and are probably multifactorial, physicians “should be aware that fatigue may be related to unrecognized anemia and not merely sleep loss owing to atopic dermatitis or airway disease,” the investigators wrote. Moreover, they noted, restricted diets to treat atopic disorders could play a role. “This finding underscores the importance of properly evaluating and ruling out suspected food allergy in children rather than placing them on empirical avoidance diets that might contribute to anemia,” they said.

The study was funded by the Agency for Healthcare Research and Quality and the Dermatology Foundation. Dr. Silverberg and his coauthors, Kerry E. Drury and Matt Schaeffer, declared no conflicts of interest.

Children with a history of atopic disease (AD) are at a significantly higher risk for an anemia diagnosis than are children without AD, according to an analysis of two large U.S. population-based studies.

In addition, the risk of anemia increased with the number of caregiver-reported atopic disorders, reported the investigators, Dr. Jonathan I. Silverberg and his associates in the department of dermatology, Northwestern University, Chicago. A current diagnosis of eczema or asthma was associated with a significantly increased risk of anemia, particularly microcytic anemia, in the study, published online on Nov. 30 in JAMA Pediatrics (doi: 10.1001/jamapediatrics.2015.3065).

The authors evaluated data from the U.S. National Health Interview Survey (NHIS) on about 207,000 children and adolescents collected between 1997 and 2013, and from the National Health and Nutrition Examination Survey (NHANES) on nearly 31,000 children and adolescents between 1999 and 2012.

Data from the NHIS cohort found a significantly elevated anemia risk among children with a caregiver-reported history of hay fever, eczema, asthma, and food allergy (P less than .001 for all 4 disorders). After adjustments for age, sex, ethnicity and socioeconomic factors, the anemia risk for a child with any single atopic disorder was modestly elevated (adjusted odds ratio, 1.84; 95% confidence interval, 1.60-2.11; P less than .001). The adjusted risk among those with all four disorders was markedly elevated (adjusted OR, 7.87; 95% CI, 5.17-12.00; P less than .001).

In the NHANES cohort, the investigators found a current asthma or eczema diagnosis associated with anemia, as defined by laboratory assessment (adjusted OR, 1.33; 95% CI, 1.04-1.70; P = .02 for asthma; and an adjusted OR 1.93; 95% CI, 1.04-3.59; P = .04 for eczema).

©roobcio/thinkstockphotos.com

In the NHANES cohort, asthma was associated with an increased risk for microcytic anemia (adjusted OR, 1.61; 95% CI 1.09-2.38 P = .02). In the 2005-2006 NHANES cohort, a history of eczema was associated with an increased risk of microcytic anemia (adjusted OR, 2.03; 95% CI, 1.20-3.46; P = .009). But no significant associations for hay fever and any type of anemia were noted.

While the reasons for the observed association between atopic disease and anemia remain unknown and are probably multifactorial, physicians “should be aware that fatigue may be related to unrecognized anemia and not merely sleep loss owing to atopic dermatitis or airway disease,” the investigators wrote. Moreover, they noted, restricted diets to treat atopic disorders could play a role. “This finding underscores the importance of properly evaluating and ruling out suspected food allergy in children rather than placing them on empirical avoidance diets that might contribute to anemia,” they said.

The study was funded by the Agency for Healthcare Research and Quality and the Dermatology Foundation. Dr. Silverberg and his coauthors, Kerry E. Drury and Matt Schaeffer, declared no conflicts of interest.

Children with a history of atopic disease (AD) are at a significantly higher risk for an anemia diagnosis than are children without AD, according to an analysis of two large U.S. population-based studies.

In addition, the risk of anemia increased with the number of caregiver-reported atopic disorders, reported the investigators, Dr. Jonathan I. Silverberg and his associates in the department of dermatology, Northwestern University, Chicago. A current diagnosis of eczema or asthma was associated with a significantly increased risk of anemia, particularly microcytic anemia, in the study, published online on Nov. 30 in JAMA Pediatrics (doi: 10.1001/jamapediatrics.2015.3065).

The authors evaluated data from the U.S. National Health Interview Survey (NHIS) on about 207,000 children and adolescents collected between 1997 and 2013, and from the National Health and Nutrition Examination Survey (NHANES) on nearly 31,000 children and adolescents between 1999 and 2012.

Data from the NHIS cohort found a significantly elevated anemia risk among children with a caregiver-reported history of hay fever, eczema, asthma, and food allergy (P less than .001 for all 4 disorders). After adjustments for age, sex, ethnicity and socioeconomic factors, the anemia risk for a child with any single atopic disorder was modestly elevated (adjusted odds ratio, 1.84; 95% confidence interval, 1.60-2.11; P less than .001). The adjusted risk among those with all four disorders was markedly elevated (adjusted OR, 7.87; 95% CI, 5.17-12.00; P less than .001).

In the NHANES cohort, the investigators found a current asthma or eczema diagnosis associated with anemia, as defined by laboratory assessment (adjusted OR, 1.33; 95% CI, 1.04-1.70; P = .02 for asthma; and an adjusted OR 1.93; 95% CI, 1.04-3.59; P = .04 for eczema).

©roobcio/thinkstockphotos.com

In the NHANES cohort, asthma was associated with an increased risk for microcytic anemia (adjusted OR, 1.61; 95% CI 1.09-2.38 P = .02). In the 2005-2006 NHANES cohort, a history of eczema was associated with an increased risk of microcytic anemia (adjusted OR, 2.03; 95% CI, 1.20-3.46; P = .009). But no significant associations for hay fever and any type of anemia were noted.

While the reasons for the observed association between atopic disease and anemia remain unknown and are probably multifactorial, physicians “should be aware that fatigue may be related to unrecognized anemia and not merely sleep loss owing to atopic dermatitis or airway disease,” the investigators wrote. Moreover, they noted, restricted diets to treat atopic disorders could play a role. “This finding underscores the importance of properly evaluating and ruling out suspected food allergy in children rather than placing them on empirical avoidance diets that might contribute to anemia,” they said.

The study was funded by the Agency for Healthcare Research and Quality and the Dermatology Foundation. Dr. Silverberg and his coauthors, Kerry E. Drury and Matt Schaeffer, declared no conflicts of interest.

ORLANDO – The number of Americans hospitalized for acute decompensated heart failure (ADHF) with preserved ejection fraction during 2003-2012 nearly equaled the number hospitalized with ADHF with reduced ejection fraction, in an analysis of more than 5 million hospitalized heart failure patients tracked in a national-sample database.

But the profile of patients hospitalized with ADHF with preserved ejection fraction (HFpEF) differed from patients hospitalized with acute heart failure and reduced ejection fraction (HFrEF), with a substantially higher percentage of women and patients aged 75 years or older, Dr. Parag Goyal said at the American Heart Association scientific sessions.

Mitchel L. Zoler/Frontline Medical News

The analysis also showed the strongest correlate for in-hospital mortality among HFpEF patients hospitalized with acute decompensation was a pulmonary circulation disorder, such as pulmonary hypertension, which nearly doubled the rate of in-hospital death among HFpEF patients. Other strong correlates of mortality during hospitalization were liver disease, which was linked with about a 50% boost in hospitalized mortality; and chronic renal failure, which was tied to a roughly one-third higher mortality, said Dr. Goyal, a cardiologist at New York–Presbyterian Hospital.

His study used data collected by the Nationwide Inpatient Sample, which included data on more than 388 million hospitalized U.S. patients during 2003-2012, including 5,046,879 hospitalized with acute heart failure. This total included 2,329,391 patients (46%) diagnosed with HFpEF and 2,717,488 patients (54%) diagnosed with HFrEF.

The HFpEF patients’ average age was 76 years, with 60% at least 75 years old, while the HFrEF patients’ average age was 72 years, with 49% age 75 years or older. Nearly two-thirds of the HFpEF patients were women, compared with 42% in the HFrEF group. The HFrEF patients also had a substantially higher prevalence of coronary artery disease, 59%, compared with 41% in the HFpEF group. The prevalence of several comorbidities – including diabetes, hypertension, and chronic renal failure – were each roughly similar in both subgroups, but the obesity rate of 19% in the HFpEF patients substantially exceeded the 12% rate in HFrEF patients.

In-hospital mortality ran 4.3% in the HFpEF patients and 5.1% in the HFrEF patients, a 13% relative-risk reduction that was statistically significant. But average length of stay was similar between the two groups, about 7 days with either type of heart failure.

Dr. Goyal and his associates also examined time trends during 2003-2012. During this period, the percentage of patients with HFpEF aged 75 years or older rose from 57% to 60%. Even more notably, the percentage of men with HFpEF rose from 31% in 2003 to 37% in 2012. Furthermore, the reduced in-hospital mortality during the period was largely driven by mortality reductions among HFpEF patients aged 65 years or older. A multivariate analysis for significant correlates of in-hospital mortality identified age 75 years or older, male sex, and white race in both the HFpEF subgroup and in those with HFrEF. Older age had the highest impact, linked with about a 60% relatively higher mortality rate in patients with either type of heart failure.

The multivariate analysis also identified three comorbidities linked with in-hospital mortality. A pulmonary circulation disorder was associated with a 90% higher mortality rate among HFpEF patients and a 79% higher rate among those with HFrEF. Liver disease and chronic renal disease linked with smaller mortality increases for both heart failure types. The presence of treatable comorbidities, including hypertension, diabetes, and coronary artery disease, linked with significantly lower in-hospital mortality rates. Dr. Goyal speculated that the reduced mortality resulted from successful treatment of these conditions.

[email protected]

On Twitter @mitchelzoler

ORLANDO – The number of Americans hospitalized for acute decompensated heart failure (ADHF) with preserved ejection fraction during 2003-2012 nearly equaled the number hospitalized with ADHF with reduced ejection fraction, in an analysis of more than 5 million hospitalized heart failure patients tracked in a national-sample database.

But the profile of patients hospitalized with ADHF with preserved ejection fraction (HFpEF) differed from patients hospitalized with acute heart failure and reduced ejection fraction (HFrEF), with a substantially higher percentage of women and patients aged 75 years or older, Dr. Parag Goyal said at the American Heart Association scientific sessions.

Mitchel L. Zoler/Frontline Medical News

The analysis also showed the strongest correlate for in-hospital mortality among HFpEF patients hospitalized with acute decompensation was a pulmonary circulation disorder, such as pulmonary hypertension, which nearly doubled the rate of in-hospital death among HFpEF patients. Other strong correlates of mortality during hospitalization were liver disease, which was linked with about a 50% boost in hospitalized mortality; and chronic renal failure, which was tied to a roughly one-third higher mortality, said Dr. Goyal, a cardiologist at New York–Presbyterian Hospital.

His study used data collected by the Nationwide Inpatient Sample, which included data on more than 388 million hospitalized U.S. patients during 2003-2012, including 5,046,879 hospitalized with acute heart failure. This total included 2,329,391 patients (46%) diagnosed with HFpEF and 2,717,488 patients (54%) diagnosed with HFrEF.

The HFpEF patients’ average age was 76 years, with 60% at least 75 years old, while the HFrEF patients’ average age was 72 years, with 49% age 75 years or older. Nearly two-thirds of the HFpEF patients were women, compared with 42% in the HFrEF group. The HFrEF patients also had a substantially higher prevalence of coronary artery disease, 59%, compared with 41% in the HFpEF group. The prevalence of several comorbidities – including diabetes, hypertension, and chronic renal failure – were each roughly similar in both subgroups, but the obesity rate of 19% in the HFpEF patients substantially exceeded the 12% rate in HFrEF patients.

In-hospital mortality ran 4.3% in the HFpEF patients and 5.1% in the HFrEF patients, a 13% relative-risk reduction that was statistically significant. But average length of stay was similar between the two groups, about 7 days with either type of heart failure.

Dr. Goyal and his associates also examined time trends during 2003-2012. During this period, the percentage of patients with HFpEF aged 75 years or older rose from 57% to 60%. Even more notably, the percentage of men with HFpEF rose from 31% in 2003 to 37% in 2012. Furthermore, the reduced in-hospital mortality during the period was largely driven by mortality reductions among HFpEF patients aged 65 years or older. A multivariate analysis for significant correlates of in-hospital mortality identified age 75 years or older, male sex, and white race in both the HFpEF subgroup and in those with HFrEF. Older age had the highest impact, linked with about a 60% relatively higher mortality rate in patients with either type of heart failure.

The multivariate analysis also identified three comorbidities linked with in-hospital mortality. A pulmonary circulation disorder was associated with a 90% higher mortality rate among HFpEF patients and a 79% higher rate among those with HFrEF. Liver disease and chronic renal disease linked with smaller mortality increases for both heart failure types. The presence of treatable comorbidities, including hypertension, diabetes, and coronary artery disease, linked with significantly lower in-hospital mortality rates. Dr. Goyal speculated that the reduced mortality resulted from successful treatment of these conditions.

[email protected]

On Twitter @mitchelzoler

ORLANDO – The number of Americans hospitalized for acute decompensated heart failure (ADHF) with preserved ejection fraction during 2003-2012 nearly equaled the number hospitalized with ADHF with reduced ejection fraction, in an analysis of more than 5 million hospitalized heart failure patients tracked in a national-sample database.

But the profile of patients hospitalized with ADHF with preserved ejection fraction (HFpEF) differed from patients hospitalized with acute heart failure and reduced ejection fraction (HFrEF), with a substantially higher percentage of women and patients aged 75 years or older, Dr. Parag Goyal said at the American Heart Association scientific sessions.

Mitchel L. Zoler/Frontline Medical News

The analysis also showed the strongest correlate for in-hospital mortality among HFpEF patients hospitalized with acute decompensation was a pulmonary circulation disorder, such as pulmonary hypertension, which nearly doubled the rate of in-hospital death among HFpEF patients. Other strong correlates of mortality during hospitalization were liver disease, which was linked with about a 50% boost in hospitalized mortality; and chronic renal failure, which was tied to a roughly one-third higher mortality, said Dr. Goyal, a cardiologist at New York–Presbyterian Hospital.

His study used data collected by the Nationwide Inpatient Sample, which included data on more than 388 million hospitalized U.S. patients during 2003-2012, including 5,046,879 hospitalized with acute heart failure. This total included 2,329,391 patients (46%) diagnosed with HFpEF and 2,717,488 patients (54%) diagnosed with HFrEF.

The HFpEF patients’ average age was 76 years, with 60% at least 75 years old, while the HFrEF patients’ average age was 72 years, with 49% age 75 years or older. Nearly two-thirds of the HFpEF patients were women, compared with 42% in the HFrEF group. The HFrEF patients also had a substantially higher prevalence of coronary artery disease, 59%, compared with 41% in the HFpEF group. The prevalence of several comorbidities – including diabetes, hypertension, and chronic renal failure – were each roughly similar in both subgroups, but the obesity rate of 19% in the HFpEF patients substantially exceeded the 12% rate in HFrEF patients.

In-hospital mortality ran 4.3% in the HFpEF patients and 5.1% in the HFrEF patients, a 13% relative-risk reduction that was statistically significant. But average length of stay was similar between the two groups, about 7 days with either type of heart failure.

Dr. Goyal and his associates also examined time trends during 2003-2012. During this period, the percentage of patients with HFpEF aged 75 years or older rose from 57% to 60%. Even more notably, the percentage of men with HFpEF rose from 31% in 2003 to 37% in 2012. Furthermore, the reduced in-hospital mortality during the period was largely driven by mortality reductions among HFpEF patients aged 65 years or older. A multivariate analysis for significant correlates of in-hospital mortality identified age 75 years or older, male sex, and white race in both the HFpEF subgroup and in those with HFrEF. Older age had the highest impact, linked with about a 60% relatively higher mortality rate in patients with either type of heart failure.

The multivariate analysis also identified three comorbidities linked with in-hospital mortality. A pulmonary circulation disorder was associated with a 90% higher mortality rate among HFpEF patients and a 79% higher rate among those with HFrEF. Liver disease and chronic renal disease linked with smaller mortality increases for both heart failure types. The presence of treatable comorbidities, including hypertension, diabetes, and coronary artery disease, linked with significantly lower in-hospital mortality rates. Dr. Goyal speculated that the reduced mortality resulted from successful treatment of these conditions.

[email protected]

On Twitter @mitchelzoler

ORLANDO – A history of asthma was independently associated with a 24% increase in the risk of new-onset coronary heart disease among postmenopausal women in an analysis from the Women’s Health Initiative.

The study cohort included 90,168 women aged 50-79 years who were free of cardiovascular disease at enrollment in the Women’s Health Initiative (WHI), of whom 6,921 reported a history of physician-diagnosed asthma at baseline. During follow-up in the prospective study, the incidence of a CHD event was 8.6% in subjects with a history of asthma and 6.97% in the no-asthma group, Dr. Fady Y. Marmoush reported at the American Heart Association scientific sessions.

Bruce Jancin/Frontline Medical News

Moreover, the incidence of a first cardiovascular event was 11.6% in the asthma group, compared with 9.7% in the no-asthma controls, added Dr. Marmoush of Memorial Hospital of Rhode Island, Pawtucket.

The asthma group had an absolute 1%-2% greater baseline prevalence of hypertension, diabetes, and family history of CHD. Those with asthma also were more likely to be obese. On the other hand, they were less likely to have ever smoked.

In a multivariate analysis adjusted for these and other potential confounders, including age, dyslipidemia, and waist-hip ratio, the women with a history of asthma had a 24% greater risk of CHD during prospective follow-up in the WHI, as well as a 21% increased rate of cardiovascular events, including stroke, compared with the no-asthma group.

Thus, a history of asthma could be a useful consideration – a tie breaker of sorts – in older women whose calculated 10-year atherosclerotic cardiovascular disease risk based on the standard risk factors places them on the borderline as candidates for statin therapy. The most likely mechanism for the observed association between asthma history and increased risk of cardiovascular disease is the chronic inflammatory state that’s a hallmark of asthma accelerating the atherosclerotic process, which also is inflammatory, she said.

The WHI is funded by the National Heart, Lung, and Blood Institute. Dr. Marmoush reported having no financial conflicts.

ORLANDO – A history of asthma was independently associated with a 24% increase in the risk of new-onset coronary heart disease among postmenopausal women in an analysis from the Women’s Health Initiative.

The study cohort included 90,168 women aged 50-79 years who were free of cardiovascular disease at enrollment in the Women’s Health Initiative (WHI), of whom 6,921 reported a history of physician-diagnosed asthma at baseline. During follow-up in the prospective study, the incidence of a CHD event was 8.6% in subjects with a history of asthma and 6.97% in the no-asthma group, Dr. Fady Y. Marmoush reported at the American Heart Association scientific sessions.

Bruce Jancin/Frontline Medical News

Moreover, the incidence of a first cardiovascular event was 11.6% in the asthma group, compared with 9.7% in the no-asthma controls, added Dr. Marmoush of Memorial Hospital of Rhode Island, Pawtucket.

The asthma group had an absolute 1%-2% greater baseline prevalence of hypertension, diabetes, and family history of CHD. Those with asthma also were more likely to be obese. On the other hand, they were less likely to have ever smoked.

In a multivariate analysis adjusted for these and other potential confounders, including age, dyslipidemia, and waist-hip ratio, the women with a history of asthma had a 24% greater risk of CHD during prospective follow-up in the WHI, as well as a 21% increased rate of cardiovascular events, including stroke, compared with the no-asthma group.

Thus, a history of asthma could be a useful consideration – a tie breaker of sorts – in older women whose calculated 10-year atherosclerotic cardiovascular disease risk based on the standard risk factors places them on the borderline as candidates for statin therapy. The most likely mechanism for the observed association between asthma history and increased risk of cardiovascular disease is the chronic inflammatory state that’s a hallmark of asthma accelerating the atherosclerotic process, which also is inflammatory, she said.

The WHI is funded by the National Heart, Lung, and Blood Institute. Dr. Marmoush reported having no financial conflicts.

ORLANDO – A history of asthma was independently associated with a 24% increase in the risk of new-onset coronary heart disease among postmenopausal women in an analysis from the Women’s Health Initiative.

The study cohort included 90,168 women aged 50-79 years who were free of cardiovascular disease at enrollment in the Women’s Health Initiative (WHI), of whom 6,921 reported a history of physician-diagnosed asthma at baseline. During follow-up in the prospective study, the incidence of a CHD event was 8.6% in subjects with a history of asthma and 6.97% in the no-asthma group, Dr. Fady Y. Marmoush reported at the American Heart Association scientific sessions.

Bruce Jancin/Frontline Medical News

Moreover, the incidence of a first cardiovascular event was 11.6% in the asthma group, compared with 9.7% in the no-asthma controls, added Dr. Marmoush of Memorial Hospital of Rhode Island, Pawtucket.

The asthma group had an absolute 1%-2% greater baseline prevalence of hypertension, diabetes, and family history of CHD. Those with asthma also were more likely to be obese. On the other hand, they were less likely to have ever smoked.

In a multivariate analysis adjusted for these and other potential confounders, including age, dyslipidemia, and waist-hip ratio, the women with a history of asthma had a 24% greater risk of CHD during prospective follow-up in the WHI, as well as a 21% increased rate of cardiovascular events, including stroke, compared with the no-asthma group.

Thus, a history of asthma could be a useful consideration – a tie breaker of sorts – in older women whose calculated 10-year atherosclerotic cardiovascular disease risk based on the standard risk factors places them on the borderline as candidates for statin therapy. The most likely mechanism for the observed association between asthma history and increased risk of cardiovascular disease is the chronic inflammatory state that’s a hallmark of asthma accelerating the atherosclerotic process, which also is inflammatory, she said.

The WHI is funded by the National Heart, Lung, and Blood Institute. Dr. Marmoush reported having no financial conflicts.

ORLANDO – A history of asthma was independently associated with a 24% increase in the risk of new-onset coronary heart disease among postmenopausal women in an analysis from the Women’s Health Initiative.

The study cohort included 90,168 women aged 50-79 years who were free of cardiovascular disease at enrollment in the Women’s Health Initiative (WHI), of whom 6,921 reported a history of physician-diagnosed asthma at baseline. During follow-up in the prospective study, the incidence of a CHD event was 8.6% in subjects with a history of asthma and 6.97% in the no-asthma group, Dr. Fady Y. Marmoush reported at the American Heart Association scientific sessions.

Bruce Jancin/Frontline Medical News

Moreover, the incidence of a first cardiovascular event was 11.6% in the asthma group, compared with 9.7% in the no-asthma controls, added Dr. Marmoush of Memorial Hospital of Rhode Island, Pawtucket.

The asthma group had an absolute 1%-2% greater baseline prevalence of hypertension, diabetes, and family history of CHD. Those with asthma also were more likely to be obese. On the other hand, they were less likely to have ever smoked.

In a multivariate analysis adjusted for these and other potential confounders, including age, dyslipidemia, and waist-hip ratio, the women with a history of asthma had a 24% greater risk of CHD during prospective follow-up in the WHI, as well as a 21% increased rate of cardiovascular events, including stroke, compared with the no-asthma group.

Thus, a history of asthma could be a useful consideration – a tie breaker of sorts – in older women whose calculated 10-year atherosclerotic cardiovascular disease risk based on the standard risk factors places them on the borderline as candidates for statin therapy. The most likely mechanism for the observed association between asthma history and increased risk of cardiovascular disease is the chronic inflammatory state that’s a hallmark of asthma accelerating the atherosclerotic process, which also is inflammatory, she said.

The WHI is funded by the National Heart, Lung, and Blood Institute. Dr. Marmoush reported having no financial conflicts.

[email protected]

ORLANDO – A history of asthma was independently associated with a 24% increase in the risk of new-onset coronary heart disease among postmenopausal women in an analysis from the Women’s Health Initiative.

The study cohort included 90,168 women aged 50-79 years who were free of cardiovascular disease at enrollment in the Women’s Health Initiative (WHI), of whom 6,921 reported a history of physician-diagnosed asthma at baseline. During follow-up in the prospective study, the incidence of a CHD event was 8.6% in subjects with a history of asthma and 6.97% in the no-asthma group, Dr. Fady Y. Marmoush reported at the American Heart Association scientific sessions.

Bruce Jancin/Frontline Medical News

Moreover, the incidence of a first cardiovascular event was 11.6% in the asthma group, compared with 9.7% in the no-asthma controls, added Dr. Marmoush of Memorial Hospital of Rhode Island, Pawtucket.

The asthma group had an absolute 1%-2% greater baseline prevalence of hypertension, diabetes, and family history of CHD. Those with asthma also were more likely to be obese. On the other hand, they were less likely to have ever smoked.

In a multivariate analysis adjusted for these and other potential confounders, including age, dyslipidemia, and waist-hip ratio, the women with a history of asthma had a 24% greater risk of CHD during prospective follow-up in the WHI, as well as a 21% increased rate of cardiovascular events, including stroke, compared with the no-asthma group.

Thus, a history of asthma could be a useful consideration – a tie breaker of sorts – in older women whose calculated 10-year atherosclerotic cardiovascular disease risk based on the standard risk factors places them on the borderline as candidates for statin therapy. The most likely mechanism for the observed association between asthma history and increased risk of cardiovascular disease is the chronic inflammatory state that’s a hallmark of asthma accelerating the atherosclerotic process, which also is inflammatory, she said.

The WHI is funded by the National Heart, Lung, and Blood Institute. Dr. Marmoush reported having no financial conflicts.

[email protected]

ORLANDO – A history of asthma was independently associated with a 24% increase in the risk of new-onset coronary heart disease among postmenopausal women in an analysis from the Women’s Health Initiative.

The study cohort included 90,168 women aged 50-79 years who were free of cardiovascular disease at enrollment in the Women’s Health Initiative (WHI), of whom 6,921 reported a history of physician-diagnosed asthma at baseline. During follow-up in the prospective study, the incidence of a CHD event was 8.6% in subjects with a history of asthma and 6.97% in the no-asthma group, Dr. Fady Y. Marmoush reported at the American Heart Association scientific sessions.

Bruce Jancin/Frontline Medical News

Moreover, the incidence of a first cardiovascular event was 11.6% in the asthma group, compared with 9.7% in the no-asthma controls, added Dr. Marmoush of Memorial Hospital of Rhode Island, Pawtucket.

The asthma group had an absolute 1%-2% greater baseline prevalence of hypertension, diabetes, and family history of CHD. Those with asthma also were more likely to be obese. On the other hand, they were less likely to have ever smoked.

In a multivariate analysis adjusted for these and other potential confounders, including age, dyslipidemia, and waist-hip ratio, the women with a history of asthma had a 24% greater risk of CHD during prospective follow-up in the WHI, as well as a 21% increased rate of cardiovascular events, including stroke, compared with the no-asthma group.

Thus, a history of asthma could be a useful consideration – a tie breaker of sorts – in older women whose calculated 10-year atherosclerotic cardiovascular disease risk based on the standard risk factors places them on the borderline as candidates for statin therapy. The most likely mechanism for the observed association between asthma history and increased risk of cardiovascular disease is the chronic inflammatory state that’s a hallmark of asthma accelerating the atherosclerotic process, which also is inflammatory, she said.

The WHI is funded by the National Heart, Lung, and Blood Institute. Dr. Marmoush reported having no financial conflicts.

[email protected]

BOSTON – Treatment of pneumonitis associated with the PD-1 axis checkpoint inhibitors requires close monitoring of patients and rapid clinical response, an oncologist advised.

“We need to be vigilant when we treat our patients. If a patient has cough or shortness of breath, you take it seriously, even if [it is] a patient who has lung cancer and is a smoker,” said Dr. Scott Gettinger of Yale Cancer Center, New Haven, Conn.

He recommended that before starting patients on a programmed death-1 (PD-1) axis inhibitor such as pembrolizumab (Keytruda) or nivolumab (Opdivo), clinicians get baseline oxygen saturation levels to obtain an objective measure for following patients during therapy.

“When you suspect pneumonitis you have to start steroids right away, or patients can spiral down,” he said at the AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics.

Pneumonitis – characterized by cough, dyspnea, and hypoxia – is a common adverse event associated with PD-1 and PD-ligand 1 (PD-L1) inhibitors, but is rarely seen in patients treated with CTLA-4 inhibitors such as ipilimumab (Yervoy). Current evidence suggests that pneumonitis is more prevalent in patients with non–small-cell lung cancer, occurring in approximately 4%-6% of patients cases, than in melanoma (1%). The difference is probably due to a history of smoking common to the majority of patients with NSCLC, Dr. Gettinger said.

“The other theme that we’re beginning to see is that maybe pneumonitis is a bit more common with anti-PD-1 vs. anti-PD-L1 antibodies,” he said.

It’s theorized that PD-1 inhibitors may block binding of PD-L2 to one of its binding partners, thereby interfering with respiratory tolerance, he said.

Evidence from the pivotal clinical trial of nivolumab in lung cancer (Checkmate 057) suggests that the time to onset of pneumonitis was a median of 31.1 weeks (range 11.7 to 56.9 weeks). The pneumonitis resolved in about 5-7 weeks.

Investigators at Memorial Sloan Kettering Cancer Center in New York City reported at the European Cancer Congress 2015 on pneumonitis in 36 of 653 patients treated with an anti PD-1/PD-L1 monoclonal antibody from 2009 through 2014, 33 of whom had received a PD-1 inhibitor, and 3 of whom received a PD-L1 inhibitor.

They found that pneumonitis in patients with lung cancer tended to resemble chronic obstructive pneumonia, whereas patients with melanoma were more likely to have ground-glass opacifications on radiography. There was a trend, falling just short of significance, toward association of COP-like pneumonitis with development of grade 3 or greater, and with a requirement for more than one type of immunosuppression, compared to other subtypes.

Algorithms for management

Dr. Gettinger briefly outlined an algorithm offered by Bristol-Myers Squibb for management of suspected pulmonary toxicity with nivolumab. For management of patients with grade 1 toxicities (asymptomatic, with radiographic changes only), it recommends that clinicians consider delay of immuno-oncologic (I-O) therapy, monitor for symptoms every 2-3 days, and consider consultations with pulmonary and infectious disease specialists.

For grade 2 pneumonitis, marked by mild to moderate new symptoms, the algorithm calls for clinicians to delay I-O therapy per protocol, consult with pulmonary and ID specialists, monitor symptoms daily and consider hospitalization, start the patient on steroids with 1.0 mg/kg per day methylprednisolone IV or the oral equivalent, and consider bronchoscopy and lung biopsy.

For patients with grade 3 or 4 toxicities, marked by severe new symptoms, new or worsening hypoxia, or other life-threatening symptoms, the algorithm states that clinicians should discontinue I-O therapy, hospitalize the patient, consult with pulmonary and ID, give 2-4 mg/kg per day methylprednisolone IV or the oral equivalent, add prophylactic antibiotics for opportunistic infections, and consider bronchoscopy and lung biopsy.

At Yale, Dr. Gettinger and colleagues, when presented with a symptomatic patient on a PD-axis inhibitor, will first rule out other etiologies such as infection, chronic obstructive pulmonary disease exacerbation, or cancer progression), typically with bronchoscopy.

For patients with moderate pneumonitis, they may treat with prednisone for 1 or 2 weeks, with a 4-6 week taper begun as symptoms start to resolve.

“In a patient who has profound hypoxia and shortness of breath, we may want to go higher: We might give them 2 mg/kg twice a day of [methylprednisolone] in the hospital, wait until they get better, and then slowly taper them, whether it be over 4 or 6 weeks or longer. Occasionally our patients need to get even higher doses of steroids and there’s really nothing to guide us. Who knows if 1 gram of [methylprednisolone] may be better than 60 g of prednisone? But we do it, and patients do get better with the higher doses,” he said.

In rare instances, patients may required other immunosuppressive agents, such as infliximab (Remicade), cyclophosphamide, or mycophenolate mofetil.

Patients who require additional immunosuppressive agents to resolve severe pneumonitis tend to have poor outcomes, Dr. Gettinger said.

Re-challenge of patients with a PD-1 or PD-L1 inhibitor following resolution of pneumonitis appears to be inadvisable for all patients except possibly those with grade 1 (asymptomatic) toxicity, due to the high risk of recurrence, he said.

BOSTON – Treatment of pneumonitis associated with the PD-1 axis checkpoint inhibitors requires close monitoring of patients and rapid clinical response, an oncologist advised.

“We need to be vigilant when we treat our patients. If a patient has cough or shortness of breath, you take it seriously, even if [it is] a patient who has lung cancer and is a smoker,” said Dr. Scott Gettinger of Yale Cancer Center, New Haven, Conn.

He recommended that before starting patients on a programmed death-1 (PD-1) axis inhibitor such as pembrolizumab (Keytruda) or nivolumab (Opdivo), clinicians get baseline oxygen saturation levels to obtain an objective measure for following patients during therapy.

“When you suspect pneumonitis you have to start steroids right away, or patients can spiral down,” he said at the AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics.

Pneumonitis – characterized by cough, dyspnea, and hypoxia – is a common adverse event associated with PD-1 and PD-ligand 1 (PD-L1) inhibitors, but is rarely seen in patients treated with CTLA-4 inhibitors such as ipilimumab (Yervoy). Current evidence suggests that pneumonitis is more prevalent in patients with non–small-cell lung cancer, occurring in approximately 4%-6% of patients cases, than in melanoma (1%). The difference is probably due to a history of smoking common to the majority of patients with NSCLC, Dr. Gettinger said.

“The other theme that we’re beginning to see is that maybe pneumonitis is a bit more common with anti-PD-1 vs. anti-PD-L1 antibodies,” he said.

It’s theorized that PD-1 inhibitors may block binding of PD-L2 to one of its binding partners, thereby interfering with respiratory tolerance, he said.

Evidence from the pivotal clinical trial of nivolumab in lung cancer (Checkmate 057) suggests that the time to onset of pneumonitis was a median of 31.1 weeks (range 11.7 to 56.9 weeks). The pneumonitis resolved in about 5-7 weeks.

Investigators at Memorial Sloan Kettering Cancer Center in New York City reported at the European Cancer Congress 2015 on pneumonitis in 36 of 653 patients treated with an anti PD-1/PD-L1 monoclonal antibody from 2009 through 2014, 33 of whom had received a PD-1 inhibitor, and 3 of whom received a PD-L1 inhibitor.

They found that pneumonitis in patients with lung cancer tended to resemble chronic obstructive pneumonia, whereas patients with melanoma were more likely to have ground-glass opacifications on radiography. There was a trend, falling just short of significance, toward association of COP-like pneumonitis with development of grade 3 or greater, and with a requirement for more than one type of immunosuppression, compared to other subtypes.

Algorithms for management

Dr. Gettinger briefly outlined an algorithm offered by Bristol-Myers Squibb for management of suspected pulmonary toxicity with nivolumab. For management of patients with grade 1 toxicities (asymptomatic, with radiographic changes only), it recommends that clinicians consider delay of immuno-oncologic (I-O) therapy, monitor for symptoms every 2-3 days, and consider consultations with pulmonary and infectious disease specialists.

For grade 2 pneumonitis, marked by mild to moderate new symptoms, the algorithm calls for clinicians to delay I-O therapy per protocol, consult with pulmonary and ID specialists, monitor symptoms daily and consider hospitalization, start the patient on steroids with 1.0 mg/kg per day methylprednisolone IV or the oral equivalent, and consider bronchoscopy and lung biopsy.

For patients with grade 3 or 4 toxicities, marked by severe new symptoms, new or worsening hypoxia, or other life-threatening symptoms, the algorithm states that clinicians should discontinue I-O therapy, hospitalize the patient, consult with pulmonary and ID, give 2-4 mg/kg per day methylprednisolone IV or the oral equivalent, add prophylactic antibiotics for opportunistic infections, and consider bronchoscopy and lung biopsy.

At Yale, Dr. Gettinger and colleagues, when presented with a symptomatic patient on a PD-axis inhibitor, will first rule out other etiologies such as infection, chronic obstructive pulmonary disease exacerbation, or cancer progression), typically with bronchoscopy.

For patients with moderate pneumonitis, they may treat with prednisone for 1 or 2 weeks, with a 4-6 week taper begun as symptoms start to resolve.

“In a patient who has profound hypoxia and shortness of breath, we may want to go higher: We might give them 2 mg/kg twice a day of [methylprednisolone] in the hospital, wait until they get better, and then slowly taper them, whether it be over 4 or 6 weeks or longer. Occasionally our patients need to get even higher doses of steroids and there’s really nothing to guide us. Who knows if 1 gram of [methylprednisolone] may be better than 60 g of prednisone? But we do it, and patients do get better with the higher doses,” he said.

In rare instances, patients may required other immunosuppressive agents, such as infliximab (Remicade), cyclophosphamide, or mycophenolate mofetil.

Patients who require additional immunosuppressive agents to resolve severe pneumonitis tend to have poor outcomes, Dr. Gettinger said.

Re-challenge of patients with a PD-1 or PD-L1 inhibitor following resolution of pneumonitis appears to be inadvisable for all patients except possibly those with grade 1 (asymptomatic) toxicity, due to the high risk of recurrence, he said.

BOSTON – Treatment of pneumonitis associated with the PD-1 axis checkpoint inhibitors requires close monitoring of patients and rapid clinical response, an oncologist advised.

“We need to be vigilant when we treat our patients. If a patient has cough or shortness of breath, you take it seriously, even if [it is] a patient who has lung cancer and is a smoker,” said Dr. Scott Gettinger of Yale Cancer Center, New Haven, Conn.

He recommended that before starting patients on a programmed death-1 (PD-1) axis inhibitor such as pembrolizumab (Keytruda) or nivolumab (Opdivo), clinicians get baseline oxygen saturation levels to obtain an objective measure for following patients during therapy.

“When you suspect pneumonitis you have to start steroids right away, or patients can spiral down,” he said at the AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics.

Pneumonitis – characterized by cough, dyspnea, and hypoxia – is a common adverse event associated with PD-1 and PD-ligand 1 (PD-L1) inhibitors, but is rarely seen in patients treated with CTLA-4 inhibitors such as ipilimumab (Yervoy). Current evidence suggests that pneumonitis is more prevalent in patients with non–small-cell lung cancer, occurring in approximately 4%-6% of patients cases, than in melanoma (1%). The difference is probably due to a history of smoking common to the majority of patients with NSCLC, Dr. Gettinger said.

“The other theme that we’re beginning to see is that maybe pneumonitis is a bit more common with anti-PD-1 vs. anti-PD-L1 antibodies,” he said.

It’s theorized that PD-1 inhibitors may block binding of PD-L2 to one of its binding partners, thereby interfering with respiratory tolerance, he said.

Evidence from the pivotal clinical trial of nivolumab in lung cancer (Checkmate 057) suggests that the time to onset of pneumonitis was a median of 31.1 weeks (range 11.7 to 56.9 weeks). The pneumonitis resolved in about 5-7 weeks.

Investigators at Memorial Sloan Kettering Cancer Center in New York City reported at the European Cancer Congress 2015 on pneumonitis in 36 of 653 patients treated with an anti PD-1/PD-L1 monoclonal antibody from 2009 through 2014, 33 of whom had received a PD-1 inhibitor, and 3 of whom received a PD-L1 inhibitor.

They found that pneumonitis in patients with lung cancer tended to resemble chronic obstructive pneumonia, whereas patients with melanoma were more likely to have ground-glass opacifications on radiography. There was a trend, falling just short of significance, toward association of COP-like pneumonitis with development of grade 3 or greater, and with a requirement for more than one type of immunosuppression, compared to other subtypes.

Algorithms for management

Dr. Gettinger briefly outlined an algorithm offered by Bristol-Myers Squibb for management of suspected pulmonary toxicity with nivolumab. For management of patients with grade 1 toxicities (asymptomatic, with radiographic changes only), it recommends that clinicians consider delay of immuno-oncologic (I-O) therapy, monitor for symptoms every 2-3 days, and consider consultations with pulmonary and infectious disease specialists.

For grade 2 pneumonitis, marked by mild to moderate new symptoms, the algorithm calls for clinicians to delay I-O therapy per protocol, consult with pulmonary and ID specialists, monitor symptoms daily and consider hospitalization, start the patient on steroids with 1.0 mg/kg per day methylprednisolone IV or the oral equivalent, and consider bronchoscopy and lung biopsy.

For patients with grade 3 or 4 toxicities, marked by severe new symptoms, new or worsening hypoxia, or other life-threatening symptoms, the algorithm states that clinicians should discontinue I-O therapy, hospitalize the patient, consult with pulmonary and ID, give 2-4 mg/kg per day methylprednisolone IV or the oral equivalent, add prophylactic antibiotics for opportunistic infections, and consider bronchoscopy and lung biopsy.

At Yale, Dr. Gettinger and colleagues, when presented with a symptomatic patient on a PD-axis inhibitor, will first rule out other etiologies such as infection, chronic obstructive pulmonary disease exacerbation, or cancer progression), typically with bronchoscopy.

For patients with moderate pneumonitis, they may treat with prednisone for 1 or 2 weeks, with a 4-6 week taper begun as symptoms start to resolve.

“In a patient who has profound hypoxia and shortness of breath, we may want to go higher: We might give them 2 mg/kg twice a day of [methylprednisolone] in the hospital, wait until they get better, and then slowly taper them, whether it be over 4 or 6 weeks or longer. Occasionally our patients need to get even higher doses of steroids and there’s really nothing to guide us. Who knows if 1 gram of [methylprednisolone] may be better than 60 g of prednisone? But we do it, and patients do get better with the higher doses,” he said.

In rare instances, patients may required other immunosuppressive agents, such as infliximab (Remicade), cyclophosphamide, or mycophenolate mofetil.

Patients who require additional immunosuppressive agents to resolve severe pneumonitis tend to have poor outcomes, Dr. Gettinger said.

Re-challenge of patients with a PD-1 or PD-L1 inhibitor following resolution of pneumonitis appears to be inadvisable for all patients except possibly those with grade 1 (asymptomatic) toxicity, due to the high risk of recurrence, he said.

SAN FRANCISCO – Pneumococcal vaccines can trigger severe local and systemic inflammatory reactions in patients with cryopyrin-associated periodic syndromes (CAPS), Behçet’s disease, and possibly other autoinflammatory disorders, according to a report from the annual meeting of the American College of Rheumatology.

The European League Against Rheumatism currently recommends pneumococcal vaccine in patients with inflammatory rheumatic diseases, and the Centers for Disease Control and Prevention recommends the vaccine in patients treated with immunosuppressive drugs.

“Careful consideration is warranted when implicating” these “guidelines in these patient populations. The risk of coming down with pneumococcal disease in these patients has to be balanced against the risk of severe reactions. We have here a 100% risk of unusually severe reactions in CAPS and Behçet’s patients with one shot, so we and others find it unethical to continue giving this vaccine to these patients. We no longer do this,” said investigator Dr. Ulrich Walker, a rheumatologist at Basel University in Switzerland and a member of the steering committee for the Ilaris registry, a Novartis database of CAPS patients treated with the company’s biologic canakinumab (Ilaris).

He and his colleagues reported on seven consecutive CAPS patients vaccinated with pneumococcal polysaccharide or conjugate vaccines according to current guidelines. Dr. Walker noted, however, that the Ilaris registry now has at least 14 CAPS patients who ran into serious trouble after receiving the vaccine.

“This is definitely real, and it’s not an adjuvant problem because not all pneumococcal vaccines contain adjuvants.” Instead, vaccine antigens trigger a flare. “The same thing happens with Behçet’s, where we’ve seen clear evidence of the triggering of underlying disease because patients had folliculitis around the vaccination site,” said Dr. Walker, who’s also published on that problem (Rheumatology [Oxford]. 2012 Apr;51[4]:761-2).

Within a few hours of vaccination, all seven patients developed severe, local injection site reactions and fever. Most received antibiotics, and two had to be hospitalized for systemic reactions. Patients ranged in age from 7 to 52 years old.

One patient, a 43-year-old woman, developed a severe headache associated with neck stiffness and photophobia. A florid red rash covered much of the arm where she got the shot. She was admitted to the hospital that evening with a presumed diagnosis of viral meningitis. Lumbar puncture revealed elevated white cells, normal glucose, and elevated protein. She was hospitalized for 18 days.

The reactions occurred with pneumococcal vaccines from three different companies and in patients with different CAPS phenotypes. Four vaccine reactions occurred in temporal association with concomitant coinjections of canakinumab; two reactions were separated by 15 days from the last canakinumab dose; and one reaction occurred in a patient who had never been exposed to canakinumab. Some patients had been vaccinated with a variety of other vaccines without any problem, so “this is something specific to pneumococcal vaccines,” Dr. Walker said.

Symptoms resolved in all the patients in 3-18 days.

The rapid onset, severity, and systemic nature of the reactions suggest that the vaccine triggers tau-like receptor activity, with subsequent inflammasome hyperactivation. “Patients with CAPS already have inflammasome constitutively turned on, so when you activate it even further you come down with a fever. The same thing happens with Behçet’s, which is also thought to be a multigenic disease associated with aberrant inflammasome activation,” Dr. Walker said.

The findings were so strong that the investigators are now testing low-dose pneumococcal vaccine for diagnostic screening before genetic testing for CAPs, Behçet’s, and some other autoimmune diseases. “A similar problem has been described in patients with mevalonate kinase deficiency,” Dr. Walker noted.

Novartis is worried the problem will be associated with canakinumab, but it doesn’t seem to be. “We had a lot of discussion about this and decided that we need to bring this out. Patients need to be aware of this,” said Dr. Jasmin Kümmerle-Deschner, a pediatrician at the University Hospital of Tübingen, Germany, and also a member of the Ilaris registry steering committee.

Dr. Walker disclosed financial relationships with Novartis, as did Dr. Kümmerle-Deschner, who also reported involvement with Sobi.

[email protected]

SAN FRANCISCO – Pneumococcal vaccines can trigger severe local and systemic inflammatory reactions in patients with cryopyrin-associated periodic syndromes (CAPS), Behçet’s disease, and possibly other autoinflammatory disorders, according to a report from the annual meeting of the American College of Rheumatology.

The European League Against Rheumatism currently recommends pneumococcal vaccine in patients with inflammatory rheumatic diseases, and the Centers for Disease Control and Prevention recommends the vaccine in patients treated with immunosuppressive drugs.

“Careful consideration is warranted when implicating” these “guidelines in these patient populations. The risk of coming down with pneumococcal disease in these patients has to be balanced against the risk of severe reactions. We have here a 100% risk of unusually severe reactions in CAPS and Behçet’s patients with one shot, so we and others find it unethical to continue giving this vaccine to these patients. We no longer do this,” said investigator Dr. Ulrich Walker, a rheumatologist at Basel University in Switzerland and a member of the steering committee for the Ilaris registry, a Novartis database of CAPS patients treated with the company’s biologic canakinumab (Ilaris).

He and his colleagues reported on seven consecutive CAPS patients vaccinated with pneumococcal polysaccharide or conjugate vaccines according to current guidelines. Dr. Walker noted, however, that the Ilaris registry now has at least 14 CAPS patients who ran into serious trouble after receiving the vaccine.

“This is definitely real, and it’s not an adjuvant problem because not all pneumococcal vaccines contain adjuvants.” Instead, vaccine antigens trigger a flare. “The same thing happens with Behçet’s, where we’ve seen clear evidence of the triggering of underlying disease because patients had folliculitis around the vaccination site,” said Dr. Walker, who’s also published on that problem (Rheumatology [Oxford]. 2012 Apr;51[4]:761-2).

Within a few hours of vaccination, all seven patients developed severe, local injection site reactions and fever. Most received antibiotics, and two had to be hospitalized for systemic reactions. Patients ranged in age from 7 to 52 years old.

One patient, a 43-year-old woman, developed a severe headache associated with neck stiffness and photophobia. A florid red rash covered much of the arm where she got the shot. She was admitted to the hospital that evening with a presumed diagnosis of viral meningitis. Lumbar puncture revealed elevated white cells, normal glucose, and elevated protein. She was hospitalized for 18 days.

The reactions occurred with pneumococcal vaccines from three different companies and in patients with different CAPS phenotypes. Four vaccine reactions occurred in temporal association with concomitant coinjections of canakinumab; two reactions were separated by 15 days from the last canakinumab dose; and one reaction occurred in a patient who had never been exposed to canakinumab. Some patients had been vaccinated with a variety of other vaccines without any problem, so “this is something specific to pneumococcal vaccines,” Dr. Walker said.

Symptoms resolved in all the patients in 3-18 days.

The rapid onset, severity, and systemic nature of the reactions suggest that the vaccine triggers tau-like receptor activity, with subsequent inflammasome hyperactivation. “Patients with CAPS already have inflammasome constitutively turned on, so when you activate it even further you come down with a fever. The same thing happens with Behçet’s, which is also thought to be a multigenic disease associated with aberrant inflammasome activation,” Dr. Walker said.

The findings were so strong that the investigators are now testing low-dose pneumococcal vaccine for diagnostic screening before genetic testing for CAPs, Behçet’s, and some other autoimmune diseases. “A similar problem has been described in patients with mevalonate kinase deficiency,” Dr. Walker noted.

Novartis is worried the problem will be associated with canakinumab, but it doesn’t seem to be. “We had a lot of discussion about this and decided that we need to bring this out. Patients need to be aware of this,” said Dr. Jasmin Kümmerle-Deschner, a pediatrician at the University Hospital of Tübingen, Germany, and also a member of the Ilaris registry steering committee.

Dr. Walker disclosed financial relationships with Novartis, as did Dr. Kümmerle-Deschner, who also reported involvement with Sobi.

[email protected]

SAN FRANCISCO – Pneumococcal vaccines can trigger severe local and systemic inflammatory reactions in patients with cryopyrin-associated periodic syndromes (CAPS), Behçet’s disease, and possibly other autoinflammatory disorders, according to a report from the annual meeting of the American College of Rheumatology.

The European League Against Rheumatism currently recommends pneumococcal vaccine in patients with inflammatory rheumatic diseases, and the Centers for Disease Control and Prevention recommends the vaccine in patients treated with immunosuppressive drugs.

“Careful consideration is warranted when implicating” these “guidelines in these patient populations. The risk of coming down with pneumococcal disease in these patients has to be balanced against the risk of severe reactions. We have here a 100% risk of unusually severe reactions in CAPS and Behçet’s patients with one shot, so we and others find it unethical to continue giving this vaccine to these patients. We no longer do this,” said investigator Dr. Ulrich Walker, a rheumatologist at Basel University in Switzerland and a member of the steering committee for the Ilaris registry, a Novartis database of CAPS patients treated with the company’s biologic canakinumab (Ilaris).

He and his colleagues reported on seven consecutive CAPS patients vaccinated with pneumococcal polysaccharide or conjugate vaccines according to current guidelines. Dr. Walker noted, however, that the Ilaris registry now has at least 14 CAPS patients who ran into serious trouble after receiving the vaccine.

“This is definitely real, and it’s not an adjuvant problem because not all pneumococcal vaccines contain adjuvants.” Instead, vaccine antigens trigger a flare. “The same thing happens with Behçet’s, where we’ve seen clear evidence of the triggering of underlying disease because patients had folliculitis around the vaccination site,” said Dr. Walker, who’s also published on that problem (Rheumatology [Oxford]. 2012 Apr;51[4]:761-2).

Within a few hours of vaccination, all seven patients developed severe, local injection site reactions and fever. Most received antibiotics, and two had to be hospitalized for systemic reactions. Patients ranged in age from 7 to 52 years old.

One patient, a 43-year-old woman, developed a severe headache associated with neck stiffness and photophobia. A florid red rash covered much of the arm where she got the shot. She was admitted to the hospital that evening with a presumed diagnosis of viral meningitis. Lumbar puncture revealed elevated white cells, normal glucose, and elevated protein. She was hospitalized for 18 days.

The reactions occurred with pneumococcal vaccines from three different companies and in patients with different CAPS phenotypes. Four vaccine reactions occurred in temporal association with concomitant coinjections of canakinumab; two reactions were separated by 15 days from the last canakinumab dose; and one reaction occurred in a patient who had never been exposed to canakinumab. Some patients had been vaccinated with a variety of other vaccines without any problem, so “this is something specific to pneumococcal vaccines,” Dr. Walker said.

Symptoms resolved in all the patients in 3-18 days.

The rapid onset, severity, and systemic nature of the reactions suggest that the vaccine triggers tau-like receptor activity, with subsequent inflammasome hyperactivation. “Patients with CAPS already have inflammasome constitutively turned on, so when you activate it even further you come down with a fever. The same thing happens with Behçet’s, which is also thought to be a multigenic disease associated with aberrant inflammasome activation,” Dr. Walker said.

The findings were so strong that the investigators are now testing low-dose pneumococcal vaccine for diagnostic screening before genetic testing for CAPs, Behçet’s, and some other autoimmune diseases. “A similar problem has been described in patients with mevalonate kinase deficiency,” Dr. Walker noted.

Novartis is worried the problem will be associated with canakinumab, but it doesn’t seem to be. “We had a lot of discussion about this and decided that we need to bring this out. Patients need to be aware of this,” said Dr. Jasmin Kümmerle-Deschner, a pediatrician at the University Hospital of Tübingen, Germany, and also a member of the Ilaris registry steering committee.

Dr. Walker disclosed financial relationships with Novartis, as did Dr. Kümmerle-Deschner, who also reported involvement with Sobi.

[email protected]

An oral inhibitor of respiratory syncytial virus replication, currently called ALS-008176, significantly reduced total viral load, peak viral load, duration of viral shedding, and clinical symptoms in a small proof-of-concept study funded by the drug’s manufacturer and published online Nov. 18 in the New England Journal of Medicine.

These findings are particularly encouraging because at present, the standard of care for RSV infection is limited to supportive care only, said Dr. John P. DeVincenzo of the departments of pediatrics, microbiology, immunology, and biochemistry, University of Tennessee, and the Children’s Foundation Research Institute at Le Bonheur Children’s Hospital, both in Memphis.

©Dr. Craig Lyerla/CDC

Dr. DeVincenzo and his colleagues performed this randomized, double-blind trial during three separate study periods in which up to 22 healthy adults were confined to a special quarantine unit for 2 weeks at a time. All 62 participants were inoculated intranasally with a clinical strain of RSV and monitored twice daily for the development of RSV infection via assays of fresh nasal washings. The participants were randomly assigned to receive the first dose of ALS-008176 or a matching placebo about 12 hours after the detection of RSV, or on the morning of day 6, whichever came first.

The active drug or the placebo were administered orally every 12 hours for 5 days, for a total of 10 doses. Three dosing regimens were assessed: In the first study period, participants were given a single loading dose of 750 mg followed by nine maintenance doses of 500 mg; in the second period, participants were given a single loading dose of 750 mg followed by nine maintenance doses of 150 mg; and in the third period, participants were given 10 doses of 375 mg each. A total of 35 study participants developed RSV infection.

Compared with placebo, all three dosing regimens significantly reduced viral load within 12 hours of starting treatment: by 88.0% in the first study period, by 85.3% in the second, and by 73.4% in the third. The mean interval until RSV RNA became undetectable ranged from 1.3 to 2.3 days for the three active-treatment groups, compared with 7.2 days for placebo. RSV RNA became undetectable within 4.5 days for all participants who received ALS-0081, compared with 11 days for those who received placebo.

In addition, mean peak viral loads were lower for all three dosing regimens than for placebo. “At the time that the peak viral load occurred in the placebo group, the mean viral load in each of the 3 ALS-008176 treatment groups was more than 1,000 times as low,” wrote Dr. DeVincenzo and his associates (N Engl J Med. 2015 Nov 19;373:2048-58. doi:10.1056/NEJMoa1413275).

As important, RSV symptoms were much less severe in all three active-treatment groups than in the placebo group, as assessed subjectively via symptom scores and objectively via the quantity of nasal mucus produced.

The small study population limited the ability to detect potential safety concerns. Nevertheless, “no serious adverse events, premature discontinuation of the study drug, or clinically significant, treatment-related adverse events were observed in any participants in the intention-to-treat population,” the investigators added.

They noted that people who are infected with RSV under natural circumstances, particularly infants, typically present later in the course of the disease, only after patients or caregivers realize that the illness is not due to a simple cold. Thus, their disease severity would be worse than that of these study participants by the time ALS-008176 could be administered. “Therefore, it may be inappropriate to directly extrapolate the results of this study to a clinical setting,” Dr. DeVincenzo and his associates said.

Alios BioPharma, maker of ALS-008176, funded the study. Dr. DeVincenzo disclosed ties with Alios BioPharma, Gilead Sciences, Alnylam Pharmaceuticals, Microdose Therapeutx–Teva, Janssen, ADMA Biologics, and MedImmune/AstraZeneca. His associates reported ties to Alios and Retroscreen Virology.

An oral inhibitor of respiratory syncytial virus replication, currently called ALS-008176, significantly reduced total viral load, peak viral load, duration of viral shedding, and clinical symptoms in a small proof-of-concept study funded by the drug’s manufacturer and published online Nov. 18 in the New England Journal of Medicine.

These findings are particularly encouraging because at present, the standard of care for RSV infection is limited to supportive care only, said Dr. John P. DeVincenzo of the departments of pediatrics, microbiology, immunology, and biochemistry, University of Tennessee, and the Children’s Foundation Research Institute at Le Bonheur Children’s Hospital, both in Memphis.

©Dr. Craig Lyerla/CDC

Dr. DeVincenzo and his colleagues performed this randomized, double-blind trial during three separate study periods in which up to 22 healthy adults were confined to a special quarantine unit for 2 weeks at a time. All 62 participants were inoculated intranasally with a clinical strain of RSV and monitored twice daily for the development of RSV infection via assays of fresh nasal washings. The participants were randomly assigned to receive the first dose of ALS-008176 or a matching placebo about 12 hours after the detection of RSV, or on the morning of day 6, whichever came first.

The active drug or the placebo were administered orally every 12 hours for 5 days, for a total of 10 doses. Three dosing regimens were assessed: In the first study period, participants were given a single loading dose of 750 mg followed by nine maintenance doses of 500 mg; in the second period, participants were given a single loading dose of 750 mg followed by nine maintenance doses of 150 mg; and in the third period, participants were given 10 doses of 375 mg each. A total of 35 study participants developed RSV infection.

Compared with placebo, all three dosing regimens significantly reduced viral load within 12 hours of starting treatment: by 88.0% in the first study period, by 85.3% in the second, and by 73.4% in the third. The mean interval until RSV RNA became undetectable ranged from 1.3 to 2.3 days for the three active-treatment groups, compared with 7.2 days for placebo. RSV RNA became undetectable within 4.5 days for all participants who received ALS-0081, compared with 11 days for those who received placebo.

In addition, mean peak viral loads were lower for all three dosing regimens than for placebo. “At the time that the peak viral load occurred in the placebo group, the mean viral load in each of the 3 ALS-008176 treatment groups was more than 1,000 times as low,” wrote Dr. DeVincenzo and his associates (N Engl J Med. 2015 Nov 19;373:2048-58. doi:10.1056/NEJMoa1413275).

As important, RSV symptoms were much less severe in all three active-treatment groups than in the placebo group, as assessed subjectively via symptom scores and objectively via the quantity of nasal mucus produced.

The small study population limited the ability to detect potential safety concerns. Nevertheless, “no serious adverse events, premature discontinuation of the study drug, or clinically significant, treatment-related adverse events were observed in any participants in the intention-to-treat population,” the investigators added.

They noted that people who are infected with RSV under natural circumstances, particularly infants, typically present later in the course of the disease, only after patients or caregivers realize that the illness is not due to a simple cold. Thus, their disease severity would be worse than that of these study participants by the time ALS-008176 could be administered. “Therefore, it may be inappropriate to directly extrapolate the results of this study to a clinical setting,” Dr. DeVincenzo and his associates said.

Alios BioPharma, maker of ALS-008176, funded the study. Dr. DeVincenzo disclosed ties with Alios BioPharma, Gilead Sciences, Alnylam Pharmaceuticals, Microdose Therapeutx–Teva, Janssen, ADMA Biologics, and MedImmune/AstraZeneca. His associates reported ties to Alios and Retroscreen Virology.

An oral inhibitor of respiratory syncytial virus replication, currently called ALS-008176, significantly reduced total viral load, peak viral load, duration of viral shedding, and clinical symptoms in a small proof-of-concept study funded by the drug’s manufacturer and published online Nov. 18 in the New England Journal of Medicine.

These findings are particularly encouraging because at present, the standard of care for RSV infection is limited to supportive care only, said Dr. John P. DeVincenzo of the departments of pediatrics, microbiology, immunology, and biochemistry, University of Tennessee, and the Children’s Foundation Research Institute at Le Bonheur Children’s Hospital, both in Memphis.

©Dr. Craig Lyerla/CDC

Dr. DeVincenzo and his colleagues performed this randomized, double-blind trial during three separate study periods in which up to 22 healthy adults were confined to a special quarantine unit for 2 weeks at a time. All 62 participants were inoculated intranasally with a clinical strain of RSV and monitored twice daily for the development of RSV infection via assays of fresh nasal washings. The participants were randomly assigned to receive the first dose of ALS-008176 or a matching placebo about 12 hours after the detection of RSV, or on the morning of day 6, whichever came first.

The active drug or the placebo were administered orally every 12 hours for 5 days, for a total of 10 doses. Three dosing regimens were assessed: In the first study period, participants were given a single loading dose of 750 mg followed by nine maintenance doses of 500 mg; in the second period, participants were given a single loading dose of 750 mg followed by nine maintenance doses of 150 mg; and in the third period, participants were given 10 doses of 375 mg each. A total of 35 study participants developed RSV infection.

Compared with placebo, all three dosing regimens significantly reduced viral load within 12 hours of starting treatment: by 88.0% in the first study period, by 85.3% in the second, and by 73.4% in the third. The mean interval until RSV RNA became undetectable ranged from 1.3 to 2.3 days for the three active-treatment groups, compared with 7.2 days for placebo. RSV RNA became undetectable within 4.5 days for all participants who received ALS-0081, compared with 11 days for those who received placebo.

In addition, mean peak viral loads were lower for all three dosing regimens than for placebo. “At the time that the peak viral load occurred in the placebo group, the mean viral load in each of the 3 ALS-008176 treatment groups was more than 1,000 times as low,” wrote Dr. DeVincenzo and his associates (N Engl J Med. 2015 Nov 19;373:2048-58. doi:10.1056/NEJMoa1413275).

As important, RSV symptoms were much less severe in all three active-treatment groups than in the placebo group, as assessed subjectively via symptom scores and objectively via the quantity of nasal mucus produced.

The small study population limited the ability to detect potential safety concerns. Nevertheless, “no serious adverse events, premature discontinuation of the study drug, or clinically significant, treatment-related adverse events were observed in any participants in the intention-to-treat population,” the investigators added.

They noted that people who are infected with RSV under natural circumstances, particularly infants, typically present later in the course of the disease, only after patients or caregivers realize that the illness is not due to a simple cold. Thus, their disease severity would be worse than that of these study participants by the time ALS-008176 could be administered. “Therefore, it may be inappropriate to directly extrapolate the results of this study to a clinical setting,” Dr. DeVincenzo and his associates said.

Alios BioPharma, maker of ALS-008176, funded the study. Dr. DeVincenzo disclosed ties with Alios BioPharma, Gilead Sciences, Alnylam Pharmaceuticals, Microdose Therapeutx–Teva, Janssen, ADMA Biologics, and MedImmune/AstraZeneca. His associates reported ties to Alios and Retroscreen Virology.