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Preterm infants at high risk for RSV morbidity without immunoprophylaxis
SAN FRANCISCO – Preterm infants born at 29-35 weeks’ gestation and hospitalized for respiratory syncytial virus (RSV) can experience particularly severe morbidity if they have not received immunoprophylaxis, according to new industry-funded research.
Across two RSV seasons at more than 40 study sites, nearly half of preterm infants admitted for lab-confirmed RSV required ICU admission, and one in five required invasive mechanical ventilation.
“Severity of illness and resource utilization are greatest in infants aged less than 3 months,” said John DeVincenzo, MD, professor in the pediatric infectious diseases division at the University of Tennessee, Memphis. “The results from the two seasons were consistent with one another and with previous and recent studies,” he said at the annual Pediatric Academic Societies meeting.
Previous research has shown that preterm infants born at 35 weeks or less gestation have a higher risk of RSV-related hospitalizations and subsequent morbidity, and that monthly immunoprophylaxis reduced RSV-related hospitalization in high-risk infants, including preterm infants.
Until 2014, the American Academy of Pediatrics recommended respiratory syncytial virus (RSV) immunoprophylaxis for all preterm infants under 32 weeks’ gestation and for infants between 32-35 weeks with additional risk factors, such as chronic lung disease or cyanotic heart disease (Pediatrics. 2003 Dec;112[6]:1442-6).
New recommendations in 2014 restricted immunoprophylaxis to preterm infants younger than 29 weeks’ gestational age unless they had additional risk factors such as chronic lung disease or hemodynamically significant heart disease (Pediatrics. 2014 Aug. doi: 10.1542/peds.2014-1665).
This study compared outcomes among all preterm infants born at 29-35 weeks’ gestation who were hospitalized during RSV season (October-April) for at least 24 hours with laboratory-confirmed RSV and who had not received RSV immunoprophylaxis within the 35 days before symptom onset. The 1,378 infants were younger than age 12 months when they were hospitalized at one of 43 sites during the 2014-2015 RSV season or one of 42 sites in the 2015-2016 season.
Of the 702 preterm infants hospitalized in 2014-2015, 42% were admitted to intensive care, and 20% needed invasive mechanical ventilation. Nearly half (48%) of the 676 infants admitted during the 2015-2016 season went to the ICU, and 19% required mechanical ventilation. One infant died of RSV in each season.
Throughout both seasons, more than three quarters (78%) of all RSV hospitalizations were infants younger than 6 months old. In 2014-2015, infants younger than 6 months accounted for 87% of all RSV admissions to the ICU and 92% of those needing mechanical ventilation. Similarly, young infants accounted for 81% of ICU admissions and 90% of RSV-related mechanical ventilation during the 2015-2016 season. Overall, preterm infants younger than 6 months old without immunoprophylaxis accounted for 84% of RSV-related ICU admissions and 91% of RSV-related mechanical ventilation.
The younger the infants were, the more likely they were to need ICU care and/or mechanical ventilation, the researchers found. Across both seasons, 56% of infants under 3 months old with RSV were admitted to the ICU, compared to 34% of those between 3 and 12 months old. Likewise, 29% of those under 3 months old and 10% of those between 3 and 12 months needed invasive mechanical ventilation.
Nearly half (46%) of all infants hospitalized for RSV had been discharged from their birth hospital within the previous 30 days, and 82% of all hospitalizations occurred within 2 months of birth discharge.
A cost analysis revealed that mean hospital charges for RSV-related hospitalizations of preterm infants ranged from $31,366 for 35-week gestation infants between ages 3-6 months to $122,301 for infants under 3 months old born between 29-32 weeks.
AstraZeneca/MedImmune funded the study. Dr. DeVincenzo and a number of his colleagues have received grants/research support from AstraZeneca/MedImmune, and some of his colleagues are or were AstraZeneca employees.
SAN FRANCISCO – Preterm infants born at 29-35 weeks’ gestation and hospitalized for respiratory syncytial virus (RSV) can experience particularly severe morbidity if they have not received immunoprophylaxis, according to new industry-funded research.
Across two RSV seasons at more than 40 study sites, nearly half of preterm infants admitted for lab-confirmed RSV required ICU admission, and one in five required invasive mechanical ventilation.
“Severity of illness and resource utilization are greatest in infants aged less than 3 months,” said John DeVincenzo, MD, professor in the pediatric infectious diseases division at the University of Tennessee, Memphis. “The results from the two seasons were consistent with one another and with previous and recent studies,” he said at the annual Pediatric Academic Societies meeting.
Previous research has shown that preterm infants born at 35 weeks or less gestation have a higher risk of RSV-related hospitalizations and subsequent morbidity, and that monthly immunoprophylaxis reduced RSV-related hospitalization in high-risk infants, including preterm infants.
Until 2014, the American Academy of Pediatrics recommended respiratory syncytial virus (RSV) immunoprophylaxis for all preterm infants under 32 weeks’ gestation and for infants between 32-35 weeks with additional risk factors, such as chronic lung disease or cyanotic heart disease (Pediatrics. 2003 Dec;112[6]:1442-6).
New recommendations in 2014 restricted immunoprophylaxis to preterm infants younger than 29 weeks’ gestational age unless they had additional risk factors such as chronic lung disease or hemodynamically significant heart disease (Pediatrics. 2014 Aug. doi: 10.1542/peds.2014-1665).
This study compared outcomes among all preterm infants born at 29-35 weeks’ gestation who were hospitalized during RSV season (October-April) for at least 24 hours with laboratory-confirmed RSV and who had not received RSV immunoprophylaxis within the 35 days before symptom onset. The 1,378 infants were younger than age 12 months when they were hospitalized at one of 43 sites during the 2014-2015 RSV season or one of 42 sites in the 2015-2016 season.
Of the 702 preterm infants hospitalized in 2014-2015, 42% were admitted to intensive care, and 20% needed invasive mechanical ventilation. Nearly half (48%) of the 676 infants admitted during the 2015-2016 season went to the ICU, and 19% required mechanical ventilation. One infant died of RSV in each season.
Throughout both seasons, more than three quarters (78%) of all RSV hospitalizations were infants younger than 6 months old. In 2014-2015, infants younger than 6 months accounted for 87% of all RSV admissions to the ICU and 92% of those needing mechanical ventilation. Similarly, young infants accounted for 81% of ICU admissions and 90% of RSV-related mechanical ventilation during the 2015-2016 season. Overall, preterm infants younger than 6 months old without immunoprophylaxis accounted for 84% of RSV-related ICU admissions and 91% of RSV-related mechanical ventilation.
The younger the infants were, the more likely they were to need ICU care and/or mechanical ventilation, the researchers found. Across both seasons, 56% of infants under 3 months old with RSV were admitted to the ICU, compared to 34% of those between 3 and 12 months old. Likewise, 29% of those under 3 months old and 10% of those between 3 and 12 months needed invasive mechanical ventilation.
Nearly half (46%) of all infants hospitalized for RSV had been discharged from their birth hospital within the previous 30 days, and 82% of all hospitalizations occurred within 2 months of birth discharge.
A cost analysis revealed that mean hospital charges for RSV-related hospitalizations of preterm infants ranged from $31,366 for 35-week gestation infants between ages 3-6 months to $122,301 for infants under 3 months old born between 29-32 weeks.
AstraZeneca/MedImmune funded the study. Dr. DeVincenzo and a number of his colleagues have received grants/research support from AstraZeneca/MedImmune, and some of his colleagues are or were AstraZeneca employees.
SAN FRANCISCO – Preterm infants born at 29-35 weeks’ gestation and hospitalized for respiratory syncytial virus (RSV) can experience particularly severe morbidity if they have not received immunoprophylaxis, according to new industry-funded research.
Across two RSV seasons at more than 40 study sites, nearly half of preterm infants admitted for lab-confirmed RSV required ICU admission, and one in five required invasive mechanical ventilation.
“Severity of illness and resource utilization are greatest in infants aged less than 3 months,” said John DeVincenzo, MD, professor in the pediatric infectious diseases division at the University of Tennessee, Memphis. “The results from the two seasons were consistent with one another and with previous and recent studies,” he said at the annual Pediatric Academic Societies meeting.
Previous research has shown that preterm infants born at 35 weeks or less gestation have a higher risk of RSV-related hospitalizations and subsequent morbidity, and that monthly immunoprophylaxis reduced RSV-related hospitalization in high-risk infants, including preterm infants.
Until 2014, the American Academy of Pediatrics recommended respiratory syncytial virus (RSV) immunoprophylaxis for all preterm infants under 32 weeks’ gestation and for infants between 32-35 weeks with additional risk factors, such as chronic lung disease or cyanotic heart disease (Pediatrics. 2003 Dec;112[6]:1442-6).
New recommendations in 2014 restricted immunoprophylaxis to preterm infants younger than 29 weeks’ gestational age unless they had additional risk factors such as chronic lung disease or hemodynamically significant heart disease (Pediatrics. 2014 Aug. doi: 10.1542/peds.2014-1665).
This study compared outcomes among all preterm infants born at 29-35 weeks’ gestation who were hospitalized during RSV season (October-April) for at least 24 hours with laboratory-confirmed RSV and who had not received RSV immunoprophylaxis within the 35 days before symptom onset. The 1,378 infants were younger than age 12 months when they were hospitalized at one of 43 sites during the 2014-2015 RSV season or one of 42 sites in the 2015-2016 season.
Of the 702 preterm infants hospitalized in 2014-2015, 42% were admitted to intensive care, and 20% needed invasive mechanical ventilation. Nearly half (48%) of the 676 infants admitted during the 2015-2016 season went to the ICU, and 19% required mechanical ventilation. One infant died of RSV in each season.
Throughout both seasons, more than three quarters (78%) of all RSV hospitalizations were infants younger than 6 months old. In 2014-2015, infants younger than 6 months accounted for 87% of all RSV admissions to the ICU and 92% of those needing mechanical ventilation. Similarly, young infants accounted for 81% of ICU admissions and 90% of RSV-related mechanical ventilation during the 2015-2016 season. Overall, preterm infants younger than 6 months old without immunoprophylaxis accounted for 84% of RSV-related ICU admissions and 91% of RSV-related mechanical ventilation.
The younger the infants were, the more likely they were to need ICU care and/or mechanical ventilation, the researchers found. Across both seasons, 56% of infants under 3 months old with RSV were admitted to the ICU, compared to 34% of those between 3 and 12 months old. Likewise, 29% of those under 3 months old and 10% of those between 3 and 12 months needed invasive mechanical ventilation.
Nearly half (46%) of all infants hospitalized for RSV had been discharged from their birth hospital within the previous 30 days, and 82% of all hospitalizations occurred within 2 months of birth discharge.
A cost analysis revealed that mean hospital charges for RSV-related hospitalizations of preterm infants ranged from $31,366 for 35-week gestation infants between ages 3-6 months to $122,301 for infants under 3 months old born between 29-32 weeks.
AstraZeneca/MedImmune funded the study. Dr. DeVincenzo and a number of his colleagues have received grants/research support from AstraZeneca/MedImmune, and some of his colleagues are or were AstraZeneca employees.
AT PAS 17
Key clinical point: Preterm infants, particularly those younger than 3 months, can experience severe respiratory syncytial virus (RSV) illness without immunoprophylaxis.
Major finding: Of the 702 preterm infants hospitalized during 2014-2015, 42% went to the ICU and 20% needed invasive mechanical ventilation. Nearly half (48%) of the 676 infants admitted during 2015-2016 went to the ICU and 19% required mechanical ventilation.
Data source: An analysis of 1,378 preterm infants born at 29-35 weeks’ gestation and hospitalized at under 1 year for lab-confirmed RSV during the 2014-2015 and 2015-2016 RSV seasons.
Disclosures: AstraZeneca/MedImmune funded the study. Dr. DeVincenzo and a number of his colleagues have received grants/research support from AstraZeneca/MedImmune, and some of his colleagues are or were AstraZeneca employees.
Mepolizumab proves effective for eosinophilic granulomatosis with polyangiitis
Adding mepolizumab to standard-of-care glucocorticoids with or without immunosuppressive agents can induce remission in many patients who have eosinophilic granulomatosis with polyangiitis (EGPA), according to a report published online May 18 in the New England Journal of Medicine.
EGPA, a rare disorder characterized by asthma, sinusitis, pulmonary infiltrates, neuropathy, and eosinophilic vasculitis in at least one end-organ, frequently relapses despite glucocorticoid therapy or fails to respond adequately to the treatment. Patients have elevated levels of the cytokine interleukin-5, which regulates eosinophil maturation, differentiation, and proliferation. Neutralizing this cytokine is thought to be a potential therapeutic approach, said Michael E. Wechsler, MD, of National Jewish Health, Denver, and his associates.
Proof-of-concept studies have demonstrated the efficacy of subcutaneous mepolizumab, an anti–interleukin-5 monoclonal antibody, in EGPA, so Dr. Wechsler and his colleagues assessed the safety and efficacy of a 1-year course of mepolizumab (300 mg) as add-on therapy in a double-blind, randomized, phase III trial, which involved 136 adults treated at 31 academic medical centers in nine countries. The study was sponsored by GlaxoSmithKline and the National Institute of Allergy and Infectious Diseases.
The first of two primary efficacy endpoints was the total accrued weeks of remission. A total of 28% of the mepolizumab group achieved remission for at least 24 weeks, compared with only 3% of the placebo group, for an odds ratio of 5.91.
The second primary efficacy endpoint was the proportion of patients in remission at both week 36 and week 48. Again, significantly more patients in the mepolizumab group (32%) than in the placebo group (3%) met this end point (OR, 16.74).
Mepolizumab also proved superior to placebo regarding numerous secondary endpoints, the investigators said (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMoa1702079). More patients who received active treatment achieved remission within the first 6 months of treatment and remained in remission for a full year (19% vs. 1%; OR, 19.65). The time to first relapse was significantly longer for mepolizumab, with only 56% of that group experiencing a relapse within 1 year, compared with 82% of the placebo group. The annualized relapse rate was half as high with mepolizumab (1.14) as with placebo (2.27).
In addition, patients in the mepolizumab group were more likely to reduce their doses of glucocorticoids (OR, 0.20) or discontinue the drugs altogether (18% vs. 3% taking placebo).
Mepolizumab was most effective among the 79 patients who had a high absolute eosinophil count (150 or more cells per cubic millimeter) at baseline. In this subgroup, 33% of patients taking mepolizumab achieved remission for 6 months or more, compared with none of the patients taking placebo (OR, 26.1).
Although the effectiveness of mepolizumab in this difficult-to-treat population was noteworthy, only about half of the patients given the active treatment achieved remission as defined by the study protocol. It is unclear why the drug was not effective in the other half of patients. One possible reason is that some manifestations of the disorder are not driven by eosinophils. Another is that nonresponsive patients may have sustained longstanding, irreversible vasculitic damage that is no longer amenable to anti–interleukin-5 therapy.
Alternatively, it’s possible that mepolizumab reduced eosinophils in the blood but not those in the body tissues of nonresponsive patients or that the patients who didn’t respond well simply required a higher dose of the drug, Dr. Wechsler and his associates said.
The NIAID is now supporting a study of blood, urine, sputum, and tissue samples from some of these participants “to address questions related to disease risk and pathological features, as well as response to treatment,” they added.
Many authors reported receiving payments from pharmaceutical companies, including several from GlaxoSmithKline. Four authors are employees of the company.
The study by Michael E. Wechsler, MD, and his associates can be considered proof of concept. Now, researchers must turn to identifying biomarkers that predict the success or failure of mepolizumab in patients.
Researchers must also elucidate the fate of eosinophils in the tissues, especially in vasculitic lesions, after treatment with mepolizumab. And they should address possible synergistic activity when the drug is given together with immunosuppressants such as azathioprine and cyclophosphamide.
In addition, future studies should include patients who have organ-threatening or life-threatening eosinophilic granulomatosis with polyangiitis, who were excluded from this trial but who are most in need of novel treatments.
Ratko Djukanovic, MD, is with the University of Southampton (England) and the National Institute for Health Research Southampton Biomedical Research Centre. Paul M. O’Byrne, MD, is with the Firestone Institute for Respiratory Health within St. Joseph’s Healthcare and McMaster University in Hamilton, Ont. Dr. Djukanovic and Dr. O’Byrne both reported financial relationships with pharmaceutical companies outside their editorial. They made these remarks in an editorial accompanying Dr. Wechsler and colleagues’ report (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMe1704402).
The study by Michael E. Wechsler, MD, and his associates can be considered proof of concept. Now, researchers must turn to identifying biomarkers that predict the success or failure of mepolizumab in patients.
Researchers must also elucidate the fate of eosinophils in the tissues, especially in vasculitic lesions, after treatment with mepolizumab. And they should address possible synergistic activity when the drug is given together with immunosuppressants such as azathioprine and cyclophosphamide.
In addition, future studies should include patients who have organ-threatening or life-threatening eosinophilic granulomatosis with polyangiitis, who were excluded from this trial but who are most in need of novel treatments.
Ratko Djukanovic, MD, is with the University of Southampton (England) and the National Institute for Health Research Southampton Biomedical Research Centre. Paul M. O’Byrne, MD, is with the Firestone Institute for Respiratory Health within St. Joseph’s Healthcare and McMaster University in Hamilton, Ont. Dr. Djukanovic and Dr. O’Byrne both reported financial relationships with pharmaceutical companies outside their editorial. They made these remarks in an editorial accompanying Dr. Wechsler and colleagues’ report (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMe1704402).
The study by Michael E. Wechsler, MD, and his associates can be considered proof of concept. Now, researchers must turn to identifying biomarkers that predict the success or failure of mepolizumab in patients.
Researchers must also elucidate the fate of eosinophils in the tissues, especially in vasculitic lesions, after treatment with mepolizumab. And they should address possible synergistic activity when the drug is given together with immunosuppressants such as azathioprine and cyclophosphamide.
In addition, future studies should include patients who have organ-threatening or life-threatening eosinophilic granulomatosis with polyangiitis, who were excluded from this trial but who are most in need of novel treatments.
Ratko Djukanovic, MD, is with the University of Southampton (England) and the National Institute for Health Research Southampton Biomedical Research Centre. Paul M. O’Byrne, MD, is with the Firestone Institute for Respiratory Health within St. Joseph’s Healthcare and McMaster University in Hamilton, Ont. Dr. Djukanovic and Dr. O’Byrne both reported financial relationships with pharmaceutical companies outside their editorial. They made these remarks in an editorial accompanying Dr. Wechsler and colleagues’ report (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMe1704402).
Adding mepolizumab to standard-of-care glucocorticoids with or without immunosuppressive agents can induce remission in many patients who have eosinophilic granulomatosis with polyangiitis (EGPA), according to a report published online May 18 in the New England Journal of Medicine.
EGPA, a rare disorder characterized by asthma, sinusitis, pulmonary infiltrates, neuropathy, and eosinophilic vasculitis in at least one end-organ, frequently relapses despite glucocorticoid therapy or fails to respond adequately to the treatment. Patients have elevated levels of the cytokine interleukin-5, which regulates eosinophil maturation, differentiation, and proliferation. Neutralizing this cytokine is thought to be a potential therapeutic approach, said Michael E. Wechsler, MD, of National Jewish Health, Denver, and his associates.
Proof-of-concept studies have demonstrated the efficacy of subcutaneous mepolizumab, an anti–interleukin-5 monoclonal antibody, in EGPA, so Dr. Wechsler and his colleagues assessed the safety and efficacy of a 1-year course of mepolizumab (300 mg) as add-on therapy in a double-blind, randomized, phase III trial, which involved 136 adults treated at 31 academic medical centers in nine countries. The study was sponsored by GlaxoSmithKline and the National Institute of Allergy and Infectious Diseases.
The first of two primary efficacy endpoints was the total accrued weeks of remission. A total of 28% of the mepolizumab group achieved remission for at least 24 weeks, compared with only 3% of the placebo group, for an odds ratio of 5.91.
The second primary efficacy endpoint was the proportion of patients in remission at both week 36 and week 48. Again, significantly more patients in the mepolizumab group (32%) than in the placebo group (3%) met this end point (OR, 16.74).
Mepolizumab also proved superior to placebo regarding numerous secondary endpoints, the investigators said (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMoa1702079). More patients who received active treatment achieved remission within the first 6 months of treatment and remained in remission for a full year (19% vs. 1%; OR, 19.65). The time to first relapse was significantly longer for mepolizumab, with only 56% of that group experiencing a relapse within 1 year, compared with 82% of the placebo group. The annualized relapse rate was half as high with mepolizumab (1.14) as with placebo (2.27).
In addition, patients in the mepolizumab group were more likely to reduce their doses of glucocorticoids (OR, 0.20) or discontinue the drugs altogether (18% vs. 3% taking placebo).
Mepolizumab was most effective among the 79 patients who had a high absolute eosinophil count (150 or more cells per cubic millimeter) at baseline. In this subgroup, 33% of patients taking mepolizumab achieved remission for 6 months or more, compared with none of the patients taking placebo (OR, 26.1).
Although the effectiveness of mepolizumab in this difficult-to-treat population was noteworthy, only about half of the patients given the active treatment achieved remission as defined by the study protocol. It is unclear why the drug was not effective in the other half of patients. One possible reason is that some manifestations of the disorder are not driven by eosinophils. Another is that nonresponsive patients may have sustained longstanding, irreversible vasculitic damage that is no longer amenable to anti–interleukin-5 therapy.
Alternatively, it’s possible that mepolizumab reduced eosinophils in the blood but not those in the body tissues of nonresponsive patients or that the patients who didn’t respond well simply required a higher dose of the drug, Dr. Wechsler and his associates said.
The NIAID is now supporting a study of blood, urine, sputum, and tissue samples from some of these participants “to address questions related to disease risk and pathological features, as well as response to treatment,” they added.
Many authors reported receiving payments from pharmaceutical companies, including several from GlaxoSmithKline. Four authors are employees of the company.
Adding mepolizumab to standard-of-care glucocorticoids with or without immunosuppressive agents can induce remission in many patients who have eosinophilic granulomatosis with polyangiitis (EGPA), according to a report published online May 18 in the New England Journal of Medicine.
EGPA, a rare disorder characterized by asthma, sinusitis, pulmonary infiltrates, neuropathy, and eosinophilic vasculitis in at least one end-organ, frequently relapses despite glucocorticoid therapy or fails to respond adequately to the treatment. Patients have elevated levels of the cytokine interleukin-5, which regulates eosinophil maturation, differentiation, and proliferation. Neutralizing this cytokine is thought to be a potential therapeutic approach, said Michael E. Wechsler, MD, of National Jewish Health, Denver, and his associates.
Proof-of-concept studies have demonstrated the efficacy of subcutaneous mepolizumab, an anti–interleukin-5 monoclonal antibody, in EGPA, so Dr. Wechsler and his colleagues assessed the safety and efficacy of a 1-year course of mepolizumab (300 mg) as add-on therapy in a double-blind, randomized, phase III trial, which involved 136 adults treated at 31 academic medical centers in nine countries. The study was sponsored by GlaxoSmithKline and the National Institute of Allergy and Infectious Diseases.
The first of two primary efficacy endpoints was the total accrued weeks of remission. A total of 28% of the mepolizumab group achieved remission for at least 24 weeks, compared with only 3% of the placebo group, for an odds ratio of 5.91.
The second primary efficacy endpoint was the proportion of patients in remission at both week 36 and week 48. Again, significantly more patients in the mepolizumab group (32%) than in the placebo group (3%) met this end point (OR, 16.74).
Mepolizumab also proved superior to placebo regarding numerous secondary endpoints, the investigators said (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMoa1702079). More patients who received active treatment achieved remission within the first 6 months of treatment and remained in remission for a full year (19% vs. 1%; OR, 19.65). The time to first relapse was significantly longer for mepolizumab, with only 56% of that group experiencing a relapse within 1 year, compared with 82% of the placebo group. The annualized relapse rate was half as high with mepolizumab (1.14) as with placebo (2.27).
In addition, patients in the mepolizumab group were more likely to reduce their doses of glucocorticoids (OR, 0.20) or discontinue the drugs altogether (18% vs. 3% taking placebo).
Mepolizumab was most effective among the 79 patients who had a high absolute eosinophil count (150 or more cells per cubic millimeter) at baseline. In this subgroup, 33% of patients taking mepolizumab achieved remission for 6 months or more, compared with none of the patients taking placebo (OR, 26.1).
Although the effectiveness of mepolizumab in this difficult-to-treat population was noteworthy, only about half of the patients given the active treatment achieved remission as defined by the study protocol. It is unclear why the drug was not effective in the other half of patients. One possible reason is that some manifestations of the disorder are not driven by eosinophils. Another is that nonresponsive patients may have sustained longstanding, irreversible vasculitic damage that is no longer amenable to anti–interleukin-5 therapy.
Alternatively, it’s possible that mepolizumab reduced eosinophils in the blood but not those in the body tissues of nonresponsive patients or that the patients who didn’t respond well simply required a higher dose of the drug, Dr. Wechsler and his associates said.
The NIAID is now supporting a study of blood, urine, sputum, and tissue samples from some of these participants “to address questions related to disease risk and pathological features, as well as response to treatment,” they added.
Many authors reported receiving payments from pharmaceutical companies, including several from GlaxoSmithKline. Four authors are employees of the company.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point:
Major finding: Of the mepolizumab group, 28% achieved remission for at least 24 weeks, compared with only 3% of the placebo group (OR, 5.91).
Data source: An international double-blind randomized placebo-controlled phase III trial involving 136 adults treated for 1 year.
Disclosures: This study was supported by GlaxoSmithKline and the National Institute of Allergy and Infectious Diseases. Many authors reported receiving payments from pharmaceutical companies, including several from GlaxoSmithKline. Four authors are employees of the company.
Imatinib cuts mast cells in severe asthma
Imatinib decreased airway mast-cell counts and airway hyperresponsiveness in adults with asthma, who were not responding well to maximal therapy, according to a report published online May 17 in the New England Journal of Medicine.
Imatinib is an inhibitor of the stem-cell factor receptor KIT, which is essential for mast-cell development and survival in bodily tissues. This study’s findings suggest that KIT-dependent processes and mast cells contribute to the pathobiology of severe asthma.
The researchers undertook this study because imatinib is known to reduce bone-marrow mast cells and tryptase levels in chronic myeloid leukemia and to reduce serum tryptase in patients with pulmonary hypertension. Tryptase is a marker of mast-cell burden and activation when detected in extracellular fluids, and it is elevated in the bronchoalveolar lavage fluid from patients with uncontrolled asthma.
To examine whether imatinib would decrease mast-cell counts and activation in the airways of adults with severe, refractory asthma, the investigators performed the randomized double-blind proof-of-principle trial at seven academic centers across the United States over the course of 5 years. A total of 62 patients were assigned to 24 weeks of either oral imatinib (32 participants) or a matching placebo (30 participants). Fifty patients, 24 in the imatinib group and 26 in the placebo group, completed the trial.
The primary outcome measure was the change in airway hyperresponsiveness at 6 months, as measured by the increase in the concentration of methacholine that causes significant bronchoconstriction (PC20). Imatinib decreased airway hyperresponsiveness to a greater degree than did placebo. Imatinib increased PC20 by a mean of 1.20 doubling doses at 3 months and by a mean of 1.73 doubling doses at 6 months, compared with 0.03 and 1.07, respectively, for placebo.
The small improvement in the placebo group is consistent with a phenomenon reported in other studies, in which patients show a delayed improvement in airway hyperresponsiveness for several months after they started inhaled glucocorticoids, Dr. Cahill and her associates noted (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMoa1613125).
Imatinib also reduced mast-cell activity as measured by serum and airway levels of tryptase. Serum tryptase decreased by 43% in the imatinib group, compared with a 12% decline in the placebo group. And tryptase levels in bronchoalveolar lavage fluid tended to decrease in the imatinib group but to increase in the placebo group.
Imatinib also increased mean forced expiratory volume in 1 second (FEV1).
“Although the increase in FEV1 may not seem substantial, it suggests that mast-cell–dependent processes contribute to airway obstruction in these patients despite high-dose, anti-inflammatory glucocorticoid therapy. The near–50-mL difference in the change in baseline FEV1 between the imatinib and placebo groups is small, but it is likely to be important in light of the population we studied,” Dr. Cahill and her associates wrote.
In addition, exploratory analyses showed that the reduction in airway hyperresponsiveness with imatinib “negatively correlated with baseline blood eosinophil counts, and baseline numbers of neutrophils in bronchoalveolar lavage fluid were strongly correlated with increases in FEV1. Together, these findings support a role for mast cells in noneosinophilic asthma. Since almost half of the patients with severe asthma have neutrophilic airway inflammation, we speculate that KIT inhibition might represent an important approach to treatment for this group,” they said.
This study was supported by the National Heart, Lung, and Blood Institute, the National Institute of Allergy and Infectious Diseases, the Vinik family, and the Kaye family; Novartis provided imatinib free of charge. The authors’ financial disclosures are available at www.nejm.org.
As Cahill et al. noted, these data suggest that the role of mast cells should be studied further, but cautiously.
It is not yet time to target mast cells in patients with asthma. Evolution has given us these cells for a reason. They appear to assist in host defense against parasites and play a role in other innate and adaptive immune responses. And they likely have other beneficial effects that haven’t been discovered yet.
However, in the unfortunate patients in whom mast cells can be strongly implicated as contributing to disease, either reducing their numbers or suppressing their function may confer more benefit than harm. This is particularly true in the case of asthma, where mast cells can be targeted locally, in the airways.
Stephen J. Galli, MD, is the Mary Hewitt Loveless, MD, Professor in the school of medicine, and is at the Sean N. Parker Center for Allergy and Asthma Research at Stanford (Calif.) University. His financial disclosures are available at www.nejm.org. Dr. Galli made these remarks in an editorial accompanying Dr. Cahill’s report (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMe1702653).
As Cahill et al. noted, these data suggest that the role of mast cells should be studied further, but cautiously.
It is not yet time to target mast cells in patients with asthma. Evolution has given us these cells for a reason. They appear to assist in host defense against parasites and play a role in other innate and adaptive immune responses. And they likely have other beneficial effects that haven’t been discovered yet.
However, in the unfortunate patients in whom mast cells can be strongly implicated as contributing to disease, either reducing their numbers or suppressing their function may confer more benefit than harm. This is particularly true in the case of asthma, where mast cells can be targeted locally, in the airways.
Stephen J. Galli, MD, is the Mary Hewitt Loveless, MD, Professor in the school of medicine, and is at the Sean N. Parker Center for Allergy and Asthma Research at Stanford (Calif.) University. His financial disclosures are available at www.nejm.org. Dr. Galli made these remarks in an editorial accompanying Dr. Cahill’s report (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMe1702653).
As Cahill et al. noted, these data suggest that the role of mast cells should be studied further, but cautiously.
It is not yet time to target mast cells in patients with asthma. Evolution has given us these cells for a reason. They appear to assist in host defense against parasites and play a role in other innate and adaptive immune responses. And they likely have other beneficial effects that haven’t been discovered yet.
However, in the unfortunate patients in whom mast cells can be strongly implicated as contributing to disease, either reducing their numbers or suppressing their function may confer more benefit than harm. This is particularly true in the case of asthma, where mast cells can be targeted locally, in the airways.
Stephen J. Galli, MD, is the Mary Hewitt Loveless, MD, Professor in the school of medicine, and is at the Sean N. Parker Center for Allergy and Asthma Research at Stanford (Calif.) University. His financial disclosures are available at www.nejm.org. Dr. Galli made these remarks in an editorial accompanying Dr. Cahill’s report (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMe1702653).
Imatinib decreased airway mast-cell counts and airway hyperresponsiveness in adults with asthma, who were not responding well to maximal therapy, according to a report published online May 17 in the New England Journal of Medicine.
Imatinib is an inhibitor of the stem-cell factor receptor KIT, which is essential for mast-cell development and survival in bodily tissues. This study’s findings suggest that KIT-dependent processes and mast cells contribute to the pathobiology of severe asthma.
The researchers undertook this study because imatinib is known to reduce bone-marrow mast cells and tryptase levels in chronic myeloid leukemia and to reduce serum tryptase in patients with pulmonary hypertension. Tryptase is a marker of mast-cell burden and activation when detected in extracellular fluids, and it is elevated in the bronchoalveolar lavage fluid from patients with uncontrolled asthma.
To examine whether imatinib would decrease mast-cell counts and activation in the airways of adults with severe, refractory asthma, the investigators performed the randomized double-blind proof-of-principle trial at seven academic centers across the United States over the course of 5 years. A total of 62 patients were assigned to 24 weeks of either oral imatinib (32 participants) or a matching placebo (30 participants). Fifty patients, 24 in the imatinib group and 26 in the placebo group, completed the trial.
The primary outcome measure was the change in airway hyperresponsiveness at 6 months, as measured by the increase in the concentration of methacholine that causes significant bronchoconstriction (PC20). Imatinib decreased airway hyperresponsiveness to a greater degree than did placebo. Imatinib increased PC20 by a mean of 1.20 doubling doses at 3 months and by a mean of 1.73 doubling doses at 6 months, compared with 0.03 and 1.07, respectively, for placebo.
The small improvement in the placebo group is consistent with a phenomenon reported in other studies, in which patients show a delayed improvement in airway hyperresponsiveness for several months after they started inhaled glucocorticoids, Dr. Cahill and her associates noted (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMoa1613125).
Imatinib also reduced mast-cell activity as measured by serum and airway levels of tryptase. Serum tryptase decreased by 43% in the imatinib group, compared with a 12% decline in the placebo group. And tryptase levels in bronchoalveolar lavage fluid tended to decrease in the imatinib group but to increase in the placebo group.
Imatinib also increased mean forced expiratory volume in 1 second (FEV1).
“Although the increase in FEV1 may not seem substantial, it suggests that mast-cell–dependent processes contribute to airway obstruction in these patients despite high-dose, anti-inflammatory glucocorticoid therapy. The near–50-mL difference in the change in baseline FEV1 between the imatinib and placebo groups is small, but it is likely to be important in light of the population we studied,” Dr. Cahill and her associates wrote.
In addition, exploratory analyses showed that the reduction in airway hyperresponsiveness with imatinib “negatively correlated with baseline blood eosinophil counts, and baseline numbers of neutrophils in bronchoalveolar lavage fluid were strongly correlated with increases in FEV1. Together, these findings support a role for mast cells in noneosinophilic asthma. Since almost half of the patients with severe asthma have neutrophilic airway inflammation, we speculate that KIT inhibition might represent an important approach to treatment for this group,” they said.
This study was supported by the National Heart, Lung, and Blood Institute, the National Institute of Allergy and Infectious Diseases, the Vinik family, and the Kaye family; Novartis provided imatinib free of charge. The authors’ financial disclosures are available at www.nejm.org.
Imatinib decreased airway mast-cell counts and airway hyperresponsiveness in adults with asthma, who were not responding well to maximal therapy, according to a report published online May 17 in the New England Journal of Medicine.
Imatinib is an inhibitor of the stem-cell factor receptor KIT, which is essential for mast-cell development and survival in bodily tissues. This study’s findings suggest that KIT-dependent processes and mast cells contribute to the pathobiology of severe asthma.
The researchers undertook this study because imatinib is known to reduce bone-marrow mast cells and tryptase levels in chronic myeloid leukemia and to reduce serum tryptase in patients with pulmonary hypertension. Tryptase is a marker of mast-cell burden and activation when detected in extracellular fluids, and it is elevated in the bronchoalveolar lavage fluid from patients with uncontrolled asthma.
To examine whether imatinib would decrease mast-cell counts and activation in the airways of adults with severe, refractory asthma, the investigators performed the randomized double-blind proof-of-principle trial at seven academic centers across the United States over the course of 5 years. A total of 62 patients were assigned to 24 weeks of either oral imatinib (32 participants) or a matching placebo (30 participants). Fifty patients, 24 in the imatinib group and 26 in the placebo group, completed the trial.
The primary outcome measure was the change in airway hyperresponsiveness at 6 months, as measured by the increase in the concentration of methacholine that causes significant bronchoconstriction (PC20). Imatinib decreased airway hyperresponsiveness to a greater degree than did placebo. Imatinib increased PC20 by a mean of 1.20 doubling doses at 3 months and by a mean of 1.73 doubling doses at 6 months, compared with 0.03 and 1.07, respectively, for placebo.
The small improvement in the placebo group is consistent with a phenomenon reported in other studies, in which patients show a delayed improvement in airway hyperresponsiveness for several months after they started inhaled glucocorticoids, Dr. Cahill and her associates noted (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMoa1613125).
Imatinib also reduced mast-cell activity as measured by serum and airway levels of tryptase. Serum tryptase decreased by 43% in the imatinib group, compared with a 12% decline in the placebo group. And tryptase levels in bronchoalveolar lavage fluid tended to decrease in the imatinib group but to increase in the placebo group.
Imatinib also increased mean forced expiratory volume in 1 second (FEV1).
“Although the increase in FEV1 may not seem substantial, it suggests that mast-cell–dependent processes contribute to airway obstruction in these patients despite high-dose, anti-inflammatory glucocorticoid therapy. The near–50-mL difference in the change in baseline FEV1 between the imatinib and placebo groups is small, but it is likely to be important in light of the population we studied,” Dr. Cahill and her associates wrote.
In addition, exploratory analyses showed that the reduction in airway hyperresponsiveness with imatinib “negatively correlated with baseline blood eosinophil counts, and baseline numbers of neutrophils in bronchoalveolar lavage fluid were strongly correlated with increases in FEV1. Together, these findings support a role for mast cells in noneosinophilic asthma. Since almost half of the patients with severe asthma have neutrophilic airway inflammation, we speculate that KIT inhibition might represent an important approach to treatment for this group,” they said.
This study was supported by the National Heart, Lung, and Blood Institute, the National Institute of Allergy and Infectious Diseases, the Vinik family, and the Kaye family; Novartis provided imatinib free of charge. The authors’ financial disclosures are available at www.nejm.org.
Key clinical point: Imatinib, a KIT inhibitor, reduced mast cell counts and airway hyperresponsiveness in severe asthma.
Major finding: Imatinib increased PC20 by a mean of 1.20 doubling doses at 3 months and by a mean of 1.73 doubling doses at 6 months, compared with 0.03 and 1.07, respectively, for placebo.
Data source: A randomized, double-blind, placebo-controlled proof-of-principle trial involving 62 adults treated for 24 weeks.
Disclosures: This study was supported by the National Heart, Lung, and Blood Institute, the National Institute of Allergy and Infectious Diseases, the Vinik family, and the Kaye family; Novartis provided imatinib free of charge. The researchers’ financial disclosures are available at www.nejm.org.
Asthma step-up therapy in children improves outcomes
SAN FRANCISCO – Stepping up pharmacotherapy in children with poorly controlled asthma resulted in fewer asthma-related emergency department (ED) visits and inpatient stays than maintaining current medication therapy, a study found.
Perhaps surprisingly, however, the patients with the worst outcomes were those who were told only to improve their medication adherence, said Dane Snyder, MD, a physician at Nationwide Children’s Hospital who is also in the department of pediatrics at Ohio State University, Columbus.
Asthma affects nearly 1 in 10 children, and national guidelines recommend step-up asthma pharmacotherapy in patients with poorly controlled asthma. The researchers assessed the impact of step-up therapy on inpatient care, and emergency and urgent care visits for children with poor asthma control in the Nationwide Children’s Hospital Primary Care Network in Columbus, Ohio. More than 10,000 asthma patients are treated at the 12 clinics in the network, and the study was part of a quality improvement initiative starting in July 2015.
Between August and October 2015, researchers used documentation in a standard asthma note to identify 908 patients aged 2-18 years who had poor asthma control based on their Asthma Control Test (ACT) score and history. Of these patients, 463 with a mean ACT score of 15.8 were assigned to step-up pharmacotherapy, while 445 with a mean ACT of 16.2 were not. The two groups also were similar in their use of unscheduled health care utilization in the 12 months before the study period.
Over the next 12 months, 1.3% of patients receiving step-up therapy had inpatient stays, compared with 4% in the other group, translating to a 68% lower risk of admission with step-up therapy (relative risk, 0.316; P = .01). Those receiving step-up therapy also were 37% less likely to visit the ED for asthma, with 7.1% of ED visits for those with step-up therapy and 11.2% of visits for those without it (RR, 0.634; P = .032). Visits to urgent care, however, showed no significant difference between those receiving step-up therapy (10.8%) and those who had not (10.3%).
After comparing these findings, the researchers went back and manually reviewed all 463 charts of the group who received step-up therapy to determine whether the children actually did receive a step up in therapy. Nearly a quarter (23%) of the children in the intervention group simply resumed taking their previously prescribed mediation, and 8% took allergy medication. The remaining 69% had step-up therapy.
The researchers then reanalyzed the data among those who truly had step-up pharmacotherapy, those who did not, and those who resumed taking their prior medication. The difference in inpatient admissions remained the same because none of the children who had resumed medication were admitted.
ED visits showed a more gradual distribution: 7.3% of those receiving step-up therapy, 8.4% of those who resumed taking their medication, and 11% of those with no intervention went to the ED. But these differences did not reach statistical significance.
Similarly, the differences among the three groups in urgent care visits was not statistically significant, but 15% of those who resumed taking prior medication had urgent care visits, compared with 10.3% of those with step-up therapy and 9.2% of those in the control group.
Those findings suggest that “stepping up pharmacotherapy, even in the face of controller nonadherence, can improve outcomes,” Dr. Snyder told his colleagues.
“While challenging, management changes in a large primary care network are possible,” Dr. Snyder said. He also emphasized that manually auditing bulk data, as they did with the 463 records, can be important in assessing outcomes of quality improvement measures.
The research did not use external funding, and Dr. Snyder had no disclosures.
SAN FRANCISCO – Stepping up pharmacotherapy in children with poorly controlled asthma resulted in fewer asthma-related emergency department (ED) visits and inpatient stays than maintaining current medication therapy, a study found.
Perhaps surprisingly, however, the patients with the worst outcomes were those who were told only to improve their medication adherence, said Dane Snyder, MD, a physician at Nationwide Children’s Hospital who is also in the department of pediatrics at Ohio State University, Columbus.
Asthma affects nearly 1 in 10 children, and national guidelines recommend step-up asthma pharmacotherapy in patients with poorly controlled asthma. The researchers assessed the impact of step-up therapy on inpatient care, and emergency and urgent care visits for children with poor asthma control in the Nationwide Children’s Hospital Primary Care Network in Columbus, Ohio. More than 10,000 asthma patients are treated at the 12 clinics in the network, and the study was part of a quality improvement initiative starting in July 2015.
Between August and October 2015, researchers used documentation in a standard asthma note to identify 908 patients aged 2-18 years who had poor asthma control based on their Asthma Control Test (ACT) score and history. Of these patients, 463 with a mean ACT score of 15.8 were assigned to step-up pharmacotherapy, while 445 with a mean ACT of 16.2 were not. The two groups also were similar in their use of unscheduled health care utilization in the 12 months before the study period.
Over the next 12 months, 1.3% of patients receiving step-up therapy had inpatient stays, compared with 4% in the other group, translating to a 68% lower risk of admission with step-up therapy (relative risk, 0.316; P = .01). Those receiving step-up therapy also were 37% less likely to visit the ED for asthma, with 7.1% of ED visits for those with step-up therapy and 11.2% of visits for those without it (RR, 0.634; P = .032). Visits to urgent care, however, showed no significant difference between those receiving step-up therapy (10.8%) and those who had not (10.3%).
After comparing these findings, the researchers went back and manually reviewed all 463 charts of the group who received step-up therapy to determine whether the children actually did receive a step up in therapy. Nearly a quarter (23%) of the children in the intervention group simply resumed taking their previously prescribed mediation, and 8% took allergy medication. The remaining 69% had step-up therapy.
The researchers then reanalyzed the data among those who truly had step-up pharmacotherapy, those who did not, and those who resumed taking their prior medication. The difference in inpatient admissions remained the same because none of the children who had resumed medication were admitted.
ED visits showed a more gradual distribution: 7.3% of those receiving step-up therapy, 8.4% of those who resumed taking their medication, and 11% of those with no intervention went to the ED. But these differences did not reach statistical significance.
Similarly, the differences among the three groups in urgent care visits was not statistically significant, but 15% of those who resumed taking prior medication had urgent care visits, compared with 10.3% of those with step-up therapy and 9.2% of those in the control group.
Those findings suggest that “stepping up pharmacotherapy, even in the face of controller nonadherence, can improve outcomes,” Dr. Snyder told his colleagues.
“While challenging, management changes in a large primary care network are possible,” Dr. Snyder said. He also emphasized that manually auditing bulk data, as they did with the 463 records, can be important in assessing outcomes of quality improvement measures.
The research did not use external funding, and Dr. Snyder had no disclosures.
SAN FRANCISCO – Stepping up pharmacotherapy in children with poorly controlled asthma resulted in fewer asthma-related emergency department (ED) visits and inpatient stays than maintaining current medication therapy, a study found.
Perhaps surprisingly, however, the patients with the worst outcomes were those who were told only to improve their medication adherence, said Dane Snyder, MD, a physician at Nationwide Children’s Hospital who is also in the department of pediatrics at Ohio State University, Columbus.
Asthma affects nearly 1 in 10 children, and national guidelines recommend step-up asthma pharmacotherapy in patients with poorly controlled asthma. The researchers assessed the impact of step-up therapy on inpatient care, and emergency and urgent care visits for children with poor asthma control in the Nationwide Children’s Hospital Primary Care Network in Columbus, Ohio. More than 10,000 asthma patients are treated at the 12 clinics in the network, and the study was part of a quality improvement initiative starting in July 2015.
Between August and October 2015, researchers used documentation in a standard asthma note to identify 908 patients aged 2-18 years who had poor asthma control based on their Asthma Control Test (ACT) score and history. Of these patients, 463 with a mean ACT score of 15.8 were assigned to step-up pharmacotherapy, while 445 with a mean ACT of 16.2 were not. The two groups also were similar in their use of unscheduled health care utilization in the 12 months before the study period.
Over the next 12 months, 1.3% of patients receiving step-up therapy had inpatient stays, compared with 4% in the other group, translating to a 68% lower risk of admission with step-up therapy (relative risk, 0.316; P = .01). Those receiving step-up therapy also were 37% less likely to visit the ED for asthma, with 7.1% of ED visits for those with step-up therapy and 11.2% of visits for those without it (RR, 0.634; P = .032). Visits to urgent care, however, showed no significant difference between those receiving step-up therapy (10.8%) and those who had not (10.3%).
After comparing these findings, the researchers went back and manually reviewed all 463 charts of the group who received step-up therapy to determine whether the children actually did receive a step up in therapy. Nearly a quarter (23%) of the children in the intervention group simply resumed taking their previously prescribed mediation, and 8% took allergy medication. The remaining 69% had step-up therapy.
The researchers then reanalyzed the data among those who truly had step-up pharmacotherapy, those who did not, and those who resumed taking their prior medication. The difference in inpatient admissions remained the same because none of the children who had resumed medication were admitted.
ED visits showed a more gradual distribution: 7.3% of those receiving step-up therapy, 8.4% of those who resumed taking their medication, and 11% of those with no intervention went to the ED. But these differences did not reach statistical significance.
Similarly, the differences among the three groups in urgent care visits was not statistically significant, but 15% of those who resumed taking prior medication had urgent care visits, compared with 10.3% of those with step-up therapy and 9.2% of those in the control group.
Those findings suggest that “stepping up pharmacotherapy, even in the face of controller nonadherence, can improve outcomes,” Dr. Snyder told his colleagues.
“While challenging, management changes in a large primary care network are possible,” Dr. Snyder said. He also emphasized that manually auditing bulk data, as they did with the 463 records, can be important in assessing outcomes of quality improvement measures.
The research did not use external funding, and Dr. Snyder had no disclosures.
AT PAS 2017
Key clinical point:
Major finding: Children with poorly controlled asthma receiving step-up pharmacotherapy had a 68% lower risk of inpatient admission and 37% lower risk of emergency department visits for asthma (P less than .05).
Data source: The findings are based on a nonrandomized trial of 903 children, aged 2-18 years, tracked for 12 months in the Nationwide Children’s Hospital Primary Care Network in Columbus, Ohio.
Disclosures: The research did not use external funding, and Dr. Snyder had no disclosures.
Tools measuring oxygen desaturation produced disparate data
WASHINGTON – Oxygen desaturation index (ODI) scores showed significant variation across two software systems, a study showed.
The researchers assessed the ODI scores of 106 patients using the ResMed ApneaLink Plus system (AL) and the Compumedics Grael Profusion PSG3 system (Comp). “AL ODI values tended to be higher than Comp ODI values, but with significant variability,” they said.
AL showed a bias of an additional 4.4 events per hour (95% limits of agreement, –5.8 to 14.6 events per hour) for ODI scores at 4% desaturation and a bias of an additional 7.1 events per hour (95% limits of agreement, –6.4 to 20.6 events per hour) at 3% desaturation (J Clin Sleep Med. 2017;13[4]:599-605).
This may be problematic for physicians evaluating patients during sleep studies who rely on ODI scores at 3% and 4% desaturations to create accurate apnea severity assessments, the investigators said.
“[The] wide limits of agreement in our study highlight that clinicians cannot be confident that an ODI4% recorded in the AL is the same as that recorded in the Comp,” wrote Yvonne Ng, MBBS, of the department of lung and sleep medicine at Monash Health, Victoria, Australia, and her colleagues. “The differences are large enough to significantly affect diagnostic thresholds for OSA [obstructive sleep apnea] and, in particular, moderate-severe OSA.”
The researchers gathered data from patients undergoing sleep analysis at the Monash Medical Centre, who were, on average, 47 years of age, had a body mass index score of 32 kg/m2, and had an apnea hypopnea index (AHI) of 23.2.
ODI3% scores analyzed through Comp diagnosed 66 patients with OSA (ODI3% greater than or equal to 5 events per hour), while desaturation events analyzed through the AL system diagnosed 90 patients, a 36% increase over Comp (P = .0002).
When researchers tested for moderate to severe OSA (ODI3% greater than or equal to 15 events per hour), 32 patients were diagnosed using the Comp system, compared with 59 patients using the AL system.
Disparities in these measurements create uncertainty among clinicians, who rely on ODI measurements for scores that are accurate and can be easily replicated using an algorithm, the researchers said.
“The current work demonstrates that significantly more patients would receive a diagnosis of OSA, or more particularly, moderate-severe OSA, with the AL ODI, compared to the Comp ODI,” Dr. Ng and her colleagues wrote.
When sensitivity scores for Comp and AL were compared, AL ODI3% scores were significantly more sensitive than Comp, with sensitivity scores of 96% vs. 58%.
Using different fingers for measuring desaturation during the test or differences in algorithms used to assess ODI scores were possible sources of the disparities, the researchers noted.
Differences in internal processing between the two systems were the most likely causes of the discrepancies between the data collected using each system, they added.
Because there is no universal standard for ODI measurements, the researchers were unable to determine which system was more accurate.
Several of the researchers reported receiving financial support, research equipment, or consultancy fees from various entities.
[email protected]
On Twitter @eaztweets
WASHINGTON – Oxygen desaturation index (ODI) scores showed significant variation across two software systems, a study showed.
The researchers assessed the ODI scores of 106 patients using the ResMed ApneaLink Plus system (AL) and the Compumedics Grael Profusion PSG3 system (Comp). “AL ODI values tended to be higher than Comp ODI values, but with significant variability,” they said.
AL showed a bias of an additional 4.4 events per hour (95% limits of agreement, –5.8 to 14.6 events per hour) for ODI scores at 4% desaturation and a bias of an additional 7.1 events per hour (95% limits of agreement, –6.4 to 20.6 events per hour) at 3% desaturation (J Clin Sleep Med. 2017;13[4]:599-605).
This may be problematic for physicians evaluating patients during sleep studies who rely on ODI scores at 3% and 4% desaturations to create accurate apnea severity assessments, the investigators said.
“[The] wide limits of agreement in our study highlight that clinicians cannot be confident that an ODI4% recorded in the AL is the same as that recorded in the Comp,” wrote Yvonne Ng, MBBS, of the department of lung and sleep medicine at Monash Health, Victoria, Australia, and her colleagues. “The differences are large enough to significantly affect diagnostic thresholds for OSA [obstructive sleep apnea] and, in particular, moderate-severe OSA.”
The researchers gathered data from patients undergoing sleep analysis at the Monash Medical Centre, who were, on average, 47 years of age, had a body mass index score of 32 kg/m2, and had an apnea hypopnea index (AHI) of 23.2.
ODI3% scores analyzed through Comp diagnosed 66 patients with OSA (ODI3% greater than or equal to 5 events per hour), while desaturation events analyzed through the AL system diagnosed 90 patients, a 36% increase over Comp (P = .0002).
When researchers tested for moderate to severe OSA (ODI3% greater than or equal to 15 events per hour), 32 patients were diagnosed using the Comp system, compared with 59 patients using the AL system.
Disparities in these measurements create uncertainty among clinicians, who rely on ODI measurements for scores that are accurate and can be easily replicated using an algorithm, the researchers said.
“The current work demonstrates that significantly more patients would receive a diagnosis of OSA, or more particularly, moderate-severe OSA, with the AL ODI, compared to the Comp ODI,” Dr. Ng and her colleagues wrote.
When sensitivity scores for Comp and AL were compared, AL ODI3% scores were significantly more sensitive than Comp, with sensitivity scores of 96% vs. 58%.
Using different fingers for measuring desaturation during the test or differences in algorithms used to assess ODI scores were possible sources of the disparities, the researchers noted.
Differences in internal processing between the two systems were the most likely causes of the discrepancies between the data collected using each system, they added.
Because there is no universal standard for ODI measurements, the researchers were unable to determine which system was more accurate.
Several of the researchers reported receiving financial support, research equipment, or consultancy fees from various entities.
[email protected]
On Twitter @eaztweets
WASHINGTON – Oxygen desaturation index (ODI) scores showed significant variation across two software systems, a study showed.
The researchers assessed the ODI scores of 106 patients using the ResMed ApneaLink Plus system (AL) and the Compumedics Grael Profusion PSG3 system (Comp). “AL ODI values tended to be higher than Comp ODI values, but with significant variability,” they said.
AL showed a bias of an additional 4.4 events per hour (95% limits of agreement, –5.8 to 14.6 events per hour) for ODI scores at 4% desaturation and a bias of an additional 7.1 events per hour (95% limits of agreement, –6.4 to 20.6 events per hour) at 3% desaturation (J Clin Sleep Med. 2017;13[4]:599-605).
This may be problematic for physicians evaluating patients during sleep studies who rely on ODI scores at 3% and 4% desaturations to create accurate apnea severity assessments, the investigators said.
“[The] wide limits of agreement in our study highlight that clinicians cannot be confident that an ODI4% recorded in the AL is the same as that recorded in the Comp,” wrote Yvonne Ng, MBBS, of the department of lung and sleep medicine at Monash Health, Victoria, Australia, and her colleagues. “The differences are large enough to significantly affect diagnostic thresholds for OSA [obstructive sleep apnea] and, in particular, moderate-severe OSA.”
The researchers gathered data from patients undergoing sleep analysis at the Monash Medical Centre, who were, on average, 47 years of age, had a body mass index score of 32 kg/m2, and had an apnea hypopnea index (AHI) of 23.2.
ODI3% scores analyzed through Comp diagnosed 66 patients with OSA (ODI3% greater than or equal to 5 events per hour), while desaturation events analyzed through the AL system diagnosed 90 patients, a 36% increase over Comp (P = .0002).
When researchers tested for moderate to severe OSA (ODI3% greater than or equal to 15 events per hour), 32 patients were diagnosed using the Comp system, compared with 59 patients using the AL system.
Disparities in these measurements create uncertainty among clinicians, who rely on ODI measurements for scores that are accurate and can be easily replicated using an algorithm, the researchers said.
“The current work demonstrates that significantly more patients would receive a diagnosis of OSA, or more particularly, moderate-severe OSA, with the AL ODI, compared to the Comp ODI,” Dr. Ng and her colleagues wrote.
When sensitivity scores for Comp and AL were compared, AL ODI3% scores were significantly more sensitive than Comp, with sensitivity scores of 96% vs. 58%.
Using different fingers for measuring desaturation during the test or differences in algorithms used to assess ODI scores were possible sources of the disparities, the researchers noted.
Differences in internal processing between the two systems were the most likely causes of the discrepancies between the data collected using each system, they added.
Because there is no universal standard for ODI measurements, the researchers were unable to determine which system was more accurate.
Several of the researchers reported receiving financial support, research equipment, or consultancy fees from various entities.
[email protected]
On Twitter @eaztweets
Key clinical point:
Major finding: ODI tests analyzed using the ResMed APneaLink Plus system vs. Compumedics Grael Profusion PSG3 system reported ODI4% bias = 4.4 events per hour (95% limits of agreement, –5.8 to 14.6 events per hour) and ODI3% bias = 7.1 events per hour (95% limits of agreement, –6.4 to 20.6 events per hour).
Data source: ODI test results for 106 participants in a sleep study at Monash Medical Centre.
Disclosures: Several of the researchers reported receiving financial support, research equipment, or consultancy fees from various entities.
Oral iron of no benefit in heart failure with iron deficiency
High-dose oral iron therapy doesn’t improve exercise capacity in the estimated 50% of patients with symptomatic heart failure who also have iron deficiency, according to a report published online May 16 in JAMA.
Iron deficiency in patients with HF, regardless of their hemoglobin status, is associated with reduced functional capacity, poorer quality of life, and increased mortality. Iron plays a crucial role in the delivery and utilization of oxygen, and “cells with high-energy demands, including skeletal and cardiac myocytes, are particularly sensitive to depleted iron stores,” said Gregory D. Lewis, MD, of the pulmonary critical care unit of Massachusetts General Hospital, Boston, and his associates.
The IRONOUT study was conducted at 23 U.S. medical centers, where outcomes after 16 weeks of oral iron therapy (150 mg twice daily) were compared against matching placebo in 225 patients. The median patient age was 63 years, and the median duration of HF was 5.7 years. Ischemic heart disease was the primary cause of HF in 78% of the study participants.
These patients had low LVEF and poor exercise capacity, despite having high rates of guideline-directed treatment with medications.
The primary endpoint was a change in peak oxygen uptake (peak VO2) at the conclusion of treatment, a measure that “reflects the multiple mechanisms by which iron repletion is expected to improve systemic oxygen delivery and utilization.” Change in peak VO2 was not significantly different between the 111 participants who took oral iron supplements (+23 mL/min) and the 114 who took placebo (–2 mL/min), the investigators wrote (JAMA Pediatr. 2017 May 16. doi: 10.1001/jama.2017.5427).
In subgroup analyses, oral iron also failed to improve peak VO2 in any subgroup of patients: neither men nor women; neither those with decreased hemoglobin nor those with normal hemoglobin levels; nor patients with or without venous congestion at baseline. Oral iron also failed to improve secondary endpoints including 6-minute walk distance, quality of life scores, NT-proBNP levels, and ventilatory efficiency.
In contrast to previous studies of IV iron repletion, oral iron supplementation “produced minimal improvement in iron stores, implicating the route of administration rather than the strategy of iron repletion in the lack of clinical benefit,” Dr. Lewis and his associates said.
This study was funded by the National Heart, Lung, and Blood Institute, which also conceived, designed, and conducted the trial. Dr. Lewis reported ties to Abbott, Novartis, Shape Systems, Stealth Bio Therapeutics, Ironwood, Cheetah Medical, Luitpold, and SoniVie. His associates reported ties to numerous industry sources.
High-dose oral iron therapy doesn’t improve exercise capacity in the estimated 50% of patients with symptomatic heart failure who also have iron deficiency, according to a report published online May 16 in JAMA.
Iron deficiency in patients with HF, regardless of their hemoglobin status, is associated with reduced functional capacity, poorer quality of life, and increased mortality. Iron plays a crucial role in the delivery and utilization of oxygen, and “cells with high-energy demands, including skeletal and cardiac myocytes, are particularly sensitive to depleted iron stores,” said Gregory D. Lewis, MD, of the pulmonary critical care unit of Massachusetts General Hospital, Boston, and his associates.
The IRONOUT study was conducted at 23 U.S. medical centers, where outcomes after 16 weeks of oral iron therapy (150 mg twice daily) were compared against matching placebo in 225 patients. The median patient age was 63 years, and the median duration of HF was 5.7 years. Ischemic heart disease was the primary cause of HF in 78% of the study participants.
These patients had low LVEF and poor exercise capacity, despite having high rates of guideline-directed treatment with medications.
The primary endpoint was a change in peak oxygen uptake (peak VO2) at the conclusion of treatment, a measure that “reflects the multiple mechanisms by which iron repletion is expected to improve systemic oxygen delivery and utilization.” Change in peak VO2 was not significantly different between the 111 participants who took oral iron supplements (+23 mL/min) and the 114 who took placebo (–2 mL/min), the investigators wrote (JAMA Pediatr. 2017 May 16. doi: 10.1001/jama.2017.5427).
In subgroup analyses, oral iron also failed to improve peak VO2 in any subgroup of patients: neither men nor women; neither those with decreased hemoglobin nor those with normal hemoglobin levels; nor patients with or without venous congestion at baseline. Oral iron also failed to improve secondary endpoints including 6-minute walk distance, quality of life scores, NT-proBNP levels, and ventilatory efficiency.
In contrast to previous studies of IV iron repletion, oral iron supplementation “produced minimal improvement in iron stores, implicating the route of administration rather than the strategy of iron repletion in the lack of clinical benefit,” Dr. Lewis and his associates said.
This study was funded by the National Heart, Lung, and Blood Institute, which also conceived, designed, and conducted the trial. Dr. Lewis reported ties to Abbott, Novartis, Shape Systems, Stealth Bio Therapeutics, Ironwood, Cheetah Medical, Luitpold, and SoniVie. His associates reported ties to numerous industry sources.
High-dose oral iron therapy doesn’t improve exercise capacity in the estimated 50% of patients with symptomatic heart failure who also have iron deficiency, according to a report published online May 16 in JAMA.
Iron deficiency in patients with HF, regardless of their hemoglobin status, is associated with reduced functional capacity, poorer quality of life, and increased mortality. Iron plays a crucial role in the delivery and utilization of oxygen, and “cells with high-energy demands, including skeletal and cardiac myocytes, are particularly sensitive to depleted iron stores,” said Gregory D. Lewis, MD, of the pulmonary critical care unit of Massachusetts General Hospital, Boston, and his associates.
The IRONOUT study was conducted at 23 U.S. medical centers, where outcomes after 16 weeks of oral iron therapy (150 mg twice daily) were compared against matching placebo in 225 patients. The median patient age was 63 years, and the median duration of HF was 5.7 years. Ischemic heart disease was the primary cause of HF in 78% of the study participants.
These patients had low LVEF and poor exercise capacity, despite having high rates of guideline-directed treatment with medications.
The primary endpoint was a change in peak oxygen uptake (peak VO2) at the conclusion of treatment, a measure that “reflects the multiple mechanisms by which iron repletion is expected to improve systemic oxygen delivery and utilization.” Change in peak VO2 was not significantly different between the 111 participants who took oral iron supplements (+23 mL/min) and the 114 who took placebo (–2 mL/min), the investigators wrote (JAMA Pediatr. 2017 May 16. doi: 10.1001/jama.2017.5427).
In subgroup analyses, oral iron also failed to improve peak VO2 in any subgroup of patients: neither men nor women; neither those with decreased hemoglobin nor those with normal hemoglobin levels; nor patients with or without venous congestion at baseline. Oral iron also failed to improve secondary endpoints including 6-minute walk distance, quality of life scores, NT-proBNP levels, and ventilatory efficiency.
In contrast to previous studies of IV iron repletion, oral iron supplementation “produced minimal improvement in iron stores, implicating the route of administration rather than the strategy of iron repletion in the lack of clinical benefit,” Dr. Lewis and his associates said.
This study was funded by the National Heart, Lung, and Blood Institute, which also conceived, designed, and conducted the trial. Dr. Lewis reported ties to Abbott, Novartis, Shape Systems, Stealth Bio Therapeutics, Ironwood, Cheetah Medical, Luitpold, and SoniVie. His associates reported ties to numerous industry sources.
Key clinical point: High-dose oral iron therapy doesn’t improve exercise capacity in the estimated 50% of patients with symptomatic heart failure and iron deficiency.
Major finding: Change in peak VO2 was not significantly different between the 111 participants who took oral iron supplements (+23 mL/min) and the 114 who took placebo (–2 mL/min).
Data source: A multicenter, randomized, double-blind, placebo-controlled phase II trial involving 225 patients treated for 16 weeks.
Disclosures: This study was funded by the National Heart, Lung, and Blood Institute (NCT02188784), which also conceived, designed, and conducted the trial. Dr. Lewis reported ties to Abbott, Novartis, Shape Systems, Stealth Bio Therapeutics, Ironwood, Cheetah Medical, Luitpold, and SoniVie. His associates reported ties to numerous industry sources.
Mycobacteria subset plagues pulmonary patients
Nontuberculous mycobacteria accounts for an increasing percentage of pulmonary disease, and nonsurgical treatment alone has not shown effectiveness, according to data from a meta-analysis of 24 studies and 1,224 patients. The study results were published online in Chest.
Data on therapeutic successes in cases of nontuberculosis mycobacteria (NTM)–related pulmonary disease are limited, in particular for those species not related to the Mycobacterium avium complex (non-MAC), wrote Roland Diel, MD, of University Medical Hospital Schleswig-Holstein, Germany, and his colleagues.
In particular, non-MAC species Mycobacterium xenopi (MX), Mycobacterium abscessus, Mycobacterium malmoense, and Mycobacterium kansasii (MK) were addressed in the studies, which included 16 retrospective chart reviews, 5 randomized trials, and 3 prospective, nonrandomized studies (Chest 2017. doi: 10.1016/j.chest.2017.04.166).
Treatment success was measured by rates of sputum culture conversion (SCC).
Overall, the average proportion of SCC for patients with M. abscessus was 41% after subtraction for posttreatment relapses, but reached 70% for subspecies M. massiliense in macrolide-containing treatments. The average proportion of SCC was 80% for patients with M. kansasii, 32% for those with MX, and 54% for those with M. malmoense.
Treatment success ranged from 9% to 73% for M. xenopi patients, but all-cause mortality was 69%. Of note, a 100% success rate was noted in M. kansasii patients using a three-drug TB regimen of isoniazid, rifampicin, and ethambutol, or with a combination of ethambutol, rifampicin, and clarithromycin, the researchers noted.
The percentage of SCC in 55 patients with lung resection and either MX or M. abscessus was considered high at 76%.
The study findings were limited by the diverse definitions of treatment success and by the variety of treatments and “an optimal multidrug treatment cannot be derived from the few studies and has yet to be determined,” the researchers said. In the absence of optimal drug therapy, functional and quality of life elements deserve greater consideration when evaluating outcomes in patients with non-MAC NTM pulmonary disease, they added.
Dr. Diel reported receiving lecturing and/or consulting fees from Insmed and Riemser.
Nontuberculous mycobacteria accounts for an increasing percentage of pulmonary disease, and nonsurgical treatment alone has not shown effectiveness, according to data from a meta-analysis of 24 studies and 1,224 patients. The study results were published online in Chest.
Data on therapeutic successes in cases of nontuberculosis mycobacteria (NTM)–related pulmonary disease are limited, in particular for those species not related to the Mycobacterium avium complex (non-MAC), wrote Roland Diel, MD, of University Medical Hospital Schleswig-Holstein, Germany, and his colleagues.
In particular, non-MAC species Mycobacterium xenopi (MX), Mycobacterium abscessus, Mycobacterium malmoense, and Mycobacterium kansasii (MK) were addressed in the studies, which included 16 retrospective chart reviews, 5 randomized trials, and 3 prospective, nonrandomized studies (Chest 2017. doi: 10.1016/j.chest.2017.04.166).
Treatment success was measured by rates of sputum culture conversion (SCC).
Overall, the average proportion of SCC for patients with M. abscessus was 41% after subtraction for posttreatment relapses, but reached 70% for subspecies M. massiliense in macrolide-containing treatments. The average proportion of SCC was 80% for patients with M. kansasii, 32% for those with MX, and 54% for those with M. malmoense.
Treatment success ranged from 9% to 73% for M. xenopi patients, but all-cause mortality was 69%. Of note, a 100% success rate was noted in M. kansasii patients using a three-drug TB regimen of isoniazid, rifampicin, and ethambutol, or with a combination of ethambutol, rifampicin, and clarithromycin, the researchers noted.
The percentage of SCC in 55 patients with lung resection and either MX or M. abscessus was considered high at 76%.
The study findings were limited by the diverse definitions of treatment success and by the variety of treatments and “an optimal multidrug treatment cannot be derived from the few studies and has yet to be determined,” the researchers said. In the absence of optimal drug therapy, functional and quality of life elements deserve greater consideration when evaluating outcomes in patients with non-MAC NTM pulmonary disease, they added.
Dr. Diel reported receiving lecturing and/or consulting fees from Insmed and Riemser.
Nontuberculous mycobacteria accounts for an increasing percentage of pulmonary disease, and nonsurgical treatment alone has not shown effectiveness, according to data from a meta-analysis of 24 studies and 1,224 patients. The study results were published online in Chest.
Data on therapeutic successes in cases of nontuberculosis mycobacteria (NTM)–related pulmonary disease are limited, in particular for those species not related to the Mycobacterium avium complex (non-MAC), wrote Roland Diel, MD, of University Medical Hospital Schleswig-Holstein, Germany, and his colleagues.
In particular, non-MAC species Mycobacterium xenopi (MX), Mycobacterium abscessus, Mycobacterium malmoense, and Mycobacterium kansasii (MK) were addressed in the studies, which included 16 retrospective chart reviews, 5 randomized trials, and 3 prospective, nonrandomized studies (Chest 2017. doi: 10.1016/j.chest.2017.04.166).
Treatment success was measured by rates of sputum culture conversion (SCC).
Overall, the average proportion of SCC for patients with M. abscessus was 41% after subtraction for posttreatment relapses, but reached 70% for subspecies M. massiliense in macrolide-containing treatments. The average proportion of SCC was 80% for patients with M. kansasii, 32% for those with MX, and 54% for those with M. malmoense.
Treatment success ranged from 9% to 73% for M. xenopi patients, but all-cause mortality was 69%. Of note, a 100% success rate was noted in M. kansasii patients using a three-drug TB regimen of isoniazid, rifampicin, and ethambutol, or with a combination of ethambutol, rifampicin, and clarithromycin, the researchers noted.
The percentage of SCC in 55 patients with lung resection and either MX or M. abscessus was considered high at 76%.
The study findings were limited by the diverse definitions of treatment success and by the variety of treatments and “an optimal multidrug treatment cannot be derived from the few studies and has yet to be determined,” the researchers said. In the absence of optimal drug therapy, functional and quality of life elements deserve greater consideration when evaluating outcomes in patients with non-MAC NTM pulmonary disease, they added.
Dr. Diel reported receiving lecturing and/or consulting fees from Insmed and Riemser.
FROM CHEST
Key clinical point: An optimal multidrug treatment has not yet been found for patients with nontuberculosis mycobacteria (NTM)–related pulmonary disease.
Major finding: The average proportion of sputum culture conversion (SCC) for patients with M. abscessus was 42% after subtraction for posttreatment relapses, but reached 79% for subspecies M. massiliense in macrolide-containing treatments. The average proportion of SCC was 80% for patients with M. kansasii, 32% for those with M. xenopi, and 54% for those with M. malmoense.
Data source: A meta-analysis of 24 studies and 1,224 patients.
Disclosures: Dr. Roland Diel reported receiving lecturing and/or consulting fees from Insmed and Riemser.
Children’s asthma risk reduced with prenatal vitamin D supplementation
SAN FRANCISCO – Vitamin D supplementation during pregnancy may reduce the incidence of asthma or allergies in children at high risk for atopic disease, a study showed.
At age 3 years, asthma or recurrent wheeze occurred in 24% of children born to mothers with substantial vitamin D3 supplementation in pregnancy, compared with 30% of children whose mothers took a placebo during pregnancy.
However, observational study findings on vitamin D deficiency in pregnancy and asthma risk have been mixed, with no effect seen in research using measurements of 25OHD levels, despite protective effects seen in studies estimating vitamin D intake based on diet. Dr. Litonjua, therefore, led a randomized, controlled trial at three clinical centers to test whether vitamin D supplementation in pregnancy could prevent children at high risk of asthma from developing the condition. High-risk status was based on the presence of maternal and/or paternal asthma, allergic rhinitis, or eczema.
The 881 initial participants, enrolled between October 2009 and January 2015, were randomized to receive either 4,000 IU daily of vitamin D3 (440 women) or a placebo daily (436 women). Both groups took a multivitamin that contained 400 IU of vitamin D3. The participants included 43% black women, 26% white women, 14% Hispanic women, and 17% of other races/ethnicities.
The researchers collected maternal blood at the start of the study, between 32 and 38 weeks’ post partum, and at 1-year post partum. They collected cord blood at birth and then children’s blood at 1, 3, and 6 years old. At the third trimester, 87% of the women in the intervention group and 72% of the control group women had at least 50 nmol/L of 25OHD. Levels of at least 75 nmol/L were present in 75% of the intervention group and 35% of the control group in the third trimester.
Primary follow-up occurred at 3 years old with continuing follow-up through 6 years old, but data also were collected every 3 months regarding asthma and allergy symptoms and environmental exposures and diet. Stool was collected for microbiome analysis at 6 months, 1 year, and 3 years, and then annually after age 3 years. Children’s lung function was assessed with impulse oscillometry annually starting at age 4 years, with spirometry annually starting at age 5 years, and with bronchodilator response at age 6 years, Dr. Litonjua reported at the Pediatric Academic Societies meeting.
Just over one-quarter (27%) of the 806 children included in the final analysis had parental report of either an asthma diagnosis or recurrent wheeze, defined using any of five criteria involving multiple wheeze reports and/or use of an asthma controller. Rates of asthma or wheeze were significantly lower in children of women supplemented with 4,400 IU of vitamin D than in those born to women in the control group.
At age 1 year, the rate of asthma or wheeze among children from the intervention group was 9 percentage points lower than that of children from the control group, a 36% reduction. By age 2 years, the rate difference was 7%, a 25% reduced risk for intervention children, compared with control children. Children from the intervention group had a 20% lower risk of asthma or wheeze at age 3 years than those from the control group, with a rate difference of 6% (P = .051).
“Both maternal baseline 25OHD levels and third-trimester 25OHD levels were inversely associated with asthma/recurrent wheeze by age 3 years,” Dr. Litonjua reported, and relative risk at age 3 years was identical in black and white children. Maternal levels of 25OHD in the first trimester, however, “modified the effects of supplementation such that children born to women with higher levels and [who] were in the treatment arm had lowest risks for asthma/recurrent wheeze,” he said.
The greater reduction among women with higher baseline levels and supplementation suggests that higher levels than 30 ng/mL may be necessary for the prevention of asthma or allergies, Dr. Litonjua said. Personalized dosing or earlier supplementation may, therefore, be needed, he said.
“One of the main findings from our trial was that there were no serious adverse effects,” he said. Other trials, however, have found concerns with vitamin D toxicity. One challenge in the study was very low adherence: Only about half the women regularly took their vitamin D supplements at first, Dr. Litonjua said, although they were eventually able to raise adherence to around 80%.
The research was funded by the National Heart, Lung, and Blood Institute. Dr. Litonjua reported royalties from UpToDate and Springer Humana Press and consultation fees from AstraZeneca.
SAN FRANCISCO – Vitamin D supplementation during pregnancy may reduce the incidence of asthma or allergies in children at high risk for atopic disease, a study showed.
At age 3 years, asthma or recurrent wheeze occurred in 24% of children born to mothers with substantial vitamin D3 supplementation in pregnancy, compared with 30% of children whose mothers took a placebo during pregnancy.
However, observational study findings on vitamin D deficiency in pregnancy and asthma risk have been mixed, with no effect seen in research using measurements of 25OHD levels, despite protective effects seen in studies estimating vitamin D intake based on diet. Dr. Litonjua, therefore, led a randomized, controlled trial at three clinical centers to test whether vitamin D supplementation in pregnancy could prevent children at high risk of asthma from developing the condition. High-risk status was based on the presence of maternal and/or paternal asthma, allergic rhinitis, or eczema.
The 881 initial participants, enrolled between October 2009 and January 2015, were randomized to receive either 4,000 IU daily of vitamin D3 (440 women) or a placebo daily (436 women). Both groups took a multivitamin that contained 400 IU of vitamin D3. The participants included 43% black women, 26% white women, 14% Hispanic women, and 17% of other races/ethnicities.
The researchers collected maternal blood at the start of the study, between 32 and 38 weeks’ post partum, and at 1-year post partum. They collected cord blood at birth and then children’s blood at 1, 3, and 6 years old. At the third trimester, 87% of the women in the intervention group and 72% of the control group women had at least 50 nmol/L of 25OHD. Levels of at least 75 nmol/L were present in 75% of the intervention group and 35% of the control group in the third trimester.
Primary follow-up occurred at 3 years old with continuing follow-up through 6 years old, but data also were collected every 3 months regarding asthma and allergy symptoms and environmental exposures and diet. Stool was collected for microbiome analysis at 6 months, 1 year, and 3 years, and then annually after age 3 years. Children’s lung function was assessed with impulse oscillometry annually starting at age 4 years, with spirometry annually starting at age 5 years, and with bronchodilator response at age 6 years, Dr. Litonjua reported at the Pediatric Academic Societies meeting.
Just over one-quarter (27%) of the 806 children included in the final analysis had parental report of either an asthma diagnosis or recurrent wheeze, defined using any of five criteria involving multiple wheeze reports and/or use of an asthma controller. Rates of asthma or wheeze were significantly lower in children of women supplemented with 4,400 IU of vitamin D than in those born to women in the control group.
At age 1 year, the rate of asthma or wheeze among children from the intervention group was 9 percentage points lower than that of children from the control group, a 36% reduction. By age 2 years, the rate difference was 7%, a 25% reduced risk for intervention children, compared with control children. Children from the intervention group had a 20% lower risk of asthma or wheeze at age 3 years than those from the control group, with a rate difference of 6% (P = .051).
“Both maternal baseline 25OHD levels and third-trimester 25OHD levels were inversely associated with asthma/recurrent wheeze by age 3 years,” Dr. Litonjua reported, and relative risk at age 3 years was identical in black and white children. Maternal levels of 25OHD in the first trimester, however, “modified the effects of supplementation such that children born to women with higher levels and [who] were in the treatment arm had lowest risks for asthma/recurrent wheeze,” he said.
The greater reduction among women with higher baseline levels and supplementation suggests that higher levels than 30 ng/mL may be necessary for the prevention of asthma or allergies, Dr. Litonjua said. Personalized dosing or earlier supplementation may, therefore, be needed, he said.
“One of the main findings from our trial was that there were no serious adverse effects,” he said. Other trials, however, have found concerns with vitamin D toxicity. One challenge in the study was very low adherence: Only about half the women regularly took their vitamin D supplements at first, Dr. Litonjua said, although they were eventually able to raise adherence to around 80%.
The research was funded by the National Heart, Lung, and Blood Institute. Dr. Litonjua reported royalties from UpToDate and Springer Humana Press and consultation fees from AstraZeneca.
SAN FRANCISCO – Vitamin D supplementation during pregnancy may reduce the incidence of asthma or allergies in children at high risk for atopic disease, a study showed.
At age 3 years, asthma or recurrent wheeze occurred in 24% of children born to mothers with substantial vitamin D3 supplementation in pregnancy, compared with 30% of children whose mothers took a placebo during pregnancy.
However, observational study findings on vitamin D deficiency in pregnancy and asthma risk have been mixed, with no effect seen in research using measurements of 25OHD levels, despite protective effects seen in studies estimating vitamin D intake based on diet. Dr. Litonjua, therefore, led a randomized, controlled trial at three clinical centers to test whether vitamin D supplementation in pregnancy could prevent children at high risk of asthma from developing the condition. High-risk status was based on the presence of maternal and/or paternal asthma, allergic rhinitis, or eczema.
The 881 initial participants, enrolled between October 2009 and January 2015, were randomized to receive either 4,000 IU daily of vitamin D3 (440 women) or a placebo daily (436 women). Both groups took a multivitamin that contained 400 IU of vitamin D3. The participants included 43% black women, 26% white women, 14% Hispanic women, and 17% of other races/ethnicities.
The researchers collected maternal blood at the start of the study, between 32 and 38 weeks’ post partum, and at 1-year post partum. They collected cord blood at birth and then children’s blood at 1, 3, and 6 years old. At the third trimester, 87% of the women in the intervention group and 72% of the control group women had at least 50 nmol/L of 25OHD. Levels of at least 75 nmol/L were present in 75% of the intervention group and 35% of the control group in the third trimester.
Primary follow-up occurred at 3 years old with continuing follow-up through 6 years old, but data also were collected every 3 months regarding asthma and allergy symptoms and environmental exposures and diet. Stool was collected for microbiome analysis at 6 months, 1 year, and 3 years, and then annually after age 3 years. Children’s lung function was assessed with impulse oscillometry annually starting at age 4 years, with spirometry annually starting at age 5 years, and with bronchodilator response at age 6 years, Dr. Litonjua reported at the Pediatric Academic Societies meeting.
Just over one-quarter (27%) of the 806 children included in the final analysis had parental report of either an asthma diagnosis or recurrent wheeze, defined using any of five criteria involving multiple wheeze reports and/or use of an asthma controller. Rates of asthma or wheeze were significantly lower in children of women supplemented with 4,400 IU of vitamin D than in those born to women in the control group.
At age 1 year, the rate of asthma or wheeze among children from the intervention group was 9 percentage points lower than that of children from the control group, a 36% reduction. By age 2 years, the rate difference was 7%, a 25% reduced risk for intervention children, compared with control children. Children from the intervention group had a 20% lower risk of asthma or wheeze at age 3 years than those from the control group, with a rate difference of 6% (P = .051).
“Both maternal baseline 25OHD levels and third-trimester 25OHD levels were inversely associated with asthma/recurrent wheeze by age 3 years,” Dr. Litonjua reported, and relative risk at age 3 years was identical in black and white children. Maternal levels of 25OHD in the first trimester, however, “modified the effects of supplementation such that children born to women with higher levels and [who] were in the treatment arm had lowest risks for asthma/recurrent wheeze,” he said.
The greater reduction among women with higher baseline levels and supplementation suggests that higher levels than 30 ng/mL may be necessary for the prevention of asthma or allergies, Dr. Litonjua said. Personalized dosing or earlier supplementation may, therefore, be needed, he said.
“One of the main findings from our trial was that there were no serious adverse effects,” he said. Other trials, however, have found concerns with vitamin D toxicity. One challenge in the study was very low adherence: Only about half the women regularly took their vitamin D supplements at first, Dr. Litonjua said, although they were eventually able to raise adherence to around 80%.
The research was funded by the National Heart, Lung, and Blood Institute. Dr. Litonjua reported royalties from UpToDate and Springer Humana Press and consultation fees from AstraZeneca.
AT PAS 2017
Key clinical point: Higher levels of vitamin D3 in pregnancy led to a reduced risk of asthma or allergies in subsequent children at high risk for the condition.
Major finding: (P = .051).
Data source: A randomized controlled trial at three clinical centers from October 2009 through January 2015, involving 881 pregnant women whose children had a high risk of asthma or allergies and 806 subsequent children.
Disclosures: The research was funded by the National Heart, Lung, and Blood Institute. Dr. Litonjua reported royalties from UpToDate and Springer Humana Press, and consultation fees from AstraZeneca.
FDA: Fluoroquinolone use not linked to retina detachment, aortic problems
The Food and Drug Administration has found no evidence of a link between fluoroquinolone usage and retinal detachment or aortic aneurysm and dissection, according to a new Drug Safety Communication update on potential serious, disabling side effects of oral and injectable fluoroquinolone antibiotics.
Fluoroquinolones are used to treat acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and uncomplicated urinary tract infections.
However, after reviewing patient cases and study findings, the FDA said the evidence didn’t support an association between fluoroquinolone usage and potential retinal or aortic dangers, according to its May 10, 2017, Drug Safety Communication update.
Serious side effects associated with fluoroquinolone use include hallucination, depression, suicidal thoughts, tendinitis and tendon rupture, a “pins and needles” feeling in the arms and legs, joint pain and swelling, skin rash, and severe diarrhea.
“We will continue to assess safety issues with fluoroquinolones, and will update the public if additional actions are needed,” the FDA said in a statement.
The Food and Drug Administration has found no evidence of a link between fluoroquinolone usage and retinal detachment or aortic aneurysm and dissection, according to a new Drug Safety Communication update on potential serious, disabling side effects of oral and injectable fluoroquinolone antibiotics.
Fluoroquinolones are used to treat acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and uncomplicated urinary tract infections.
However, after reviewing patient cases and study findings, the FDA said the evidence didn’t support an association between fluoroquinolone usage and potential retinal or aortic dangers, according to its May 10, 2017, Drug Safety Communication update.
Serious side effects associated with fluoroquinolone use include hallucination, depression, suicidal thoughts, tendinitis and tendon rupture, a “pins and needles” feeling in the arms and legs, joint pain and swelling, skin rash, and severe diarrhea.
“We will continue to assess safety issues with fluoroquinolones, and will update the public if additional actions are needed,” the FDA said in a statement.
The Food and Drug Administration has found no evidence of a link between fluoroquinolone usage and retinal detachment or aortic aneurysm and dissection, according to a new Drug Safety Communication update on potential serious, disabling side effects of oral and injectable fluoroquinolone antibiotics.
Fluoroquinolones are used to treat acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and uncomplicated urinary tract infections.
However, after reviewing patient cases and study findings, the FDA said the evidence didn’t support an association between fluoroquinolone usage and potential retinal or aortic dangers, according to its May 10, 2017, Drug Safety Communication update.
Serious side effects associated with fluoroquinolone use include hallucination, depression, suicidal thoughts, tendinitis and tendon rupture, a “pins and needles” feeling in the arms and legs, joint pain and swelling, skin rash, and severe diarrhea.
“We will continue to assess safety issues with fluoroquinolones, and will update the public if additional actions are needed,” the FDA said in a statement.
Lung cancer metastatic sites differ by histology, tumor factors
GENEVA – A review of data on more than 75,000 patients with lung cancer has revealed distinct patterns of metastasis according to subtype, a finding that could help in surveillance, treatment planning, and prophylaxis, an investigator contends.
Patients with small cell lung cancer (SCLC) had significantly higher rates of liver metastases than patients with non–small cell lung cancer (NSCLC), while patients with NSCLC had significantly higher rates of metastases to bone, reported Mohamed Hendawi, MD, a visiting scholar at the Ohio State University Medical Center in Columbus.
“Predictors for liver metastasis were small cell and adenocarcinoma histology, lower and upper lobe locations, and high grade tumors. Predictors for metastasis to brain were advanced age at diagnosis, adenocarcinoma and small-cell histology, lower lobe [and] main bronchus locations, and high grade tumors,” he wrote in a scientific poster presented at the European Lung Cancer Conference.
Dr. Hendawi drew records on all patients with metastatic lung cancer included in the 2010-2013 Surveillance, Epidemiology, and End Results database. He used univariate and multivariate logistic regression models to evaluate predictors of metastasis.
The data set included a total of 76,254 patients with metastatic lung cancer, of which 17% were SCLC and 83% were NSCLC tumors. In 54% of patients, the primary tumor was in the right lung; in 38%, it was in the left lung; and, in 8% of patients, the primary tumor was bilateral.
The rates of metastases to bone were high in both major lung cancer types but, as noted before, were significantly higher in patients with NSCLC: 37% compared with 34% for patients with SCLC (P less than .001).
In contrast, the incidence of liver metastases in SCLC was more than double that of NSCLC: 46% vs. 20%, respectively (P less than .001). There were slightly, but significantly, fewer cases of brain metastases at the time of diagnosis among patients with SCLC: 25% vs. 26% (P = .003).
Histologic subtypes significantly associated with both brain and liver metastases were, in descending order, adenocarcinomas, small cell, and squamous cell cancers.
Although carcinoid lung cancers accounted for only 2.1% of all tumors, they were associated with a high rate of metastasis to brain at diagnosis (44.8%).
As noted, independent risk factors for liver metastasis were small cell and adenocarcinoma histologies (P less than .001), tumors in the upper lobe (P = .028), and high-grade tumor (P less than .001).
Independent predictors for brain metastases were advanced age at diagnosis (P less than .001), adenocarcinoma and small-cell histologies (P less than .001), lower lobe or main bronchus locations (P = .004), and higher-grade tumors (P less than .001).
In a poster discussion session, Paolo Boffetta, MD, MPH, from the Icahn School of Medicine at Mount Sinai in New York City, the invited discussant, commented that, while he thought that the data were interesting, “the main issue I had with this poster is that it’s limited to patients with metastasis, so we cannot really evaluate the risk of metastasis according to the different histological types and the absolute risk of developing metastases in one or the other organ but only the relative risk of developing metastasis in one organ versus the other having one or the other histology.”
“So, we really don’t know whether the risk is increased in one group or decreased in the other one that generates these differences,” he said.
The study did not receive outside support. Dr. Hendawi declared no conflicts of interest.
GENEVA – A review of data on more than 75,000 patients with lung cancer has revealed distinct patterns of metastasis according to subtype, a finding that could help in surveillance, treatment planning, and prophylaxis, an investigator contends.
Patients with small cell lung cancer (SCLC) had significantly higher rates of liver metastases than patients with non–small cell lung cancer (NSCLC), while patients with NSCLC had significantly higher rates of metastases to bone, reported Mohamed Hendawi, MD, a visiting scholar at the Ohio State University Medical Center in Columbus.
“Predictors for liver metastasis were small cell and adenocarcinoma histology, lower and upper lobe locations, and high grade tumors. Predictors for metastasis to brain were advanced age at diagnosis, adenocarcinoma and small-cell histology, lower lobe [and] main bronchus locations, and high grade tumors,” he wrote in a scientific poster presented at the European Lung Cancer Conference.
Dr. Hendawi drew records on all patients with metastatic lung cancer included in the 2010-2013 Surveillance, Epidemiology, and End Results database. He used univariate and multivariate logistic regression models to evaluate predictors of metastasis.
The data set included a total of 76,254 patients with metastatic lung cancer, of which 17% were SCLC and 83% were NSCLC tumors. In 54% of patients, the primary tumor was in the right lung; in 38%, it was in the left lung; and, in 8% of patients, the primary tumor was bilateral.
The rates of metastases to bone were high in both major lung cancer types but, as noted before, were significantly higher in patients with NSCLC: 37% compared with 34% for patients with SCLC (P less than .001).
In contrast, the incidence of liver metastases in SCLC was more than double that of NSCLC: 46% vs. 20%, respectively (P less than .001). There were slightly, but significantly, fewer cases of brain metastases at the time of diagnosis among patients with SCLC: 25% vs. 26% (P = .003).
Histologic subtypes significantly associated with both brain and liver metastases were, in descending order, adenocarcinomas, small cell, and squamous cell cancers.
Although carcinoid lung cancers accounted for only 2.1% of all tumors, they were associated with a high rate of metastasis to brain at diagnosis (44.8%).
As noted, independent risk factors for liver metastasis were small cell and adenocarcinoma histologies (P less than .001), tumors in the upper lobe (P = .028), and high-grade tumor (P less than .001).
Independent predictors for brain metastases were advanced age at diagnosis (P less than .001), adenocarcinoma and small-cell histologies (P less than .001), lower lobe or main bronchus locations (P = .004), and higher-grade tumors (P less than .001).
In a poster discussion session, Paolo Boffetta, MD, MPH, from the Icahn School of Medicine at Mount Sinai in New York City, the invited discussant, commented that, while he thought that the data were interesting, “the main issue I had with this poster is that it’s limited to patients with metastasis, so we cannot really evaluate the risk of metastasis according to the different histological types and the absolute risk of developing metastases in one or the other organ but only the relative risk of developing metastasis in one organ versus the other having one or the other histology.”
“So, we really don’t know whether the risk is increased in one group or decreased in the other one that generates these differences,” he said.
The study did not receive outside support. Dr. Hendawi declared no conflicts of interest.
GENEVA – A review of data on more than 75,000 patients with lung cancer has revealed distinct patterns of metastasis according to subtype, a finding that could help in surveillance, treatment planning, and prophylaxis, an investigator contends.
Patients with small cell lung cancer (SCLC) had significantly higher rates of liver metastases than patients with non–small cell lung cancer (NSCLC), while patients with NSCLC had significantly higher rates of metastases to bone, reported Mohamed Hendawi, MD, a visiting scholar at the Ohio State University Medical Center in Columbus.
“Predictors for liver metastasis were small cell and adenocarcinoma histology, lower and upper lobe locations, and high grade tumors. Predictors for metastasis to brain were advanced age at diagnosis, adenocarcinoma and small-cell histology, lower lobe [and] main bronchus locations, and high grade tumors,” he wrote in a scientific poster presented at the European Lung Cancer Conference.
Dr. Hendawi drew records on all patients with metastatic lung cancer included in the 2010-2013 Surveillance, Epidemiology, and End Results database. He used univariate and multivariate logistic regression models to evaluate predictors of metastasis.
The data set included a total of 76,254 patients with metastatic lung cancer, of which 17% were SCLC and 83% were NSCLC tumors. In 54% of patients, the primary tumor was in the right lung; in 38%, it was in the left lung; and, in 8% of patients, the primary tumor was bilateral.
The rates of metastases to bone were high in both major lung cancer types but, as noted before, were significantly higher in patients with NSCLC: 37% compared with 34% for patients with SCLC (P less than .001).
In contrast, the incidence of liver metastases in SCLC was more than double that of NSCLC: 46% vs. 20%, respectively (P less than .001). There were slightly, but significantly, fewer cases of brain metastases at the time of diagnosis among patients with SCLC: 25% vs. 26% (P = .003).
Histologic subtypes significantly associated with both brain and liver metastases were, in descending order, adenocarcinomas, small cell, and squamous cell cancers.
Although carcinoid lung cancers accounted for only 2.1% of all tumors, they were associated with a high rate of metastasis to brain at diagnosis (44.8%).
As noted, independent risk factors for liver metastasis were small cell and adenocarcinoma histologies (P less than .001), tumors in the upper lobe (P = .028), and high-grade tumor (P less than .001).
Independent predictors for brain metastases were advanced age at diagnosis (P less than .001), adenocarcinoma and small-cell histologies (P less than .001), lower lobe or main bronchus locations (P = .004), and higher-grade tumors (P less than .001).
In a poster discussion session, Paolo Boffetta, MD, MPH, from the Icahn School of Medicine at Mount Sinai in New York City, the invited discussant, commented that, while he thought that the data were interesting, “the main issue I had with this poster is that it’s limited to patients with metastasis, so we cannot really evaluate the risk of metastasis according to the different histological types and the absolute risk of developing metastases in one or the other organ but only the relative risk of developing metastasis in one organ versus the other having one or the other histology.”
“So, we really don’t know whether the risk is increased in one group or decreased in the other one that generates these differences,” he said.
The study did not receive outside support. Dr. Hendawi declared no conflicts of interest.
FROM ELCC
Key clinical point: Lung cancers tend to metastasize to different organs based on histology and other clinical factors.
Major finding: The incidence of metastasis to bone was higher in patients with NSCLC than SCLC, while liver metastases were more than twice as high among patients with SCLC.
Data source: Review of Surveillance, Epidemiology, and End Results data on 76,254 patients with metastatic lung cancer.
Disclosures: The study did not receive outside support. Dr. Hendawi declared no conflicts of interest.