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C-section linked to serious infection in preschoolers
LJUBLJANA, SLOVENIA – Delivery by C-section – especially when elective – carries a significantly higher hospitalization risk for severe infection in the first 5 years of life than vaginal delivery in a study of nearly 7.3 million singleton deliveries in four asset-rich countries, David Burgner, MD, PhD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
“This is something that obstetricians might need to consider when discussing with the family the pros and cons for an elective C-section, particularly one that isn’t otherwise indicated for the baby or the mother,” said Dr. Burgner of the Murdoch Children’s Research Institute in Melbourne.
He presented an observational study of 7.29 million singleton births in Denmark, Great Britain, Scotland, and two Australian states during 1996-2015. C-section rates ranged from a low of 17.5% in Denmark to 29.4% in Western Australia, all of which are greater than the 10%-15% rate endorsed by the World Health Organization. Elective C-section rates varied by country from 39% to 57%. Of note, pediatric hospital care in all four countries is free, so economic considerations didn’t drive admission.
The impetus for this international collaboration was to gain new insight into the differential susceptibility to childhood infection, he explained.
“We know from our clinical practice that pretty much all of the children are exposed to pretty much all potentially serious pathogens during early life. And yet it’s only a minority that develop severe infection. It’s an extremely interesting scientific question and an extremely important clinical question as to what’s driving that differential susceptibility,” according to the pediatric infectious disease specialist.
There are a number of established risk factors for infection-related hospitalization in children, including parental smoking, maternal antibiotic exposure during pregnancy, and growth measurements at birth. Dr. Burgner and coinvestigators hypothesized that another important risk factor is the nature of the microbiome transmitted from mother to baby during delivery. This postnatal microbiome varies depending upon mode of delivery: Vaginal delivery transmits the maternal enteric microbiome, which they reasoned might be through direct immunomodulation that sets up protective immune responses early in life, especially against respiratory and gastrointestinal tract infections. In contrast, delivery by C-section causes the baby to pick up the maternal skin and hospital environment microbiomes, but not the maternal enteric microbiome.
Thus, the investigators hypothesized that C-section poses a greater risk of infection-related hospitalization during the first 5 years of life than does vaginal delivery, and that elective C-section poses a higher risk than does emergency C-section because it is more likely to involve rupture of membranes.
The center-specific rates of C-section and infection-related pediatric infection, when combined into a meta-analysis, bore out the study hypothesis. Emergency C-section was associated with a 9% greater risk of infection-related hospitalization through 5 years of age than was vaginal delivery, while elective C-section was associated with a 13% increased risk, both of which were statistically significant and clinically important.
“We were quite taken with these results. We think they provide evidence that C-section is consistently associated with infection-related hospitalization. It’s an association study that can’t prove causality, but the results implicate the postnatal microbiome as the most plausible explanation in terms of what’s driving this association,” according to Dr. Burgner.
The association between C-section and infection-related hospitalization was persistent throughout the preschool years. For example, the increased risk associated with elective C-section was 16% during age 0-3 months, 20% during months 4-6, 14% in months 7-12, 13% during ages 1-2 years, and 11% among 2- to 5-year-olds, he continued.
The increased risk of severe preschool infection was highest for upper and lower respiratory tract and gastrointestinal infections, which involve the organ systems most likely to experience direct inoculation of the maternal microbiome, he noted.
Because the investigators recognized that the study results were potentially vulnerable to confounding by indication – that is, that the reason for doing a C-section might itself confer increased risk of subsequent preschool infection-related hospitalization – they repeated their analysis in a predefined low-risk subpopulation. The results closely mirrored those in the overall study population: an 8% increased risk in the emergency C-section group and a 14% increased risk with elective C-section.
Results of this large multinational study should provide further support for ongoing research aimed at supporting the infant microbiome after delivery by C-section via vaginal microbial transfer and other methods, he observed.
Dr. Burgner reported having no financial conflicts regarding the study, which was cosponsored by the National Health and Medical Research Council of Australia, the Danish Council for Independent Research, and nonprofit foundations.
LJUBLJANA, SLOVENIA – Delivery by C-section – especially when elective – carries a significantly higher hospitalization risk for severe infection in the first 5 years of life than vaginal delivery in a study of nearly 7.3 million singleton deliveries in four asset-rich countries, David Burgner, MD, PhD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
“This is something that obstetricians might need to consider when discussing with the family the pros and cons for an elective C-section, particularly one that isn’t otherwise indicated for the baby or the mother,” said Dr. Burgner of the Murdoch Children’s Research Institute in Melbourne.
He presented an observational study of 7.29 million singleton births in Denmark, Great Britain, Scotland, and two Australian states during 1996-2015. C-section rates ranged from a low of 17.5% in Denmark to 29.4% in Western Australia, all of which are greater than the 10%-15% rate endorsed by the World Health Organization. Elective C-section rates varied by country from 39% to 57%. Of note, pediatric hospital care in all four countries is free, so economic considerations didn’t drive admission.
The impetus for this international collaboration was to gain new insight into the differential susceptibility to childhood infection, he explained.
“We know from our clinical practice that pretty much all of the children are exposed to pretty much all potentially serious pathogens during early life. And yet it’s only a minority that develop severe infection. It’s an extremely interesting scientific question and an extremely important clinical question as to what’s driving that differential susceptibility,” according to the pediatric infectious disease specialist.
There are a number of established risk factors for infection-related hospitalization in children, including parental smoking, maternal antibiotic exposure during pregnancy, and growth measurements at birth. Dr. Burgner and coinvestigators hypothesized that another important risk factor is the nature of the microbiome transmitted from mother to baby during delivery. This postnatal microbiome varies depending upon mode of delivery: Vaginal delivery transmits the maternal enteric microbiome, which they reasoned might be through direct immunomodulation that sets up protective immune responses early in life, especially against respiratory and gastrointestinal tract infections. In contrast, delivery by C-section causes the baby to pick up the maternal skin and hospital environment microbiomes, but not the maternal enteric microbiome.
Thus, the investigators hypothesized that C-section poses a greater risk of infection-related hospitalization during the first 5 years of life than does vaginal delivery, and that elective C-section poses a higher risk than does emergency C-section because it is more likely to involve rupture of membranes.
The center-specific rates of C-section and infection-related pediatric infection, when combined into a meta-analysis, bore out the study hypothesis. Emergency C-section was associated with a 9% greater risk of infection-related hospitalization through 5 years of age than was vaginal delivery, while elective C-section was associated with a 13% increased risk, both of which were statistically significant and clinically important.
“We were quite taken with these results. We think they provide evidence that C-section is consistently associated with infection-related hospitalization. It’s an association study that can’t prove causality, but the results implicate the postnatal microbiome as the most plausible explanation in terms of what’s driving this association,” according to Dr. Burgner.
The association between C-section and infection-related hospitalization was persistent throughout the preschool years. For example, the increased risk associated with elective C-section was 16% during age 0-3 months, 20% during months 4-6, 14% in months 7-12, 13% during ages 1-2 years, and 11% among 2- to 5-year-olds, he continued.
The increased risk of severe preschool infection was highest for upper and lower respiratory tract and gastrointestinal infections, which involve the organ systems most likely to experience direct inoculation of the maternal microbiome, he noted.
Because the investigators recognized that the study results were potentially vulnerable to confounding by indication – that is, that the reason for doing a C-section might itself confer increased risk of subsequent preschool infection-related hospitalization – they repeated their analysis in a predefined low-risk subpopulation. The results closely mirrored those in the overall study population: an 8% increased risk in the emergency C-section group and a 14% increased risk with elective C-section.
Results of this large multinational study should provide further support for ongoing research aimed at supporting the infant microbiome after delivery by C-section via vaginal microbial transfer and other methods, he observed.
Dr. Burgner reported having no financial conflicts regarding the study, which was cosponsored by the National Health and Medical Research Council of Australia, the Danish Council for Independent Research, and nonprofit foundations.
LJUBLJANA, SLOVENIA – Delivery by C-section – especially when elective – carries a significantly higher hospitalization risk for severe infection in the first 5 years of life than vaginal delivery in a study of nearly 7.3 million singleton deliveries in four asset-rich countries, David Burgner, MD, PhD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
“This is something that obstetricians might need to consider when discussing with the family the pros and cons for an elective C-section, particularly one that isn’t otherwise indicated for the baby or the mother,” said Dr. Burgner of the Murdoch Children’s Research Institute in Melbourne.
He presented an observational study of 7.29 million singleton births in Denmark, Great Britain, Scotland, and two Australian states during 1996-2015. C-section rates ranged from a low of 17.5% in Denmark to 29.4% in Western Australia, all of which are greater than the 10%-15% rate endorsed by the World Health Organization. Elective C-section rates varied by country from 39% to 57%. Of note, pediatric hospital care in all four countries is free, so economic considerations didn’t drive admission.
The impetus for this international collaboration was to gain new insight into the differential susceptibility to childhood infection, he explained.
“We know from our clinical practice that pretty much all of the children are exposed to pretty much all potentially serious pathogens during early life. And yet it’s only a minority that develop severe infection. It’s an extremely interesting scientific question and an extremely important clinical question as to what’s driving that differential susceptibility,” according to the pediatric infectious disease specialist.
There are a number of established risk factors for infection-related hospitalization in children, including parental smoking, maternal antibiotic exposure during pregnancy, and growth measurements at birth. Dr. Burgner and coinvestigators hypothesized that another important risk factor is the nature of the microbiome transmitted from mother to baby during delivery. This postnatal microbiome varies depending upon mode of delivery: Vaginal delivery transmits the maternal enteric microbiome, which they reasoned might be through direct immunomodulation that sets up protective immune responses early in life, especially against respiratory and gastrointestinal tract infections. In contrast, delivery by C-section causes the baby to pick up the maternal skin and hospital environment microbiomes, but not the maternal enteric microbiome.
Thus, the investigators hypothesized that C-section poses a greater risk of infection-related hospitalization during the first 5 years of life than does vaginal delivery, and that elective C-section poses a higher risk than does emergency C-section because it is more likely to involve rupture of membranes.
The center-specific rates of C-section and infection-related pediatric infection, when combined into a meta-analysis, bore out the study hypothesis. Emergency C-section was associated with a 9% greater risk of infection-related hospitalization through 5 years of age than was vaginal delivery, while elective C-section was associated with a 13% increased risk, both of which were statistically significant and clinically important.
“We were quite taken with these results. We think they provide evidence that C-section is consistently associated with infection-related hospitalization. It’s an association study that can’t prove causality, but the results implicate the postnatal microbiome as the most plausible explanation in terms of what’s driving this association,” according to Dr. Burgner.
The association between C-section and infection-related hospitalization was persistent throughout the preschool years. For example, the increased risk associated with elective C-section was 16% during age 0-3 months, 20% during months 4-6, 14% in months 7-12, 13% during ages 1-2 years, and 11% among 2- to 5-year-olds, he continued.
The increased risk of severe preschool infection was highest for upper and lower respiratory tract and gastrointestinal infections, which involve the organ systems most likely to experience direct inoculation of the maternal microbiome, he noted.
Because the investigators recognized that the study results were potentially vulnerable to confounding by indication – that is, that the reason for doing a C-section might itself confer increased risk of subsequent preschool infection-related hospitalization – they repeated their analysis in a predefined low-risk subpopulation. The results closely mirrored those in the overall study population: an 8% increased risk in the emergency C-section group and a 14% increased risk with elective C-section.
Results of this large multinational study should provide further support for ongoing research aimed at supporting the infant microbiome after delivery by C-section via vaginal microbial transfer and other methods, he observed.
Dr. Burgner reported having no financial conflicts regarding the study, which was cosponsored by the National Health and Medical Research Council of Australia, the Danish Council for Independent Research, and nonprofit foundations.
REPORTING FROM ESPID 2019
CPAP for infants with OSA is effective with high adherence
DALLAS – ), according to a study.
“Positive airway pressure is a common treatment for OSA in children,” wrote Christopher Cielo, DO, of Children’s Hospital of Philadelphia Sleep Center, and his colleagues. But the authors note that treating infants with CPAP can be more challenging because infants have less consolidated sleep, may have greater medical complexity, and have smaller faces that make mask fit, titration, and adherence difficult.
The researchers therefore compared use of CPAP for OSA on 32 infants who began the therapy before age 6 months and 102 school-age children who began the therapy between ages 5 and 10 years, all treated at a single sleep center between March 2013 and September 2018.
Only one of the infants (mean age 3 months) had obesity, compared with 37.3% of the school-age children (mean age 7.7 years), but more of the infants (50%) had a craniofacial abnormality compared with the older children (8.9%) (P less than .001).
None of the infants had had an adenotonsillectomy, whereas the majority of the older children (80.4%) had (P less than .001). Rates of neurological abnormality and genetic syndromes (including Down syndrome) were similar between the groups.
In baseline polysomnograms, infants had a higher mean obstructive apnea-hypopnea index (AHI) compared with older children (22.6 vs. 12; P less than .001) and a slightly, but significantly, lower oxygen saturation nadir (81% vs. 87%; P = .002).
Only 9.8% of the children and none of the infants used autotitrating. Similar proportions of both groups – 90.6% of infants and 93.1% of children – achieved a mean AHI below 5 with CPAP treatment, and both CPAP pressure and mean oxygen saturation nadir at final pressure were similar in both groups.
Adherence was higher in infants than in children: Infants used CPAP for at least some time for 93.3% of nights compared with children (83.4%) (P = .009), and infants used CPAP for more than 4 hours for 78.4% of nights, compared with 59.5% of nights among children (P = .04).
Barriers to adherence reported by caregivers were similar between both groups. The most common barrier was child behavior, such as crying or refusing the CPAP, which 25% of infant caregivers and 35.3% of child caregivers reported. While a higher proportion of caregivers reported a poor mask fit for infants (15.6%) than for children (10.8%), the difference was not significant (P = .47). Rates of skin irritation also did not significantly differ between the groups.
In addition to the limitations accompanying any retrospective analysis from a single center, another study limitation was the inability to account for differences in total sleep time between infants and school-age children in comparing CPAP usage.
The National Institutes of Health and the Francis Family Foundation funded the research. The authors had no disclosures.
DALLAS – ), according to a study.
“Positive airway pressure is a common treatment for OSA in children,” wrote Christopher Cielo, DO, of Children’s Hospital of Philadelphia Sleep Center, and his colleagues. But the authors note that treating infants with CPAP can be more challenging because infants have less consolidated sleep, may have greater medical complexity, and have smaller faces that make mask fit, titration, and adherence difficult.
The researchers therefore compared use of CPAP for OSA on 32 infants who began the therapy before age 6 months and 102 school-age children who began the therapy between ages 5 and 10 years, all treated at a single sleep center between March 2013 and September 2018.
Only one of the infants (mean age 3 months) had obesity, compared with 37.3% of the school-age children (mean age 7.7 years), but more of the infants (50%) had a craniofacial abnormality compared with the older children (8.9%) (P less than .001).
None of the infants had had an adenotonsillectomy, whereas the majority of the older children (80.4%) had (P less than .001). Rates of neurological abnormality and genetic syndromes (including Down syndrome) were similar between the groups.
In baseline polysomnograms, infants had a higher mean obstructive apnea-hypopnea index (AHI) compared with older children (22.6 vs. 12; P less than .001) and a slightly, but significantly, lower oxygen saturation nadir (81% vs. 87%; P = .002).
Only 9.8% of the children and none of the infants used autotitrating. Similar proportions of both groups – 90.6% of infants and 93.1% of children – achieved a mean AHI below 5 with CPAP treatment, and both CPAP pressure and mean oxygen saturation nadir at final pressure were similar in both groups.
Adherence was higher in infants than in children: Infants used CPAP for at least some time for 93.3% of nights compared with children (83.4%) (P = .009), and infants used CPAP for more than 4 hours for 78.4% of nights, compared with 59.5% of nights among children (P = .04).
Barriers to adherence reported by caregivers were similar between both groups. The most common barrier was child behavior, such as crying or refusing the CPAP, which 25% of infant caregivers and 35.3% of child caregivers reported. While a higher proportion of caregivers reported a poor mask fit for infants (15.6%) than for children (10.8%), the difference was not significant (P = .47). Rates of skin irritation also did not significantly differ between the groups.
In addition to the limitations accompanying any retrospective analysis from a single center, another study limitation was the inability to account for differences in total sleep time between infants and school-age children in comparing CPAP usage.
The National Institutes of Health and the Francis Family Foundation funded the research. The authors had no disclosures.
DALLAS – ), according to a study.
“Positive airway pressure is a common treatment for OSA in children,” wrote Christopher Cielo, DO, of Children’s Hospital of Philadelphia Sleep Center, and his colleagues. But the authors note that treating infants with CPAP can be more challenging because infants have less consolidated sleep, may have greater medical complexity, and have smaller faces that make mask fit, titration, and adherence difficult.
The researchers therefore compared use of CPAP for OSA on 32 infants who began the therapy before age 6 months and 102 school-age children who began the therapy between ages 5 and 10 years, all treated at a single sleep center between March 2013 and September 2018.
Only one of the infants (mean age 3 months) had obesity, compared with 37.3% of the school-age children (mean age 7.7 years), but more of the infants (50%) had a craniofacial abnormality compared with the older children (8.9%) (P less than .001).
None of the infants had had an adenotonsillectomy, whereas the majority of the older children (80.4%) had (P less than .001). Rates of neurological abnormality and genetic syndromes (including Down syndrome) were similar between the groups.
In baseline polysomnograms, infants had a higher mean obstructive apnea-hypopnea index (AHI) compared with older children (22.6 vs. 12; P less than .001) and a slightly, but significantly, lower oxygen saturation nadir (81% vs. 87%; P = .002).
Only 9.8% of the children and none of the infants used autotitrating. Similar proportions of both groups – 90.6% of infants and 93.1% of children – achieved a mean AHI below 5 with CPAP treatment, and both CPAP pressure and mean oxygen saturation nadir at final pressure were similar in both groups.
Adherence was higher in infants than in children: Infants used CPAP for at least some time for 93.3% of nights compared with children (83.4%) (P = .009), and infants used CPAP for more than 4 hours for 78.4% of nights, compared with 59.5% of nights among children (P = .04).
Barriers to adherence reported by caregivers were similar between both groups. The most common barrier was child behavior, such as crying or refusing the CPAP, which 25% of infant caregivers and 35.3% of child caregivers reported. While a higher proportion of caregivers reported a poor mask fit for infants (15.6%) than for children (10.8%), the difference was not significant (P = .47). Rates of skin irritation also did not significantly differ between the groups.
In addition to the limitations accompanying any retrospective analysis from a single center, another study limitation was the inability to account for differences in total sleep time between infants and school-age children in comparing CPAP usage.
The National Institutes of Health and the Francis Family Foundation funded the research. The authors had no disclosures.
REPORTING FROM ATS 2019
10-valent pneumococcal conjugate vaccine confers similar protection to boys and girls
according to Heta Nieminen, MD, of the National Institute for Health and Welfare in Tampere, Finland, and associates.
For the study, published in Vaccine, the investigators conducted a post hoc analysis of the phase III/IV, cluster-randomized, double-blind FinIP trial, in which more than 30,000 infants received the PHiD-CV10 vaccine or a placebo. Patients were aged less than 7 months when they received their first vaccination, and received two or three primary doses, plus a booster shot after the age of 11 months (Vaccine. 2019 May 20. doi: 10.1016/j.vaccine.2019.05.033).
In term infants, vaccine effectiveness was similar in boys and girls; while the vaccine worked marginally better in girls, the difference was not significant. Infants who received the 2 + 1 schedule had vaccine effectiveness similar to that of those who received the 3 + 1 schedule. In a smaller subanalysis of 1,519 preterm infants, outcomes of pneumonia were more common, but the vaccine seemed to confer protection, although the sample size was not large enough for statistical significance to be reached.
“The point estimates of vaccine effectiveness suggest protection in both sexes, and also among the preterm and low-birth-weight infants. ... There were no significant differences between the 2 + 1 and 3 + 1 schedules in any of the subgroups analyzed. Based on this study, the 2 + 1 or “Nordic” schedule is sufficient also for the risk groups such as the preterm or low-birth-weight infants,” the investigators concluded.
Five study authors are employees of the National Institute for Health and Welfare, which received funding for the study from GlaxoSmithKline. Four coauthors are employees of GlaxoSmithKline; three of them own shares in the company.
according to Heta Nieminen, MD, of the National Institute for Health and Welfare in Tampere, Finland, and associates.
For the study, published in Vaccine, the investigators conducted a post hoc analysis of the phase III/IV, cluster-randomized, double-blind FinIP trial, in which more than 30,000 infants received the PHiD-CV10 vaccine or a placebo. Patients were aged less than 7 months when they received their first vaccination, and received two or three primary doses, plus a booster shot after the age of 11 months (Vaccine. 2019 May 20. doi: 10.1016/j.vaccine.2019.05.033).
In term infants, vaccine effectiveness was similar in boys and girls; while the vaccine worked marginally better in girls, the difference was not significant. Infants who received the 2 + 1 schedule had vaccine effectiveness similar to that of those who received the 3 + 1 schedule. In a smaller subanalysis of 1,519 preterm infants, outcomes of pneumonia were more common, but the vaccine seemed to confer protection, although the sample size was not large enough for statistical significance to be reached.
“The point estimates of vaccine effectiveness suggest protection in both sexes, and also among the preterm and low-birth-weight infants. ... There were no significant differences between the 2 + 1 and 3 + 1 schedules in any of the subgroups analyzed. Based on this study, the 2 + 1 or “Nordic” schedule is sufficient also for the risk groups such as the preterm or low-birth-weight infants,” the investigators concluded.
Five study authors are employees of the National Institute for Health and Welfare, which received funding for the study from GlaxoSmithKline. Four coauthors are employees of GlaxoSmithKline; three of them own shares in the company.
according to Heta Nieminen, MD, of the National Institute for Health and Welfare in Tampere, Finland, and associates.
For the study, published in Vaccine, the investigators conducted a post hoc analysis of the phase III/IV, cluster-randomized, double-blind FinIP trial, in which more than 30,000 infants received the PHiD-CV10 vaccine or a placebo. Patients were aged less than 7 months when they received their first vaccination, and received two or three primary doses, plus a booster shot after the age of 11 months (Vaccine. 2019 May 20. doi: 10.1016/j.vaccine.2019.05.033).
In term infants, vaccine effectiveness was similar in boys and girls; while the vaccine worked marginally better in girls, the difference was not significant. Infants who received the 2 + 1 schedule had vaccine effectiveness similar to that of those who received the 3 + 1 schedule. In a smaller subanalysis of 1,519 preterm infants, outcomes of pneumonia were more common, but the vaccine seemed to confer protection, although the sample size was not large enough for statistical significance to be reached.
“The point estimates of vaccine effectiveness suggest protection in both sexes, and also among the preterm and low-birth-weight infants. ... There were no significant differences between the 2 + 1 and 3 + 1 schedules in any of the subgroups analyzed. Based on this study, the 2 + 1 or “Nordic” schedule is sufficient also for the risk groups such as the preterm or low-birth-weight infants,” the investigators concluded.
Five study authors are employees of the National Institute for Health and Welfare, which received funding for the study from GlaxoSmithKline. Four coauthors are employees of GlaxoSmithKline; three of them own shares in the company.
FROM VACCINE
Severe respiratory failure strikes healthy teens on trimethoprim-sulfamethoxazole
TMP-SMX, a frequently prescribed antibiotic, has been associated with “idiosyncratic adverse drug reactions, including cutaneous reactions and hypersensitivity syndromes,” but pulmonary complications are rare, especially in children, wrote Jenna O. Miller, MD, of the University of Missouri–Kansas City and colleagues.
In a case series published in Pediatrics, the researchers described the patients, who were aged 13-18 years; the 18-year-old was male, the others were female. Four of the patients (three females, one male) were taking TMP-SMX for acne vulgaris. One of these patients, a 13-year-old girl, underwent a bilateral lung and heart transplant after developing interstitial lung disease and died as a result of solid organ transplant complications. The other death occurred in a 15-year-old girl who was taking TMP-SMX to treat a urinary tract infection. This patient developed interstitial lung disease and died of complications from the disease while awaiting a lung transplant.
“In all cases, patients were transferred to academic medical facilities, and pediatric pulmonologists and infectious diseases specialists performed extensive evaluations,” the researchers wrote. The patients did not improve when the drug was discontinued, and four of the five were considered or listed for organ transplants. The spectrum of disease was varied among the patients, and the pathophysiology remains poorly understood.
Although no clinical test could confirm causality between TMP-SMX and ARDS in the five teens, “the extensive negative workup, paired with recent TMP-SMX exposure and similarity among these cases, raises the possibility that the observed ARDS was TMP-SMX triggered,” they wrote.
The researchers had no financial conflicts to disclose.
SOURCE: Miller JO et al. Pediatrics. 2019 May 29. doi: 10.1542/peds.2018.3242.
TMP-SMX, a frequently prescribed antibiotic, has been associated with “idiosyncratic adverse drug reactions, including cutaneous reactions and hypersensitivity syndromes,” but pulmonary complications are rare, especially in children, wrote Jenna O. Miller, MD, of the University of Missouri–Kansas City and colleagues.
In a case series published in Pediatrics, the researchers described the patients, who were aged 13-18 years; the 18-year-old was male, the others were female. Four of the patients (three females, one male) were taking TMP-SMX for acne vulgaris. One of these patients, a 13-year-old girl, underwent a bilateral lung and heart transplant after developing interstitial lung disease and died as a result of solid organ transplant complications. The other death occurred in a 15-year-old girl who was taking TMP-SMX to treat a urinary tract infection. This patient developed interstitial lung disease and died of complications from the disease while awaiting a lung transplant.
“In all cases, patients were transferred to academic medical facilities, and pediatric pulmonologists and infectious diseases specialists performed extensive evaluations,” the researchers wrote. The patients did not improve when the drug was discontinued, and four of the five were considered or listed for organ transplants. The spectrum of disease was varied among the patients, and the pathophysiology remains poorly understood.
Although no clinical test could confirm causality between TMP-SMX and ARDS in the five teens, “the extensive negative workup, paired with recent TMP-SMX exposure and similarity among these cases, raises the possibility that the observed ARDS was TMP-SMX triggered,” they wrote.
The researchers had no financial conflicts to disclose.
SOURCE: Miller JO et al. Pediatrics. 2019 May 29. doi: 10.1542/peds.2018.3242.
TMP-SMX, a frequently prescribed antibiotic, has been associated with “idiosyncratic adverse drug reactions, including cutaneous reactions and hypersensitivity syndromes,” but pulmonary complications are rare, especially in children, wrote Jenna O. Miller, MD, of the University of Missouri–Kansas City and colleagues.
In a case series published in Pediatrics, the researchers described the patients, who were aged 13-18 years; the 18-year-old was male, the others were female. Four of the patients (three females, one male) were taking TMP-SMX for acne vulgaris. One of these patients, a 13-year-old girl, underwent a bilateral lung and heart transplant after developing interstitial lung disease and died as a result of solid organ transplant complications. The other death occurred in a 15-year-old girl who was taking TMP-SMX to treat a urinary tract infection. This patient developed interstitial lung disease and died of complications from the disease while awaiting a lung transplant.
“In all cases, patients were transferred to academic medical facilities, and pediatric pulmonologists and infectious diseases specialists performed extensive evaluations,” the researchers wrote. The patients did not improve when the drug was discontinued, and four of the five were considered or listed for organ transplants. The spectrum of disease was varied among the patients, and the pathophysiology remains poorly understood.
Although no clinical test could confirm causality between TMP-SMX and ARDS in the five teens, “the extensive negative workup, paired with recent TMP-SMX exposure and similarity among these cases, raises the possibility that the observed ARDS was TMP-SMX triggered,” they wrote.
The researchers had no financial conflicts to disclose.
SOURCE: Miller JO et al. Pediatrics. 2019 May 29. doi: 10.1542/peds.2018.3242.
FROM PEDIATRICS
Subsegmental PEs overtreated despite link with patient harm
Background: CT pulmonary angiography (CTPA) often detects distal, subsegmental pulmonary embolisms (SSPE) for which there is unclear clinical significance. For these isolated SSPEs, the 2016 CHEST guidelines recommend clinical surveillance in lieu of treatment. Such clinical surveillance has not been associated with an increased recurrence of venous thromboembolism (VTE) over 3 months.
Study design: Retrospective review.
Setting: Tertiary care center in Quebec.
Synopsis: A review of all CTPAs at McGill University in Montreal, from 2014-2016 yielded 222 acute pulmonary emboli (PEs), 71 of which were SSPEs without associated Doppler imaging positive for deep vein thrombosis. Of those 71, 62 (87%) were systemically anticoagulated, compared with 135/143 (94%) of the more proximal PEs. The adverse events of both groups of anticoagulated patients were common and similar. Over the following 3 months, 26 patients in the SSPE group visited the ED or were readmitted (42%; 95% confidence interval, 30%-55%), 21 had a drop in hemoglobin level of 2 g/dL or greater and/or received a blood transfusion (34%; 95% CI, 22%-47%), and 10 died from causes unrelated to VTE (16%; 95% CI, 8%-28%). Limitations of this study included the small number of participants and short time to follow-up.
Bottom line: Although SSPEs have unknown clinical significance, they are being treated with systemic anticoagulation at a similar rate to more proximal PEs and are associated with patient harm.
Citation: Raslan IA et al. Rates of overtreatment and treatment-related adverse effects among patients with subsegmental pulmonary embolism. JAMA Intern Med. 2018 Sep 1;178(9):1272-4.
Dr. Shaw is an assistant professor in the division of hospital medicine, University of New Mexico.
Background: CT pulmonary angiography (CTPA) often detects distal, subsegmental pulmonary embolisms (SSPE) for which there is unclear clinical significance. For these isolated SSPEs, the 2016 CHEST guidelines recommend clinical surveillance in lieu of treatment. Such clinical surveillance has not been associated with an increased recurrence of venous thromboembolism (VTE) over 3 months.
Study design: Retrospective review.
Setting: Tertiary care center in Quebec.
Synopsis: A review of all CTPAs at McGill University in Montreal, from 2014-2016 yielded 222 acute pulmonary emboli (PEs), 71 of which were SSPEs without associated Doppler imaging positive for deep vein thrombosis. Of those 71, 62 (87%) were systemically anticoagulated, compared with 135/143 (94%) of the more proximal PEs. The adverse events of both groups of anticoagulated patients were common and similar. Over the following 3 months, 26 patients in the SSPE group visited the ED or were readmitted (42%; 95% confidence interval, 30%-55%), 21 had a drop in hemoglobin level of 2 g/dL or greater and/or received a blood transfusion (34%; 95% CI, 22%-47%), and 10 died from causes unrelated to VTE (16%; 95% CI, 8%-28%). Limitations of this study included the small number of participants and short time to follow-up.
Bottom line: Although SSPEs have unknown clinical significance, they are being treated with systemic anticoagulation at a similar rate to more proximal PEs and are associated with patient harm.
Citation: Raslan IA et al. Rates of overtreatment and treatment-related adverse effects among patients with subsegmental pulmonary embolism. JAMA Intern Med. 2018 Sep 1;178(9):1272-4.
Dr. Shaw is an assistant professor in the division of hospital medicine, University of New Mexico.
Background: CT pulmonary angiography (CTPA) often detects distal, subsegmental pulmonary embolisms (SSPE) for which there is unclear clinical significance. For these isolated SSPEs, the 2016 CHEST guidelines recommend clinical surveillance in lieu of treatment. Such clinical surveillance has not been associated with an increased recurrence of venous thromboembolism (VTE) over 3 months.
Study design: Retrospective review.
Setting: Tertiary care center in Quebec.
Synopsis: A review of all CTPAs at McGill University in Montreal, from 2014-2016 yielded 222 acute pulmonary emboli (PEs), 71 of which were SSPEs without associated Doppler imaging positive for deep vein thrombosis. Of those 71, 62 (87%) were systemically anticoagulated, compared with 135/143 (94%) of the more proximal PEs. The adverse events of both groups of anticoagulated patients were common and similar. Over the following 3 months, 26 patients in the SSPE group visited the ED or were readmitted (42%; 95% confidence interval, 30%-55%), 21 had a drop in hemoglobin level of 2 g/dL or greater and/or received a blood transfusion (34%; 95% CI, 22%-47%), and 10 died from causes unrelated to VTE (16%; 95% CI, 8%-28%). Limitations of this study included the small number of participants and short time to follow-up.
Bottom line: Although SSPEs have unknown clinical significance, they are being treated with systemic anticoagulation at a similar rate to more proximal PEs and are associated with patient harm.
Citation: Raslan IA et al. Rates of overtreatment and treatment-related adverse effects among patients with subsegmental pulmonary embolism. JAMA Intern Med. 2018 Sep 1;178(9):1272-4.
Dr. Shaw is an assistant professor in the division of hospital medicine, University of New Mexico.
mTORC1 inhibitor protects elderly asthmatics from viral respiratory tract infections
DALLAS – A molecule that boosts innate viral immunity may protect elderly people with asthma from the root cause of most exacerbations – viral respiratory tract infections.
Dubbed RTB101, the oral medication is a selective, potent inhibitor of target of rapamycin complex 1 (TORC1). In phase 2b data presented at the American Thoracic Society’s international conference, RTB101 decreased by 52% the number of elderly subjects with severe, lab-confirmed respiratory tract infections (RTI) symptoms.
But the molecule was even more effective in patients with asthma aged 65 years and older, Joan Mannick, MD, said in an interview during the meeting. In this group, it reduced by 69% the percentage of subjects who developed RTIs and reduced the rate of infection by about 79%, compared with placebo.
“The core cause of asthma exacerbations in these patients is viral respiratory tract infection,” said Dr. Mannick, chief medical officer of resTORbio, the Boston company developing RTB101. “About 80% of the viruses detected in these infections are rhinoviruses, and there are 170 rhinovirus serotypes. We have never been able to develop a vaccine against rhinovirus, and we have no treatment other than to treat the inflammation caused by the infection.”
Centers for Disease Control and Prevention mortality records confirm the impact of viral respiratory infections on older people who experience asthma exacerbations: 6 of 10,000 will die, compared with less than 2 per 10,000 for all other age groups. Decreasing the number of these infections in older people with asthma would prevent morbidity and mortality and save considerable health care dollars.
“One of the reasons that asthmatics have such difficulty when they get respiratory infections is that they seem to have deficient antiviral immunity in the airways,” Dr. Mannick said. She pointed to a 2008 study of bronchial epithelial cells from both patients with asthma and healthy controls. When inoculated with rhinovirus, the cells from asthmatic airways were unable to mount a healthy immune response and were particularly deficient in producing interferon-beta.
By inhibiting mammalian TORC1 (mTORC1), RBT101 also inhibits sterol regulatory element binding transcription factor 2, a pathway that influences cholesterol synthesis. Cells perceive cholesterol synthesis attenuation as a threat, Dr. Mannick said, and react by up-regulating a number of immune response genes – including some specifically antiviral genes that up-regulate interferon-alpha and -beta production and immune cytokine signaling pathways.
RTB101 is not a particularly new molecule; Novartis originally investigated it as an anticancer agent. “It failed, because it was too selective for mTORC1,” Dr. Mannick said. After Novartis dropped the molecule, resTORbio, a Novartis spin-off, began to investigate it as an immunotherapy for RTIs, particularly in patients with asthma.
reSTORbio’s phase 2 studies on RTB101 comprised 264 healthy subjects aged 65 years and older, who received placebo or 10 mg RTB101 daily for 6 weeks, during cold and flu season. They were followed for a year, confirming the antiviral gene up-regulation. Treatment was also associated with a 42% reduction in the rate of respiratory tract infections.
Conversations with the Food and Drug Administration and payers collected, Dr. Mannick said. “They said that where this drug could really make a difference was if it could decrease these infections in high-risk elderly, who are expensive to treat. So, we targeted people 65 years and older with asthma, chronic obstructive pulmonary disease, and smokers, and people who are 85 years or older.”
The phase 2b trial comprised 652 of these elderly high-risk subjects randomized to the following treatment arms: RTB101 5 mg once daily (n = 61), RTB101 10 mg once daily (n = 176), RTB101 10 mg b.i.d. (n = 120), RTB101 10 mg plus everolimus 0.1 mg daily (n = 115), or matching placebo (n = 180) over 16 weeks, during the entire cold and flu season. The primary endpoint was laboratory-confirmed RTIs in all groups.
The RTB101 10-mg, once-daily group had the best results with a 30.6% reduction in the percentage of patients with lab-confirmed RTIs, compared with placebo, and a 52% reduction in the percentage with severe symptoms.
A subgroup analysis found even more benefit to those with asthma. Among these patients, RTB101 effected a 58.2% decrease in patients with RTIs, and a 66.4% decrease in the rate of infections, compared with placebo.
RTB101 was most effective against rhinoviruses, but it also prevented RTIs associated with influenza A and coronavirus OC43. It also decreased the incidence of RTIs caused by respiratory syncytial virus, parainfluenza 4, influenza B, metapneumovirus, or other coronavirus serotypes.
There were no safety signals, Dr. Mannick noted. Adverse events were similar in both placebo and active groups, and none were deemed related to the study drug. About 5% of each group discontinued the drug because an adverse event.
Plans for a phase 3 trial are underway. A phase 3, placebo-controlled study in the Southern Hemisphere is now ongoing, during the winter cold and flu season. The Northern Hemisphere phase 3 will commence fall and winter of 2019.
Whether RBT101 can help younger people with asthma is an open question. Elderly patients not only have the asthma-related immune deficiency, but also the general age-related immune issues. Younger patients, however, still express the same asthma-related impairment of bronchial immunity.
“We would like to investigate this in younger people and in children, but that will have to wait until our other phase 3 studies are complete,” Dr. Mannick said.
The trial was sponsored by resTORbio.
SOURCE: Mannick J et al. ATS 2019, Abstract A2623.
CORRECTION 5/24/2019 The article was corrected to state a decreased the incidence of RTIs caused by respiratory syncytial virus, parainfluenza 4, influenza B, metapneumovirus, or other coronavirus serotypes.
DALLAS – A molecule that boosts innate viral immunity may protect elderly people with asthma from the root cause of most exacerbations – viral respiratory tract infections.
Dubbed RTB101, the oral medication is a selective, potent inhibitor of target of rapamycin complex 1 (TORC1). In phase 2b data presented at the American Thoracic Society’s international conference, RTB101 decreased by 52% the number of elderly subjects with severe, lab-confirmed respiratory tract infections (RTI) symptoms.
But the molecule was even more effective in patients with asthma aged 65 years and older, Joan Mannick, MD, said in an interview during the meeting. In this group, it reduced by 69% the percentage of subjects who developed RTIs and reduced the rate of infection by about 79%, compared with placebo.
“The core cause of asthma exacerbations in these patients is viral respiratory tract infection,” said Dr. Mannick, chief medical officer of resTORbio, the Boston company developing RTB101. “About 80% of the viruses detected in these infections are rhinoviruses, and there are 170 rhinovirus serotypes. We have never been able to develop a vaccine against rhinovirus, and we have no treatment other than to treat the inflammation caused by the infection.”
Centers for Disease Control and Prevention mortality records confirm the impact of viral respiratory infections on older people who experience asthma exacerbations: 6 of 10,000 will die, compared with less than 2 per 10,000 for all other age groups. Decreasing the number of these infections in older people with asthma would prevent morbidity and mortality and save considerable health care dollars.
“One of the reasons that asthmatics have such difficulty when they get respiratory infections is that they seem to have deficient antiviral immunity in the airways,” Dr. Mannick said. She pointed to a 2008 study of bronchial epithelial cells from both patients with asthma and healthy controls. When inoculated with rhinovirus, the cells from asthmatic airways were unable to mount a healthy immune response and were particularly deficient in producing interferon-beta.
By inhibiting mammalian TORC1 (mTORC1), RBT101 also inhibits sterol regulatory element binding transcription factor 2, a pathway that influences cholesterol synthesis. Cells perceive cholesterol synthesis attenuation as a threat, Dr. Mannick said, and react by up-regulating a number of immune response genes – including some specifically antiviral genes that up-regulate interferon-alpha and -beta production and immune cytokine signaling pathways.
RTB101 is not a particularly new molecule; Novartis originally investigated it as an anticancer agent. “It failed, because it was too selective for mTORC1,” Dr. Mannick said. After Novartis dropped the molecule, resTORbio, a Novartis spin-off, began to investigate it as an immunotherapy for RTIs, particularly in patients with asthma.
reSTORbio’s phase 2 studies on RTB101 comprised 264 healthy subjects aged 65 years and older, who received placebo or 10 mg RTB101 daily for 6 weeks, during cold and flu season. They were followed for a year, confirming the antiviral gene up-regulation. Treatment was also associated with a 42% reduction in the rate of respiratory tract infections.
Conversations with the Food and Drug Administration and payers collected, Dr. Mannick said. “They said that where this drug could really make a difference was if it could decrease these infections in high-risk elderly, who are expensive to treat. So, we targeted people 65 years and older with asthma, chronic obstructive pulmonary disease, and smokers, and people who are 85 years or older.”
The phase 2b trial comprised 652 of these elderly high-risk subjects randomized to the following treatment arms: RTB101 5 mg once daily (n = 61), RTB101 10 mg once daily (n = 176), RTB101 10 mg b.i.d. (n = 120), RTB101 10 mg plus everolimus 0.1 mg daily (n = 115), or matching placebo (n = 180) over 16 weeks, during the entire cold and flu season. The primary endpoint was laboratory-confirmed RTIs in all groups.
The RTB101 10-mg, once-daily group had the best results with a 30.6% reduction in the percentage of patients with lab-confirmed RTIs, compared with placebo, and a 52% reduction in the percentage with severe symptoms.
A subgroup analysis found even more benefit to those with asthma. Among these patients, RTB101 effected a 58.2% decrease in patients with RTIs, and a 66.4% decrease in the rate of infections, compared with placebo.
RTB101 was most effective against rhinoviruses, but it also prevented RTIs associated with influenza A and coronavirus OC43. It also decreased the incidence of RTIs caused by respiratory syncytial virus, parainfluenza 4, influenza B, metapneumovirus, or other coronavirus serotypes.
There were no safety signals, Dr. Mannick noted. Adverse events were similar in both placebo and active groups, and none were deemed related to the study drug. About 5% of each group discontinued the drug because an adverse event.
Plans for a phase 3 trial are underway. A phase 3, placebo-controlled study in the Southern Hemisphere is now ongoing, during the winter cold and flu season. The Northern Hemisphere phase 3 will commence fall and winter of 2019.
Whether RBT101 can help younger people with asthma is an open question. Elderly patients not only have the asthma-related immune deficiency, but also the general age-related immune issues. Younger patients, however, still express the same asthma-related impairment of bronchial immunity.
“We would like to investigate this in younger people and in children, but that will have to wait until our other phase 3 studies are complete,” Dr. Mannick said.
The trial was sponsored by resTORbio.
SOURCE: Mannick J et al. ATS 2019, Abstract A2623.
CORRECTION 5/24/2019 The article was corrected to state a decreased the incidence of RTIs caused by respiratory syncytial virus, parainfluenza 4, influenza B, metapneumovirus, or other coronavirus serotypes.
DALLAS – A molecule that boosts innate viral immunity may protect elderly people with asthma from the root cause of most exacerbations – viral respiratory tract infections.
Dubbed RTB101, the oral medication is a selective, potent inhibitor of target of rapamycin complex 1 (TORC1). In phase 2b data presented at the American Thoracic Society’s international conference, RTB101 decreased by 52% the number of elderly subjects with severe, lab-confirmed respiratory tract infections (RTI) symptoms.
But the molecule was even more effective in patients with asthma aged 65 years and older, Joan Mannick, MD, said in an interview during the meeting. In this group, it reduced by 69% the percentage of subjects who developed RTIs and reduced the rate of infection by about 79%, compared with placebo.
“The core cause of asthma exacerbations in these patients is viral respiratory tract infection,” said Dr. Mannick, chief medical officer of resTORbio, the Boston company developing RTB101. “About 80% of the viruses detected in these infections are rhinoviruses, and there are 170 rhinovirus serotypes. We have never been able to develop a vaccine against rhinovirus, and we have no treatment other than to treat the inflammation caused by the infection.”
Centers for Disease Control and Prevention mortality records confirm the impact of viral respiratory infections on older people who experience asthma exacerbations: 6 of 10,000 will die, compared with less than 2 per 10,000 for all other age groups. Decreasing the number of these infections in older people with asthma would prevent morbidity and mortality and save considerable health care dollars.
“One of the reasons that asthmatics have such difficulty when they get respiratory infections is that they seem to have deficient antiviral immunity in the airways,” Dr. Mannick said. She pointed to a 2008 study of bronchial epithelial cells from both patients with asthma and healthy controls. When inoculated with rhinovirus, the cells from asthmatic airways were unable to mount a healthy immune response and were particularly deficient in producing interferon-beta.
By inhibiting mammalian TORC1 (mTORC1), RBT101 also inhibits sterol regulatory element binding transcription factor 2, a pathway that influences cholesterol synthesis. Cells perceive cholesterol synthesis attenuation as a threat, Dr. Mannick said, and react by up-regulating a number of immune response genes – including some specifically antiviral genes that up-regulate interferon-alpha and -beta production and immune cytokine signaling pathways.
RTB101 is not a particularly new molecule; Novartis originally investigated it as an anticancer agent. “It failed, because it was too selective for mTORC1,” Dr. Mannick said. After Novartis dropped the molecule, resTORbio, a Novartis spin-off, began to investigate it as an immunotherapy for RTIs, particularly in patients with asthma.
reSTORbio’s phase 2 studies on RTB101 comprised 264 healthy subjects aged 65 years and older, who received placebo or 10 mg RTB101 daily for 6 weeks, during cold and flu season. They were followed for a year, confirming the antiviral gene up-regulation. Treatment was also associated with a 42% reduction in the rate of respiratory tract infections.
Conversations with the Food and Drug Administration and payers collected, Dr. Mannick said. “They said that where this drug could really make a difference was if it could decrease these infections in high-risk elderly, who are expensive to treat. So, we targeted people 65 years and older with asthma, chronic obstructive pulmonary disease, and smokers, and people who are 85 years or older.”
The phase 2b trial comprised 652 of these elderly high-risk subjects randomized to the following treatment arms: RTB101 5 mg once daily (n = 61), RTB101 10 mg once daily (n = 176), RTB101 10 mg b.i.d. (n = 120), RTB101 10 mg plus everolimus 0.1 mg daily (n = 115), or matching placebo (n = 180) over 16 weeks, during the entire cold and flu season. The primary endpoint was laboratory-confirmed RTIs in all groups.
The RTB101 10-mg, once-daily group had the best results with a 30.6% reduction in the percentage of patients with lab-confirmed RTIs, compared with placebo, and a 52% reduction in the percentage with severe symptoms.
A subgroup analysis found even more benefit to those with asthma. Among these patients, RTB101 effected a 58.2% decrease in patients with RTIs, and a 66.4% decrease in the rate of infections, compared with placebo.
RTB101 was most effective against rhinoviruses, but it also prevented RTIs associated with influenza A and coronavirus OC43. It also decreased the incidence of RTIs caused by respiratory syncytial virus, parainfluenza 4, influenza B, metapneumovirus, or other coronavirus serotypes.
There were no safety signals, Dr. Mannick noted. Adverse events were similar in both placebo and active groups, and none were deemed related to the study drug. About 5% of each group discontinued the drug because an adverse event.
Plans for a phase 3 trial are underway. A phase 3, placebo-controlled study in the Southern Hemisphere is now ongoing, during the winter cold and flu season. The Northern Hemisphere phase 3 will commence fall and winter of 2019.
Whether RBT101 can help younger people with asthma is an open question. Elderly patients not only have the asthma-related immune deficiency, but also the general age-related immune issues. Younger patients, however, still express the same asthma-related impairment of bronchial immunity.
“We would like to investigate this in younger people and in children, but that will have to wait until our other phase 3 studies are complete,” Dr. Mannick said.
The trial was sponsored by resTORbio.
SOURCE: Mannick J et al. ATS 2019, Abstract A2623.
CORRECTION 5/24/2019 The article was corrected to state a decreased the incidence of RTIs caused by respiratory syncytial virus, parainfluenza 4, influenza B, metapneumovirus, or other coronavirus serotypes.
REPORTING FROM ATS 2019
Nintedanib cut lung function decline in interstitial lung disease with systemic sclerosis
DALLAS – Nintedanib, a tyrosine kinase inhibitor, decreased by 44% the annual rate of lung function decline among patients with interstitial lung disease associated with systemic sclerosis, a year-long study has found.
In a placebo-controlled 52-week trial, forced vital capacity (FVC) in patients who took nintedanib (Ofev) declined by a mean of 52 mL – significantly less than the mean 93 mL decline seen among those who were given placebo, Oliver Distler, MD, said at the annual meeting of the American Thoracic Society.
“These are people in their mid-40s and -50s,” said Dr. Distler of the University of Zürich. “They have a long time to go. If there is an annual preservation of lung function by 40%, if you have that every year, it becomes very surely clinically significant. A decline in FVC is also a good surrogate marker of mortality in interstitial lung disease associated with systemic sclerosis. Assuming the effects are ongoing above the 1 year we looked at, then indeed these results are clinically important.”
The study was simultaneously published in the New England Journal of Medicine. Nintedanib is already approved for idiopathic pulmonary fibrosis. But some data suggest that it also exerts antifibrotic and anti-inflammatory effects in animal models of systemic sclerosis and inflammatory lung disease (ILD). SENSCIS (the Safety and Efficacy of Nintedanib in Systemic Sclerosis trial) investigated the molecule’s use in patients with ILD associated with systemic sclerosis.
Conducted in 32 countries, SENSCIS comprised 576 patients with the disorder, whose sclerosis affected at least 10% of their lungs. They were assigned to 52 weeks of either placebo or 150 mg nintedanib twice weekly. However, patients stayed on their blinded treatment until the last patient enrolled had finished the year of treatment; some patients took the drug for 100 weeks, Dr. Distler said. The primary endpoint was annual rate of decline in the forced vital capacity (FEV). Secondary endpoints included changes of the modified Rodnan skin score and in the total score on the St. George’s Respiratory Questionnaire.
Patients were a mean of 54 years old, with a mean disease duration of about 3 years. About half had diffuse cutaneous systemic sclerosis; the sclerosis was limited in the remainder. The mean extent of lung fibrosis was about 36%. Half were taking mycophenolate at baseline, which was allowed as background treatment, along with up to 10 mg/day of prednisone. Any patient who experienced clinically significant lung function deterioration could receive additional therapy at the investigator’s discretion.
The mean baseline FEV for these patients was 72.5% of predicted value. The mean diffusing capacity of the lungs for carbon monoxide was 53% of expected capacity.
Most patients completed the study (80% of the active group and 89% of the placebo group). The mean drug exposure duration was 10 months in the active group and 11 in the placebo group.
Improvement began early in treatment, with the efficacy curves separating by week 12 and continuing to diverge. After 52 weeks of therapy, the annual rate of change was 41 mL less in the active group than in the placebo group (–54.4 mL vs. –93.3 mL). The mean adjusted absolute change from baseline was –54.6 mL in the active group and –101 mL in the placebo at week 52. Significantly fewer patients taking nintedanib also lost more than 10% of FVC by week 52 (16.7% vs. 18%).
The St. George’s Respiratory Questionnaire score improved about one point in the active group and declined about one point in the placebo group.
Nintedanib was equally effective across a number of subgroups, including those divided by sex, age, and race. Antitopoisomerase antibodies and so-called antitopoisomerase I antibody status did not affect nintedanib’s action. Nintedanib also significantly improved scores on the Health Assessment Questionnaire without Disability Index and dyspnea.
More patients in the active group than in on placebo discontinued treatment because of a serious adverse event (16% vs. 8.7%). The most common of these were diarrhea (75.7% vs. 31%), nausea (31.6% vs. 13.5%), and vomiting (24.7% vs.10.4%). Skin ulcers occurred in about 18% of each group. Patients in the active group were significantly more likely to develop elevated alanine and aspartate aminotransferase of up to three times normal levels (4.9% vs. 0.7%).
Treatment did not significantly affect mortality rates, however. Over the treatment period, 10 patients in the nintedanib group and 9 in the placebo group died (3.5% vs. 3.1%).
The study was sponsored by Boehringer Ingelheim. Dr. Distler was the primary investigator on the trial.
SOURCE: Distler O et al. ATS 2019, Abstract A7360.
DALLAS – Nintedanib, a tyrosine kinase inhibitor, decreased by 44% the annual rate of lung function decline among patients with interstitial lung disease associated with systemic sclerosis, a year-long study has found.
In a placebo-controlled 52-week trial, forced vital capacity (FVC) in patients who took nintedanib (Ofev) declined by a mean of 52 mL – significantly less than the mean 93 mL decline seen among those who were given placebo, Oliver Distler, MD, said at the annual meeting of the American Thoracic Society.
“These are people in their mid-40s and -50s,” said Dr. Distler of the University of Zürich. “They have a long time to go. If there is an annual preservation of lung function by 40%, if you have that every year, it becomes very surely clinically significant. A decline in FVC is also a good surrogate marker of mortality in interstitial lung disease associated with systemic sclerosis. Assuming the effects are ongoing above the 1 year we looked at, then indeed these results are clinically important.”
The study was simultaneously published in the New England Journal of Medicine. Nintedanib is already approved for idiopathic pulmonary fibrosis. But some data suggest that it also exerts antifibrotic and anti-inflammatory effects in animal models of systemic sclerosis and inflammatory lung disease (ILD). SENSCIS (the Safety and Efficacy of Nintedanib in Systemic Sclerosis trial) investigated the molecule’s use in patients with ILD associated with systemic sclerosis.
Conducted in 32 countries, SENSCIS comprised 576 patients with the disorder, whose sclerosis affected at least 10% of their lungs. They were assigned to 52 weeks of either placebo or 150 mg nintedanib twice weekly. However, patients stayed on their blinded treatment until the last patient enrolled had finished the year of treatment; some patients took the drug for 100 weeks, Dr. Distler said. The primary endpoint was annual rate of decline in the forced vital capacity (FEV). Secondary endpoints included changes of the modified Rodnan skin score and in the total score on the St. George’s Respiratory Questionnaire.
Patients were a mean of 54 years old, with a mean disease duration of about 3 years. About half had diffuse cutaneous systemic sclerosis; the sclerosis was limited in the remainder. The mean extent of lung fibrosis was about 36%. Half were taking mycophenolate at baseline, which was allowed as background treatment, along with up to 10 mg/day of prednisone. Any patient who experienced clinically significant lung function deterioration could receive additional therapy at the investigator’s discretion.
The mean baseline FEV for these patients was 72.5% of predicted value. The mean diffusing capacity of the lungs for carbon monoxide was 53% of expected capacity.
Most patients completed the study (80% of the active group and 89% of the placebo group). The mean drug exposure duration was 10 months in the active group and 11 in the placebo group.
Improvement began early in treatment, with the efficacy curves separating by week 12 and continuing to diverge. After 52 weeks of therapy, the annual rate of change was 41 mL less in the active group than in the placebo group (–54.4 mL vs. –93.3 mL). The mean adjusted absolute change from baseline was –54.6 mL in the active group and –101 mL in the placebo at week 52. Significantly fewer patients taking nintedanib also lost more than 10% of FVC by week 52 (16.7% vs. 18%).
The St. George’s Respiratory Questionnaire score improved about one point in the active group and declined about one point in the placebo group.
Nintedanib was equally effective across a number of subgroups, including those divided by sex, age, and race. Antitopoisomerase antibodies and so-called antitopoisomerase I antibody status did not affect nintedanib’s action. Nintedanib also significantly improved scores on the Health Assessment Questionnaire without Disability Index and dyspnea.
More patients in the active group than in on placebo discontinued treatment because of a serious adverse event (16% vs. 8.7%). The most common of these were diarrhea (75.7% vs. 31%), nausea (31.6% vs. 13.5%), and vomiting (24.7% vs.10.4%). Skin ulcers occurred in about 18% of each group. Patients in the active group were significantly more likely to develop elevated alanine and aspartate aminotransferase of up to three times normal levels (4.9% vs. 0.7%).
Treatment did not significantly affect mortality rates, however. Over the treatment period, 10 patients in the nintedanib group and 9 in the placebo group died (3.5% vs. 3.1%).
The study was sponsored by Boehringer Ingelheim. Dr. Distler was the primary investigator on the trial.
SOURCE: Distler O et al. ATS 2019, Abstract A7360.
DALLAS – Nintedanib, a tyrosine kinase inhibitor, decreased by 44% the annual rate of lung function decline among patients with interstitial lung disease associated with systemic sclerosis, a year-long study has found.
In a placebo-controlled 52-week trial, forced vital capacity (FVC) in patients who took nintedanib (Ofev) declined by a mean of 52 mL – significantly less than the mean 93 mL decline seen among those who were given placebo, Oliver Distler, MD, said at the annual meeting of the American Thoracic Society.
“These are people in their mid-40s and -50s,” said Dr. Distler of the University of Zürich. “They have a long time to go. If there is an annual preservation of lung function by 40%, if you have that every year, it becomes very surely clinically significant. A decline in FVC is also a good surrogate marker of mortality in interstitial lung disease associated with systemic sclerosis. Assuming the effects are ongoing above the 1 year we looked at, then indeed these results are clinically important.”
The study was simultaneously published in the New England Journal of Medicine. Nintedanib is already approved for idiopathic pulmonary fibrosis. But some data suggest that it also exerts antifibrotic and anti-inflammatory effects in animal models of systemic sclerosis and inflammatory lung disease (ILD). SENSCIS (the Safety and Efficacy of Nintedanib in Systemic Sclerosis trial) investigated the molecule’s use in patients with ILD associated with systemic sclerosis.
Conducted in 32 countries, SENSCIS comprised 576 patients with the disorder, whose sclerosis affected at least 10% of their lungs. They were assigned to 52 weeks of either placebo or 150 mg nintedanib twice weekly. However, patients stayed on their blinded treatment until the last patient enrolled had finished the year of treatment; some patients took the drug for 100 weeks, Dr. Distler said. The primary endpoint was annual rate of decline in the forced vital capacity (FEV). Secondary endpoints included changes of the modified Rodnan skin score and in the total score on the St. George’s Respiratory Questionnaire.
Patients were a mean of 54 years old, with a mean disease duration of about 3 years. About half had diffuse cutaneous systemic sclerosis; the sclerosis was limited in the remainder. The mean extent of lung fibrosis was about 36%. Half were taking mycophenolate at baseline, which was allowed as background treatment, along with up to 10 mg/day of prednisone. Any patient who experienced clinically significant lung function deterioration could receive additional therapy at the investigator’s discretion.
The mean baseline FEV for these patients was 72.5% of predicted value. The mean diffusing capacity of the lungs for carbon monoxide was 53% of expected capacity.
Most patients completed the study (80% of the active group and 89% of the placebo group). The mean drug exposure duration was 10 months in the active group and 11 in the placebo group.
Improvement began early in treatment, with the efficacy curves separating by week 12 and continuing to diverge. After 52 weeks of therapy, the annual rate of change was 41 mL less in the active group than in the placebo group (–54.4 mL vs. –93.3 mL). The mean adjusted absolute change from baseline was –54.6 mL in the active group and –101 mL in the placebo at week 52. Significantly fewer patients taking nintedanib also lost more than 10% of FVC by week 52 (16.7% vs. 18%).
The St. George’s Respiratory Questionnaire score improved about one point in the active group and declined about one point in the placebo group.
Nintedanib was equally effective across a number of subgroups, including those divided by sex, age, and race. Antitopoisomerase antibodies and so-called antitopoisomerase I antibody status did not affect nintedanib’s action. Nintedanib also significantly improved scores on the Health Assessment Questionnaire without Disability Index and dyspnea.
More patients in the active group than in on placebo discontinued treatment because of a serious adverse event (16% vs. 8.7%). The most common of these were diarrhea (75.7% vs. 31%), nausea (31.6% vs. 13.5%), and vomiting (24.7% vs.10.4%). Skin ulcers occurred in about 18% of each group. Patients in the active group were significantly more likely to develop elevated alanine and aspartate aminotransferase of up to three times normal levels (4.9% vs. 0.7%).
Treatment did not significantly affect mortality rates, however. Over the treatment period, 10 patients in the nintedanib group and 9 in the placebo group died (3.5% vs. 3.1%).
The study was sponsored by Boehringer Ingelheim. Dr. Distler was the primary investigator on the trial.
SOURCE: Distler O et al. ATS 2019, Abstract A7360.
AT ATS 2019
Key clinical point: The tyrosine kinase inhibitor nintedanib may be a useful treatment for interstitial lung disease associated with systemic sclerosis (SS-ILD).
Major finding: Nintedanib decreased the annual rate of lung function decline by 44% among patients with SS-ILD.
Study details: The randomized, placebo-controlled study comprised 576 patients.
Disclosures: The trial was sponsored by Boehringer Ingelheim. Dr. Distler is the primary investigator.
Source: Distler O et al. ATS 2019, Abstract A7360.
U.S. measles total sees smallest increase in 2 months
according to the Centers for Disease Control and Prevention.
That weekly increase of 41 cases is the smallest since the week ending March 14, when the total rose by 40. The largest 1-week rise of the year came during the week ending April 11, when there were 90 new cases, CDC data show.
A case that has been reported by the media in the last week but not officially through the CDC would make New Mexico the 25th state with a measles case this year. The state’s health department has confirmed measles in a 1-year-old from Sierra County, which is New Mexico’s first case since 2014, the Las Cruces Sun News reported, adding that 4,441 school-aged children had an exemption for vaccination filed with the state in 2018.
Making a return appearance to the CDC’s list of outbreaks is Washington State, which reported six new cases last week in three Puget Sound counties (King, Pierce, and Snohomish). The most likely location and date of exposure was at Seattle-Tacoma International Airport on April 25, the Washington State Department of Health said. In February and March, there were 71 cases in Clark County on the state’s border with Oregon.
The ongoing outbreak in Michigan had been quiet since April, but the state’s Department of Health and Human Services confirmed a measles case in St. Clair County on May 17, bringing the total to 44 for the year. The new case, which is not related to an earlier outbreak that occurred mainly in Oakland County, involves an international traveler visiting Michigan.
according to the Centers for Disease Control and Prevention.
That weekly increase of 41 cases is the smallest since the week ending March 14, when the total rose by 40. The largest 1-week rise of the year came during the week ending April 11, when there were 90 new cases, CDC data show.
A case that has been reported by the media in the last week but not officially through the CDC would make New Mexico the 25th state with a measles case this year. The state’s health department has confirmed measles in a 1-year-old from Sierra County, which is New Mexico’s first case since 2014, the Las Cruces Sun News reported, adding that 4,441 school-aged children had an exemption for vaccination filed with the state in 2018.
Making a return appearance to the CDC’s list of outbreaks is Washington State, which reported six new cases last week in three Puget Sound counties (King, Pierce, and Snohomish). The most likely location and date of exposure was at Seattle-Tacoma International Airport on April 25, the Washington State Department of Health said. In February and March, there were 71 cases in Clark County on the state’s border with Oregon.
The ongoing outbreak in Michigan had been quiet since April, but the state’s Department of Health and Human Services confirmed a measles case in St. Clair County on May 17, bringing the total to 44 for the year. The new case, which is not related to an earlier outbreak that occurred mainly in Oakland County, involves an international traveler visiting Michigan.
according to the Centers for Disease Control and Prevention.
That weekly increase of 41 cases is the smallest since the week ending March 14, when the total rose by 40. The largest 1-week rise of the year came during the week ending April 11, when there were 90 new cases, CDC data show.
A case that has been reported by the media in the last week but not officially through the CDC would make New Mexico the 25th state with a measles case this year. The state’s health department has confirmed measles in a 1-year-old from Sierra County, which is New Mexico’s first case since 2014, the Las Cruces Sun News reported, adding that 4,441 school-aged children had an exemption for vaccination filed with the state in 2018.
Making a return appearance to the CDC’s list of outbreaks is Washington State, which reported six new cases last week in three Puget Sound counties (King, Pierce, and Snohomish). The most likely location and date of exposure was at Seattle-Tacoma International Airport on April 25, the Washington State Department of Health said. In February and March, there were 71 cases in Clark County on the state’s border with Oregon.
The ongoing outbreak in Michigan had been quiet since April, but the state’s Department of Health and Human Services confirmed a measles case in St. Clair County on May 17, bringing the total to 44 for the year. The new case, which is not related to an earlier outbreak that occurred mainly in Oakland County, involves an international traveler visiting Michigan.
AFib on the rise in end-stage COPD patients hospitalized for exacerbations
Atrial fibrillation is being seen with increasing frequency in patients admitted to U.S. hospitals for exacerbations of end-stage chronic obstructive pulmonary disease, based on a retrospective analysis of data from the Nationwide Inpatient Sample.
The prevalence of atrial fibrillation (AFib) among patients with end-stage chronic obstructive pulmonary disease (COPD) on home oxygen who were admitted with COPD exacerbations increased from 12.9% in 2003 to 21.3% in 2014, according to Xiaochun Xiao of the department of health statistics at Second Military Medical University in Shanghai and colleagues.
Additionally, “we found that comorbid [AFib] was associated with an increased risk of the need for mechanical ventilation, especially invasive mechanical ventilation. Moreover, comorbid [AFib] was associated with adverse clinical outcomes, including increased in-hospital death, acute respiratory failure, acute kidney injury, sepsis, and stroke,” the researchers wrote in the study published in the journal CHEST.
Patients included in the study were aged at least 18 years, were diagnosed with end-stage COPD and on home oxygen, and were hospitalized because of a COPD-related exacerbation. Based on 1,345,270 weighted hospital admissions of adults with end-stage COPD on home oxygen who met the inclusion criteria for the study, 18.2% (244,488 admissions) of patients had AFib, and the prevalence of AFib in COPD patients increased over time from 2003 (12.9%) to 2014 (21.3%; P less than .0001).
Patients with AFib, compared with patients without AFib, were older (75.5 years vs. 69.6 years; P less than .0001) and more likely to be male (50.7% vs. 59.1%; P less than .0001) and white (80.9% vs. 74.4%; P less than .0001). Patients with AFib also had higher stroke risk reflected in higher CHA2DS2-VASc scores (3.26 vs. 2.45; P less than .0001), and higher likelihood of in-hospital mortality and readmission reflected in Elixhauser scores greater than or equal to 4 (51.2% vs. 35.6%).
In addition, the prevalence of AFib increased with increasing income. Larger hospitals in terms of bed size, urban environment, and Medicare insurance status also were associated with a higher AFib prevalence.
AFib was associated with an increased cost of $1,415 and an increased length of stay of 0.6 days after adjustment for potential confounders. AFib also predicted risk for several adverse events, including stroke (odds ratio, 1.80; in-hospital death, [OR, 1.54]), invasive mechanical ventilation (OR, 1.37), sepsis (OR, 1.23), noninvasive mechanical ventilation (OR, 1.14), acute kidney injury (OR, 1.09), and acute respiratory failure (OR, 1.09).
The researchers noted the database could have potentially overinflated AFib prevalence, as they could not differentiate index admissions and readmissions. The database also does not contain information about secondary diagnoses codes present on admission, which could make it difficult to identify adverse events that occurred during hospitalization.
“Our findings should prompt further efforts to identify the reasons for increased [AFib] prevalence and provide better management strategies for end-stage COPD patients comorbid with [AFib],” the researchers concluded.
This study was funded by a grant from the Fourth Round of the Shanghai 3-year Action Plan on Public Health Discipline and Talent Program. The authors reported no relevant conflict of interest.
SOURCE: Xiao X et al. CHEST. 2019 Jan 23. doi: 10.1016/j.chest.2018.12.021.
Atrial fibrillation is being seen with increasing frequency in patients admitted to U.S. hospitals for exacerbations of end-stage chronic obstructive pulmonary disease, based on a retrospective analysis of data from the Nationwide Inpatient Sample.
The prevalence of atrial fibrillation (AFib) among patients with end-stage chronic obstructive pulmonary disease (COPD) on home oxygen who were admitted with COPD exacerbations increased from 12.9% in 2003 to 21.3% in 2014, according to Xiaochun Xiao of the department of health statistics at Second Military Medical University in Shanghai and colleagues.
Additionally, “we found that comorbid [AFib] was associated with an increased risk of the need for mechanical ventilation, especially invasive mechanical ventilation. Moreover, comorbid [AFib] was associated with adverse clinical outcomes, including increased in-hospital death, acute respiratory failure, acute kidney injury, sepsis, and stroke,” the researchers wrote in the study published in the journal CHEST.
Patients included in the study were aged at least 18 years, were diagnosed with end-stage COPD and on home oxygen, and were hospitalized because of a COPD-related exacerbation. Based on 1,345,270 weighted hospital admissions of adults with end-stage COPD on home oxygen who met the inclusion criteria for the study, 18.2% (244,488 admissions) of patients had AFib, and the prevalence of AFib in COPD patients increased over time from 2003 (12.9%) to 2014 (21.3%; P less than .0001).
Patients with AFib, compared with patients without AFib, were older (75.5 years vs. 69.6 years; P less than .0001) and more likely to be male (50.7% vs. 59.1%; P less than .0001) and white (80.9% vs. 74.4%; P less than .0001). Patients with AFib also had higher stroke risk reflected in higher CHA2DS2-VASc scores (3.26 vs. 2.45; P less than .0001), and higher likelihood of in-hospital mortality and readmission reflected in Elixhauser scores greater than or equal to 4 (51.2% vs. 35.6%).
In addition, the prevalence of AFib increased with increasing income. Larger hospitals in terms of bed size, urban environment, and Medicare insurance status also were associated with a higher AFib prevalence.
AFib was associated with an increased cost of $1,415 and an increased length of stay of 0.6 days after adjustment for potential confounders. AFib also predicted risk for several adverse events, including stroke (odds ratio, 1.80; in-hospital death, [OR, 1.54]), invasive mechanical ventilation (OR, 1.37), sepsis (OR, 1.23), noninvasive mechanical ventilation (OR, 1.14), acute kidney injury (OR, 1.09), and acute respiratory failure (OR, 1.09).
The researchers noted the database could have potentially overinflated AFib prevalence, as they could not differentiate index admissions and readmissions. The database also does not contain information about secondary diagnoses codes present on admission, which could make it difficult to identify adverse events that occurred during hospitalization.
“Our findings should prompt further efforts to identify the reasons for increased [AFib] prevalence and provide better management strategies for end-stage COPD patients comorbid with [AFib],” the researchers concluded.
This study was funded by a grant from the Fourth Round of the Shanghai 3-year Action Plan on Public Health Discipline and Talent Program. The authors reported no relevant conflict of interest.
SOURCE: Xiao X et al. CHEST. 2019 Jan 23. doi: 10.1016/j.chest.2018.12.021.
Atrial fibrillation is being seen with increasing frequency in patients admitted to U.S. hospitals for exacerbations of end-stage chronic obstructive pulmonary disease, based on a retrospective analysis of data from the Nationwide Inpatient Sample.
The prevalence of atrial fibrillation (AFib) among patients with end-stage chronic obstructive pulmonary disease (COPD) on home oxygen who were admitted with COPD exacerbations increased from 12.9% in 2003 to 21.3% in 2014, according to Xiaochun Xiao of the department of health statistics at Second Military Medical University in Shanghai and colleagues.
Additionally, “we found that comorbid [AFib] was associated with an increased risk of the need for mechanical ventilation, especially invasive mechanical ventilation. Moreover, comorbid [AFib] was associated with adverse clinical outcomes, including increased in-hospital death, acute respiratory failure, acute kidney injury, sepsis, and stroke,” the researchers wrote in the study published in the journal CHEST.
Patients included in the study were aged at least 18 years, were diagnosed with end-stage COPD and on home oxygen, and were hospitalized because of a COPD-related exacerbation. Based on 1,345,270 weighted hospital admissions of adults with end-stage COPD on home oxygen who met the inclusion criteria for the study, 18.2% (244,488 admissions) of patients had AFib, and the prevalence of AFib in COPD patients increased over time from 2003 (12.9%) to 2014 (21.3%; P less than .0001).
Patients with AFib, compared with patients without AFib, were older (75.5 years vs. 69.6 years; P less than .0001) and more likely to be male (50.7% vs. 59.1%; P less than .0001) and white (80.9% vs. 74.4%; P less than .0001). Patients with AFib also had higher stroke risk reflected in higher CHA2DS2-VASc scores (3.26 vs. 2.45; P less than .0001), and higher likelihood of in-hospital mortality and readmission reflected in Elixhauser scores greater than or equal to 4 (51.2% vs. 35.6%).
In addition, the prevalence of AFib increased with increasing income. Larger hospitals in terms of bed size, urban environment, and Medicare insurance status also were associated with a higher AFib prevalence.
AFib was associated with an increased cost of $1,415 and an increased length of stay of 0.6 days after adjustment for potential confounders. AFib also predicted risk for several adverse events, including stroke (odds ratio, 1.80; in-hospital death, [OR, 1.54]), invasive mechanical ventilation (OR, 1.37), sepsis (OR, 1.23), noninvasive mechanical ventilation (OR, 1.14), acute kidney injury (OR, 1.09), and acute respiratory failure (OR, 1.09).
The researchers noted the database could have potentially overinflated AFib prevalence, as they could not differentiate index admissions and readmissions. The database also does not contain information about secondary diagnoses codes present on admission, which could make it difficult to identify adverse events that occurred during hospitalization.
“Our findings should prompt further efforts to identify the reasons for increased [AFib] prevalence and provide better management strategies for end-stage COPD patients comorbid with [AFib],” the researchers concluded.
This study was funded by a grant from the Fourth Round of the Shanghai 3-year Action Plan on Public Health Discipline and Talent Program. The authors reported no relevant conflict of interest.
SOURCE: Xiao X et al. CHEST. 2019 Jan 23. doi: 10.1016/j.chest.2018.12.021.
FROM CHEST
Key clinical point: Comorbid atrial fibrillation was associated with an increased risk of the need for mechanical ventilation, especially invasive mechanical ventilation, and of adverse outcomes including in-hospital death, acute respiratory failure, acute kidney injury, sepsis, and stroke.
Major finding: The prevalence of atrial fibrillation with end-stage chronic obstructive pulmonary disease increased over time from 2003 (12.9%) to 2014 (21.3%). Study details: A retrospective analysis based on 1,345,270 weighted hospital admissions of adults with end-stage chronic obstructive pulmonary disease on home oxygen from the Nationwide Impatient Sample during 2003-2014.
Disclosures: The study was funded by a grant from the Fourth Round of the Shanghai 3-Year Action Plan on Public Health Discipline and Talent Program. The authors reported no conflicts of interest.
Source: Xiao X et al. CHEST. 2019 Jan 23. doi: 10.1016/j.chest.2018.12.021.
Smoking rates remain steady among the poor
While an increasing number of U.S. citizens are saying no to cigarettes, a recent study shows.
The odds of current smoking, versus never smoking, declined significantly during 2008-2017 for individuals with none of six disadvantages tied to cigarette use, including disability, unemployment, poverty, low education, psychological distress, and heavy alcohol intake, according to researchers.
Individuals with one or two of those disadvantages have also been cutting back, the data suggest. But, by contrast, odds of current versus never smoking did not significantly change for those with three or more disadvantages, according to Adam M. Leventhal, PhD, of the University of Southern California, Los Angeles, and coinvestigators.
“How this pattern can inform a cohesive policy agenda is unknown, but it is clear from these findings that the crux of the recently expanding tobacco-related health disparity problem in the United States is not tied to groups facing merely a single form of disadvantage,” Dr. Leventhal and coauthors wrote in a report on the study in JAMA Internal Medicine.
The cross-sectional analysis by Dr. Leventhal and colleagues was based on National Health Interview Survey (NHIS) data from 2008-2017 including more than 278,000 respondents aged 25 years or older.
A snapshot of that 10-year period showed that current smoking prevalence was successively higher depending on the number of socioeconomic or health-related disadvantages.
The mean prevalence of current smoking over that entire time period was just 13.8% for people with zero of the six disadvantages, 21.4% for those with one disadvantage, and so on, up to 58.2% for those with all six disadvantages, according to data in the published report.
Encouragingly, overall smoking prevalence fell from 20.8% in 2008-2009 to 15.8% in 2016-2017, the researchers found. However, the decreasing trend was not apparent for individuals with many disadvantages.
The odds ratio for change in odds of smoking per year was 0.951 (95% confidence interval, 0.944-0.958) for those with zero disadvantages, 0.96 (95% CI, 0.95-0.97) for one disadvantage, and 0.98 (95% CI, 0.97-0.99) for two, all representing significant annual reductions in current versus never smoking, investigators said. By contrast, no such significant changes were apparent for those with three, four, five, or six such disadvantages.
Tobacco control or regulatory policies that consider these disadvantages separately may be overlooking a “broader pattern” showing that the cumulative number of disadvantages correlates with the magnitude of disparity, wrote Dr. Leventhal and colleagues in their report.
“Successful prevention of smoking initiation and promotion of smoking cessation in multi-disadvantaged populations would substantially reduce the smoking-related public health burden in the United States,” they concluded.
Dr. Leventhal and colleagues reported no conflicts related to their research, which was supported in part by a Tobacco Centers of Regulatory Science award from the National Cancer Institute and the Food and Drug Administration, among other sources.
SOURCE: Leventhal AM et al. JAMA Intern Med. 2019 Apr 22. doi: 10.1001/jamainternmed.2019.0192.
While an increasing number of U.S. citizens are saying no to cigarettes, a recent study shows.
The odds of current smoking, versus never smoking, declined significantly during 2008-2017 for individuals with none of six disadvantages tied to cigarette use, including disability, unemployment, poverty, low education, psychological distress, and heavy alcohol intake, according to researchers.
Individuals with one or two of those disadvantages have also been cutting back, the data suggest. But, by contrast, odds of current versus never smoking did not significantly change for those with three or more disadvantages, according to Adam M. Leventhal, PhD, of the University of Southern California, Los Angeles, and coinvestigators.
“How this pattern can inform a cohesive policy agenda is unknown, but it is clear from these findings that the crux of the recently expanding tobacco-related health disparity problem in the United States is not tied to groups facing merely a single form of disadvantage,” Dr. Leventhal and coauthors wrote in a report on the study in JAMA Internal Medicine.
The cross-sectional analysis by Dr. Leventhal and colleagues was based on National Health Interview Survey (NHIS) data from 2008-2017 including more than 278,000 respondents aged 25 years or older.
A snapshot of that 10-year period showed that current smoking prevalence was successively higher depending on the number of socioeconomic or health-related disadvantages.
The mean prevalence of current smoking over that entire time period was just 13.8% for people with zero of the six disadvantages, 21.4% for those with one disadvantage, and so on, up to 58.2% for those with all six disadvantages, according to data in the published report.
Encouragingly, overall smoking prevalence fell from 20.8% in 2008-2009 to 15.8% in 2016-2017, the researchers found. However, the decreasing trend was not apparent for individuals with many disadvantages.
The odds ratio for change in odds of smoking per year was 0.951 (95% confidence interval, 0.944-0.958) for those with zero disadvantages, 0.96 (95% CI, 0.95-0.97) for one disadvantage, and 0.98 (95% CI, 0.97-0.99) for two, all representing significant annual reductions in current versus never smoking, investigators said. By contrast, no such significant changes were apparent for those with three, four, five, or six such disadvantages.
Tobacco control or regulatory policies that consider these disadvantages separately may be overlooking a “broader pattern” showing that the cumulative number of disadvantages correlates with the magnitude of disparity, wrote Dr. Leventhal and colleagues in their report.
“Successful prevention of smoking initiation and promotion of smoking cessation in multi-disadvantaged populations would substantially reduce the smoking-related public health burden in the United States,” they concluded.
Dr. Leventhal and colleagues reported no conflicts related to their research, which was supported in part by a Tobacco Centers of Regulatory Science award from the National Cancer Institute and the Food and Drug Administration, among other sources.
SOURCE: Leventhal AM et al. JAMA Intern Med. 2019 Apr 22. doi: 10.1001/jamainternmed.2019.0192.
While an increasing number of U.S. citizens are saying no to cigarettes, a recent study shows.
The odds of current smoking, versus never smoking, declined significantly during 2008-2017 for individuals with none of six disadvantages tied to cigarette use, including disability, unemployment, poverty, low education, psychological distress, and heavy alcohol intake, according to researchers.
Individuals with one or two of those disadvantages have also been cutting back, the data suggest. But, by contrast, odds of current versus never smoking did not significantly change for those with three or more disadvantages, according to Adam M. Leventhal, PhD, of the University of Southern California, Los Angeles, and coinvestigators.
“How this pattern can inform a cohesive policy agenda is unknown, but it is clear from these findings that the crux of the recently expanding tobacco-related health disparity problem in the United States is not tied to groups facing merely a single form of disadvantage,” Dr. Leventhal and coauthors wrote in a report on the study in JAMA Internal Medicine.
The cross-sectional analysis by Dr. Leventhal and colleagues was based on National Health Interview Survey (NHIS) data from 2008-2017 including more than 278,000 respondents aged 25 years or older.
A snapshot of that 10-year period showed that current smoking prevalence was successively higher depending on the number of socioeconomic or health-related disadvantages.
The mean prevalence of current smoking over that entire time period was just 13.8% for people with zero of the six disadvantages, 21.4% for those with one disadvantage, and so on, up to 58.2% for those with all six disadvantages, according to data in the published report.
Encouragingly, overall smoking prevalence fell from 20.8% in 2008-2009 to 15.8% in 2016-2017, the researchers found. However, the decreasing trend was not apparent for individuals with many disadvantages.
The odds ratio for change in odds of smoking per year was 0.951 (95% confidence interval, 0.944-0.958) for those with zero disadvantages, 0.96 (95% CI, 0.95-0.97) for one disadvantage, and 0.98 (95% CI, 0.97-0.99) for two, all representing significant annual reductions in current versus never smoking, investigators said. By contrast, no such significant changes were apparent for those with three, four, five, or six such disadvantages.
Tobacco control or regulatory policies that consider these disadvantages separately may be overlooking a “broader pattern” showing that the cumulative number of disadvantages correlates with the magnitude of disparity, wrote Dr. Leventhal and colleagues in their report.
“Successful prevention of smoking initiation and promotion of smoking cessation in multi-disadvantaged populations would substantially reduce the smoking-related public health burden in the United States,” they concluded.
Dr. Leventhal and colleagues reported no conflicts related to their research, which was supported in part by a Tobacco Centers of Regulatory Science award from the National Cancer Institute and the Food and Drug Administration, among other sources.
SOURCE: Leventhal AM et al. JAMA Intern Med. 2019 Apr 22. doi: 10.1001/jamainternmed.2019.0192.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Current U.S. smoking rates have not declined among individuals with multiple socioeconomic or health-related disadvantages.
Major finding: The odds ratio for change in odds of smoking per year was 0.951 for individuals with zero disadvantages, 0.96 for one disadvantage, and 0.97-0.99 for two, with no significant annual reductions in those with three or more disadvantages.
Study details: Cross-sectional analysis of 278,048 respondents aged 25 years or older in the National Health Interview Survey during 2008-2017.
Disclosures: Authors reported no conflicts of interest related to the study, which was supported in part by a Tobacco Centers of Regulatory Science award from the National Cancer Institute and the Food and Drug Administration, among other sources.
Source: Leventhal AM et al. JAMA Intern Med. 2019 Apr 22. doi: 10.1001/jamainternmed.2019.0192.