News

The gold-standard treatment is no more effective than placebo for patients with mild persistent asthma, say researchers from the Steroids in Eosinophil Negative Asthma (SIENA) study, funded by the National Heart, Lung, and Blood Institute.

The researchers divided 295 participants into groups based on low- or high-sputum eosinophil levels and assigned them randomly to each of 3 treatment groups for 12-week periods: inhaled steroids (mometasone), a long-acting muscarinic antagonist (LAMA) (tiotropium), or placebo. 

Surprisingly, 221 participants—nearly 73%—were classified as having low-sputum eosinophils (< 2%), a much higher frequency than the researchers expected. And of those, the number who responded better to steroids was no different from the number responding to placebo. Of the Eos-low group, 60% had better symptom control with LAMA; 40% had better symptom control with placebo.

By contrast, patients classified as “Eos-high” were nearly 3 times as likely to respond to inhaled steroids compared with placebo.

Other research has indicated that about half the population with mild persistent asthma have < 2% sputum eosinophils and are not likely to respond well to steroids. But laboratory tests to measure sputum eosinophils are not routinely used in most clinics, the researchers say.

The difference between the groups is not large enough to conclude that patients are more likely to do better on LAMA drugs, the researchers say, but their study highlights the need to look for alternatives to inhaled steroids for patients with mild asthma.

The research underscores the value of customizing treatments to help people with asthma, said James Kiley, PhD, director of the Division of Lung Diseases at NHLBI. “This study adds to a growing body of evidence that different patients with mild asthma should be treated differently, perhaps using biomarkers like sputum eosinophils to select which drugs should be used—a precision medicine approach.”

The gold-standard treatment is no more effective than placebo for patients with mild persistent asthma, say researchers from the Steroids in Eosinophil Negative Asthma (SIENA) study, funded by the National Heart, Lung, and Blood Institute.

The researchers divided 295 participants into groups based on low- or high-sputum eosinophil levels and assigned them randomly to each of 3 treatment groups for 12-week periods: inhaled steroids (mometasone), a long-acting muscarinic antagonist (LAMA) (tiotropium), or placebo. 

Surprisingly, 221 participants—nearly 73%—were classified as having low-sputum eosinophils (< 2%), a much higher frequency than the researchers expected. And of those, the number who responded better to steroids was no different from the number responding to placebo. Of the Eos-low group, 60% had better symptom control with LAMA; 40% had better symptom control with placebo.

By contrast, patients classified as “Eos-high” were nearly 3 times as likely to respond to inhaled steroids compared with placebo.

Other research has indicated that about half the population with mild persistent asthma have < 2% sputum eosinophils and are not likely to respond well to steroids. But laboratory tests to measure sputum eosinophils are not routinely used in most clinics, the researchers say.

The difference between the groups is not large enough to conclude that patients are more likely to do better on LAMA drugs, the researchers say, but their study highlights the need to look for alternatives to inhaled steroids for patients with mild asthma.

The research underscores the value of customizing treatments to help people with asthma, said James Kiley, PhD, director of the Division of Lung Diseases at NHLBI. “This study adds to a growing body of evidence that different patients with mild asthma should be treated differently, perhaps using biomarkers like sputum eosinophils to select which drugs should be used—a precision medicine approach.”

The gold-standard treatment is no more effective than placebo for patients with mild persistent asthma, say researchers from the Steroids in Eosinophil Negative Asthma (SIENA) study, funded by the National Heart, Lung, and Blood Institute.

The researchers divided 295 participants into groups based on low- or high-sputum eosinophil levels and assigned them randomly to each of 3 treatment groups for 12-week periods: inhaled steroids (mometasone), a long-acting muscarinic antagonist (LAMA) (tiotropium), or placebo. 

Surprisingly, 221 participants—nearly 73%—were classified as having low-sputum eosinophils (< 2%), a much higher frequency than the researchers expected. And of those, the number who responded better to steroids was no different from the number responding to placebo. Of the Eos-low group, 60% had better symptom control with LAMA; 40% had better symptom control with placebo.

By contrast, patients classified as “Eos-high” were nearly 3 times as likely to respond to inhaled steroids compared with placebo.

Other research has indicated that about half the population with mild persistent asthma have < 2% sputum eosinophils and are not likely to respond well to steroids. But laboratory tests to measure sputum eosinophils are not routinely used in most clinics, the researchers say.

The difference between the groups is not large enough to conclude that patients are more likely to do better on LAMA drugs, the researchers say, but their study highlights the need to look for alternatives to inhaled steroids for patients with mild asthma.

The research underscores the value of customizing treatments to help people with asthma, said James Kiley, PhD, director of the Division of Lung Diseases at NHLBI. “This study adds to a growing body of evidence that different patients with mild asthma should be treated differently, perhaps using biomarkers like sputum eosinophils to select which drugs should be used—a precision medicine approach.”

LJUBLJANA, SLOVENIA – A high body mass index in pregnant women who receive a seasonal influenza vaccine doesn’t impair their vaccine response; indeed, it might actually improve their seroconversion rate, Michelle Clarke reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

She presented a prospective cohort study of 90 women vaccinated against influenza during pregnancy, 24 of whom had a BMI of 30 kg/m² or more. The impetus for the study was the investigators’ understanding that influenza in pregnancy carries an increased risk of severe complications, obesity is a known risk factor for more severe episodes of influenza, and vaccine responses could potentially be adversely affected by obesity, either because of the associated inflammatory state and altered cytokine profile or inadequate vaccine delivery via the intramuscular route. Yet the impact of obesity on vaccine responses in pregnancy has been unclear.

Blood samples obtained before and 1 month after vaccination showed similarly high-titer postvaccination seropositivity rates against influenza B, H3N2, and H1N1 regardless of the women’s weight status. Indeed, the seropositivity rate against all three influenza viruses was higher in the obese subgroup, by a margin of 92%-74%. Also, postvaccination geometric mean antibody titers were significantly higher in the obese group. Particularly impressive was the difference in H1N1 seroconversion, defined as a fourfold increase in titer 28 days after vaccination: 79% versus 55%, noted Ms. Clarke of the University of Adelaide.

Of note, influenza vaccination in the first trimester resulted in a significantly lower seropositive antibody rate than vaccination in the second or third trimesters. The implication is that gestational age at vaccination, regardless of BMI, may be an important determinant of optimal vaccine protection for mothers and their newborns. However, this tentative conclusion requires confirmation in an independent larger sample, because the patient numbers in the study were small: Seropositive antibodies to all three vaccine antigens were documented in just 7 of 12 women (58%) vaccinated in the first trimester, compared with 47 of 53 (89%) vaccinated in the second trimester and 18 of 25 (72%) in the third.

Ms. Clarke reported having no financial conflicts regarding the study, which was supported by the Women’s and Children’s Hospital Research Foundation.

bjancin@mdedge.com

LJUBLJANA, SLOVENIA – A high body mass index in pregnant women who receive a seasonal influenza vaccine doesn’t impair their vaccine response; indeed, it might actually improve their seroconversion rate, Michelle Clarke reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

She presented a prospective cohort study of 90 women vaccinated against influenza during pregnancy, 24 of whom had a BMI of 30 kg/m² or more. The impetus for the study was the investigators’ understanding that influenza in pregnancy carries an increased risk of severe complications, obesity is a known risk factor for more severe episodes of influenza, and vaccine responses could potentially be adversely affected by obesity, either because of the associated inflammatory state and altered cytokine profile or inadequate vaccine delivery via the intramuscular route. Yet the impact of obesity on vaccine responses in pregnancy has been unclear.

Blood samples obtained before and 1 month after vaccination showed similarly high-titer postvaccination seropositivity rates against influenza B, H3N2, and H1N1 regardless of the women’s weight status. Indeed, the seropositivity rate against all three influenza viruses was higher in the obese subgroup, by a margin of 92%-74%. Also, postvaccination geometric mean antibody titers were significantly higher in the obese group. Particularly impressive was the difference in H1N1 seroconversion, defined as a fourfold increase in titer 28 days after vaccination: 79% versus 55%, noted Ms. Clarke of the University of Adelaide.

Of note, influenza vaccination in the first trimester resulted in a significantly lower seropositive antibody rate than vaccination in the second or third trimesters. The implication is that gestational age at vaccination, regardless of BMI, may be an important determinant of optimal vaccine protection for mothers and their newborns. However, this tentative conclusion requires confirmation in an independent larger sample, because the patient numbers in the study were small: Seropositive antibodies to all three vaccine antigens were documented in just 7 of 12 women (58%) vaccinated in the first trimester, compared with 47 of 53 (89%) vaccinated in the second trimester and 18 of 25 (72%) in the third.

Ms. Clarke reported having no financial conflicts regarding the study, which was supported by the Women’s and Children’s Hospital Research Foundation.

bjancin@mdedge.com

LJUBLJANA, SLOVENIA – A high body mass index in pregnant women who receive a seasonal influenza vaccine doesn’t impair their vaccine response; indeed, it might actually improve their seroconversion rate, Michelle Clarke reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

She presented a prospective cohort study of 90 women vaccinated against influenza during pregnancy, 24 of whom had a BMI of 30 kg/m² or more. The impetus for the study was the investigators’ understanding that influenza in pregnancy carries an increased risk of severe complications, obesity is a known risk factor for more severe episodes of influenza, and vaccine responses could potentially be adversely affected by obesity, either because of the associated inflammatory state and altered cytokine profile or inadequate vaccine delivery via the intramuscular route. Yet the impact of obesity on vaccine responses in pregnancy has been unclear.

Blood samples obtained before and 1 month after vaccination showed similarly high-titer postvaccination seropositivity rates against influenza B, H3N2, and H1N1 regardless of the women’s weight status. Indeed, the seropositivity rate against all three influenza viruses was higher in the obese subgroup, by a margin of 92%-74%. Also, postvaccination geometric mean antibody titers were significantly higher in the obese group. Particularly impressive was the difference in H1N1 seroconversion, defined as a fourfold increase in titer 28 days after vaccination: 79% versus 55%, noted Ms. Clarke of the University of Adelaide.

Of note, influenza vaccination in the first trimester resulted in a significantly lower seropositive antibody rate than vaccination in the second or third trimesters. The implication is that gestational age at vaccination, regardless of BMI, may be an important determinant of optimal vaccine protection for mothers and their newborns. However, this tentative conclusion requires confirmation in an independent larger sample, because the patient numbers in the study were small: Seropositive antibodies to all three vaccine antigens were documented in just 7 of 12 women (58%) vaccinated in the first trimester, compared with 47 of 53 (89%) vaccinated in the second trimester and 18 of 25 (72%) in the third.

Ms. Clarke reported having no financial conflicts regarding the study, which was supported by the Women’s and Children’s Hospital Research Foundation.

bjancin@mdedge.com

BALTIMORE – Experiencing panic-fear during asthma exacerbations predicted several beneficial outcomes in Mexican and Puerto Rican children with asthma, according to new research.

Tara Haelle/MDedge News

“When kids are anxious specifically during their asthma attacks, that can be a good thing because it means that they’re more vigilant,” lead author Jonathan M. Feldman, PhD, of the Albert Einstein College of Medicine’s Children’s Hospital at Montefiore and of Yeshiva University in the New York said in an interview. “They may be more likely to react during the early stages of an attack, and they may be more likely to be using self-management strategies at home and using their controller medications on a daily basis.”

He said pediatric providers can ask their patients with asthma how they feel during asthma attacks, such as whether they ever feel scared or worried.

“If a kid says no, not at all, then I would be concerned as a provider because they may not be paying attention to their asthma symptoms and they may not be taking it seriously,” Dr. Feldman said.

Past research has suggested that “illness-specific panic-fear” – the amount of anxiety someone experiences during asthma exacerbations – helps adults develop adaptive asthma management strategies, so Dr. Feldman and his colleagues examined the phenomenon as a potential protective factor in children. They shared their findings at the annual meeting of the Pediatric Academic Societies.

The research focused on Puerto Rican (n = 79) and Mexican (n = 188) children because of the substantial disparity in asthma prevalence and control between these two different Latino populations. Puerto Rican children have the highest asthma prevalence and morbidity among American children, whereas Mexican children have the lowest rates.

The 267 participants, aged 5-12 years, included 110 children from two inner-city hospitals in the New York and 157 children from two school-based health clinics and a Breathmobile in Phoenix. Nearly all the Arizona children were Mexican, and most (71%) of the Bronx children were Puerto Rican.

The authors collected the following measures at baseline and at 3, 6, 9, and 12 months follow-up: spirometry (forced expiratory volume in 1 second [FEV₁]), Childhood Asthma Control Test (CACT) for children 5-11 years old, the Asthma Control Test (ACT) for 12-year-olds, adherence to inhaled corticosteroids (ICS), and acute health care utilizations (clinic sick visits, ED visits, and hospitalizations).

The authors also queried patients on four illness-specific panic-fear measures from the Childhood Asthma Symptoms Checklist: how often they felt frightened, panicky, afraid of being alone, and afraid of dying during an asthma attack (Likert 1-5 scale).

Mexican children reported higher levels of illness-specific panic-fear at the start of the study. They also tended to have lower severity of asthma, better asthma control, and better adherence to ICS, compared with Puerto Rican children.

Also at baseline, the Mexican children’s caregivers tended to be younger, poorer, and more likely to be married and to speak Spanish. The Puerto Rican caregivers, on the other hand, had a higher educational level, including 61% high school graduates, and had more depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D).

One-year data revealed several links between baseline reports of panic-fear and better outcomes. Mexican children who reported experiencing panic-fear at baseline were more likely to have higher FEV₁ measures at 1 year of follow-up than were those who didn’t experience panic-fear (P = .02). Similarly, Puerto Rican children initially reporting panic-fear had better asthma control at 1 year, compared with those who didn’t report panic-fear (P = .007).

The researchers reported their effect sizes in terms of predicted variance in a model that accounted for the child’s age, sex, asthma duration, asthma severity, social support, acculturation, health care provider relationship, and number of family members with asthma. The model also factored in the caregiver’s age, sex, marital status, poverty level, education, and depressive symptoms.

For example, in their model, experiencing panic-fear accounted for 67% of the variance in FEV₁ levels in Mexican children and 53% of the variance in asthma control in Puerto Rican children.

Less acute health care utilization also was associated with children’s baseline levels of illness-specific panic-fear. In the model, 12% of the variance in acute health care utilization among Mexican children (P = .03) and 41% of the variance among Puerto Rican children (P = .02) was explained by child-reported panic-fear. No association was seen with medication adherence.

Although caregivers’ reports of children feeling panic-fear were linked to better FEV₁ outcomes in Mexican children (P = .02), the association was only slightly significant in Puerto Rican children (P = .05). Caregiver reports of children’s panic-fear were not associated with asthma control, acute health care utilization, or medication adherence.

“Providers should be aware that anxiety focused on asthma may be beneficial and facilitate adaptive asthma management strategies,” the authors concluded.

The research was funded by the National Institutes of Health. The authors reported no relevant financial disclosures.

BALTIMORE – Experiencing panic-fear during asthma exacerbations predicted several beneficial outcomes in Mexican and Puerto Rican children with asthma, according to new research.

Tara Haelle/MDedge News

“When kids are anxious specifically during their asthma attacks, that can be a good thing because it means that they’re more vigilant,” lead author Jonathan M. Feldman, PhD, of the Albert Einstein College of Medicine’s Children’s Hospital at Montefiore and of Yeshiva University in the New York said in an interview. “They may be more likely to react during the early stages of an attack, and they may be more likely to be using self-management strategies at home and using their controller medications on a daily basis.”

He said pediatric providers can ask their patients with asthma how they feel during asthma attacks, such as whether they ever feel scared or worried.

“If a kid says no, not at all, then I would be concerned as a provider because they may not be paying attention to their asthma symptoms and they may not be taking it seriously,” Dr. Feldman said.

Past research has suggested that “illness-specific panic-fear” – the amount of anxiety someone experiences during asthma exacerbations – helps adults develop adaptive asthma management strategies, so Dr. Feldman and his colleagues examined the phenomenon as a potential protective factor in children. They shared their findings at the annual meeting of the Pediatric Academic Societies.

The research focused on Puerto Rican (n = 79) and Mexican (n = 188) children because of the substantial disparity in asthma prevalence and control between these two different Latino populations. Puerto Rican children have the highest asthma prevalence and morbidity among American children, whereas Mexican children have the lowest rates.

The 267 participants, aged 5-12 years, included 110 children from two inner-city hospitals in the New York and 157 children from two school-based health clinics and a Breathmobile in Phoenix. Nearly all the Arizona children were Mexican, and most (71%) of the Bronx children were Puerto Rican.

The authors collected the following measures at baseline and at 3, 6, 9, and 12 months follow-up: spirometry (forced expiratory volume in 1 second [FEV₁]), Childhood Asthma Control Test (CACT) for children 5-11 years old, the Asthma Control Test (ACT) for 12-year-olds, adherence to inhaled corticosteroids (ICS), and acute health care utilizations (clinic sick visits, ED visits, and hospitalizations).

The authors also queried patients on four illness-specific panic-fear measures from the Childhood Asthma Symptoms Checklist: how often they felt frightened, panicky, afraid of being alone, and afraid of dying during an asthma attack (Likert 1-5 scale).

Mexican children reported higher levels of illness-specific panic-fear at the start of the study. They also tended to have lower severity of asthma, better asthma control, and better adherence to ICS, compared with Puerto Rican children.

Also at baseline, the Mexican children’s caregivers tended to be younger, poorer, and more likely to be married and to speak Spanish. The Puerto Rican caregivers, on the other hand, had a higher educational level, including 61% high school graduates, and had more depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D).

One-year data revealed several links between baseline reports of panic-fear and better outcomes. Mexican children who reported experiencing panic-fear at baseline were more likely to have higher FEV₁ measures at 1 year of follow-up than were those who didn’t experience panic-fear (P = .02). Similarly, Puerto Rican children initially reporting panic-fear had better asthma control at 1 year, compared with those who didn’t report panic-fear (P = .007).

The researchers reported their effect sizes in terms of predicted variance in a model that accounted for the child’s age, sex, asthma duration, asthma severity, social support, acculturation, health care provider relationship, and number of family members with asthma. The model also factored in the caregiver’s age, sex, marital status, poverty level, education, and depressive symptoms.

For example, in their model, experiencing panic-fear accounted for 67% of the variance in FEV₁ levels in Mexican children and 53% of the variance in asthma control in Puerto Rican children.

Less acute health care utilization also was associated with children’s baseline levels of illness-specific panic-fear. In the model, 12% of the variance in acute health care utilization among Mexican children (P = .03) and 41% of the variance among Puerto Rican children (P = .02) was explained by child-reported panic-fear. No association was seen with medication adherence.

Although caregivers’ reports of children feeling panic-fear were linked to better FEV₁ outcomes in Mexican children (P = .02), the association was only slightly significant in Puerto Rican children (P = .05). Caregiver reports of children’s panic-fear were not associated with asthma control, acute health care utilization, or medication adherence.

“Providers should be aware that anxiety focused on asthma may be beneficial and facilitate adaptive asthma management strategies,” the authors concluded.

The research was funded by the National Institutes of Health. The authors reported no relevant financial disclosures.

BALTIMORE – Experiencing panic-fear during asthma exacerbations predicted several beneficial outcomes in Mexican and Puerto Rican children with asthma, according to new research.

Tara Haelle/MDedge News

“When kids are anxious specifically during their asthma attacks, that can be a good thing because it means that they’re more vigilant,” lead author Jonathan M. Feldman, PhD, of the Albert Einstein College of Medicine’s Children’s Hospital at Montefiore and of Yeshiva University in the New York said in an interview. “They may be more likely to react during the early stages of an attack, and they may be more likely to be using self-management strategies at home and using their controller medications on a daily basis.”

He said pediatric providers can ask their patients with asthma how they feel during asthma attacks, such as whether they ever feel scared or worried.

“If a kid says no, not at all, then I would be concerned as a provider because they may not be paying attention to their asthma symptoms and they may not be taking it seriously,” Dr. Feldman said.

Past research has suggested that “illness-specific panic-fear” – the amount of anxiety someone experiences during asthma exacerbations – helps adults develop adaptive asthma management strategies, so Dr. Feldman and his colleagues examined the phenomenon as a potential protective factor in children. They shared their findings at the annual meeting of the Pediatric Academic Societies.

The research focused on Puerto Rican (n = 79) and Mexican (n = 188) children because of the substantial disparity in asthma prevalence and control between these two different Latino populations. Puerto Rican children have the highest asthma prevalence and morbidity among American children, whereas Mexican children have the lowest rates.

The 267 participants, aged 5-12 years, included 110 children from two inner-city hospitals in the New York and 157 children from two school-based health clinics and a Breathmobile in Phoenix. Nearly all the Arizona children were Mexican, and most (71%) of the Bronx children were Puerto Rican.

The authors collected the following measures at baseline and at 3, 6, 9, and 12 months follow-up: spirometry (forced expiratory volume in 1 second [FEV₁]), Childhood Asthma Control Test (CACT) for children 5-11 years old, the Asthma Control Test (ACT) for 12-year-olds, adherence to inhaled corticosteroids (ICS), and acute health care utilizations (clinic sick visits, ED visits, and hospitalizations).

The authors also queried patients on four illness-specific panic-fear measures from the Childhood Asthma Symptoms Checklist: how often they felt frightened, panicky, afraid of being alone, and afraid of dying during an asthma attack (Likert 1-5 scale).

Mexican children reported higher levels of illness-specific panic-fear at the start of the study. They also tended to have lower severity of asthma, better asthma control, and better adherence to ICS, compared with Puerto Rican children.

Also at baseline, the Mexican children’s caregivers tended to be younger, poorer, and more likely to be married and to speak Spanish. The Puerto Rican caregivers, on the other hand, had a higher educational level, including 61% high school graduates, and had more depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D).

One-year data revealed several links between baseline reports of panic-fear and better outcomes. Mexican children who reported experiencing panic-fear at baseline were more likely to have higher FEV₁ measures at 1 year of follow-up than were those who didn’t experience panic-fear (P = .02). Similarly, Puerto Rican children initially reporting panic-fear had better asthma control at 1 year, compared with those who didn’t report panic-fear (P = .007).

The researchers reported their effect sizes in terms of predicted variance in a model that accounted for the child’s age, sex, asthma duration, asthma severity, social support, acculturation, health care provider relationship, and number of family members with asthma. The model also factored in the caregiver’s age, sex, marital status, poverty level, education, and depressive symptoms.

For example, in their model, experiencing panic-fear accounted for 67% of the variance in FEV₁ levels in Mexican children and 53% of the variance in asthma control in Puerto Rican children.

Less acute health care utilization also was associated with children’s baseline levels of illness-specific panic-fear. In the model, 12% of the variance in acute health care utilization among Mexican children (P = .03) and 41% of the variance among Puerto Rican children (P = .02) was explained by child-reported panic-fear. No association was seen with medication adherence.

Although caregivers’ reports of children feeling panic-fear were linked to better FEV₁ outcomes in Mexican children (P = .02), the association was only slightly significant in Puerto Rican children (P = .05). Caregiver reports of children’s panic-fear were not associated with asthma control, acute health care utilization, or medication adherence.

“Providers should be aware that anxiety focused on asthma may be beneficial and facilitate adaptive asthma management strategies,” the authors concluded.

The research was funded by the National Institutes of Health. The authors reported no relevant financial disclosures.

DALLAS – Warfarin appears to increase the risk of lung transplant or death for patients with fibrotic lung disease who need anticoagulation therapy, Christopher King, MD, said at the American Thoracic Society’s international conference.

Michele G. Sullivan/MDedge News

Compared with direct oral anticoagulation (DOAC), warfarin doubled the risk of those outcomes, even after the researchers controlled for multiple morbidities that accompany the need for anticoagulation, said Dr. King, medical director of the transplant and advanced lung disease critical care program at Inova Fairfax (Va.) Hospital.

“The need for anticoagulation in patients with interstitial lung disease is already associated with an increased risk of death or transplant,” he said. Warfarin – but not oral anticoagulation – seems to increase that risk even more “no matter how you analyze it,” he said.

“We know now that fibrosis and coagulation are entwined, and there’s background epidemiologic data showing an increased incidence of venous thromboembolism and acute coronary syndrome in patients with pulmonary fibrosis. This suggests that a dysregulated coagulation cascade may play a role in the pathogenesis of fibrosis.”

The relationship has been explored for the last decade or so. Two recent meta-analyses came to similar conclusions.

In 2013, a 125-patient retrospective cohort study compared clinical characteristics and survival among patients with idiopathic pulmonary fibrosis (IPF) who received anticoagulant therapy with those who did not (Sarcoidosis Vasc Diffuse Lung Dis. 2013 Aug 1;30[2]:121-7). Those who got the treatment had worse survival outcomes at 1 and 3 years than did those who received no therapy (84% vs. 53% and 89% vs. 64%, respectively).

In 2016, a post hoc analysis of three placebo-controlled studies determined that any anticoagulant use independently increased the risk of death among patients with IPF, compared with nonuse: 15.6% vs 6.3% all-cause mortality (Eur Respir J. 2016. doi: 10.1183/13993003.02087-2015).

But these investigations didn’t parse out the types of anticoagulation. Direct oral anticoagulation (DOAC) is much more common now, however, and Dr. King and colleagues wanted to find out how warfarin and DOAC compared.

They retrospectively analyzed data from the Pulmonary Fibrosis Foundation’s database and compared the risk of lung transplant and death for patients on anticoagulation or no anticoagulation and for those receiving DOACs versus warfarin versus no anticoagulation.

The study comprised 1,918 patients, 91% of whom were not on anticoagulation therapy. The remaining 164 were either taking DOAC (n = 83) or warfarin (n = 81). Both of these groups were significantly older than those not on anticoagulation (70 vs. 67 years). As expected , they were significantly more likely to have cardiac arrhythmias, heart failure, or pulmonary embolism or deep vein thrombosis and significantly more likely to be on immunosuppressant therapy or steroids. Their diffusing capacity of lung for carbon dioxide was also significantly lower.

There were no significant lung disease–related differences in anticoagulation therapy, other than a trend toward more use among those with connective tissue disease–associated interstitial lung disease.

Over 2 years, the entire cohort experienced 110 deaths (5.7%), 52 transplants (2.7%), and 29 withdrawals (1.5%). Among patients with IPF, there were 80 deaths (6.7%), 43 transplants (3.6%) and 20 withdrawals (1.7%).

In an unadjusted analysis, anticoagulation more than doubled the risk of an event, compared with no anticoagulation (hazard ratio, 2.4). This was slightly attenuated, but still significant, in a multivariate model that controlled for age, gender, oxygen use, gastroesophageal reflux disease, obstructive sleep apnea, arrhythmia, cancer, heart failure, obesity, venous thromboembolism, and antifibrotics (HR, 1.88).

A second whole-cohort analysis looked at the survival ratios for both warfarin and DOAC, compared with no treatment. In the fully adjusted model, warfarin was associated with a significantly increased risk HR (2.28) but DOAC was not.

The investigators then examined risk in only patients with lung disease. Among those with IPF, the fully adjusted model showed that warfarin nearly tripled the risk of transplant or death (HR, 2.8), while DOAC had no significant effect.

The reason for this association remains unclear, Dr. King said. “Renal failure may be a big reason patients get warfarin instead of DOAC. It’s difficult to say whether these patients were frail or prone to bleeding. Even something like the care team not being as up to date with treatment could be affecting the numbers. And is it the direct effect of warfarin on fibrotic lung disease? Or maybe DOAC has some beneficial effect on pulmonary fibrosis? We don’t know.

“But what we can take away from this is that warfarin is associated with worse outcomes than DOAC in patients with IPF. It seems reasonable to use DOAC over warfarin if there’s no specific contraindication to DOAC. If you have a patient with pulmonary thrombosis who has indications for anticoagulation I would use DOAC, based on the evidence that we now have available.”

Dr. King had no disclosures.

msullivan@mdedge.com

DALLAS – Warfarin appears to increase the risk of lung transplant or death for patients with fibrotic lung disease who need anticoagulation therapy, Christopher King, MD, said at the American Thoracic Society’s international conference.

Michele G. Sullivan/MDedge News

Compared with direct oral anticoagulation (DOAC), warfarin doubled the risk of those outcomes, even after the researchers controlled for multiple morbidities that accompany the need for anticoagulation, said Dr. King, medical director of the transplant and advanced lung disease critical care program at Inova Fairfax (Va.) Hospital.

“The need for anticoagulation in patients with interstitial lung disease is already associated with an increased risk of death or transplant,” he said. Warfarin – but not oral anticoagulation – seems to increase that risk even more “no matter how you analyze it,” he said.

“We know now that fibrosis and coagulation are entwined, and there’s background epidemiologic data showing an increased incidence of venous thromboembolism and acute coronary syndrome in patients with pulmonary fibrosis. This suggests that a dysregulated coagulation cascade may play a role in the pathogenesis of fibrosis.”

The relationship has been explored for the last decade or so. Two recent meta-analyses came to similar conclusions.

In 2013, a 125-patient retrospective cohort study compared clinical characteristics and survival among patients with idiopathic pulmonary fibrosis (IPF) who received anticoagulant therapy with those who did not (Sarcoidosis Vasc Diffuse Lung Dis. 2013 Aug 1;30[2]:121-7). Those who got the treatment had worse survival outcomes at 1 and 3 years than did those who received no therapy (84% vs. 53% and 89% vs. 64%, respectively).

In 2016, a post hoc analysis of three placebo-controlled studies determined that any anticoagulant use independently increased the risk of death among patients with IPF, compared with nonuse: 15.6% vs 6.3% all-cause mortality (Eur Respir J. 2016. doi: 10.1183/13993003.02087-2015).

But these investigations didn’t parse out the types of anticoagulation. Direct oral anticoagulation (DOAC) is much more common now, however, and Dr. King and colleagues wanted to find out how warfarin and DOAC compared.

They retrospectively analyzed data from the Pulmonary Fibrosis Foundation’s database and compared the risk of lung transplant and death for patients on anticoagulation or no anticoagulation and for those receiving DOACs versus warfarin versus no anticoagulation.

The study comprised 1,918 patients, 91% of whom were not on anticoagulation therapy. The remaining 164 were either taking DOAC (n = 83) or warfarin (n = 81). Both of these groups were significantly older than those not on anticoagulation (70 vs. 67 years). As expected , they were significantly more likely to have cardiac arrhythmias, heart failure, or pulmonary embolism or deep vein thrombosis and significantly more likely to be on immunosuppressant therapy or steroids. Their diffusing capacity of lung for carbon dioxide was also significantly lower.

There were no significant lung disease–related differences in anticoagulation therapy, other than a trend toward more use among those with connective tissue disease–associated interstitial lung disease.

Over 2 years, the entire cohort experienced 110 deaths (5.7%), 52 transplants (2.7%), and 29 withdrawals (1.5%). Among patients with IPF, there were 80 deaths (6.7%), 43 transplants (3.6%) and 20 withdrawals (1.7%).

In an unadjusted analysis, anticoagulation more than doubled the risk of an event, compared with no anticoagulation (hazard ratio, 2.4). This was slightly attenuated, but still significant, in a multivariate model that controlled for age, gender, oxygen use, gastroesophageal reflux disease, obstructive sleep apnea, arrhythmia, cancer, heart failure, obesity, venous thromboembolism, and antifibrotics (HR, 1.88).

A second whole-cohort analysis looked at the survival ratios for both warfarin and DOAC, compared with no treatment. In the fully adjusted model, warfarin was associated with a significantly increased risk HR (2.28) but DOAC was not.

The investigators then examined risk in only patients with lung disease. Among those with IPF, the fully adjusted model showed that warfarin nearly tripled the risk of transplant or death (HR, 2.8), while DOAC had no significant effect.

The reason for this association remains unclear, Dr. King said. “Renal failure may be a big reason patients get warfarin instead of DOAC. It’s difficult to say whether these patients were frail or prone to bleeding. Even something like the care team not being as up to date with treatment could be affecting the numbers. And is it the direct effect of warfarin on fibrotic lung disease? Or maybe DOAC has some beneficial effect on pulmonary fibrosis? We don’t know.

“But what we can take away from this is that warfarin is associated with worse outcomes than DOAC in patients with IPF. It seems reasonable to use DOAC over warfarin if there’s no specific contraindication to DOAC. If you have a patient with pulmonary thrombosis who has indications for anticoagulation I would use DOAC, based on the evidence that we now have available.”

Dr. King had no disclosures.

msullivan@mdedge.com

DALLAS – Warfarin appears to increase the risk of lung transplant or death for patients with fibrotic lung disease who need anticoagulation therapy, Christopher King, MD, said at the American Thoracic Society’s international conference.

Michele G. Sullivan/MDedge News

Compared with direct oral anticoagulation (DOAC), warfarin doubled the risk of those outcomes, even after the researchers controlled for multiple morbidities that accompany the need for anticoagulation, said Dr. King, medical director of the transplant and advanced lung disease critical care program at Inova Fairfax (Va.) Hospital.

“The need for anticoagulation in patients with interstitial lung disease is already associated with an increased risk of death or transplant,” he said. Warfarin – but not oral anticoagulation – seems to increase that risk even more “no matter how you analyze it,” he said.

“We know now that fibrosis and coagulation are entwined, and there’s background epidemiologic data showing an increased incidence of venous thromboembolism and acute coronary syndrome in patients with pulmonary fibrosis. This suggests that a dysregulated coagulation cascade may play a role in the pathogenesis of fibrosis.”

The relationship has been explored for the last decade or so. Two recent meta-analyses came to similar conclusions.

In 2013, a 125-patient retrospective cohort study compared clinical characteristics and survival among patients with idiopathic pulmonary fibrosis (IPF) who received anticoagulant therapy with those who did not (Sarcoidosis Vasc Diffuse Lung Dis. 2013 Aug 1;30[2]:121-7). Those who got the treatment had worse survival outcomes at 1 and 3 years than did those who received no therapy (84% vs. 53% and 89% vs. 64%, respectively).

In 2016, a post hoc analysis of three placebo-controlled studies determined that any anticoagulant use independently increased the risk of death among patients with IPF, compared with nonuse: 15.6% vs 6.3% all-cause mortality (Eur Respir J. 2016. doi: 10.1183/13993003.02087-2015).

But these investigations didn’t parse out the types of anticoagulation. Direct oral anticoagulation (DOAC) is much more common now, however, and Dr. King and colleagues wanted to find out how warfarin and DOAC compared.

They retrospectively analyzed data from the Pulmonary Fibrosis Foundation’s database and compared the risk of lung transplant and death for patients on anticoagulation or no anticoagulation and for those receiving DOACs versus warfarin versus no anticoagulation.

The study comprised 1,918 patients, 91% of whom were not on anticoagulation therapy. The remaining 164 were either taking DOAC (n = 83) or warfarin (n = 81). Both of these groups were significantly older than those not on anticoagulation (70 vs. 67 years). As expected , they were significantly more likely to have cardiac arrhythmias, heart failure, or pulmonary embolism or deep vein thrombosis and significantly more likely to be on immunosuppressant therapy or steroids. Their diffusing capacity of lung for carbon dioxide was also significantly lower.

There were no significant lung disease–related differences in anticoagulation therapy, other than a trend toward more use among those with connective tissue disease–associated interstitial lung disease.

Over 2 years, the entire cohort experienced 110 deaths (5.7%), 52 transplants (2.7%), and 29 withdrawals (1.5%). Among patients with IPF, there were 80 deaths (6.7%), 43 transplants (3.6%) and 20 withdrawals (1.7%).

In an unadjusted analysis, anticoagulation more than doubled the risk of an event, compared with no anticoagulation (hazard ratio, 2.4). This was slightly attenuated, but still significant, in a multivariate model that controlled for age, gender, oxygen use, gastroesophageal reflux disease, obstructive sleep apnea, arrhythmia, cancer, heart failure, obesity, venous thromboembolism, and antifibrotics (HR, 1.88).

A second whole-cohort analysis looked at the survival ratios for both warfarin and DOAC, compared with no treatment. In the fully adjusted model, warfarin was associated with a significantly increased risk HR (2.28) but DOAC was not.

The investigators then examined risk in only patients with lung disease. Among those with IPF, the fully adjusted model showed that warfarin nearly tripled the risk of transplant or death (HR, 2.8), while DOAC had no significant effect.

The reason for this association remains unclear, Dr. King said. “Renal failure may be a big reason patients get warfarin instead of DOAC. It’s difficult to say whether these patients were frail or prone to bleeding. Even something like the care team not being as up to date with treatment could be affecting the numbers. And is it the direct effect of warfarin on fibrotic lung disease? Or maybe DOAC has some beneficial effect on pulmonary fibrosis? We don’t know.

“But what we can take away from this is that warfarin is associated with worse outcomes than DOAC in patients with IPF. It seems reasonable to use DOAC over warfarin if there’s no specific contraindication to DOAC. If you have a patient with pulmonary thrombosis who has indications for anticoagulation I would use DOAC, based on the evidence that we now have available.”

Dr. King had no disclosures.

msullivan@mdedge.com

With 971 cases of measles reported after just 5 months of 2019, the United States has hit another dubious milestone by surpassing the 963 cases reported in the preelimination year of 1994, according to the Centers for Disease Control and Prevention.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

That leaves 1992, when there were 2,237 cases reported, as the next big obstacle on measles’ current path of distinction, the CDC data show. Only 312 cases were reported in 1993.

“Outbreaks in New York City and Rockland County, New York have continued for nearly 8 months. If these outbreaks continue through summer and fall, the United States may lose its measles elimination status. That loss would be a huge blow for the nation and erase the hard work done by all levels of public health,” the CDC said May 30.

The CDC defines measles elimination as “the absence of continuous disease transmission for 12 months or more in a specific geographic area” and notes that “measles is no longer endemic [constantly present] in the United States.”

“Measles is preventable and the way to end this outbreak is to ensure that all children and adults who can get vaccinated, do get vaccinated. Again, I want to reassure parents that vaccines are safe, they do not cause autism. The greater danger is the disease that vaccination prevents,” CDC director Robert Redfield, MD, said in a statement.

rfranki@mdedge.com

With 971 cases of measles reported after just 5 months of 2019, the United States has hit another dubious milestone by surpassing the 963 cases reported in the preelimination year of 1994, according to the Centers for Disease Control and Prevention.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

That leaves 1992, when there were 2,237 cases reported, as the next big obstacle on measles’ current path of distinction, the CDC data show. Only 312 cases were reported in 1993.

“Outbreaks in New York City and Rockland County, New York have continued for nearly 8 months. If these outbreaks continue through summer and fall, the United States may lose its measles elimination status. That loss would be a huge blow for the nation and erase the hard work done by all levels of public health,” the CDC said May 30.

The CDC defines measles elimination as “the absence of continuous disease transmission for 12 months or more in a specific geographic area” and notes that “measles is no longer endemic [constantly present] in the United States.”

“Measles is preventable and the way to end this outbreak is to ensure that all children and adults who can get vaccinated, do get vaccinated. Again, I want to reassure parents that vaccines are safe, they do not cause autism. The greater danger is the disease that vaccination prevents,” CDC director Robert Redfield, MD, said in a statement.

rfranki@mdedge.com

With 971 cases of measles reported after just 5 months of 2019, the United States has hit another dubious milestone by surpassing the 963 cases reported in the preelimination year of 1994, according to the Centers for Disease Control and Prevention.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

That leaves 1992, when there were 2,237 cases reported, as the next big obstacle on measles’ current path of distinction, the CDC data show. Only 312 cases were reported in 1993.

“Outbreaks in New York City and Rockland County, New York have continued for nearly 8 months. If these outbreaks continue through summer and fall, the United States may lose its measles elimination status. That loss would be a huge blow for the nation and erase the hard work done by all levels of public health,” the CDC said May 30.

The CDC defines measles elimination as “the absence of continuous disease transmission for 12 months or more in a specific geographic area” and notes that “measles is no longer endemic [constantly present] in the United States.”

“Measles is preventable and the way to end this outbreak is to ensure that all children and adults who can get vaccinated, do get vaccinated. Again, I want to reassure parents that vaccines are safe, they do not cause autism. The greater danger is the disease that vaccination prevents,” CDC director Robert Redfield, MD, said in a statement.

rfranki@mdedge.com

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.

Bruce Jancin/MDedge News

“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.

bjancin@mdedge.com
 

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.

Bruce Jancin/MDedge News

“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.

bjancin@mdedge.com
 

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.

Bruce Jancin/MDedge News

“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.

bjancin@mdedge.com
 

The causes of death differ throughout pregnancy and postpartum. Overall, heart disease and stroke cause > 1 in 3 deaths. At delivery, most deaths are due to obstetric emergencies, such as severe bleeding and amniotic fluid embolism. In the week after delivery, severe bleeding, high blood pressure, and infection are most common.  But one-third of the deaths happen 1 week to 1 year after delivery, most often caused by cardiomyopathy.

The findings also confirm racial disparities, the CDC says. Black and Native American women were about 3 times as likely as white women to die of a pregnancy-related cause.

The researchers analyzed 2011-2015 national data on pregnancy mortality and 2013-2017 data from 13 state maternal mortality review committees. Their analysis revealed that most pregnancy-related deaths were preventable regardless of race or ethnicity. Each death represents a “web of missed opportunities,” the CDC says. The mortality review committees determined that each death was associated with several contributing factors, including lack of access to appropriate care, missed or delayed diagnoses, and lack of knowledge among patients and providers about warning signs.

The CDC offers advice on how to help keep patients safe during and after pregnancy. For example:

• Help patients manage their chronic conditions;
• Teach patients about warning signs; and
• Use tools to flag warning signs early so women can receive timely treatment

Hospitals also can standardize patient care, the CDC advises, including delivering high-risk women at hospitals with specialized providers and equipment. They can train nonobstetric providers to consider the patient’s recent pregnancy history. Importantly, health care practitioners should continue to provide high-quality care for mothers up to at least 1 year after birth.

The causes of death differ throughout pregnancy and postpartum. Overall, heart disease and stroke cause > 1 in 3 deaths. At delivery, most deaths are due to obstetric emergencies, such as severe bleeding and amniotic fluid embolism. In the week after delivery, severe bleeding, high blood pressure, and infection are most common.  But one-third of the deaths happen 1 week to 1 year after delivery, most often caused by cardiomyopathy.

The findings also confirm racial disparities, the CDC says. Black and Native American women were about 3 times as likely as white women to die of a pregnancy-related cause.

The researchers analyzed 2011-2015 national data on pregnancy mortality and 2013-2017 data from 13 state maternal mortality review committees. Their analysis revealed that most pregnancy-related deaths were preventable regardless of race or ethnicity. Each death represents a “web of missed opportunities,” the CDC says. The mortality review committees determined that each death was associated with several contributing factors, including lack of access to appropriate care, missed or delayed diagnoses, and lack of knowledge among patients and providers about warning signs.

The CDC offers advice on how to help keep patients safe during and after pregnancy. For example:

• Help patients manage their chronic conditions;
• Teach patients about warning signs; and
• Use tools to flag warning signs early so women can receive timely treatment

Hospitals also can standardize patient care, the CDC advises, including delivering high-risk women at hospitals with specialized providers and equipment. They can train nonobstetric providers to consider the patient’s recent pregnancy history. Importantly, health care practitioners should continue to provide high-quality care for mothers up to at least 1 year after birth.

The causes of death differ throughout pregnancy and postpartum. Overall, heart disease and stroke cause > 1 in 3 deaths. At delivery, most deaths are due to obstetric emergencies, such as severe bleeding and amniotic fluid embolism. In the week after delivery, severe bleeding, high blood pressure, and infection are most common.  But one-third of the deaths happen 1 week to 1 year after delivery, most often caused by cardiomyopathy.

The findings also confirm racial disparities, the CDC says. Black and Native American women were about 3 times as likely as white women to die of a pregnancy-related cause.

The researchers analyzed 2011-2015 national data on pregnancy mortality and 2013-2017 data from 13 state maternal mortality review committees. Their analysis revealed that most pregnancy-related deaths were preventable regardless of race or ethnicity. Each death represents a “web of missed opportunities,” the CDC says. The mortality review committees determined that each death was associated with several contributing factors, including lack of access to appropriate care, missed or delayed diagnoses, and lack of knowledge among patients and providers about warning signs.

The CDC offers advice on how to help keep patients safe during and after pregnancy. For example:

• Help patients manage their chronic conditions;
• Teach patients about warning signs; and
• Use tools to flag warning signs early so women can receive timely treatment

Hospitals also can standardize patient care, the CDC advises, including delivering high-risk women at hospitals with specialized providers and equipment. They can train nonobstetric providers to consider the patient’s recent pregnancy history. Importantly, health care practitioners should continue to provide high-quality care for mothers up to at least 1 year after birth.

A new virus has been associated with febrile illness in China in patients with histories of tick bites. The data on the discovery, isolation, and characterization of the virus were reported in the New England Journal of Medicine.

The segmented RNA virus now known as Alongshan virus (ALSV) “belongs to the unclassified jingmenvirus group in the family Flaviviridae, which includes the genera flavivirus, pestivirus, hepacivirus, and pegivirus,” wrote Ze-Dong Wang, PhD, of Foshan (China) University, and colleagues.

The index patient with ALSV was a 42-year-old female farmer from the town of Alongshan, China, who presented to a regional hospital in April 2017 with fever, headache, and a history of tick bites. The initial clinical features were similar to those seen in tickborne diseases, but a blood sample showed no RNA or antibodies for tickborne encephalitis virus. Investigators obtained a blood specimen from the index patient 4 days after the onset of illness. After culturing the sample, the investigators extracted the viral RNA genome and sequenced it.

Sequence analysis found that the new pathogen was related to segmented viruses in the jingmenvirus group of the family Flaviviridae; however, “comparison of the amino acids further confirmed that ALSV is genetically distinct from other jingmenviruses,” the investigators said.

The investigators identified 374 patients who presented to the hospital with fever, headache, and a history of tick bites during May 2017–September 2017; 86 patients had confirmed ALSV infections via nested reverse-transcription polymerase chain reaction testing. Of these, 63 were men and 84 were farmers or forestry workers. Although ticks were common in the patients’ environments, no other evidence of tickborne diseases was noted. The patients ranged in age from 24 to 77 years, and the average duration of the infection was 3-7 days.

Symptoms were nonspecific and included fever, headache, fatigue, nausea, cough, and sore throat. All 86 patients were treated with intravenous ribavirin (0.5 g/day), and intramuscular benzylpenicillin sodium (2 million U/day) for 3-5 days. The median hospital stay was 11 days, and no deaths or long-term clinical complications occurred in the confirmed ALSV patients.

ALSV is similar to other jingmenviruses, but is distinct from other infections in part because of the absence of a rash or jaundice, the investigators said.

Although the investigators said they suspected the disease was carried by ticks, they would not rule out mosquitoes as a possible carrier because ALSV RNA was found in mosquitoes in a Northeastern province of China, and the RNA from those mosquitoes was found to be genetically related to the RNA assessed in this study.

Overall, “our findings suggest that ALSV may be the cause of a previously unknown febrile disease, and more studies should be conducted to determine the geographic distribution of this disease outside its current areas of identification,” they said.

The research was supported by the National Key Research and Development Program of China and the National Natural Science Foundation of China.
 

SOURCE: Wang Z et al. N Engl J Med. 2019 May 29. doi: 10.1056/NEJMoa1805068.

A new virus has been associated with febrile illness in China in patients with histories of tick bites. The data on the discovery, isolation, and characterization of the virus were reported in the New England Journal of Medicine.

The segmented RNA virus now known as Alongshan virus (ALSV) “belongs to the unclassified jingmenvirus group in the family Flaviviridae, which includes the genera flavivirus, pestivirus, hepacivirus, and pegivirus,” wrote Ze-Dong Wang, PhD, of Foshan (China) University, and colleagues.

The index patient with ALSV was a 42-year-old female farmer from the town of Alongshan, China, who presented to a regional hospital in April 2017 with fever, headache, and a history of tick bites. The initial clinical features were similar to those seen in tickborne diseases, but a blood sample showed no RNA or antibodies for tickborne encephalitis virus. Investigators obtained a blood specimen from the index patient 4 days after the onset of illness. After culturing the sample, the investigators extracted the viral RNA genome and sequenced it.

Sequence analysis found that the new pathogen was related to segmented viruses in the jingmenvirus group of the family Flaviviridae; however, “comparison of the amino acids further confirmed that ALSV is genetically distinct from other jingmenviruses,” the investigators said.

The investigators identified 374 patients who presented to the hospital with fever, headache, and a history of tick bites during May 2017–September 2017; 86 patients had confirmed ALSV infections via nested reverse-transcription polymerase chain reaction testing. Of these, 63 were men and 84 were farmers or forestry workers. Although ticks were common in the patients’ environments, no other evidence of tickborne diseases was noted. The patients ranged in age from 24 to 77 years, and the average duration of the infection was 3-7 days.

Symptoms were nonspecific and included fever, headache, fatigue, nausea, cough, and sore throat. All 86 patients were treated with intravenous ribavirin (0.5 g/day), and intramuscular benzylpenicillin sodium (2 million U/day) for 3-5 days. The median hospital stay was 11 days, and no deaths or long-term clinical complications occurred in the confirmed ALSV patients.

ALSV is similar to other jingmenviruses, but is distinct from other infections in part because of the absence of a rash or jaundice, the investigators said.

Although the investigators said they suspected the disease was carried by ticks, they would not rule out mosquitoes as a possible carrier because ALSV RNA was found in mosquitoes in a Northeastern province of China, and the RNA from those mosquitoes was found to be genetically related to the RNA assessed in this study.

Overall, “our findings suggest that ALSV may be the cause of a previously unknown febrile disease, and more studies should be conducted to determine the geographic distribution of this disease outside its current areas of identification,” they said.

The research was supported by the National Key Research and Development Program of China and the National Natural Science Foundation of China.
 

SOURCE: Wang Z et al. N Engl J Med. 2019 May 29. doi: 10.1056/NEJMoa1805068.

A new virus has been associated with febrile illness in China in patients with histories of tick bites. The data on the discovery, isolation, and characterization of the virus were reported in the New England Journal of Medicine.

The segmented RNA virus now known as Alongshan virus (ALSV) “belongs to the unclassified jingmenvirus group in the family Flaviviridae, which includes the genera flavivirus, pestivirus, hepacivirus, and pegivirus,” wrote Ze-Dong Wang, PhD, of Foshan (China) University, and colleagues.

The index patient with ALSV was a 42-year-old female farmer from the town of Alongshan, China, who presented to a regional hospital in April 2017 with fever, headache, and a history of tick bites. The initial clinical features were similar to those seen in tickborne diseases, but a blood sample showed no RNA or antibodies for tickborne encephalitis virus. Investigators obtained a blood specimen from the index patient 4 days after the onset of illness. After culturing the sample, the investigators extracted the viral RNA genome and sequenced it.

Sequence analysis found that the new pathogen was related to segmented viruses in the jingmenvirus group of the family Flaviviridae; however, “comparison of the amino acids further confirmed that ALSV is genetically distinct from other jingmenviruses,” the investigators said.

The investigators identified 374 patients who presented to the hospital with fever, headache, and a history of tick bites during May 2017–September 2017; 86 patients had confirmed ALSV infections via nested reverse-transcription polymerase chain reaction testing. Of these, 63 were men and 84 were farmers or forestry workers. Although ticks were common in the patients’ environments, no other evidence of tickborne diseases was noted. The patients ranged in age from 24 to 77 years, and the average duration of the infection was 3-7 days.

Symptoms were nonspecific and included fever, headache, fatigue, nausea, cough, and sore throat. All 86 patients were treated with intravenous ribavirin (0.5 g/day), and intramuscular benzylpenicillin sodium (2 million U/day) for 3-5 days. The median hospital stay was 11 days, and no deaths or long-term clinical complications occurred in the confirmed ALSV patients.

ALSV is similar to other jingmenviruses, but is distinct from other infections in part because of the absence of a rash or jaundice, the investigators said.

Although the investigators said they suspected the disease was carried by ticks, they would not rule out mosquitoes as a possible carrier because ALSV RNA was found in mosquitoes in a Northeastern province of China, and the RNA from those mosquitoes was found to be genetically related to the RNA assessed in this study.

Overall, “our findings suggest that ALSV may be the cause of a previously unknown febrile disease, and more studies should be conducted to determine the geographic distribution of this disease outside its current areas of identification,” they said.

The research was supported by the National Key Research and Development Program of China and the National Natural Science Foundation of China.
 

SOURCE: Wang Z et al. N Engl J Med. 2019 May 29. doi: 10.1056/NEJMoa1805068.

A 10-valent pneumococcal conjugate vaccine appeared equally effective against pneumococcal disease in boys and girls, according to Heta Nieminen, MD, of the National Institute for Health and Welfare in Tampere, Finland, and associates.

MarianVejcik/Getty Images

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.

lfranki@mdedge.com

A 10-valent pneumococcal conjugate vaccine appeared equally effective against pneumococcal disease in boys and girls, according to Heta Nieminen, MD, of the National Institute for Health and Welfare in Tampere, Finland, and associates.

MarianVejcik/Getty Images

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.

lfranki@mdedge.com

A 10-valent pneumococcal conjugate vaccine appeared equally effective against pneumococcal disease in boys and girls, according to Heta Nieminen, MD, of the National Institute for Health and Welfare in Tampere, Finland, and associates.

MarianVejcik/Getty Images

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.

lfranki@mdedge.com

Trimethoprim-sulfamethoxazole (TMP-SMX) was linked to severe acute respiratory distress syndrome (ARDS) in five previously healthy teens, two of whom died.

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.

Trimethoprim-sulfamethoxazole (TMP-SMX) was linked to severe acute respiratory distress syndrome (ARDS) in five previously healthy teens, two of whom died.

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.

Trimethoprim-sulfamethoxazole (TMP-SMX) was linked to severe acute respiratory distress syndrome (ARDS) in five previously healthy teens, two of whom died.

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.