Heidi Splete

The incidence of lice and scabies decreased significantly among children and adults in North Carolina during the confinement period of the COVID-19 pandemic, between March 2020 and February 2021, according to a report in Pediatric Dermatology.

When COVID-19 was declared a public health emergency by the World Health Organization in March 2020, many countries including the United States enacted lockdown and isolation measures to help contain the spread of the disease. Since scabies and lice are both spread by direct contact, “we hypothesized that the nationwide lockdown would influence the transmission of these two conditions among individuals,” wrote Marianne Bonanno, MD, of the University of North Carolina, Chapel Hill, and colleagues.

“The pandemic created a unique opportunity for real-life observations following physical distancing measures being put in place,” coauthor Christopher Sayed, MD, associate professor of dermatology at UNC, said in an interview. “It makes intuitive sense that since lice and scabies spread by cost physical contact that rates would decrease with school closures and other physical distancing measures. Reports from other countries in which extended families more often live together and were forced to spend more time in close quarters saw increased rates so it was interesting to see this contrast,” he noted.

In the study, the researchers reviewed data from 1,858 cases of adult scabies, 893 cases of pediatric scabies, and 804 cases of pediatric lice reported in North Carolina between March 2017 and February 2021. They compared monthly cases of scabies and lice, and prescriptions during the period before the pandemic (March 2017 to February 2020), and during the pandemic (March 2020 to February 2021).

Pediatric lice cases decreased by 60.6% over the study period (P < .001). Significant decreases also occurred in adult scabies (31.1%, P < .001) and pediatric scabies (39%, P < .01).

The number of prescriptions for lice and scabies also decreased significantly (P < .01) during the study period, although these numbers differed from the actual cases. Prescriptions decreased by 41.4%, 29.9%, and 69.3% for pediatric scabies, adult scabies, and pediatric lice, respectively.

Both pediatric scabies and pediatric lice showed a greater drop in prescriptions than in cases, while the drop in prescriptions for adult scabies was slightly less than the drop in cases.

The difference in the decreased numbers between cases and prescriptions may stem from the decrease in close contacts during the pandemic, which decreased the need for multiple prescriptions, but other potential explanations could be examined in future studies, the researchers wrote in their discussion.

The study findings were limited by several factors including the cross-sectional design and potential underdiagnosis and underreporting, as well as the focus only on a population in a single state, which may limit generalizability, the researchers noted.

However, the results offer preliminary insights on the impact of COVID-19 restrictions on scabies and lice, and suggest the potential value of physical distancing to reduce transmission of both conditions, especially in settings such as schools and prisons, to help contain future outbreaks, they concluded.

The study findings reinforce physical contact as the likely route of disease transmission, for lice and scabies, Dr. Sayed said in the interview. “It’s possible distancing measures on a small scale could be considered for outbreaks in institutional settings, though the risks of these infestations are much lower than with COVID-19,” he said. “It will be interesting to observe trends as physical distancing measures end to see if cases rebound in the next few years,” he added.

Drop in cases likely temporary

“Examining the epidemiology of different infectious diseases over time is an interesting and important area of study,” said Sheilagh Maguiness, MD, associate professor of dermatology and pediatrics at the University of Minnesota, Minneapolis, who was asked to comment on the results.

“The pandemic dramatically altered the daily lives of adults and children across the globe, and we can learn a lot from studying how social distancing and prolonged masking has made an impact on the incidence and prevalence of different infectious illnesses in the country and across the world,” she said in an interview.

Dr. Maguiness said she was not surprised by the study findings. “In fact, other countries have published similar studies documenting a reduction in both head lice and scabies infestations during the time of the pandemic,” she said. “In France, it was noted that during March to December 2020, there was a reduction in sales for topical head lice and scabies treatments of 44% and 14%, respectively. Similarly, a study from Argentina documented a decline in head lice infestations by about 25% among children,” she said.

“I personally noted a marked decrease in both of these diagnoses among children in my own clinic,” she added.

“Since both of these conditions are spread through close physical contact with others, it makes sense that there would be a steep decline in ectoparasitic infections during times of social distancing. However, anecdotally we are now diagnosing and treating these infestations again more regularly in our clinic,” said Dr. Maguiness. “As social distancing relaxes, I would expect that the incidence of both head lice and scabies will again increase.” 

The study received no outside funding. The researchers and Dr. Maguiness had no financial conflicts to disclose.

The incidence of lice and scabies decreased significantly among children and adults in North Carolina during the confinement period of the COVID-19 pandemic, between March 2020 and February 2021, according to a report in Pediatric Dermatology.

When COVID-19 was declared a public health emergency by the World Health Organization in March 2020, many countries including the United States enacted lockdown and isolation measures to help contain the spread of the disease. Since scabies and lice are both spread by direct contact, “we hypothesized that the nationwide lockdown would influence the transmission of these two conditions among individuals,” wrote Marianne Bonanno, MD, of the University of North Carolina, Chapel Hill, and colleagues.

“The pandemic created a unique opportunity for real-life observations following physical distancing measures being put in place,” coauthor Christopher Sayed, MD, associate professor of dermatology at UNC, said in an interview. “It makes intuitive sense that since lice and scabies spread by cost physical contact that rates would decrease with school closures and other physical distancing measures. Reports from other countries in which extended families more often live together and were forced to spend more time in close quarters saw increased rates so it was interesting to see this contrast,” he noted.

In the study, the researchers reviewed data from 1,858 cases of adult scabies, 893 cases of pediatric scabies, and 804 cases of pediatric lice reported in North Carolina between March 2017 and February 2021. They compared monthly cases of scabies and lice, and prescriptions during the period before the pandemic (March 2017 to February 2020), and during the pandemic (March 2020 to February 2021).

Pediatric lice cases decreased by 60.6% over the study period (P < .001). Significant decreases also occurred in adult scabies (31.1%, P < .001) and pediatric scabies (39%, P < .01).

The number of prescriptions for lice and scabies also decreased significantly (P < .01) during the study period, although these numbers differed from the actual cases. Prescriptions decreased by 41.4%, 29.9%, and 69.3% for pediatric scabies, adult scabies, and pediatric lice, respectively.

Both pediatric scabies and pediatric lice showed a greater drop in prescriptions than in cases, while the drop in prescriptions for adult scabies was slightly less than the drop in cases.

The difference in the decreased numbers between cases and prescriptions may stem from the decrease in close contacts during the pandemic, which decreased the need for multiple prescriptions, but other potential explanations could be examined in future studies, the researchers wrote in their discussion.

The study findings were limited by several factors including the cross-sectional design and potential underdiagnosis and underreporting, as well as the focus only on a population in a single state, which may limit generalizability, the researchers noted.

However, the results offer preliminary insights on the impact of COVID-19 restrictions on scabies and lice, and suggest the potential value of physical distancing to reduce transmission of both conditions, especially in settings such as schools and prisons, to help contain future outbreaks, they concluded.

The study findings reinforce physical contact as the likely route of disease transmission, for lice and scabies, Dr. Sayed said in the interview. “It’s possible distancing measures on a small scale could be considered for outbreaks in institutional settings, though the risks of these infestations are much lower than with COVID-19,” he said. “It will be interesting to observe trends as physical distancing measures end to see if cases rebound in the next few years,” he added.

Drop in cases likely temporary

“Examining the epidemiology of different infectious diseases over time is an interesting and important area of study,” said Sheilagh Maguiness, MD, associate professor of dermatology and pediatrics at the University of Minnesota, Minneapolis, who was asked to comment on the results.

“The pandemic dramatically altered the daily lives of adults and children across the globe, and we can learn a lot from studying how social distancing and prolonged masking has made an impact on the incidence and prevalence of different infectious illnesses in the country and across the world,” she said in an interview.

Dr. Maguiness said she was not surprised by the study findings. “In fact, other countries have published similar studies documenting a reduction in both head lice and scabies infestations during the time of the pandemic,” she said. “In France, it was noted that during March to December 2020, there was a reduction in sales for topical head lice and scabies treatments of 44% and 14%, respectively. Similarly, a study from Argentina documented a decline in head lice infestations by about 25% among children,” she said.

“I personally noted a marked decrease in both of these diagnoses among children in my own clinic,” she added.

“Since both of these conditions are spread through close physical contact with others, it makes sense that there would be a steep decline in ectoparasitic infections during times of social distancing. However, anecdotally we are now diagnosing and treating these infestations again more regularly in our clinic,” said Dr. Maguiness. “As social distancing relaxes, I would expect that the incidence of both head lice and scabies will again increase.” 

The study received no outside funding. The researchers and Dr. Maguiness had no financial conflicts to disclose.

The incidence of lice and scabies decreased significantly among children and adults in North Carolina during the confinement period of the COVID-19 pandemic, between March 2020 and February 2021, according to a report in Pediatric Dermatology.

When COVID-19 was declared a public health emergency by the World Health Organization in March 2020, many countries including the United States enacted lockdown and isolation measures to help contain the spread of the disease. Since scabies and lice are both spread by direct contact, “we hypothesized that the nationwide lockdown would influence the transmission of these two conditions among individuals,” wrote Marianne Bonanno, MD, of the University of North Carolina, Chapel Hill, and colleagues.

“The pandemic created a unique opportunity for real-life observations following physical distancing measures being put in place,” coauthor Christopher Sayed, MD, associate professor of dermatology at UNC, said in an interview. “It makes intuitive sense that since lice and scabies spread by cost physical contact that rates would decrease with school closures and other physical distancing measures. Reports from other countries in which extended families more often live together and were forced to spend more time in close quarters saw increased rates so it was interesting to see this contrast,” he noted.

In the study, the researchers reviewed data from 1,858 cases of adult scabies, 893 cases of pediatric scabies, and 804 cases of pediatric lice reported in North Carolina between March 2017 and February 2021. They compared monthly cases of scabies and lice, and prescriptions during the period before the pandemic (March 2017 to February 2020), and during the pandemic (March 2020 to February 2021).

Pediatric lice cases decreased by 60.6% over the study period (P < .001). Significant decreases also occurred in adult scabies (31.1%, P < .001) and pediatric scabies (39%, P < .01).

The number of prescriptions for lice and scabies also decreased significantly (P < .01) during the study period, although these numbers differed from the actual cases. Prescriptions decreased by 41.4%, 29.9%, and 69.3% for pediatric scabies, adult scabies, and pediatric lice, respectively.

Both pediatric scabies and pediatric lice showed a greater drop in prescriptions than in cases, while the drop in prescriptions for adult scabies was slightly less than the drop in cases.

The difference in the decreased numbers between cases and prescriptions may stem from the decrease in close contacts during the pandemic, which decreased the need for multiple prescriptions, but other potential explanations could be examined in future studies, the researchers wrote in their discussion.

The study findings were limited by several factors including the cross-sectional design and potential underdiagnosis and underreporting, as well as the focus only on a population in a single state, which may limit generalizability, the researchers noted.

However, the results offer preliminary insights on the impact of COVID-19 restrictions on scabies and lice, and suggest the potential value of physical distancing to reduce transmission of both conditions, especially in settings such as schools and prisons, to help contain future outbreaks, they concluded.

The study findings reinforce physical contact as the likely route of disease transmission, for lice and scabies, Dr. Sayed said in the interview. “It’s possible distancing measures on a small scale could be considered for outbreaks in institutional settings, though the risks of these infestations are much lower than with COVID-19,” he said. “It will be interesting to observe trends as physical distancing measures end to see if cases rebound in the next few years,” he added.

Drop in cases likely temporary

“Examining the epidemiology of different infectious diseases over time is an interesting and important area of study,” said Sheilagh Maguiness, MD, associate professor of dermatology and pediatrics at the University of Minnesota, Minneapolis, who was asked to comment on the results.

“The pandemic dramatically altered the daily lives of adults and children across the globe, and we can learn a lot from studying how social distancing and prolonged masking has made an impact on the incidence and prevalence of different infectious illnesses in the country and across the world,” she said in an interview.

Dr. Maguiness said she was not surprised by the study findings. “In fact, other countries have published similar studies documenting a reduction in both head lice and scabies infestations during the time of the pandemic,” she said. “In France, it was noted that during March to December 2020, there was a reduction in sales for topical head lice and scabies treatments of 44% and 14%, respectively. Similarly, a study from Argentina documented a decline in head lice infestations by about 25% among children,” she said.

“I personally noted a marked decrease in both of these diagnoses among children in my own clinic,” she added.

“Since both of these conditions are spread through close physical contact with others, it makes sense that there would be a steep decline in ectoparasitic infections during times of social distancing. However, anecdotally we are now diagnosing and treating these infestations again more regularly in our clinic,” said Dr. Maguiness. “As social distancing relaxes, I would expect that the incidence of both head lice and scabies will again increase.” 

The study received no outside funding. The researchers and Dr. Maguiness had no financial conflicts to disclose.

The Food and Drug Administration has sent warning letters to three companies, including Amazon, for selling mole and skin tag removal products that have not been approved by the agency, according to a press release issued on Aug. 9.

In addition to Amazon.com, the other two companies are Ariella Naturals, and Justified Laboratories.

Currently, no over-the-counter products are FDA-approved for the at-home removal of moles and skin tags, and use of unapproved products could be dangerous to consumers, according to the statement. These products may be sold as ointments, gels, sticks, or liquids, and may contain high concentrations of salicylic acid or other harmful ingredients. Introducing unapproved products in to interstate commerce violates the Federal Food, Drug, and Cosmetic Act.

Two products sold on Amazon are the “Deisana Skin Tag Remover, Mole Remover and Repair Gel Set” and “Skincell Mole Skin Tag Corrector Serum,” according to the letter sent to Amazon.

The warning letters alert the three companies that they have 15 days from receipt to address any violations. However, warning letters are not a final FDA action, according to the statement.

“The agency’s rigorous surveillance works to identify threats to public health and stop these products from reaching our communities,” Donald D. Ashley, JD, director of the Office of Compliance in the FDA’s Center for Drug Evaluation and Research, said in the press release. “This includes where online retailers like Amazon are involved in the interstate sale of unapproved drug products. We will continue to work diligently to ensure that online retailers do not sell products that violate federal law,” he added.

The statement emphasized that moles should be evaluated by a health care professional, as attempts at self-diagnosis and at-home treatment could lead to a delayed cancer diagnosis, and potentially to cancer progression.

Products marketed to consumers for at-home removal of moles, skin tags, and other skin lesions could cause injuries, infections, and scarring, according to a related consumer update first posted by the FDA in June, which was updated after the warning letters were sent out.

Consumers and health care professionals are encouraged to report any adverse events related to mole removal or skin tag removal products to the agency’s MedWatch Adverse Event Reporting program.

The FDA also offers an online guide, BeSafeRx, with advice for consumers about potential risks of using online pharmacies and how to do so safely.

The Food and Drug Administration has sent warning letters to three companies, including Amazon, for selling mole and skin tag removal products that have not been approved by the agency, according to a press release issued on Aug. 9.

In addition to Amazon.com, the other two companies are Ariella Naturals, and Justified Laboratories.

Currently, no over-the-counter products are FDA-approved for the at-home removal of moles and skin tags, and use of unapproved products could be dangerous to consumers, according to the statement. These products may be sold as ointments, gels, sticks, or liquids, and may contain high concentrations of salicylic acid or other harmful ingredients. Introducing unapproved products in to interstate commerce violates the Federal Food, Drug, and Cosmetic Act.

Two products sold on Amazon are the “Deisana Skin Tag Remover, Mole Remover and Repair Gel Set” and “Skincell Mole Skin Tag Corrector Serum,” according to the letter sent to Amazon.

The warning letters alert the three companies that they have 15 days from receipt to address any violations. However, warning letters are not a final FDA action, according to the statement.

“The agency’s rigorous surveillance works to identify threats to public health and stop these products from reaching our communities,” Donald D. Ashley, JD, director of the Office of Compliance in the FDA’s Center for Drug Evaluation and Research, said in the press release. “This includes where online retailers like Amazon are involved in the interstate sale of unapproved drug products. We will continue to work diligently to ensure that online retailers do not sell products that violate federal law,” he added.

The statement emphasized that moles should be evaluated by a health care professional, as attempts at self-diagnosis and at-home treatment could lead to a delayed cancer diagnosis, and potentially to cancer progression.

Products marketed to consumers for at-home removal of moles, skin tags, and other skin lesions could cause injuries, infections, and scarring, according to a related consumer update first posted by the FDA in June, which was updated after the warning letters were sent out.

Consumers and health care professionals are encouraged to report any adverse events related to mole removal or skin tag removal products to the agency’s MedWatch Adverse Event Reporting program.

The FDA also offers an online guide, BeSafeRx, with advice for consumers about potential risks of using online pharmacies and how to do so safely.

The Food and Drug Administration has sent warning letters to three companies, including Amazon, for selling mole and skin tag removal products that have not been approved by the agency, according to a press release issued on Aug. 9.

In addition to Amazon.com, the other two companies are Ariella Naturals, and Justified Laboratories.

Currently, no over-the-counter products are FDA-approved for the at-home removal of moles and skin tags, and use of unapproved products could be dangerous to consumers, according to the statement. These products may be sold as ointments, gels, sticks, or liquids, and may contain high concentrations of salicylic acid or other harmful ingredients. Introducing unapproved products in to interstate commerce violates the Federal Food, Drug, and Cosmetic Act.

Two products sold on Amazon are the “Deisana Skin Tag Remover, Mole Remover and Repair Gel Set” and “Skincell Mole Skin Tag Corrector Serum,” according to the letter sent to Amazon.

The warning letters alert the three companies that they have 15 days from receipt to address any violations. However, warning letters are not a final FDA action, according to the statement.

“The agency’s rigorous surveillance works to identify threats to public health and stop these products from reaching our communities,” Donald D. Ashley, JD, director of the Office of Compliance in the FDA’s Center for Drug Evaluation and Research, said in the press release. “This includes where online retailers like Amazon are involved in the interstate sale of unapproved drug products. We will continue to work diligently to ensure that online retailers do not sell products that violate federal law,” he added.

The statement emphasized that moles should be evaluated by a health care professional, as attempts at self-diagnosis and at-home treatment could lead to a delayed cancer diagnosis, and potentially to cancer progression.

Products marketed to consumers for at-home removal of moles, skin tags, and other skin lesions could cause injuries, infections, and scarring, according to a related consumer update first posted by the FDA in June, which was updated after the warning letters were sent out.

Consumers and health care professionals are encouraged to report any adverse events related to mole removal or skin tag removal products to the agency’s MedWatch Adverse Event Reporting program.

The FDA also offers an online guide, BeSafeRx, with advice for consumers about potential risks of using online pharmacies and how to do so safely.

Adults with major depressive disorder (MDD) had significantly reduced expression of chemokine receptor 4 on blood T lymphocytes, which predicted disease severity in combination with polygenic risk scores in a study of 54 individuals.

Chemokines and their receptors “influence neuroendocrine signaling, neurotransmission, and interaction between neurons and microglia and have therefore been suggested to be involved in the pathophysiology of MDD and depression-like behavior,” but their potential as a predictor of disease severity has not been explored, Jana Freff, a PhD candidate at the University of Münster (Germany), and colleagues wrote.

Recent research has identified disease-associated single-nucleotide polymorphisms that can be used to calculate a cumulative polygenic risk score (PRS) for an individual, they said. “While PRS only explain a small proportion of the phenotypic variance, they provide a valuable tool to study the influence of common genetic factors in complex disorders, such as MDD.”

In a study published in the Journal of Affective Disorders , the researchers identified 33 adult inpatients with MDD and 21 healthy controls. Blood samples were collected at the time of inpatient admission and after 6 weeks of treatment. MDD severity was measured using the Hamilton Rating Scale for Depression and Inventory of Depressive Symptomatology. Chemokine receptor 4 (CCR4) was measured using mean fluorescence intensity (MFI).

The MDD patients showed significant decreases in CCR4 expression on CD4+ T cells; these patients also had elevated serum levels of the ligands CLL17 and CLL22, compared with healthy controls.

The researchers examined the relationship between CCR4 expression on T cells and MDD severity. Individuals with severe depression had lower levels of CCR4 on CD4+ T cells, compared with nondepressed or mildly depressed individuals.

CCR4 expression also was significantly associated with several somatic and cognitive-affective items on the Beck Depression Inventory II including loss of pleasure (P < .05), agitation (P < .01), and difficulty concentrating (P < .05). “In addition, the total score of BDI-II correlated negatively with the CCR4 MFI (P < .05) emphasizing that greater MDD severity is associated with lower CCR4 expression on CD4+ T cells,” the researchers said.

The researchers also assessed the predictive value of immune parameters and PRS for MDD severity. They did not find significant correlations between PRS and these parameters; however, “including PRS for a cross-disorder phenotype and chronotype could improve the predictive performance of immune parameters on MDD severity,” and genetic data should be considered in future studies.

The study findings were limited mainly by the small size, the researchers noted. Additional studies with larger patient populations are needed, not only to investigate the functional role of CCR4 in MDD, and the association between CCR4 and remission or treatment resistance, but also the impact of genetic factors on MDD status, they said.

However, the results of the current study show an altered expression of CCR4 in MDD, and “Future augmented strategies to treat depression may therefore target CCR4 specifically on CD4+ T cells,” they concluded.

The study was funded in part by grants to several coauthors from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy. Ms. Freff had no financial conflicts to disclose.
 

Adults with major depressive disorder (MDD) had significantly reduced expression of chemokine receptor 4 on blood T lymphocytes, which predicted disease severity in combination with polygenic risk scores in a study of 54 individuals.

Chemokines and their receptors “influence neuroendocrine signaling, neurotransmission, and interaction between neurons and microglia and have therefore been suggested to be involved in the pathophysiology of MDD and depression-like behavior,” but their potential as a predictor of disease severity has not been explored, Jana Freff, a PhD candidate at the University of Münster (Germany), and colleagues wrote.

Recent research has identified disease-associated single-nucleotide polymorphisms that can be used to calculate a cumulative polygenic risk score (PRS) for an individual, they said. “While PRS only explain a small proportion of the phenotypic variance, they provide a valuable tool to study the influence of common genetic factors in complex disorders, such as MDD.”

In a study published in the Journal of Affective Disorders , the researchers identified 33 adult inpatients with MDD and 21 healthy controls. Blood samples were collected at the time of inpatient admission and after 6 weeks of treatment. MDD severity was measured using the Hamilton Rating Scale for Depression and Inventory of Depressive Symptomatology. Chemokine receptor 4 (CCR4) was measured using mean fluorescence intensity (MFI).

The MDD patients showed significant decreases in CCR4 expression on CD4+ T cells; these patients also had elevated serum levels of the ligands CLL17 and CLL22, compared with healthy controls.

The researchers examined the relationship between CCR4 expression on T cells and MDD severity. Individuals with severe depression had lower levels of CCR4 on CD4+ T cells, compared with nondepressed or mildly depressed individuals.

CCR4 expression also was significantly associated with several somatic and cognitive-affective items on the Beck Depression Inventory II including loss of pleasure (P < .05), agitation (P < .01), and difficulty concentrating (P < .05). “In addition, the total score of BDI-II correlated negatively with the CCR4 MFI (P < .05) emphasizing that greater MDD severity is associated with lower CCR4 expression on CD4+ T cells,” the researchers said.

The researchers also assessed the predictive value of immune parameters and PRS for MDD severity. They did not find significant correlations between PRS and these parameters; however, “including PRS for a cross-disorder phenotype and chronotype could improve the predictive performance of immune parameters on MDD severity,” and genetic data should be considered in future studies.

The study findings were limited mainly by the small size, the researchers noted. Additional studies with larger patient populations are needed, not only to investigate the functional role of CCR4 in MDD, and the association between CCR4 and remission or treatment resistance, but also the impact of genetic factors on MDD status, they said.

However, the results of the current study show an altered expression of CCR4 in MDD, and “Future augmented strategies to treat depression may therefore target CCR4 specifically on CD4+ T cells,” they concluded.

The study was funded in part by grants to several coauthors from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy. Ms. Freff had no financial conflicts to disclose.
 

Adults with major depressive disorder (MDD) had significantly reduced expression of chemokine receptor 4 on blood T lymphocytes, which predicted disease severity in combination with polygenic risk scores in a study of 54 individuals.

Chemokines and their receptors “influence neuroendocrine signaling, neurotransmission, and interaction between neurons and microglia and have therefore been suggested to be involved in the pathophysiology of MDD and depression-like behavior,” but their potential as a predictor of disease severity has not been explored, Jana Freff, a PhD candidate at the University of Münster (Germany), and colleagues wrote.

Recent research has identified disease-associated single-nucleotide polymorphisms that can be used to calculate a cumulative polygenic risk score (PRS) for an individual, they said. “While PRS only explain a small proportion of the phenotypic variance, they provide a valuable tool to study the influence of common genetic factors in complex disorders, such as MDD.”

In a study published in the Journal of Affective Disorders , the researchers identified 33 adult inpatients with MDD and 21 healthy controls. Blood samples were collected at the time of inpatient admission and after 6 weeks of treatment. MDD severity was measured using the Hamilton Rating Scale for Depression and Inventory of Depressive Symptomatology. Chemokine receptor 4 (CCR4) was measured using mean fluorescence intensity (MFI).

The MDD patients showed significant decreases in CCR4 expression on CD4+ T cells; these patients also had elevated serum levels of the ligands CLL17 and CLL22, compared with healthy controls.

The researchers examined the relationship between CCR4 expression on T cells and MDD severity. Individuals with severe depression had lower levels of CCR4 on CD4+ T cells, compared with nondepressed or mildly depressed individuals.

CCR4 expression also was significantly associated with several somatic and cognitive-affective items on the Beck Depression Inventory II including loss of pleasure (P < .05), agitation (P < .01), and difficulty concentrating (P < .05). “In addition, the total score of BDI-II correlated negatively with the CCR4 MFI (P < .05) emphasizing that greater MDD severity is associated with lower CCR4 expression on CD4+ T cells,” the researchers said.

The researchers also assessed the predictive value of immune parameters and PRS for MDD severity. They did not find significant correlations between PRS and these parameters; however, “including PRS for a cross-disorder phenotype and chronotype could improve the predictive performance of immune parameters on MDD severity,” and genetic data should be considered in future studies.

The study findings were limited mainly by the small size, the researchers noted. Additional studies with larger patient populations are needed, not only to investigate the functional role of CCR4 in MDD, and the association between CCR4 and remission or treatment resistance, but also the impact of genetic factors on MDD status, they said.

However, the results of the current study show an altered expression of CCR4 in MDD, and “Future augmented strategies to treat depression may therefore target CCR4 specifically on CD4+ T cells,” they concluded.

The study was funded in part by grants to several coauthors from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy. Ms. Freff had no financial conflicts to disclose.
 

Hormone therapy remains a topic for debate, but a constant in the 2 decades since the Women’s Health Initiative has been the demonstrated effectiveness for relief of vasomotor symptoms and reduction of fracture risk in menopausal women, according to the latest hormone therapy position statement of the North American Menopause Society.

“Healthcare professionals caring for menopausal women should understand the basic concepts of relative risk and absolute risk,” wrote Stephanie S. Faubion, MD, director of the Mayo Clinic Center for Women’s Health and medical director of NAMS, and members of the NAMS 2022 Hormone Therapy Position Statement Advisory Panel in Menopause.

The authors noted that the risks of hormone therapy vary considerably based on type, dose, duration, route of administration, timing of the start of therapy, and whether or not a progestogen is included.

The 2022 statement was commissioned to review new literature and identify the strength of recommendations and quality of evidence since the previous statement in 2017.

The current statement represents not so much a practice-changing update, “but rather that the literature has filled out in some areas,” Dr. Faubion said in an interview. “The recommendations overall haven’t changed,” she said. “The position statement reiterates that hormone therapy, which is significantly underutilized, remains a safe and effective treatment for menopause symptoms, which remain undertreated, with the benefits outweighing the risks for most healthy women who are within 10 years of menopause onset and under the age of 60 years,” she emphasized. “Individualizing therapy is key to maximizing benefits and minimizing risks,” she added.

Overall, the authors confirmed that hormone therapy remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM), and has been shown to prevent bone loss and fracture. The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used.

Risks and benefits should be stratified by age and time since the start of menopause, according to the statement.

For women younger than 60 years or within 10 years of the onset of menopause who have no contraindications, the potential benefits outweigh the risks in most cases for use of hormone therapy to manage vasomotor symptoms and to help prevent bone loss and reduce fracture risk.

For women who begin hormone therapy more than 10 or 20 years from the start of menopause, or who are aged 60 years and older, the risk-benefit ratio may be less favorable because of the increased absolute risk of coronary heart disease, stroke, venous thromboembolism, and dementia. However, strategies such as lower doses and transdermal administration may reduce this risk, according to the statement.

The authors continue to recommend that longer durations of hormone therapy be for documented indications, such as VMS relief, and that patients on longer duration of therapy be reassessed periodically as part of a shared decision-making process. Women with persistent VMS or quality of life issues, or those at risk for osteoporosis, may continue hormone therapy beyond age 60 or 65 years after appropriate evaluation and risk-benefit counseling.

Women with ongoing GSM without indications for systemic therapy whose GSM persists after over-the-counter therapies may try low-dose vaginal estrogen or other nonestrogen therapies regardless of age and for an extended duration if needed, according to the statement.
 

Challenges, research gaps, and goals

“Barriers to the use of hormone therapy include lack of access to high quality care,” Dr. Faubion said in an interview. The NAMS website, menopause.org, features an option to search for a NAMS-certified provider by ZIP code, she noted.

“Coverage of hormone therapy is highly variable and depends on the insurance company, but most women have access to one form or another with insurance coverage,” she said. “We need to continue to advocate for adequate coverage of menopause symptom treatments, including hormone therapy, so that women’s symptoms – which can significantly affect quality of life – are adequately managed.

“Additional research is needed on the thrombotic risk (venous thromboembolism, pulmonary embolism, and stroke) of oral versus transdermal therapies (including different formulations, doses, and durations of therapy),” Dr. Faubion told this news organization. “More clinical trial data are needed to confirm or refute the potential beneficial effects of hormone therapy on coronary heart disease and all-cause mortality when initiated in perimenopause or early postmenopause,” she said.

Other areas for research include “the breast effects of different estrogen preparations, including the role for selective estrogen receptor modulator (SERM) and tissue selective estrogen complex therapies, optimal progestogen or SERM regimens to prevent endometrial hyperplasia, the relationship between vasomotor symptoms and the risk for heart disease and cognitive changes, and the risks of premature ovarian insufficiency,” Dr. Faubion emphasized.

Looking ahead, “Studies are needed on the effects of longer use of low-dose vaginal estrogen therapy after breast or endometrial cancer, extended use of hormone therapy in women who are early initiators, improved tools to personalize or individualize benefits and risks of hormone therapy, and the role of aging and genetics,” said Dr. Faubion. Other areas for further research include “the long-term benefits and risks on women’s health of lifestyle modification or complementary or nonhormone therapies, if chosen in addition to or over hormone therapy for vasomotor symptoms, bone health, and cardiovascular disease risk reduction,” she added.

The complete statement was published in Menopause: The Journal of the North American Menopause Society.

The position statement received no outside funding. The authors had no financial conflicts to disclose.

Hormone therapy remains a topic for debate, but a constant in the 2 decades since the Women’s Health Initiative has been the demonstrated effectiveness for relief of vasomotor symptoms and reduction of fracture risk in menopausal women, according to the latest hormone therapy position statement of the North American Menopause Society.

“Healthcare professionals caring for menopausal women should understand the basic concepts of relative risk and absolute risk,” wrote Stephanie S. Faubion, MD, director of the Mayo Clinic Center for Women’s Health and medical director of NAMS, and members of the NAMS 2022 Hormone Therapy Position Statement Advisory Panel in Menopause.

The authors noted that the risks of hormone therapy vary considerably based on type, dose, duration, route of administration, timing of the start of therapy, and whether or not a progestogen is included.

The 2022 statement was commissioned to review new literature and identify the strength of recommendations and quality of evidence since the previous statement in 2017.

The current statement represents not so much a practice-changing update, “but rather that the literature has filled out in some areas,” Dr. Faubion said in an interview. “The recommendations overall haven’t changed,” she said. “The position statement reiterates that hormone therapy, which is significantly underutilized, remains a safe and effective treatment for menopause symptoms, which remain undertreated, with the benefits outweighing the risks for most healthy women who are within 10 years of menopause onset and under the age of 60 years,” she emphasized. “Individualizing therapy is key to maximizing benefits and minimizing risks,” she added.

Overall, the authors confirmed that hormone therapy remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM), and has been shown to prevent bone loss and fracture. The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used.

Risks and benefits should be stratified by age and time since the start of menopause, according to the statement.

For women younger than 60 years or within 10 years of the onset of menopause who have no contraindications, the potential benefits outweigh the risks in most cases for use of hormone therapy to manage vasomotor symptoms and to help prevent bone loss and reduce fracture risk.

For women who begin hormone therapy more than 10 or 20 years from the start of menopause, or who are aged 60 years and older, the risk-benefit ratio may be less favorable because of the increased absolute risk of coronary heart disease, stroke, venous thromboembolism, and dementia. However, strategies such as lower doses and transdermal administration may reduce this risk, according to the statement.

The authors continue to recommend that longer durations of hormone therapy be for documented indications, such as VMS relief, and that patients on longer duration of therapy be reassessed periodically as part of a shared decision-making process. Women with persistent VMS or quality of life issues, or those at risk for osteoporosis, may continue hormone therapy beyond age 60 or 65 years after appropriate evaluation and risk-benefit counseling.

Women with ongoing GSM without indications for systemic therapy whose GSM persists after over-the-counter therapies may try low-dose vaginal estrogen or other nonestrogen therapies regardless of age and for an extended duration if needed, according to the statement.
 

Challenges, research gaps, and goals

“Barriers to the use of hormone therapy include lack of access to high quality care,” Dr. Faubion said in an interview. The NAMS website, menopause.org, features an option to search for a NAMS-certified provider by ZIP code, she noted.

“Coverage of hormone therapy is highly variable and depends on the insurance company, but most women have access to one form or another with insurance coverage,” she said. “We need to continue to advocate for adequate coverage of menopause symptom treatments, including hormone therapy, so that women’s symptoms – which can significantly affect quality of life – are adequately managed.

“Additional research is needed on the thrombotic risk (venous thromboembolism, pulmonary embolism, and stroke) of oral versus transdermal therapies (including different formulations, doses, and durations of therapy),” Dr. Faubion told this news organization. “More clinical trial data are needed to confirm or refute the potential beneficial effects of hormone therapy on coronary heart disease and all-cause mortality when initiated in perimenopause or early postmenopause,” she said.

Other areas for research include “the breast effects of different estrogen preparations, including the role for selective estrogen receptor modulator (SERM) and tissue selective estrogen complex therapies, optimal progestogen or SERM regimens to prevent endometrial hyperplasia, the relationship between vasomotor symptoms and the risk for heart disease and cognitive changes, and the risks of premature ovarian insufficiency,” Dr. Faubion emphasized.

Looking ahead, “Studies are needed on the effects of longer use of low-dose vaginal estrogen therapy after breast or endometrial cancer, extended use of hormone therapy in women who are early initiators, improved tools to personalize or individualize benefits and risks of hormone therapy, and the role of aging and genetics,” said Dr. Faubion. Other areas for further research include “the long-term benefits and risks on women’s health of lifestyle modification or complementary or nonhormone therapies, if chosen in addition to or over hormone therapy for vasomotor symptoms, bone health, and cardiovascular disease risk reduction,” she added.

The complete statement was published in Menopause: The Journal of the North American Menopause Society.

The position statement received no outside funding. The authors had no financial conflicts to disclose.

Hormone therapy remains a topic for debate, but a constant in the 2 decades since the Women’s Health Initiative has been the demonstrated effectiveness for relief of vasomotor symptoms and reduction of fracture risk in menopausal women, according to the latest hormone therapy position statement of the North American Menopause Society.

“Healthcare professionals caring for menopausal women should understand the basic concepts of relative risk and absolute risk,” wrote Stephanie S. Faubion, MD, director of the Mayo Clinic Center for Women’s Health and medical director of NAMS, and members of the NAMS 2022 Hormone Therapy Position Statement Advisory Panel in Menopause.

The authors noted that the risks of hormone therapy vary considerably based on type, dose, duration, route of administration, timing of the start of therapy, and whether or not a progestogen is included.

The 2022 statement was commissioned to review new literature and identify the strength of recommendations and quality of evidence since the previous statement in 2017.

The current statement represents not so much a practice-changing update, “but rather that the literature has filled out in some areas,” Dr. Faubion said in an interview. “The recommendations overall haven’t changed,” she said. “The position statement reiterates that hormone therapy, which is significantly underutilized, remains a safe and effective treatment for menopause symptoms, which remain undertreated, with the benefits outweighing the risks for most healthy women who are within 10 years of menopause onset and under the age of 60 years,” she emphasized. “Individualizing therapy is key to maximizing benefits and minimizing risks,” she added.

Overall, the authors confirmed that hormone therapy remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM), and has been shown to prevent bone loss and fracture. The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used.

Risks and benefits should be stratified by age and time since the start of menopause, according to the statement.

For women younger than 60 years or within 10 years of the onset of menopause who have no contraindications, the potential benefits outweigh the risks in most cases for use of hormone therapy to manage vasomotor symptoms and to help prevent bone loss and reduce fracture risk.

For women who begin hormone therapy more than 10 or 20 years from the start of menopause, or who are aged 60 years and older, the risk-benefit ratio may be less favorable because of the increased absolute risk of coronary heart disease, stroke, venous thromboembolism, and dementia. However, strategies such as lower doses and transdermal administration may reduce this risk, according to the statement.

The authors continue to recommend that longer durations of hormone therapy be for documented indications, such as VMS relief, and that patients on longer duration of therapy be reassessed periodically as part of a shared decision-making process. Women with persistent VMS or quality of life issues, or those at risk for osteoporosis, may continue hormone therapy beyond age 60 or 65 years after appropriate evaluation and risk-benefit counseling.

Women with ongoing GSM without indications for systemic therapy whose GSM persists after over-the-counter therapies may try low-dose vaginal estrogen or other nonestrogen therapies regardless of age and for an extended duration if needed, according to the statement.
 

Challenges, research gaps, and goals

“Barriers to the use of hormone therapy include lack of access to high quality care,” Dr. Faubion said in an interview. The NAMS website, menopause.org, features an option to search for a NAMS-certified provider by ZIP code, she noted.

“Coverage of hormone therapy is highly variable and depends on the insurance company, but most women have access to one form or another with insurance coverage,” she said. “We need to continue to advocate for adequate coverage of menopause symptom treatments, including hormone therapy, so that women’s symptoms – which can significantly affect quality of life – are adequately managed.

“Additional research is needed on the thrombotic risk (venous thromboembolism, pulmonary embolism, and stroke) of oral versus transdermal therapies (including different formulations, doses, and durations of therapy),” Dr. Faubion told this news organization. “More clinical trial data are needed to confirm or refute the potential beneficial effects of hormone therapy on coronary heart disease and all-cause mortality when initiated in perimenopause or early postmenopause,” she said.

Other areas for research include “the breast effects of different estrogen preparations, including the role for selective estrogen receptor modulator (SERM) and tissue selective estrogen complex therapies, optimal progestogen or SERM regimens to prevent endometrial hyperplasia, the relationship between vasomotor symptoms and the risk for heart disease and cognitive changes, and the risks of premature ovarian insufficiency,” Dr. Faubion emphasized.

Looking ahead, “Studies are needed on the effects of longer use of low-dose vaginal estrogen therapy after breast or endometrial cancer, extended use of hormone therapy in women who are early initiators, improved tools to personalize or individualize benefits and risks of hormone therapy, and the role of aging and genetics,” said Dr. Faubion. Other areas for further research include “the long-term benefits and risks on women’s health of lifestyle modification or complementary or nonhormone therapies, if chosen in addition to or over hormone therapy for vasomotor symptoms, bone health, and cardiovascular disease risk reduction,” she added.

The complete statement was published in Menopause: The Journal of the North American Menopause Society.

The position statement received no outside funding. The authors had no financial conflicts to disclose.

Raising phototherapy thresholds and revising risk assessment are among the key changes in the American Academy of Pediatrics’ updated guidelines for managing hyperbilirubinemia in infants 35 weeks’ gestation and older.

“More than 80% of newborn infants will have some degree of jaundice,” Alex R. Kemper, MD, of Nationwide Children’s Hospital, Columbus, Ohio, and coauthors wrote. Careful monitoring is needed manage high bilirubin concentrations and avoid acute bilirubin encephalopathy (ABE) and kernicterus, a disabling neurologic condition.

The current revision, published in Pediatrics, updates and replaces the 2004 AAP clinical practice guidelines for the management and prevention of hyperbilirubinemia in newborns of at least 35 weeks’ gestation.

The guideline committee reviewed evidence published since the previous guidelines were issued in 2004, and addressed similar issues of prevention, risk assessment, monitoring, and treatment.

A notable change from 2004 was the inclusion of a 2009 recommendation update for “universal predischarge bilirubin screening with measures of total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) linked to specific recommendations for follow-up,” the authors wrote.

In terms of prevention, recommendations include a direct antiglobulin test (DAT) for infants whose mother’s antibody screen was positive or unknown. In addition, exclusive breastfeeding is known to be associated with hyperbilirubinemia, but clinicians should support breastfeeding while monitoring for signs of hyperbilirubinemia because of suboptimal feeding, the authors noted. However, the guidelines recommend against oral supplementation with water or dextrose water to prevent hyperbilirubinemia.

For assessment and monitoring, the guidelines advise the use of total serum bilirubin (TSB) as the definitive test for hyperbilirubinemia to guide phototherapy and escalation of care, including exchange transfusion. “The presence of hyperbilirubinemia neurotoxicity risk factors lowers the threshold for treatment with phototherapy and the level at which care should be escalated,” the authors wrote. They also emphasized the need to consider glucose-6-phosphate dehydrogenase deficiency, a genetic condition that decreases protection against oxidative stress and has been identified as a leading cause of hazardous hyperbilirubinemia worldwide.

The guidelines recommend assessing all infants for jaundice at least every 12 hours after delivery until discharge, with TSB or TcB measured as soon as possible for those with suspected jaundice. The complete guidelines include charts for TSB levels to guide escalation of care. “Blood for TSB can be obtained at the time it is collected for newborn screening tests to avoid an additional heel stick,” the authors noted.

The rate of increase in TSB or TcB, if more than one measure is available, may identify infants at higher risk of hyperbilirubinemia, according to the guidelines, and a possible delay of hospital discharge may be needed for infants if appropriate follow-up is not feasible.

In terms of treatment, new evidence that bilirubin neurotoxicity does not occur until concentrations well above those given in the 2004 guidelines justified raising the treatment thresholds, although by a narrow range. “With the increased phototherapy thresholds, appropriately following the current guidelines including bilirubin screening during the birth hospitalization and timely postdischarge follow-up is important,” the authors wrote. The new thresholds, outlined in the complete guidelines, are based on gestational age, hyperbilirubinemia neurotoxicity risk factors, and the age of the infant in hours. However, infants may be treated at lower levels, based on individual circumstances, family preferences, and shared decision-making with clinicians. Home-based phototherapy may be used in some infants, but should not be used if there is a question about the device quality, delivery time, and ability of caregivers to use the device correctly.

“Discontinuing phototherapy is an option when the TSB has decreased by at least 2 mg/dL below the hour-specific threshold at the initiation of phototherapy,” and follow-up should be based on risk of rebound hyperbilirubinemia, according to the guidelines.

“This clinical practice guideline provides indications and approaches for phototherapy and escalation of care and when treatment and monitoring can be safely discontinued,” However, clinicians should understand the rationale for the recommendations and combine them with their clinical judgment, including shared decision-making when appropriate, the authors concluded.
 

Updated evidence supports escalating care

The take-home message for pediatricians is that neonatal hyperbilirubinemia is a very common finding, and complications are rare, but the condition can result in devastating life-long results, Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., said in an interview.

“Previous guidelines published in 2004 and updated in 2009 included evidence-based recommendations, but additional research was still needed to provide guidance for providers to prevent complications of hyperbilirubinemia,” said Dr. Haut, who was not involved in producing the guidelines.

“New data documenting additional risk factors, the importance of ongoing breastfeeding support, and addressing hyperbilirubinemia as an urgent problem” are additions to prevention methods in the latest published guidelines, she said.

“Acute encephalopathy and kernicterus can result from hyperbilirubinemia with severe and devastating neurologic effects, but are preventable by early identification and treatment,” said Dr. Haut. Therefore, “it is not surprising that the AAP utilized continuing and more recent evidence to support new recommendations. Both maternal and neonatal risk factors have long been considered in the development of neonatal hyperbilirubinemia, but recent recommendations incorporate additional risk factor evaluation and urgency in time to appropriate care. Detailed thresholds for phototherapy and exchange transfusion will benefit the families of full-term infants without other risk factors and escalate care for those neonates with risk factors.”

However, potential barriers to following the guidelines persist, Dr. Haut noted.

“Frequent infant follow-up can be challenging for busy primary care offices with outpatient laboratory results often taking much longer to obtain than in a hospital setting,” she said.

Also, “taking a newborn to the emergency department or an inpatient laboratory can be frightening for families with the risk of illness exposure. Frequent monitoring of serum bilirubin levels is disturbing for parents and inconvenient immediately postpartum,” Dr. Haut explained. “Few practices utilize transcutaneous bilirubin monitoring which may be one method of added screening.”

In addition, “despite the importance of breastfeeding, ongoing support is not readily available for mothers after hospital discharge. A lactation specialist in the office setting can take the burden off providers and add opportunity for family education.”

As for additional research, “continued evaluation of the comparison of transcutaneous bilirubin monitoring and serum levels along with the use of transcutaneous monitoring in facilities outside the hospital setting may be warranted,” Dr. Haut said. “Data collection on incidence and accompanying risk factors of neonates who develop acute hyperbilirubinemia encephalopathy and kernicterus is a long-term study opportunity.”

The guidelines received no external funding. Lead author Dr. Kemper had no financial conflicts to disclose. Dr. Haut had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

Raising phototherapy thresholds and revising risk assessment are among the key changes in the American Academy of Pediatrics’ updated guidelines for managing hyperbilirubinemia in infants 35 weeks’ gestation and older.

“More than 80% of newborn infants will have some degree of jaundice,” Alex R. Kemper, MD, of Nationwide Children’s Hospital, Columbus, Ohio, and coauthors wrote. Careful monitoring is needed manage high bilirubin concentrations and avoid acute bilirubin encephalopathy (ABE) and kernicterus, a disabling neurologic condition.

The current revision, published in Pediatrics, updates and replaces the 2004 AAP clinical practice guidelines for the management and prevention of hyperbilirubinemia in newborns of at least 35 weeks’ gestation.

The guideline committee reviewed evidence published since the previous guidelines were issued in 2004, and addressed similar issues of prevention, risk assessment, monitoring, and treatment.

A notable change from 2004 was the inclusion of a 2009 recommendation update for “universal predischarge bilirubin screening with measures of total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) linked to specific recommendations for follow-up,” the authors wrote.

In terms of prevention, recommendations include a direct antiglobulin test (DAT) for infants whose mother’s antibody screen was positive or unknown. In addition, exclusive breastfeeding is known to be associated with hyperbilirubinemia, but clinicians should support breastfeeding while monitoring for signs of hyperbilirubinemia because of suboptimal feeding, the authors noted. However, the guidelines recommend against oral supplementation with water or dextrose water to prevent hyperbilirubinemia.

For assessment and monitoring, the guidelines advise the use of total serum bilirubin (TSB) as the definitive test for hyperbilirubinemia to guide phototherapy and escalation of care, including exchange transfusion. “The presence of hyperbilirubinemia neurotoxicity risk factors lowers the threshold for treatment with phototherapy and the level at which care should be escalated,” the authors wrote. They also emphasized the need to consider glucose-6-phosphate dehydrogenase deficiency, a genetic condition that decreases protection against oxidative stress and has been identified as a leading cause of hazardous hyperbilirubinemia worldwide.

The guidelines recommend assessing all infants for jaundice at least every 12 hours after delivery until discharge, with TSB or TcB measured as soon as possible for those with suspected jaundice. The complete guidelines include charts for TSB levels to guide escalation of care. “Blood for TSB can be obtained at the time it is collected for newborn screening tests to avoid an additional heel stick,” the authors noted.

The rate of increase in TSB or TcB, if more than one measure is available, may identify infants at higher risk of hyperbilirubinemia, according to the guidelines, and a possible delay of hospital discharge may be needed for infants if appropriate follow-up is not feasible.

In terms of treatment, new evidence that bilirubin neurotoxicity does not occur until concentrations well above those given in the 2004 guidelines justified raising the treatment thresholds, although by a narrow range. “With the increased phototherapy thresholds, appropriately following the current guidelines including bilirubin screening during the birth hospitalization and timely postdischarge follow-up is important,” the authors wrote. The new thresholds, outlined in the complete guidelines, are based on gestational age, hyperbilirubinemia neurotoxicity risk factors, and the age of the infant in hours. However, infants may be treated at lower levels, based on individual circumstances, family preferences, and shared decision-making with clinicians. Home-based phototherapy may be used in some infants, but should not be used if there is a question about the device quality, delivery time, and ability of caregivers to use the device correctly.

“Discontinuing phototherapy is an option when the TSB has decreased by at least 2 mg/dL below the hour-specific threshold at the initiation of phototherapy,” and follow-up should be based on risk of rebound hyperbilirubinemia, according to the guidelines.

“This clinical practice guideline provides indications and approaches for phototherapy and escalation of care and when treatment and monitoring can be safely discontinued,” However, clinicians should understand the rationale for the recommendations and combine them with their clinical judgment, including shared decision-making when appropriate, the authors concluded.
 

Updated evidence supports escalating care

The take-home message for pediatricians is that neonatal hyperbilirubinemia is a very common finding, and complications are rare, but the condition can result in devastating life-long results, Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., said in an interview.

“Previous guidelines published in 2004 and updated in 2009 included evidence-based recommendations, but additional research was still needed to provide guidance for providers to prevent complications of hyperbilirubinemia,” said Dr. Haut, who was not involved in producing the guidelines.

“New data documenting additional risk factors, the importance of ongoing breastfeeding support, and addressing hyperbilirubinemia as an urgent problem” are additions to prevention methods in the latest published guidelines, she said.

“Acute encephalopathy and kernicterus can result from hyperbilirubinemia with severe and devastating neurologic effects, but are preventable by early identification and treatment,” said Dr. Haut. Therefore, “it is not surprising that the AAP utilized continuing and more recent evidence to support new recommendations. Both maternal and neonatal risk factors have long been considered in the development of neonatal hyperbilirubinemia, but recent recommendations incorporate additional risk factor evaluation and urgency in time to appropriate care. Detailed thresholds for phototherapy and exchange transfusion will benefit the families of full-term infants without other risk factors and escalate care for those neonates with risk factors.”

However, potential barriers to following the guidelines persist, Dr. Haut noted.

“Frequent infant follow-up can be challenging for busy primary care offices with outpatient laboratory results often taking much longer to obtain than in a hospital setting,” she said.

Also, “taking a newborn to the emergency department or an inpatient laboratory can be frightening for families with the risk of illness exposure. Frequent monitoring of serum bilirubin levels is disturbing for parents and inconvenient immediately postpartum,” Dr. Haut explained. “Few practices utilize transcutaneous bilirubin monitoring which may be one method of added screening.”

In addition, “despite the importance of breastfeeding, ongoing support is not readily available for mothers after hospital discharge. A lactation specialist in the office setting can take the burden off providers and add opportunity for family education.”

As for additional research, “continued evaluation of the comparison of transcutaneous bilirubin monitoring and serum levels along with the use of transcutaneous monitoring in facilities outside the hospital setting may be warranted,” Dr. Haut said. “Data collection on incidence and accompanying risk factors of neonates who develop acute hyperbilirubinemia encephalopathy and kernicterus is a long-term study opportunity.”

The guidelines received no external funding. Lead author Dr. Kemper had no financial conflicts to disclose. Dr. Haut had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

Raising phototherapy thresholds and revising risk assessment are among the key changes in the American Academy of Pediatrics’ updated guidelines for managing hyperbilirubinemia in infants 35 weeks’ gestation and older.

“More than 80% of newborn infants will have some degree of jaundice,” Alex R. Kemper, MD, of Nationwide Children’s Hospital, Columbus, Ohio, and coauthors wrote. Careful monitoring is needed manage high bilirubin concentrations and avoid acute bilirubin encephalopathy (ABE) and kernicterus, a disabling neurologic condition.

The current revision, published in Pediatrics, updates and replaces the 2004 AAP clinical practice guidelines for the management and prevention of hyperbilirubinemia in newborns of at least 35 weeks’ gestation.

The guideline committee reviewed evidence published since the previous guidelines were issued in 2004, and addressed similar issues of prevention, risk assessment, monitoring, and treatment.

A notable change from 2004 was the inclusion of a 2009 recommendation update for “universal predischarge bilirubin screening with measures of total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) linked to specific recommendations for follow-up,” the authors wrote.

In terms of prevention, recommendations include a direct antiglobulin test (DAT) for infants whose mother’s antibody screen was positive or unknown. In addition, exclusive breastfeeding is known to be associated with hyperbilirubinemia, but clinicians should support breastfeeding while monitoring for signs of hyperbilirubinemia because of suboptimal feeding, the authors noted. However, the guidelines recommend against oral supplementation with water or dextrose water to prevent hyperbilirubinemia.

For assessment and monitoring, the guidelines advise the use of total serum bilirubin (TSB) as the definitive test for hyperbilirubinemia to guide phototherapy and escalation of care, including exchange transfusion. “The presence of hyperbilirubinemia neurotoxicity risk factors lowers the threshold for treatment with phototherapy and the level at which care should be escalated,” the authors wrote. They also emphasized the need to consider glucose-6-phosphate dehydrogenase deficiency, a genetic condition that decreases protection against oxidative stress and has been identified as a leading cause of hazardous hyperbilirubinemia worldwide.

The guidelines recommend assessing all infants for jaundice at least every 12 hours after delivery until discharge, with TSB or TcB measured as soon as possible for those with suspected jaundice. The complete guidelines include charts for TSB levels to guide escalation of care. “Blood for TSB can be obtained at the time it is collected for newborn screening tests to avoid an additional heel stick,” the authors noted.

The rate of increase in TSB or TcB, if more than one measure is available, may identify infants at higher risk of hyperbilirubinemia, according to the guidelines, and a possible delay of hospital discharge may be needed for infants if appropriate follow-up is not feasible.

In terms of treatment, new evidence that bilirubin neurotoxicity does not occur until concentrations well above those given in the 2004 guidelines justified raising the treatment thresholds, although by a narrow range. “With the increased phototherapy thresholds, appropriately following the current guidelines including bilirubin screening during the birth hospitalization and timely postdischarge follow-up is important,” the authors wrote. The new thresholds, outlined in the complete guidelines, are based on gestational age, hyperbilirubinemia neurotoxicity risk factors, and the age of the infant in hours. However, infants may be treated at lower levels, based on individual circumstances, family preferences, and shared decision-making with clinicians. Home-based phototherapy may be used in some infants, but should not be used if there is a question about the device quality, delivery time, and ability of caregivers to use the device correctly.

“Discontinuing phototherapy is an option when the TSB has decreased by at least 2 mg/dL below the hour-specific threshold at the initiation of phototherapy,” and follow-up should be based on risk of rebound hyperbilirubinemia, according to the guidelines.

“This clinical practice guideline provides indications and approaches for phototherapy and escalation of care and when treatment and monitoring can be safely discontinued,” However, clinicians should understand the rationale for the recommendations and combine them with their clinical judgment, including shared decision-making when appropriate, the authors concluded.
 

Updated evidence supports escalating care

The take-home message for pediatricians is that neonatal hyperbilirubinemia is a very common finding, and complications are rare, but the condition can result in devastating life-long results, Cathy Haut, DNP, CPNP-AC, CPNP-PC, a pediatric nurse practitioner in Rehoboth Beach, Del., said in an interview.

“Previous guidelines published in 2004 and updated in 2009 included evidence-based recommendations, but additional research was still needed to provide guidance for providers to prevent complications of hyperbilirubinemia,” said Dr. Haut, who was not involved in producing the guidelines.

“New data documenting additional risk factors, the importance of ongoing breastfeeding support, and addressing hyperbilirubinemia as an urgent problem” are additions to prevention methods in the latest published guidelines, she said.

“Acute encephalopathy and kernicterus can result from hyperbilirubinemia with severe and devastating neurologic effects, but are preventable by early identification and treatment,” said Dr. Haut. Therefore, “it is not surprising that the AAP utilized continuing and more recent evidence to support new recommendations. Both maternal and neonatal risk factors have long been considered in the development of neonatal hyperbilirubinemia, but recent recommendations incorporate additional risk factor evaluation and urgency in time to appropriate care. Detailed thresholds for phototherapy and exchange transfusion will benefit the families of full-term infants without other risk factors and escalate care for those neonates with risk factors.”

However, potential barriers to following the guidelines persist, Dr. Haut noted.

“Frequent infant follow-up can be challenging for busy primary care offices with outpatient laboratory results often taking much longer to obtain than in a hospital setting,” she said.

Also, “taking a newborn to the emergency department or an inpatient laboratory can be frightening for families with the risk of illness exposure. Frequent monitoring of serum bilirubin levels is disturbing for parents and inconvenient immediately postpartum,” Dr. Haut explained. “Few practices utilize transcutaneous bilirubin monitoring which may be one method of added screening.”

In addition, “despite the importance of breastfeeding, ongoing support is not readily available for mothers after hospital discharge. A lactation specialist in the office setting can take the burden off providers and add opportunity for family education.”

As for additional research, “continued evaluation of the comparison of transcutaneous bilirubin monitoring and serum levels along with the use of transcutaneous monitoring in facilities outside the hospital setting may be warranted,” Dr. Haut said. “Data collection on incidence and accompanying risk factors of neonates who develop acute hyperbilirubinemia encephalopathy and kernicterus is a long-term study opportunity.”

The guidelines received no external funding. Lead author Dr. Kemper had no financial conflicts to disclose. Dr. Haut had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

Infants with bronchopulmonary dysplasia (BPD) who were born to Black mothers were significantly more likely to die or to have a longer hospital stay than infants of other ethnicities, based on data from more than 800 infants.

The overall incidence of BPD is rising, in part because of improved survival for extremely preterm infants, wrote Tamorah R. Lewis, MD, of the University of Missouri, Kansas City, and colleagues.

Previous studies suggest that racial disparities may affect outcomes for preterm infants with a range of neonatal morbidities during neonatal ICU (NICU) hospitalization, including respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis. However, the association of racial disparities with outcomes for preterm infants with BPD remains unclear, they said.

In a study published in JAMA Pediatrics, the researchers, on behalf of the Bronchopulmonary Dysplasia Collaborative, reviewed data from 834 preterm infants enrolled in the BPD Collaborative registry from Jan. 1, 2015, to July 19, 2021, at eight centers in the United States.

The study infants were born at less than 32 weeks’ gestation and were diagnosed with severe BPD according to the 2001 National Institutes of Health Consensus Criteria. The study population included 276 Black infants and 558 white infants. The median gestational age was 24 weeks, and 41% of the infants were female.

The primary outcomes were infant death and length of hospital stay.

Although death was infrequent (4% overall), Black maternal race was significantly associated with an increased risk of death from BPD (adjusted odds ratio, 2.1). Black maternal race also was significantly associated with a longer hospital stay for the infants, with an adjusted between-group difference of 10 days.

Infants of Black mothers also were more likely than those with White mothers to receive invasive respiratory support at the time of delivery. Black infants were more likely than White infants to have lower gestational age, lower birth weight and length, and smaller head circumference.

However, the proportions of cesarean deliveries, gender distribution, and infants small for gestational age were similar between Black and White infant groups. Medication exposure at 36 weeks postmenstrual age (PMA) also was similar for Black and White infants, and 50% of patients overall were treated with nasal continuous positive airway pressure at 36 weeks’ PMA. Awareness of the increased risk of death and longer hospital stay for Black infants is critical, “given the highly variable outcomes for patients with BPD and the uncertainty regarding demographic factors that contribute to late respiratory morbidity in severe BPD,” the researchers wrote.

The study findings were limited by several factors including variations among study centers in the identification and recording of maternal race, lack of data on paternal race, and the focus specifically on Black maternal race and not other ethnicities. Given the documented health disparities for Black individuals in the United States, “we restricted our cohort to only those patients born to Black or White mothers to estimate the association of Black maternal race and adverse in-hospital outcomes in infants with severe BPD,” the researchers wrote

Other limitations include the lack of data surrounding infant death and inability to adjust for all potential modifiers of BPD pathogenesis and progression, such as BPD comorbidities.

Prospective studies are needed to identify the sociodemographic mechanisms that may contribute to health outcome disparities for Black infants with severe BPD, the researchers emphasized.

In the meantime, the results highlight the need for more attention to variations in care for infants with BPD of different races, and approaches to family-centered care should consider “the precise needs of high-risk, structurally disadvantaged families while informing the design of prospective trials that improve outcomes for high-risk subgroups of children with severe BPD,” they concluded.
 

Data raise questions about the origin of disparities

The current study findings contribute to the knowledge and awareness of disparities in the high-risk NICU population, Nicolas A. Bamat, MD, and colleagues wrote in an accompanying editorial. “Further, their findings oppose the central tendency in the literature: that infants of Black mothers have less severe lung disease of prematurity during the birth hospitalization.”

The editorial authors noted that the study’s inclusion of racial characteristics as confounding variables to assess the effect of race on health “can imply questionable assumptions about where in a causal pathway racism begins to exert an effect,” whether after a diagnosis of BPD, during pregnancy in response to inequitable obstetric care, or “centuries ago, propagating forward through the shared experience of communities oppressed by the legacy of racism and its ongoing contemporary manifestations.”

The editorial authors added that, “in lung disease of prematurity, few variables are reliable antecedents to race as an exposure. Complex adjustment is necessary to reduce bias in targeted research questions.” However, the current study findings highlight the need to move toward more equitable neonatal care, and to prioritize interventions to reduce racial health disparities at the level of the NICU as well as at the hospital and government policy levels.
 

Consider range of contributing factors and confounders

The current study is important because “it is imperative to measure racial outcomes in health care in order to highlight and address disparities and biases,” Tim Joos, MD, said in an interview. However, “it can be difficult to determine how much race is a factor in itself versus a proxy for other important characteristics, such as socioeconomic status and level of education, that can confound the results.”

In the current study, the twofold-increased death rate in the premature infants of Black mothers is concerning and deserves further attention, Dr. Joos said. “The 10-day longer length of stay for infants of Black mothers seems quite shocking at first glance, but because of the long hospital stays for these extremely premature infants in general, it is about 7% longer than the infants born to White mothers.”

The take-home message is that this difference is still significant, and can reflect many factors including disease severity and complications, need for feeding assistance, teaching, and setting up home supports, said Dr. Joos.

As for additional research, “it would be useful for hospitals to break down why the differences exist, although I worry a provider or institution will feel they need to discharge Black families sooner to avoid being biased. Family preference and comfort level should be given high priority,” he emphasized.

The study received no outside funding, but lead author Dr. Lewis was supported by the National Institute on Child Health and Development and the Robert Wood Johnson Foundation. Several coauthors were supported by other grants from the National Institutes of Health. Dr. Barnat and one coauthor were supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Joos had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.


 

Infants with bronchopulmonary dysplasia (BPD) who were born to Black mothers were significantly more likely to die or to have a longer hospital stay than infants of other ethnicities, based on data from more than 800 infants.

The overall incidence of BPD is rising, in part because of improved survival for extremely preterm infants, wrote Tamorah R. Lewis, MD, of the University of Missouri, Kansas City, and colleagues.

Previous studies suggest that racial disparities may affect outcomes for preterm infants with a range of neonatal morbidities during neonatal ICU (NICU) hospitalization, including respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis. However, the association of racial disparities with outcomes for preterm infants with BPD remains unclear, they said.

In a study published in JAMA Pediatrics, the researchers, on behalf of the Bronchopulmonary Dysplasia Collaborative, reviewed data from 834 preterm infants enrolled in the BPD Collaborative registry from Jan. 1, 2015, to July 19, 2021, at eight centers in the United States.

The study infants were born at less than 32 weeks’ gestation and were diagnosed with severe BPD according to the 2001 National Institutes of Health Consensus Criteria. The study population included 276 Black infants and 558 white infants. The median gestational age was 24 weeks, and 41% of the infants were female.

The primary outcomes were infant death and length of hospital stay.

Although death was infrequent (4% overall), Black maternal race was significantly associated with an increased risk of death from BPD (adjusted odds ratio, 2.1). Black maternal race also was significantly associated with a longer hospital stay for the infants, with an adjusted between-group difference of 10 days.

Infants of Black mothers also were more likely than those with White mothers to receive invasive respiratory support at the time of delivery. Black infants were more likely than White infants to have lower gestational age, lower birth weight and length, and smaller head circumference.

However, the proportions of cesarean deliveries, gender distribution, and infants small for gestational age were similar between Black and White infant groups. Medication exposure at 36 weeks postmenstrual age (PMA) also was similar for Black and White infants, and 50% of patients overall were treated with nasal continuous positive airway pressure at 36 weeks’ PMA. Awareness of the increased risk of death and longer hospital stay for Black infants is critical, “given the highly variable outcomes for patients with BPD and the uncertainty regarding demographic factors that contribute to late respiratory morbidity in severe BPD,” the researchers wrote.

The study findings were limited by several factors including variations among study centers in the identification and recording of maternal race, lack of data on paternal race, and the focus specifically on Black maternal race and not other ethnicities. Given the documented health disparities for Black individuals in the United States, “we restricted our cohort to only those patients born to Black or White mothers to estimate the association of Black maternal race and adverse in-hospital outcomes in infants with severe BPD,” the researchers wrote

Other limitations include the lack of data surrounding infant death and inability to adjust for all potential modifiers of BPD pathogenesis and progression, such as BPD comorbidities.

Prospective studies are needed to identify the sociodemographic mechanisms that may contribute to health outcome disparities for Black infants with severe BPD, the researchers emphasized.

In the meantime, the results highlight the need for more attention to variations in care for infants with BPD of different races, and approaches to family-centered care should consider “the precise needs of high-risk, structurally disadvantaged families while informing the design of prospective trials that improve outcomes for high-risk subgroups of children with severe BPD,” they concluded.
 

Data raise questions about the origin of disparities

The current study findings contribute to the knowledge and awareness of disparities in the high-risk NICU population, Nicolas A. Bamat, MD, and colleagues wrote in an accompanying editorial. “Further, their findings oppose the central tendency in the literature: that infants of Black mothers have less severe lung disease of prematurity during the birth hospitalization.”

The editorial authors noted that the study’s inclusion of racial characteristics as confounding variables to assess the effect of race on health “can imply questionable assumptions about where in a causal pathway racism begins to exert an effect,” whether after a diagnosis of BPD, during pregnancy in response to inequitable obstetric care, or “centuries ago, propagating forward through the shared experience of communities oppressed by the legacy of racism and its ongoing contemporary manifestations.”

The editorial authors added that, “in lung disease of prematurity, few variables are reliable antecedents to race as an exposure. Complex adjustment is necessary to reduce bias in targeted research questions.” However, the current study findings highlight the need to move toward more equitable neonatal care, and to prioritize interventions to reduce racial health disparities at the level of the NICU as well as at the hospital and government policy levels.
 

Consider range of contributing factors and confounders

The current study is important because “it is imperative to measure racial outcomes in health care in order to highlight and address disparities and biases,” Tim Joos, MD, said in an interview. However, “it can be difficult to determine how much race is a factor in itself versus a proxy for other important characteristics, such as socioeconomic status and level of education, that can confound the results.”

In the current study, the twofold-increased death rate in the premature infants of Black mothers is concerning and deserves further attention, Dr. Joos said. “The 10-day longer length of stay for infants of Black mothers seems quite shocking at first glance, but because of the long hospital stays for these extremely premature infants in general, it is about 7% longer than the infants born to White mothers.”

The take-home message is that this difference is still significant, and can reflect many factors including disease severity and complications, need for feeding assistance, teaching, and setting up home supports, said Dr. Joos.

As for additional research, “it would be useful for hospitals to break down why the differences exist, although I worry a provider or institution will feel they need to discharge Black families sooner to avoid being biased. Family preference and comfort level should be given high priority,” he emphasized.

The study received no outside funding, but lead author Dr. Lewis was supported by the National Institute on Child Health and Development and the Robert Wood Johnson Foundation. Several coauthors were supported by other grants from the National Institutes of Health. Dr. Barnat and one coauthor were supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Joos had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.


 

Infants with bronchopulmonary dysplasia (BPD) who were born to Black mothers were significantly more likely to die or to have a longer hospital stay than infants of other ethnicities, based on data from more than 800 infants.

The overall incidence of BPD is rising, in part because of improved survival for extremely preterm infants, wrote Tamorah R. Lewis, MD, of the University of Missouri, Kansas City, and colleagues.

Previous studies suggest that racial disparities may affect outcomes for preterm infants with a range of neonatal morbidities during neonatal ICU (NICU) hospitalization, including respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis. However, the association of racial disparities with outcomes for preterm infants with BPD remains unclear, they said.

In a study published in JAMA Pediatrics, the researchers, on behalf of the Bronchopulmonary Dysplasia Collaborative, reviewed data from 834 preterm infants enrolled in the BPD Collaborative registry from Jan. 1, 2015, to July 19, 2021, at eight centers in the United States.

The study infants were born at less than 32 weeks’ gestation and were diagnosed with severe BPD according to the 2001 National Institutes of Health Consensus Criteria. The study population included 276 Black infants and 558 white infants. The median gestational age was 24 weeks, and 41% of the infants were female.

The primary outcomes were infant death and length of hospital stay.

Although death was infrequent (4% overall), Black maternal race was significantly associated with an increased risk of death from BPD (adjusted odds ratio, 2.1). Black maternal race also was significantly associated with a longer hospital stay for the infants, with an adjusted between-group difference of 10 days.

Infants of Black mothers also were more likely than those with White mothers to receive invasive respiratory support at the time of delivery. Black infants were more likely than White infants to have lower gestational age, lower birth weight and length, and smaller head circumference.

However, the proportions of cesarean deliveries, gender distribution, and infants small for gestational age were similar between Black and White infant groups. Medication exposure at 36 weeks postmenstrual age (PMA) also was similar for Black and White infants, and 50% of patients overall were treated with nasal continuous positive airway pressure at 36 weeks’ PMA. Awareness of the increased risk of death and longer hospital stay for Black infants is critical, “given the highly variable outcomes for patients with BPD and the uncertainty regarding demographic factors that contribute to late respiratory morbidity in severe BPD,” the researchers wrote.

The study findings were limited by several factors including variations among study centers in the identification and recording of maternal race, lack of data on paternal race, and the focus specifically on Black maternal race and not other ethnicities. Given the documented health disparities for Black individuals in the United States, “we restricted our cohort to only those patients born to Black or White mothers to estimate the association of Black maternal race and adverse in-hospital outcomes in infants with severe BPD,” the researchers wrote

Other limitations include the lack of data surrounding infant death and inability to adjust for all potential modifiers of BPD pathogenesis and progression, such as BPD comorbidities.

Prospective studies are needed to identify the sociodemographic mechanisms that may contribute to health outcome disparities for Black infants with severe BPD, the researchers emphasized.

In the meantime, the results highlight the need for more attention to variations in care for infants with BPD of different races, and approaches to family-centered care should consider “the precise needs of high-risk, structurally disadvantaged families while informing the design of prospective trials that improve outcomes for high-risk subgroups of children with severe BPD,” they concluded.
 

Data raise questions about the origin of disparities

The current study findings contribute to the knowledge and awareness of disparities in the high-risk NICU population, Nicolas A. Bamat, MD, and colleagues wrote in an accompanying editorial. “Further, their findings oppose the central tendency in the literature: that infants of Black mothers have less severe lung disease of prematurity during the birth hospitalization.”

The editorial authors noted that the study’s inclusion of racial characteristics as confounding variables to assess the effect of race on health “can imply questionable assumptions about where in a causal pathway racism begins to exert an effect,” whether after a diagnosis of BPD, during pregnancy in response to inequitable obstetric care, or “centuries ago, propagating forward through the shared experience of communities oppressed by the legacy of racism and its ongoing contemporary manifestations.”

The editorial authors added that, “in lung disease of prematurity, few variables are reliable antecedents to race as an exposure. Complex adjustment is necessary to reduce bias in targeted research questions.” However, the current study findings highlight the need to move toward more equitable neonatal care, and to prioritize interventions to reduce racial health disparities at the level of the NICU as well as at the hospital and government policy levels.
 

Consider range of contributing factors and confounders

The current study is important because “it is imperative to measure racial outcomes in health care in order to highlight and address disparities and biases,” Tim Joos, MD, said in an interview. However, “it can be difficult to determine how much race is a factor in itself versus a proxy for other important characteristics, such as socioeconomic status and level of education, that can confound the results.”

In the current study, the twofold-increased death rate in the premature infants of Black mothers is concerning and deserves further attention, Dr. Joos said. “The 10-day longer length of stay for infants of Black mothers seems quite shocking at first glance, but because of the long hospital stays for these extremely premature infants in general, it is about 7% longer than the infants born to White mothers.”

The take-home message is that this difference is still significant, and can reflect many factors including disease severity and complications, need for feeding assistance, teaching, and setting up home supports, said Dr. Joos.

As for additional research, “it would be useful for hospitals to break down why the differences exist, although I worry a provider or institution will feel they need to discharge Black families sooner to avoid being biased. Family preference and comfort level should be given high priority,” he emphasized.

The study received no outside funding, but lead author Dr. Lewis was supported by the National Institute on Child Health and Development and the Robert Wood Johnson Foundation. Several coauthors were supported by other grants from the National Institutes of Health. Dr. Barnat and one coauthor were supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Joos had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.


 

Psittacosis, a rare disease, has been underdiagnosed or misdiagnosed during the COVID-19 pandemic, likely because the symptoms of the disease are similar to COVID-19 symptoms, researchers suggest on the basis of data from 32 individuals.

Diagnosis of and screening for COVID-19 continues to increase; however, cases of atypical pneumonia caused by uncommon pathogens, which presents with similar symptoms, may be missed, wrote Qiaoqiao Yin, MS, of Zhejiang Provincial People’s Hospital, China, and colleagues.

“The clinical manifestations of human psittacosis can present as rapidly progressing severe pneumonia, acute respiratory distress syndrome, sepsis, and multiple organ failure,” but human cases have not been well studied, they say.

In a study  published in the International Journal of Infectious Diseases, the researchers reviewed data from 32 adults diagnosed with Chlamydia psittaci pneumonia during the COVID-19 pandemic between April 2020 and June 2021 in China. The median age of the patients was 63 years, 20 were men, and 20 had underlying diseases.

A total of 17 patients presented with fever, cough, and expectoration of yellow-white sputum. At the time of hospital admission, three patients had myalgia, two had headache, and two had hypertension. The patients were originally suspected of having COVID-19.

“All patients showed atypical pneumonia, including inflammatory infiltration, pleural effusion, multiple inflammatory exudative lesions with interstitial edema, lung abscesses, and white lung,” all of which could be observed in COVID-19 patients as well, the researchers wrote.

Reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) testing were used to rule out COVID-19. The researchers then used metagenomic next-generation sequencing (mNGS) to identify the disease-causing pathogens. They collected 18 bronchoalveolar lavage fluid (BALF) samples, 9 peripheral blood samples, and 5 sputum samples. The mNGS identified C. psittaci as the suspected pathogen within 48 hours. Suspected C. psittaci infections were confirmed by endpoint PCR for the BALF and sputum samples and six of nine blood samples, “indicating a lower sensitivity of PCR compared to mNGS for blood samples,” the researchers say. No other potential pathogens were identified.

Psittacosis is common in birds but is rare in humans. C. psittaci is responsible for 1%-8% of cases involving community-acquired pneumonia in China, the researchers note. Although poultry is a source of infection, 25 of the patients in the study did not report a history of exposure to poultry or pigeons at the time of their initial hospital admission. Many patients may be unaware of exposures to poultry, which further complicates the C. psittaci diagnosis, they note.

All patients were treated with doxycycline-based regimens and showed improvement.

The findings were limited by several factors, including the lack of a definitive diagnostic tool for C. psittaci and the lack of convalescent serum samples to confirm cases, the researchers note. In addition, molecular detections for PCR are unavailable in most hospitals in China, they say. The results represent the largest known collection of suspected C. psittaci pneumonia cases and highlight the need for clinician vigilance and awareness of this rare condition, especially in light of the potential for misdiagnosis during the ongoing COVID-19 pandemic, they conclude.

The study received no outside funding. The researchers have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Psittacosis, a rare disease, has been underdiagnosed or misdiagnosed during the COVID-19 pandemic, likely because the symptoms of the disease are similar to COVID-19 symptoms, researchers suggest on the basis of data from 32 individuals.

Diagnosis of and screening for COVID-19 continues to increase; however, cases of atypical pneumonia caused by uncommon pathogens, which presents with similar symptoms, may be missed, wrote Qiaoqiao Yin, MS, of Zhejiang Provincial People’s Hospital, China, and colleagues.

“The clinical manifestations of human psittacosis can present as rapidly progressing severe pneumonia, acute respiratory distress syndrome, sepsis, and multiple organ failure,” but human cases have not been well studied, they say.

In a study  published in the International Journal of Infectious Diseases, the researchers reviewed data from 32 adults diagnosed with Chlamydia psittaci pneumonia during the COVID-19 pandemic between April 2020 and June 2021 in China. The median age of the patients was 63 years, 20 were men, and 20 had underlying diseases.

A total of 17 patients presented with fever, cough, and expectoration of yellow-white sputum. At the time of hospital admission, three patients had myalgia, two had headache, and two had hypertension. The patients were originally suspected of having COVID-19.

“All patients showed atypical pneumonia, including inflammatory infiltration, pleural effusion, multiple inflammatory exudative lesions with interstitial edema, lung abscesses, and white lung,” all of which could be observed in COVID-19 patients as well, the researchers wrote.

Reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) testing were used to rule out COVID-19. The researchers then used metagenomic next-generation sequencing (mNGS) to identify the disease-causing pathogens. They collected 18 bronchoalveolar lavage fluid (BALF) samples, 9 peripheral blood samples, and 5 sputum samples. The mNGS identified C. psittaci as the suspected pathogen within 48 hours. Suspected C. psittaci infections were confirmed by endpoint PCR for the BALF and sputum samples and six of nine blood samples, “indicating a lower sensitivity of PCR compared to mNGS for blood samples,” the researchers say. No other potential pathogens were identified.

Psittacosis is common in birds but is rare in humans. C. psittaci is responsible for 1%-8% of cases involving community-acquired pneumonia in China, the researchers note. Although poultry is a source of infection, 25 of the patients in the study did not report a history of exposure to poultry or pigeons at the time of their initial hospital admission. Many patients may be unaware of exposures to poultry, which further complicates the C. psittaci diagnosis, they note.

All patients were treated with doxycycline-based regimens and showed improvement.

The findings were limited by several factors, including the lack of a definitive diagnostic tool for C. psittaci and the lack of convalescent serum samples to confirm cases, the researchers note. In addition, molecular detections for PCR are unavailable in most hospitals in China, they say. The results represent the largest known collection of suspected C. psittaci pneumonia cases and highlight the need for clinician vigilance and awareness of this rare condition, especially in light of the potential for misdiagnosis during the ongoing COVID-19 pandemic, they conclude.

The study received no outside funding. The researchers have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Psittacosis, a rare disease, has been underdiagnosed or misdiagnosed during the COVID-19 pandemic, likely because the symptoms of the disease are similar to COVID-19 symptoms, researchers suggest on the basis of data from 32 individuals.

Diagnosis of and screening for COVID-19 continues to increase; however, cases of atypical pneumonia caused by uncommon pathogens, which presents with similar symptoms, may be missed, wrote Qiaoqiao Yin, MS, of Zhejiang Provincial People’s Hospital, China, and colleagues.

“The clinical manifestations of human psittacosis can present as rapidly progressing severe pneumonia, acute respiratory distress syndrome, sepsis, and multiple organ failure,” but human cases have not been well studied, they say.

In a study  published in the International Journal of Infectious Diseases, the researchers reviewed data from 32 adults diagnosed with Chlamydia psittaci pneumonia during the COVID-19 pandemic between April 2020 and June 2021 in China. The median age of the patients was 63 years, 20 were men, and 20 had underlying diseases.

A total of 17 patients presented with fever, cough, and expectoration of yellow-white sputum. At the time of hospital admission, three patients had myalgia, two had headache, and two had hypertension. The patients were originally suspected of having COVID-19.

“All patients showed atypical pneumonia, including inflammatory infiltration, pleural effusion, multiple inflammatory exudative lesions with interstitial edema, lung abscesses, and white lung,” all of which could be observed in COVID-19 patients as well, the researchers wrote.

Reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) testing were used to rule out COVID-19. The researchers then used metagenomic next-generation sequencing (mNGS) to identify the disease-causing pathogens. They collected 18 bronchoalveolar lavage fluid (BALF) samples, 9 peripheral blood samples, and 5 sputum samples. The mNGS identified C. psittaci as the suspected pathogen within 48 hours. Suspected C. psittaci infections were confirmed by endpoint PCR for the BALF and sputum samples and six of nine blood samples, “indicating a lower sensitivity of PCR compared to mNGS for blood samples,” the researchers say. No other potential pathogens were identified.

Psittacosis is common in birds but is rare in humans. C. psittaci is responsible for 1%-8% of cases involving community-acquired pneumonia in China, the researchers note. Although poultry is a source of infection, 25 of the patients in the study did not report a history of exposure to poultry or pigeons at the time of their initial hospital admission. Many patients may be unaware of exposures to poultry, which further complicates the C. psittaci diagnosis, they note.

All patients were treated with doxycycline-based regimens and showed improvement.

The findings were limited by several factors, including the lack of a definitive diagnostic tool for C. psittaci and the lack of convalescent serum samples to confirm cases, the researchers note. In addition, molecular detections for PCR are unavailable in most hospitals in China, they say. The results represent the largest known collection of suspected C. psittaci pneumonia cases and highlight the need for clinician vigilance and awareness of this rare condition, especially in light of the potential for misdiagnosis during the ongoing COVID-19 pandemic, they conclude.

The study received no outside funding. The researchers have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Approximately 80% of patients in intensive care showed clinical improvement in gram-positive bacterial infections after treatment with linezolid, based on data from more than 300 individuals.

Bacterial infections remain a challenge in the management of critically ill patients, as many gram-positive pathogens have become resistant to multiple drug options, Aijia Ma, MD, of West China Hospital of Sichuan University, and colleagues wrote.

Linezolid has demonstrated effectiveness against MRSA and skin and soft-tissue infections (SSTIs), but its use in critically ill patients with gram-positive infections in the ICU has not been characterized, they said.

In a multicenter, real-world study published in the Journal of Intensive Medicine, the researchers reviewed data from 52 hospitals between June 2018 and December 2019. The study population included 366 patients admitted to the ICU with a clinical or laboratory diagnosis of a gram-positive bacterial infection. Patients were treated with linezolid injections (200 mg/100 mL) and followed up once a day until 48 hours after discontinuing therapy, transferring out of the ICU, or death. Most of the patients (243) were older than 65 years; 90 were aged 18-65 years, and 30 were younger than 18 years. Approximately two-thirds (67%) were men. The primary outcome of clinical efficacy was success (cured or improved).

Linezolid was used as second-line and first-line treatment in 232 (63.4%) and 134 (36.6%) patients, respectively. The most common isolated strain was Staphylococcus aureus (31% MRSA; 12.6% methicillin-susceptible S. aureus [MSSA]) followed by Enterococci (6.7% vancomycin resistant, 9.2% vancomycin susceptible) and Streptococcus pneumoniae (3.4% multidrug resistant, 1.7% non–multidrug resistant).

Overall, 82.2% of patients met the criteria for clinical success; 34 (9.3%) were cured and 267 (73%) improved. Clinical success rates for first-line and second-line linezolid therapy were 79.9% and 83.6%, respectively. Failure rates for linezolid were higher for second-line versus first-line treatment (9.5% vs. 5.2%).

The clinical success rate was highest against MSSA (93.3%), followed by MRSA (83.8%). The average daily linezolid dose was 1,109 mg, and the mean treatment time was 5.1 days.

A total of eight patients (2.2%) reported linezolid-related adverse events, and four patients discontinued the medication because of them; none reported treatment-related serious adverse events. The low incidence of thrombocytopenia in the current study (two patients), compared with previous studies may have been related to avoidance of linezolid for at-risk patients as determined by clinicians, and the relatively short duration of linezolid use, the researchers wrote.

The study findings were limited by several factors, including the observational design and inability to compare the efficacy of different drugs; the small sample size; and the lack of data on drugs used prior to ICU admission, the researchers noted. Other limitations included the low detection rate of gram-positive bacteria and potential underreporting of adverse events.

However, the results suggest that linezolid is a safe and effective treatment for gram-positive bacterial infections, although clinicians will need to pay close attention to possible side effects and evaluate patient conditions on an individual basis before using linezolid in the clinic, they concluded.

The study was supported by grants from West China Hospital of Sichuan University. The researchers reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Approximately 80% of patients in intensive care showed clinical improvement in gram-positive bacterial infections after treatment with linezolid, based on data from more than 300 individuals.

Bacterial infections remain a challenge in the management of critically ill patients, as many gram-positive pathogens have become resistant to multiple drug options, Aijia Ma, MD, of West China Hospital of Sichuan University, and colleagues wrote.

Linezolid has demonstrated effectiveness against MRSA and skin and soft-tissue infections (SSTIs), but its use in critically ill patients with gram-positive infections in the ICU has not been characterized, they said.

In a multicenter, real-world study published in the Journal of Intensive Medicine, the researchers reviewed data from 52 hospitals between June 2018 and December 2019. The study population included 366 patients admitted to the ICU with a clinical or laboratory diagnosis of a gram-positive bacterial infection. Patients were treated with linezolid injections (200 mg/100 mL) and followed up once a day until 48 hours after discontinuing therapy, transferring out of the ICU, or death. Most of the patients (243) were older than 65 years; 90 were aged 18-65 years, and 30 were younger than 18 years. Approximately two-thirds (67%) were men. The primary outcome of clinical efficacy was success (cured or improved).

Linezolid was used as second-line and first-line treatment in 232 (63.4%) and 134 (36.6%) patients, respectively. The most common isolated strain was Staphylococcus aureus (31% MRSA; 12.6% methicillin-susceptible S. aureus [MSSA]) followed by Enterococci (6.7% vancomycin resistant, 9.2% vancomycin susceptible) and Streptococcus pneumoniae (3.4% multidrug resistant, 1.7% non–multidrug resistant).

Overall, 82.2% of patients met the criteria for clinical success; 34 (9.3%) were cured and 267 (73%) improved. Clinical success rates for first-line and second-line linezolid therapy were 79.9% and 83.6%, respectively. Failure rates for linezolid were higher for second-line versus first-line treatment (9.5% vs. 5.2%).

The clinical success rate was highest against MSSA (93.3%), followed by MRSA (83.8%). The average daily linezolid dose was 1,109 mg, and the mean treatment time was 5.1 days.

A total of eight patients (2.2%) reported linezolid-related adverse events, and four patients discontinued the medication because of them; none reported treatment-related serious adverse events. The low incidence of thrombocytopenia in the current study (two patients), compared with previous studies may have been related to avoidance of linezolid for at-risk patients as determined by clinicians, and the relatively short duration of linezolid use, the researchers wrote.

The study findings were limited by several factors, including the observational design and inability to compare the efficacy of different drugs; the small sample size; and the lack of data on drugs used prior to ICU admission, the researchers noted. Other limitations included the low detection rate of gram-positive bacteria and potential underreporting of adverse events.

However, the results suggest that linezolid is a safe and effective treatment for gram-positive bacterial infections, although clinicians will need to pay close attention to possible side effects and evaluate patient conditions on an individual basis before using linezolid in the clinic, they concluded.

The study was supported by grants from West China Hospital of Sichuan University. The researchers reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Approximately 80% of patients in intensive care showed clinical improvement in gram-positive bacterial infections after treatment with linezolid, based on data from more than 300 individuals.

Bacterial infections remain a challenge in the management of critically ill patients, as many gram-positive pathogens have become resistant to multiple drug options, Aijia Ma, MD, of West China Hospital of Sichuan University, and colleagues wrote.

Linezolid has demonstrated effectiveness against MRSA and skin and soft-tissue infections (SSTIs), but its use in critically ill patients with gram-positive infections in the ICU has not been characterized, they said.

In a multicenter, real-world study published in the Journal of Intensive Medicine, the researchers reviewed data from 52 hospitals between June 2018 and December 2019. The study population included 366 patients admitted to the ICU with a clinical or laboratory diagnosis of a gram-positive bacterial infection. Patients were treated with linezolid injections (200 mg/100 mL) and followed up once a day until 48 hours after discontinuing therapy, transferring out of the ICU, or death. Most of the patients (243) were older than 65 years; 90 were aged 18-65 years, and 30 were younger than 18 years. Approximately two-thirds (67%) were men. The primary outcome of clinical efficacy was success (cured or improved).

Linezolid was used as second-line and first-line treatment in 232 (63.4%) and 134 (36.6%) patients, respectively. The most common isolated strain was Staphylococcus aureus (31% MRSA; 12.6% methicillin-susceptible S. aureus [MSSA]) followed by Enterococci (6.7% vancomycin resistant, 9.2% vancomycin susceptible) and Streptococcus pneumoniae (3.4% multidrug resistant, 1.7% non–multidrug resistant).

Overall, 82.2% of patients met the criteria for clinical success; 34 (9.3%) were cured and 267 (73%) improved. Clinical success rates for first-line and second-line linezolid therapy were 79.9% and 83.6%, respectively. Failure rates for linezolid were higher for second-line versus first-line treatment (9.5% vs. 5.2%).

The clinical success rate was highest against MSSA (93.3%), followed by MRSA (83.8%). The average daily linezolid dose was 1,109 mg, and the mean treatment time was 5.1 days.

A total of eight patients (2.2%) reported linezolid-related adverse events, and four patients discontinued the medication because of them; none reported treatment-related serious adverse events. The low incidence of thrombocytopenia in the current study (two patients), compared with previous studies may have been related to avoidance of linezolid for at-risk patients as determined by clinicians, and the relatively short duration of linezolid use, the researchers wrote.

The study findings were limited by several factors, including the observational design and inability to compare the efficacy of different drugs; the small sample size; and the lack of data on drugs used prior to ICU admission, the researchers noted. Other limitations included the low detection rate of gram-positive bacteria and potential underreporting of adverse events.

However, the results suggest that linezolid is a safe and effective treatment for gram-positive bacterial infections, although clinicians will need to pay close attention to possible side effects and evaluate patient conditions on an individual basis before using linezolid in the clinic, they concluded.

The study was supported by grants from West China Hospital of Sichuan University. The researchers reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Adults with hypertension who were vaccinated for COVID-19 with at least one booster were more than twice as likely as vaccinated and boosted individuals without hypertension to be hospitalized for severe COVID-19, according to data from more than 900 individuals.

“We were surprised to learn that many people who were hospitalized with COVID-19 had hypertension and no other risk factors,” said Susan Cheng, MD, MPH, director of the Institute for Research on Healthy Aging in the department of cardiology at the Smidt Heart Institute, Los Angeles, and a senior author of the study. “This is concerning when you consider that almost half of American adults have high blood pressure.”

Vishnu Kumar/Thinkstock

COVID-19 vaccines demonstrated ability to reduce death and some of the most severe side effects from the infection in the early stages of the pandemic. Although the Omicron surge prompted recommendations for a third mRNA vaccine dose, “a proportion of individuals who received three mRNA vaccine doses still required hospitalization for COVID-19 during the Omicron surge,” and the characteristics associated with severe illness in vaccinated and boosted patients have not been explored, Joseph Ebinger, MD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues wrote.

Previous research has shown an association between high blood pressure an increased risk for developing severe COVID-19 compared to several other chronic health conditions, including kidney disease, type 2 diabetes, chronic obstructive pulmonary disease, and heart failure, the researchers noted.

In a study published in Hypertension, the researchers identified 912 adults who received at least three doses of mRNA COVID-19 vaccine and were later diagnosed with COVID-19 during the surge in infections from the Omicron variant between December 2021 and April 2022.

A total of 145 of the individuals were hospitalized (16%); of these, 125 (86%) had hypertension.

Patients with hypertension were the most likely to be hospitalized, with an odds ratio of 2.9. In addition to high blood pressure, factors including older age (OR, 1.3), chronic kidney disease (OR, 2.2), prior myocardial infarction or heart failure (OR, 2.2), and longer time since the last vaccination and COVID-19 infection were associated with increased risk of hospitalization in a multivariate analysis.

However, the increased risk of severe illness and hospitalization associated with high blood pressure persisted, with an OR of 2.6, in the absence of comorbid conditions such as type 2 diabetes, kidney disease, and heart failure, the researchers emphasized.

“Although the mechanism for hypertension-associated COVID-19 risk remains unclear, prior studies have identified delayed SARS-CoV-2 viral clearance and prolonged inflammatory response among hypertensive patients, which may contribute to greater disease severity,” they wrote.

The findings were limited by several factors, including the use of data from a single center and lack of information on which Omicron variants and subvariants were behind the infections, the researchers noted.

However, the results highlight the need for more research on how to reduce the risks of severe COVID-19 in vulnerable populations, and on the mechanism for a potential connection between high blood pressure and severe COVID-19, they said.

Given the high prevalence of hypertension worldwide, increased understanding of the hypertension-specific risks and identification of individual and population-level risk reduction strategies will be important to the transition of COVID-19 from pandemic to endemic, they concluded.
 

Omicron changes the game

“When the pandemic initially started, many conditions were seen to increase risk for more severe COVID illness, and hypertension was one of those factors – and then things changed,” lead author Dr. Ebinger said in an interview. “First, vaccines arrived on the scene and substantially reduced risk of severe COVID for everyone who received them. Second, Omicron arrived and, while more transmissible, this variant has been less likely to cause severe COVID. On the one hand, we have vaccines and boosters that we want to think of as ‘the great equalizer’ when it comes to preexisting conditions. On the other hand, we have a dominant set of SARS-CoV-2 subvariants that seem less virulent in most people.

“Taken together, we have been hoping and even assuming that we have been doing pretty well with minimizing risks. Unfortunately, our study results indicate this is not exactly the case,” he said.

“Although vaccines and boosters appear to have equalized or minimized the risks of severe COVID for some people, this has not happened for others – even in the setting of the milder Omicron variant. Of individuals who were fully vaccinated and boosted, having hypertension increased the odds of needing to be hospitalized after getting infected with Omicron by 2.6-fold, even when accounting for or in the absence of having any major chronic disease that might otherwise predispose to more severe COVID-19 illness,” Dr. Ebinger added.

“So, while the originally seen risks of having obesity or diabetes seem to have been minimized during this current era of pandemic, the risk of having hypertension has persisted. We found this both surprising and concerning, because hypertension is very common and present in over half of people over age 50.”

Surprisingly, “we found that a fair number of people, even after being fully vaccinated plus a having gotten a booster, will not only catch Omicron but get sick enough to need hospital care,” Dr. Ebinger emphasized. “Moreover, it is not just older adults with major comorbid conditions who are vulnerable. Our data show that this can happen to an adult of any age and especially if a person has only hypertension and otherwise no major chronic disease.”

The first takeaway message for clinicians at this time is to raise awareness, Dr. Ebinger stressed in the interview. “We need to raise understanding around the fact that receiving three doses of vaccine may not prevent severe COVID-19 illness in everyone, even when the circulating viral variant is presumed to be causing only mild disease in most people. Moreover, the people who are most at risk are not whom we might think they are. They are not the sickest of the sick. They include people who might not have major conditions such as heart disease or kidney disease, but they do have hypertension.”

Second, “we need more research to understand out why there is this link between hypertension and excess risk for the more severe forms of COVID-19, despite it arising from a supposedly milder variant,” said Dr. Ebinger.

“Third, we need to determine how to reduce these risks, whether through more tailored vaccine regimens or novel therapeutics or a combination approach,” he said.

Looking ahead, “the biological mechanism underpinning the association between hypertension and severe COVID-19 remains underexplored. Future work should focus on understanding the factors linking hypertension to severe COVID-19, as this may elucidate both information on how SARS-CoV-2 effects the body and potential targets for intervention,” Dr. Ebinger added.

The study was supported in part by Cedars-Sinai Medical Center, the Erika J. Glazer Family Foundation and the National Institutes of Health. The researchers had no financial conflicts to disclose.

Adults with hypertension who were vaccinated for COVID-19 with at least one booster were more than twice as likely as vaccinated and boosted individuals without hypertension to be hospitalized for severe COVID-19, according to data from more than 900 individuals.

“We were surprised to learn that many people who were hospitalized with COVID-19 had hypertension and no other risk factors,” said Susan Cheng, MD, MPH, director of the Institute for Research on Healthy Aging in the department of cardiology at the Smidt Heart Institute, Los Angeles, and a senior author of the study. “This is concerning when you consider that almost half of American adults have high blood pressure.”

Vishnu Kumar/Thinkstock

COVID-19 vaccines demonstrated ability to reduce death and some of the most severe side effects from the infection in the early stages of the pandemic. Although the Omicron surge prompted recommendations for a third mRNA vaccine dose, “a proportion of individuals who received three mRNA vaccine doses still required hospitalization for COVID-19 during the Omicron surge,” and the characteristics associated with severe illness in vaccinated and boosted patients have not been explored, Joseph Ebinger, MD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues wrote.

Previous research has shown an association between high blood pressure an increased risk for developing severe COVID-19 compared to several other chronic health conditions, including kidney disease, type 2 diabetes, chronic obstructive pulmonary disease, and heart failure, the researchers noted.

In a study published in Hypertension, the researchers identified 912 adults who received at least three doses of mRNA COVID-19 vaccine and were later diagnosed with COVID-19 during the surge in infections from the Omicron variant between December 2021 and April 2022.

A total of 145 of the individuals were hospitalized (16%); of these, 125 (86%) had hypertension.

Patients with hypertension were the most likely to be hospitalized, with an odds ratio of 2.9. In addition to high blood pressure, factors including older age (OR, 1.3), chronic kidney disease (OR, 2.2), prior myocardial infarction or heart failure (OR, 2.2), and longer time since the last vaccination and COVID-19 infection were associated with increased risk of hospitalization in a multivariate analysis.

However, the increased risk of severe illness and hospitalization associated with high blood pressure persisted, with an OR of 2.6, in the absence of comorbid conditions such as type 2 diabetes, kidney disease, and heart failure, the researchers emphasized.

“Although the mechanism for hypertension-associated COVID-19 risk remains unclear, prior studies have identified delayed SARS-CoV-2 viral clearance and prolonged inflammatory response among hypertensive patients, which may contribute to greater disease severity,” they wrote.

The findings were limited by several factors, including the use of data from a single center and lack of information on which Omicron variants and subvariants were behind the infections, the researchers noted.

However, the results highlight the need for more research on how to reduce the risks of severe COVID-19 in vulnerable populations, and on the mechanism for a potential connection between high blood pressure and severe COVID-19, they said.

Given the high prevalence of hypertension worldwide, increased understanding of the hypertension-specific risks and identification of individual and population-level risk reduction strategies will be important to the transition of COVID-19 from pandemic to endemic, they concluded.
 

Omicron changes the game

“When the pandemic initially started, many conditions were seen to increase risk for more severe COVID illness, and hypertension was one of those factors – and then things changed,” lead author Dr. Ebinger said in an interview. “First, vaccines arrived on the scene and substantially reduced risk of severe COVID for everyone who received them. Second, Omicron arrived and, while more transmissible, this variant has been less likely to cause severe COVID. On the one hand, we have vaccines and boosters that we want to think of as ‘the great equalizer’ when it comes to preexisting conditions. On the other hand, we have a dominant set of SARS-CoV-2 subvariants that seem less virulent in most people.

“Taken together, we have been hoping and even assuming that we have been doing pretty well with minimizing risks. Unfortunately, our study results indicate this is not exactly the case,” he said.

“Although vaccines and boosters appear to have equalized or minimized the risks of severe COVID for some people, this has not happened for others – even in the setting of the milder Omicron variant. Of individuals who were fully vaccinated and boosted, having hypertension increased the odds of needing to be hospitalized after getting infected with Omicron by 2.6-fold, even when accounting for or in the absence of having any major chronic disease that might otherwise predispose to more severe COVID-19 illness,” Dr. Ebinger added.

“So, while the originally seen risks of having obesity or diabetes seem to have been minimized during this current era of pandemic, the risk of having hypertension has persisted. We found this both surprising and concerning, because hypertension is very common and present in over half of people over age 50.”

Surprisingly, “we found that a fair number of people, even after being fully vaccinated plus a having gotten a booster, will not only catch Omicron but get sick enough to need hospital care,” Dr. Ebinger emphasized. “Moreover, it is not just older adults with major comorbid conditions who are vulnerable. Our data show that this can happen to an adult of any age and especially if a person has only hypertension and otherwise no major chronic disease.”

The first takeaway message for clinicians at this time is to raise awareness, Dr. Ebinger stressed in the interview. “We need to raise understanding around the fact that receiving three doses of vaccine may not prevent severe COVID-19 illness in everyone, even when the circulating viral variant is presumed to be causing only mild disease in most people. Moreover, the people who are most at risk are not whom we might think they are. They are not the sickest of the sick. They include people who might not have major conditions such as heart disease or kidney disease, but they do have hypertension.”

Second, “we need more research to understand out why there is this link between hypertension and excess risk for the more severe forms of COVID-19, despite it arising from a supposedly milder variant,” said Dr. Ebinger.

“Third, we need to determine how to reduce these risks, whether through more tailored vaccine regimens or novel therapeutics or a combination approach,” he said.

Looking ahead, “the biological mechanism underpinning the association between hypertension and severe COVID-19 remains underexplored. Future work should focus on understanding the factors linking hypertension to severe COVID-19, as this may elucidate both information on how SARS-CoV-2 effects the body and potential targets for intervention,” Dr. Ebinger added.

The study was supported in part by Cedars-Sinai Medical Center, the Erika J. Glazer Family Foundation and the National Institutes of Health. The researchers had no financial conflicts to disclose.

Adults with hypertension who were vaccinated for COVID-19 with at least one booster were more than twice as likely as vaccinated and boosted individuals without hypertension to be hospitalized for severe COVID-19, according to data from more than 900 individuals.

“We were surprised to learn that many people who were hospitalized with COVID-19 had hypertension and no other risk factors,” said Susan Cheng, MD, MPH, director of the Institute for Research on Healthy Aging in the department of cardiology at the Smidt Heart Institute, Los Angeles, and a senior author of the study. “This is concerning when you consider that almost half of American adults have high blood pressure.”

Vishnu Kumar/Thinkstock

COVID-19 vaccines demonstrated ability to reduce death and some of the most severe side effects from the infection in the early stages of the pandemic. Although the Omicron surge prompted recommendations for a third mRNA vaccine dose, “a proportion of individuals who received three mRNA vaccine doses still required hospitalization for COVID-19 during the Omicron surge,” and the characteristics associated with severe illness in vaccinated and boosted patients have not been explored, Joseph Ebinger, MD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues wrote.

Previous research has shown an association between high blood pressure an increased risk for developing severe COVID-19 compared to several other chronic health conditions, including kidney disease, type 2 diabetes, chronic obstructive pulmonary disease, and heart failure, the researchers noted.

In a study published in Hypertension, the researchers identified 912 adults who received at least three doses of mRNA COVID-19 vaccine and were later diagnosed with COVID-19 during the surge in infections from the Omicron variant between December 2021 and April 2022.

A total of 145 of the individuals were hospitalized (16%); of these, 125 (86%) had hypertension.

Patients with hypertension were the most likely to be hospitalized, with an odds ratio of 2.9. In addition to high blood pressure, factors including older age (OR, 1.3), chronic kidney disease (OR, 2.2), prior myocardial infarction or heart failure (OR, 2.2), and longer time since the last vaccination and COVID-19 infection were associated with increased risk of hospitalization in a multivariate analysis.

However, the increased risk of severe illness and hospitalization associated with high blood pressure persisted, with an OR of 2.6, in the absence of comorbid conditions such as type 2 diabetes, kidney disease, and heart failure, the researchers emphasized.

“Although the mechanism for hypertension-associated COVID-19 risk remains unclear, prior studies have identified delayed SARS-CoV-2 viral clearance and prolonged inflammatory response among hypertensive patients, which may contribute to greater disease severity,” they wrote.

The findings were limited by several factors, including the use of data from a single center and lack of information on which Omicron variants and subvariants were behind the infections, the researchers noted.

However, the results highlight the need for more research on how to reduce the risks of severe COVID-19 in vulnerable populations, and on the mechanism for a potential connection between high blood pressure and severe COVID-19, they said.

Given the high prevalence of hypertension worldwide, increased understanding of the hypertension-specific risks and identification of individual and population-level risk reduction strategies will be important to the transition of COVID-19 from pandemic to endemic, they concluded.
 

Omicron changes the game

“When the pandemic initially started, many conditions were seen to increase risk for more severe COVID illness, and hypertension was one of those factors – and then things changed,” lead author Dr. Ebinger said in an interview. “First, vaccines arrived on the scene and substantially reduced risk of severe COVID for everyone who received them. Second, Omicron arrived and, while more transmissible, this variant has been less likely to cause severe COVID. On the one hand, we have vaccines and boosters that we want to think of as ‘the great equalizer’ when it comes to preexisting conditions. On the other hand, we have a dominant set of SARS-CoV-2 subvariants that seem less virulent in most people.

“Taken together, we have been hoping and even assuming that we have been doing pretty well with minimizing risks. Unfortunately, our study results indicate this is not exactly the case,” he said.

“Although vaccines and boosters appear to have equalized or minimized the risks of severe COVID for some people, this has not happened for others – even in the setting of the milder Omicron variant. Of individuals who were fully vaccinated and boosted, having hypertension increased the odds of needing to be hospitalized after getting infected with Omicron by 2.6-fold, even when accounting for or in the absence of having any major chronic disease that might otherwise predispose to more severe COVID-19 illness,” Dr. Ebinger added.

“So, while the originally seen risks of having obesity or diabetes seem to have been minimized during this current era of pandemic, the risk of having hypertension has persisted. We found this both surprising and concerning, because hypertension is very common and present in over half of people over age 50.”

Surprisingly, “we found that a fair number of people, even after being fully vaccinated plus a having gotten a booster, will not only catch Omicron but get sick enough to need hospital care,” Dr. Ebinger emphasized. “Moreover, it is not just older adults with major comorbid conditions who are vulnerable. Our data show that this can happen to an adult of any age and especially if a person has only hypertension and otherwise no major chronic disease.”

The first takeaway message for clinicians at this time is to raise awareness, Dr. Ebinger stressed in the interview. “We need to raise understanding around the fact that receiving three doses of vaccine may not prevent severe COVID-19 illness in everyone, even when the circulating viral variant is presumed to be causing only mild disease in most people. Moreover, the people who are most at risk are not whom we might think they are. They are not the sickest of the sick. They include people who might not have major conditions such as heart disease or kidney disease, but they do have hypertension.”

Second, “we need more research to understand out why there is this link between hypertension and excess risk for the more severe forms of COVID-19, despite it arising from a supposedly milder variant,” said Dr. Ebinger.

“Third, we need to determine how to reduce these risks, whether through more tailored vaccine regimens or novel therapeutics or a combination approach,” he said.

Looking ahead, “the biological mechanism underpinning the association between hypertension and severe COVID-19 remains underexplored. Future work should focus on understanding the factors linking hypertension to severe COVID-19, as this may elucidate both information on how SARS-CoV-2 effects the body and potential targets for intervention,” Dr. Ebinger added.

The study was supported in part by Cedars-Sinai Medical Center, the Erika J. Glazer Family Foundation and the National Institutes of Health. The researchers had no financial conflicts to disclose.

An overreliance on spirometry to identify emphysema led to missed cases in Black individuals, particularly men, based on a secondary data analysis of 2,674 people.

“Over the last few years, there has been growing debate around the use of race adjustment in diagnostic algorithms and equations commonly used in medicine,” lead author Gabrielle Yi-Hui Liu, MD, said in an interview. “Whereas, previously it was common to accept racial or ethnic differences in clinical measures and outcomes as inherent differences among populations, there is now more recognition of how racism, socioeconomic status, and environmental exposures can cause these racial differences. Our initial interest in this study was to examine how the use of race-specific spirometry reference equations, and the use of spirometry in general, may be contributing to racial disparities.”

“Previous studies have suggested that the use of race-specific equations in spirometry can exacerbate racial inequities in healthcare outcomes by under-recognition of early disease in Black adults, and this study adds to that evidence,” said Suman Pal, MBBS, of the University of New Mexico, Albuquerque, in an interview.
“By examining the crucial ways in which systemic factors in medicine, such as race-specific equations, exacerbate racial inequities in healthcare, this study is a timely analysis in a moment of national reckoning of structural racism,” said Dr. Pal, who was not involved in the study.

jgaunion/Thinkstock

In a study published in Annals of Internal Medicine, Dr. Liu and colleagues at Northwestern University, Chicago, conducted a secondary analysis of data from the CARDIA Lung study (Coronary Artery Risk Development In Young Adults).

The primary outcome of the study was the prevalence of emphysema among participants with various measures of normal spirometry results, stratified by sex and race. The normal results included an forced expiratory volume in 1 second (FEV₁₎–forced vital capacity (FVC) ratio greater than or equal to 0.7 or greater than or equal to the lower limit of normal. The participants also were stratified by FEV₁ percent predicted, using race-specific reference equations, for FEV₁ between 80% and 99% of predicted, or an FEV₁ between 100% and 120% of predicted.

The study population included 485 Black men, 762 Black women, 659 White men, and 768 White women who received both a CT scan (in 2010-2011) and spirometry (obtained in 2015-2016) in the CARDIA study. The mean age of the participants at the spirometry exam was 55 years.

A total of 5.3% of the participants had emphysema after stratifying by FEV₁-FVC ratio. The prevalence was significantly higher for Black men, compared with White men (12.3% vs. 4.0%; relative risk, 3.0), and for Black women, compared with White women (5.0% vs. 2.6%; RR, 1.9).

The association between Black race and emphysema risk persisted but decreased when the researchers used a race-neutral estimate.

When the participants were stratified by race-specific FEV₁ percent predicted, 6.5% of individuals with a race-specific FEV₁ between 80% and 99% had emphysema. After controlling for factors including age and smoking, emphysema was significantly more prevalent in Black men versus White men (15.5% vs. 4.0%) and in Black women, compared with White women (6.6% vs. 3.4%).

The racial difference persisted in men with a race-specific FEV₁ between 100% and 120% of predicted. Of these, 4.0% had emphysema. The prevalence was significantly higher in Black men, compared with White men (13.9% vs. 2.2%), but similar between Black women and White women (2.6% vs. 2.0%).

The use of race-neutral equations reduced, but did not eliminate, these disparities, the researchers said.

The findings were limited by the lack of CT imaging data from the same visit as the final spirometry collection, the researchers noted. “Given that imaging was obtained 5 years before spirometry and emphysema is an irreversible finding, this may have led to an overall underestimation of the prevalence of emphysema.”
 

Spirometry alone misses cases

“We were surprised by the substantial rates of emphysema we saw among Black men in our cohort with normal spirometry,” Dr. Liu said in an interview. “We did not expect to find than more than one in eight Black men with an FEV₁ between 100% and 120% predicted would have emphysema – a rate more than six times higher than White men with the same range of FEV₁.”

“One takeaway is that we are likely missing a lot of people with impaired respiratory health or true lung disease by only using spirometry to diagnose COPD,” said Dr. Liu. In clinical practice, “physicians should consider ordering CT scans on patients with normal spirometry who have respiratory symptoms such as cough or shortness of breath. If emphysema is found, physicians should discuss mitigating any potential risk factors and consider the use of COPD medications such as inhalers.

“Our findings also support using race-neutral reference equations to interpret spirometry instead of race-specific equations. Racial disparities in rates of emphysema among those with ‘normal’ FEV₁ [between 80% and 120% predicted], were attenuated or eliminated when race-neutral equations were used to calculate FEV₁. This suggests that race-specific equations are normalizing worse lung health in Black adults,” Dr. Liu explained.

“We need to continue research into additional tools that can be used to assess respiratory health and diagnose COPD, while keeping in mind how these tools may affect racial disparities,” said Dr. Liu. “Our study suggests that our reliance on spirometry measures such as FEV₁/FVC ratio and FEV₁ is missing a number of people with respiratory symptoms and CT evidence of lung disease, and that this is disproportionately affecting Black adults in the United States.” Looking ahead, “it is important to find better tools to identify people with impaired respiratory health or early manifestations of disease so we can intercept chronic lung disease before it becomes clinically apparent and patients have sustained significant lung damage.”

The CARDIA study was supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Dr. Liu was supported by a grant from the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Pal had no financial conflicts to disclose.

*This article was updated 7/22/2022.

An overreliance on spirometry to identify emphysema led to missed cases in Black individuals, particularly men, based on a secondary data analysis of 2,674 people.

“Over the last few years, there has been growing debate around the use of race adjustment in diagnostic algorithms and equations commonly used in medicine,” lead author Gabrielle Yi-Hui Liu, MD, said in an interview. “Whereas, previously it was common to accept racial or ethnic differences in clinical measures and outcomes as inherent differences among populations, there is now more recognition of how racism, socioeconomic status, and environmental exposures can cause these racial differences. Our initial interest in this study was to examine how the use of race-specific spirometry reference equations, and the use of spirometry in general, may be contributing to racial disparities.”

“Previous studies have suggested that the use of race-specific equations in spirometry can exacerbate racial inequities in healthcare outcomes by under-recognition of early disease in Black adults, and this study adds to that evidence,” said Suman Pal, MBBS, of the University of New Mexico, Albuquerque, in an interview.
“By examining the crucial ways in which systemic factors in medicine, such as race-specific equations, exacerbate racial inequities in healthcare, this study is a timely analysis in a moment of national reckoning of structural racism,” said Dr. Pal, who was not involved in the study.

jgaunion/Thinkstock

In a study published in Annals of Internal Medicine, Dr. Liu and colleagues at Northwestern University, Chicago, conducted a secondary analysis of data from the CARDIA Lung study (Coronary Artery Risk Development In Young Adults).

The primary outcome of the study was the prevalence of emphysema among participants with various measures of normal spirometry results, stratified by sex and race. The normal results included an forced expiratory volume in 1 second (FEV₁₎–forced vital capacity (FVC) ratio greater than or equal to 0.7 or greater than or equal to the lower limit of normal. The participants also were stratified by FEV₁ percent predicted, using race-specific reference equations, for FEV₁ between 80% and 99% of predicted, or an FEV₁ between 100% and 120% of predicted.

The study population included 485 Black men, 762 Black women, 659 White men, and 768 White women who received both a CT scan (in 2010-2011) and spirometry (obtained in 2015-2016) in the CARDIA study. The mean age of the participants at the spirometry exam was 55 years.

A total of 5.3% of the participants had emphysema after stratifying by FEV₁-FVC ratio. The prevalence was significantly higher for Black men, compared with White men (12.3% vs. 4.0%; relative risk, 3.0), and for Black women, compared with White women (5.0% vs. 2.6%; RR, 1.9).

The association between Black race and emphysema risk persisted but decreased when the researchers used a race-neutral estimate.

When the participants were stratified by race-specific FEV₁ percent predicted, 6.5% of individuals with a race-specific FEV₁ between 80% and 99% had emphysema. After controlling for factors including age and smoking, emphysema was significantly more prevalent in Black men versus White men (15.5% vs. 4.0%) and in Black women, compared with White women (6.6% vs. 3.4%).

The racial difference persisted in men with a race-specific FEV₁ between 100% and 120% of predicted. Of these, 4.0% had emphysema. The prevalence was significantly higher in Black men, compared with White men (13.9% vs. 2.2%), but similar between Black women and White women (2.6% vs. 2.0%).

The use of race-neutral equations reduced, but did not eliminate, these disparities, the researchers said.

The findings were limited by the lack of CT imaging data from the same visit as the final spirometry collection, the researchers noted. “Given that imaging was obtained 5 years before spirometry and emphysema is an irreversible finding, this may have led to an overall underestimation of the prevalence of emphysema.”
 

Spirometry alone misses cases

“We were surprised by the substantial rates of emphysema we saw among Black men in our cohort with normal spirometry,” Dr. Liu said in an interview. “We did not expect to find than more than one in eight Black men with an FEV₁ between 100% and 120% predicted would have emphysema – a rate more than six times higher than White men with the same range of FEV₁.”

“One takeaway is that we are likely missing a lot of people with impaired respiratory health or true lung disease by only using spirometry to diagnose COPD,” said Dr. Liu. In clinical practice, “physicians should consider ordering CT scans on patients with normal spirometry who have respiratory symptoms such as cough or shortness of breath. If emphysema is found, physicians should discuss mitigating any potential risk factors and consider the use of COPD medications such as inhalers.

“Our findings also support using race-neutral reference equations to interpret spirometry instead of race-specific equations. Racial disparities in rates of emphysema among those with ‘normal’ FEV₁ [between 80% and 120% predicted], were attenuated or eliminated when race-neutral equations were used to calculate FEV₁. This suggests that race-specific equations are normalizing worse lung health in Black adults,” Dr. Liu explained.

“We need to continue research into additional tools that can be used to assess respiratory health and diagnose COPD, while keeping in mind how these tools may affect racial disparities,” said Dr. Liu. “Our study suggests that our reliance on spirometry measures such as FEV₁/FVC ratio and FEV₁ is missing a number of people with respiratory symptoms and CT evidence of lung disease, and that this is disproportionately affecting Black adults in the United States.” Looking ahead, “it is important to find better tools to identify people with impaired respiratory health or early manifestations of disease so we can intercept chronic lung disease before it becomes clinically apparent and patients have sustained significant lung damage.”

The CARDIA study was supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Dr. Liu was supported by a grant from the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Pal had no financial conflicts to disclose.

*This article was updated 7/22/2022.

An overreliance on spirometry to identify emphysema led to missed cases in Black individuals, particularly men, based on a secondary data analysis of 2,674 people.

“Over the last few years, there has been growing debate around the use of race adjustment in diagnostic algorithms and equations commonly used in medicine,” lead author Gabrielle Yi-Hui Liu, MD, said in an interview. “Whereas, previously it was common to accept racial or ethnic differences in clinical measures and outcomes as inherent differences among populations, there is now more recognition of how racism, socioeconomic status, and environmental exposures can cause these racial differences. Our initial interest in this study was to examine how the use of race-specific spirometry reference equations, and the use of spirometry in general, may be contributing to racial disparities.”

“Previous studies have suggested that the use of race-specific equations in spirometry can exacerbate racial inequities in healthcare outcomes by under-recognition of early disease in Black adults, and this study adds to that evidence,” said Suman Pal, MBBS, of the University of New Mexico, Albuquerque, in an interview.
“By examining the crucial ways in which systemic factors in medicine, such as race-specific equations, exacerbate racial inequities in healthcare, this study is a timely analysis in a moment of national reckoning of structural racism,” said Dr. Pal, who was not involved in the study.

jgaunion/Thinkstock

In a study published in Annals of Internal Medicine, Dr. Liu and colleagues at Northwestern University, Chicago, conducted a secondary analysis of data from the CARDIA Lung study (Coronary Artery Risk Development In Young Adults).

The primary outcome of the study was the prevalence of emphysema among participants with various measures of normal spirometry results, stratified by sex and race. The normal results included an forced expiratory volume in 1 second (FEV₁₎–forced vital capacity (FVC) ratio greater than or equal to 0.7 or greater than or equal to the lower limit of normal. The participants also were stratified by FEV₁ percent predicted, using race-specific reference equations, for FEV₁ between 80% and 99% of predicted, or an FEV₁ between 100% and 120% of predicted.

The study population included 485 Black men, 762 Black women, 659 White men, and 768 White women who received both a CT scan (in 2010-2011) and spirometry (obtained in 2015-2016) in the CARDIA study. The mean age of the participants at the spirometry exam was 55 years.

A total of 5.3% of the participants had emphysema after stratifying by FEV₁-FVC ratio. The prevalence was significantly higher for Black men, compared with White men (12.3% vs. 4.0%; relative risk, 3.0), and for Black women, compared with White women (5.0% vs. 2.6%; RR, 1.9).

The association between Black race and emphysema risk persisted but decreased when the researchers used a race-neutral estimate.

When the participants were stratified by race-specific FEV₁ percent predicted, 6.5% of individuals with a race-specific FEV₁ between 80% and 99% had emphysema. After controlling for factors including age and smoking, emphysema was significantly more prevalent in Black men versus White men (15.5% vs. 4.0%) and in Black women, compared with White women (6.6% vs. 3.4%).

The racial difference persisted in men with a race-specific FEV₁ between 100% and 120% of predicted. Of these, 4.0% had emphysema. The prevalence was significantly higher in Black men, compared with White men (13.9% vs. 2.2%), but similar between Black women and White women (2.6% vs. 2.0%).

The use of race-neutral equations reduced, but did not eliminate, these disparities, the researchers said.

The findings were limited by the lack of CT imaging data from the same visit as the final spirometry collection, the researchers noted. “Given that imaging was obtained 5 years before spirometry and emphysema is an irreversible finding, this may have led to an overall underestimation of the prevalence of emphysema.”
 

Spirometry alone misses cases

“We were surprised by the substantial rates of emphysema we saw among Black men in our cohort with normal spirometry,” Dr. Liu said in an interview. “We did not expect to find than more than one in eight Black men with an FEV₁ between 100% and 120% predicted would have emphysema – a rate more than six times higher than White men with the same range of FEV₁.”

“One takeaway is that we are likely missing a lot of people with impaired respiratory health or true lung disease by only using spirometry to diagnose COPD,” said Dr. Liu. In clinical practice, “physicians should consider ordering CT scans on patients with normal spirometry who have respiratory symptoms such as cough or shortness of breath. If emphysema is found, physicians should discuss mitigating any potential risk factors and consider the use of COPD medications such as inhalers.

“Our findings also support using race-neutral reference equations to interpret spirometry instead of race-specific equations. Racial disparities in rates of emphysema among those with ‘normal’ FEV₁ [between 80% and 120% predicted], were attenuated or eliminated when race-neutral equations were used to calculate FEV₁. This suggests that race-specific equations are normalizing worse lung health in Black adults,” Dr. Liu explained.

“We need to continue research into additional tools that can be used to assess respiratory health and diagnose COPD, while keeping in mind how these tools may affect racial disparities,” said Dr. Liu. “Our study suggests that our reliance on spirometry measures such as FEV₁/FVC ratio and FEV₁ is missing a number of people with respiratory symptoms and CT evidence of lung disease, and that this is disproportionately affecting Black adults in the United States.” Looking ahead, “it is important to find better tools to identify people with impaired respiratory health or early manifestations of disease so we can intercept chronic lung disease before it becomes clinically apparent and patients have sustained significant lung damage.”

The CARDIA study was supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Dr. Liu was supported by a grant from the National Institutes of Health. The researchers had no financial conflicts to disclose. Dr. Pal had no financial conflicts to disclose.

*This article was updated 7/22/2022.