Asthma

Exposure to antibiotics in mid- to late pregnancy was associated with childhood asthma in vaginally born children, in a Danish birth cohort study.

The reason behind the correlation is unclear. Maternal infections, rather than antibiotics, “could explain the observed association,” said study author Cecilie Skaarup Uldbjerg, a researcher in the department of public health at Aarhus University in Denmark.

Still, the “results are in keeping with the hypothesis that effects of antibiotics impact the maternally derived microbiome in vaginally born children and that this may increase the odds of childhood asthma,” Ms. Uldbjerg and coauthors wrote in their study, which was published online Feb. 9 in Archives of Disease in Childhood . “However, this observational study did not address underlying mechanisms, and this interpretation, while plausible, remains speculative.”
 

Antibiotic use in pregnancy likely to continue

Patrick Duff, MD, who was not involved in the research, does not expect the findings will alter clinical practice.

The association was relatively weak, and the study does not account for factors such as antibiotic exposure during early childhood or tobacco smoke in the house, said Dr. Duff, professor of maternal-fetal medicine at University of Florida, Gainesville.

“Although I agree that we should not use antibiotics indiscriminately during pregnancy, we definitely need to treat certain infections,” Dr. Duff said. “Thus we cannot avoid some degree of antibiotic exposure.”

Although prior research has indicated that antibiotic use in pregnancy may increase the risk of asthma in children, results have been inconsistent.

To study whether antibiotic exposure during pregnancy is associated with childhood asthma and whether the timing of antibiotic exposure or mode of delivery influence the relationship, the investigators analyzed data from more than 32,000 children in the Danish National Birth Cohort, which was established in 1996.
 

Children of mothers who took and did not take antibiotics compared

In all, 17% of the children were born to mothers who used antibiotics during pregnancy. Compared with mothers who did not take antibiotics, those who did reported more maternal asthma, smoking during pregnancy, and having overweight or obesity. In addition, they were less likely to have been in their first pregnancy.

During follow-up at age 11 years, 4,238 children (13%) had asthma, including 12.7% of those whose mothers had not been exposed to antibiotics, and 14.6% of those whose mothers had used antibiotics during pregnancy.

In adjusted analyses, children born to mothers who received antibiotics were more likely to have asthma (OR, 1.14).

Antibiotic exposure in the second to third trimester, but not in the first trimester, was associated with asthma. The association was observed in vaginally born children, but not in children born by cesarean section.

The study is limited by its reliance on maternal reporting for data about antibiotics and asthma diagnoses, the authors noted. Mothers completed telephone interviews twice during pregnancy and once at 6 months postpartum. They completed online questionnaires to provide follow-up information at 11 years.
 

Mode of delivery may matter

The researchers said their analysis indicates that mode of delivery may modify the association between antibiotic exposure during pregnancy and childhood asthma.

Fourteen percent of the children in the study were delivered by cesarean section. Further research may clarify the relationship between antibiotics in pregnancy, mode of delivery, and asthma risk, another doctor who was not involved the study added.

“I do not think that the evidence indicates that mode of delivery clearly has an impact,” said Santina J. G. Wheat, MD, MPH, associate professor of family and community medicine at Northwestern University in Chicago, “as the number of cesarean deliveries was not large enough to fully support such a statement.

“It will be interesting to see if an association holds in future studies with increased cesarean deliveries,” Dr. Wheat said.

How and why antibiotics were used may be other important factors to investigate, Dr. Duff suggested.

“The authors did not provide any specific information about which antibiotics were used by the mothers, duration of use, and indication for use. Those are very important confounders,” Dr. Duff said. “Perhaps the key exposure is to a particular maternal infection rather than to the antibiotic per se.”

The Danish National Birth Cohort was established with a grant from the Danish National Research Foundation and support from regional committees and other organizations. Its biobank has been supported by the Novo Nordisk Foundation and the Lundbeck Foundation, and follow-up of mothers and children has been supported by the Danish Medical Research Council, the Lundbeck Foundation, Innovation Fund Denmark, the Nordea Foundation, Aarhus Ideas, a University of Copenhagen strategic grant, and the Danish Council for Independent Research. The study was partially funded by the Health Research Fund of Central Denmark Region, which supported one of the authors. Other authors were supported by the DHB Foundation and the Australian National Health and Medical Research Council. One author is affiliated with Murdoch Children’s Research Institute in Australia, where the Victorian Government’s Operational Infrastructure Support Program supports research.

The authors had no competing interests. Dr. Wheat serves on the editorial advisory board of Family Practice News. Dr. Duff had no relevant financial disclosures.

jremaly@mdedge.com

Exposure to antibiotics in mid- to late pregnancy was associated with childhood asthma in vaginally born children, in a Danish birth cohort study.

The reason behind the correlation is unclear. Maternal infections, rather than antibiotics, “could explain the observed association,” said study author Cecilie Skaarup Uldbjerg, a researcher in the department of public health at Aarhus University in Denmark.

Still, the “results are in keeping with the hypothesis that effects of antibiotics impact the maternally derived microbiome in vaginally born children and that this may increase the odds of childhood asthma,” Ms. Uldbjerg and coauthors wrote in their study, which was published online Feb. 9 in Archives of Disease in Childhood . “However, this observational study did not address underlying mechanisms, and this interpretation, while plausible, remains speculative.”
 

Antibiotic use in pregnancy likely to continue

Patrick Duff, MD, who was not involved in the research, does not expect the findings will alter clinical practice.

The association was relatively weak, and the study does not account for factors such as antibiotic exposure during early childhood or tobacco smoke in the house, said Dr. Duff, professor of maternal-fetal medicine at University of Florida, Gainesville.

“Although I agree that we should not use antibiotics indiscriminately during pregnancy, we definitely need to treat certain infections,” Dr. Duff said. “Thus we cannot avoid some degree of antibiotic exposure.”

Although prior research has indicated that antibiotic use in pregnancy may increase the risk of asthma in children, results have been inconsistent.

To study whether antibiotic exposure during pregnancy is associated with childhood asthma and whether the timing of antibiotic exposure or mode of delivery influence the relationship, the investigators analyzed data from more than 32,000 children in the Danish National Birth Cohort, which was established in 1996.
 

Children of mothers who took and did not take antibiotics compared

In all, 17% of the children were born to mothers who used antibiotics during pregnancy. Compared with mothers who did not take antibiotics, those who did reported more maternal asthma, smoking during pregnancy, and having overweight or obesity. In addition, they were less likely to have been in their first pregnancy.

During follow-up at age 11 years, 4,238 children (13%) had asthma, including 12.7% of those whose mothers had not been exposed to antibiotics, and 14.6% of those whose mothers had used antibiotics during pregnancy.

In adjusted analyses, children born to mothers who received antibiotics were more likely to have asthma (OR, 1.14).

Antibiotic exposure in the second to third trimester, but not in the first trimester, was associated with asthma. The association was observed in vaginally born children, but not in children born by cesarean section.

The study is limited by its reliance on maternal reporting for data about antibiotics and asthma diagnoses, the authors noted. Mothers completed telephone interviews twice during pregnancy and once at 6 months postpartum. They completed online questionnaires to provide follow-up information at 11 years.
 

Mode of delivery may matter

The researchers said their analysis indicates that mode of delivery may modify the association between antibiotic exposure during pregnancy and childhood asthma.

Fourteen percent of the children in the study were delivered by cesarean section. Further research may clarify the relationship between antibiotics in pregnancy, mode of delivery, and asthma risk, another doctor who was not involved the study added.

“I do not think that the evidence indicates that mode of delivery clearly has an impact,” said Santina J. G. Wheat, MD, MPH, associate professor of family and community medicine at Northwestern University in Chicago, “as the number of cesarean deliveries was not large enough to fully support such a statement.

“It will be interesting to see if an association holds in future studies with increased cesarean deliveries,” Dr. Wheat said.

How and why antibiotics were used may be other important factors to investigate, Dr. Duff suggested.

“The authors did not provide any specific information about which antibiotics were used by the mothers, duration of use, and indication for use. Those are very important confounders,” Dr. Duff said. “Perhaps the key exposure is to a particular maternal infection rather than to the antibiotic per se.”

The Danish National Birth Cohort was established with a grant from the Danish National Research Foundation and support from regional committees and other organizations. Its biobank has been supported by the Novo Nordisk Foundation and the Lundbeck Foundation, and follow-up of mothers and children has been supported by the Danish Medical Research Council, the Lundbeck Foundation, Innovation Fund Denmark, the Nordea Foundation, Aarhus Ideas, a University of Copenhagen strategic grant, and the Danish Council for Independent Research. The study was partially funded by the Health Research Fund of Central Denmark Region, which supported one of the authors. Other authors were supported by the DHB Foundation and the Australian National Health and Medical Research Council. One author is affiliated with Murdoch Children’s Research Institute in Australia, where the Victorian Government’s Operational Infrastructure Support Program supports research.

The authors had no competing interests. Dr. Wheat serves on the editorial advisory board of Family Practice News. Dr. Duff had no relevant financial disclosures.

jremaly@mdedge.com

Exposure to antibiotics in mid- to late pregnancy was associated with childhood asthma in vaginally born children, in a Danish birth cohort study.

The reason behind the correlation is unclear. Maternal infections, rather than antibiotics, “could explain the observed association,” said study author Cecilie Skaarup Uldbjerg, a researcher in the department of public health at Aarhus University in Denmark.

Still, the “results are in keeping with the hypothesis that effects of antibiotics impact the maternally derived microbiome in vaginally born children and that this may increase the odds of childhood asthma,” Ms. Uldbjerg and coauthors wrote in their study, which was published online Feb. 9 in Archives of Disease in Childhood . “However, this observational study did not address underlying mechanisms, and this interpretation, while plausible, remains speculative.”
 

Antibiotic use in pregnancy likely to continue

Patrick Duff, MD, who was not involved in the research, does not expect the findings will alter clinical practice.

The association was relatively weak, and the study does not account for factors such as antibiotic exposure during early childhood or tobacco smoke in the house, said Dr. Duff, professor of maternal-fetal medicine at University of Florida, Gainesville.

“Although I agree that we should not use antibiotics indiscriminately during pregnancy, we definitely need to treat certain infections,” Dr. Duff said. “Thus we cannot avoid some degree of antibiotic exposure.”

Although prior research has indicated that antibiotic use in pregnancy may increase the risk of asthma in children, results have been inconsistent.

To study whether antibiotic exposure during pregnancy is associated with childhood asthma and whether the timing of antibiotic exposure or mode of delivery influence the relationship, the investigators analyzed data from more than 32,000 children in the Danish National Birth Cohort, which was established in 1996.
 

Children of mothers who took and did not take antibiotics compared

In all, 17% of the children were born to mothers who used antibiotics during pregnancy. Compared with mothers who did not take antibiotics, those who did reported more maternal asthma, smoking during pregnancy, and having overweight or obesity. In addition, they were less likely to have been in their first pregnancy.

During follow-up at age 11 years, 4,238 children (13%) had asthma, including 12.7% of those whose mothers had not been exposed to antibiotics, and 14.6% of those whose mothers had used antibiotics during pregnancy.

In adjusted analyses, children born to mothers who received antibiotics were more likely to have asthma (OR, 1.14).

Antibiotic exposure in the second to third trimester, but not in the first trimester, was associated with asthma. The association was observed in vaginally born children, but not in children born by cesarean section.

The study is limited by its reliance on maternal reporting for data about antibiotics and asthma diagnoses, the authors noted. Mothers completed telephone interviews twice during pregnancy and once at 6 months postpartum. They completed online questionnaires to provide follow-up information at 11 years.
 

Mode of delivery may matter

The researchers said their analysis indicates that mode of delivery may modify the association between antibiotic exposure during pregnancy and childhood asthma.

Fourteen percent of the children in the study were delivered by cesarean section. Further research may clarify the relationship between antibiotics in pregnancy, mode of delivery, and asthma risk, another doctor who was not involved the study added.

“I do not think that the evidence indicates that mode of delivery clearly has an impact,” said Santina J. G. Wheat, MD, MPH, associate professor of family and community medicine at Northwestern University in Chicago, “as the number of cesarean deliveries was not large enough to fully support such a statement.

“It will be interesting to see if an association holds in future studies with increased cesarean deliveries,” Dr. Wheat said.

How and why antibiotics were used may be other important factors to investigate, Dr. Duff suggested.

“The authors did not provide any specific information about which antibiotics were used by the mothers, duration of use, and indication for use. Those are very important confounders,” Dr. Duff said. “Perhaps the key exposure is to a particular maternal infection rather than to the antibiotic per se.”

The Danish National Birth Cohort was established with a grant from the Danish National Research Foundation and support from regional committees and other organizations. Its biobank has been supported by the Novo Nordisk Foundation and the Lundbeck Foundation, and follow-up of mothers and children has been supported by the Danish Medical Research Council, the Lundbeck Foundation, Innovation Fund Denmark, the Nordea Foundation, Aarhus Ideas, a University of Copenhagen strategic grant, and the Danish Council for Independent Research. The study was partially funded by the Health Research Fund of Central Denmark Region, which supported one of the authors. Other authors were supported by the DHB Foundation and the Australian National Health and Medical Research Council. One author is affiliated with Murdoch Children’s Research Institute in Australia, where the Victorian Government’s Operational Infrastructure Support Program supports research.

The authors had no competing interests. Dr. Wheat serves on the editorial advisory board of Family Practice News. Dr. Duff had no relevant financial disclosures.

jremaly@mdedge.com

Patients with asthma–chronic obstructive pulmonary disease overlap (ACO) experienced a higher burden of disease than patients with either asthma or COPD alone, a recent study has found.

Approximately 20% of chronic obstructive airway disease cases are ACO, but data on these patients are limited, as they are often excluded from clinical trials, wrote Sarah A. Hiles, MD, of the University of Newcastle (Australia) and colleagues.

“Comparing the burden of eosinophilic ACO, eosinophilic severe asthma, and eosinophilic COPD may also help contextualize findings from phenotype-targeted treatments in different diagnostic groups, such as the limited success of anti-IL [interleukin]–5 monoclonal antibodies as therapy in eosinophilic COPD,” they said.

In a cross-sectional, observational study published in Respirology the researchers recruited patients aged 18 years and older with a confirmed diagnosis of COPD only (153) severe asthma only (64), or ACO (106). Patients were assessed for demographic and clinical factors including health-related quality of life, past-year exacerbation, and other indicators of disease burden. In addition, patients were identified as having eosinophilic airway disease based on a blood eosinophil count of at least 0.3x109/L.

Overall, eosinophilic airway disease was present in 41% of the patients; 55%, 44%, and 29% for those with ACO, severe asthma, and COPD, respectively. Reports of poor health-related quality of life and past-year exacerbations were similar for eosinophilic patients across all three conditions.

However, patients with eosinophilic ACO experienced significantly more past-year exacerbations, notably those requiring oral corticosteroids, compared with patients with asthma alone. In addition, the cumulative number of past-year exacerbations in patient with eosinophilic disease was 164 in those with ACO, compared with severe asthma alone (44) and COPD alone (59).

Patients with ACO also had significantly higher disease burden based on the St. George’s Respiratory Questionnaire (SGRQ), which assessed functional limitation. “For 100 patients, the cumulative SGRQ score attributable to eosinophilic airways disease in ACO was 2,872.8, which was higher than in severe asthma (1,942.5) or COPD (1,638.1),” the researchers said.

The study was limited by several factors including the cross-sectional design and use of a single measurement to classify eosinophilia, the researchers noted. “The non-eosinophilic group likely included a mix of patients with treated eosinophilia and patients without eosinophilia, regardless of treatment, which is a limitation to consider when interpreting the disease burden estimates in this group,” they added.

However, the results add to the understanding of blood eosinophils in airway disease and the study “supports eosinophilia as a phenotype that spans across disease labels of severe asthma and COPD, and their overlap,” they concluded.

The study was supported by AstraZeneca; lead author Dr. Hiles received a salary through a grant from AstraZeneca to the University of Newcastle while conducting the study. Other coauthors disclosed relationships with companies including AstraZeneca, GlaxoSmithKline, Menarini, and Novartis.

Patients with asthma–chronic obstructive pulmonary disease overlap (ACO) experienced a higher burden of disease than patients with either asthma or COPD alone, a recent study has found.

Approximately 20% of chronic obstructive airway disease cases are ACO, but data on these patients are limited, as they are often excluded from clinical trials, wrote Sarah A. Hiles, MD, of the University of Newcastle (Australia) and colleagues.

“Comparing the burden of eosinophilic ACO, eosinophilic severe asthma, and eosinophilic COPD may also help contextualize findings from phenotype-targeted treatments in different diagnostic groups, such as the limited success of anti-IL [interleukin]–5 monoclonal antibodies as therapy in eosinophilic COPD,” they said.

In a cross-sectional, observational study published in Respirology the researchers recruited patients aged 18 years and older with a confirmed diagnosis of COPD only (153) severe asthma only (64), or ACO (106). Patients were assessed for demographic and clinical factors including health-related quality of life, past-year exacerbation, and other indicators of disease burden. In addition, patients were identified as having eosinophilic airway disease based on a blood eosinophil count of at least 0.3x109/L.

Overall, eosinophilic airway disease was present in 41% of the patients; 55%, 44%, and 29% for those with ACO, severe asthma, and COPD, respectively. Reports of poor health-related quality of life and past-year exacerbations were similar for eosinophilic patients across all three conditions.

However, patients with eosinophilic ACO experienced significantly more past-year exacerbations, notably those requiring oral corticosteroids, compared with patients with asthma alone. In addition, the cumulative number of past-year exacerbations in patient with eosinophilic disease was 164 in those with ACO, compared with severe asthma alone (44) and COPD alone (59).

Patients with ACO also had significantly higher disease burden based on the St. George’s Respiratory Questionnaire (SGRQ), which assessed functional limitation. “For 100 patients, the cumulative SGRQ score attributable to eosinophilic airways disease in ACO was 2,872.8, which was higher than in severe asthma (1,942.5) or COPD (1,638.1),” the researchers said.

The study was limited by several factors including the cross-sectional design and use of a single measurement to classify eosinophilia, the researchers noted. “The non-eosinophilic group likely included a mix of patients with treated eosinophilia and patients without eosinophilia, regardless of treatment, which is a limitation to consider when interpreting the disease burden estimates in this group,” they added.

However, the results add to the understanding of blood eosinophils in airway disease and the study “supports eosinophilia as a phenotype that spans across disease labels of severe asthma and COPD, and their overlap,” they concluded.

The study was supported by AstraZeneca; lead author Dr. Hiles received a salary through a grant from AstraZeneca to the University of Newcastle while conducting the study. Other coauthors disclosed relationships with companies including AstraZeneca, GlaxoSmithKline, Menarini, and Novartis.

Patients with asthma–chronic obstructive pulmonary disease overlap (ACO) experienced a higher burden of disease than patients with either asthma or COPD alone, a recent study has found.

Approximately 20% of chronic obstructive airway disease cases are ACO, but data on these patients are limited, as they are often excluded from clinical trials, wrote Sarah A. Hiles, MD, of the University of Newcastle (Australia) and colleagues.

“Comparing the burden of eosinophilic ACO, eosinophilic severe asthma, and eosinophilic COPD may also help contextualize findings from phenotype-targeted treatments in different diagnostic groups, such as the limited success of anti-IL [interleukin]–5 monoclonal antibodies as therapy in eosinophilic COPD,” they said.

In a cross-sectional, observational study published in Respirology the researchers recruited patients aged 18 years and older with a confirmed diagnosis of COPD only (153) severe asthma only (64), or ACO (106). Patients were assessed for demographic and clinical factors including health-related quality of life, past-year exacerbation, and other indicators of disease burden. In addition, patients were identified as having eosinophilic airway disease based on a blood eosinophil count of at least 0.3x109/L.

Overall, eosinophilic airway disease was present in 41% of the patients; 55%, 44%, and 29% for those with ACO, severe asthma, and COPD, respectively. Reports of poor health-related quality of life and past-year exacerbations were similar for eosinophilic patients across all three conditions.

However, patients with eosinophilic ACO experienced significantly more past-year exacerbations, notably those requiring oral corticosteroids, compared with patients with asthma alone. In addition, the cumulative number of past-year exacerbations in patient with eosinophilic disease was 164 in those with ACO, compared with severe asthma alone (44) and COPD alone (59).

Patients with ACO also had significantly higher disease burden based on the St. George’s Respiratory Questionnaire (SGRQ), which assessed functional limitation. “For 100 patients, the cumulative SGRQ score attributable to eosinophilic airways disease in ACO was 2,872.8, which was higher than in severe asthma (1,942.5) or COPD (1,638.1),” the researchers said.

The study was limited by several factors including the cross-sectional design and use of a single measurement to classify eosinophilia, the researchers noted. “The non-eosinophilic group likely included a mix of patients with treated eosinophilia and patients without eosinophilia, regardless of treatment, which is a limitation to consider when interpreting the disease burden estimates in this group,” they added.

However, the results add to the understanding of blood eosinophils in airway disease and the study “supports eosinophilia as a phenotype that spans across disease labels of severe asthma and COPD, and their overlap,” they concluded.

The study was supported by AstraZeneca; lead author Dr. Hiles received a salary through a grant from AstraZeneca to the University of Newcastle while conducting the study. Other coauthors disclosed relationships with companies including AstraZeneca, GlaxoSmithKline, Menarini, and Novartis.

There is a significant association between routine attendance at annual well-child care visits and a reduction in both total asthma exacerbations and severe exacerbations, Jason E. Lang, MD, MPH, of Duke University, Durham, N.C. reported in a study published in Pediatrics.

Louis-Paul St-Onge/iStockphoto

In a retrospective cohort study of 5,656 pediatric asthma patients under care at the Duke University Health System, Dr. Lang and colleagues sought to determine the effect yearly well-child care (WCC) visits have on the hazard rate of asthma exacerbations occurring during the following year. Patients included in the study were aged 5-17 years and had been receiving care between Jan. 1, 2014, and Dec. 31, 2019.
 

WCC visits demonstrate reduced exacerbations and hospitalizations

Nearly one-third of patients were found to have full WCC visit attendance, half were partially compliant, and 14% did not attend at all. A total of 2,974 asthma exacerbations were reported during the study period. Of those with a WCC visit during the previous year, exacerbations were reduced by 10% and asthma hospitalizations were lowered by 47%. Children with recent WCC visits were also more likely to be prescribed daily preventive medication and to experience an exacerbation in ambulatory care, which could play a crucial role in preventing further progression of the disease.

Of the WCC visits reported, 9.9% represented prescribing of new or changed asthma medication, 28.2% represented delivery of seasonal influenza vaccine, and 11% addressed assessment or management of asthma-related comorbidities. There was no observed difference in attendance between younger and older children.

Given that pediatric WCC visit attendance is “far from optimal,” with attendance improving from 46% in 1996-1998 to almost 60% in 2007-2008, “improving access to and attendance of WCC visits (especially from previously low-adhering families) may be an important public health intervention to reduce the problems of severe exacerbations and outcome disparities,” observed Dr. Lang and colleagues. The Abdus study also found that low WCC attendance appeared to be more common in those with lower income, lower parental education, and African American race.
 

Continuity of care providers across WCC visits plays a crucial role

Primary care pediatricians play a key role in successful management of chronic asthma, as evidenced in several studies showing the importance of continuity of care with the same provider for WCC. Such continuity encourages ongoing dialogue about asthma, and as the researchers speculated, may even reduce asthma hospitalization through better parental understanding of disease management, prevention, and management of comorbid conditions.

Although the study did not include measures of health literacy, the authors did conclude that pediatric asthma patients seen annually are more likely to be more knowledgeable about asthma and in a better position to recognize symptom exacerbation so they can seek timely care. In the past, lower health literacy has demonstrated both lower WCC visit attendance and increased emergency care visits and hospitalizations.

Because the study was conducted in a single university-based health system, the researchers were not able to capture fragmented care data. They also acknowledged the possible omission of confounding factors, especially those related to parental influence behaviors affecting daily disease management. One strength of the study was the ability researchers had to abstract granular data from their EHR system to document the time-varying effects that insurance status, obesity status, and WCC visits may have played. Given that they were able to assess effects according to sociodemographic factors, such as race and insurance status, the results should prove very helpful to other cities and health systems aiming to improve pediatric asthma control, observed Dr. Lang and colleagues.

Future studies should seek to further evaluate the role of WCC visits in promoting asthma control. Making WCC visits a renewed public health priority offers the possibility to limit severe asthma exacerbations, the researchers advised.

In a separate interview, Sydney Leibel, MD, MPH, a pediatric allergist/immunologist at Rady Children’s Hospital, San Diego, noted: “The outcomes of this study shine a light on the importance of regular primary care pediatrician follow-up in decreasing asthma-related health care utilization. Childhood asthma is a dynamic condition and follow-up with the pediatrician allows for modification of the treatment plan and reinforcement of good inhaler technique. It also allows for patients to express their concerns and gives the opportunity for subspecialty referral, if symptoms remain uncontrolled.

“This article also highlights the health disparities that exist in pediatric asthma in the United States. In our experience, treating children from lower-socioeconomic communities with difficult-to-control and severe asthma, case management has been very important in making sure our patient population understands our instructions, pick up their medications, and make their scheduled follow-up appointments,” Dr. Leibel continued.

“Regardless of the patient’s background, efforts to improve attendance of WCC visits, where good asthma control can be promoted, would be in our patient’s best interest and could go a long way in preventing unnecessary asthma exacerbations that require an ED visit or hospitalization,” the specialist concluded.

The study was funded by a grant from the National Heart, Lung, and Blood Institute, Duke Children’s Health & Discovery Initiative, and the National Institutes of Health. Dr. Lang and colleagues had no conflicts of interest and no relevant financial disclosures. Dr. Leibel said he had no relevant financial disclosures.

SOURCE: Lang JE et al. Pediatrics. 2020. doi: 10.1542/peds.2020-1023.

There is a significant association between routine attendance at annual well-child care visits and a reduction in both total asthma exacerbations and severe exacerbations, Jason E. Lang, MD, MPH, of Duke University, Durham, N.C. reported in a study published in Pediatrics.

Louis-Paul St-Onge/iStockphoto

In a retrospective cohort study of 5,656 pediatric asthma patients under care at the Duke University Health System, Dr. Lang and colleagues sought to determine the effect yearly well-child care (WCC) visits have on the hazard rate of asthma exacerbations occurring during the following year. Patients included in the study were aged 5-17 years and had been receiving care between Jan. 1, 2014, and Dec. 31, 2019.
 

WCC visits demonstrate reduced exacerbations and hospitalizations

Nearly one-third of patients were found to have full WCC visit attendance, half were partially compliant, and 14% did not attend at all. A total of 2,974 asthma exacerbations were reported during the study period. Of those with a WCC visit during the previous year, exacerbations were reduced by 10% and asthma hospitalizations were lowered by 47%. Children with recent WCC visits were also more likely to be prescribed daily preventive medication and to experience an exacerbation in ambulatory care, which could play a crucial role in preventing further progression of the disease.

Of the WCC visits reported, 9.9% represented prescribing of new or changed asthma medication, 28.2% represented delivery of seasonal influenza vaccine, and 11% addressed assessment or management of asthma-related comorbidities. There was no observed difference in attendance between younger and older children.

Given that pediatric WCC visit attendance is “far from optimal,” with attendance improving from 46% in 1996-1998 to almost 60% in 2007-2008, “improving access to and attendance of WCC visits (especially from previously low-adhering families) may be an important public health intervention to reduce the problems of severe exacerbations and outcome disparities,” observed Dr. Lang and colleagues. The Abdus study also found that low WCC attendance appeared to be more common in those with lower income, lower parental education, and African American race.
 

Continuity of care providers across WCC visits plays a crucial role

Primary care pediatricians play a key role in successful management of chronic asthma, as evidenced in several studies showing the importance of continuity of care with the same provider for WCC. Such continuity encourages ongoing dialogue about asthma, and as the researchers speculated, may even reduce asthma hospitalization through better parental understanding of disease management, prevention, and management of comorbid conditions.

Although the study did not include measures of health literacy, the authors did conclude that pediatric asthma patients seen annually are more likely to be more knowledgeable about asthma and in a better position to recognize symptom exacerbation so they can seek timely care. In the past, lower health literacy has demonstrated both lower WCC visit attendance and increased emergency care visits and hospitalizations.

Because the study was conducted in a single university-based health system, the researchers were not able to capture fragmented care data. They also acknowledged the possible omission of confounding factors, especially those related to parental influence behaviors affecting daily disease management. One strength of the study was the ability researchers had to abstract granular data from their EHR system to document the time-varying effects that insurance status, obesity status, and WCC visits may have played. Given that they were able to assess effects according to sociodemographic factors, such as race and insurance status, the results should prove very helpful to other cities and health systems aiming to improve pediatric asthma control, observed Dr. Lang and colleagues.

Future studies should seek to further evaluate the role of WCC visits in promoting asthma control. Making WCC visits a renewed public health priority offers the possibility to limit severe asthma exacerbations, the researchers advised.

In a separate interview, Sydney Leibel, MD, MPH, a pediatric allergist/immunologist at Rady Children’s Hospital, San Diego, noted: “The outcomes of this study shine a light on the importance of regular primary care pediatrician follow-up in decreasing asthma-related health care utilization. Childhood asthma is a dynamic condition and follow-up with the pediatrician allows for modification of the treatment plan and reinforcement of good inhaler technique. It also allows for patients to express their concerns and gives the opportunity for subspecialty referral, if symptoms remain uncontrolled.

“This article also highlights the health disparities that exist in pediatric asthma in the United States. In our experience, treating children from lower-socioeconomic communities with difficult-to-control and severe asthma, case management has been very important in making sure our patient population understands our instructions, pick up their medications, and make their scheduled follow-up appointments,” Dr. Leibel continued.

“Regardless of the patient’s background, efforts to improve attendance of WCC visits, where good asthma control can be promoted, would be in our patient’s best interest and could go a long way in preventing unnecessary asthma exacerbations that require an ED visit or hospitalization,” the specialist concluded.

The study was funded by a grant from the National Heart, Lung, and Blood Institute, Duke Children’s Health & Discovery Initiative, and the National Institutes of Health. Dr. Lang and colleagues had no conflicts of interest and no relevant financial disclosures. Dr. Leibel said he had no relevant financial disclosures.

SOURCE: Lang JE et al. Pediatrics. 2020. doi: 10.1542/peds.2020-1023.

There is a significant association between routine attendance at annual well-child care visits and a reduction in both total asthma exacerbations and severe exacerbations, Jason E. Lang, MD, MPH, of Duke University, Durham, N.C. reported in a study published in Pediatrics.

Louis-Paul St-Onge/iStockphoto

In a retrospective cohort study of 5,656 pediatric asthma patients under care at the Duke University Health System, Dr. Lang and colleagues sought to determine the effect yearly well-child care (WCC) visits have on the hazard rate of asthma exacerbations occurring during the following year. Patients included in the study were aged 5-17 years and had been receiving care between Jan. 1, 2014, and Dec. 31, 2019.
 

WCC visits demonstrate reduced exacerbations and hospitalizations

Nearly one-third of patients were found to have full WCC visit attendance, half were partially compliant, and 14% did not attend at all. A total of 2,974 asthma exacerbations were reported during the study period. Of those with a WCC visit during the previous year, exacerbations were reduced by 10% and asthma hospitalizations were lowered by 47%. Children with recent WCC visits were also more likely to be prescribed daily preventive medication and to experience an exacerbation in ambulatory care, which could play a crucial role in preventing further progression of the disease.

Of the WCC visits reported, 9.9% represented prescribing of new or changed asthma medication, 28.2% represented delivery of seasonal influenza vaccine, and 11% addressed assessment or management of asthma-related comorbidities. There was no observed difference in attendance between younger and older children.

Given that pediatric WCC visit attendance is “far from optimal,” with attendance improving from 46% in 1996-1998 to almost 60% in 2007-2008, “improving access to and attendance of WCC visits (especially from previously low-adhering families) may be an important public health intervention to reduce the problems of severe exacerbations and outcome disparities,” observed Dr. Lang and colleagues. The Abdus study also found that low WCC attendance appeared to be more common in those with lower income, lower parental education, and African American race.
 

Continuity of care providers across WCC visits plays a crucial role

Primary care pediatricians play a key role in successful management of chronic asthma, as evidenced in several studies showing the importance of continuity of care with the same provider for WCC. Such continuity encourages ongoing dialogue about asthma, and as the researchers speculated, may even reduce asthma hospitalization through better parental understanding of disease management, prevention, and management of comorbid conditions.

Although the study did not include measures of health literacy, the authors did conclude that pediatric asthma patients seen annually are more likely to be more knowledgeable about asthma and in a better position to recognize symptom exacerbation so they can seek timely care. In the past, lower health literacy has demonstrated both lower WCC visit attendance and increased emergency care visits and hospitalizations.

Because the study was conducted in a single university-based health system, the researchers were not able to capture fragmented care data. They also acknowledged the possible omission of confounding factors, especially those related to parental influence behaviors affecting daily disease management. One strength of the study was the ability researchers had to abstract granular data from their EHR system to document the time-varying effects that insurance status, obesity status, and WCC visits may have played. Given that they were able to assess effects according to sociodemographic factors, such as race and insurance status, the results should prove very helpful to other cities and health systems aiming to improve pediatric asthma control, observed Dr. Lang and colleagues.

Future studies should seek to further evaluate the role of WCC visits in promoting asthma control. Making WCC visits a renewed public health priority offers the possibility to limit severe asthma exacerbations, the researchers advised.

In a separate interview, Sydney Leibel, MD, MPH, a pediatric allergist/immunologist at Rady Children’s Hospital, San Diego, noted: “The outcomes of this study shine a light on the importance of regular primary care pediatrician follow-up in decreasing asthma-related health care utilization. Childhood asthma is a dynamic condition and follow-up with the pediatrician allows for modification of the treatment plan and reinforcement of good inhaler technique. It also allows for patients to express their concerns and gives the opportunity for subspecialty referral, if symptoms remain uncontrolled.

“This article also highlights the health disparities that exist in pediatric asthma in the United States. In our experience, treating children from lower-socioeconomic communities with difficult-to-control and severe asthma, case management has been very important in making sure our patient population understands our instructions, pick up their medications, and make their scheduled follow-up appointments,” Dr. Leibel continued.

“Regardless of the patient’s background, efforts to improve attendance of WCC visits, where good asthma control can be promoted, would be in our patient’s best interest and could go a long way in preventing unnecessary asthma exacerbations that require an ED visit or hospitalization,” the specialist concluded.

The study was funded by a grant from the National Heart, Lung, and Blood Institute, Duke Children’s Health & Discovery Initiative, and the National Institutes of Health. Dr. Lang and colleagues had no conflicts of interest and no relevant financial disclosures. Dr. Leibel said he had no relevant financial disclosures.

SOURCE: Lang JE et al. Pediatrics. 2020. doi: 10.1542/peds.2020-1023.

Among children with moderate or severe persistent asthma, monitoring daily inhaler use with sensors and a mobile application may improve asthma symptom control and caregiver quality of life, a randomized trial suggests.

But the intervention also may lead to more ED visits and increased hospitalization rates.

“We improved asthma symptom control but did not reduce health care use,” Ruchi S. Gupta, MD, MPH, and colleagues, wrote in a study published in Pediatrics.

The monitoring system alerted clinicians when a patient used a short-acting beta-agonist more than four times in a day. It could be that the “alerts enabled providers to detect asthma exacerbation virtually and refer for clinically appropriate care that included directing children to the ED,” the authors suggested. It also is possible that the intervention led caregivers to be more vigilant about symptoms and more empowered to seek care.
 

Adherence to preventive regimens

Many patients with asthma need to use preventive medications such as daily inhaled corticosteroids to control symptoms. Researchers have developed sensor-based inhaler monitoring interventions to improve treatment adherence, but the effectiveness of these interventions in improving asthma outcomes in urban and minority populations is unclear.

To assess the effectiveness of a clinically integrated, sensor-based inhaler monitoring intervention on improving asthma symptom control and related outcomes in children, Dr. Gupta, of Northwestern University and Ann & Robert H. Lurie Children’s Hospital of Chicago, and colleagues conducted a randomized, unblinded study, known as the Improving Technology-Assisted Recording of Asthma Control in Children (iTRACC) trial. They included 252 children: 127 in the control group and 125 in the intervention group.

Patients in the intervention group received Propeller Health’s Food and Drug Administration–cleared inhaler sensors for inhaled corticosteroids and short-acting beta-agonists. Caregivers could use a mobile application and clinicians could use a Web portal to track patients’ medication use. The app featured personalized insights, educational content, encouragement, surveys, and care team services.

Researchers recruited caregivers and children from five Chicago clinics for the study, which was conducted between 2016 and 2018. They included children aged 4-17 years who had a prescription for daily inhaled corticosteroids for at least 1 year before enrollment. In addition, participants had at least 1 exacerbation requiring oral corticosteroids in the previous year. They excluded children with other respiratory conditions. They also excluded participants who did not speak English because the app was available only in English.

“Sensors monitored inhaled medication use, capturing the date, time, and number of uses, and transmitted this information via Bluetooth to a paired smartphone and the provider portal in real-time,” the authors said.

Clinicians were alerted to call participants if a patient missed inhaled corticosteroid doses for 4 continuous days or used more than 4 short-acting beta-agonist doses per day. Clinicians could help guide asthma management, schedule an appointment, refill medications, and address technical difficulties with the sensors.

The intervention and control groups had similar baseline characteristics. About one-third of the patients were female, and the mean age was 9.3 years. In the control group, 28% identified as Hispanic, and 33% identified as non-Hispanic Black. In the intervention group, 40% identified as Hispanic, and 23% identified as non-Hispanic Black. About 59% reported Medicaid insurance. The intervention and control arms completed electronic surveys at 1, 3, 6, 9, and 12 months.

Average Asthma Control Test score increased from 19 to 22 in the intervention group, compared with an increase from 19 to 20 in the control group. Adjusted rates of emergency department visits and hospitalizations were greater in the intervention group (incidence rate ratios, 2.2 and 3.4, respectively). A measure of caregiver quality of life was greater in the intervention group, although the difference was not significant.

During the trial, more caregivers in the intervention group reported asthma attacks for which steroids were prescribed by a medical office (73% vs. 35%).

Some participants had to manually enter the number of daily puffs into the app because their inhalers were incompatible with the sensors. In addition, some data were missing because of incomplete or missing survey responses and sensor failure over time. “The number of intervention participants with actively transmitting sensors decreased from 102 at baseline to 56 at 12 months,” Dr. Gupta and associates noted.
 

Important area of research

“One interesting finding of this study is the increase in health care use in the intervention group to nearly twice as many emergency department (ED) visits and three times as many hospitalizations as the control group over 12 months,” Rachelle R. Ramsey, PhD, and Theresa W. Guilbert, MD, MS, of the University of Cincinnati, wrote in a related commentary. “Although it is plausible that, as the authors suggest, greater asthma knowledge and monitoring may have led to increased vigilance of asthma symptoms, it seems that this would have only led to an increase in ED visits but not hospitalizations.”

The mixture of objective electronic monitoring and subjective self-reported adherence may complicate interpretation of the results, they added.

“Overall, this article underscores the feasibility and importance of sensor-based electronic monitoring of adherence in pediatric asthma and encourages future research in this area,” Dr. Ramsey and Dr. Guilbert said.

The trial was supported by the UnitedHealth Group. Dr. Gupta has received grants from the National Institutes of Health, Rho, and other organizations, and has served as a medical consultant and adviser for a variety of companies. Dr. Ramsey is supported by the NIH. Dr. Guilbert reported fees from the American Board of Pediatrics, the Pediatric Pulmonary Subboard, and some pharmaceutical companies, plus grants from the NIH, grants and personal fees from Sanofi, Regeneron, and AstraZeneca, and royalties from UpToDate.

jremaly@mdedge.com

SOURCE: Gupta RS et al. Pediatrics. 2020 Dec 22. doi: 10.1542/peds.2020-1330.

Among children with moderate or severe persistent asthma, monitoring daily inhaler use with sensors and a mobile application may improve asthma symptom control and caregiver quality of life, a randomized trial suggests.

But the intervention also may lead to more ED visits and increased hospitalization rates.

“We improved asthma symptom control but did not reduce health care use,” Ruchi S. Gupta, MD, MPH, and colleagues, wrote in a study published in Pediatrics.

The monitoring system alerted clinicians when a patient used a short-acting beta-agonist more than four times in a day. It could be that the “alerts enabled providers to detect asthma exacerbation virtually and refer for clinically appropriate care that included directing children to the ED,” the authors suggested. It also is possible that the intervention led caregivers to be more vigilant about symptoms and more empowered to seek care.
 

Adherence to preventive regimens

Many patients with asthma need to use preventive medications such as daily inhaled corticosteroids to control symptoms. Researchers have developed sensor-based inhaler monitoring interventions to improve treatment adherence, but the effectiveness of these interventions in improving asthma outcomes in urban and minority populations is unclear.

To assess the effectiveness of a clinically integrated, sensor-based inhaler monitoring intervention on improving asthma symptom control and related outcomes in children, Dr. Gupta, of Northwestern University and Ann & Robert H. Lurie Children’s Hospital of Chicago, and colleagues conducted a randomized, unblinded study, known as the Improving Technology-Assisted Recording of Asthma Control in Children (iTRACC) trial. They included 252 children: 127 in the control group and 125 in the intervention group.

Patients in the intervention group received Propeller Health’s Food and Drug Administration–cleared inhaler sensors for inhaled corticosteroids and short-acting beta-agonists. Caregivers could use a mobile application and clinicians could use a Web portal to track patients’ medication use. The app featured personalized insights, educational content, encouragement, surveys, and care team services.

Researchers recruited caregivers and children from five Chicago clinics for the study, which was conducted between 2016 and 2018. They included children aged 4-17 years who had a prescription for daily inhaled corticosteroids for at least 1 year before enrollment. In addition, participants had at least 1 exacerbation requiring oral corticosteroids in the previous year. They excluded children with other respiratory conditions. They also excluded participants who did not speak English because the app was available only in English.

“Sensors monitored inhaled medication use, capturing the date, time, and number of uses, and transmitted this information via Bluetooth to a paired smartphone and the provider portal in real-time,” the authors said.

Clinicians were alerted to call participants if a patient missed inhaled corticosteroid doses for 4 continuous days or used more than 4 short-acting beta-agonist doses per day. Clinicians could help guide asthma management, schedule an appointment, refill medications, and address technical difficulties with the sensors.

The intervention and control groups had similar baseline characteristics. About one-third of the patients were female, and the mean age was 9.3 years. In the control group, 28% identified as Hispanic, and 33% identified as non-Hispanic Black. In the intervention group, 40% identified as Hispanic, and 23% identified as non-Hispanic Black. About 59% reported Medicaid insurance. The intervention and control arms completed electronic surveys at 1, 3, 6, 9, and 12 months.

Average Asthma Control Test score increased from 19 to 22 in the intervention group, compared with an increase from 19 to 20 in the control group. Adjusted rates of emergency department visits and hospitalizations were greater in the intervention group (incidence rate ratios, 2.2 and 3.4, respectively). A measure of caregiver quality of life was greater in the intervention group, although the difference was not significant.

During the trial, more caregivers in the intervention group reported asthma attacks for which steroids were prescribed by a medical office (73% vs. 35%).

Some participants had to manually enter the number of daily puffs into the app because their inhalers were incompatible with the sensors. In addition, some data were missing because of incomplete or missing survey responses and sensor failure over time. “The number of intervention participants with actively transmitting sensors decreased from 102 at baseline to 56 at 12 months,” Dr. Gupta and associates noted.
 

Important area of research

“One interesting finding of this study is the increase in health care use in the intervention group to nearly twice as many emergency department (ED) visits and three times as many hospitalizations as the control group over 12 months,” Rachelle R. Ramsey, PhD, and Theresa W. Guilbert, MD, MS, of the University of Cincinnati, wrote in a related commentary. “Although it is plausible that, as the authors suggest, greater asthma knowledge and monitoring may have led to increased vigilance of asthma symptoms, it seems that this would have only led to an increase in ED visits but not hospitalizations.”

The mixture of objective electronic monitoring and subjective self-reported adherence may complicate interpretation of the results, they added.

“Overall, this article underscores the feasibility and importance of sensor-based electronic monitoring of adherence in pediatric asthma and encourages future research in this area,” Dr. Ramsey and Dr. Guilbert said.

The trial was supported by the UnitedHealth Group. Dr. Gupta has received grants from the National Institutes of Health, Rho, and other organizations, and has served as a medical consultant and adviser for a variety of companies. Dr. Ramsey is supported by the NIH. Dr. Guilbert reported fees from the American Board of Pediatrics, the Pediatric Pulmonary Subboard, and some pharmaceutical companies, plus grants from the NIH, grants and personal fees from Sanofi, Regeneron, and AstraZeneca, and royalties from UpToDate.

jremaly@mdedge.com

SOURCE: Gupta RS et al. Pediatrics. 2020 Dec 22. doi: 10.1542/peds.2020-1330.

Among children with moderate or severe persistent asthma, monitoring daily inhaler use with sensors and a mobile application may improve asthma symptom control and caregiver quality of life, a randomized trial suggests.

But the intervention also may lead to more ED visits and increased hospitalization rates.

“We improved asthma symptom control but did not reduce health care use,” Ruchi S. Gupta, MD, MPH, and colleagues, wrote in a study published in Pediatrics.

The monitoring system alerted clinicians when a patient used a short-acting beta-agonist more than four times in a day. It could be that the “alerts enabled providers to detect asthma exacerbation virtually and refer for clinically appropriate care that included directing children to the ED,” the authors suggested. It also is possible that the intervention led caregivers to be more vigilant about symptoms and more empowered to seek care.
 

Adherence to preventive regimens

Many patients with asthma need to use preventive medications such as daily inhaled corticosteroids to control symptoms. Researchers have developed sensor-based inhaler monitoring interventions to improve treatment adherence, but the effectiveness of these interventions in improving asthma outcomes in urban and minority populations is unclear.

To assess the effectiveness of a clinically integrated, sensor-based inhaler monitoring intervention on improving asthma symptom control and related outcomes in children, Dr. Gupta, of Northwestern University and Ann & Robert H. Lurie Children’s Hospital of Chicago, and colleagues conducted a randomized, unblinded study, known as the Improving Technology-Assisted Recording of Asthma Control in Children (iTRACC) trial. They included 252 children: 127 in the control group and 125 in the intervention group.

Patients in the intervention group received Propeller Health’s Food and Drug Administration–cleared inhaler sensors for inhaled corticosteroids and short-acting beta-agonists. Caregivers could use a mobile application and clinicians could use a Web portal to track patients’ medication use. The app featured personalized insights, educational content, encouragement, surveys, and care team services.

Researchers recruited caregivers and children from five Chicago clinics for the study, which was conducted between 2016 and 2018. They included children aged 4-17 years who had a prescription for daily inhaled corticosteroids for at least 1 year before enrollment. In addition, participants had at least 1 exacerbation requiring oral corticosteroids in the previous year. They excluded children with other respiratory conditions. They also excluded participants who did not speak English because the app was available only in English.

“Sensors monitored inhaled medication use, capturing the date, time, and number of uses, and transmitted this information via Bluetooth to a paired smartphone and the provider portal in real-time,” the authors said.

Clinicians were alerted to call participants if a patient missed inhaled corticosteroid doses for 4 continuous days or used more than 4 short-acting beta-agonist doses per day. Clinicians could help guide asthma management, schedule an appointment, refill medications, and address technical difficulties with the sensors.

The intervention and control groups had similar baseline characteristics. About one-third of the patients were female, and the mean age was 9.3 years. In the control group, 28% identified as Hispanic, and 33% identified as non-Hispanic Black. In the intervention group, 40% identified as Hispanic, and 23% identified as non-Hispanic Black. About 59% reported Medicaid insurance. The intervention and control arms completed electronic surveys at 1, 3, 6, 9, and 12 months.

Average Asthma Control Test score increased from 19 to 22 in the intervention group, compared with an increase from 19 to 20 in the control group. Adjusted rates of emergency department visits and hospitalizations were greater in the intervention group (incidence rate ratios, 2.2 and 3.4, respectively). A measure of caregiver quality of life was greater in the intervention group, although the difference was not significant.

During the trial, more caregivers in the intervention group reported asthma attacks for which steroids were prescribed by a medical office (73% vs. 35%).

Some participants had to manually enter the number of daily puffs into the app because their inhalers were incompatible with the sensors. In addition, some data were missing because of incomplete or missing survey responses and sensor failure over time. “The number of intervention participants with actively transmitting sensors decreased from 102 at baseline to 56 at 12 months,” Dr. Gupta and associates noted.
 

Important area of research

“One interesting finding of this study is the increase in health care use in the intervention group to nearly twice as many emergency department (ED) visits and three times as many hospitalizations as the control group over 12 months,” Rachelle R. Ramsey, PhD, and Theresa W. Guilbert, MD, MS, of the University of Cincinnati, wrote in a related commentary. “Although it is plausible that, as the authors suggest, greater asthma knowledge and monitoring may have led to increased vigilance of asthma symptoms, it seems that this would have only led to an increase in ED visits but not hospitalizations.”

The mixture of objective electronic monitoring and subjective self-reported adherence may complicate interpretation of the results, they added.

“Overall, this article underscores the feasibility and importance of sensor-based electronic monitoring of adherence in pediatric asthma and encourages future research in this area,” Dr. Ramsey and Dr. Guilbert said.

The trial was supported by the UnitedHealth Group. Dr. Gupta has received grants from the National Institutes of Health, Rho, and other organizations, and has served as a medical consultant and adviser for a variety of companies. Dr. Ramsey is supported by the NIH. Dr. Guilbert reported fees from the American Board of Pediatrics, the Pediatric Pulmonary Subboard, and some pharmaceutical companies, plus grants from the NIH, grants and personal fees from Sanofi, Regeneron, and AstraZeneca, and royalties from UpToDate.

jremaly@mdedge.com

SOURCE: Gupta RS et al. Pediatrics. 2020 Dec 22. doi: 10.1542/peds.2020-1330.

Evidence continues to accumulate linking e-cigarettes to a range of lung diseases.

ArminStautBerlin/Thinkstock

Results from a large national prospective cohort study of adults demonstrated that the use of electronic cigarettes is associated with an increased risk of asthma, chronic obstructive pulmonary disease (COPD), emphysema, and chronic bronchitis – independent of cigarette smoking and other combustible tobacco product use.

“Our longitudinal results are consistent with the findings of prior population studies,” researchers led by Wubin Xie, DrPH, MPH, wrote in a study published online in JAMA Network Open. “With a more refined study design assessing multiple respiratory conditions and extensive sensitivity checks to mitigate bias from reverse causation and residual confounding by cigarette smoking and other tobacco product use, our results strengthen the evidence of the potential role of e-cigarette use in pulmonary disease pathogenesis. The findings may be used to inform counseling of patients on the potential risks of e-cigarette use.”

Dr. Xie of Boston University, and colleagues used data from the Population Assessment of Tobacco and Health (PATH) study waves 1-4 to examine the association of e-cigarette use with incident respiratory conditions, including COPD, emphysema, chronic bronchitis, and asthma. An earlier analysis of PATH data found an association between e-cigarette use with a composite respiratory disease outcome, but it did not consider the timing of respiratory events over follow-up and was underpowered to evaluate specific respiratory conditions.

The current analysis included data from 21,618 U.S. adults who were surveyed in four waves of PATH between 2013 and 2018. Of these, 49% were men, 65% were non-Hispanic White, 12% were non-Hispanic Black, 16% were Hispanic, and the remainder were non-Hispanic other. Their mean pack-years was 6.7 at baseline, 26% had self-reported hypertension, and their mean body mass index was 27.8 kg/m². The analysis was limited to data from the wave 1 cohort of adults and the prospective follow-up at waves 2-4 from public use files. It excluded adults who reported a history of a respiratory condition such as COPD, emphysema, chronic bronchitis, or asthma at wave 1 (baseline).

Two-thirds of respondents (66%) were never e-cigarette users, 12% were former e-cigarette users, and 5% were current e-cigarette users. After the researchers adjusted for cigarette and other combustible tobacco product use, demographic characteristics, and chronic health conditions, they observed an increased risk of respiratory disease among former e-cigarette users (incidence rate ratio, 1.28) and current e-cigarette users (IRR, 1.31). Among respondents with good self-reported health, the IRR for former e-cigarette users was 1.21 and the IRR for current e-cigarette users was 1.43. As for specific respiratory diseases among current e-cigarette users, the IRR was 1.33 for chronic bronchitis, 1.69 for emphysema, 1.57 for COPD, and 1.31 for asthma.

“Our findings on clinical outcome were consistent with studies assessing in vivo biomarkers of e-cigarette exposure in animal subjects, human participants, and population studies,” the authors wrote. “Studies have documented that exclusive e-cigarette use may be associated with higher exposure to harmful and potentially harmful constituents, compared with tobacco nonuse. The potential mechanisms of the association of e-cigarette exposure with pulmonary diseases include pulmonary inflammation, increased oxidative stress, and inhibited immune response. Animal studies have generated substantial evidence on e-cigarette exposure and emphysematous lung destruction, loss of pulmonary capillaries, reduced small airway function, and airway hyperresponsiveness, suggesting the plausibility of e-cigarettes causing chronic lung diseases.”

They acknowledged certain limitations of the study, including its reliance on self-reported measures of e-cigarette and other tobacco product use and its reliance on self-reported diagnoses of respiratory diseases.

The study was supported by grants from the National Heart, Lung, and Blood Institute; the Food and Drug Administration Center for Tobacco Products; and the American Lung Association Public Policy Research Award. Dr. Xie reported having no financial disclosures. His coauthors reported having received research grants and personal fees from a variety of sources.

SOURCE: Xie W et al. JAMA Netw Open. 2020 Nov 12. doi: 10.1001/jamanetworkopen.2020.20816

Evidence continues to accumulate linking e-cigarettes to a range of lung diseases.

ArminStautBerlin/Thinkstock

Results from a large national prospective cohort study of adults demonstrated that the use of electronic cigarettes is associated with an increased risk of asthma, chronic obstructive pulmonary disease (COPD), emphysema, and chronic bronchitis – independent of cigarette smoking and other combustible tobacco product use.

“Our longitudinal results are consistent with the findings of prior population studies,” researchers led by Wubin Xie, DrPH, MPH, wrote in a study published online in JAMA Network Open. “With a more refined study design assessing multiple respiratory conditions and extensive sensitivity checks to mitigate bias from reverse causation and residual confounding by cigarette smoking and other tobacco product use, our results strengthen the evidence of the potential role of e-cigarette use in pulmonary disease pathogenesis. The findings may be used to inform counseling of patients on the potential risks of e-cigarette use.”

Dr. Xie of Boston University, and colleagues used data from the Population Assessment of Tobacco and Health (PATH) study waves 1-4 to examine the association of e-cigarette use with incident respiratory conditions, including COPD, emphysema, chronic bronchitis, and asthma. An earlier analysis of PATH data found an association between e-cigarette use with a composite respiratory disease outcome, but it did not consider the timing of respiratory events over follow-up and was underpowered to evaluate specific respiratory conditions.

The current analysis included data from 21,618 U.S. adults who were surveyed in four waves of PATH between 2013 and 2018. Of these, 49% were men, 65% were non-Hispanic White, 12% were non-Hispanic Black, 16% were Hispanic, and the remainder were non-Hispanic other. Their mean pack-years was 6.7 at baseline, 26% had self-reported hypertension, and their mean body mass index was 27.8 kg/m². The analysis was limited to data from the wave 1 cohort of adults and the prospective follow-up at waves 2-4 from public use files. It excluded adults who reported a history of a respiratory condition such as COPD, emphysema, chronic bronchitis, or asthma at wave 1 (baseline).

Two-thirds of respondents (66%) were never e-cigarette users, 12% were former e-cigarette users, and 5% were current e-cigarette users. After the researchers adjusted for cigarette and other combustible tobacco product use, demographic characteristics, and chronic health conditions, they observed an increased risk of respiratory disease among former e-cigarette users (incidence rate ratio, 1.28) and current e-cigarette users (IRR, 1.31). Among respondents with good self-reported health, the IRR for former e-cigarette users was 1.21 and the IRR for current e-cigarette users was 1.43. As for specific respiratory diseases among current e-cigarette users, the IRR was 1.33 for chronic bronchitis, 1.69 for emphysema, 1.57 for COPD, and 1.31 for asthma.

“Our findings on clinical outcome were consistent with studies assessing in vivo biomarkers of e-cigarette exposure in animal subjects, human participants, and population studies,” the authors wrote. “Studies have documented that exclusive e-cigarette use may be associated with higher exposure to harmful and potentially harmful constituents, compared with tobacco nonuse. The potential mechanisms of the association of e-cigarette exposure with pulmonary diseases include pulmonary inflammation, increased oxidative stress, and inhibited immune response. Animal studies have generated substantial evidence on e-cigarette exposure and emphysematous lung destruction, loss of pulmonary capillaries, reduced small airway function, and airway hyperresponsiveness, suggesting the plausibility of e-cigarettes causing chronic lung diseases.”

They acknowledged certain limitations of the study, including its reliance on self-reported measures of e-cigarette and other tobacco product use and its reliance on self-reported diagnoses of respiratory diseases.

The study was supported by grants from the National Heart, Lung, and Blood Institute; the Food and Drug Administration Center for Tobacco Products; and the American Lung Association Public Policy Research Award. Dr. Xie reported having no financial disclosures. His coauthors reported having received research grants and personal fees from a variety of sources.

SOURCE: Xie W et al. JAMA Netw Open. 2020 Nov 12. doi: 10.1001/jamanetworkopen.2020.20816

Evidence continues to accumulate linking e-cigarettes to a range of lung diseases.

ArminStautBerlin/Thinkstock

Results from a large national prospective cohort study of adults demonstrated that the use of electronic cigarettes is associated with an increased risk of asthma, chronic obstructive pulmonary disease (COPD), emphysema, and chronic bronchitis – independent of cigarette smoking and other combustible tobacco product use.

“Our longitudinal results are consistent with the findings of prior population studies,” researchers led by Wubin Xie, DrPH, MPH, wrote in a study published online in JAMA Network Open. “With a more refined study design assessing multiple respiratory conditions and extensive sensitivity checks to mitigate bias from reverse causation and residual confounding by cigarette smoking and other tobacco product use, our results strengthen the evidence of the potential role of e-cigarette use in pulmonary disease pathogenesis. The findings may be used to inform counseling of patients on the potential risks of e-cigarette use.”

Dr. Xie of Boston University, and colleagues used data from the Population Assessment of Tobacco and Health (PATH) study waves 1-4 to examine the association of e-cigarette use with incident respiratory conditions, including COPD, emphysema, chronic bronchitis, and asthma. An earlier analysis of PATH data found an association between e-cigarette use with a composite respiratory disease outcome, but it did not consider the timing of respiratory events over follow-up and was underpowered to evaluate specific respiratory conditions.

The current analysis included data from 21,618 U.S. adults who were surveyed in four waves of PATH between 2013 and 2018. Of these, 49% were men, 65% were non-Hispanic White, 12% were non-Hispanic Black, 16% were Hispanic, and the remainder were non-Hispanic other. Their mean pack-years was 6.7 at baseline, 26% had self-reported hypertension, and their mean body mass index was 27.8 kg/m². The analysis was limited to data from the wave 1 cohort of adults and the prospective follow-up at waves 2-4 from public use files. It excluded adults who reported a history of a respiratory condition such as COPD, emphysema, chronic bronchitis, or asthma at wave 1 (baseline).

Two-thirds of respondents (66%) were never e-cigarette users, 12% were former e-cigarette users, and 5% were current e-cigarette users. After the researchers adjusted for cigarette and other combustible tobacco product use, demographic characteristics, and chronic health conditions, they observed an increased risk of respiratory disease among former e-cigarette users (incidence rate ratio, 1.28) and current e-cigarette users (IRR, 1.31). Among respondents with good self-reported health, the IRR for former e-cigarette users was 1.21 and the IRR for current e-cigarette users was 1.43. As for specific respiratory diseases among current e-cigarette users, the IRR was 1.33 for chronic bronchitis, 1.69 for emphysema, 1.57 for COPD, and 1.31 for asthma.

“Our findings on clinical outcome were consistent with studies assessing in vivo biomarkers of e-cigarette exposure in animal subjects, human participants, and population studies,” the authors wrote. “Studies have documented that exclusive e-cigarette use may be associated with higher exposure to harmful and potentially harmful constituents, compared with tobacco nonuse. The potential mechanisms of the association of e-cigarette exposure with pulmonary diseases include pulmonary inflammation, increased oxidative stress, and inhibited immune response. Animal studies have generated substantial evidence on e-cigarette exposure and emphysematous lung destruction, loss of pulmonary capillaries, reduced small airway function, and airway hyperresponsiveness, suggesting the plausibility of e-cigarettes causing chronic lung diseases.”

They acknowledged certain limitations of the study, including its reliance on self-reported measures of e-cigarette and other tobacco product use and its reliance on self-reported diagnoses of respiratory diseases.

The study was supported by grants from the National Heart, Lung, and Blood Institute; the Food and Drug Administration Center for Tobacco Products; and the American Lung Association Public Policy Research Award. Dr. Xie reported having no financial disclosures. His coauthors reported having received research grants and personal fees from a variety of sources.

SOURCE: Xie W et al. JAMA Netw Open. 2020 Nov 12. doi: 10.1001/jamanetworkopen.2020.20816

A long-awaited update to asthma management guidelines, developed by an expert panel at the National Heart, Lung, and Blood Institute, has been released.

Courtesy University of Wisconsin Health System

The updated guidelines address six priority topics, including refined recommendations for the use of fractional exhaled nitric oxide (FeNO) testing, intermittent inhaled corticosteroids (ICS), long-acting muscarinic antagonists (LAMA), and bronchial thermoplasty, but notably exclude any recommendations for the use of fast-emerging biological therapy.

“Biological therapy is the major step forward,” said William W. Busse, MD, professor of allergy and immunology at the University of Wisconsin–Madison, and lead author of the previous guidelines (Bethesda, Md.: NHLBI, 2007). “It wasn’t within the scope of work, so it’s not a criticism, but it is an important shortcoming,” he said. The omission identifies the need for the next update. “This is an area that has to be dealt with,” Dr. Busse stated in an interview.

Including biologic agents would have delayed the release of the recommendations for another year or 2, wrote the expert panel working group of the NHLBI, “and this was felt to be unacceptable.” The working group, overseen by the National Asthma Education and Prevention Program Coordinating Committee, also acknowledged the update is “not a complete revision” of the 2007 guidelines.

The update provides an evidenced-based review of six key topics in asthma care, as Mary Cataletto, MD, FCCP, professor of pediatrics at New York University Long Island, Mineola, pointed out: use of FeNO, indoor allergen mitigation, use of intermittent ICS and LAMA for asthma, role of subcutaneous and sublingual immunotherapy in the treatment of allergic asthma, and the use of bronchial thermoplasty.

“It has been 13 years since the last update and substantial progress has been made since then in understanding how to best treat children and adults with asthma,” said working group member Michael Schatz, MD, MS, FCCP, an allergy specialist at Kaiser Permanente Medical Center in San Diego.

According to Dr. Schatz, the most important updated recommendations are:

• Conditional recommendation for the use of ICS in children aged infant to 4 years with recurrent wheezing with respiratory infections.
• Use of combination ICS-formoterol for maintenance and to relieve flares in patients with moderate to severe asthma.
• Addition of the LAMA inhaled bronchodilator as add-on therapy for severe asthma not controlled by long-acting beta-agonist (LABA)/ICS combination medications.

Another important update, Dr. Cataletto said, is “shared decision-making among members of asthma teams in order to improve asthma care across all age groups.”

In all, the update includes 19 recommendations in the six subject areas. Each recommendation is notated with two values: its strength, either strong or conditional, and the certainty of evidence behind it, either low, moderate, or high. For example, the recommendation for ICS in young children that Dr. Schatz referred to has a conditional strength of recommendation with moderate certainty of evidence.

Using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology to determine strength of recommendation is a notable innovation of the latest guidelines, Dr. Busse noted.

Recommendations (strength of recommendation/certainty of evidence) include:

• Use of FeNO in children and adults when the asthma diagnosis is uncertain (conditional/moderate) or in those with allergic asthma and an uncertain course of management (conditional/low).
• Avoid standalone FeNO to evaluate asthma control or the likelihood or severity of future exacerbations, or for in infants to 4-year-olds with recurrent wheezing (strong/low for both).
• Avoid allergen mitigation in routine asthma management for patients who don’t have sensitivity to specific indoor allergens (conditional/low).
• Multicomponent allergen-specific mitigation when specific allergen sensitivity has been identified and pest management alone for symptoms related to specific pest exposure (conditional/low for both).
• Impermeable bedding covers should be part of a multicomponent mitigation strategy, not as a standalone tool, for patients with asthma and dust mite sensitivity (conditional/moderate).
• Daily ICS at onset of a respiratory tract infection along with as-needed short-acting beta-agonists in children aged 4 years and younger with recurrent wheezing but no wheezing between infections rather than as-needed standalone SABA (conditional/high).
• For adults and children aged 12 years and older with mild persistent asthma, either daily low-dose ICS with as-needed SABA or as-needed ICS and SABA concomitantly (conditional/moderate).
• Avoid short-course increased ICS dosing for patients aged 4 years and older with good adherence to daily ICS therapy (conditional/low).
• For patients aged 4 years and older with moderate to severe persistent asthma, a preference for combined ICS-formoterol inhaler over higher dose ICS daily and intermittent SABA or daily ICS-LABA with intermittent SABA (strong/high [aged 12 years and older]; moderate [aged 4-11 years]).
• A preference for combined ICS-formoterol for both daily and relief therapy for patients 12 years and older with severe persistent asthma over higher-dose ICS-LABA daily and intermittent SABA (conditional/high).
• A preference for adding LABA rather than LAMA to ICS in patients aged 12 years and older with uncontrolled persistent asthma (conditional/moderate).
• If LABA isn’t used, add LAMA to ICS in patients aged 12 years and older with uncontrolled persistent asthma rather than continuing the same dose of ICS alone (conditional/moderate).
• In those same patients already on combined ICS-LABA therapy, add LAMA rather than continuing the same dose of ICS-LABA (conditional/moderate).
• Use subcutaneous immunotherapy as a potential adjunct to standard drug therapy in patients aged 5 years and older with mild to moderate allergic asthma when their asthma is controlled on immunotherapy (conditional/moderate).
• Avoid sublingual immunotherapy in patients with persistent allergic asthma (conditional/moderate).
• Avoid bronchial thermoplasty in those 18 years and older with persistent asthma, but consider it in patients who can accept the short-term worsening symptoms or unknown long-term side effects in exchange for the potential benefits (conditional/moderate).

One of the key elements of the guidelines is the use of the SMART (single maintenance and reliever therapy) approach to evaluate the comparative effectiveness of intermittent ICS with formoterol, Dr. Busse noted. “I think that’s a very significant advance. The literature is replete with evidence to support this. Secondly, it really makes life convenient for patients; you have one inhaler.”

The recommendation on SABA use is also significant, Dr. Busse said. “Data have emerged to suggest that if you’re having a need for one of these rescue medications, it’s due to an increase in inflammation in the lower airway, and you want to give an ICS which will act on the inflammation along with the bronchodilator. That’s a new concept, and it’s a very significant step forward.”

Dr. Schatz disclosed financial relationships with Merck, Teva, and ALK-Abello, but was recused from the writing, discussion, and voting related to the immunotherapy recommendation. Dr. Cataletto and Dr. Busse have no relevant relationships to disclose.

SOURCE: Schatz M et al. J Allergy Clin Immunol. 2020;146:1217-70.

A long-awaited update to asthma management guidelines, developed by an expert panel at the National Heart, Lung, and Blood Institute, has been released.

Courtesy University of Wisconsin Health System

The updated guidelines address six priority topics, including refined recommendations for the use of fractional exhaled nitric oxide (FeNO) testing, intermittent inhaled corticosteroids (ICS), long-acting muscarinic antagonists (LAMA), and bronchial thermoplasty, but notably exclude any recommendations for the use of fast-emerging biological therapy.

“Biological therapy is the major step forward,” said William W. Busse, MD, professor of allergy and immunology at the University of Wisconsin–Madison, and lead author of the previous guidelines (Bethesda, Md.: NHLBI, 2007). “It wasn’t within the scope of work, so it’s not a criticism, but it is an important shortcoming,” he said. The omission identifies the need for the next update. “This is an area that has to be dealt with,” Dr. Busse stated in an interview.

Including biologic agents would have delayed the release of the recommendations for another year or 2, wrote the expert panel working group of the NHLBI, “and this was felt to be unacceptable.” The working group, overseen by the National Asthma Education and Prevention Program Coordinating Committee, also acknowledged the update is “not a complete revision” of the 2007 guidelines.

The update provides an evidenced-based review of six key topics in asthma care, as Mary Cataletto, MD, FCCP, professor of pediatrics at New York University Long Island, Mineola, pointed out: use of FeNO, indoor allergen mitigation, use of intermittent ICS and LAMA for asthma, role of subcutaneous and sublingual immunotherapy in the treatment of allergic asthma, and the use of bronchial thermoplasty.

“It has been 13 years since the last update and substantial progress has been made since then in understanding how to best treat children and adults with asthma,” said working group member Michael Schatz, MD, MS, FCCP, an allergy specialist at Kaiser Permanente Medical Center in San Diego.

According to Dr. Schatz, the most important updated recommendations are:

• Conditional recommendation for the use of ICS in children aged infant to 4 years with recurrent wheezing with respiratory infections.
• Use of combination ICS-formoterol for maintenance and to relieve flares in patients with moderate to severe asthma.
• Addition of the LAMA inhaled bronchodilator as add-on therapy for severe asthma not controlled by long-acting beta-agonist (LABA)/ICS combination medications.

Another important update, Dr. Cataletto said, is “shared decision-making among members of asthma teams in order to improve asthma care across all age groups.”

In all, the update includes 19 recommendations in the six subject areas. Each recommendation is notated with two values: its strength, either strong or conditional, and the certainty of evidence behind it, either low, moderate, or high. For example, the recommendation for ICS in young children that Dr. Schatz referred to has a conditional strength of recommendation with moderate certainty of evidence.

Using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology to determine strength of recommendation is a notable innovation of the latest guidelines, Dr. Busse noted.

Recommendations (strength of recommendation/certainty of evidence) include:

• Use of FeNO in children and adults when the asthma diagnosis is uncertain (conditional/moderate) or in those with allergic asthma and an uncertain course of management (conditional/low).
• Avoid standalone FeNO to evaluate asthma control or the likelihood or severity of future exacerbations, or for in infants to 4-year-olds with recurrent wheezing (strong/low for both).
• Avoid allergen mitigation in routine asthma management for patients who don’t have sensitivity to specific indoor allergens (conditional/low).
• Multicomponent allergen-specific mitigation when specific allergen sensitivity has been identified and pest management alone for symptoms related to specific pest exposure (conditional/low for both).
• Impermeable bedding covers should be part of a multicomponent mitigation strategy, not as a standalone tool, for patients with asthma and dust mite sensitivity (conditional/moderate).
• Daily ICS at onset of a respiratory tract infection along with as-needed short-acting beta-agonists in children aged 4 years and younger with recurrent wheezing but no wheezing between infections rather than as-needed standalone SABA (conditional/high).
• For adults and children aged 12 years and older with mild persistent asthma, either daily low-dose ICS with as-needed SABA or as-needed ICS and SABA concomitantly (conditional/moderate).
• Avoid short-course increased ICS dosing for patients aged 4 years and older with good adherence to daily ICS therapy (conditional/low).
• For patients aged 4 years and older with moderate to severe persistent asthma, a preference for combined ICS-formoterol inhaler over higher dose ICS daily and intermittent SABA or daily ICS-LABA with intermittent SABA (strong/high [aged 12 years and older]; moderate [aged 4-11 years]).
• A preference for combined ICS-formoterol for both daily and relief therapy for patients 12 years and older with severe persistent asthma over higher-dose ICS-LABA daily and intermittent SABA (conditional/high).
• A preference for adding LABA rather than LAMA to ICS in patients aged 12 years and older with uncontrolled persistent asthma (conditional/moderate).
• If LABA isn’t used, add LAMA to ICS in patients aged 12 years and older with uncontrolled persistent asthma rather than continuing the same dose of ICS alone (conditional/moderate).
• In those same patients already on combined ICS-LABA therapy, add LAMA rather than continuing the same dose of ICS-LABA (conditional/moderate).
• Use subcutaneous immunotherapy as a potential adjunct to standard drug therapy in patients aged 5 years and older with mild to moderate allergic asthma when their asthma is controlled on immunotherapy (conditional/moderate).
• Avoid sublingual immunotherapy in patients with persistent allergic asthma (conditional/moderate).
• Avoid bronchial thermoplasty in those 18 years and older with persistent asthma, but consider it in patients who can accept the short-term worsening symptoms or unknown long-term side effects in exchange for the potential benefits (conditional/moderate).

One of the key elements of the guidelines is the use of the SMART (single maintenance and reliever therapy) approach to evaluate the comparative effectiveness of intermittent ICS with formoterol, Dr. Busse noted. “I think that’s a very significant advance. The literature is replete with evidence to support this. Secondly, it really makes life convenient for patients; you have one inhaler.”

The recommendation on SABA use is also significant, Dr. Busse said. “Data have emerged to suggest that if you’re having a need for one of these rescue medications, it’s due to an increase in inflammation in the lower airway, and you want to give an ICS which will act on the inflammation along with the bronchodilator. That’s a new concept, and it’s a very significant step forward.”

Dr. Schatz disclosed financial relationships with Merck, Teva, and ALK-Abello, but was recused from the writing, discussion, and voting related to the immunotherapy recommendation. Dr. Cataletto and Dr. Busse have no relevant relationships to disclose.

SOURCE: Schatz M et al. J Allergy Clin Immunol. 2020;146:1217-70.

A long-awaited update to asthma management guidelines, developed by an expert panel at the National Heart, Lung, and Blood Institute, has been released.

Courtesy University of Wisconsin Health System

The updated guidelines address six priority topics, including refined recommendations for the use of fractional exhaled nitric oxide (FeNO) testing, intermittent inhaled corticosteroids (ICS), long-acting muscarinic antagonists (LAMA), and bronchial thermoplasty, but notably exclude any recommendations for the use of fast-emerging biological therapy.

“Biological therapy is the major step forward,” said William W. Busse, MD, professor of allergy and immunology at the University of Wisconsin–Madison, and lead author of the previous guidelines (Bethesda, Md.: NHLBI, 2007). “It wasn’t within the scope of work, so it’s not a criticism, but it is an important shortcoming,” he said. The omission identifies the need for the next update. “This is an area that has to be dealt with,” Dr. Busse stated in an interview.

Including biologic agents would have delayed the release of the recommendations for another year or 2, wrote the expert panel working group of the NHLBI, “and this was felt to be unacceptable.” The working group, overseen by the National Asthma Education and Prevention Program Coordinating Committee, also acknowledged the update is “not a complete revision” of the 2007 guidelines.

The update provides an evidenced-based review of six key topics in asthma care, as Mary Cataletto, MD, FCCP, professor of pediatrics at New York University Long Island, Mineola, pointed out: use of FeNO, indoor allergen mitigation, use of intermittent ICS and LAMA for asthma, role of subcutaneous and sublingual immunotherapy in the treatment of allergic asthma, and the use of bronchial thermoplasty.

“It has been 13 years since the last update and substantial progress has been made since then in understanding how to best treat children and adults with asthma,” said working group member Michael Schatz, MD, MS, FCCP, an allergy specialist at Kaiser Permanente Medical Center in San Diego.

According to Dr. Schatz, the most important updated recommendations are:

• Conditional recommendation for the use of ICS in children aged infant to 4 years with recurrent wheezing with respiratory infections.
• Use of combination ICS-formoterol for maintenance and to relieve flares in patients with moderate to severe asthma.
• Addition of the LAMA inhaled bronchodilator as add-on therapy for severe asthma not controlled by long-acting beta-agonist (LABA)/ICS combination medications.

Another important update, Dr. Cataletto said, is “shared decision-making among members of asthma teams in order to improve asthma care across all age groups.”

In all, the update includes 19 recommendations in the six subject areas. Each recommendation is notated with two values: its strength, either strong or conditional, and the certainty of evidence behind it, either low, moderate, or high. For example, the recommendation for ICS in young children that Dr. Schatz referred to has a conditional strength of recommendation with moderate certainty of evidence.

Using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology to determine strength of recommendation is a notable innovation of the latest guidelines, Dr. Busse noted.

Recommendations (strength of recommendation/certainty of evidence) include:

• Use of FeNO in children and adults when the asthma diagnosis is uncertain (conditional/moderate) or in those with allergic asthma and an uncertain course of management (conditional/low).
• Avoid standalone FeNO to evaluate asthma control or the likelihood or severity of future exacerbations, or for in infants to 4-year-olds with recurrent wheezing (strong/low for both).
• Avoid allergen mitigation in routine asthma management for patients who don’t have sensitivity to specific indoor allergens (conditional/low).
• Multicomponent allergen-specific mitigation when specific allergen sensitivity has been identified and pest management alone for symptoms related to specific pest exposure (conditional/low for both).
• Impermeable bedding covers should be part of a multicomponent mitigation strategy, not as a standalone tool, for patients with asthma and dust mite sensitivity (conditional/moderate).
• Daily ICS at onset of a respiratory tract infection along with as-needed short-acting beta-agonists in children aged 4 years and younger with recurrent wheezing but no wheezing between infections rather than as-needed standalone SABA (conditional/high).
• For adults and children aged 12 years and older with mild persistent asthma, either daily low-dose ICS with as-needed SABA or as-needed ICS and SABA concomitantly (conditional/moderate).
• Avoid short-course increased ICS dosing for patients aged 4 years and older with good adherence to daily ICS therapy (conditional/low).
• For patients aged 4 years and older with moderate to severe persistent asthma, a preference for combined ICS-formoterol inhaler over higher dose ICS daily and intermittent SABA or daily ICS-LABA with intermittent SABA (strong/high [aged 12 years and older]; moderate [aged 4-11 years]).
• A preference for combined ICS-formoterol for both daily and relief therapy for patients 12 years and older with severe persistent asthma over higher-dose ICS-LABA daily and intermittent SABA (conditional/high).
• A preference for adding LABA rather than LAMA to ICS in patients aged 12 years and older with uncontrolled persistent asthma (conditional/moderate).
• If LABA isn’t used, add LAMA to ICS in patients aged 12 years and older with uncontrolled persistent asthma rather than continuing the same dose of ICS alone (conditional/moderate).
• In those same patients already on combined ICS-LABA therapy, add LAMA rather than continuing the same dose of ICS-LABA (conditional/moderate).
• Use subcutaneous immunotherapy as a potential adjunct to standard drug therapy in patients aged 5 years and older with mild to moderate allergic asthma when their asthma is controlled on immunotherapy (conditional/moderate).
• Avoid sublingual immunotherapy in patients with persistent allergic asthma (conditional/moderate).
• Avoid bronchial thermoplasty in those 18 years and older with persistent asthma, but consider it in patients who can accept the short-term worsening symptoms or unknown long-term side effects in exchange for the potential benefits (conditional/moderate).

One of the key elements of the guidelines is the use of the SMART (single maintenance and reliever therapy) approach to evaluate the comparative effectiveness of intermittent ICS with formoterol, Dr. Busse noted. “I think that’s a very significant advance. The literature is replete with evidence to support this. Secondly, it really makes life convenient for patients; you have one inhaler.”

The recommendation on SABA use is also significant, Dr. Busse said. “Data have emerged to suggest that if you’re having a need for one of these rescue medications, it’s due to an increase in inflammation in the lower airway, and you want to give an ICS which will act on the inflammation along with the bronchodilator. That’s a new concept, and it’s a very significant step forward.”

Dr. Schatz disclosed financial relationships with Merck, Teva, and ALK-Abello, but was recused from the writing, discussion, and voting related to the immunotherapy recommendation. Dr. Cataletto and Dr. Busse have no relevant relationships to disclose.

SOURCE: Schatz M et al. J Allergy Clin Immunol. 2020;146:1217-70.

Medication adherence remains a truly challenging issue. For most chronic diseases, up to 20%-30% of the pills that are prescribed are not taken. In the case of inhalers for asthma and COPD, patients miss over half of the prescribed doses.

There are many things that contribute to the problem of poor adherence, but people often just simply forget. Thankfully, there are tools designed to help remind patients of what they need to take and when. A survey of apps developed to help patients remember to take their medicines found more than 700 available in Apple and Android app stores.¹ Most apps focus on medication alerts, reminders, and medication logs.² A recent review showed that apps have some – yet limited – effectiveness in increasing adherence, with patient self-reported improvements of 7%-40%.³

Another perhaps more promising area of improving adherence involves high-tech advances in the way medications can be taken. Inhalers are a primary target as they are complicated devices. A patient has to breathe in at the correct time after the inhaler is actuated, and the inhaler works optimally only if the rate of inhalation is sufficient to carry the medication into the lungs.

A number of companies have developed attachments for inhalers (and even inhalers themselves) that can record when the medication is taken through a Bluetooth connection to a patient’s smartphone. These can also assess inspiratory flow. Reminders to take the medication are built into the app, and those reminders disappear if the medication is taken. Patients can receive feedback about the quality of their timing and inspiratory rate to maximize medication delivery to the lungs.⁴

We learned long ago that it is difficult to take medications three to four times a day, so extended-release tablets were developed to reduce the frequency to once or twice a day. A great deal of work is now being done behind the scenes to develop medications that decrease the need for patients to remember to take their medications. The best examples of this are the long-acting reversible contraception (LARC) devices, specifically IUDs and Nexplanon. Compared with traditional oral contraceptives that need to be taken daily, LARCs reduce the rate of pregnancy by five- to tenfold.

We also now have medications for osteoporosis that can be taken monthly, or even annually. When bisphosphonates were first developed for osteoporosis prevention, they needed to be taken daily. Then a weekly bisphosphonate was developed. Now there is a once-monthly oral bisphosphonate, Ibandronate, and even a once yearly IV bisphosphonate.

Exciting developments have also occurred in the management of diabetes. We may be tempted to take for granted how once-daily long-acting insulin, which releases insulin slowly over the course of a day, has revolutionized the diabetic treatment since its Food and Drug Administration approval in 2000. Yet progress did not end there. The first GLP-1 receptor agonist for diabetes was approved in 2005 and was a twice-a-day medicine. Shortly afterward, a daily GLP-1 was approved, and now there are three once-weekly GLP-1 receptor agonists.

Several pharmaceutical manufacturers are now working on a once-weekly insulin,⁵ as well as an implantable GLP-1 receptor agonist that will need to be replaced every 6-12 months.⁶ Imagine your patient coming in once a year to replace his or her potent glucose lowering medication – one that offers a low incidence of hypoglycemia, maintains glucose control all year long, and requires no adherence to a complicated medication regimen.

Similar technology is being used to develop a once-yearly anti-HIV prophylactic medication delivery system.⁷ This could help prevent the spread of HIV in areas of the world where it may be difficult for people to take daily medications.⁷

The many technological advances we have described may help us reduce our likelihood of missing a dose of a medication. We are hopeful that progress in this area will continue, and that one day medication adherence will require even less effort from patients than it does today.
 

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

References

1. Tabi K et al. Mobile apps for medication management: Review and analysis. JMIR Mhealth Uhealth. 2019 Sep 7(9):13608.

2. Park JYE et al. Mobile phone apps targeting medication adherence: Quality assessment and content analysis of user reviews. JMIR Mhealth Uhealth. 2019 Jan 31;7(1):e11919.

3. Pérez-Jover V et al. Mobile apps for increasing treatment adherence: Systematic review. J Med Internet Res. 2019;21(6):e12505. doi: 10.2196/12505.

4. 4 Smart inhalers that could be lifesaving for people living with asthma & COPD. MyTherapy, July 11, 2019.

5. Rosenstock J et al. Once-weekly insulin for type 2 diabetes without previous insulin treatment. N Engl J Med. 2020 Sep 22. doi: 10.1056/NEJMoa2022474.

6. GLP-1 agonists: From 2 daily injections to 1 per week and beyond. DiaTribe, Jan. 10, 2018.

7. Long-acting HIV prevention tools. Hiv.gov, July 20, 2019.

Medication adherence remains a truly challenging issue. For most chronic diseases, up to 20%-30% of the pills that are prescribed are not taken. In the case of inhalers for asthma and COPD, patients miss over half of the prescribed doses.

There are many things that contribute to the problem of poor adherence, but people often just simply forget. Thankfully, there are tools designed to help remind patients of what they need to take and when. A survey of apps developed to help patients remember to take their medicines found more than 700 available in Apple and Android app stores.¹ Most apps focus on medication alerts, reminders, and medication logs.² A recent review showed that apps have some – yet limited – effectiveness in increasing adherence, with patient self-reported improvements of 7%-40%.³

Another perhaps more promising area of improving adherence involves high-tech advances in the way medications can be taken. Inhalers are a primary target as they are complicated devices. A patient has to breathe in at the correct time after the inhaler is actuated, and the inhaler works optimally only if the rate of inhalation is sufficient to carry the medication into the lungs.

A number of companies have developed attachments for inhalers (and even inhalers themselves) that can record when the medication is taken through a Bluetooth connection to a patient’s smartphone. These can also assess inspiratory flow. Reminders to take the medication are built into the app, and those reminders disappear if the medication is taken. Patients can receive feedback about the quality of their timing and inspiratory rate to maximize medication delivery to the lungs.⁴

We learned long ago that it is difficult to take medications three to four times a day, so extended-release tablets were developed to reduce the frequency to once or twice a day. A great deal of work is now being done behind the scenes to develop medications that decrease the need for patients to remember to take their medications. The best examples of this are the long-acting reversible contraception (LARC) devices, specifically IUDs and Nexplanon. Compared with traditional oral contraceptives that need to be taken daily, LARCs reduce the rate of pregnancy by five- to tenfold.

We also now have medications for osteoporosis that can be taken monthly, or even annually. When bisphosphonates were first developed for osteoporosis prevention, they needed to be taken daily. Then a weekly bisphosphonate was developed. Now there is a once-monthly oral bisphosphonate, Ibandronate, and even a once yearly IV bisphosphonate.

Exciting developments have also occurred in the management of diabetes. We may be tempted to take for granted how once-daily long-acting insulin, which releases insulin slowly over the course of a day, has revolutionized the diabetic treatment since its Food and Drug Administration approval in 2000. Yet progress did not end there. The first GLP-1 receptor agonist for diabetes was approved in 2005 and was a twice-a-day medicine. Shortly afterward, a daily GLP-1 was approved, and now there are three once-weekly GLP-1 receptor agonists.

Several pharmaceutical manufacturers are now working on a once-weekly insulin,⁵ as well as an implantable GLP-1 receptor agonist that will need to be replaced every 6-12 months.⁶ Imagine your patient coming in once a year to replace his or her potent glucose lowering medication – one that offers a low incidence of hypoglycemia, maintains glucose control all year long, and requires no adherence to a complicated medication regimen.

Similar technology is being used to develop a once-yearly anti-HIV prophylactic medication delivery system.⁷ This could help prevent the spread of HIV in areas of the world where it may be difficult for people to take daily medications.⁷

The many technological advances we have described may help us reduce our likelihood of missing a dose of a medication. We are hopeful that progress in this area will continue, and that one day medication adherence will require even less effort from patients than it does today.
 

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

References

1. Tabi K et al. Mobile apps for medication management: Review and analysis. JMIR Mhealth Uhealth. 2019 Sep 7(9):13608.

2. Park JYE et al. Mobile phone apps targeting medication adherence: Quality assessment and content analysis of user reviews. JMIR Mhealth Uhealth. 2019 Jan 31;7(1):e11919.

3. Pérez-Jover V et al. Mobile apps for increasing treatment adherence: Systematic review. J Med Internet Res. 2019;21(6):e12505. doi: 10.2196/12505.

4. 4 Smart inhalers that could be lifesaving for people living with asthma & COPD. MyTherapy, July 11, 2019.

5. Rosenstock J et al. Once-weekly insulin for type 2 diabetes without previous insulin treatment. N Engl J Med. 2020 Sep 22. doi: 10.1056/NEJMoa2022474.

6. GLP-1 agonists: From 2 daily injections to 1 per week and beyond. DiaTribe, Jan. 10, 2018.

7. Long-acting HIV prevention tools. Hiv.gov, July 20, 2019.

Medication adherence remains a truly challenging issue. For most chronic diseases, up to 20%-30% of the pills that are prescribed are not taken. In the case of inhalers for asthma and COPD, patients miss over half of the prescribed doses.

There are many things that contribute to the problem of poor adherence, but people often just simply forget. Thankfully, there are tools designed to help remind patients of what they need to take and when. A survey of apps developed to help patients remember to take their medicines found more than 700 available in Apple and Android app stores.¹ Most apps focus on medication alerts, reminders, and medication logs.² A recent review showed that apps have some – yet limited – effectiveness in increasing adherence, with patient self-reported improvements of 7%-40%.³

Another perhaps more promising area of improving adherence involves high-tech advances in the way medications can be taken. Inhalers are a primary target as they are complicated devices. A patient has to breathe in at the correct time after the inhaler is actuated, and the inhaler works optimally only if the rate of inhalation is sufficient to carry the medication into the lungs.

A number of companies have developed attachments for inhalers (and even inhalers themselves) that can record when the medication is taken through a Bluetooth connection to a patient’s smartphone. These can also assess inspiratory flow. Reminders to take the medication are built into the app, and those reminders disappear if the medication is taken. Patients can receive feedback about the quality of their timing and inspiratory rate to maximize medication delivery to the lungs.⁴

We learned long ago that it is difficult to take medications three to four times a day, so extended-release tablets were developed to reduce the frequency to once or twice a day. A great deal of work is now being done behind the scenes to develop medications that decrease the need for patients to remember to take their medications. The best examples of this are the long-acting reversible contraception (LARC) devices, specifically IUDs and Nexplanon. Compared with traditional oral contraceptives that need to be taken daily, LARCs reduce the rate of pregnancy by five- to tenfold.

We also now have medications for osteoporosis that can be taken monthly, or even annually. When bisphosphonates were first developed for osteoporosis prevention, they needed to be taken daily. Then a weekly bisphosphonate was developed. Now there is a once-monthly oral bisphosphonate, Ibandronate, and even a once yearly IV bisphosphonate.

Exciting developments have also occurred in the management of diabetes. We may be tempted to take for granted how once-daily long-acting insulin, which releases insulin slowly over the course of a day, has revolutionized the diabetic treatment since its Food and Drug Administration approval in 2000. Yet progress did not end there. The first GLP-1 receptor agonist for diabetes was approved in 2005 and was a twice-a-day medicine. Shortly afterward, a daily GLP-1 was approved, and now there are three once-weekly GLP-1 receptor agonists.

Several pharmaceutical manufacturers are now working on a once-weekly insulin,⁵ as well as an implantable GLP-1 receptor agonist that will need to be replaced every 6-12 months.⁶ Imagine your patient coming in once a year to replace his or her potent glucose lowering medication – one that offers a low incidence of hypoglycemia, maintains glucose control all year long, and requires no adherence to a complicated medication regimen.

Similar technology is being used to develop a once-yearly anti-HIV prophylactic medication delivery system.⁷ This could help prevent the spread of HIV in areas of the world where it may be difficult for people to take daily medications.⁷

The many technological advances we have described may help us reduce our likelihood of missing a dose of a medication. We are hopeful that progress in this area will continue, and that one day medication adherence will require even less effort from patients than it does today.
 

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

References

1. Tabi K et al. Mobile apps for medication management: Review and analysis. JMIR Mhealth Uhealth. 2019 Sep 7(9):13608.

2. Park JYE et al. Mobile phone apps targeting medication adherence: Quality assessment and content analysis of user reviews. JMIR Mhealth Uhealth. 2019 Jan 31;7(1):e11919.

3. Pérez-Jover V et al. Mobile apps for increasing treatment adherence: Systematic review. J Med Internet Res. 2019;21(6):e12505. doi: 10.2196/12505.

4. 4 Smart inhalers that could be lifesaving for people living with asthma & COPD. MyTherapy, July 11, 2019.

5. Rosenstock J et al. Once-weekly insulin for type 2 diabetes without previous insulin treatment. N Engl J Med. 2020 Sep 22. doi: 10.1056/NEJMoa2022474.

6. GLP-1 agonists: From 2 daily injections to 1 per week and beyond. DiaTribe, Jan. 10, 2018.

7. Long-acting HIV prevention tools. Hiv.gov, July 20, 2019.

Wildfires burned millions of acres in California, Oregon, and Washington this year. Record numbers of tropical storms and hurricanes formed in the Atlantic. “Climate change is here. Disasters are here. They are going to be increasing, which is why we want to talk about this and talk about how pediatricians can help and respond to these events,” Scott Needle, MD, said at the annual meeting American Academy of Pediatrics, held virtually this year.

SounderBruce/flickr.com/CC BY-SA 2.0

“We have seen from past disasters that people look to us ... as a trusted source of information,” said Dr. Needle, chief medical officer of Elica Health Centers in Sacramento, California. “We can be a positive influence in terms of getting out proactive messaging and keeping people informed.”

The Federal Emergency Management Agency (FEMA) 2019 National Household Survey found that about half of households had an emergency plan. A theme across surveys is that, although households take some steps to get ready for disasters, the public generally “is not as prepared for these events as they really need to be,” Dr. Needle said.

The AAP, the Red Cross, and FEMA are among the organizations that offer planning guides, most of which emphasize three simple things: have a kit, have a plan, and be informed, he said.

To prepare for a disaster, parents might refill a child’s medications ahead of time if possible, Dr. Needle suggested. And during the COVID-19 pandemic, families should add masks, sanitizers, and wipes to their go-bags.

Physicians also can help families by asking how they are coping.
 

Wildfire smoke

“Smoke from wildfires can blanket large, large areas,” Mark Miller, MD, MPH, said during the presentation at the AAP meeting. “This year, we have seen wildfire smoke from the western states reach all the way to the East Coast. So this impacts your patients and your own families sometimes, regardless of wherever you live.”

Children may be more vulnerable to wildfire smoke because they often spend more time outdoors and tend to be more active. In addition, their ongoing development means exposure to air pollutants could have lifelong consequences, said Dr. Miller, who recently reviewed the effects of wildfire smoke on children.

“Children with asthma should have some information about wildfires built into their asthma management plan,” said Dr. Miller, who is affiliated with Western States Pediatric Environmental Health Specialty Unit (PEHSU) and University of California, San Francisco. Pollutants are associated with respiratory visits and admissions, asthma exacerbations, decreased lung function, and neurocognitive effects. They also may be carcinogenic.

A study in monkeys found that smoke exposure during California wildfires in 2008 was associated with immune dysregulation and compromised lung function in adolescence.

Another study of three cohorts of children in southern California found that air pollutant levels were associated with children’s lung function.

Organizations have provided resources on creating cleaner air spaces during wildfires, including guides to build DIY air filter fans. AirNow.gov provides air quality and fire maps that can inform decisions about school closures and outdoor activities. Communities should prioritize establishing schools as clean air shelters, Dr. Miller suggested.

Studies have found that respirators and medical masks may decrease children’s exposure to smoke. Children should not use face coverings, however, if they are younger than 2 years, if they are not able to remove the face covering on their own or tell an adult that they need help, or if they have difficulty breathing with a face covering. Younger children should be observed by an adult.

During the pandemic, families should be aware that some types of masks are sold only for health care use, many foreign respirators are counterfeit, and cloth masks used for COVID-19 are not suitable for reducing wildfire smoke exposure, Dr. Miller said.
 

Hazards may linger

Long-term mental health issues may be the disaster consequence that pediatricians encounter most often, Dr. Needle said.

Eighteen months after a major wildfire in Canada, more than one-third of middle and high school students in one community had probable posttraumatic stress disorder (that is, intrusive thoughts, avoidance, and increased arousal). In addition, 31% of students had probable depression. Rates were elevated relative to a control group of students in another community that was not affected by the fire.

Findings indicate that a patient’s degree of exposure to a disaster affects the likelihood of adverse outcomes. On the other hand, resiliency may help mitigate adverse effects. “The hope is that if we can find ways to encourage resiliency before or in the aftermath of an event, we may be able to, in a sense, reduce some of these mental health sequelae,” Dr. Needle said.

Posttraumatic reactions in kids are likely after a disaster. “They may not rise to the level of a diagnosable condition, but they are very common in kids,” he said. “It is important to at least be able to counsel parents to recognize some of the common reactions,” such as acting withdrawn or aggressive, somatic complaints, and having trouble sleeping.

The AAP has a policy statement that encourages talking to children about their concerns with honest and age-appropriate responses, he noted.

When returning to an area after a disaster, many hazards may remain, such as floodwaters, ash pits, mold, and carbon monoxide from generators. “Generally speaking, you don’t want to have kids return to these areas until it is safe,” Dr. Needle said.

Exacerbation of existing conditions – perhaps because of lost medications, smoke exposure, or stress – may be another common problem. Other problems after a disaster could include domestic violence (direct or witnessed) and substance abuse.

“We have a responsibility to take care of our own health as well,” Dr. Needle added. “You can’t take care of others if you’re not taking care of yourself. It’s not being selfish. As a matter of fact, it’s being prudent. It’s survival.”

Dr. Needle and Dr. Miller had no relevant financial disclosures. Dr. Miller’s presentation was supported by the AAP and funded in part by the Agency for Toxic Substances and Disease Registry. The U.S. Environmental Protection Agency (EPA) provides funding support for the Pediatric Environmental Health Specialty Unit.

jremaly@mdedge.com

Wildfires burned millions of acres in California, Oregon, and Washington this year. Record numbers of tropical storms and hurricanes formed in the Atlantic. “Climate change is here. Disasters are here. They are going to be increasing, which is why we want to talk about this and talk about how pediatricians can help and respond to these events,” Scott Needle, MD, said at the annual meeting American Academy of Pediatrics, held virtually this year.

SounderBruce/flickr.com/CC BY-SA 2.0

“We have seen from past disasters that people look to us ... as a trusted source of information,” said Dr. Needle, chief medical officer of Elica Health Centers in Sacramento, California. “We can be a positive influence in terms of getting out proactive messaging and keeping people informed.”

The Federal Emergency Management Agency (FEMA) 2019 National Household Survey found that about half of households had an emergency plan. A theme across surveys is that, although households take some steps to get ready for disasters, the public generally “is not as prepared for these events as they really need to be,” Dr. Needle said.

The AAP, the Red Cross, and FEMA are among the organizations that offer planning guides, most of which emphasize three simple things: have a kit, have a plan, and be informed, he said.

To prepare for a disaster, parents might refill a child’s medications ahead of time if possible, Dr. Needle suggested. And during the COVID-19 pandemic, families should add masks, sanitizers, and wipes to their go-bags.

Physicians also can help families by asking how they are coping.
 

Wildfire smoke

“Smoke from wildfires can blanket large, large areas,” Mark Miller, MD, MPH, said during the presentation at the AAP meeting. “This year, we have seen wildfire smoke from the western states reach all the way to the East Coast. So this impacts your patients and your own families sometimes, regardless of wherever you live.”

Children may be more vulnerable to wildfire smoke because they often spend more time outdoors and tend to be more active. In addition, their ongoing development means exposure to air pollutants could have lifelong consequences, said Dr. Miller, who recently reviewed the effects of wildfire smoke on children.

“Children with asthma should have some information about wildfires built into their asthma management plan,” said Dr. Miller, who is affiliated with Western States Pediatric Environmental Health Specialty Unit (PEHSU) and University of California, San Francisco. Pollutants are associated with respiratory visits and admissions, asthma exacerbations, decreased lung function, and neurocognitive effects. They also may be carcinogenic.

A study in monkeys found that smoke exposure during California wildfires in 2008 was associated with immune dysregulation and compromised lung function in adolescence.

Another study of three cohorts of children in southern California found that air pollutant levels were associated with children’s lung function.

Organizations have provided resources on creating cleaner air spaces during wildfires, including guides to build DIY air filter fans. AirNow.gov provides air quality and fire maps that can inform decisions about school closures and outdoor activities. Communities should prioritize establishing schools as clean air shelters, Dr. Miller suggested.

Studies have found that respirators and medical masks may decrease children’s exposure to smoke. Children should not use face coverings, however, if they are younger than 2 years, if they are not able to remove the face covering on their own or tell an adult that they need help, or if they have difficulty breathing with a face covering. Younger children should be observed by an adult.

During the pandemic, families should be aware that some types of masks are sold only for health care use, many foreign respirators are counterfeit, and cloth masks used for COVID-19 are not suitable for reducing wildfire smoke exposure, Dr. Miller said.
 

Hazards may linger

Long-term mental health issues may be the disaster consequence that pediatricians encounter most often, Dr. Needle said.

Eighteen months after a major wildfire in Canada, more than one-third of middle and high school students in one community had probable posttraumatic stress disorder (that is, intrusive thoughts, avoidance, and increased arousal). In addition, 31% of students had probable depression. Rates were elevated relative to a control group of students in another community that was not affected by the fire.

Findings indicate that a patient’s degree of exposure to a disaster affects the likelihood of adverse outcomes. On the other hand, resiliency may help mitigate adverse effects. “The hope is that if we can find ways to encourage resiliency before or in the aftermath of an event, we may be able to, in a sense, reduce some of these mental health sequelae,” Dr. Needle said.

Posttraumatic reactions in kids are likely after a disaster. “They may not rise to the level of a diagnosable condition, but they are very common in kids,” he said. “It is important to at least be able to counsel parents to recognize some of the common reactions,” such as acting withdrawn or aggressive, somatic complaints, and having trouble sleeping.

The AAP has a policy statement that encourages talking to children about their concerns with honest and age-appropriate responses, he noted.

When returning to an area after a disaster, many hazards may remain, such as floodwaters, ash pits, mold, and carbon monoxide from generators. “Generally speaking, you don’t want to have kids return to these areas until it is safe,” Dr. Needle said.

Exacerbation of existing conditions – perhaps because of lost medications, smoke exposure, or stress – may be another common problem. Other problems after a disaster could include domestic violence (direct or witnessed) and substance abuse.

“We have a responsibility to take care of our own health as well,” Dr. Needle added. “You can’t take care of others if you’re not taking care of yourself. It’s not being selfish. As a matter of fact, it’s being prudent. It’s survival.”

Dr. Needle and Dr. Miller had no relevant financial disclosures. Dr. Miller’s presentation was supported by the AAP and funded in part by the Agency for Toxic Substances and Disease Registry. The U.S. Environmental Protection Agency (EPA) provides funding support for the Pediatric Environmental Health Specialty Unit.

jremaly@mdedge.com

Wildfires burned millions of acres in California, Oregon, and Washington this year. Record numbers of tropical storms and hurricanes formed in the Atlantic. “Climate change is here. Disasters are here. They are going to be increasing, which is why we want to talk about this and talk about how pediatricians can help and respond to these events,” Scott Needle, MD, said at the annual meeting American Academy of Pediatrics, held virtually this year.

SounderBruce/flickr.com/CC BY-SA 2.0

“We have seen from past disasters that people look to us ... as a trusted source of information,” said Dr. Needle, chief medical officer of Elica Health Centers in Sacramento, California. “We can be a positive influence in terms of getting out proactive messaging and keeping people informed.”

The Federal Emergency Management Agency (FEMA) 2019 National Household Survey found that about half of households had an emergency plan. A theme across surveys is that, although households take some steps to get ready for disasters, the public generally “is not as prepared for these events as they really need to be,” Dr. Needle said.

The AAP, the Red Cross, and FEMA are among the organizations that offer planning guides, most of which emphasize three simple things: have a kit, have a plan, and be informed, he said.

To prepare for a disaster, parents might refill a child’s medications ahead of time if possible, Dr. Needle suggested. And during the COVID-19 pandemic, families should add masks, sanitizers, and wipes to their go-bags.

Physicians also can help families by asking how they are coping.
 

Wildfire smoke

“Smoke from wildfires can blanket large, large areas,” Mark Miller, MD, MPH, said during the presentation at the AAP meeting. “This year, we have seen wildfire smoke from the western states reach all the way to the East Coast. So this impacts your patients and your own families sometimes, regardless of wherever you live.”

Children may be more vulnerable to wildfire smoke because they often spend more time outdoors and tend to be more active. In addition, their ongoing development means exposure to air pollutants could have lifelong consequences, said Dr. Miller, who recently reviewed the effects of wildfire smoke on children.

“Children with asthma should have some information about wildfires built into their asthma management plan,” said Dr. Miller, who is affiliated with Western States Pediatric Environmental Health Specialty Unit (PEHSU) and University of California, San Francisco. Pollutants are associated with respiratory visits and admissions, asthma exacerbations, decreased lung function, and neurocognitive effects. They also may be carcinogenic.

A study in monkeys found that smoke exposure during California wildfires in 2008 was associated with immune dysregulation and compromised lung function in adolescence.

Another study of three cohorts of children in southern California found that air pollutant levels were associated with children’s lung function.

Organizations have provided resources on creating cleaner air spaces during wildfires, including guides to build DIY air filter fans. AirNow.gov provides air quality and fire maps that can inform decisions about school closures and outdoor activities. Communities should prioritize establishing schools as clean air shelters, Dr. Miller suggested.

Studies have found that respirators and medical masks may decrease children’s exposure to smoke. Children should not use face coverings, however, if they are younger than 2 years, if they are not able to remove the face covering on their own or tell an adult that they need help, or if they have difficulty breathing with a face covering. Younger children should be observed by an adult.

During the pandemic, families should be aware that some types of masks are sold only for health care use, many foreign respirators are counterfeit, and cloth masks used for COVID-19 are not suitable for reducing wildfire smoke exposure, Dr. Miller said.
 

Hazards may linger

Long-term mental health issues may be the disaster consequence that pediatricians encounter most often, Dr. Needle said.

Eighteen months after a major wildfire in Canada, more than one-third of middle and high school students in one community had probable posttraumatic stress disorder (that is, intrusive thoughts, avoidance, and increased arousal). In addition, 31% of students had probable depression. Rates were elevated relative to a control group of students in another community that was not affected by the fire.

Findings indicate that a patient’s degree of exposure to a disaster affects the likelihood of adverse outcomes. On the other hand, resiliency may help mitigate adverse effects. “The hope is that if we can find ways to encourage resiliency before or in the aftermath of an event, we may be able to, in a sense, reduce some of these mental health sequelae,” Dr. Needle said.

Posttraumatic reactions in kids are likely after a disaster. “They may not rise to the level of a diagnosable condition, but they are very common in kids,” he said. “It is important to at least be able to counsel parents to recognize some of the common reactions,” such as acting withdrawn or aggressive, somatic complaints, and having trouble sleeping.

The AAP has a policy statement that encourages talking to children about their concerns with honest and age-appropriate responses, he noted.

When returning to an area after a disaster, many hazards may remain, such as floodwaters, ash pits, mold, and carbon monoxide from generators. “Generally speaking, you don’t want to have kids return to these areas until it is safe,” Dr. Needle said.

Exacerbation of existing conditions – perhaps because of lost medications, smoke exposure, or stress – may be another common problem. Other problems after a disaster could include domestic violence (direct or witnessed) and substance abuse.

“We have a responsibility to take care of our own health as well,” Dr. Needle added. “You can’t take care of others if you’re not taking care of yourself. It’s not being selfish. As a matter of fact, it’s being prudent. It’s survival.”

Dr. Needle and Dr. Miller had no relevant financial disclosures. Dr. Miller’s presentation was supported by the AAP and funded in part by the Agency for Toxic Substances and Disease Registry. The U.S. Environmental Protection Agency (EPA) provides funding support for the Pediatric Environmental Health Specialty Unit.

jremaly@mdedge.com

Although “biologics have been really revolutionary for the treatment of severe uncontrolled asthma, we still don’t have evidence to know the right drug for the right patient,” said Wendy Moore, MD, of Wake Forest University, Winston-Salem, N.C.

“You start with your best guess and then switch,” she said in an interview.

There are no real-world contemporary measurements of biologic therapy in the United States at this time, Dr. Moore explained during her presentation of findings from the CHRONICLE trial at the annual meeting of the American College of Chest Physicians (CHEST 2020), held virtually this year.

The agents have different targets: omalizumab targets immunoglobulin E, mepolizumab and reslizumab target interleukin (IL)-5, benralizumab targets the IL-5 receptor, and dupilumab targets the common receptor IL-4 receptor A for IL-4 and IL-13.

When the starting biologic doesn’t get the desired results, there is no evidence to show whether another will work better. What we say is, “This one is not working as well as I’d like, let’s try something new?” said Dr. Moore.

However, when looking at data on patients with severe asthma who change from one biologic to another, “I was actually pleased to see that only 10% are switching,” she said in an interview.

But, she added, “if you add that up with the 8% who are stopping, that means that almost 20% don’t get the clinical response they want.”
 

CHRONICLE trial

In the ongoing observational CHRONICLE trial, Dr. Moore and colleagues assessed biologic initiations, discontinuations, and switches to a different agent.

All 1,884 study participants had a diagnosis of severe asthma and were being treated by an allergist/immunologist or a pulmonologist. All were taking high-dose inhaled corticosteroids and additional controllers, or had received an Food and Drug Administration–approved monoclonal antibody, systemic corticosteroid, or another systemic immunosuppressant for at least half of the previous 12 months.

In the study cohort, 1,219 participants were receiving one biologic and 27 were receiving two.

Before November 2018, “it was almost universally all benralizumab being prescribed.” An earlier preference was omalizumab, which was prescribed to 99% of patients before November 2015 and to 45% from November 2017 to November 2018.

“As new drugs were introduced, patients were switched if the desired outcome was not achieved,” Dr. Moore explained.

Over the 2-year period from February 2018 to February 2020, 134 patients – about 10% of all participants taking a biologic – made 148 switches to another biologic.

“The most common reasons reported for switching were lack of efficacy, worsening of asthma control, or waning efficacy,” Dr. Moore reported.

Of the 101 patients (8%) who discontinued 106 biologics, reasons cited were a worsening of asthma symptoms, a desire to change to a cheaper medication, and a waning of effectiveness.

“It seems that the biologic used depended on when you started and whether you were prescribed by an immunologist or pulmonologist,” said Dr. Moore. “I don’t think we understand the perfect patient for any one of these drugs.”

Large-population studies need to be done on each of the drugs. “You have to look at who’s the super responder, the partial responder, compared with the nonresponders, for each medication, but those comparative studies are unlikely to happen,” she said.

In her own practice, her 175 patients are “pretty evenly split between dupilumab, benralizumab, and mepolizumab.”

I have opinions on what works, said Dr. Moore, but none of it is evidence-based. “Those with upper airway involvement with chronic sinusitis tend to do better with mepolizumab than benralizumab. My opinion,” she emphasized.

“People with nasal problems may do better with dupilumab and mepolizumab,” she added. “Also in my opinion.

“But more likely, the issue is you have a partial responder who’s on a T2 high drug but has a T2 low problem too.”
 

PATHWAY study

Findings from the phase 2B PATHWAY study showed that tezepelumab reduced exacerbations in patients with uncontrolled asthma better than inhaled corticosteroids, and improved forced expiratory volume in 1 second.

“Adherence was monitored very carefully,” said investigator Jonathan Corren, MD, of the University of California, Los Angeles, who presented the PATHWAY data. This could explain, in part, why some patients in the control group “showed improvement from baseline.”

Before switching to a biologic, “we should always consider some of these issues that might contribute to better asthma control, like patient adherence or the inability to use an inhaler properly,” Dr. Corren said.

Some people have never been “shown how to use their inhalers properly,” said Moore. “Some of them come back fine when we show them.”

Dr. Moore has been on the advisory board for AstraZeneca, Genentech, GlaxoSmithKline (GSK), Regeneron, and Sanofi. Dr. Corren reports receiving honoraria from AstraZeneca.
 

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

Although “biologics have been really revolutionary for the treatment of severe uncontrolled asthma, we still don’t have evidence to know the right drug for the right patient,” said Wendy Moore, MD, of Wake Forest University, Winston-Salem, N.C.

“You start with your best guess and then switch,” she said in an interview.

There are no real-world contemporary measurements of biologic therapy in the United States at this time, Dr. Moore explained during her presentation of findings from the CHRONICLE trial at the annual meeting of the American College of Chest Physicians (CHEST 2020), held virtually this year.

The agents have different targets: omalizumab targets immunoglobulin E, mepolizumab and reslizumab target interleukin (IL)-5, benralizumab targets the IL-5 receptor, and dupilumab targets the common receptor IL-4 receptor A for IL-4 and IL-13.

When the starting biologic doesn’t get the desired results, there is no evidence to show whether another will work better. What we say is, “This one is not working as well as I’d like, let’s try something new?” said Dr. Moore.

However, when looking at data on patients with severe asthma who change from one biologic to another, “I was actually pleased to see that only 10% are switching,” she said in an interview.

But, she added, “if you add that up with the 8% who are stopping, that means that almost 20% don’t get the clinical response they want.”
 

CHRONICLE trial

In the ongoing observational CHRONICLE trial, Dr. Moore and colleagues assessed biologic initiations, discontinuations, and switches to a different agent.

All 1,884 study participants had a diagnosis of severe asthma and were being treated by an allergist/immunologist or a pulmonologist. All were taking high-dose inhaled corticosteroids and additional controllers, or had received an Food and Drug Administration–approved monoclonal antibody, systemic corticosteroid, or another systemic immunosuppressant for at least half of the previous 12 months.

In the study cohort, 1,219 participants were receiving one biologic and 27 were receiving two.

Before November 2018, “it was almost universally all benralizumab being prescribed.” An earlier preference was omalizumab, which was prescribed to 99% of patients before November 2015 and to 45% from November 2017 to November 2018.

“As new drugs were introduced, patients were switched if the desired outcome was not achieved,” Dr. Moore explained.

Over the 2-year period from February 2018 to February 2020, 134 patients – about 10% of all participants taking a biologic – made 148 switches to another biologic.

“The most common reasons reported for switching were lack of efficacy, worsening of asthma control, or waning efficacy,” Dr. Moore reported.

Of the 101 patients (8%) who discontinued 106 biologics, reasons cited were a worsening of asthma symptoms, a desire to change to a cheaper medication, and a waning of effectiveness.

“It seems that the biologic used depended on when you started and whether you were prescribed by an immunologist or pulmonologist,” said Dr. Moore. “I don’t think we understand the perfect patient for any one of these drugs.”

Large-population studies need to be done on each of the drugs. “You have to look at who’s the super responder, the partial responder, compared with the nonresponders, for each medication, but those comparative studies are unlikely to happen,” she said.

In her own practice, her 175 patients are “pretty evenly split between dupilumab, benralizumab, and mepolizumab.”

I have opinions on what works, said Dr. Moore, but none of it is evidence-based. “Those with upper airway involvement with chronic sinusitis tend to do better with mepolizumab than benralizumab. My opinion,” she emphasized.

“People with nasal problems may do better with dupilumab and mepolizumab,” she added. “Also in my opinion.

“But more likely, the issue is you have a partial responder who’s on a T2 high drug but has a T2 low problem too.”
 

PATHWAY study

Findings from the phase 2B PATHWAY study showed that tezepelumab reduced exacerbations in patients with uncontrolled asthma better than inhaled corticosteroids, and improved forced expiratory volume in 1 second.

“Adherence was monitored very carefully,” said investigator Jonathan Corren, MD, of the University of California, Los Angeles, who presented the PATHWAY data. This could explain, in part, why some patients in the control group “showed improvement from baseline.”

Before switching to a biologic, “we should always consider some of these issues that might contribute to better asthma control, like patient adherence or the inability to use an inhaler properly,” Dr. Corren said.

Some people have never been “shown how to use their inhalers properly,” said Moore. “Some of them come back fine when we show them.”

Dr. Moore has been on the advisory board for AstraZeneca, Genentech, GlaxoSmithKline (GSK), Regeneron, and Sanofi. Dr. Corren reports receiving honoraria from AstraZeneca.
 

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

Although “biologics have been really revolutionary for the treatment of severe uncontrolled asthma, we still don’t have evidence to know the right drug for the right patient,” said Wendy Moore, MD, of Wake Forest University, Winston-Salem, N.C.

“You start with your best guess and then switch,” she said in an interview.

There are no real-world contemporary measurements of biologic therapy in the United States at this time, Dr. Moore explained during her presentation of findings from the CHRONICLE trial at the annual meeting of the American College of Chest Physicians (CHEST 2020), held virtually this year.

The agents have different targets: omalizumab targets immunoglobulin E, mepolizumab and reslizumab target interleukin (IL)-5, benralizumab targets the IL-5 receptor, and dupilumab targets the common receptor IL-4 receptor A for IL-4 and IL-13.

When the starting biologic doesn’t get the desired results, there is no evidence to show whether another will work better. What we say is, “This one is not working as well as I’d like, let’s try something new?” said Dr. Moore.

However, when looking at data on patients with severe asthma who change from one biologic to another, “I was actually pleased to see that only 10% are switching,” she said in an interview.

But, she added, “if you add that up with the 8% who are stopping, that means that almost 20% don’t get the clinical response they want.”
 

CHRONICLE trial

In the ongoing observational CHRONICLE trial, Dr. Moore and colleagues assessed biologic initiations, discontinuations, and switches to a different agent.

All 1,884 study participants had a diagnosis of severe asthma and were being treated by an allergist/immunologist or a pulmonologist. All were taking high-dose inhaled corticosteroids and additional controllers, or had received an Food and Drug Administration–approved monoclonal antibody, systemic corticosteroid, or another systemic immunosuppressant for at least half of the previous 12 months.

In the study cohort, 1,219 participants were receiving one biologic and 27 were receiving two.

Before November 2018, “it was almost universally all benralizumab being prescribed.” An earlier preference was omalizumab, which was prescribed to 99% of patients before November 2015 and to 45% from November 2017 to November 2018.

“As new drugs were introduced, patients were switched if the desired outcome was not achieved,” Dr. Moore explained.

Over the 2-year period from February 2018 to February 2020, 134 patients – about 10% of all participants taking a biologic – made 148 switches to another biologic.

“The most common reasons reported for switching were lack of efficacy, worsening of asthma control, or waning efficacy,” Dr. Moore reported.

Of the 101 patients (8%) who discontinued 106 biologics, reasons cited were a worsening of asthma symptoms, a desire to change to a cheaper medication, and a waning of effectiveness.

“It seems that the biologic used depended on when you started and whether you were prescribed by an immunologist or pulmonologist,” said Dr. Moore. “I don’t think we understand the perfect patient for any one of these drugs.”

Large-population studies need to be done on each of the drugs. “You have to look at who’s the super responder, the partial responder, compared with the nonresponders, for each medication, but those comparative studies are unlikely to happen,” she said.

In her own practice, her 175 patients are “pretty evenly split between dupilumab, benralizumab, and mepolizumab.”

I have opinions on what works, said Dr. Moore, but none of it is evidence-based. “Those with upper airway involvement with chronic sinusitis tend to do better with mepolizumab than benralizumab. My opinion,” she emphasized.

“People with nasal problems may do better with dupilumab and mepolizumab,” she added. “Also in my opinion.

“But more likely, the issue is you have a partial responder who’s on a T2 high drug but has a T2 low problem too.”
 

PATHWAY study

Findings from the phase 2B PATHWAY study showed that tezepelumab reduced exacerbations in patients with uncontrolled asthma better than inhaled corticosteroids, and improved forced expiratory volume in 1 second.

“Adherence was monitored very carefully,” said investigator Jonathan Corren, MD, of the University of California, Los Angeles, who presented the PATHWAY data. This could explain, in part, why some patients in the control group “showed improvement from baseline.”

Before switching to a biologic, “we should always consider some of these issues that might contribute to better asthma control, like patient adherence or the inability to use an inhaler properly,” Dr. Corren said.

Some people have never been “shown how to use their inhalers properly,” said Moore. “Some of them come back fine when we show them.”

Dr. Moore has been on the advisory board for AstraZeneca, Genentech, GlaxoSmithKline (GSK), Regeneron, and Sanofi. Dr. Corren reports receiving honoraria from AstraZeneca.
 

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

Asthma effects about 10% of pregnant women worldwide. About 10% of these will have severe disease requiring oral corticosteroids. Brief reviews of asthma drugs are shown below. Because asthma can be a serious disease, selective treatment should not be withheld in pregnancy.

The trade names (if available) and molecular weights (rounded to the nearest whole number) are shown in parentheses. Nearly all of these drugs will cross the placenta.
 

Beclomethasone (Beconase AQ) (539)

Either beclomethasone or budesonide was considered the inhaled steroids of choice for use during pregnancy, according to a position statement from a joint committee of the American College of Obstetricians and Gynecologists and the American College of Allergy, Asthma, and Immunology published in 2000. Although the drug is teratogenic in animals, no human reports associating the use of inhaled beclomethasone with human congenital anomalies have been found.

Benralizumab (Fasenra) (150,000)

There is no published human pregnancy data. Based on studies in monkeys, the drug crosses the placenta in the third trimester. It caused no fetal harm in monkeys when given throughout pregnancy. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to the drug during pregnancy. Health care providers can enroll patients or encourage patients to enroll themselves by calling 1-877-311-8972 or visiting mothertobaby.org/Fasenra.

Budesonide (Rhinocort) (431)

Either budesonide or beclomethasone was considered the inhaled steroids of choice for use during pregnancy in a position statement from a joint committee of ACOG and ACAAI published in 2000. Although the drug is teratogenic in animals, no human reports associating the use of inhaled beclomethasone with human congenital anomalies have been found.

Caffeine (194)

Although the amount of caffeine in commonly used beverages varies widely, caffeine consumption in pregnancy in moderate amounts does not pose a risk to the fetus. When used in moderation, no association with congenital malformations, spontaneous abortions, preterm birth, and low birth weight have been proven.

Ciclesonide (Alvesco) (541)

Ciclesonide is an inhaled corticosteroid. There is no published human pregnancy data but the molecular weight suggests that it will cross the placenta throughout pregnancy. The drug produced no defects in rats but caused fetal toxicity in rabbits. Although the risk may be low because it is inhaled, avoiding it in the first trimester should be considered (see dexamethasone).

Cromolyn sodium (490)

Cromolyn was available as a nasal spray and oral solution, but it is no longer available in the United States. It is poorly absorbed into the systemic circulation. Neither the human nor the animal data suggest a risk of embryo-fetal harm.

Dexamethasone (392)

This is a corticosteroid with potency similar to betamethasone. Because large epidemiologic studies have found positive associations between systemic corticosteroids and nonsyndromic orofacial clefts, it is best to avoid this agent in the first trimester. However, when used for the treatment of asthma, other studies have not found a significantly increased risk of maternal or fetal complications. The difference in these outcomes may be related to the systemic concentrations of the drug.

Dyphylline (254) + guaifenesin (198) (Difil-G Forte) (Dilex-G 400) (Dy-G)

This is an OTC liquid drug taken orally. It has not been studied in pregnant animals, and there is no published human pregnancy data. However, these bronchodilator agents probably can be classified as low risk for the embryo and fetus. Dyphylline alone has been removed from the market.

Fluticasone (539) + vilanterol (Breo Ellipta) (775)

Fluticasone is a corticosteroid and vilanterol is a long acting beta2-adrenergic agonist that are given by inhalation. The molecular weights suggest that the two agents will cross the placenta throughout pregnancy. The drug did not cause fetal harm in animals. There is no published human pregnancy data for this fixed combination.

Fluticasone (539) + umeclidinium (509) + vilanterol (Trelegy Ellipta) (776)

The combination of fluticasone (glucocorticoid), umeclidinium, and vilanterol (long-acting beta2-adrenergic agonists) is given by inhalation. The molecular weights suggest that the three agents will cross the placenta throughout pregnancy. Although the three-drug combination has not been studied in pregnant rats and rabbits, the individual agents did not cause embryo-fetal harm in these species. There is no evidence that these agents, when given by inhalation, will harm the human embryo and/or fetus. No published human pregnancy reports for this fixed combination have been located.

Formoterol + mometasone (Dulera Aerosol) (841 / 521)

This combination is an aerosol product. Formoterol is a long-acting beta2-adrenergic agonist and mometasone is a topical corticosteroid. There is no published human pregnancy data for this fixed combination. The molecular weights suggest that both drugs will cross the placenta throughout pregnancy. In animals given high oral doses, both were teratogenic.

Ipratropium (Atrovent) (430)

Inhaled ipratropium, an anticholinergic bronchodilator, is recommended for asthma in patients not responding adequately to other therapy. It was not teratogenic mice, rats, and rabbits. Although the human pregnancy data is limited, there is no evidence that the drug is hazardous to the fetus. It produces fewer systemic effects then atropine and may have an additive bronchodilatory effect to beta2 agonists.

Isoproterenol (211)

Isoproterenol is a sympathomimetic (bronchodilator) with beta-adrenergic effects that is given intravenously. No reports linking this agent with congenital defects have been located. The drug was not teratogenic in rats and rabbits but was in hamsters.

Levalbuterol (Xopenex HFA) (240)

Levalbuterol is the (R)-enantiomer of racemic albuterol. It is given by inhalation. No reports of its use in human pregnancy have been located. However, racemic albuterol is considered compatible in pregnancy, and there is no apparent reason not to classify levalbuterol the same way. The drug, when given orally, is teratogenic in animals. If levalbuterol is used in pregnancy for the treatment of asthma, health care professionals are encouraged to call the toll-free number (1-877-311-8972) for information about patient enrollment in an Organization of Teratology Specialists study.

Mepolizumab (Nucala) (149,000)

Mepolizumab is given by subcutaneous injection. It is not indicated for status asthmaticus. There is no published human pregnancy data but the molecular weight suggests that it will not cross the placenta in the first half of pregnancy. The drug did not cause defects in monkeys and mice. There is a pregnancy exposure registry that monitors pregnancy outcomes in women with asthma exposed to Nucala during pregnancy. Health care providers can enroll patients or encourage patients to enroll themselves by calling 1-877-311-8972 or visiting www.mothertobaby.org/asthma.

Metaproterenol (521)

Metaproterenol, a selective beta2-adrenergic agonist, is a respiratory (bronchodilator) that is given orally. Use of this agent in pregnancy has not been linked with congenital defects. However, the drug is teratogenic in animals.

Methylprednisolone (Medrol) (374)

This is an oral glucocorticoid. The molecular weight suggests that it will cross the placenta throughout pregnancy. No reports relating to its use in human pregnancy or in pregnant animals have been located. However, teratogenicity is a potential problem (see below). If high doses of the drug are used in pregnancy, the newborn infants should be carefully observed for signs of hypoadrenalism. In addition, all corticosteroids increase calcium excretion.

Methylprednisolone acetate (Depo-Medrol) (417)

This is an injectable glucocorticoid. See below.

Methylprednisolone sodium succinate (Solu-Medrol) (497)

Methylprednisolone is a glucocorticoid given parenterally. The molecular weight suggests that it will cross the placenta throughout pregnancy. As with other corticosteroids, the drug was teratogenic, at doses equivalent to the human dose, in mice, rats, and rabbits. If the drug is used in pregnancy, the newborn infant should be carefully observed for signs of hypoadrenalism. In addition, all corticosteroids increase calcium excretion.

Mometasone + formoterol (Dulera) (321 + 841)

Dulera is a combination product of mometasone (corticosteroid) and formoterol (beta2-adrenergic agonist). There is no published human data for Dulera but the molecular weights suggest that the drugs will cross the placenta. Oral doses of formoterol were not teratogenic in animals but were with mometasone. The limited human pregnancy data with formoterol did not suggest a risk of embryo/fetal harm, but there is no human pregnancy data for mometasone.

Montelukast (Singulair) (608)

Montelukast is a leukotriene receptor antagonist that is given orally. Although the human data are limited, the drug does not appear to cause harm to the embryo and/or fetus. The drug was not teratogenic in rats and rabbits. The manufacturer maintains a pregnancy registry for women exposed to montelukast. Health care professionals are encouraged to report pregnancy exposures to the registry by calling the toll-free number 1-800-986-8999.

Omalizumab (Xolair) (149,000)

Omalizumab is a recombinant DNA–derived humanized immunoglobulin (IgG1k) monoclonal antibody that is administered subcutaneously for patients with moderate to severe persistent asthma. In monkeys, the drug did not cause embryotoxicity or teratogenicity. The human pregnancy data is very limited but does not suggest an increased embryo-fetal risk.

Prednisone (Rayos) (358)

The use of oral prednisone appears to represent a small risk to the developing fetus. One of these risks appears to be orofacial clefts. The drug causes birth defects in rats, mice, rabbits, and hamsters. However, the available evidence supports its use to control various maternal diseases, one of which is asthma.
 

Reslizumab (Cinqair) (147,000)

Reslizumab is given intravenously. Even though the molecular weight is high, the drug crosses the placenta during pregnancy. In placebo-controlled studies, anaphylaxis occurred in 0.3% of patients receiving the drug. No adverse effects were observed when the drug was given to pregnant mice and rabbits.

Salmeterol (Serevent Diskus) (416)

Salmeterol is a long-acting beta2-adrenergic agonist that is given as an aerosol or dry powder for oral inhalation. Because the drug acts locally in the lung, plasma levels are very low or undetectable and are a result of swallowed salmeterol. The limited human pregnancy data does not suggest risk of embryo-fetal harm. High oral doses in animals were not teratogenic.

Theophylline (180)

Oral theophylline is a methylxanthine that is indicated for the treatment of symptoms of chronic asthma and other chronic lung diseases. According to ACOG, theophylline is not a preferred asthma therapy but considered an alternative agent. No published reports linking the use of theophylline with congenital defects have been located. However, the drug is teratogenic in mice, rats, and rabbits at doses close to the human dose.

Tiotropium (Spiriva Respimat) (490)

Tiotropium, an anticholinergic bronchodilator, is given by oral inhalation only. No reports describing the use of tiotropium during human pregnancy have been located. The animal data suggest low risk. However, because of its long elimination half-life (about 25 hours), use of tiotropium immediately before the diagnosis of an inadvertent pregnancy would most likely result in the exposure of a portion of organogenesis.

Triamcinolone (Kenalog-40) (435)

Triamcinolone is an inhaled corticosteroid with potency slightly greater than prednisone. Although the systemic use of the drug has a small absolute risk of oral clefts and fetal growth restriction, inhaled triamcinolone does not appear to cause embryo-fetal harm. The drug is teratogenic when given orally to animals.

Breastfeeding

It is not known if the above drugs are excreted into breast milk. Agents with relatively low molecular weights will probably be in milk. However, if the maternal levels are low, the amount in milk will probably be very small, if at all. Nevertheless, it is doubtful if any of these agents, even if they are excreted into milk, will have a harmful effect on a nursing infant.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at obnews@mdedge.com.

Asthma effects about 10% of pregnant women worldwide. About 10% of these will have severe disease requiring oral corticosteroids. Brief reviews of asthma drugs are shown below. Because asthma can be a serious disease, selective treatment should not be withheld in pregnancy.

The trade names (if available) and molecular weights (rounded to the nearest whole number) are shown in parentheses. Nearly all of these drugs will cross the placenta.
 

Beclomethasone (Beconase AQ) (539)

Either beclomethasone or budesonide was considered the inhaled steroids of choice for use during pregnancy, according to a position statement from a joint committee of the American College of Obstetricians and Gynecologists and the American College of Allergy, Asthma, and Immunology published in 2000. Although the drug is teratogenic in animals, no human reports associating the use of inhaled beclomethasone with human congenital anomalies have been found.

Benralizumab (Fasenra) (150,000)

There is no published human pregnancy data. Based on studies in monkeys, the drug crosses the placenta in the third trimester. It caused no fetal harm in monkeys when given throughout pregnancy. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to the drug during pregnancy. Health care providers can enroll patients or encourage patients to enroll themselves by calling 1-877-311-8972 or visiting mothertobaby.org/Fasenra.

Budesonide (Rhinocort) (431)

Either budesonide or beclomethasone was considered the inhaled steroids of choice for use during pregnancy in a position statement from a joint committee of ACOG and ACAAI published in 2000. Although the drug is teratogenic in animals, no human reports associating the use of inhaled beclomethasone with human congenital anomalies have been found.

Caffeine (194)

Although the amount of caffeine in commonly used beverages varies widely, caffeine consumption in pregnancy in moderate amounts does not pose a risk to the fetus. When used in moderation, no association with congenital malformations, spontaneous abortions, preterm birth, and low birth weight have been proven.

Ciclesonide (Alvesco) (541)

Ciclesonide is an inhaled corticosteroid. There is no published human pregnancy data but the molecular weight suggests that it will cross the placenta throughout pregnancy. The drug produced no defects in rats but caused fetal toxicity in rabbits. Although the risk may be low because it is inhaled, avoiding it in the first trimester should be considered (see dexamethasone).

Cromolyn sodium (490)

Cromolyn was available as a nasal spray and oral solution, but it is no longer available in the United States. It is poorly absorbed into the systemic circulation. Neither the human nor the animal data suggest a risk of embryo-fetal harm.

Dexamethasone (392)

This is a corticosteroid with potency similar to betamethasone. Because large epidemiologic studies have found positive associations between systemic corticosteroids and nonsyndromic orofacial clefts, it is best to avoid this agent in the first trimester. However, when used for the treatment of asthma, other studies have not found a significantly increased risk of maternal or fetal complications. The difference in these outcomes may be related to the systemic concentrations of the drug.

Dyphylline (254) + guaifenesin (198) (Difil-G Forte) (Dilex-G 400) (Dy-G)

This is an OTC liquid drug taken orally. It has not been studied in pregnant animals, and there is no published human pregnancy data. However, these bronchodilator agents probably can be classified as low risk for the embryo and fetus. Dyphylline alone has been removed from the market.

Fluticasone (539) + vilanterol (Breo Ellipta) (775)

Fluticasone is a corticosteroid and vilanterol is a long acting beta2-adrenergic agonist that are given by inhalation. The molecular weights suggest that the two agents will cross the placenta throughout pregnancy. The drug did not cause fetal harm in animals. There is no published human pregnancy data for this fixed combination.

Fluticasone (539) + umeclidinium (509) + vilanterol (Trelegy Ellipta) (776)

The combination of fluticasone (glucocorticoid), umeclidinium, and vilanterol (long-acting beta2-adrenergic agonists) is given by inhalation. The molecular weights suggest that the three agents will cross the placenta throughout pregnancy. Although the three-drug combination has not been studied in pregnant rats and rabbits, the individual agents did not cause embryo-fetal harm in these species. There is no evidence that these agents, when given by inhalation, will harm the human embryo and/or fetus. No published human pregnancy reports for this fixed combination have been located.

Formoterol + mometasone (Dulera Aerosol) (841 / 521)

This combination is an aerosol product. Formoterol is a long-acting beta2-adrenergic agonist and mometasone is a topical corticosteroid. There is no published human pregnancy data for this fixed combination. The molecular weights suggest that both drugs will cross the placenta throughout pregnancy. In animals given high oral doses, both were teratogenic.

Ipratropium (Atrovent) (430)

Inhaled ipratropium, an anticholinergic bronchodilator, is recommended for asthma in patients not responding adequately to other therapy. It was not teratogenic mice, rats, and rabbits. Although the human pregnancy data is limited, there is no evidence that the drug is hazardous to the fetus. It produces fewer systemic effects then atropine and may have an additive bronchodilatory effect to beta2 agonists.

Isoproterenol (211)

Isoproterenol is a sympathomimetic (bronchodilator) with beta-adrenergic effects that is given intravenously. No reports linking this agent with congenital defects have been located. The drug was not teratogenic in rats and rabbits but was in hamsters.

Levalbuterol (Xopenex HFA) (240)

Levalbuterol is the (R)-enantiomer of racemic albuterol. It is given by inhalation. No reports of its use in human pregnancy have been located. However, racemic albuterol is considered compatible in pregnancy, and there is no apparent reason not to classify levalbuterol the same way. The drug, when given orally, is teratogenic in animals. If levalbuterol is used in pregnancy for the treatment of asthma, health care professionals are encouraged to call the toll-free number (1-877-311-8972) for information about patient enrollment in an Organization of Teratology Specialists study.

Mepolizumab (Nucala) (149,000)

Mepolizumab is given by subcutaneous injection. It is not indicated for status asthmaticus. There is no published human pregnancy data but the molecular weight suggests that it will not cross the placenta in the first half of pregnancy. The drug did not cause defects in monkeys and mice. There is a pregnancy exposure registry that monitors pregnancy outcomes in women with asthma exposed to Nucala during pregnancy. Health care providers can enroll patients or encourage patients to enroll themselves by calling 1-877-311-8972 or visiting www.mothertobaby.org/asthma.

Metaproterenol (521)

Metaproterenol, a selective beta2-adrenergic agonist, is a respiratory (bronchodilator) that is given orally. Use of this agent in pregnancy has not been linked with congenital defects. However, the drug is teratogenic in animals.

Methylprednisolone (Medrol) (374)

This is an oral glucocorticoid. The molecular weight suggests that it will cross the placenta throughout pregnancy. No reports relating to its use in human pregnancy or in pregnant animals have been located. However, teratogenicity is a potential problem (see below). If high doses of the drug are used in pregnancy, the newborn infants should be carefully observed for signs of hypoadrenalism. In addition, all corticosteroids increase calcium excretion.

Methylprednisolone acetate (Depo-Medrol) (417)

This is an injectable glucocorticoid. See below.

Methylprednisolone sodium succinate (Solu-Medrol) (497)

Methylprednisolone is a glucocorticoid given parenterally. The molecular weight suggests that it will cross the placenta throughout pregnancy. As with other corticosteroids, the drug was teratogenic, at doses equivalent to the human dose, in mice, rats, and rabbits. If the drug is used in pregnancy, the newborn infant should be carefully observed for signs of hypoadrenalism. In addition, all corticosteroids increase calcium excretion.

Mometasone + formoterol (Dulera) (321 + 841)

Dulera is a combination product of mometasone (corticosteroid) and formoterol (beta2-adrenergic agonist). There is no published human data for Dulera but the molecular weights suggest that the drugs will cross the placenta. Oral doses of formoterol were not teratogenic in animals but were with mometasone. The limited human pregnancy data with formoterol did not suggest a risk of embryo/fetal harm, but there is no human pregnancy data for mometasone.

Montelukast (Singulair) (608)

Montelukast is a leukotriene receptor antagonist that is given orally. Although the human data are limited, the drug does not appear to cause harm to the embryo and/or fetus. The drug was not teratogenic in rats and rabbits. The manufacturer maintains a pregnancy registry for women exposed to montelukast. Health care professionals are encouraged to report pregnancy exposures to the registry by calling the toll-free number 1-800-986-8999.

Omalizumab (Xolair) (149,000)

Omalizumab is a recombinant DNA–derived humanized immunoglobulin (IgG1k) monoclonal antibody that is administered subcutaneously for patients with moderate to severe persistent asthma. In monkeys, the drug did not cause embryotoxicity or teratogenicity. The human pregnancy data is very limited but does not suggest an increased embryo-fetal risk.

Prednisone (Rayos) (358)

The use of oral prednisone appears to represent a small risk to the developing fetus. One of these risks appears to be orofacial clefts. The drug causes birth defects in rats, mice, rabbits, and hamsters. However, the available evidence supports its use to control various maternal diseases, one of which is asthma.
 

Reslizumab (Cinqair) (147,000)

Reslizumab is given intravenously. Even though the molecular weight is high, the drug crosses the placenta during pregnancy. In placebo-controlled studies, anaphylaxis occurred in 0.3% of patients receiving the drug. No adverse effects were observed when the drug was given to pregnant mice and rabbits.

Salmeterol (Serevent Diskus) (416)

Salmeterol is a long-acting beta2-adrenergic agonist that is given as an aerosol or dry powder for oral inhalation. Because the drug acts locally in the lung, plasma levels are very low or undetectable and are a result of swallowed salmeterol. The limited human pregnancy data does not suggest risk of embryo-fetal harm. High oral doses in animals were not teratogenic.

Theophylline (180)

Oral theophylline is a methylxanthine that is indicated for the treatment of symptoms of chronic asthma and other chronic lung diseases. According to ACOG, theophylline is not a preferred asthma therapy but considered an alternative agent. No published reports linking the use of theophylline with congenital defects have been located. However, the drug is teratogenic in mice, rats, and rabbits at doses close to the human dose.

Tiotropium (Spiriva Respimat) (490)

Tiotropium, an anticholinergic bronchodilator, is given by oral inhalation only. No reports describing the use of tiotropium during human pregnancy have been located. The animal data suggest low risk. However, because of its long elimination half-life (about 25 hours), use of tiotropium immediately before the diagnosis of an inadvertent pregnancy would most likely result in the exposure of a portion of organogenesis.

Triamcinolone (Kenalog-40) (435)

Triamcinolone is an inhaled corticosteroid with potency slightly greater than prednisone. Although the systemic use of the drug has a small absolute risk of oral clefts and fetal growth restriction, inhaled triamcinolone does not appear to cause embryo-fetal harm. The drug is teratogenic when given orally to animals.

Breastfeeding

It is not known if the above drugs are excreted into breast milk. Agents with relatively low molecular weights will probably be in milk. However, if the maternal levels are low, the amount in milk will probably be very small, if at all. Nevertheless, it is doubtful if any of these agents, even if they are excreted into milk, will have a harmful effect on a nursing infant.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at obnews@mdedge.com.

Asthma effects about 10% of pregnant women worldwide. About 10% of these will have severe disease requiring oral corticosteroids. Brief reviews of asthma drugs are shown below. Because asthma can be a serious disease, selective treatment should not be withheld in pregnancy.

The trade names (if available) and molecular weights (rounded to the nearest whole number) are shown in parentheses. Nearly all of these drugs will cross the placenta.
 

Beclomethasone (Beconase AQ) (539)

Either beclomethasone or budesonide was considered the inhaled steroids of choice for use during pregnancy, according to a position statement from a joint committee of the American College of Obstetricians and Gynecologists and the American College of Allergy, Asthma, and Immunology published in 2000. Although the drug is teratogenic in animals, no human reports associating the use of inhaled beclomethasone with human congenital anomalies have been found.

Benralizumab (Fasenra) (150,000)

There is no published human pregnancy data. Based on studies in monkeys, the drug crosses the placenta in the third trimester. It caused no fetal harm in monkeys when given throughout pregnancy. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to the drug during pregnancy. Health care providers can enroll patients or encourage patients to enroll themselves by calling 1-877-311-8972 or visiting mothertobaby.org/Fasenra.

Budesonide (Rhinocort) (431)

Either budesonide or beclomethasone was considered the inhaled steroids of choice for use during pregnancy in a position statement from a joint committee of ACOG and ACAAI published in 2000. Although the drug is teratogenic in animals, no human reports associating the use of inhaled beclomethasone with human congenital anomalies have been found.

Caffeine (194)

Although the amount of caffeine in commonly used beverages varies widely, caffeine consumption in pregnancy in moderate amounts does not pose a risk to the fetus. When used in moderation, no association with congenital malformations, spontaneous abortions, preterm birth, and low birth weight have been proven.

Ciclesonide (Alvesco) (541)

Ciclesonide is an inhaled corticosteroid. There is no published human pregnancy data but the molecular weight suggests that it will cross the placenta throughout pregnancy. The drug produced no defects in rats but caused fetal toxicity in rabbits. Although the risk may be low because it is inhaled, avoiding it in the first trimester should be considered (see dexamethasone).

Cromolyn sodium (490)

Cromolyn was available as a nasal spray and oral solution, but it is no longer available in the United States. It is poorly absorbed into the systemic circulation. Neither the human nor the animal data suggest a risk of embryo-fetal harm.

Dexamethasone (392)

This is a corticosteroid with potency similar to betamethasone. Because large epidemiologic studies have found positive associations between systemic corticosteroids and nonsyndromic orofacial clefts, it is best to avoid this agent in the first trimester. However, when used for the treatment of asthma, other studies have not found a significantly increased risk of maternal or fetal complications. The difference in these outcomes may be related to the systemic concentrations of the drug.

Dyphylline (254) + guaifenesin (198) (Difil-G Forte) (Dilex-G 400) (Dy-G)

This is an OTC liquid drug taken orally. It has not been studied in pregnant animals, and there is no published human pregnancy data. However, these bronchodilator agents probably can be classified as low risk for the embryo and fetus. Dyphylline alone has been removed from the market.

Fluticasone (539) + vilanterol (Breo Ellipta) (775)

Fluticasone is a corticosteroid and vilanterol is a long acting beta2-adrenergic agonist that are given by inhalation. The molecular weights suggest that the two agents will cross the placenta throughout pregnancy. The drug did not cause fetal harm in animals. There is no published human pregnancy data for this fixed combination.

Fluticasone (539) + umeclidinium (509) + vilanterol (Trelegy Ellipta) (776)

The combination of fluticasone (glucocorticoid), umeclidinium, and vilanterol (long-acting beta2-adrenergic agonists) is given by inhalation. The molecular weights suggest that the three agents will cross the placenta throughout pregnancy. Although the three-drug combination has not been studied in pregnant rats and rabbits, the individual agents did not cause embryo-fetal harm in these species. There is no evidence that these agents, when given by inhalation, will harm the human embryo and/or fetus. No published human pregnancy reports for this fixed combination have been located.

Formoterol + mometasone (Dulera Aerosol) (841 / 521)

This combination is an aerosol product. Formoterol is a long-acting beta2-adrenergic agonist and mometasone is a topical corticosteroid. There is no published human pregnancy data for this fixed combination. The molecular weights suggest that both drugs will cross the placenta throughout pregnancy. In animals given high oral doses, both were teratogenic.

Ipratropium (Atrovent) (430)

Inhaled ipratropium, an anticholinergic bronchodilator, is recommended for asthma in patients not responding adequately to other therapy. It was not teratogenic mice, rats, and rabbits. Although the human pregnancy data is limited, there is no evidence that the drug is hazardous to the fetus. It produces fewer systemic effects then atropine and may have an additive bronchodilatory effect to beta2 agonists.

Isoproterenol (211)

Isoproterenol is a sympathomimetic (bronchodilator) with beta-adrenergic effects that is given intravenously. No reports linking this agent with congenital defects have been located. The drug was not teratogenic in rats and rabbits but was in hamsters.

Levalbuterol (Xopenex HFA) (240)

Levalbuterol is the (R)-enantiomer of racemic albuterol. It is given by inhalation. No reports of its use in human pregnancy have been located. However, racemic albuterol is considered compatible in pregnancy, and there is no apparent reason not to classify levalbuterol the same way. The drug, when given orally, is teratogenic in animals. If levalbuterol is used in pregnancy for the treatment of asthma, health care professionals are encouraged to call the toll-free number (1-877-311-8972) for information about patient enrollment in an Organization of Teratology Specialists study.

Mepolizumab (Nucala) (149,000)

Mepolizumab is given by subcutaneous injection. It is not indicated for status asthmaticus. There is no published human pregnancy data but the molecular weight suggests that it will not cross the placenta in the first half of pregnancy. The drug did not cause defects in monkeys and mice. There is a pregnancy exposure registry that monitors pregnancy outcomes in women with asthma exposed to Nucala during pregnancy. Health care providers can enroll patients or encourage patients to enroll themselves by calling 1-877-311-8972 or visiting www.mothertobaby.org/asthma.

Metaproterenol (521)

Metaproterenol, a selective beta2-adrenergic agonist, is a respiratory (bronchodilator) that is given orally. Use of this agent in pregnancy has not been linked with congenital defects. However, the drug is teratogenic in animals.

Methylprednisolone (Medrol) (374)

This is an oral glucocorticoid. The molecular weight suggests that it will cross the placenta throughout pregnancy. No reports relating to its use in human pregnancy or in pregnant animals have been located. However, teratogenicity is a potential problem (see below). If high doses of the drug are used in pregnancy, the newborn infants should be carefully observed for signs of hypoadrenalism. In addition, all corticosteroids increase calcium excretion.

Methylprednisolone acetate (Depo-Medrol) (417)

This is an injectable glucocorticoid. See below.

Methylprednisolone sodium succinate (Solu-Medrol) (497)

Methylprednisolone is a glucocorticoid given parenterally. The molecular weight suggests that it will cross the placenta throughout pregnancy. As with other corticosteroids, the drug was teratogenic, at doses equivalent to the human dose, in mice, rats, and rabbits. If the drug is used in pregnancy, the newborn infant should be carefully observed for signs of hypoadrenalism. In addition, all corticosteroids increase calcium excretion.

Mometasone + formoterol (Dulera) (321 + 841)

Dulera is a combination product of mometasone (corticosteroid) and formoterol (beta2-adrenergic agonist). There is no published human data for Dulera but the molecular weights suggest that the drugs will cross the placenta. Oral doses of formoterol were not teratogenic in animals but were with mometasone. The limited human pregnancy data with formoterol did not suggest a risk of embryo/fetal harm, but there is no human pregnancy data for mometasone.

Montelukast (Singulair) (608)

Montelukast is a leukotriene receptor antagonist that is given orally. Although the human data are limited, the drug does not appear to cause harm to the embryo and/or fetus. The drug was not teratogenic in rats and rabbits. The manufacturer maintains a pregnancy registry for women exposed to montelukast. Health care professionals are encouraged to report pregnancy exposures to the registry by calling the toll-free number 1-800-986-8999.

Omalizumab (Xolair) (149,000)

Omalizumab is a recombinant DNA–derived humanized immunoglobulin (IgG1k) monoclonal antibody that is administered subcutaneously for patients with moderate to severe persistent asthma. In monkeys, the drug did not cause embryotoxicity or teratogenicity. The human pregnancy data is very limited but does not suggest an increased embryo-fetal risk.

Prednisone (Rayos) (358)

The use of oral prednisone appears to represent a small risk to the developing fetus. One of these risks appears to be orofacial clefts. The drug causes birth defects in rats, mice, rabbits, and hamsters. However, the available evidence supports its use to control various maternal diseases, one of which is asthma.
 

Reslizumab (Cinqair) (147,000)

Reslizumab is given intravenously. Even though the molecular weight is high, the drug crosses the placenta during pregnancy. In placebo-controlled studies, anaphylaxis occurred in 0.3% of patients receiving the drug. No adverse effects were observed when the drug was given to pregnant mice and rabbits.

Salmeterol (Serevent Diskus) (416)

Salmeterol is a long-acting beta2-adrenergic agonist that is given as an aerosol or dry powder for oral inhalation. Because the drug acts locally in the lung, plasma levels are very low or undetectable and are a result of swallowed salmeterol. The limited human pregnancy data does not suggest risk of embryo-fetal harm. High oral doses in animals were not teratogenic.

Theophylline (180)

Oral theophylline is a methylxanthine that is indicated for the treatment of symptoms of chronic asthma and other chronic lung diseases. According to ACOG, theophylline is not a preferred asthma therapy but considered an alternative agent. No published reports linking the use of theophylline with congenital defects have been located. However, the drug is teratogenic in mice, rats, and rabbits at doses close to the human dose.

Tiotropium (Spiriva Respimat) (490)

Tiotropium, an anticholinergic bronchodilator, is given by oral inhalation only. No reports describing the use of tiotropium during human pregnancy have been located. The animal data suggest low risk. However, because of its long elimination half-life (about 25 hours), use of tiotropium immediately before the diagnosis of an inadvertent pregnancy would most likely result in the exposure of a portion of organogenesis.

Triamcinolone (Kenalog-40) (435)

Triamcinolone is an inhaled corticosteroid with potency slightly greater than prednisone. Although the systemic use of the drug has a small absolute risk of oral clefts and fetal growth restriction, inhaled triamcinolone does not appear to cause embryo-fetal harm. The drug is teratogenic when given orally to animals.

Breastfeeding

It is not known if the above drugs are excreted into breast milk. Agents with relatively low molecular weights will probably be in milk. However, if the maternal levels are low, the amount in milk will probably be very small, if at all. Nevertheless, it is doubtful if any of these agents, even if they are excreted into milk, will have a harmful effect on a nursing infant.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at obnews@mdedge.com.