Feature

Pediatric asthma over 3 decades: The plateau beyond the epidemic

To mark our 30th anniversary, Infectious Diseases in Children will be examining some of the chronic conditions and infectious diseases that have impacted pediatric care over the past 3 decades.

From 1980 to 1987, the death rate from asthma in the United States rose from 1.3 per 100,000 population to 1.7, according to the CDC. Although asthma mortality rates had been steadily declining in the U.S. and Canada from 1965 through 1978, a relatively abrupt 31% increase provided cause for alarm.

Subsequent nationwide asthma surveillance reports identified a disparate asthma burden for certain demographics, with notably higher population-based prevalence rates, emergency department rates and hospitalization rates among blacks compared with whites and girls compared with boys.

However, surveillance also recognized that these rates were higher among children than among adults; in fact, the mortality rate was the only asthma measure in which adults exceeded children.

Gary Rachelefsky
Gary Rachelefsky

Although asthma prevalence among children more than doubled from 1980 (3.6%) to 1995 (7.5%), according to the U.S. Department of Health and Human Services, asthma attacks among children have remained relatively constant, due, in part, to a better understanding of the mechanisms of asthma.

Recognized as a chronic inflammatory condition occasionally complicated by bronchospasms – rather than the reverse of earlier years – asthma was treated with a variety of bronchodilators, including theophylline, ephedrine, adrenaline and isoprenaline, as well as steroids. However, an over-reliance on these medications and inadequate asthma control also contributed to an escalating number of asthma-related deaths among children in the U.S., U.K. and Australia.

“When I first went into the business [of treating asthma] in 1972, I would have four or five patients at one time in the hospital treated with steroids,” Gary Rachelefsky, MD, FAAP, FAAAI, professor of allergy and immunology at the David Geffen School of Medicine at UCLA, told Infectious Diseases in Children. “This would be especially noticeable in the fall, when children returned to school and picked up viral illnesses that would trigger asthma.”

Although significant progress has been made in epidemiological research and therapy for pediatric asthma over the past 30 years, scant adherence to asthma medications and inadequate education on the risk of poor asthma control contribute heavily to soaring asthma rates: Asthma remains the third highest cause for hospitalization among children and one of the leading causes of school absenteeism.

Entering the ‘asthma epidemic’

Despite the variety of asthma controller medications available in the 1980s and into the present day, pediatric asthma rates have continued to climb. According to a study by Akinbami and colleagues published in Pediatrics, the overall prevalence of asthma in children rose steadily from 2001 (8.7%) to 2009 (9.7%), before declining slightly in 2010 (9.3%).

In 2015, the CDC reported that pediatric asthma prevalence had continued its decline, dropping to 8.4%. Following its peak in 2009, the widespread ‘asthma epidemic’ appeared to have plateaued and began its decline – a trend offset by widening racial and socioeconomic disparities in asthma prevalence.

In a 2009 study, Akinbami and colleagues had determined that, compared with white children, asthma prevalence was significantly higher among Puerto Rican (2.4 times), black (1.6 times) and Native American (1.3 times) children. Although racial discrepancies are largely believed to be linked to poverty, increased exposure to air pollution and a lack of access to preventive medical care, experts remain uncertain about what is contributing to soaring asthma rates across all pediatric demographics.

Among the more notable theories for the skyrocketing asthma prevalence has been the “hygiene hypothesis.” First described in 1989 by David P. Strachan, MD, PhD, the hypothesis posits that consistent exposure to allergens in early childhood strengthened the immune system against developing allergies, and improved sanitary conditions in developed countries were responsible for increased asthma rates.

Although the theory was supported by migration studies in which people migrating from a low-incidence to a high-incidence country acquired immune disorders with a high incidence in the first generation, more recent data compiled by Jean-Francois Bach, MD, PhD, has established no causal connection between asthma, other immune disorders and infection.

“Overall, people may be recognizing [asthma in children] better, and in this country, we may be seeing some influence of tremendous immigration that has occurred that would especially allow the Hispanic communities to get diagnosed more often,” Bobby Lanier, MD, FACAAI, executive medical director at the American College of Allergy, Asthma & Immunology, said in an interview with Infectious Diseases in Children. “In their previous countries, their condition might not have been recognized at all.”

Stanley J. Szefler
Stanley J. Szefler

One explanation for why researchers have not been able to observe a direct cause for the increase in prevalence rates among children is that testing for many of these theories, including antibiotic use altering genetics or vitamin D deficiency, is difficult to demonstrate clinically.

“There are a number of theories that have been put forward for the etiology of asthma and its rising prevalence, but all of them are hard studies to design and conduct,” Stanley J. Szefler, MD, director of the pediatric asthma research program at Children’s Hospital Colorado and the department of pediatrics at University of Colorado School of medicine, said in an interview. “I don’t think asthma is increasing as rapidly as it was in the ‘80s and ‘90s, but what I find more concerning is where the higher rates of prevalence are – in inner cities and in the African-American population. There are no firm reasons for what is causing it, but it may be environmental or socioeconomic.”

Medication management

Among the more notable advancements and concerns in the area of pediatric asthma is the appropriate use of medication to prevent and control symptoms. Currently, standard of care may include inhaled corticosteroids as an anti-inflammatory medication, long-acting bronchodilators to open the airways and albuterol inhalers for loss of control and significant exacerbations of asthma. Biologics, which inhibit the specific set of cytokines that catalyzes inflammation, have also been developed, and studies are currently underway for use in children and adults.

Although these treatments are widely available, many patients do not regularly take them or are prescribed “quick fixes.” Lanier claims that many children and their families have not been educated on the topic, and many come out of an ED or pediatrician’s office with a nebulizer and oral steroids. Part of this inadequate education may result from the ease in which some of these medications can be used, he said, because oral steroids now come in flavors and they are inexpensive.

“If we look at the level of education from the standpoint of the people who prescribe oral steroids, primary care physicians that were board-certified pediatricians were less likely to prescribe steroids to kids as compared to other doctors in primary care,” Lanier told Infectious Diseases in Children. “There is a lot of variation among pediatricians and family physicians across the country; the use of steroids and nebulizers four or five times a year for short-term approaches to asthma is probably not the best way to handle a chronic disease process.”

The development of inhaled corticosteroids has been a major advancement in the treatment and prevention of asthma, but these medications can, in fact, only control and prevent symptoms. If medication is discontinued, symptoms may return and a child may experience severe exacerbations.

“Medication adherence is a huge issue if we want to alter the disease pattern,” Szefler said. “I think there is better appreciation now [than in the past] that certain patients can develop an irreversible pulmonary function component that may in some ways be like [chronic obstructive pulmonary disease] because of their disease’s progression, possibly as a result of repeated asthma exacerbations.”

A stronger sense of the disease process and the treatment of the conditions has been gained, but the progression of medical understanding of asthma does not appear to have carried over into the field of monitoring disease progression and managing chronic asthma.

Lessons learned

Rachelefsky noted that in the past 3 decades, pediatricians and primary care providers have gained a better understanding of asthma on a cellular level, with similar understanding observed in other pulmonary conditions that affect children, namely cystic fibrosis.

“The techniques we use for cystic fibrosis and asthma have complimented each other,” he said. “We are understanding [asthma] on a genetic and cellular level, and we are learning how to alter the cell and the chemicals that cause the disease. The past 30 years have given us the tools to look at other diseases of the airways, especially the nose, the sinuses and the bronchial tubes.”

Compared with the 6.2 million children living with asthma in the U.S., only 30,000 people are living with cystic fibrosis, according to the Cystic Fibrosis Foundation Patient Registry – however, approximately 75% of these individuals are diagnosed by 2 years of age.

“Cystic fibrosis is a chronic disease that has received a concerted approach, including medication development by the clinicians in collaboration with industry and network collaboration to conduct studies, but with asthma, it’s been a more fragmented process that is not as well coordinated,” Szefler said in an interview. “It’s more difficult because we don’t have a gene to focus on; asthma is significantly more prevalent and is heterogeneous in terms of its presentation.”

According to Szefler, the advances in understanding asthma over the last 30 years has also spurred a trend in personalized medicine in asthma and allergy treatment.

“I think we’ve learned about driving forces like the interaction between allergy and allergic inflammation and viral infection that relate to the risk of asthma exacerbation,” he said in an interview. “We’re now using biomarkers and patient characteristics and beginning to identify patients at risk for exacerbations. I think that our newer drugs are more effective than they were in the ‘80s, but we have a lot to learn and to apply in terms of population surveillance and collaborative management strategies to minimize these exacerbations.”

Although the understanding of the condition has strengthened, its rising prevalence over the last 3 decades has created concerns about the future of the children who are prescribed steroids to be taken daily. A similar concern can be seen when considering antibiotic resistance, according to Lanier.

“I think that people are no longer afraid of corticosteroids, but at the same time, we look at them and see that the problems associated with steroids are long term,” Lanier said. “While you may not get a lot of weight gain and growth retardation, you may set them up for adult osteoporosis and cataracts. I think that the reversal of the ‘steroid phobia’ came with a lesson in that you should not advocate the use of powerful drugs as ‘harmless’ because people may overdo that.” — by Katherine Bortz

Disclosures: Lanier, Rachelefsky and Szefler report no relevant financial disclosures.

To mark our 30th anniversary, Infectious Diseases in Children will be examining some of the chronic conditions and infectious diseases that have impacted pediatric care over the past 3 decades.

From 1980 to 1987, the death rate from asthma in the United States rose from 1.3 per 100,000 population to 1.7, according to the CDC. Although asthma mortality rates had been steadily declining in the U.S. and Canada from 1965 through 1978, a relatively abrupt 31% increase provided cause for alarm.

Subsequent nationwide asthma surveillance reports identified a disparate asthma burden for certain demographics, with notably higher population-based prevalence rates, emergency department rates and hospitalization rates among blacks compared with whites and girls compared with boys.

However, surveillance also recognized that these rates were higher among children than among adults; in fact, the mortality rate was the only asthma measure in which adults exceeded children.

Gary Rachelefsky
Gary Rachelefsky

Although asthma prevalence among children more than doubled from 1980 (3.6%) to 1995 (7.5%), according to the U.S. Department of Health and Human Services, asthma attacks among children have remained relatively constant, due, in part, to a better understanding of the mechanisms of asthma.

Recognized as a chronic inflammatory condition occasionally complicated by bronchospasms – rather than the reverse of earlier years – asthma was treated with a variety of bronchodilators, including theophylline, ephedrine, adrenaline and isoprenaline, as well as steroids. However, an over-reliance on these medications and inadequate asthma control also contributed to an escalating number of asthma-related deaths among children in the U.S., U.K. and Australia.

“When I first went into the business [of treating asthma] in 1972, I would have four or five patients at one time in the hospital treated with steroids,” Gary Rachelefsky, MD, FAAP, FAAAI, professor of allergy and immunology at the David Geffen School of Medicine at UCLA, told Infectious Diseases in Children. “This would be especially noticeable in the fall, when children returned to school and picked up viral illnesses that would trigger asthma.”

Although significant progress has been made in epidemiological research and therapy for pediatric asthma over the past 30 years, scant adherence to asthma medications and inadequate education on the risk of poor asthma control contribute heavily to soaring asthma rates: Asthma remains the third highest cause for hospitalization among children and one of the leading causes of school absenteeism.

Entering the ‘asthma epidemic’

Despite the variety of asthma controller medications available in the 1980s and into the present day, pediatric asthma rates have continued to climb. According to a study by Akinbami and colleagues published in Pediatrics, the overall prevalence of asthma in children rose steadily from 2001 (8.7%) to 2009 (9.7%), before declining slightly in 2010 (9.3%).

In 2015, the CDC reported that pediatric asthma prevalence had continued its decline, dropping to 8.4%. Following its peak in 2009, the widespread ‘asthma epidemic’ appeared to have plateaued and began its decline – a trend offset by widening racial and socioeconomic disparities in asthma prevalence.

In a 2009 study, Akinbami and colleagues had determined that, compared with white children, asthma prevalence was significantly higher among Puerto Rican (2.4 times), black (1.6 times) and Native American (1.3 times) children. Although racial discrepancies are largely believed to be linked to poverty, increased exposure to air pollution and a lack of access to preventive medical care, experts remain uncertain about what is contributing to soaring asthma rates across all pediatric demographics.

Among the more notable theories for the skyrocketing asthma prevalence has been the “hygiene hypothesis.” First described in 1989 by David P. Strachan, MD, PhD, the hypothesis posits that consistent exposure to allergens in early childhood strengthened the immune system against developing allergies, and improved sanitary conditions in developed countries were responsible for increased asthma rates.

Although the theory was supported by migration studies in which people migrating from a low-incidence to a high-incidence country acquired immune disorders with a high incidence in the first generation, more recent data compiled by Jean-Francois Bach, MD, PhD, has established no causal connection between asthma, other immune disorders and infection.

“Overall, people may be recognizing [asthma in children] better, and in this country, we may be seeing some influence of tremendous immigration that has occurred that would especially allow the Hispanic communities to get diagnosed more often,” Bobby Lanier, MD, FACAAI, executive medical director at the American College of Allergy, Asthma & Immunology, said in an interview with Infectious Diseases in Children. “In their previous countries, their condition might not have been recognized at all.”

Stanley J. Szefler
Stanley J. Szefler

One explanation for why researchers have not been able to observe a direct cause for the increase in prevalence rates among children is that testing for many of these theories, including antibiotic use altering genetics or vitamin D deficiency, is difficult to demonstrate clinically.

“There are a number of theories that have been put forward for the etiology of asthma and its rising prevalence, but all of them are hard studies to design and conduct,” Stanley J. Szefler, MD, director of the pediatric asthma research program at Children’s Hospital Colorado and the department of pediatrics at University of Colorado School of medicine, said in an interview. “I don’t think asthma is increasing as rapidly as it was in the ‘80s and ‘90s, but what I find more concerning is where the higher rates of prevalence are – in inner cities and in the African-American population. There are no firm reasons for what is causing it, but it may be environmental or socioeconomic.”

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Medication management

Among the more notable advancements and concerns in the area of pediatric asthma is the appropriate use of medication to prevent and control symptoms. Currently, standard of care may include inhaled corticosteroids as an anti-inflammatory medication, long-acting bronchodilators to open the airways and albuterol inhalers for loss of control and significant exacerbations of asthma. Biologics, which inhibit the specific set of cytokines that catalyzes inflammation, have also been developed, and studies are currently underway for use in children and adults.

Although these treatments are widely available, many patients do not regularly take them or are prescribed “quick fixes.” Lanier claims that many children and their families have not been educated on the topic, and many come out of an ED or pediatrician’s office with a nebulizer and oral steroids. Part of this inadequate education may result from the ease in which some of these medications can be used, he said, because oral steroids now come in flavors and they are inexpensive.

“If we look at the level of education from the standpoint of the people who prescribe oral steroids, primary care physicians that were board-certified pediatricians were less likely to prescribe steroids to kids as compared to other doctors in primary care,” Lanier told Infectious Diseases in Children. “There is a lot of variation among pediatricians and family physicians across the country; the use of steroids and nebulizers four or five times a year for short-term approaches to asthma is probably not the best way to handle a chronic disease process.”

The development of inhaled corticosteroids has been a major advancement in the treatment and prevention of asthma, but these medications can, in fact, only control and prevent symptoms. If medication is discontinued, symptoms may return and a child may experience severe exacerbations.

“Medication adherence is a huge issue if we want to alter the disease pattern,” Szefler said. “I think there is better appreciation now [than in the past] that certain patients can develop an irreversible pulmonary function component that may in some ways be like [chronic obstructive pulmonary disease] because of their disease’s progression, possibly as a result of repeated asthma exacerbations.”

A stronger sense of the disease process and the treatment of the conditions has been gained, but the progression of medical understanding of asthma does not appear to have carried over into the field of monitoring disease progression and managing chronic asthma.

Lessons learned

Rachelefsky noted that in the past 3 decades, pediatricians and primary care providers have gained a better understanding of asthma on a cellular level, with similar understanding observed in other pulmonary conditions that affect children, namely cystic fibrosis.

“The techniques we use for cystic fibrosis and asthma have complimented each other,” he said. “We are understanding [asthma] on a genetic and cellular level, and we are learning how to alter the cell and the chemicals that cause the disease. The past 30 years have given us the tools to look at other diseases of the airways, especially the nose, the sinuses and the bronchial tubes.”

Compared with the 6.2 million children living with asthma in the U.S., only 30,000 people are living with cystic fibrosis, according to the Cystic Fibrosis Foundation Patient Registry – however, approximately 75% of these individuals are diagnosed by 2 years of age.

“Cystic fibrosis is a chronic disease that has received a concerted approach, including medication development by the clinicians in collaboration with industry and network collaboration to conduct studies, but with asthma, it’s been a more fragmented process that is not as well coordinated,” Szefler said in an interview. “It’s more difficult because we don’t have a gene to focus on; asthma is significantly more prevalent and is heterogeneous in terms of its presentation.”

According to Szefler, the advances in understanding asthma over the last 30 years has also spurred a trend in personalized medicine in asthma and allergy treatment.

“I think we’ve learned about driving forces like the interaction between allergy and allergic inflammation and viral infection that relate to the risk of asthma exacerbation,” he said in an interview. “We’re now using biomarkers and patient characteristics and beginning to identify patients at risk for exacerbations. I think that our newer drugs are more effective than they were in the ‘80s, but we have a lot to learn and to apply in terms of population surveillance and collaborative management strategies to minimize these exacerbations.”

Although the understanding of the condition has strengthened, its rising prevalence over the last 3 decades has created concerns about the future of the children who are prescribed steroids to be taken daily. A similar concern can be seen when considering antibiotic resistance, according to Lanier.

“I think that people are no longer afraid of corticosteroids, but at the same time, we look at them and see that the problems associated with steroids are long term,” Lanier said. “While you may not get a lot of weight gain and growth retardation, you may set them up for adult osteoporosis and cataracts. I think that the reversal of the ‘steroid phobia’ came with a lesson in that you should not advocate the use of powerful drugs as ‘harmless’ because people may overdo that.” — by Katherine Bortz

Disclosures: Lanier, Rachelefsky and Szefler report no relevant financial disclosures.

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