Childhood Asthma Treatment: Not One-Size-Fits-All

Childhood Asthma Treatment: Not One-Size-Fits-All: Study helps guide treatment choices

A new study has found the addition of long-acting beta-agonist therapy to be the most effective of three step-up, or supplemental, treatments for children whose asthma is not well controlled on low doses of inhaled corticosteroids alone.

The study was designed to provide needed evidence for selecting step-up care for such children and was supported by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health. Researchers also identified patient characteristics, such as race, that can help predict which step-up therapy is more likely to be the most effective for a child with persistent asthma.

The study found that almost all of its participants had a different response to the three different treatments. Although adding the long acting beta-agonist step-up was one and one-half times more likely to be the best treatment for most of the study group, many children responded best to other two treatments instead.

“These results fill an important gap in our asthma guidelines,” said NHLBI Acting Director Susan B. Shurin, M.D., a board-certified pediatrician. “At the time the guidelines were written, there were very few comparison studies conducted in children whose asthma was poorly controlled with low-dose inhaled corticosteroids. Now that we have these study data, we can more confidently make recommendations for these children.”

The NHLBI’s Guidelines for the Diagnosis and Management of Asthma (EPR-3) recommend three treatment options for children with mild to moderate persistent asthma – for example, those experiencing symptoms at least two days per week – whose asthma is not well controlled on low doses of inhaled corticosteroids. These treatments, which were featured in the study, are adding a long acting beta agonist to the low-dose inhaled corticosteroids; adding a leukotriene receptor antagonist to the low-dose inhaled corticosteroids; and doubling the dose of inhaled corticosteroids. These recommendations were based on data collected from adults.

The study, called Best Add on Therapy Giving Effective Responses (BADGER), compared how effectively the three different step-up treatments improved asthma control in 182 children ages 6 to 18 years. All participants had mild to moderate persistent asthma that was not controlled on low-dose inhaled corticosteroids. Participants received each of the three treatments, with each treatment period lasting 16 weeks.

Responses were measured based on three factors: number of asthma episodes requiring oral corticosteroids, number of days of well controlled asthma, and lung function as measured by the amount of air exhaled in one second.

Overall, adding a long-acting beta-agonist to inhaled corticosteroids was significantly more likely (1.5 times) to be the best step-up therapy as compared to adding a leukotriene receptor antagonist to inhaled corticosteroids or to doubling inhaled corticosteroids.

Nearly all the children responded differently to the three treatments, with 45 percent of children responding best to adding a long-acting beta-agonist, 28 percent responding best to adding leukotriene receptor antagonist, and 27 percent responding best to doubling the dose of inhaled corticosteroids.

The study also identified several patient characteristics that increased the likelihood of identifying which step-up treatment would be more effective for an individual child. For example, African-American study participants were equally likely to respond best to long-acting beta-agonist step-up or inhaled corticosteroids step-up, and least likely to respond best to leukotriene receptor antagonist step-up. For white participants, the addition of a long-acting beta-agonist was clearly the most likely step-up therapy to give the best response, with inhaled corticosteroids step-up the least favorable therapy.

In addition, a long-acting beta-agonist was more likely to be the most effective step-up therapy among children who started the study with high scores on the Asthma Control Test, a five-item health survey used to measure asthma control, and among those who did not have eczema, an allergic skin condition.

“This study underscores the fact that individuals respond differently to different therapies ” childhood asthma treatment is not one-size-fits-all,” said Robert F. Lemanske, Jr., M.D., of the University of Wisconsin Hospital-Madison, one of the principal investigators of the study and lead author of the paper. “It is important to monitor the child’s response closely and, if necessary, adjust therapy with one of the other options within this step of care before moving to a higher step of care.”

The benefit of adding a different class of medication may be because of a possible ceiling effect for low-dose inhaled corticosteroids in some children, Dr. Lemanske said.

The observed overall best performance of long-acting beta-agonist step-up should be weighed against the increased risk of severe worsening of asthma symptoms leading to hospitalization and, in rare cases, death, as noted in the U.S. Food and Drug Administration approved labeling for long-acting beta agonists. Although there were no safety differences among the treatments during this study, the researchers assert the BADGER trial was not designed or powered to evaluate long-term safety of long-acting beta-agonists in children.

“This is the kind of study that will advance strategies for personalized medicine and improve treatment for children who have asthma,” said James Kiley, Ph.D, director of the NHLBI Division of Lung Diseases.

According to the Centers for Disease Control and Prevention, almost 7 million children in the United States have asthma, a leading cause of hospitalizations and school absenteeism. Common asthma symptoms include wheezing, shortness of breath, chest tightness, and coughing. While there is no cure for asthma, most children who receive effective treatment are able to control symptoms.

The study was conducted by researchers with the NHLBI’s Childhood Asthma Research and Education Network (CARE) centers. The CARE Network was established in 1999 to evaluate treatments for children with asthma; study sites are Penn State College of Medicine, Hershey, Pa.; National Jewish Health, Denver; University of Wisconsin – Madison; University of California, San Diego/Kaiser Permanente Medical Center; Washington University School of Medicine, St. Louis, Mo.; and University of Arizona College of Medicine, Tucson.

CARE centers also received support for this study from the National Center for Research Resources and the National Institute of Allergy and Infectious Disease, both part of NIH. Medications were provided by GlaxoSmithKline and Merck, Inc.

Part of the National Institutes of Health, the National Heart, Lung, and Blood Institute (NHLBI) plans, conducts, and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The Institute also administers national health education campaigns on women and heart disease, healthy weight for children, and other topics. NHLBI press releases and other materials are available online at

The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit

GSK begins Phase III Study of Relovair, a New Daily Treatment for Asthma

GlaxoSmithKline has begun a new phase III study of Relovair, its new daily treatment for sufferers of asthma according to press reports and press releases on the GSK website.

The pharmaceutical company revealed that the first patient to participate in the trial has now commenced treatment with the drug, which is an inhaler-administered therapy based on the compound fluticasone furoate/vilanterol trifenatate.

It has been developed in partnership with biopharmaceutical firm Theravance as part of the two companies’ long-acting beta2 agonist collaboration, which commenced in 2002.

This study, which is taking place across Europe and the US, will aim to establish the safety and efficacy of Relovair while comparing its performance to that of existing treatments for the condition.

The company expressed confidence that the treatment can prove to be a beneficial option for patients suffering from the “serious and chronic disease”.

Last week, the company received marketing authorization from the European Medicines Agency for Revolade, its treatment for chronic immune thrombocytopenic purpura.

GlaxoSmithKline commences Relovair Phase III asthma programme

GlaxoSmithKline (GSK) announced today that the first asthma patient has commenced treatment with Relovair™ (fluticasone furoate/vilanterol trifenatate) in an asthma exacerbation study, marking the start of the Phase III clinical development programme with this once daily therapy, for this serious and chronic disease.

The asthma programme for Relovair (previously referred to as ‘Horizon’) will assess the potential benefit of the combination of inhaled corticosteroid, fluticasone furoate, and long-acting beta agonist, vilanterol trifenatate (642444) versus the component products and existing treatments for asthma.

The programme will consist of a range of eight studies to determine the efficacy and safety of Relovair in asthma patients who remained uncontrolled on current treatment. The initiation of the exacerbation study complements a 12-month safety study that is already underway in support of the COPD programme. An additional six efficacy studies, including three comparator studies, are scheduled to start within the next quarter.

GSK is in ongoing discussions with the FDA regarding the US component of the global asthma programme following the recent FDA Advisory Committee meeting and the FDA’s proposed changes to the use of LABA-containing products in asthma.

Study designs
The asthma exacerbation study is a randomised, double-blind, parallel-group study being conducted in Europe, the US and other international locations. This study will evaluate Relovair 100/25mcg against fluticasone furoate 100mcg in patients whose asthma remains uncontrolled on current therapy. The primary endpoint – time to first severe asthma exacerbation – will inform on both safety and efficacy. The ongoing 12 month safety study, will evaluate the overall safety profile of Relovair and has been designed to support both the asthma and COPD indications.

The additional six efficacy studies comprise: a 24 week head to head study of Relovair vs Advair/Seretide, a 24 week fluticasone furoate vs fluticasone propionate vs placebo study, a 12 week vilanterol trifenatate vs salmeterol vs placebo study, a 12 week low dose combination study and a 24 week higher dose combination study vs components and an HPA axis study.

Patients across all of the Relovair programmes will be dosed using a unique single step activation inhaler. This novel delivery device has been developed utilising GSK’s expertise in device development and valuable patient input.

Relovair is being developed under the long-acting beta2 agonist (LABA) collaboration entered into in November 2002 with Theravance, Inc. a biopharmaceutical company with a pipeline of internally discovered product candidates.

Asthma Continues to be a Serious Public Health Problem

Asthma continues to be a serious public health problem. According to the Centers for Disease Control and Prevention

• About 23 million people, including almost 7 million children, have asthma.
* Asthma prevalence is higher among families with lower incomes.
• 12 million people report having an asthma attack in the past year.
• Asthma accounts for nearly 17 million physician office and hospital visits, 4 and nearly 2 million emergency department visits each year.
• African Americans continue to have higher rates of asthma emergency department visits, hospitalizations, and deaths than do Caucasians:
* The rate of emergency department visits is 350% higher.
* The hospitalization rate is 240% higher.
* The asthma death rate is 200% higher.
• Approximately 2 million Hispanics in the U.S. have asthma and Puerto Ricans are disproportionately impacted:
• The rate of asthma among Puerto Ricans is 125% higher than non-Hispanic white people and 80% higher than non-Hispanic black people.
• The prevalence of asthma attacks is highest among Puerto Ricans.

Asthma in Children:

• Asthma is one of the most common serious chronic diseases of childhood.
• Asthma is the third-ranking cause of hospitalization among children under 15.
• Asthma in children is the cause of seven million physician visits and nearly 200,000 hospitalizations.
• An average of one out of every 10 school-aged child has asthma.
• 13 million school days are missed each year due to asthma.

The Cost of Asthma:

• Annual expenditures for health and lost productivity due to asthma are estimated at over $20 billion, according to the National Heart, Lung, and Blood Institute.

Asthma and the Environment

Research by EPA and others has shown that:

• Dust mites, molds, cockroaches, pet dander, and secondhand smoke trigger asthma
• Exposure to secondhand smoke can cause asthma in pre-school aged children.
• Exposure to dust mites can cause asthma.
• Ozone and particle pollution can cause asthma attacks.
* When ozone levels are high, more people with asthma have attacks that require adoctor’s attention.
* Ozone makes people more sensitive to asthma triggers such as pet dander, pollen, dust mites, and mold.

Vitamin D and Asthma Attacks

Vitamin D helps fend Asthma attacks According to New Study

A new study of Japanese schoolchildren, vitamin D supplements taken during the winter and early spring helped prevent seasonal flu and asthma attacks states according to the American Journal of Clinical Nutrition.

Press reports reflect that the idea for the study came from an earlier study looking at whether vitamin D could help prevent the bone-thinning disease osteoporosis. The researchers in that study noticed that people taking vitamin D were three times less likely to report cold and flu symptoms.

During the study, conducted between December 2008 and March 2009, 31 of 167 children taking placebo caught influenza A, the most common form of the virus, compared with only 18 of 167 taking vitamin D.

The vitamin D group was 58 percent less likely to catch influenza A, the researchers report in the American Journal of Clinical Nutrition.

Vitamin D also appeared to suppress asthma attacks in children with a history of asthma. Two children taking vitamin D had asthma attacks during the study, compared to 12 children taking placebo. Urashima admitted to being a bit surprised by this finding and hopes to confirm it in a randomized trial targeting children with asthma.

Based on the current study, giving kids vitamin D supplements during the winter may help reduce cases of influenza A, the researchers conclude. Urashima suggests that children could take 1,200 IU per day starting in September to prevent flu and asthma attacks during the flu season, but best for parents to check with their pediatrician first.

SOURCE: American Journal of Clinical Nutrition, online March 10, 2010.

Asthma and Sleep Apnea

Asthma and Obstructive Sleep Apnea

According to research conducted by the National Institute of Health (NIH), mounting evidence implicates OSAS as a risk factor for asthma exacerbations, thereby linking these 2 major epidemics.

OBJECTIVE: To review the concept of a possible link between asthma and obstructive sleep apnea syndrome (OSAS) and the impact on asthma symptoms of treatment of OSAS with continuous positive airway pressure (CPAP) in patients with both conditions. DATA SOURCES: The Ovid, MEDLINE, and PubMed databases from 1950 to the present were searched for relevant articles regarding a possible relationship between asthma and OSAS and the effectiveness of CPAP in treating OSAS. STUDY

SELECTION: Articles describing pathophysiologic conditions occurring in OSAS that may be linked to asthma pathogenesis were used for this review. RESULTS: The data suggest that OSAS is an independent risk factor for asthma exacerbations. CPAP has been shown in prospective clinical studies to have a positive impact on asthma outcome in patients with concomitant OSAS. Ameliorative mechanisms of treatment with CPAP include mechanical and neuromechanical effects, gastroesophageal acid reflux suppression, local and systemic anti-inflammatory effects (including suppression of increased serum levels of inflammatory cytokines, chemokines, and vascular endothelial growth factor), cardiac function improvements, leptin level suppression, weight reduction, and sleep restoration.

CONCLUSIONS: Asthma and OSAS are increasingly troublesome public health issues. Mounting evidence implicates OSAS as a risk factor for asthma exacerbations, thereby linking these 2 major epidemics. We describe potential mechanisms whereby CPAP, the first line of therapy for OSAS, might modify airway smooth muscle function and asthma control in patients with both disorders. Despite the ever-increasing population of patients with both disorders, large, prospective, randomized controlled studies are necessary to more fully evaluate CPAP and asthma outcomes.

PLEASE NOTE: The information provided above is offered to you as a public service and not intended to replace your relationship with your physician. Please seek medical attention with any and all of your questions regarding your health.

Asthma Study Announced

Asthma and Flu Study Announced is reporting that researchers from Boston University are embarking on a national study of women who take medications or get vaccinated while they are pregnant, starting with flu and asthma treatments because they are widely taken and a common cause of concern.

BU’s Slone Epidemiology Center will compare women whose babies have major birth defects to mothers of normal babies, assessing their exposure to asthma medications, seasonal and H1N1 vaccine, and antiviral drugs such as Tamiflu. Based on information obtained from hospitals and birth registries, the researchers will interview mothers by telephone in Massachusetts, Philadelphia, San Diego, and New York state.

In another arm of the study, the Organization of Teratology Information Specialists will enroll pregnant women who use these medications or vaccines and compare them to pregnant women who don’t, following both groups after the babies are born.

“Our hope is to offer reassurance that a previously neglected area is going to receive some attention,” Slone director Dr. Allen Mitchell said in an interview.

Asthma drugs are the most commonly prescribed medications for pregnant women, he said, and health officials have noted pregnant women’s concerns about flu vaccine and medications.

“It’s not as though there’s good evidence that any of these agents are causing major problems,” Mitchell said. “Rather, there isn’t much data in the first place and some of the little data there are, are conflicting. Our hope is a large, rigorous study will be able to provide some credible answers.”

The study is funded by two federal bodies. The Agency for Healthcare Research and Quality is giving $2.5 million over five years and the Biomedical Advanced Research and Development Authority is spending $7.5 million for two years. Both grants are renewable. The effort, called the Vaccines and Medications in Pregnancy Surveillance System, or VAMPSS, is coordinated by the American Academy of Allergy, Asthma, and Immunology.

While the initial focus will be on flu and asthma, the surveillance system could be adapted to study other products pregnant women take in order to fill gaps in medical evidence, Mitchell said. “Postmarketing studies of drugs in pregnancy have been extremely haphazard.”