Half of Children With Treatment-Resistant Asthma Not Treated According to Guidelines

Becky McCall

September 14, 2010

September 14, 2010 — Many children with treatment-resistant asthma under specialist care are misdiagnosed. More than half would be successfully managed with a re-evaluation and better use of standard therapies, British researchers report.

In a review published in the September 4 issue of the Lancet, Andrew Bush, MD, consultant pediatric chest physician, and his colleague Sejal Saglani, MD, both from Royal Brompton Hospital in London, United Kingdom, examined evidence drawn from children with mild to moderate asthma and data extrapolated from adults with severe asthma. They will present the full results next week at the European Respiratory Society 2010 Annual Meeting in Barcelona, Spain.

"Despite the interest in innovative approaches, getting the basics right in children with apparently severe asthma will remain the foundation of management for the foreseeable future," Drs. Bush and Saglani write.

"The current best approach is thorough multidisciplinary assessment of children with problematic severe asthma, which should result in at least half of these children being successfully managed with conventional treatments," they continue.

According to the authors, management strategies — incorporating improved asthma education related to adherence to treatment, inhaler technique, dose, and frequency — and minimization of environmental triggers need to be reviewed in these apparently treatment-resistant patients.

The review examines studies that have been published in the past 15 years. The authors make recommendations on the basis of findings from a literature review and from their own clinical practice. Drawing data from their own series of home visits to investigate therapy use, the authors report that "treatment-related issues contributed to poor control in about half the patients."

Among areas discussed during home visits with patients, the investigators addressed psychosocial issues as a trigger for asthma exacerbations. They found anxiety and depression were common among children with severe asthma and their parents.

"Any major illness will have spin-offs on the child's life. A child is more than a pair of lungs, so anxiety and depression are common in children and parents, very naturally, and need to be addressed," Dr. Bush told Medscape Medical News.

Comorbidities such as reflux, rhinosinusitus, dysfunctional breathing, food allergy, and obesity were reviewed for their role in the potential exacerbation of asthma.

Once these potentially reversible factors have been identified in treatment-resistant patients, the authors recommend that the next step be a discussion with a multidisciplinary team.

"The aim is to decide whether further invasive investigations are justified and, if not, to develop a plan to address the reversible factors identified," they write.

Dr. Bush added that good respiratory nurses find out far more than professors in clinics, "so we need a full multidisciplinary team to try to sort out an individualized treatment plan on the basis of what is causing the pathology. Let's work together to get more information."

However, if satisfied that the basic patient management needs are met, the review showed that there was less evidence available to help decide on the next steps.

Dr. Bush recommends open discussion of the options available. "The best trials are in omalizumab, which would be my first choice if the child met the criteria; otherwise we develop an individualized treatment plan based on the type of inflammation of the airway," he said.

Commenting on the review, Jonathan Grigg, MD, professor of paediatric respiratory and environmental medicine at Barts and the London School of Medicine, Queen Mary University, United Kingdom, said difficult-to-treat asthma is a major problem but receives little attention.

"Bush and Saglani's comprehensive review in the Lancet is welcome. What is now needed is a concerted effort by funders to support comprehensive trials of new therapies. Governments should also recognize the importance of innovation when evaluating the cost-effectiveness of therapies that may be used in children with difficult asthma," he said.

Warren Lenney, MD, consultant respiratory paediatrician from the University Hospital of North Staffordshire in the United Kingdom, who also commented on the review, agrees that home visits are essential to understand if and how therapies are being used.

"Once these basic failings have been rectified there remain a small number of children with asthma who are problematic to manage and need the expertise of specialized children's asthma centers. This paper gives an excellent plan to address the need at the very severe end of the spectrum," he pointed out.

He added that often labeling a child's asthma as "very severe disease" is unfounded. "Despite huge increases in our knowledge of childhood asthma over the past 30 years, the striking feature for all to consider is that basic diagnosis and decision making is weak."

Dr. Bush emphasized a need for further research and collation of patient data, adding that an adult registry already exists and a pediatric one is being set up. His team is also part of European initiatives.

Dr. Bush's emphasis "on reconsidering the diagnosis and carefully assessing whether there has been good adherence with treatment is crucial," said Raezelle Zinman, MD, from the Division of Pulmonary Medicine at the Children's Hospital of Philadelphia in Pennsylvania, in an interview with Medscape Medical News.

"I am not sure that this necessitates an admission to hospital or home visit as a first step," Dr. Zinman added. "There needs to be documentation of what medication has been prescribed and with what frequency the prescription is actually being filled. This can be clarified with a call to the pharmacy. Simply checking the technique of medication delivery can be done in the office and can be very informative. For example, I have seen patients with vocal cord dysfunction and asthma who have been instructed to take their medication by performing an inspiratory capacity and breath-hold maneuver. In this condition, the vocal cords come together rather than separate when trying to take a breath in and the medication is not able to penetrate to the lungs."

"A better technique is to have the patient breathe in and out of a valved holding chamber 5 times after actuating the metered dose inhaler into the chamber," Dr. Zinman suggested.

"Another frequent comorbidity in difficult-to-treat asthmatics is sinusitis. I frequently am able to gain control [of asthma] after initiating therapy for rhinitis and sinusitis," she pointed out. "In children who have not responded to therapy, I have used a clinical trial of oral steroids for 2 weeks on an outpatient basis, with reassessment of lung function at the end of that period to look for improvement. These results are interpreted as evidence of reversibility but should not be presumed to be the ultimate improvement achievable."

"It is rare that invasive investigations are required beyond [computed tomography] imaging of the chest and sinus to rule out other diagnoses if the patient fails to respond to the above," Dr. Zinman asserted. "The difficult-to-control pediatric asthmatic patient warrants referral to a pediatric pulmonologist who has the expertise to work through these issues and determine appropriate therapy. We have all seen patients who have been misdiagnosed and overtreated with chronic steroid therapy to the point of becoming Cushingoid. Earlier referral should prevent this and decrease morbidity."

Dr. Bush, Dr. Grigg, Dr. Lenney, and Dr. Zinman have disclosed no relevant financial relationships.

Lancet. 2010;376:814-825. Abstract

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