Managing Severe Asthma

Vol. 16 •Issue 8 • Page 45
Managing Severe Asthma

The keys to success are timely diagnosis, appropriate medications, and effective education.

Asking an asthma specialist to recall one case that best represents severe, difficult-to-treat asthma is a little unfair.

No single flavor of ice cream represents all ice cream, no single movie represents all movies, and no single asthma patient represents all asthma patients.

“There are lots of different very bad asthmatics, certainly not all responding in the same manner, to the same things,” said Sally Wenzel, MD, director of Asthma and Allergic Disease Programs at University of Pittsburgh Medical Center.

Nevertheless, Dr. Wenzel did her best to comply with our request. “I had one very severe African-American patient who had arrested in the waiting room of the clinic and had been on and off steroids for many years,” she recalled. “She was highly allergic, with an FEV1 in the 40 to 50 percent range. She was on combination therapy, short-acting beta-agonists, etc.”

Eventually, the woman was treated successfully with anti-IgE therapy.

Another woman had developed particularly severe asthma just five years before Dr. Wenzel saw her. “She was bad right from the start, on high doses of meds, lots of prednisone bursts,” the pulmonologist recalled.

She had high eosinophils in her sputum and blood. Despite being treated with leukotriene receptor antagonists in the past with no response, she was started on 5-lipoxygenase inhibitor with dramatic improvement in symptoms, prednisone needs, and FEV1 (28 percent predicted to 75 percent predicted).

These two cases illustrate why asthma poses such a clinical challenge: The disease is so complex, the factors so varied, the patients so different, their environments unique, that treatment often requires a highly individualized approach.

Below the surface

In order to recognize and treat a medical condition, clinicians need a working definition of that condition. Severe, or refractory, asthma is no exception.

“Severe refractory asthma requires a definition in order to assess its prevalence, morbidity, and mortality, estimate its medical cost and burden to society, and to help diagnose high-risk patients early on — before severe asthma becomes fatal asthma,” said Elizabeth Bel, MD, a pulmonologist at Leiden University Medical Center, the Netherlands.

Traditional definitions of severe asthma encompass only its exterior presentation: daily symptoms, frequent exacerbations, an FEV1 of 60 percent of predicted with > 30 percent variability, all in spite of high-dose, appropriate therapy.

Put simply, moderate asthmatics differ from severe asthmatics (in general) because they improve with therapy, Dr. Wenzel said.

“Moderate asthmatics improve with high-dose steroids/combination therapy, whereas severe asthmatics do not improve, often until they get systemic steroids, with all the side effects,” she said.

What’s needed now is a definition that goes below the surface of severe asthma and encompasses its underlying pathology, Dr. Bel said. Just why are these patients refractory to known treatments such as inhaled corticosteroids and beta-agonists?

Asthma’s many forms

The latest thinking is severe asthma consists of several phenotypes. These can be generally divided by whether or not there’s persistent inflammation with high doses of steroids, and whether there’s a strong allergic component, more commonly seen in early onset asthma, or not, more commonly seen in late-onset asthma.

“Traditional definitions of asthma are not specific enough,” Dr. Bel told attendees at a recent conference of the American Thoracic Society. “We have to link the phenotype with the genotype. Only a phenotypic approach will explain fully what the interaction might be between genes and the environment in severe asthma.”

In the years ahead, researchers will try to separate groups of people with severe asthma based on their distinct phenotypes and study each group’s symptoms and responses to therapy. Better understanding of what’s driving the persistent inflammation in those with severe asthma should help to target therapies. And better understanding of what’s driving symptoms in the other non-inflammatory group should help physicians to think of ways to treat those patients.

“Severe asthma,” Dr. Bel assured her listeners, “is a very hot topic at the moment.”

Full gamut

To stabilize any asthma patient, especially more difficult cases, a caregiver must diagnose the level of asthma severity, choose the appropriate medications, and educate the patient in self-management. Do these three things well, and you not only save lives but reduce the cost of asthma care, which totals more than $11 billion annually in the U.S. alone, according to some estimates.

“There are many, many severe asthmatics that I do too little for,” Dr. Wenzel modestly admitted.

Before patients are classified as having severe or refractory asthma, they must be seen by a specialist for six months or more. Such patients require the full gamut of interventions.

“We work on compliance/adherence, obviously,” she said. “We also treat associated conditions, try to help them lose weight; try to get them to be as active as they can. Making ourselves available to adjust their steroids helps to some degree.”

An injection of systemic steroids (triamcinolone) can be useful in determining whether patients respond to steroids, completely removing compliance/adherence from the equation, Dr. Wenzel added.

Overuse of rescue meds

Many patients have difficult-to-treat asthma because they fall into a dangerous pattern: Rather than developing an asthma management routine, they wait until their airways become severely constricted and then rely entirely on their rescue meds.

“It is important to look at what you are doing as a provider that may be facilitating their poor self-care,” said Harold Farber, MD, medical director, Pediatric Asthma Care Management Program for Kaiser Permanente, Vallejo, Calif. “Are you giving unlimited access to quick relief medication so that they can get themselves into deeper trouble before they come in for care?”

Dr. Farber drastically has cut some patients’ access to quick-relief medicine and instructed them to rely more on their asthma controller medicine and to come into the hospital for urgent or emergent care.

“Though some providers are nervous about restricting access to quick-relief medicine, it has been well-established that overuse of quick-relief medicine leads to increased risk for ER visits, hospitalizations, and death from asthma,” he said.

Value of education

The third pillar of asthma management, alongside proper diagnosis and treatment, is patient education.

Respiratory therapists at a California hospital have demonstrated the value of patient education in preventing asthma from reaching the severe stage.

In years past, when patients entered the emergency department at Santa Barbara Cottage Hospital with asthma exacerbations, RTs administered meds via a handheld nebulizer and checked pulse, respirations, and breath sounds before, during, and after the ordered therapy.

That changed in 2000 when the department implemented a therapist-driven protocol for asthma care based on the premise that most people with asthma self-medicate at home with a metered dose inhaler.

The department launched a vigorous campaign to have RTs teach patients more effective self-management immediately upon admission to the ED. They taught patients to use an MDI with a valved holding chamber, to read a peak flow meter to determine when their lungs are most open or most narrow, and to identify sign of an imminent flare-up.

“Peak flow meters are amazing in how patients can actually visualize how tight they are and how to control it,” said Jane Chancellor, RRT, a staff therapist for 38 years at Santa Barbara Cottage Hospital.

All this plus diligent follow-up phone calls to patients dropped the ED admission rate and return rate for asthma both by 40 percent, a statistic that still holds today.

The only change in the works for the asthma protocol in the ED is substituting levalbuterol inhalation solution in place of albuterol for mild asthma, and ipratropium bromide and albuterol sulfate inhalation aerosol for moderate to severe asthma, said Paul Sherman, MS, RRT, RPFT, director of the respiratory care department.

Of 115 asthma patients treated in the first six months of this year, no one returned after two weeks and only seven patients returned within two weeks, a return rate of just 6 percent. “We don’t run into out-of-control asthma much anymore,” Chancellor said.

Michael Gibbons is senior associate editor of ADVANCE. He can be reached at [email protected].

TENOR Risk Score

Caregivers first must identify which patients are most at risk for difficult-to-manage asthma in order to treat it successfully.

Sally Wenzel, MD, director of Asthma and Allergic Disease Programs at University of Pittsburgh Medical Center, and others published a risk assessment tool for severe asthma as part of The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study.1

Their tool determines asthma severity via a scoring system that weighs factors such as a patient’s age, weight, smoking status, medical history, medication use, and whether or not the patient exercises.

In the three-year multicenter, observational study of more than 2,800 asthma patients, those assigned the highest TENOR risk scores proved to be 10 times more likely to need emergency treatment or be admitted to a hospital than patients who were assigned low scores.

Advocates say the TENOR risk score can determine which patients are most likely to require asthma-related hospitalization or ER visits, thereby improving asthma care and reducing costs.

But it begs a question: Don’t physicians already ask patients with asthma about such details as smoking status, exercise habits, and the like? Too often, the answer is, “No.”

“Many physicians do not ask these questions,” Dr. Wenzel said. “The more common question is ‘How is your asthma?’ The patient responds ‘OK,’ and they move on to the next subject.”

Funded by the pharmaceutical firm Genentech, the TENOR risk score “will probably be implemented by a large managed care organization to help identify patients in their population at high risk,” she said. “Then they can intervene as best they can, and see if their scores change.”

Michael Gibbons


1. Miller M, Lee J, Blanc P, et al. TENOR risk score predicts healthcare in adults with severe or difficult-to-treat asthma. Eur Respir J. 2006; 28:1145-55.

The Asthma-Allergy Connection

Asthma affects millions of people directly or indirectly. But most aren’t aware of its most common form allergic asthma.

Between 60 percent and 78 percent of patients with asthma have co-existing allergic rhinitis.1 One in three people with allergic rhinitis eventually develops asthma.2

Our understanding of asthma and allergic rhinitis has evolved to a new level. Historically, these allergen-induced disease conditions were viewed as separate entities. We know now the relationship between asthma and allergic rhinitis is a single continuum of inflammation involving one common airway.

Role of IgE

For almost 25 years, the medical community has recognized that immunoglobulin E (IgE) is responsible for allergic responses, and most patients with asthma have elevated serum IgE levels.3 Serum IgE levels are a marker of the immune response to allergens that results in the development of airway hyperresponsiveness.4

Debate continues about the level of IgE needed to cause asthma and whether it can predict the severity of the disease.

Serum IgE levels are age-related, with peak levels occurring during childhood and typically decreasing thereafter.5 Applying what we now know about the relationship between asthma and allergies, it makes sense that the prevalence of asthma was greater in 2004 in children birth to 17 years (85.1 per 1,000) than in adults 18 years and older (63.9 per 1,000).6 Similarly, over the past eight years, the rate of asthma attacks in 5- to 17-year-olds was higher than in any other age group.6

Allergic cascade

The allergic cascade of asthma begins when an allergen is inhaled by someone who is sensitive to that allergen. A macrophage, part of the first line of defense in the immune system, engulfs and breaks down the allergen in an attempt to eliminate it from the body. This initiates a series of reactions among cells within the immune system, and the reactions lead to the production of plasma cells.

Plasma cells produce IgE and release it into the blood. Patients who have allergies continue to make IgE as long as they breathe in allergens. Ultimately, IgE attaches to mast cells.

As mast cells encounter allergens a second time, the allergen binds to the IgE on the cell surface. This causes the mast cells to open and release histamine, prostaglandins, and leukotrienes. These contribute to airway inflammation, bronchoconstriction, and the allergic response in asthma patients.


In light of the abundance of recent data on allergic asthma and its prevalence, it’s essential asthma patients know their allergic triggers. The National Asthma Education and Prevention Program expert panel recommends allergy testing for patients with persistent asthma who require daily pharmacologic therapy.7 Patient education should emphasize avoidance of specific triggers and implementation of environmental controls.

For a list of references, look under the “From Print” toolbar on the left side of our home page at

Karen Rance, PNP, CAE, works at Tidewater Pediatric Consultants in Virginia Beach, Va.