Treatment of Chronic Asthma

Asthma is a chronic respiratory disease in which the lungs airways are narrowed, resulting in difficulty breathing. Very common in the U.S., the disease afflicts more than 16 million American adults and 6 million children. While many people with asthma have mild and infrequent symptoms, the disease can be deadly. Asthma kills more than 3,600 sufferers every year, highlighting the importance of continuous treatment in moderate to severe cases. But recent studies have demonstrated that, in certain cases, some asthma drugs also can be harmful or even fatal, making it important that patients understand their options.

Background and diagnosis

Asthma is characterized by wheezing, shortness of breath, chest tightness or cough. These symptoms tend to vary over time and can increase in response to various triggers. Diagnosis of asthma involves assessing the presence of these symptoms and conducting spirometry, a breathing test that measures how well the lungs airways function.

Asthma is classified into two major types: allergic asthma and non-allergic asthma. Allergic asthma often begins in childhood and is associated with a personal or family history of allergic diseases. Non-allergic asthma usually occurs in adults, with some cases that start in adulthood known as late-onset asthma. Most adults with asthma, especially those with late-onset asthma, do not respond as well to some treatments as do children with the disease.

The precise cause of asthma is unclear, but genetics, a tendency to develop allergies and certain respiratory infections during childhood are major risk factors.

Treatment

Treatment for chronic asthma aims both to control daily symptoms and to reduce the risk of future asthma attacks, hospitalizations and death. Two main types of medications are used to treat asthma . The first group of drugs works by reducing the chronic inflammation that makes the airways highly sensitive to irritants. The most commonly used anti-inflammatory drugs are inhaled corticosteroids (ICS). The other group of drugs works by opening the airways, helping some patients breathe easier. These are known as short-acting and long-acting beta-2 agonists — or SABAs and LABAs, respectively.

According to comprehensive asthma treatment guidelines issued by the Global Initiative for Asthma, the following patients should be given only a SABA inhaler as needed for short-term relief of symptoms: those who are newly diagnosed and have infrequent (less than twice a month) daytime symptoms, no nighttime symptoms, normal lung function and low risk for an asthma attack. All other asthma patients should begin treatment with varying doses of ICS in addition to an as-needed SABA inhaler — and, if significant symptoms persist, an ICS/LABA combination inhaler.

Patients symptoms and lung function then should be monitored every two to three months and treatment adjusted as necessary. Patients with severe cases that do not respond to high ICS and ICS/LABA doses may consider other treatments, including a short course of low-dose oral corticosteroids.

Other oral or intravenous drugs known as leukotriene receptor antagonists (singulair), are less effective than ICS, and are therefore not recommended if patients can tolerate and achieve relief on an ICS.

The guidelines also recommend lifestyle changes for all asthma patients. These include quitting smoking, getting regular exercise, avoiding occupational or environmental asthma triggers, and maintaining a healthy weight.

Controversy over LABA and SABA therapies

Use of regular ICS is now well established as an effective therapy for controlling asthma symptoms and preventing future attacks. However, there has long been evidence that using a SABA inhaler multiple times a day on a regular schedule (as opposed to its appropriate use on an as-needed basis) without ICS results in an increase in asthma attacks. It was later found that LABAs developed for daily or twice-daily use carry the same risks as regularly scheduled SABAs, when taken alone. Therefore, in 2010, the Food and Drug Administration (FDA) issued a warning against the use of LABAs without an anti-inflammatory medication, such as ICS, due to these risks.

It remains unclear, however, whether taking ICS in combination with LABA or regularly scheduled SABA inhalers eliminates this risk entirely and, if so, what dose of ICS is necessary to do so. A review of all clinical trials of the two approved LABAs in the U.S. — formoterol and salmeterol, alone and in combination with ICS — found that there was not enough evidence to rule out a risk of asthma-related deaths and other fatal outcomes from LABAs even when used with ICS. For this reason, four very large clinical trials of LABAs added to ICS, mandated by the FDA, are now underway to find out for sure. These safety concerns are now included in black-box warnings on the labels of all LABA-containing medicines. The labels also note that taking LABAs may be especially risky for children and adolescents.

Inhaled Medications Approved for Asthma In the U.S.

SABAs

• albuterol (ACCUNEB, PROAIR, PROVENTIL HFA, VENTOLIN HFA, VOSPIRE ER)
• levalbuterol (XOPENEX)

LABAs

• formoterol (FORADIL)
• salmeterol (SEREVENT)

ICS

• beclomethasone (QVAR)
• budesonide (PULMICORT FLEXHALER, PULMICORT RESPULES)
• ciclesonide (ALVESCO)
• flunisolide (AEROSPAN HFA)
• fluticasone furoate (ARNUITY ELLIPTA)
• fluticasone propionate (FLOVENT DISKUS, FLOVENT HFA)
• mometasone (ASMANEX, NASONEX)

ICS/LABA combinations

• budesonide-formoterol (SYMBICORT)
• fluticasone-salmeterol (ADVAIR)
• fluticasone-vilanterol (BREO ELLIPTA)
• mometasone-formoterol (DULERA)

Our Health Research Group agrees that all patients with asthma should carry a SABA inhaler at all times — but use it only as needed to relieve symptoms and in the event of an asthma attack. Regarding chronic therapy, we agree that patients who experience frequent daytime symptoms, have any nighttime symptoms or have lower-than-normal lung function should take an ICS, starting at a low dose and increasing gradually as needed. We recommend that LABAs, even in combination with ICS, not be used in children or adolescents with asthma due to the LABAs increased risks and minimal to no benefit in these age groups. In adults, we recommend that LABAs, always accompanied by ICS, be used cautiously for asthma and only when symptoms or lung dysfunction is severe and not responding adequately to ICS. If LABAs are needed, a combination LABA/ICS inhaler is the safest option. Taking a LABA in a separate inhaler raises the risk of missing ICS doses, which would put patients at increased risk of asthma attacks or death. Combination LABA/ICS inhalers should be used at the lowest dose and for the shortest duration possible. Every few months, patients should be evaluated to see whether therapy can be stepped back down to an ICS inhaler alone without worsening symptoms or lung function. It is very important that patients learn the proper technique for using ICS or ICS/LABA inhalers to ensure that the correct dose is inhaled.

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