E-Mail Message to Ms. Smith
Dear Ms. Smith,
Thank you for asking me to provide you with a direct personal consultation concerning your asthma and your asthma care. I will summarize the salient facts from the detailed written history and physician’s note you kindly provided.
As pointed out in your written history, you have had asthma since childhood. Among your earliest recollections is receiving injection treatments and later inhalation treatments for asthma in an emergency room. In your early teenage years you started treatment with inhaled Vanceril (beclomethasone), two puffs twice a day; 10 years ago, you switched to inhaled Qvar (beclomethasone driven by a hydrofluoroalkane [an ozone-layer–friendly] propellant), and Singulair (montelukast) was added to your regimen. Over the past 10 years, you have tried two different “combination inhalers,” containing both inhaled glucocorticoids and long-acting β2-agonists — namely, Advair (fluticasone propionate and salmeterol) and Symbicort (budesonide and formoterol fumarate dehydrate). These medications did not improve your symptoms or lung function as compared with inhaled beclomethasone alone, and you switched backed to Qvar.
Even with this regimen, however, your asthma symptoms are still present and bothersome. For example, two to three times a month you are awakened from your sleep between 3 a.m. and 4 a.m. by shortness of breath and cough; you can hear yourself wheeze. If you use your rescue albuterol inhaler, you are usually able to get back to sleep by 5 a.m.
Two years ago, skin tests were performed, and your total IgE level was measured. Your only positive skin tests were for house-dust mites and ragweed. Your total IgE level was 75 IU per milliliter. The allergist who did the testing suggested that you add a nonsedating antihistamine, such as loratadine, to your treatment during the times of year when you are most susceptible to symptoms; the loratadine was of some small help in controlling your runny nose, but there was no change in your asthma symptoms. Your allergist also referred you to a gastroenterologist, who performed 24-hour esophageal pH monitoring and found no abnormalities.
In the past decade, you have required treatment with oral prednisone on three occasions; the last instance was in 2009. Each of these exacerbations occurred during your allergy season. You have a peak-flow meter, which you use occasionally. Your best reading is 500 liters per minute; on most days, your peak-flow values are between 350 and 400 liters per minute.
You work in an office. You live with your husband and two children in a single-family home heated and air-conditioned with forced air. You have taken extensive measures to remove allergens from your home, including having the air ducts cleaned and tested for allergens. You have no pets. You have never smoked, and the same is true for your husband and your children. Smoking has not been allowed in your workplace for more than a decade. Your mother had asthma.
Your current medications are Qvar, 80 μg per puff, two puffs twice a day; Singulair, 10 mg per day, taken at night; and one multivitamin per day.
You would like a single consultation and confidential second opinion as to how your asthma has been managed and how to improve your asthma control.
On physical examination today, you looked well. Your weight was 135 lb [61.2 kg]. Your blood pressure was 110/75 mm Hg, and your pulse was 77 beats per minute according to the pulse oximeter, which also indicated that your hemoglobin saturation while you were breathing ambient air was 95%. Your physical examination was largely normal. No abnormalities were noted in your eyes, nose, or ears. Your chest examination was normal except for the presence of scattered expiratory wheezes, which were heard best during rapid, shallow breathing. There were no abnormalities in your extremities. Your neurologic examination was normal as well. Lung-function testing was performed in our laboratory; the results are attached to this letter (Figure 3Figure 3Spirometric Results for Ms. Smith.).
I think that the diagnosis of asthma is well established. You have a long history of asthma and have had salutary symptomatic responses to asthma treatments, your lung-function tests still show reversibility of airway obstruction of more than 15% with albuterol, and no other competing diagnosis has emerged over many years. The major issue now is to determine whether there are additional treatments that could help suppress your asthmatic symptoms without increasing the treatment burden.
You and your physicians have done an excellent job of managing your asthma. The treatments you are using now are well established and known to be effective. There are three treatments that could be added to your regimen, but it is difficult to be certain that they would be effective. First, oral theophylline could be added to your regimen. Although you cannot recall having received treatment with theophylline, given your age and asthma history, it is likely that you were treated with this agent as a child. This therapy could be of value, but it is necessary to monitor blood levels of the drug to obtain an optimum response, and some patients find testing to be burdensome. There is a small chance that theophylline could make your asthma worse by relaxing the muscle that separates your stomach from your esophagus; if this occurred, the treatment would be stopped.
Second, Singulair could be replaced with Zyflo CR (zileuton, controlled release). The active ingredient in Singulair is montelukast, which blocks the action of the cysteinyl leukotrienes at the CysLT1 receptor, whereas zileuton prevents the synthesis of both cysteinyl leukotrienes and dihydroxy leukotrienes. There are theoretical reasons to believe that controlled-release zileuton would yield a clinical benefit, but there are no compelling data to support this approach. Monitoring of liver function is required during initiation of treatment with zileuton.
Third, Xolair (omalizumab) could be added to your regimen. This anti-IgE monoclonal antibody is given once a month by injection. There is clearly an allergic component of your disease; your total IgE level is elevated, but it is not so high as to preclude the use of omalizumab.
As we discussed, I think your primary care physician has done an excellent job in designing your asthma treatment. You should discuss our consultation with her and decide what is in your best interest.
Comment: There have been three major changes in our understanding of asthma between 1928 and 2012. First, spirometry, which had been invented in the 1840s,13 was refined by adding time to volume output, and between the late 1940s and early 1950s, measurements made from forced exhalations were used in the diagnosis and treatment of asthma.14 Other lung-function tests were developed and used, and the relationships between clinical physiology and symptoms were delineated.15 Second, glucocorticoids were identified as an effective and useful asthma treatment. They were first used systemically in the early 1950s16 and were subsequently made available in inhaled form17,18,; these agents remain the standard of care today. Third, our understanding of the immunobiology of asthma progressed beyond the view that the essential mechanism was an immediate hypersensitivity reaction.19,20, Unfortunately, these advances in understanding the cell biology of asthma have not yet been translated into new therapies, although new therapies have been derived from our improved understanding of immediate hypersensitivity responses — notably, the use of leukotriene modifiers21 and anti-IgE antibodies.22
Our patient is current in her medical knowledge and is using medical information widely available on the Internet to help in the management of her chronic condition. The consultant used measures of lung function to quantify her physiological deficit. The consultant also measured the patient’s IgE level, which was consistent with allergic asthma, and provided the information needed for anti-IgE treatment, should the patient elect this approach. The patient has used all the standard asthma therapies but has residual symptoms. The consultant outlines other asthma treatments that the patient could try, highlighting the need to try different treatments to see whether one or another will work. Sadly, we still do not have a way to predict a given patient’s response to therapy.