Monday, January 20, 2014

Our New Year's Asthma Wish List

Living with asthma can be full of frustrations and sometimes worse, imposing limitations and causing frightening flare-ups or “attacks.” We would like the asthma to just “go away,” so that at the top of our 2014 Wish List for asthma is finding a cure. And some days it feels as though we are getting closer – if not to a cure, at least to primary prevention. Interesting research into the low rates of asthma among children reared on small farms, brought up in close contact with farm animals and the detritus in their stalls, has led to speculation that introducing harmless germs into the environment of young children … the right germs in the right combination, at the right time, by the right route (ingested or inhaled?), in the right amount, and for the right duration … might lessen the risk of developing asthma. But short of eliminating asthma all together, here is our wish list – the “short list” -- for improvements in asthma care that we think are, or should be, within our grasp.

1. Low-cost, generic asthma medications. Ten years ago a generic albuterol inhaler was available without insurance coverage for less than $20. With the banning of inhaled medications using chlorofluorocarbon (CFC) propellants beginning in 2009, generic albuterol disappeared from sale, replaced by brand-name versions of albuterol with the hydrofluoroalkane (HFA) propellant, such as ProAir, Proventil, and Ventolin, all considerably more expensive. And despite their availability now for several decades, inhaled corticosteroids by metered-dose inhaler or dry-powder inhaler have never had a generic version available. It is true that generic albuterol and the inhaled steroid, budesonide, are available for nebulization, but it is not practical to ask all persons with asthma to administer their medications by nebulizer over 5-10 minutes for each dose, let alone carry a nebulizer with them at all times for emergency use. The Food and Drug Administration (FDA) should ease whatever restrictive regulations prevent release of generic albuterol-HFA and at least one generic inhaled corticosteroid, such as beclomethasone (first released in the United States in the early 1970s) or fluticasone (first released in the US more than 30 years ago).

2. Reduced medication side effects. On the bright side, most persons with asthma can achieve good asthma control (rare symptoms and freedom from asthma exacerbations) with currently available medications taken once or twice daily. Unfortunately, though generally well tolerated, these medications are not free of side effects. In particular, we are struck by how often our patients taking an inhaled medication that contains a corticosteroid complain of hoarse voice. Other side effects from the inhaled steroids include the risk of a yeast infection in the mouth (oral candidiasis or “thrush”) and, after many years of use at high doses, a slightly increased risk of cataracts, glaucoma, and loss of bone mass (osteoporosis). In growing children, slightly slowed vertical growth (ultimate height reduced on average by approximately 1/4-1/2 inch) is a concern. Although we can’t expect our medications to be entirely free of all undesirable effects, these are annoying side effects that sometimes limit use and are a worthy target for drug development or drug modification.

3. Identical health outcomes for people of color with asthma. More than twenty years ago epidemiologic studies identified the unequal distribution of asthma morbidity and mortality in the US. The rates of hospitalization and death due to asthma among African-Americans and Hispanics were 3-4 times greater than among whites. Now, after three releases of Guidelines for the Diagnosis and Management of Asthma by the National Heart, Lung, and Blood Institute of the National Institutes of Health to care providers throughout the US, the overall rates of hospitalization and death from asthma are decreasing, but racial and ethnic inequalities remain unchanged. In the US the color of one’s skin is a risk factor for dying from a severe asthma attack. Exactly why this injustice persists is uncertain, but it is likely that increased rates of poverty among persons of color play a major role. Addressing poverty and its link to poor asthma care is not an easy assignment, but it is not insurmountable. The work of Dr. Paul Farmer and Partners in Health in Haiti and elsewhere around the world should inspire our efforts in asthma care here in the US.

4. Novel therapies for severe, refractory asthma. Although most persons with asthma can achieve good asthma control with currently available medications, some cannot. It is estimated that as many as 20-25% of persons with asthma continue with frequent symptoms and multiple asthmatic attacks despite faithful use of strong, best-that-we-have asthma medications. Even if the true percentage were less, say 10%, that would mean that nearly two million Americans are in need of newer, more effective therapy for their asthma. Research is progressing in the development of novel medications for this subgroup of persons with “refractory” asthma. Designer molecules (called monoclonal antibodies) are being developed that will block the recruitment of allergy cells (eosinophils) to the bronchial tubes and inhibit powerful inflammation-stimulating molecules. Examples include monoclonal antibodies against interleukin 5 (mepolizumab and reslizumab), interleukin 13 (lebrikizumab), and the shared molecular receptor for interleukin-4 and 13 (dupilumab). Although the promise of these new biologic therapies is great, they are destined to be hugely expensive and require administration by injection or intravenous infusion. The search for alternative, simpler small molecular inhibitors of key biologic processes in asthma continues.

5. Preventing dangerous asthma attacks: “An app for that.” Despite our progress in treating asthma -- by targeting the underlying inflammation of the bronchial tubes as well as preventing spasm of the bronchial muscles that can tighten around our airways -- dangerous asthma attacks continue to occur. Nearly two million times a year persons with asthma rush to the emergency department of a hospital for treatment of asthma attacks. Sometimes these attacks develop gradually, as cough and chest tightness evolve into greater and greater breathlessness. Sometimes they catch us by surprise, lacking the usual warning signs; suddenly we are in a crisis, unable to breathe and desperately seeking quick relief. Even then, some of these sudden attacks may have had warning signals, if we had been able to perceive them. In general, narrowing of the breathing tubes comes on gradually, over hours to days, as swelling of the tubes develops, mucus forms, and the bronchial muscles tighten their grip. In this age of electronic self-monitoring, we need a smartphone app for tracking asthma and preventing early asthma attacks from progressing to such severity that they become life-threatening. There exist apps with fitness wristbands that track our activity level, calories burned, and even how much and how well we slept. Our New Year’s asthma wish list includes the asthma app that will sound the alarm to tell us when to take action because our asthma is getting out of control.

With our best wishes for a healthy and wheeze-free New Year!