Hospital Rounds: Focus on Allergy

Author: L. Kendall Shaw, PharmD

Desloratadine: A Closer Look
As the primary active metabolite of loratadine, deslorata- dine has shown itself to be at least as effective as its prede- cessor,  as  well  as  the  other  nonsedating  histamine1  (H1) receptor antagonists, in managing the usual symptoms of allergic  rhinitis  for  which  such  agents  are  generally  pre- scribed, with a single daily dose. Because desloratadine is   the active metabolite, it obviously requires no metabolism   for activation and thus requires a lower dose than lorata-   dine  to  be  effective.  It  too  is  metabolized  to  3-hydroxy- desloratadine, which is itself an active H1 receptor antago- nist. The lower dose required to attain clinical efficacy may also be a function of the agent?s demonstrably greater affin- ity for the H1 receptor than other agents.

Whereas antihistaminic potency is essential in managing  the  symptoms  of  allergic  rhinitis,  desloratadine  has been demonstrated in addition to affect other inflammatory  components  that  contribute  to  those  symptoms, specifically inhibiting generation of cytokines interleukin (IL)-4  and  IL-13.  Thus,  while  it  inhibits  release  of  hista- mine and other mediators from human basophils, deslo- ratadine is more effective at targeting the signals regulating  IL-4  and  IL-13  generation  in  these  cells  without impairing  normal  function  of  these  cells.  This  concept may help to explain why desloratadine is generally equally effective for both perennial and seasonal allergic rhinitis,  and  why  it  is  not  only  considered  safe  for  patients with asthma but might actually be beneficial in the overall treatment of asthma.

It also may help to explain how the agent is generally effective at treating both the nasal and nonnasal symptoms of allergic rhinitis, including nasal itching, congestion, rhinorrhea, sneezing, and itching/burning of the eyes, ears, and palate. Desloratadine seems uniquely effective at reducing nasal congestion, which can reduce the need for decongestant agents that can be more prone to side effects. Thus, it may be a logical choice for the patient with hypertension, cardiovascular disease, thyroid disease, or diabetes. Not only does it not cause complicating side effects, addition of a decongestant to the patient?s regimen may be obviated. Although Clarinex is ~22% less expensive than its predecessor, Claritin, eliminating the need for a decongestant can further reduce the cost of therapy.

Ladybugs: Growing Allergy Threat
Finding a ladybug has long been recognized as a portent of good luck. With the obvious potential toxic pitfalls of utilizing chemical agents in pest control in agriculture and home gardening, ladybugs (Hippodamia con-vergens) have gained popularity as a viable nontoxic option. A predator of aphids and other pests that hinder growth and cause damage to vegetable plants grown for food on any  scale, the ladybug has proven to be an effective and nontoxic "organic" means of pest control, opening the door for an entire industry devoted to growing, selling, distributing, and applying these beneficial insects.

The problem is, with such massive efforts to proliferate this beneficial species, it seems that ladybugs are allergenic; so along with vast increases in numbers and exposure to humans, more people are showing up with atopic symptoms associated with ladybugs. People involved in growth and distributive efforts, people involved in horticulture, and people whose homes have become infested with these otherwise benign bugs have started presenting with typical allergic symptoms ranging from annoying to life-threatening in intensity. Literature is now proliferating that documents hypersensitivity to the ladybug as the cause of rashes, allergic rhinitis and conjunctivitis, and asthma in people with known atopic tendencies, as well as people with no atopic history.

So finding a ladybug may lose its appeal as a sign of good luck to come. Rather, it may be a reason to reach for the inhaler.


Asthma: Better Treatment By Treating Comorbidities
With advances in the treatment of asthma, along with better understanding of its pathophysiology and potential for exacerbation and escalation with time and under-treatment, has come the recognition that treating certain other comorbid conditions can contribute significantly to asthma control. Those who treat asthma now recognize that they must treat the whole patient, not just that condition; following the guidelines for treating asthma is only half the battle.

Gastroesophageal reflux disease (GERD) is undeniably associated with asthma, with the prevalence of GERD in asthma patients ~70%, much higher than in the general population. Although precise mechanisms involved in this comorbidity are not fully defined, theories abound. Autonomic dysregulation can lead to hypervagal response and increased pressure gradient between the esophagus and stomach. Airway obstruction and negative pleural pressure can reduce esophageal sphincter pressure. Esophageal acid affects airway responsiveness via the vagal-esophageal-bronchial reflex, which leads to bronchial hyperreactivity, microaspiration, increased substance P and tachykinin release, and increased minute ventilation and respiratory rate. Proper treatment of GERD in asthmatic patients reduces asthma symptoms, reduces rescue asthma medication use, improves peak expiratory flow, and ultimately reduces health care utilization for asthma.

Obesity, too, has recently been associated with asthma, although controversy continues as to which condition causes the other. A possible explanation may be that obesity decreases forced vital capacity and tidal volume, decreasing tidal stretch of smooth muscle in the lungs with increased bronchoconstriction and airway hyperre-activity. There are also demonstrable increases among the obese in proinflammatory mediators and inflammatory cells, including interleukin (IL)-6, IL-8, neutrophils, and estrogen. Although studies have been limited, lung function generally improves with loss of weight.

Finally, allergic rhinitis is a common comorbidity with asthma. Obviously, since both are atopic inflammatory disease states, mechanisms of pathogenesis are similar, and genetic predispostion is common. Yet, both conditions can be induced by long-term high-level  exposure to respiratory irritants, even in patients with no history of either. Since the underlying pathogenesis of these two diseases is so similar, treatment is also similar, with an emphasis on prevention, not only of acute exacerbations but of long-term escalation. Both conditions predispose the patient to upper respiratory infections and increase the cost of overall health care. Proper management of both is essential in minimizing exacerbation and maximizing control.