Antihistamines for asthmatics?

You walk into the exam room, and find an older female patient complaining of an asthma exacerbation. She reports three days of symptoms consistent with her prior asthma exacerbations, including dry cough, wheezing, increased work of breathing, and exertional dyspnea. She had tried her home MDI and continued her maintenance medications, but her symptoms had gradually worsened to the point that she did not feel she could manage at home.

Her exam is significant for wheezing bilateral full fields, somewhat prolonged expiratory phase but good air exchange. She is speaking in full sentences, and maintaining adequate SpO2 on room air. She is afebrile, and the rest of her VS are stable. The patient's only other complaint is that her "allergies had been acting up lately." The patient appears to have a life-long history of seasonal and recurrent allergic rhinitis, but is not prescribed a daily antihistamine or other anti-allergy therapy.

Clinical Question:

Is there any evidence that antihistamine treatment has a clinically significant effect on asthma symptoms?

The Literature:

A systematic review of the efficacy of 2nd-generation antihistamines in patients with allergic rhinitis (AR) and comorbid asthma was published in the Journal of Asthma in 2011. Epidemiological and histopathological evidence confirms the strong association of AR and asthma. The two conditions share histaminergic mediators released by mast cells & basophils, and the cumulative weight of clinical & laboratory evidence suggests a strong pathophysiologic role.

The study authors performed a comprehensive literature search for double-blind randomized controlled trials in which patients with both asthma & AR were treated with 2nd-gen antihistamines -- cetirizine, loratadine, & fexofenadine being the most common. The authors first summarized the findings of several older trials which did not meet their inclusion criteria (i.e., were not double-blind RCTs). Overall, 1st-gen antihistamines (e.g., diphenhydramine, doxylamine, hydroxyzine, meclizine) have not been shown to have an effect on asthma symptoms except at doses high enough to cause anti-cholinergic and CNS-related ADRs. Some in vitro studies have suggested a steroid-sparing effect or diminished airway hyperreactivity with 2nd-gen antihistamines, but these results are inconsistent in the literature. There is fairly strong evidence in the form of large retrospective studies that effective treatment of AR reduces health-care utilization and improves quality-of-life scores in patients with concomitant asthma, but these cohorts included patients utilizing other AR therapies such as intranasal steroids as well as antihistamines.

A multicenter RCT with N=274 comparing cetirizine-D (cetirizine + pseudoephredine) to placebo found improvement in AR & PM asthma symptoms, but no significant effect on AM symptoms or pulmonary function scores. Another RCT of cetirizine alone had similar results. Several double-blind RCTs comparing the drug desloratadine to placebo, with total N >1100, showed significant reductions in both AM/PM & total asthma sx scores (including specific scores for wheezing & cough) and rescue inhaler use.

As is the case for 1st-gen antihistamines, in vitro data suggests higher doses may be needed to treat asthma as compared with AR. A small RCT (N=28) compared cetirizine 20mg daily to placebo (usual dosing 5-10mg daily), and found significant improvement in reported asthma & AR symptoms without a significant rate of adverse effects compared to placebo. Unfortunately, this dosing regimen has not been compared to standard dosing.

Take home:

- Overall, these studies suggest that antihistamine treatment may improve overall asthma symptom severity in patients with concomitant allergic rhinitis.
- Unfortunately, no study to date has evaluated effects, if any, of antihistamines during acute asthma exacerbation, or if addition of antihistamine prevents ED visits or hospitalizations.
- It seems reasonable to offer these patients antihistamine prescription if they are not already taking them.

1) J Asthma, 48(2011):965–973.

Contributed by Sam Smith, PGY-3.