The discordance between the treatment guidelines for managing chronic cough (CC) and the lack of information available on the optimal dose and duration of these respiratory agents led investigators to conduct a systematic review to determine the efficacy of NS-H1RAs in adults and children with CC.

CC pertains to cough lasting more than 8 weeks. CC due to upper-airway abnormalities is associated with nonspecific accompanying nasal symptoms. A trial of H1-receptor antihistamines (H1RAs) is often used to confirm the diagnosis. The American College of Chest Physicians recommends the use of nonsedating H1RAs (NS-H1RAs) for this type of CC, while Australian, Chinese, Japanese, and Korean societies do not specifically recommend second-generation antihistamines over first-generation antihistamines.

However, this trial-and-error approach to the diagnosis of CC remains controversial. The British Thoracic Society and the European Respiratory Society have not endorsed the use of H1RAs in this situation.

The researchers tried to answer the following questions: Are NS-H1RAs more effective than placebo in improving cough outcomes in adolescents or adults with CC? Are NS-H1RAs more effective than placebo in improving cough outcomes in adolescents or adults with allergic respiratory diseases that may present with CC (such as allergic rhinitis, asthma, or atopic cough)?

To answer these questions, the authors searched PubMed, Embase, and the Cochrane library database for information on the use of NS-H1RAs for cough, rhinitis, bronchitis, sinusitis, or asthma in the target populations. Randomized, placebo-controlled (RPC) studies were included. Studies that only involved children younger than age 12 years, even if they were RPC, were excluded.

The authors identified 10 articles involving 1,629 participants with allergic asthma (2 studies), allergic rhinitis with asthma (4 studies), allergic rhinitis without asthma (3 studies), or atopic cough (1 study) to include in the systematic review. All except one study were conducted between 1988 and 2004; data from the one outlier were posted in 2018. While five studies included both adolescents and adults, the other half involved adults only.

The antihistamines utilized in these studies included azelastine, loratadine, cetirizine, epinastine (an ophthalmic antihistamine that is no longer available in the U.S.), desloratadine, and levocetirizine. Antihistamines were administered for a period ranging from 2 days to 26 weeks. Only subjective assessments of cough, such as severity or frequency, were included in these studies.

There was a high risk of bias in the included studies. This added to the investigators' difficulty in drawing conclusions, which was further compounded by the limited number of trials, differences in study populations, use of varying clinical endpoints, incomplete reporting of cough scores, small effect size, and inconsistent results across trials.

Among the 10 trials, 70% lacked baseline cough scores or failed to determine the validity of their cough scores. There was some evidence to support a possible benefit of the use of NS-H1RAs in patients with nonasthmatic allergic rhinitis (2 out of the 3 studies) or atopic cough (1 study). NS-H1RAs were not found to be effective in reducing cough in patients with allergic asthma based on the finding of two studies. The positive findings from four studies of the use of NS-H1RAs in patients with allergic rhinitis and comorbid asthma were not thought to be clinically significant.

Despite this paper being the most comprehensive systematic review of RPC trials evaluating the efficacy of NS-H1RAs in CC, the authors were unable to draw firm conclusions. However, the limited evidence points to minimal effects of these agents when used in unselected patients with CC.

When counseling patients on the use of these OTC medications, pharmacists should be aware that those most likely to benefit include nonasthmatic patients with seasonal allergic rhinitis or those with atopic cough.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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