Phosphodiesterase 4 Inhibitors in Allergic Rhinitis/Rhinosinusitis

Abstract

Allergic rhinitis/rhinosinusitis (AR) is the most common allergic disease. It affects patients’ quality of life and may influence the severity of lower airway disease such as asthma. Therefore, its treatment is of great importance. AR is treated by a combination of effective approaches; however, in some patients, the disease is uncontrolled. In the last several years, the concept of AR has shifted from increased T helper 2 (Th2) cell signaling and downstream inflammation to disease phenotypes with non-Th2-mediated inflammation. AR is a largely heterogenous group of airway diseases, and as such, research should not only focus on immunosuppressive agents (e.g., corticosteroids) but should also include targeted immunomodulatory pathways. Here, we provide an overview of novel therapies, focusing on the role of phosphodiesterase-4 (PDE4) inhibitors in AR. PDE4 inhibitors are potent anti-inflammatory agents that are used for the treatment of inflammatory airway diseases including AR. The PDE4 inhibitor roflumilast was shown to effectively control symptoms of AR in a randomized, placebo-controlled, double-blinded, crossover study in patients with a history of AR. However, only a few PDE4 inhibitors have proceeded to phase II and III clinical trials, due to insufficient clinical efficacy and adverse effects. Research is ongoing to develop more effective compounds with fewer side effects that target specific inflammatory pathways in disease pathogenesis and can provide more consistent benefit to patients with upper airway allergic diseases. Novel specific PDE4 inhibitors seem to fulfill these criteria.

Phosphodiesterase-4 Inhibitors for Non-COPD Respiratory Diseases

“…However, the limitation of roflumilast is systemic side effects compared to nasal corticosteroid. Hence, there are no further clinical trials of roflumilast and other oral PDE4 inhibitors in allergic rhinitis ( Janosova et al, 2020 ).…”

“…The potential role of PDE4 inhibitors in allergic rhinitis is related to the differential PDE4D gene expression in patients with allergic rhinitis and nasal polyposis ( Apuhan et al, 2013 ). Hence, the new formulation, for instance, nasal spray, may be the potential solution for managing chronic rhinosinusitis ( Janosova et al, 2020 ).…”

Can Phosphodiesterase 4 Inhibitor Therapy Be Used in Respiratory Diseases Other Than Chronic Obstructive Pulmonary Disease?

“…Clinical data provide promising results for the potential use of PDE4 inhibitors in asthmatic patients [ 4 ]. Its effectiveness has also been tested for various other inflammatory respiratory diseases, including allergic rhinitis, non-cystic fibrosis bronchiectasis, and chronic cough [ 6 , 10 ]. However, PDE4 inhibitors are not approved as a treatment strategy for any other respiratory diseases except COPD [ 7 ].…”

Yiqi Jiemin decoction alleviates allergic rhinitis in a guinea pig model by suppressing inflammation, restoring Th1/Th2 balance, and improving cellular metabolism

“…Allergic rhinitis (AR) is an IgE-mediated inflammatory disease of the nasal mucosa in response to allergen exposure, with symptoms such as airflow obstruction, nasal itching, rhinorrhoea, and sneezing [ 1 ]. The worldwide incidence of AR has increased dramatically over the last few decades [ 2 , 3 ]. The prevalence of allergic rhinitis is about 10%-30% in adults and approximately 40% in children [ 4 ].…”

“…AR is clinically diagnosed by thorough evaluation of patient medical history as well as allergen testing with in vivo skin prick tests (SPTs) and in vitro estimation of serum allergen-specific IgE levels [ 11 – 13 ]. Second-generation H1 anti-histamines, nasal glucocorticosteroids, and leukotriene antagonists are the first-line drugs for AR patients, whereas, allergen immunotherapy and surgery is prescribed when the first-line drugs are ineffective [ 2 , 14 ]. In most cases, drugs provide only temporary relief and symptoms relapse after drug withdrawal [ 15 ].…”