Antihistamines targeting the histamine H₁ receptor play an important role in improving and maintaining the quality of life of patients with allergic rhinitis. For more effective and safer use of second-generation drugs, which are recommended by various guidelines, a classification based on their detailed characteristics is necessary. Antihistamines for first-line therapy should not have central depressant/sedative activities. Sedative properties (drowsiness and impaired performance) are associated with the inhibition of central histamine neurons. Brain H₁ receptor occupancy (H₁RO) is a useful index shown to be correlated with indices based on clinical findings. Antihistamines are classified into non-sedating (<20%), less-sedating (20–50%), and sedating (≥50%) groups based on H₁RO. Among the non-sedating group, fexofenadine and bilastine are classified into “non-brain-penetrating antihistamines” based on the H₁RO. These two drugs have many common chemical properties. However, bilastine has more potent binding affinity to the H₁ receptor, and its action tends to last longer. In well-controlled studies using objective indices, bilastine does not affect psychomotor or driving performance even at twice the usual dose (20 mg). Upon selecting antihistamines for allergic rhinitis, various situations should be taken into our consideration. This review summarizes that the non-brain-penetrating antihistamines should be chosen for the first-line therapy of mild allergic rhinitis.

The concept of united airway disease comprises allergic rhinitis (AR) with asthma, and eosinophilic chronic rhinosinusitis (ECRS) with asthma. It embodies a comprehensive approach to the treatment of upper and lower airway inflammation. The treatment of upper airway inflammation reduces asthma symptoms and decreases the dose of inhaled corticosteroids (ICS) necessary to treat asthma. However, little is known about the mechanisms of interaction between upper and lower airway inflammation. Here we review these mechanisms, focusing on neural modulation and introduce a novel therapeutic approach to united airway disease using a fine-particle ICS. Our understanding of the relationship between the upper and lower airways and its contribution to T helper 2 (Th2)-skewed disease, such as AR and/or ECRS with asthma, has led us to this novel therapeutic strategy for a comprehensive approach to the treatment of upper airway inflammation with asthma.

Sublingual immunotherapy (SLIT) has been considered to be a painless and efficacious therapeutic treatment of allergic rhinitis which is known as type I allergy of nasal mucosa. Nevertheless, its mechanisms need to be further investigated. In this study, we constructed an effective murine model of sublingual immunotherapy in allergic rhinitis, in which mice were sublingually administered with ovalbumin (OVA) followed by intraperitoneal sensitization and nasal challenge of OVA. Sublingually treated mice showed significantly decreased specific IgE responses as well as suppressed Th2 immune responses. Sublingual administration of OVA did not alter the frequency of CD4⁺CD25⁺regulatory T cells (Tregs), but led to upregulation of Foxp3- and IL-10-specific mRNAs in the Tregs of cervical lymph nodes (CLN), which strongly suppressed Th2 cytokine production from CD4⁺CD25⁻effector T cellsin vitro. Furthermore, sublingual administration of plasmids encoding the lymphoid chemokines CCL19 and CCL21-Ser DNA together with OVA suppressed allergic responses. These results suggest that IL-10-expressing CD4⁺CD25⁺Foxp3⁺Tregs in CLN are involved in the suppression of allergic responses and that CCL19/CCL21 may contribute to it in mice that received SLIT.

Aims:  Human olfactory epithelium becomes functional at birth, but prenatal development remains unclear. In the present study, we aimed to clarify the development of human olfactory epithelium using scanning electron microscopy (SEM).Methods:  The development of human olfactory epithelium was observed in 24 externally normal fetuses, which were formalin‐fixed and long‐preserved, with a crown‐rump length (CRL) of 102–336 mm (gestational week 14–38). The olfactory mucosa in the superior wall of the nasal septum near the choana were dissected and observed under SEM. We examined the number of olfactory vesicles per unit area, diameter of olfactory vesicles, and number and length of cilia on olfactory vesicles.Results:  At circa (ca) CRL 100 mm (ca 14 weeks), olfactory epithelium displayed several olfactory vesicles with 1–2 short cilia per unit area. At ca CRL 150 mm (ca 18 weeks), olfactory vesicles were present in small clusters, and cilia were longer. At CRL lager than 225 mm (ca 26 weeks), olfactory vesicles became located separately from each other, while length and number of cilia per olfactory vesicle were further increased.Conclusion:  The present findings suggest that fetal olfactory epithelium becomes morphologically almost the same as that in adults in late gestation, much later than previously thought.

Background: Microbial infection or exposure to endotoxin later in life exacerbates established asthma. Mast cells are involved in the exacerbation of asthma. This exacerbation involves a toll-like receptor (TLR)–mediated response of mast cells. In the clinical practice of otolaryngology, otolaryngologists experience an exacerbation of nasal congestion when infectious rhinitis develops in patients with allergic rhinitis, but the mechanisms are unknown. Therefore, this study investigated the effect of lipopolysaccharide (LPS) on allergic rhinitis using a mouse allergic rhinitis model. Methods: Female BALB/c mice, TLR4 gene mutant C3H/HeJ mice or mast cell–deficient WBB6F1-^W/Wv mice were sensitized intraperitoneally with ovalbumin (OVA)/alum, and were intranasal challenged with OVA and/or LPS. Nasal symptoms and histologic changes were examined. Cytokines in nasal tissue were examined by Western blot. The effects of LPS on degranulation and cytokine production of bone marrow–derived mast cells (BMMCs) were investigated. Results: Nasal administration of LPS together with the antigen exacerbated nasal symptoms, eosinophil infiltration of the nasal mucosa, and increased IL-5 production in the nasal mucosa. It was not observed in C3H/HeJ mice and WBB6F1-^W/Wv mice. The addition of LPS increased the production of IL-5 from BMMCs in a dose-dependent manner, but no effect on degranulation was observed. Conclusions: Intranasal administration of LPS exacerbates allergic rhinitis through Th2 cytokine production from mast cells. This observation provides clues to the mechanism of exacerbation of allergic rhinitis caused by an infection in daily clinical practice.

Chronic rhinitis is defined as an inflammation of the nasal epithelium, and is characterized by the presence of two or more specific nasal symptoms including obstruction, rhinorrhea, sneezing, and/or itching for at least 12 weeks. In childhood, this clinical entity is very common and carries a significant socioeconomic burden. The impact on the physical, social, and psychological well-being of family cannot be underestimated. Rhinitis is an umbrella term which includes different phenotypes of rhinitis with distinct underlying pathophysiologic mechanisms. In most cases the diagnosis of rhinitis is rather straightforward; however, sometimes when based on clinical symptomatology, characterization may be challenging. Herein, we provide guidance for getting all the data needed for the differential diagnosis of rhinitis based on medical history and clinical examination.