After the emergence of biologics for the treatment of asthma, airway inflammation in bronchial asthma and sinusitis requires the implementation of precision medicine. This enhances the efficacy with the appropriate choice of a drug by identifying the end-type disease based on pathophysiology. The discovery of innate lymphoid cells (ILCs) clarified the mechanism of immunological diversity of eosinophilic inflammation in asthma and sinusitis that was once thought to involve Th2 cells. Such a concept has also been introduced in the proper use of IgE, IL-5, and IL-4/13 antibody preparations. Moreover, the mechanism of actions of the drugs can now be explained. Eosinophilic inflammation is the pathophysiological process that forms the basis of asthma and its mechanism of onset is diverse, such as inflammation triggered by type 1 allergy though allergens, activation of Th2 cells, and activation of ILC2. The pathological mechanisms involved in the onset of asthma and the underlying immunological mechanisms differ. However, understanding these concepts and using them in drug selection will become important in the treatment of this disease in the future. This article aims to strengthen understanding to enable use of the diversity of eosinophilic airway inflammation pathophysiology in therapy.

Allergic rhinitis (AR), eosinophilic chronic rhinosinusitis (ECRS), and eosinophilic otitis media (EOM) are well-known eosinophilic inflammatory diseases in the otorhinolaryngological area. Several chemical mediators and cytokines released from eosinophils are associated with nasal blockage in the late phase of AR. ECRS is characterized by bilateral lesions with nasal polyps and viscous nasal secretion, and much severer lesions are observed in the ethmoid sinuses compared with the maxillary sinuses. Nasal polyps and mucosal inflammation of ECRS are intractable and recur easily even after performing endoscopic sinus surgery. Th2-type cytokines such as IL-4, IL-5, and IL-13 and periostin induce eosinophilic infiltration, and extracellular trap cell death is thought to contribute to the formation of viscous nasal secretion. EOM is also a refractory disease, characterized by glue middle ear effusion infiltrated with eosinophils, which sometimes causes sensorineural hearing loss. The pathogenesis of EOM is similar to that of ECRS. Since eosinophilic inflammatory diseases are frequently complicated with bronchial asthma, it is important to treat patients with these diseases in cooperation with pulmonologists.

Eosinophils are multifunctional leukocytes involved in the etiology of inflammatory reactions in various organs. Eosinophilic respiratory diseases comprise diverse ailments presenting with tissue or peripheral eosinophilia. Primary eosinophilic respiratory diseases include simple pulmonary eosinophilia, acute eosinophilic pneumonia, chronic eosinophilic pneumonia, hypereosinophilic syndrome, and eosinophilic bronchitis. Eosinophilia can occur as a secondary condition in patients with allergic bronchopulmonary aspergillosis, bronchocentric granulomatosis, parasitic infection, or fungal infection, or as an adverse reaction to drugs or toxins. Furthermore, eosinophilia sometimes may occur in patients with vasculitis such as allergic granulomatosis. Asthma is a common comorbidity and a possible prerequisite condition for diagnosing eosinophilia. Although mild eosinophilia is sometimes associated with other respiratory diseases (e.g., lung cancer, pulmonary fibrosis, and mycobacterial infection), its association with such respiratory diseases is insignificant and does not affect disease progression. Thus, these respiratory diseases are not generally regarded as eosinophilic lung diseases. This study presents an overview of the characteristic clinical, histological, and radiological findings of various eosinophilic respiratory diseases.

Eosinophilic esophagitis (EoE) is a chronic allergic disease defined as the presence of esophageal symptoms such as food impaction and dysphagia and intraepithelial eosinophil infiltration ≥15 per high-power field on biopsy specimens. Although a clinical condition similar to EoE that responds to PPI was earlier referred to as PPI-responsive esophageal eosinophilia (PPI-REE), several studies have shown similar pathogenesis between PPI-REE and EoE. Therefore, recent guidelines propose that the definition of EoE not require unresponsiveness to PPI, indicating that PPI-REE should be included in EoE. EoE is rare but has been increasing in Japan, especially cases found incidentally during health check-ups. The pathogenesis of EoE includes genetic susceptibility as well as environmental factors, and divides into an inflammation phase of eosinophil infiltration with TSLP, IL-13, and eotaxin-3, and a fibrostenotic phase of submucosal fibrosis with TGF-β1 and periostin. PPI is effective in approximately two-thirds of EoE cases, and most other cases are successfully treated with steroid swallowing therapy. In Western countries, the six food elimination diet, balloon dilation, and biologics are reported as therapeutic options.

Eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES) are included in systemic eosinophilic diseases. If peripheral blood eosinophilia >1500/μl persists for a long time, irreversible organ damage occurs. EGPA is preceded by bronchial asthma and eosinophilic rhinosinusitis, and is characterized by eosinophilic inflammation and vasculitis (organic ischemia) in various organs with marked eosinophilia. About 40% of cases are positive for p-ANCA, and in addition to general symptoms, vasculitis symptoms include multiple mononeuropathy, purpura, cardiac disorder, gastrointestinal ischemia, pauci-immune necrotizing glomerulonephritis, etc. The pathophysiology is Th2-type inflammation, tissue damage due to granule proteins released from eosinophils, and granulomatous vasculitis. The main treatment of EGPA is corticosteroids, and cyclophosphamide is used for vasculitis. High-dosegγ-globulin is used for peripheral neuropathy. Recent reporting shows that anti-IL-5 antibody is effective in relapsed or refractory EGPA. The survival rate is relatively good, but cardiac disorder may cause death. When HES represents a clonal disorder based on WHO classification, PDGFRA, PDGFRB, and FGFR1 genes should be examined. In mutation-positive cases, tyrosine kinase inhibitors are effective.