Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one‐airway‐one‐disease,” coined over 20 years ago, is a simplistic approach of the links between upper‐ and lower‐airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper‐ and lower‐airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined that the “one‐airway‐one‐disease” concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme “allergic” (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll‐Like Receptors and IL‐17 for rhinitis alone as a local disease; IL‐33 and IL‐5 for allergic and non‐allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono‐ or pauci‐sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.

The tyrosine kinase activity of epidermal growth factor receptors (EGFRs) plays critical roles in cell proliferation, regeneration, tumorigenesis, and anticancer resistance. Non-small-cell lung cancer patients who responded to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) and obtained survival benefits had somatic EGFR mutations. EGFR-TKI-related adverse events (AEs) are usually tolerable and manageable, although serious AEs, including lung injury (specifically, interstitial lung disease (ILD), causing 58% of EGFR-TKI treatment-related deaths), occur infrequently. The etiopathogenesis of EGFR-TKI-induced ILD remains unknown. Risk factors, such as tobacco exposure, pre-existing lung fibrosis, chronic obstructive pulmonary disease, and poor performance status, indicate that lung inflammatory circumstances may worsen with EGFR-TKI treatment because of impaired epithelial healing of lung injuries. There is limited evidence from preclinical and clinical studies of the mechanisms underlying EGFR-TKI-induced ILD in the available literature. Herein, we evaluated the relationship between EGFR-TKIs and AEs, especially ILD. Recent reports on mechanisms inducing lung injury or resistance in cytokine-rich circumstances were reviewed. We discussed the relevance of cytotoxic agents or immunotherapeutic agents in combination with EGFR-TKIs as a potential mechanism of EGFR-TKI-related lung injury and reviewed recent developments in diagnostics and therapeutics that facilitate recovery from lung injury or overcoming resistance to anti-EGFR treatment.

When selecting the best inhaler and drug combination for a patient with respiratory disease, a number of factors should be considered. While efficacy and safety of medical treatments are always a priority, in recent years the environmental impacts of all aspects of life have become an increasingly necessary consideration and inhaled therapies are no exception. The carbon footprint of an item, individual or organisation is one of the most important and quantifiable environmental impacts, assessed by the amount of greenhouse gases (often expressed in terms of carbon dioxide equivalents) generated throughout the life cycle. The two most commonly prescribed and manufactured inhaler types worldwide are pressurised metered-dose inhalers (pMDIs) containing hydrofluorocarbon (HFC) propellants and dry powder inhalers (DPIs). Most of the carbon footprint of current pMDIs is a result of the propellants that they contain (HFC-134a and HFC-227ea, which are potent greenhouse gases). In comparison, the powder in DPIs is dispersed by the patient's own inhalation, meaning DPIs do not contain a propellant and have a lower carbon footprint than most pMDIs currently available. Soft mist inhalers are another propellant-free option: the device contains a spring, which provides the energy to disperse the aqueous medication. In this review, we examine the published data on carbon footprint data for inhalers, providing an analysis of potential implications for treatment decision making and industry initiatives.

Airway epithelium plays an important role as the first barrier from external pathogens, including bacteria, viruses, chemical substances, and allergic components. Airway epithelial cells also have pivotal roles as immunological coordinators of defense mechanisms to transfer signals to immunologic cells to eliminate external pathogens from airways. Impaired airway epithelium allows the pathogens to remain in the airway epithelium, which induces aberrant immunological reactions. Dysregulated functions of asthmatic airway epithelium have been reported in terms of impaired wound repair, fragile tight junctions, and excessive proliferation, leading to airway remodeling, which contributes to aberrant airway responses caused by external pathogens. To maintain airway epithelium integrity, a family of epidermal growth factor receptors (EGFR) have pivotal roles in mechanisms of cell growth, proliferation, and differentiation. There are extensive studies focusing on the relation between EGFR and asthma pathophysiology, which describe airway remodeling, airway hypermucus secretion, as well as immunological responses of airway inflammation. Furthermore, the second EGFR family member, erythroblastosis oncogene B2 (ErbB2), has been recognized to be involved with impaired wound recovery and epithelial differentiation in asthmatic airway epithelium. In this review, the roles of the EGFR family in asthmatic airway epithelium are focused on to elucidate the pathogenesis of airway epithelial dysfunction in asthma.

Immunoglobulin (Ig) E is well-known to play a critical role in allergic diseases. We investigated the association between longitudinal change in total IgE level and the asthma control in patients with adult asthma. For this retrospective study, 154 patients with asthma aged 21–82 years were recruited from the allergy and pulmonary units of the Showa University Hospital. Data on longitudinal changes in IgE over the preceding 10 years were collected and logarithmically transformed. Associations between longitudinal change in IgE and clinical characteristics including asthma control test (ACT) score, asthma control, pulmonary function test, and antigen specific IgE, were assessed. Patients with increased IgE tended to have significantly higher mean age, more episodes of acute exacerbation within a year, lower ACT scores, and used oral corticosteroids more frequently than those with decreased or unchanged IgE. The prevalence of uncontrolled asthma was higher in patients with increased IgE than in those with decreased or unchanged IgE. Mean %FEV1 and FEV1% were lower in patients with increased IgE than in those with decreased or unchanged IgE. Moreover, the prevalence of Aspergillus-specific IgE was higher in patients with increased IgE than in those with decreased or unchanged IgE. These data suggest that a longitudinal increase in total IgE is associated with both poor asthma control and Aspergillus-specific IgE in patients with adult asthma.

The anti-thymic stromal lymphopoietin antibody (tezepelumab) has therapeutical potential for inadequately controlled asthma. However, evidence comparing tezepelumab with other biologics is scarce. To address this issue, we performed a network meta-analysis to compare and rank the efficacy of five treatments (tezepelumab, dupilumab, benralizumab, mepolizumab, and placebo) in overall participants and in subgroups stratified by the thresholds of type 2 inflammatory biomarkers, including peripheral blood eosinophil count (PBEC) and fractional exhaled nitric oxide (FeNO). The primary endpoints were annualized exacerbation rate (AER) and any adverse events (AAEs). In the ranking assessment using surface under the cumulative ranking curve (SUCRA) of AER, tezepelumab ranked the highest overall and across subgroups (based on PBEC and FeNO level thresholds). A significant difference was observed between tezepelumab and dupilumab in the patient subgroup with PBEC < 150, and between tezepelumab and benralizumab in overall participants and the patient subgroup with PBEC ≥ 300 and ≥150, respectively. There was no significant difference in the incidence of AAEs in the overall participants between each pair of five treatment arms. These results provide a basis for the development of treatment strategies for asthma and may guide basic, clinical, or translational research.