United Airway Disease Research Articles

Co-Occurrence of Equine Asthma and Pharyngeal Lymphoid Hyperplasia in Pleasure Horses

With the increasing awareness of the “united airway disease” theory, more horses, not only sport horses but also pleasure horses, undergo detailed examinations of the respiratory tract. Using endoscopy, equine asthma (EA) is most commonly diagnosed in the lower airway, while pharyngeal lymphoid hyperplasia (PLH) is common in the upper airway. Grading EA as mild–moderate (MEA) and severe (SEA), this study aims to compare the co-occurrence and investigate the possible relationship between the clinical symptoms and endoscopic signs of MEA/SEA and PLH in pleasure horses. In this retrospective study, 80 out of 93 pleasure horses suspected of EA were enrolled and underwent a standardized protocol for a complete airway examination, including resting endoscopy with mucus accumulation assessment and cytology. The obtained results were scored and analyzed. In the studied pleasure horses, PLH co-occurred more frequently in horses with EA than without (p < 0.0001) and more in horses with SEA than with MEA (p = 0.025). However, when EA and PLH co-occurred, the severity of the clinical symptoms of EA did not increase (p > 0.05). In both EA and PLH, the amount of tracheal and nasopharyngeal mucus increased with the severity of the disease; however, it was positively correlated (ρ = 0.33; p = 0.02) only in SEA horses. In conclusion, it is likely that EA is often accompanied by PLH; however, PLH did not play a role in increasing the severity of EA’s clinical symptoms. The role of the severity of accumulated mucus in the lower and upper airways when EA/PLH co-occur requires further research to confirm the morphological and functional unity of the respiratory tract, aligning with the concept of “united airways disease”.

Causal associations between pediatric asthma and united airways disease: a two-sample Mendelian randomization analysis.

Prior observational research has indicated a potential link between pediatric asthma and united airways disease (UAD). However, these findings could be subject to confounding factors and reverse causation. Therefore, our study utilizes Mendelian randomization (MR) method to further investigate the causal relationship between pediatric asthma and UAD. We conducted a comprehensive two-sample Mendelian randomization (MR) analysis to investigate the association between pediatric asthma and seven groups of UAD, including chronic sinusitis, chronic rhinitis, nasopharyngitis and pharyngitis, chronic diseases of tonsils and adenoids, chronic laryngitis and laryngotracheitis, chronic bronchitis, bronchiectasis, chronic obstructive pulmonary disease (COPD). The present study employed a range of methods for two-sample MR analysis, including inverse variance weighted (IVW), MR-Egger regression, Simple mode, weighted median, and weighted models. The conclusion of the MR analysis primarily relies on the IVW results, while other analytical methods are utilized as supplementary evidence to ensure result robustness in this MR analysis. And sensitivity analyses were conducted, including heterogeneity test, horizontal pleiotropy test, MR-PRESSO test, and leave-one-out analysis to validate the results. The results of the MR analysis indicate significant causal effects of pediatric asthma on chronic rhinitis, nasopharyngitis and pharyngitis (IVW: OR = 1.15, 95%CI: 1.05-1.26, p-value = 0.003), chronic diseases of tonsils and adenoids (IVW: OR = 1.07, 95%CI: 1.00-1.15, p-value = 0.038), chronic bronchitis (IVW: OR = 1.51, 95%CI: 1.42-1.62, p-value <0.001), bronchiectasis (IVW: OR = 1.51, 95%CI: (1.30-1.75), p-value <0.001), and COPD (IVW: OR = 1.43, 95%CI: 1.34-1.51, p-value <0.001). However, no significant causal association was observed between pediatric asthma and chronic sinusitis (IVW: OR = 1.00, 95%CI: 1.00-1.00, p-value = 0.085), chronic laryngitis and laryngotracheitis (IVW: OR = 1.05, 95%CI: 0.90-1.21, p-value = 0.558). Our findings support a potential causal relationship between pediatric asthma and UAD, suggesting that pediatric asthma may be a potential risk factor for various UAD.

Allergy/Atopic March and United Airway Disease: What We Know and What We Need to Know?

Abstract “Allergy/atopic march” refers to a typical sequence in which the allergic or atopic features appear at a certain age, and may or may not persist thereafter. In general, atopic dermatitis or atopic eczema occurs first, which progresses to immunoglobulin-E-mediated food allergy, asthma, and then allergic rhinitis (AR). However, this sequence may not be conspicuous in many cases. AR is an independent risk factor for asthma; in fact, AR often precedes that of asthma. United airway disease (allergic rhino-bronchitis) means the coexistence of AR and asthma. This has been shown in clinical and experimental studies, which suggest a similar immune pathology between the upper and lower airways in allergic subjects. In children with asthma, coexistent AR leads to an increased risk of asthma exacerbation leading to hospitalization and/or emergency visits as well as increased health-care cost. Treatment of AR in asthmatic children results in a lowered risk of asthma-related hospitalizations and emergency visits, and improved quality of life. In this article, we have discussed the current evidence for the clinically relevant effects that allergic conditions (from food allergies to atopic march, united airways disease, and AR) can have on children with asthma along with the future of allergic diagnosis (precision allergy molecular diagnosis) and allergen immunotherapy.

The impact of allergic rhinitis on bronchial asthma: What therapy?

Childhood asthma constitutes a significant healthcare burden due to its chronic nature and prevalence, affecting approximately 5–10 % of the pediatric population. Asthma is often heterogeneous and characterized by chronic airway inflammation. It is classified into two main phenotypes based on airway inflammation: T2-high (eosinophilic) and T2-low (neutrophilic/pauci-granulocytic) phenotype. Allergic sensitization is commonly associated with T2-high asthma, involving T helper 2 and innate immunity cells and type 2-associated cytokines, including interleuikin-4 (IL-4), IL-5, and IL-13. Type 2 inflammation is characterized by eosinophilic infiltrate. Asthma and allergic rhinitis share common mechanisms, and their association, known as united airways disease, highlights the close interconnection between upper and lower airways. Effective allergic rhinitis control positively impacts asthma, emphasizing the importance of early identification and personalized therapeutic strategies. One is allergen immunotherapy, a disease-modifying approach demonstrating preventive and therapeutic efficacy in children. However, more research is needed to optimize pediatric allergic rhinitis management.

The effect of biologics in lung function and quality of life of patients with united airways disease: A systematic review

Increasing evidence supports the united airway disease concept for the management of upper and lower respiratory tract diseases, particularly in patients with asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). However, evidence for a combined approach in asthma and CRSwNP is scarce. In this systematic review, we focused on the role of biologics in the lung function and quality of life in patients with severe asthma and CRSwNP. We conducted a systematic search of 3 electronic databases using 2 search strategies to identify studies published from January 2010 to March 2022. Quality assessment was performed with the Critical Appraisal Skills Programme. Of 1030 studies identified, 48 original studies reporting data of benralizumab (12), dupilumab (14), mepolizumab (10), omalizumab (13), and reslizumab (2) were analyzed. Primary diagnosis was mostly asthma or CRSwNP, with only 15 studies, mainly observational, performed in populations with united airway disease. In total, 18 studies reported data on quality of life (mostly 22-item Sino-Nasal Outcome Test score), 8 on lung function (mostly FEV1), and 22 on both outcomes. Significant FEV1 and 22-item Sino-Nasal Outcome Test score improvements were consistently observed after 24-week treatment, and thereafter, mostly in real-world studies that included variable proportions of patients with asthma/CRSwNP. The use of biologics in patients with severe asthma and CRSwNP was overall associated with significant improvements in lung function and quality of life. However, we observed a high heterogeneity of populations and outcome measurements across studies. Notwithstanding the need of larger studies, our results reinforce the joint management of asthma and CRSwNP as united airway disease in clinical practice.

Co-Occurrence of Severe Equine Asthma and Palatal Disorders in Privately Owned Pleasure Horses.

According to the "unified or united airway disease" theory, diseases in the upper and lower airways frequently co-occur because they represent a single morphological and functional unit. Palatal disorders (PDs) and severe equine asthma (SEA) are frequent diseases that, respectively, affect upper and lower equine airways; however, clinical studies focusing on the co-occurrence of PDs and SEA are limited. The present study investigated the prevalence of PDs in horses affected by SEA, and whether prevalence decreased after SEA treatment. Forty-six privately owned horses affected by SEA in exacerbation were included. For each horse, the severity of the asthma clinical signs was assessed using a previously described scoring system, and the co-occurrence of palatal disorders was investigated using overground endoscopy, before and after treatment for SEA. Before treatment (in exacerbation), 67.4% of SEA-affected horses showed evidence of PDs, including 39.1% showing evidence of palatal instability (PI) and 28.3% of dorsal displacement of the soft palate (DDSP). Airway inflammation (neutrophil percentage in the tracheal wash and bronchoalveolar lavage fluid) was worse in horses with co-occurring PDs. After treatment (in remission), no horses showed evidence of PI, while DDSP was diagnosed in 8.7% of horses. These findings suggest that palatal disorders respond to asthma treatment, supporting the hypothesis that both diseases could be manifestation of a common underlying disorder.

Pathobiology of Type 2 Inflammation in Asthma and Nasal Polyposis.

Asthma and nasal polyposis often coexist and are frequently intertwined by tight pathogenic links, mainly consisting of the cellular and molecular pathways underpinning type 2 airway inflammation. The latter is characterized by a structural and functional impairment of the epithelial barrier, associated with the eosinophilic infiltration of both the lower and upper airways, which can be driven by either allergic or non-allergic mechanisms. Type 2 inflammatory changes are predominantly due to the biological actions exerted by interleukins 4 (IL-4), 13 (IL-13), and 5 (IL-5), produced by T helper 2 (Th2) lymphocytes and group 2 innate lymphoid cells (ILC2). In addition to the above cytokines, other proinflammatory mediators involved in the pathobiology of asthma and nasal polyposis include prostaglandin D2 and cysteinyl leukotrienes. Within this context of 'united airway diseases', nasal polyposis encompasses several nosological entities such as chronic rhinosinusitis with nasal polyps (CRSwNP) and aspirin-exacerbated respiratory disease (AERD). Because of the common pathogenic origins of asthma and nasal polyposis, it is not surprising that the more severe forms of both these disorders can be successfully treated by the same biologic drugs, targeting many molecular components (IgE, IL-5 and its receptor, IL-4/IL-13 receptors) of the type 2 inflammatory trait.

Consensus on the management of united airways disease with type 2 inflammation: a multidisciplinary Delphi study

BackgroundScientific evidence on patients with multimorbid type 2 asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) from a united airways disease (UAD) perspective remains scarce, despite the frequent coexistence of these entities. We aimed to generate expert consensus-based recommendations for the management of UAD patients.MethodsUsing a two-round Delphi method, Spanish expert allergists, pulmonologists and otolaryngologists expressed their agreement on 32 statements (52 items) on a 9-point Likert scale, classified as appropriate (median 7–9), uncertain (4–6) or inappropriate (1–3). Consensus was considered when at least two-thirds of the panel scored within the range containing the median.ResultsA panel of 30 experts reached consensus on the appropriateness of 43 out of the 52 (82.7%) items. The usefulness of certain biomarkers (tissue and peripheral blood eosinophil count, serum total IgE, and fraction of exhaled nitric oxide [FeNO]) in the identification and follow-up of type 2 inflammation, and assessment of the response to biologics, were agreed. Some of these biomarkers were also associated with disease severity and/or recurrence after endoscopic sinus surgery (ESS). Consensus was achieved on treatment strategies related to the prescription of anti-IL-4/IL-13 or anti-IgE agents, concomitant treatment with systemic corticosteroids, and combining or switching to biologics with a different mechanism of action, considering a number of UAD clinical scenarios.ConclusionWe provide expert-based recommendations to assist in clinical decision-making for the management of patients with multimorbid type 2 asthma and CRSwNP. Specific clinical trials and real-world studies focusing on the single-entity UAD are required to address controversial items.

A real world study of anti-IgE monoclonal antibody in the treatment of allergic united airway disease

Objective: To investigate the clinical efficacy and safety of anti-IgE monoclonal antibody (omazumab) in the treatment of allergic united airway disease (UAD) in the real-wold. Methods: Retrospective cohort study summarizes the case data of patients with allergic united airway disease who were treated with anti IgE monoclonal antibody (omalizumab) for more than 16 weeks from March 1, 2018 to June 30, 2022 in the Peking University First Hospital.The allergic UAD is defined as allergic asthma combined with allergic rhinitis (AA+AR) or allergic asthma combined with chronic sinusitis with nasal polyps (AA+CRSwNP) or allergic asthma combined with allergic rhinitis and nasal polyps (AA+AR+CRSwNP). The control of asthma was evaluated by asthma control test (ACT), lung function test and fractional exhaled nitric oxide (FeNO). The AR was assessed by total nasal symptom score (TNSS). The CRSwNP was evaluated by nasal visual analogue scale (n-VAS), sino-nasal outcome test-22 (SNOT-22), nasal polyps score (TPS) and Lund-Mackay sinus CT grading system. The global evaluation of omalizumab for the treatment of allergic UADwas performed by Global Evaluation of Treatment Effectiveness(GETE).The drug-related side effects were also recorded. Matched t test and Wilcoxon signed-rank test were used to compare the score changes of IgE monoclonal antibody (omazumab) before and after treatment, and multivariate logistic regression analysis was used to determine the influencing factors of IgE monoclonal antibody (omazumab) response. Results: A total of 117 patients with UAD were enrolled, ranging in age from 19 to 77 years; The median age of patients was 48.7 years; Among them, 60 were male, ranging from 19 to 77 years old, with a median age of 49.9 years; There were 57 females, ranging from 19 to 68 years old, with a median age of 47.2 years. There were 32 cases in AA+AR subgroup, 59 cases in AA+CRSwNP subgroup, and 26 cases in AA+AR+CRSwNP subgroup. The total serum IgE level was 190.5 (103.8,391.3) IU/ml. The treatment course of anti IgE monoclonal antibody was 24 (16, 32) weeks. Compared with pre-treatment, omalizumab increased ACT from 20.0 (19.5,22.0) to 24.0 (23.0,25.0) (Z=-8.537, P<0.001), increased pre-bronchodilator FEV1 from 90.2 (74.8,103.0)% predicted value to 95.4 (83.2,106.0)% predicted value (Z=-5.315,P<0.001), increased FEV1/FVC from 80.20 (66.83,88.38)% to 82.72 (71.26,92.25)% (Z=-4.483,P<0.001), decreased FeNO from(49.1±24.8) ppb to (32.8±24.4) ppb (t=5.235, P<0.001), decreased TNSS from (6.5±2.6)to (2.4±1.9) (t=14.171, P<0.001), decreased n-VAS from (6.8±1.2) to (3.4±2.0)(t=14.448, P<0.001), decreased SNOT-22 from (40.0±7.9) to (21.3±10.2)(t=15.360, P<0.001), decreased TPS from (4.1±0.8) to (2.4±1.0)(t=14.718, P<0.001) and decreased Lund-Mackay CT score from (6.0±1.3) to (3.1±1.6)(t=17.012, P<0.001). The global response rate to omalizumab was 67.5%(79/117). The response rate in AA+AR (90.6%,29/32) was significantly higher than that in AA+CRSwNP (61.0%,36/59) and AA+AR+CRSwNP (53.8%,14/26) subgroups (χ2=11.144,P=0.004). Only 4 patients (3.4%,4/117) had mild side effects. Conclusion: The real-world study showed favorable effectiveness and safety of anti-IgE monoclonal antibody for treatment of allergic UAD. To provide basis for preventing the progress and precise treatment of allergic UAD.

Anti-IL-4,13 strategy in management of comormid patients in the regional register of severe bronchial asthma

BACKGROUND: T2 inflammation underlies bronchial asthma and inflammatory nasal diseases, supporting the concept of a united airway disease. Dupilumab, by blocking interleukin-4 and -13 receptors, can improve the clinical and functional parameters and life quality of comorbid patients with T2 diseases.&#x0D; AIM: To evaluate efficacy of anti-IL4R,13 therapy in patients with severe asthma with chronic inflammatory nasal diseases in real clinical practice.&#x0D; MATERIALS AND METHODS: The study of dupilumab efficacy was conducted by comparing related populations based on a regional register of patients with severe asthma and concomitant chronic inflammatory nasal diseases. Asthma control achievement and decrease in the rate of patients with uncontrolled asthma were assessed as primary endpoint. The need for bronchodilators and systemic glucocorticosteroids, number of asthma exacerbations, emergency calls and hospitalizations, AQLQ scores, level of peripheral blood eosinophils, and respiratory function were also assessed. Nasal symptoms were assessed using SNOT-22 and VAS. A subgroup analysis of ACT scores was performed depending on chronic inflammatory nasal disease phenotypes.&#x0D; RESULTS: Within 12 months of dupilumab therapy, ACT increased from 11 (Q1Q3: 713) to 20 (Q1Q3: 1824) points (p 0.001). The rate of patients with partially and fully controlled asthma increased from 0 to 57.9% (p 0.001). The need for bronchodilators decreased from 17.5 doses per week (Q1Q3: 5.824.5) to 1.0 (Q1Q3: 0.02.2) (p 0.001). Before the dupilumab therapy, 68.5% of the patients took systemic corticosteroids and, after 12 months, 10.5% of patients (p 0.001). The number of asthma exacerbations decreased from 2.191.83 (95% CI 1.283.11) to 0.220.55 (0.050.49) (p 0.001) and hospitalizations from 1.001.27 (95% CI 0.371.63) to 0.170.51 (95% CI 0.090.42) (p 0.001). AQLQ scores increased from 2.91 (Q1Q3: 2.433.86) to 5.89 points (Q1Q3: 4.706.58) (p 0.001). The volume of forced exhalation in 1 sec increased from 55.38%16.66% (95% CI 47.1063.67) to 81.5%19.14% (95% CI 71.9891.02) (p 0.001). SNOT-22 scores decreased from 4729 (95% CI 3461) to 2518 (95% CI 1734) points (p 0.001) and the VAS score from 72 (95% CI 68) to 42 (95% CI 35) (p 0.001).&#x0D; CONCLUSIONS: Dupilumab improved asthma and nasal symptoms control, improved quality of life and respiratory function, and reduce asthma exacerbations and hospitalizations. Patients with severe asthma and comorbid allergic rhinitis and chronic rhinosinusitis with polyps responded better to dupilumab therapy than patients with chronic rhinosinusitis without polyps.

Comprehensive therapy in united airway disease: Evidence Based Case Report

ABSTRACTBackground: The concept of the united airway disease (UAD) recognises the association between allergic inflammation in the upper and lower airways. Patients with asthma and concomitant allergic rhinitis experience more asthma-related primary and secondary care visits. Purpose: To determine the best treatment option in the case of patients with asthma related allergic rhinitis, both in the control of nasal and pulmonary symptoms. Case report: A case case of 45 years old woman with asthma related to allergic rhinitis treated with combination of intranasal steroid and asthma therapy. Clinical question: In adult patient with allergic rhinitis related to asthma, does the combination of intranasal and inhaled steroids give better clinical improvement subjectively and objectively compared to monotherapy? Method: Literature search through two different databases (PubMed and Cochrane Library) and by searching the bibliography of articles to evaluate the outcome of combination therapy and monotherapy for the disease. Result: Two articles were found relevant with the topic fulfilled the requirements and relevant with the formulation or clinical question. Conclusion: Treating the inflammation associated with allergic rhinitis may have a true impact on the control of asthma, while the failure to treat rhinitis may impair asthma control.ABSTRAKLatar belakang: Konsep United Airway Disease (UAD) mengenali adanya hubungan antara inflamasi alergi pada saluran napas atas dan bawah. Pasien asma yang bersamaan dengan rinitis alergi melakukan lebih banyak kunjungan ke perawatan primer dan sekunder terkait asma. Tujuan: Menentukan pilihan pengobatan terbaik pada pasien dengan rinitis alergi terkait asma, baik dalam pengendalian keluhan hidung maupun paru. Laporan kasus: Satu kasus seorang wanita berusia 45 tahun dengan asma yang berhubungan dengan rinitis alergi. Metode: Mengumpulkan jurnal terkait dari dua database yang berbeda (PubMed dan Cochrane Library). Pencarian artikel juga dilakukan dengan mencari pada daftar pustaka artikel untuk mengevaluasi luaran dari terapi kombinasi dan terapi tunggal untuk penyakit ini. Pertanyaan klinis: Apakah terapi kombinasi dengan steroid intranasal dan steroid hirup dapat memberikan perbaikan lebih signifikan secara subjektif maupun objektif dibandingkan dengan terapi tunggal pada pasien dewasa dengan rinitis alergi dan asma? Hasil: Didapatkan dua artikel yang relevan dengan topik, sesuai dengan pertanyaan klinis serta memiliki penilaian kritis yang baik. Kesimpulan: Mengobati peradangan yang terkait dengan rinitis alergi dapat berdampak nyata pada pengendalian asma, sedangkan kegagalan untuk mengobati rinitis dapat mengganggu pengendalian asma.

Allergic Rhinosinusitis and Airway Diseases

The concept of united airway disease interaction, which comprises chronic rhinosinusitis and other lower airway disorders such as asthma, has been recognized for over a decade [...]

Management of United Airway Disease Focused on Patients With Asthma and Chronic Rhinosinusitis With Nasal Polyps: A Systematic Review

The clinical approach to upper and lower respiratory diseases from a joint perspective, known as united airways disease (UAD), is challenging for health care professionals owing to a paucity of specific studies. This study reviews recent scientific evidence on the management of asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) from a UAD perspective. A systematic search of PubMed, Scopus, and Web of Science was conducted for 9 research questions, and studies published from January 2015 to July 2021 were included. Quality assessment was performed with the Critical Appraisal Skills Programme. In total, 32 publications met the inclusion criteria. Control of type 2 inflammation in UAD (reported in 9 studies) was associated with biologic therapies, for which an impact on asthma, CRSwNP, and/or aspirin/nonsteroidal anti-inflammatory drug-exacerbated respiratory disease outcomes was described in 9 studies. However, there was a lack of scientific evidence on clinical and/or biochemical markers associated with response to biologics in patients with UAD. The benefit on corticosteroid reduction in patients receiving biologics was reported in 9 studies. Three publications reported a positive impact of surgery on asthma and/or CRSwNP outcomes, and the effect of biologics on reducing the need of surgery was consistent across 6 studies. Our results underscore an overall scarcity of scientific evidence on the treatment strategies for these frequent coexisting entities from an UAD approach but also identify several research gaps and unmet needs that should be addressed to ensure optimal diagnosis, management, and follow-up of these patients.

Can united airway disease be the cause of variable severity experience of COVID-19 in health care workers?

Can united airway disease be the cause of variable severity experience of COVID-19 in health care workers?

Cross-sectional study on exhaled nitric oxide in relation to upper airway inflammatory disorders with regard to asthma and perennial sensitization.

Fractional exhaled nitric oxide (FeNO) is a well-known marker of type-2 inflammation. FeNO is elevated in asthma and allergic rhinitis, with IgE sensitization as a major determinant. We aimed to see whether there was an independent association between upper airway inflammatory disorders (UAID) and FeNO, after adjustment for asthma and sensitization, in a multi-centre population-based study. A total of 741 subjects with current asthma and 4155 non-asthmatic subjects participating in the second follow-up of the European Community Respiratory Health Survey (ECRHS III) underwent FeNO measurements. Sensitization status was based on measurement of IgE against airborne allergens; information on asthma, UAID and medication was collected through interview-led questionnaires. Independent associations between UAID and FeNO were assessed in adjusted multivariate regression models and test for interaction with perennial sensitization and asthma on the relation between UAID and FeNO were made. UAID were associated with higher FeNO after adjusting for perennial sensitization, asthma and other confounders: with 4.4 (0.9-7.9) % higher FeNO in relation to current rhinitis and 4.8 (0.7-9.2) % higher FeNO in relation to rhinoconjunctivitis. A significant interaction with perennial sensitization was found in the relationship between current rhinitis and FeNO (p=.03) and between rhinoconjunctivitis and FeNO (p=.03). After stratification by asthma and perennial sensitization, the association between current rhinitis and FeNO remained in non-asthmatic subjects with perennial sensitization, with 12.1 (0.2-25.5) % higher FeNO in subjects with current rhinitis than in those without. Current rhinitis and rhinoconjunctivitis was associated with higher FeNO, with an interaction with perennial sensitization. This further highlights the concept of united airway disease, with correlations between symptoms and inflammation in the upper and lower airways and that sensitization needs to be accounted for in the relation between FeNO and rhinitis.

Effects on hearing and tinnitus following Dupilumab treatment of severe asthma with chronic rhinosinusitis - a case report

Background: Dupilumab (anti-IL-4R) is a novel biological agent approved for treatment of severe asthma with chronic rhinosinusitis. Beneficial effects on hearing have only been sparsely decribed. Case presentation: In this case story we present a 48-year woman, who experienced remarkably improved hearing and reduction of tinnitus after initiation of Dupilumab. Progress was monitored by respiratory physicians in collaboration with rhinologists and audiologists. SNOT-22 score improved from 83 to 27 and audiograms obtained before and during treatment illustrate a reduced air-bone gap and an improvement of speech recognition threshold from 25 dB (both ears) to 15 and 10 (left and right ear respectively). Conclusions: This case story implies a beneficial effect of Dupilumab treatment in patients with united airway disease with hearing impairment. The authors suggest an additional otological perspective in addition to standard monitoring.

Immunological and microRNA Features of Allergic Rhinitis in the Context of United Airway Disease

Inflammation of the upper respiratory tract in patients with allergic rhinitis (AR) may contribute to lower respiratory airways’ inflammation. T-helper 17 (Th17) cells and related cytokines are also involved in the immunological mechanism of AR along with the classical Th2 cells. It is hypothesized that upon Th2 pressure, the inflammatory response in the lungs may lead to Th17-induced neutrophilic inflammation. However, the findings for interleukin-17 (IL-17) are bidirectional. Furthermore, the role of Th17 cells and their counterpart—T regulatory cells—remains unclear in AR patients. It was also shown that a regulator of inflammation might be the individual circulating specific non-coding microRNAs (miRNAs), which were distinctively expressed in AR and bronchial asthma (BA) patients. However, although several circulating miRNAs have been related to upper and lower respiratory tract diseases, their function and clinical value are far from being clarified. Still, they can serve as noninvasive biomarkers for diagnosing, characterizing, and providing therapeutic targets for anti-inflammatory treatment along with the confirmed contributors to the pathogenesis—Th17 cells and related cytokines. The narrow pathogenetic relationship between the nose and the bronchi, e.g., upper and lower respiratory tracts, confirms the concept of unified airway diseases. Thus, there is no doubt that AR and BA should be diagnosed, managed, and treated in an integrated manner.

United airway disease.

Nose and lungs are considered as anatomic and functional unit, as they share morphological, pathophysiological and immunological basis. Allergic rhinitis and asthma often coexist in the same individual, and the treatment of one also improves the symptoms of the other (one airway, one disease). The aim of this review is to discuss the interaction between upper and lower airways, based on recent scientific evidence and, critically, analyze the important implications the new findings have for the future therapy and prevention of these common diseases. (www.actabiomedica.it)

Allergic rhinitis as a key factor for the development of gastroesophageal reflux disease in children.

Gastroesophageal reflux disease (GERD) may cause airway symptoms and some airway diseases exacerbate GERD symptoms. Asthma and allergic rhinitis (AR) have been identified as united airway disease because of their similar epidemiology and pathophysiology. Asthma has been considered a risk factor to develop GERD. However, the association between AR and GERD is not clear. We tried to investigate whether AR could increase the development of GERD. Children diagnosed as AR without a prior history of GERD were conducted from the National Health Insurance Research Database between 2000 and 2005. After propensity score matching, we enrolled 36,588 children with AR and 36,588 non-AR children as the controls. Cox regression models were adopted to calculate the hazard ratio (HR) of GERD. AR children had a significantly increased risk of GERD than non-AR children (adjusted HR 1.91, 95% CI=1.73-2.11, p<0.001), especially in the age less than 6 years old (adjusted HR 2.68, 95% CI=1.64-4.38, p<0.001). The risk factor related to increased risk of GERD including age, gender, and chronic sinusitis. AR is a risk factor associated with the development of GERD in children.

Role of IL-25, IL-33, and TSLP in triggering united airway diseases toward type 2 inflammation.

Under the concept of "united airway diseases," the airway is a single organ wherein upper and lower airway diseases are commonly comorbid. The upper and lower airways are lined with respiratory epithelium that plays a vital role in immune surveillance and modulation as the first line of defense to various infective pathogens, allergens, and physical insults. Recently, there is a common hypothesis emphasizing epithelium-derived cytokines, namely IL-25, IL-33, and TSLP, as key regulatory factors that link in immune-pathogenic mechanisms of allergic rhinitis (AR), chronic rhinosinusitis (CRS), and asthma, mainly involving in type 2 inflammatory responses and linking innate and adaptive immunities. Herein, we review studies that elucidated the role of epithelium-derived triple cytokines in both upper and lower airways with the purpose of expediting better clinical treatments and managements of AR, CRS, asthma, and other associated allergic diseases via applications of the modulators of these cytokines.