United Airway Research Articles

Two inflammatory phenotypes of nasal polyps and comorbid asthma

BackgroundNasal polyps and comorbid asthma (NPCA) is a common united airway disease. However, the inflammatory phenotyes of NPCA are not clear. ObjectiveTo identify inflammatory phenotypes of NPCA. MethodsA total of 106 patients diagnosed with NPCA were recruited from rhinologic clinics. A combined method of biopsies from nasal polyps and fractional exhaled nitric oxide (FeNO) was used to explore inflammatory phenotyes of NPCA. Patients were evaluated with respect to clinical, functional, and inflammatory parameters. Clinical outcomes after medical treatment were also assessed. ResultsTwo distinct inflammatory phenotypes (eosinophilic [64.15%] and noneosinophilic phenotypes [35.85%]) were identified. Inflammatory patterns of upper and lower airways were consistent in NPCA. Patients with eosinophilic NPCA had a higher nasal polyps recurrence rate than did patients with noneosinophilic NPCA, a more severe asthma phenotype (P < .001), higher exhaled nitric oxide levels (P < .001), higher IgE levels (P < .001), higher Lund-Mackay scores (P < .05), and more blood eosinophilia (P < .001). In addition, eosinophilic NPCA was associated with worse pulmonary function and responded well to an 8-week course of medical treatment based on computed tomographic findings and the ratio of forced expiratory volume in 1 second to forced vital capacity. The total IgE concentration was a marker for eosinophilic NPCA (optimal cutoff, >55.5 kU/L; sensitivity, 86.2%; specificity, 85.4%). ConclusionPatients with NPCA had 2 inflammatory phenotypes with distinct clinical profiles. Total IgE is a marker of eosinophilic NPCA.

P.3.f.026 - The role of psychiatrists’ attitudes on the prescription of long-acting injectable antipsychotics

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.

Following up infant bronchiolitis patients provided new evidence for and against the united airway disease hypothesis

The united airway disease (UAD) hypothesis suggests that allergic rhinitis and asthma develop together. We evaluated the evidence for and against the UAD hypothesis at five to seven years of age after hospitalisation for bronchiolitis at less than six months. This study used prospective follow-up data for 102 children hospitalised for bronchiolitis under the age of six months. We included the presence of previous and current asthma, prolonged rhinitis and skin prick tests (SPT) to common inhaled allergens and lung function by impulse oscillometry (IOS) at five to seven years of age. Bronchial hyper-reactivity (BHR) was assessed using the exercise challenge test and bronchodilation test. Current asthma, but not previous transient asthma, was associated with prolonged rhinitis and a positive SPT. BHR, which reflected reactive airways, but not lung function, was associated with respiratory allergy, namely the combination of current asthma, prolonged rhinitis and a positive SPT. This post-bronchiolitis follow-up study suggested an association between respiratory allergy and reactive airways at five to seven years of age, which supported the UAD hypothesis. However, previous transient asthma and a reduction in lung function reduction did not support the hypothesis.

The link between chronic rhinosinusitis and asthma: A questionnaire-based study.

Treatments for chronic rhinosinusitis (CRS) and asthma can affect both conditions, based on the united airway concept. This study aimed to evaluate the link between CRS and asthma, based on disease-specific quality of life measures.We performed a prospective cohort study to investigate the correlations between results from CRS- and asthma-specific questionnaires. Thirty-two patients with asthma and CRS were evaluated before and after undergoing nasal surgery at a tertiary medical center.There were significant correlations between the results from the Asthma Control Test (ACT) and the Sino-Nasal Outcome Test-22, as well as between the results of the ACT and Rhinoconjunctivitis Quality of Life Questionnaire, at both the preoperative and 3-month postoperative evaluations (P < 0.01). Moreover, nasal surgery improved the sinonasal symptoms, asthma control, and pulmonary function (P < 0.01).Increasingly severe sinonasal symptoms of CRS were associated with poor asthma control. Therefore, CRS and asthma should be considered and treated as common airway diseases.

MicroRNA in United Airway Diseases.

The concept of united airway diseases (UAD) has received increasing attention in recent years. Sustained and increased inflammation is a common feature of UAD, which is inevitably accompanied with marked gene modification and tight gene regulation. However, gene regulation in the common inflammatory processes in UAD remains unclear. MicroRNA (miRNA), a novel regulator of gene expression, has been considered to be involved in many inflammatory diseases. Although there are an increasing number of studies of miRNAs in inflammatory upper and lower airway diseases, few miRNAs have been identified that directly link the upper and lower airways. In this article, therefore, we reviewed the relevant studies available in order to improve the understanding of the roles of miRNAs in the interaction and pathogenesis of UAD.

Asthma in ear, nose, and throat primary care patients with chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disorder associated with asthma. This association is well described in patients with CRSwNP undergoing endoscopic sinus surgery (ESS); however, some patients are never referred for surgery, and the frequency of asthma in this group is largely unknown. To determine the frequency of asthma in patients with CRSwNP treated in a primary care (PC) setting who have never been referred for surgery and to compare this with ESS patients. Fifty-seven patients with CRSwNP who had never undergone ESS were prospectively recruited from nine PC ear, nose, and throat clinics in the Copenhagen area. CRSwNP was diagnosed according to the European Position Paper on Chronic Rhinosinusitis and Nasal Polyps; severity was assessed by using a visual analog scale. Allergy, lung function, and asthma tests (reversibility to β2-agonist, peak expiratory flow variability, and mannitol challenge) were performed. Findings were compared with our previously published data from patients with CRSwNP referred for surgery. Asthma was diagnosed in 25 patients (44%) based on respiratory symptoms and a positive asthma test; of these, 12 (48%) had undiagnosed asthma prior to study onset. Furthermore, when using the same methods, we found a lower frequency of asthma in PC patients compared with ESS patients (44% versus 65%, p = 0.04). A high prevalence of asthma in PC patients with CRSwNP was found. Frequently, asthma was undiagnosed. However, asthma was significantly less prevalent in PC patients compared with patients referred for ESS. The frequent concomitance of asthma, i.e., united airways disease, in PC patients calls for closer collaboration between ear, nose, and throat specialists, and asthma specialists.

United airway disease: current perspectives.

Upper and lower airways are considered a unified morphological and functional unit, and the connection existing between them has been observed for many years, both in health and in disease. There is strong epidemiologic, pathophysiologic, and clinical evidence supporting an integrated view of rhinitis and asthma: united airway disease in the present review. The term “united airway disease” is opportune, because rhinitis and asthma are chronic inflammatory diseases of the upper and lower airways, which can be induced by allergic or nonallergic reproducible mechanisms, and present several phenotypes. Management of rhinitis and asthma must be jointly carried out, leading to better control of both diseases, and the lessons of the Allergic Rhinitis and Its Impact on Asthma initiative cannot be forgotten.

United Airway Disease Among Crop Farmers

ABSTRACTAlthough there are observed relationships between agriculture and respiratory health problems, little attention has been given to relationship between lower and upper airway problems among farmers in the United States. The objective was to investigate the possible relationship between occupational risk factors and “united airway disease” among farmers in eastern North Carolina. Farmers and farm workers were selected from eastern North Carolina by using a cluster sampling method. A total of 180 farmers and farm workers completed the questionnaire. Data analyses were conducted to test associations and correlations between working conditions and symptoms. Lower airway symptom prevalence was 35%, and 66% had upper airway symptoms. Only 1% of farmers had physician-diagnosed rhinitis. Self-reported rhinitis and asthma symptoms were significantly correlated (r = .228, P = .003) among farmer/farm workers. Upper airway diseases are prevalent yet overlooked among farmer/farm workers. Early management of upper airway symptoms may prevent severe lower airway diseases, which will lead to increased productivity in the agricultural workforce.

Nasal polyps in patients with asthma: prevalence, impact, and management challenges.

Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often have coexisting asthma under the concept of “United Airway Disease”, being the combination of both diseases, which is one of the most challenging phenotypes to treat. Although clinicians have recognized this difficult-to-treat phenotype for many years, it remained poorly characterized. There is increasing epidemiological evidence linking chronic rhinosinusitis and asthma, but a good understanding of the pathophysiology and the combined management is still lacking. Bronchial asthma is more prevalent in patients who suffer chronic rhinosinusitis, while asthmatic patients have a greater prevalence of CRSwNP than patients without asthma. The effect of CRSwNP treatment, whether medical or surgical, in asthma is today less controversial after some studies have shown improvement of asthma after medical and/or surgical treatment of CRSwNP. However, direct comparisons between surgical and medical treatments are limited. Further randomized clinical trials are, however, still needed to better understand the management when both asthma and CRSwNP occur together. This review aims at summarizing the prevalence, impact, and management challenges regarding both asthma and CRSwNP.

Association between Asthma and Primary Nocturnal Enuresis in Children

Enuresis, sleep respiratory disorders and asthma compromise the quality of sleep in children and may occur in association with each other. An association between sleep respiratory disorders and enuresis has already been demonstrated. According to united airways disease abnormalities of the upper and lower airways may coexist. A child who wheezes has a greater chance of snoring and having obstructive sleep apnea. Since asthma and sleep respiratory disorders may be associated, and sleep respiratory disorders are associated with enuresis, we determined the possibility of an association between asthma and enuresis. Between August 20 and March 2015 parents/guardians of children 6 to 14 years old from 16 elementary schools in our area were randomly chosen for study. Children with nonmonosymptomatic enuresis and urological or neurological disease were excluded. The Tucson and ISAAC (International Study of Asthma and Allergies in Childhood) questionnaires wereused to assess sleep respiratory disorders and asthma, respectively. A total of 523 children (283 males and 240 females) with a mean ± SD age of 9.42 ± 2.46 years were included in analysis. The overall prevalence of enuresis was 15.87% (95% CI 12.98-19.26). Asthmatic children with wheezing in the last 12 months were 2.33 times more likely to have had enuresis at some point in life (OR 2.33, 95% CI 1.37-3.95, p = 0.0017). If enuresis was present, the chance increased to 2.78 (95% CI 1.38-5.61, p = 0.0041). Enuretic children were 5.34 times more prone to have apnea reported by parents (95% CI 2.19-13.03, p= 0.0002). These findings demonstrate that asthma as well as sleep respiratory disorders is associated with primary nocturnal enuresis.

The risk of respiratory symptoms on allergen exposure increases with increasing specific IgE levels.

The relation between IgE sensitization and allergic respiratory symptoms has usually been evaluated by dichotomizing specific IgE levels. The aim of this study was to evaluate the association between specific IgE levels and risk of symptoms on allergen-related exposure, with special reference to allergen-related asthma-rhinitis comorbidity. We considered 6391 subjects enrolled within the European Community Respiratory Health Survey 2, having information on cat/grass/D. pteronyssinus IgE levels and symptoms on exposure to animals/pollen/dust. The risk of oculonasal/asthmalike/both symptoms was evaluated by a multinomial logistic model. A clear positive association was observed between specific IgE levels to cat/grass/mite and the risk of symptoms on each allergen-related exposure (test for trend with P < 0.001). This trend was particularly pronounced when considering the coexistence of asthmalike and oculonasal symptoms. Compared to non-sensitized subjects, subjects with specific IgE to cat >= 3.5 kU/l presented relative risk ratios of 11.4 (95% CI 6.7-19.2), 18.8 (8.2-42.8), and 55.3 (30.5-100.2) when considering, respectively, only oculonasal symptoms, only asthmalike symptoms, or both. A similar pattern was observed when considering specific IgE to grass/mite and symptoms on exposure to pollen/dust. Also the proportion of people using inhaled medicines or visiting a general practitioner for breathing problems in the previous year increased with increasing sum of specific IgE to cat/grass/mite. Specific IgE level is the most important predictor of allergen-related symptoms. The risk of both oculonasal/asthmalike symptoms increases with specific IgE levels, suggesting that specific IgE contributes to the 'united airways disease'.

The united airways concept: from bench to bedside

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Airway Diseases Education and Expertise (ADEX ) in Pediatrics: Adaptation for Clinical Practice in India.

Asthma and allergic rhinitis together are part of the concept of one airway, one disease or united airway disease. The management of allergic airway diseases should address this united concept and manage the issue by educating the patients and their parents and health care providers, along with environmental control measures, pharmacotherapy and immunotherapy. Here, we present recommendations from the module of Airway Diseases Education and Expertise (ADEX) that focused on allergic rhinitis, asthma and sleep disorder breathing as a single entity or Allergic Airway Disease. A working committee was formed by the collaboration of Pediatric Allergy Association of India (PAAI) and Indian Academy of Pediatrics (IAP) Allergy and Applied Immunology chapter to develop a training module on united airway disease. To increase awareness, understanding and acceptance of the concept of United Airway disease and to educate the primary health care providers for children and public health officials, in the management of united airway diseases. Recommendations for diagnosis, management and follow-up of Allergic airway disease are presented in this document. A better compliance by linking education of child, parent, grandparents and other health care providers, and scientific progress by collaboration between practitioners, academicians, researchers and pharmaceutical companies is suggested.

Identification of common allergens for united airway disease by skin prick test

Objective: Identification of common allergens by skin prick test in patients of united airway disease. Materials and Methods: Skin prick test was performed in 60 patients of United Airway Disease to identify the common allergens. A total of 62 allergens consisting of 36 types of pollen, 5 fungi, 4 insects, 8 type of dusts, 4 dander, 3 fabrics, Dust mite and Parthenium leaves were tested. Result: Most common allergens were Dust mite (60%) followed by Parthenium leaves (45%), insects (18.75%), pollen (14.81%), dust allergens (8.51%), fabrics (8.33%), fungi (5.66%), dander (5%). Most common insect allergens were cockroach (female) (30%), cockroach (male) (23.33%). Common pollens were Ricinus communis (28.33%), Amaranthus spinosus (28.33%), Parthenium hysterophorus (26.66%), Eucalyptus tereticornis (26.66%) and Cynodon dactylon (25%). Common dust allergens were house dust (21.66%), paper dust (11.66%) and cotton mill dust (10%). Among fabrics kapok cotton (13.33%) showed maximum positivity. Among fungi Aspergillus fumigatus (10%) followed by A. niger (6.66%) were most common. In animal dander group common ones were cat dander followed by dog dander. Conclusion: In conclusion it can be said that the knowledge drawn by above study will help to treat patients by immunotherapy or avoidance strategy.

Synergistic Effect of Dermatophagoides farinae and Lipopolysaccharides in Human Middle ear Epithelial Cells.

PurposeAlthough the concept of "one airway, one disease," which includes the middle ear space as part of the united airway is well recognized, the role of allergens in otitis media with effusion (OME) is not clearly understood. We aimed to investigate the effect of the interaction between Dermatophagoides farinae (Der f) and lipopolysaccharide (LPS) on the induction of epithelial inflammatory response in vitro.MethodsPrimary human middle ear epithelial cells were exposed to Der f, LPS, or both in different sequences, and the magnitude of the immunologic responses was compared. The mRNA expressiona of mucin (MUC) 4, 5AC, 5B, 8, GM-CSF, TNF-α, TLR4, and MD-2 were evaluated using real-time PCR. MUC levels before and after siRNA-mediated knockout of TLR4 and MD-2 were assessed. Lastly, the involved cell signaling pathway was evaluated.ResultsThe expressiona of cytokines, and the MUC 4, 5AC, 5B, and 8 genes were augmented by pretreatment with Der f followed by LPS; however, reverse treatment or combined treatment did not induce the same magnitude of response. Increased MUC expression was decreased by TLR4 knockdown, but not by MD-2 knockdown. The signal intensity of MUC 8 was higher in MD-2 over-expressed cells than in those exposed to LPS only. The translocation of nuclear factor-κB was observed in cells pretreated with Der f followed by LPS.ConclusionsWhen Der f treatment preceded LPS exposure, Der f and LPS acted synergistically in the induction of pro-inflammatory cytokines and the MUC gene, suggesting an important role in the development of OME in patients with concealed allergy airway sensitization.

Paranasal sinus opacification at MRI in lower airway disease (the HUNT study-MRI)

The study builds on the concept of united airways, which describes the link between the upper and lower airways. Explorations of this concept have mainly related to asthma and less to chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate paranasal sinus opacification at magnetic resonance imaging (MRI) in COPD, self-reported asthma and respiratory symptoms. In this cross-sectional study, 880 randomly selected participants in the Nord-Trøndelag health survey (HUNT) (mean age 57.7years, range 50-66years, 463 women) were investigated using MRI of the paranasal sinuses. Participants were allocated to four mutually exclusive groups: (1) COPD (n=20), (2) asthma (n=89), (3) respiratory symptoms (n=199), and (4) reference group (n=572). Paranasal sinus opacifications were categorised as mucosal thickening, polyps and retention cysts, and fluid. In each participant, measurements ≥1mm from all sinuses were summed to give a total for each category of opacities. The sums for these three categories were further added together, and referred to as the total sum. Using the 75th percentile cut-off values, the likelihood of having paranasal sinus opacifications was more than six times higher in participants with COPD and twice as high in participants with asthma than among the reference group. Respiratory symptoms were only associated with mucosal thickening. The present study shows that paranasal sinus opacification is associated not only with asthma, but also with COPD and respiratory symptoms. This is in accordance with the united airways hypothesis, and should be kept in mind when handling patients with these conditions.

Are atopy and eosinophilic bronchial inflammation associated with relapsing forms of chronic rhinosinusitis with nasal polyps?

BackgroundThe aetiopathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) is still unknown. The role of atopy and the concept of united airways in such patients are still a matter of debate. In this pilot study we aimed at evaluating the degree of eosinophilic inflammation and the frequency of atopy in a cohort of CRSwNP patients candidate for Functional Endoscopic Sinus Surgery (FESS) and assessing the association between these factors and relapsing forms of CRSwNP.Methods30 patients (18 men, 12 women) with CRSwNP eligible for FESS were evaluated before and after surgery. Preoperative investigation included: history of previous relapse after FESS, clinical and laboratory allergologic assessment, spirometry, methacholine challenge, blood eosinophilia and determination of the fraction of nitric oxide in exhaled air (FeNO). Nasal fibroendoscopy, spirometry and FeNO determination were also assessed prospectively at 3 and 27 months post-FESS.Results18/30 subjects were atopic, 6/18 (33 %) were monosensitized, 16/30 (53 %) were asthmatics and 10/30 (33 %) had non steroidalantinflammatory drugs (NSAIDs) hypersensitivity. Twenty-one patients (70 %) were classified as relapsers, 15/18 (83 %) among atopics, 6/12 (50 %) among non atopics (p = 0.05). Among patients with NSAIDs hypersensitivity, 9/10 (90 %) were relapsers. The median IgE concentration was 161.5 UI/mL in relapsers and 79 UI/mL in non-relapsers (ns). The mean FeNO decreased after FESS (43.1–26.6 ppb) in 84 % of patients, but this effect disappeared over time (FeNO = 37.7 ppb at 27 months). Higher levels of FeNO pre-FESS were detected in atopics, and in particular in relapsing ones (median 51.1 ppb vs 22.1, ns). Higher levels of FeNO pre-FESS were detected in asthmatic patients, especially in those who relapsed (median: 67 vs 64.85 ppb in non-relapsed patients, ns). The Tiffeneau Index (FEV1/FVC) was significantly lower in asthmatic relapsers than in non relapsers asthmatics (94.7 ± 11.1 versus 105 ± 5.9—p = 0.04). Patients with asthma and atopy had a major risk of relapse (p = 0.05).ConclusionIn our pilot study, atopy, severe asthma, bronchial inflammation, NSAIDs hypersensitivity and high level of total IgE are possible useful prognostic factors for the proneness to relapse after FESS. The role of allergy in CRSwNP pathogenesis should consequently be given deeper consideration. Allergen specific immunotherapy, combined with anti-IgE therapy, may have an immunomodulatory effect preventing polyps relapse and need to be investigated.Electronic supplementary materialThe online version of this article (doi:10.1186/s12948-015-0026-8) contains supplementary material, which is available to authorized users.

Type 5 and 6 nasal septal deformities: Could we predict and prevent acute coronary syndrome attacks in the future?

Undisturbed nasal breathing is essential for normal breathing physiology as a whole. Nasal septal deformities (NSD) are well known as a factor which can remarkably and substantially affect the quality of nasal and pulmonary breathing. However, it is well known that type 5 and type 6 nasal septal deformities may cause only a moderate, unilateral nasal obstruction or none at all. The effects of nasal obstruction on the respiratory and cardiovascular systems have been well studied so far: right ventricle problems, ischemic heart diseases, sleep disorders, mucociliary clearance system disturbances, paranasal sinus pathology, have all been described as a result of impaired nasal breathing. The connection between the upper and lower respiratory systems has been recognized in allergic rhinitis and asthma as well, resulting in the united airways concept. Most recently, the ostensible connection between chronic rhinosinusitis (CRS) and acute myocardial infarction has been said to be proven. However, the results of this study might have not been well founded since there are no direct and clear proofs that CRS as a chronic inflammatory process has anything to do with the acute coronary syndrome (ACS). On the other hand, a large international study on the incidence of NSD in CRS patients, based on the Mladina classification, showed that NSD were present in a high incidence and that the most frequent deformities were types 5 (36.18%) and 7 (29.92%). The vast majority of those types 7 consisted of types 3 and (again) types 5 or types 6 (76.32%). The fact that in CRS patients a remarkably high incidence of type 5 septal deformity can be seen, gives rise to thinking that this factor perhaps plays a role in the onset of ACS. Acute coronary syndrome is one of the leading causes of death all over the world. Traditional risk factors such as family history, overweight body, smoking, stress, hypertension, hypercholesterolemia, diabetes mellitus, coronary artery calcium score, C-reactive protein, lipoprotein, homocysteine, lipoprotein-associated phospholipase A2, as well as high-density lipoprotein functionality perhaps cannot account for the entire risk for incident coronary events. Several other potential risk factors have been identified in an effort to improve risk assessment for ACS. This article reviews one of them: the possible influence of an unusual, so far unknown predisposing factor: type 5 or type 6 nasal septal deformities. They have been found as pure, isolated types or as a part of combined nasal septal deformity (type 7).

Airway Inflammation in Chronic Rhinosinusitis with Nasal Polyps and Asthma: The United Airways Concept Further Supported.

BackgroundIt has been established that patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often have co-existing asthma.ObjectiveWe aimed to test two hypotheses: (i) upper and lower airway inflammation in CRSwNP is uniform in agreement with the united airways concept; and (ii) bronchial inflammation exists in all CRSwNP patients irrespective of clinical asthma status.MethodsWe collected biopsies from nasal polyps, inferior turbinates and bronchi of 27 CRSwNP patients and 6 controls. All participants were evaluated for lower airway disease according to international guidelines. Inflammatory cytokines were investigated using a Th1/Th2 assay including 14 chemokines and cytokines; tissue concentrations were normalized according to tissue weight and total protein concentration. Individual cytokines and multivariate inflammatory profiles were compared between biopsy sites and between patients and controls.ResultsWe found significantly higher concentrations of Th2 cytokines in nasal polyps compared to inferior turbinate and bronchial biopsies. In addition, we showed that the inflammatory profile of nasal polyps and bronchial biopsies correlated significantly (p<0.01). From the Th2 cytokines measured, IL-13 was significantly increased in bronchial biopsies from CRSwNP patients with, but not without asthma.ConclusionOur findings support the united airways concept; however, we did not find evidence for subclinical bronchial inflammation in CRSwNP patients without asthma. Finally, this study indicates for the first time that nasal polyps potentially play an important role in the airway inflammation rather than being a secondary phenomenon.

Neural Abnormalities in Nonallergic Rhinitis

Sensory nerve endings within the airway epithelial cells and the solitary chemoreceptor cells, synapsing with sensory nerves, respond to airborne irritants. Transient receptor potential (TRP) channels (A1 and V1 subtypes, specifically) on these nerve endings initiate local antidromic reflexes resulting in the release of neuropeptides such as substance P and calcitonin G-related peptides. These neuropeptides dilate epithelial submucosal blood vessels and may therefore increase transudation across these vessels resulting in submucosal edema, congestion, and rhinitis. Altered expression or activity of these TRP channels can therefore influence responsiveness to irritants. Besides these pathogenic mechanisms, additional mechanisms such as dysautonomia resulting in diminished sympathetic activity and comparative parasympathetic overactivity have also been suggested as a probable mechanism. Therapeutic effectiveness for this condition has been demonstrated through desensitization of TRPV1 channels with typical agonists such as capsaicin. Other agents effective in treating nonallergic rhinitis (NAR) such as azelastine have been demonstrated to exhibit TRPV1 channel activity through the modulation of Ca(2+) signaling on sensory neurons and in nasal epithelial cells. Roles of antimuscarinic agents such as tiotropium in NAR have been suggested by associations of muscarinic cholinergic receptors with TRPV1. The associations between these channels have also been suggested as mechanisms of airway hyperreactivity in asthma. The concept of the united airway disease hypothesis suggests a significant association between rhinitis and asthma. This concept is supported by the development of late-onset asthma in about 10-40 % of NAR patients who also exhibit a greater severity in their asthma. The factors and mechanisms associating NAR with nonallergic asthma are currently unknown. Nonetheless, free immunoglobulin light chains and microRNA alteration as mediators of these inflammatory conditions may play key roles in this association.