Mechanisms of nasal hyper-reactivity

Hyper-reactivity to non-specific challenges has been considered a hallmark of asthma and is defined as an abnormal responsiveness of the bronchial airways to a variety of provocative agents. The mechanisms underlying hyper-reactivity in the upper and lower airways are not known. By using the nose to study the inflammatory response possible abnormalities can be investigated carefully and pathophysiology of specific airway hyper-reactivities can be better understood. Other factors than merely constriction of the bronchial smooth muscles can cause narrowing of the free lumen to airflow. Functionally different and very distinct mucosal end-organ reactivities may also be increased. If these reactivities can be well assessed, specific airway hyper-reactivity can be defined. In the present report, specific mucosal end-organ hyper-reactivites in the allergic nasal mucosa are presented. Certain widespread hypotheses, such as the role of the eosinophil and the “increased absorption permeability theory”, are disputed.     

变应原气道激发在变应性鼻炎和哮喘研究中的作用研究进展

随着城市化进程，环境及生活方式的改变，我国变应性疾病发病率逐年升高。目前认为变应性鼻炎和哮喘的发病主要是在遗传基因、环境因素共同作用下导致，但具体发病机制复杂，尚未完全清楚。慢性气道炎症和气道高反应性是变应性鼻炎和哮喘的典型的病理生理特征。环境中变应原的暴露可诱发疾病症状发作，引起气道及全身炎症反应增加，并导致气道敏感性/反应性升高。人为给予变应性鼻炎或哮喘患者呼吸道变应原吸入刺激，可以模拟其变应原自然暴露所致疾病症状发作，研究其病理生理变化，尚可通过药物干预评估其对症状及炎症抑制程度评估药物治疗效果。同时变应性鼻炎和哮喘作为上下气道疾病，相互影响，通过一端变应原刺激研究气道另一端症状及炎症反应，探讨上下气道之间的联系。屋尘螨为我国,特别是南方地区最主要、最常见的变应原，与疾病关系密切。主要从屋尘螨变应原鼻激发和支气管激发方法学及其在鼻炎和哮喘的研究中的应用作一综述。     

Objective assessment of lower airway involvement in chronic rhinosinusitis

BACKGROUND: When associated with lower airway involvement, the morbidity and the cost of chronic rhinosinusitis (CRS) can increase. The aim of this prospective study was to assess the clinical and radiological characteristics of the upper airways in CRS patients scheduled for functional endoscopic sinus surgery and to correlate these findings with the functional changes of the lower airways. METHODS: Twenty-five adult patients with CRS were subjected to clinical and endoscopic assessments, computed tomography scan, and allergic assessments using validated scoring systems. Lower airways were assessed by clinical history, pulmonary function test, histamine bronchial provocation test, and chest x rays. RESULTS: Sixty percent of CRS patients were shown to have associated lower airway involvement, i.e., 24% had asthma and 36% had small airway disease (SAD). Nasal congestion and nasal polyps were the most common clinical findings in both of these subgroups of patients. In addition, there was a negative correlation between computed tomography scan findings of the sinuses and the obstructive parameters on pulmonary function test in SAD but not in the asthma subgroup. CONCLUSION: These results showed that different kinds of lower airway involvement frequently could be associated with CRS. Some are manifest such as asthma and some are hidden such as SAD and histamine bronchial hyperresponsiveness.     

Nasal Histamine Reactivity; Relationships to Skin-test Responses,Allergen Provocation and Symptom Severity in Patients with Long-continuing Allergic Rhinitis

It has been reported that skin-test reactivity and rhinitis symptom severity weaken in the course of time. A corresponding weakening might also be seen in non-specific nasal hyper-reactivity, but the relationships of these responses are poorly understood. Our aim was to measure nasal responsiveness to histamine in a series of patients with long-continuing allergic rhinitis and to compare these measurements with skin test responses, allergen provocation and changes in severity of allergic rhinitis symptoms. A total of 73 patients in whom allergic rhinitis had been verified over 20 years earlier were re-interviewed and re-investigated. Skin prick tests with common allergens were performed and the presence of nasal allergy was confirmed by allergen provocation. Non-specific nasal hyper-reactivity was determined with nasal histamine challenge using four concentrations of histamine phosphate. The response was registered by counting sneezes, recording changes in nasal discharge and mucosal swelling and measuring nasal airway resistance. Sneezing and discharge scores showed that milder non-specific nasal hyper-reactivity was associated with lack of reactivity in skin prick tests and nasal allergen challenge. No association was observed between allergy test results and changes in nasal airway resistance during the histamine provocation. In most patients the symptoms of rhinitis had become milder or disappeared during the follow-up, but the results of the histamine challenge showed no relationship with the changes in symptom severity. In patients with allergic rhinitis, reactivity to histamine is associated with a concomitant change in skin and nasal mucosal reactivity to allergens.     

Nasal histamine reactivity; relationships to skin-test responses, allergen provocation and symptom severity in patients with long-continuing allergic rhinitis

It has been reported that skin-test reactivity and rhinitis symptom severity weaken in the course of time. A corresponding weakening might also be seen in non-specific nasal hyper-reactivity, but the relationships of these responses are poorly understood. Our aim was to measure nasal responsiveness to histamine in a series of patients with long-continuing allergic rhinitis and to compare these measurements with skin test responses, allergen provocation and changes in severity of allergic rhinitis symptoms. A total of 73 patients in whom allergic rhinitis had been verified over 20 years earlier were re-interviewed and re-investigated. Skin prick tests with common allergens were performed and the presence of nasal allergy was confirmed by allergen provocation. Non-specific nasal hyper-reactivity was determined with nasal histamine challenge using four concentrations of histamine phosphate. The response was registered by counting sneezes, recording changes in nasal discharge and mucosal swelling and measuring nasal airway resistance. Sneezing and discharge scores showed that milder non-specific nasal hyper-reactivity was associated with lack of reactivity in skin prick tests and nasal allergen challenge. No association was observed between allergy test results and changes in nasal airway resistance during the histamine provocation. In most patients the symptoms of rhinitis had become milder or disappeared during the follow-up, but the results of the histamine challenge showed no relationship with the changes in symptom severity. In patients with allergic rhinitis, reactivity to histamine is associated with a concomitant change in skin and nasal mucosal reactivity to allergens.     

Sinus surgery in cystic fibrosis patients: comparison of sinus and lower airway cultures

OBJECTIVE: The aim of this study is to determine whether cross-infection occurs between infections in the sinuses and lower airways in Cystic Fibrosis patients, and to determine whether the infections begin in the sinuses before spreading to the lungs. METHODS: Retrospective study of pediatric Cystic Fibrosis patients who underwent simultaneous sinus surgery and bronchial washings. The results of the cultures were reviewed to determine if the same organisms colonized both the sinuses and lower airways. RESULTS: Staphylococcus aureus (Staph. Aureus) was found in 40.7% of the sinuses but only 33.3% of the lower airways. One patient had Staph. Aureus in the lower airway but not the sinuses. Pseudomonas, Hemophilus Influenza, and Moraxella showed similar patterns: multiple instances of positive sinus cultures and negative bronchial cultures, but only a small number of cases with positive lower airway cultures and negative sinus cultures. CONCLUSION: The data showed that as patients age, they are more likely to have infections in both upper and lower airways, but infections start in the upper airways at a younger age. In many cases, organisms were cultured from sinuses in patients who had negative lower airway cultures. In only a few instances, organisms grew in the lower airways and not the sinuses. In most cases, the bacteria that caused sinus infections at a young age caused the lung infections in older patients. This is the paper to show that bacteria spread from the sinuses to the lungs to cause infections in Cystic Fibrosis patients, and not vice-versa.     

Relationship between inflammation of upper and lower respiratory airways

Dysfunction of the upper and lower airways frequently coexists, and they appear to share key elements of pathogenesis. Data from epidemiologic studies indicate that nasal symptoms are experienced by as many as 78% of patients with asthma and that asthma is experienced by as many as 38% of patients with allergic rhinitis. Among patients with nasal polyps 27-51% have asthma. Polyps of nasal mucosa usually exacerbates symptoms of concomitant asthma. Studies also have identified a temporal relation between the onset of rhinitis and asthma, with rhinitis frequently preceding the development of asthma. Patients with allergic rhinitis and no clinical evidence of asthma commonly exhibit nonspecific bronchial hyperresponsivenes. The mechanisms upper and lower airway dysfunction are under investigation. They include nasal-bronchial reflex, mouth breathing caused by nasal obstruction, and pulmonary aspiration of nasal contents. Nasal allergen challenge results in increases in lower airway reactivity within 30 minutes, suggesting a neural reflex. Improvements in asthma associated with increased nasal breathing may be the result of superior humidification, warming of inspired air, and decreased inhalation of airborne allergens. Postnasal drainage of inflammatory cells during sleep also may affect lower airway responsiveness. The effective management of allergic rhinitis relieves symptoms of asthma. A link between allergic rhinitis and asthma is evident from epidemiologic, pathophysiologic, and clinical studies. The development of differential diagnosis of rhinitis has multiplied their present classifications. This article presents classifications of rhinitis connected with lower airways dysfunction.     

Suspected foreign body aspiration in a child with endobronchial tuberculosis

Endobronchial tuberculosis is a form of pulmonary tuberculosis, thought to result from rupture of an infected node through the bronchial wall or from lymphatic spread to the mucosal surface of the bronchial tree. With the presence of multidrug resistant isolates of TB, and its incidence in an increasing number of foreign-born persons immigrating to the US, otolaryngologists must be aware of its often subtle presentation. The following case is an unusual presentation of endobronchial tuberculosis initially diagnosed as an airway foreign body.     

Allergic rhinitis: past,present and the future

Allergic rhinitis: past, present and the future Allergic rhinitis represents a global health issue affecting between 10% to 25% of the world population, with increasing prevalence over the last decade. Although often trivialized by patients and doctors, allergic rhinitis is a significant cause of morbidity, in addition to its substantial economic impact. While allergic rhinitis is an inflammatory disorder of the upper airways, inflammation alone is insufficient to explain the chronic nature of the disease. An exciting concept which has recently emerged in asthma concerns the role of the bronchial epithelium as a key regulator of airway inflammatory and remodelling responses in asthma. It has been shown by our group that the disruption and alteration in the function of the lower airway epithelium in asthma leads to the generation of a variety of stimuli that lead to the restructuring of the airway wall. This raises interesting questions regarding a similar role for the upper airway epithelium in allergic rhinitis. This review aims to interpret past and current research into allergic rhinitis, and to address specific areas where future research is warranted, particularly in relation to the possibility of an altered upper airway epithelial phenotype in allergic rhinitis.     

Allergic rhinitis: past,present and the future

Allergic rhinitis represents a global health issue affecting between 10% to 25% of the world population, with increasing prevalence over the last decade. Although often trivialized by patients and doctors, allergic rhinitis is a significant cause of morbidity, in addition to its substantial economic impact. While allergic rhinitis is an inflammatory disorder of the upper airways, inflammation alone is insufficient to explain the chronic nature of the disease. An exciting concept which has recently emerged in asthma concerns the role of the bronchial epithelium as a key regulator of airway inflammatory and remodelling responses in asthma. It has been shown by our group that the disruption and alteration in the function of the lower airway epithelium in asthma leads to the generation of a variety of stimuli that lead to the restructuring of the airway wall. This raises interesting questions regarding a similar role for the upper airway epithelium in allergic rhinitis. This review aims to interpret past and current research into allergic rhinitis, and to address specific areas where future research is warranted, particularly in relation to the possibility of an altered upper airway epithelial phenotype in allergic rhinitis.     

Correlation between nasal anatomy and subjective patency: a prospective MRI study

Background: Variations in the thickness of the nasal septum are well documented¹ Objective: To determine if septal mucosal thickness and other parameters derived from MRI imaging correlate significantly with subjective sensation of nasal resistance. Methods: Forty patients undergoing MRI head scans for non-nasal disease were asked to complete a questionnaire immediately prior to the scan being taken. Subjective patency was scored for each nasal airway, patients were also asked about hayfever, URTIs, medication and history of nasal surgery or trauma. Scans were assessed using image analysis software. The following parameters were assessed at the level of the nasal valve: cross-sectional area of airway, horizontal thickness of inferior turbinate and maximum septal mucosal thickness. In addition, the presence of septal deviation (lateral to the vertical plane of the middle turbinate), and sinus mucosal thickening of 4 mm or more was assessed. Repeatability and inter-observer error was calculated. Data was analysed using non-parametric tests and multiple stepwise regression. Results: Overall correlation between anatomical parameters and subjective patency was low. Patients with sinus mucosal thickness greater than 4 mm on MRI scanning had subjectively poorer nasal airways (left P = 0.003, right P = 0.029). Multiple regression confirmed sinus mucosal thickening as the most significant predictor of patency but also negative correlation between ipsilateral mucosal thickness and patency (P < 0.002) and positive correlation between contralateral turbinate thickness (P < 0.01) and patency. Conclusions: Anatomical factors in both ipsilateral and contralateral nasal airways are of importance in subjective nasal patency. Sinus mucosal thickening correlates strongly with subjective nasal obstruction although the mechanism of this relationship is unclear. Non-anatomical and psychological factors are likely to be of considerable importance.     

Nasal and bronchial histamine responsiveness in pollen-exposed patients with seasonal rhinitis

In a previous study, we found an increased nasal responsiveness as measured by rhinostereometry and histamine challenge out of season in a sample of 12 patients suffering mainly from hay fever. The aim of the present study was to investigate whether airway responsiveness in these patients was further increased after direct pollen exposure, after a single nasal pollen provocation as well as by repeated exposure during the pollen season. In spite of increased allergic symptoms, the basal degree of nasal mucosal swelling was unchanged before histamine challenge under these circumstances. After histamine challenge, nasal mucosal swelling was increased in the same way over the seasons. Also bronchial responsiveness was unchanged during the pollen season. It correlated to frequent sneezing following nasal histamine challenge during the season (p = 0.0071, r = -0.74). We interpret the results as an indication of a continuos airway inflammation regardless of season in these patients with pollen allergy, with acute symptoms added on direct exposure to the allergen.     

Vascular effects of topical oxymetazoline on human nasal mucosa

Oxymetazoline, a derivative of imidazoline, is a widely used nasal decongestant. In contrast to other topical decongestants related to phenylephrine, sympathomimetic amines, it also induces a reduced nasal mucosal blood flow. The purpose of the present investigation was to evaluate the duration of effect of oxymetazoline on nasal airway resistance and mucosal blood flow. During the eight hours of study, the blood flow was reduced by 30-40 per cent in six hours. A similar decongestant effect of about 30 per cent was found during the same interval. The pharmacological profile of oxymetazoline seems questionable, since a reduced nasal mucosal blood flow might not be of value in the treatment of upper airways infections.     

Is hyperventilation-induced nystagmus more common in retrocochlear vestibular disease than in end-organ vestibular disease?

Hyperventilation-induced nystagmus (HVIN) has previously been shown by the senior author to be common in patients with both acoustic neuromas and following resection. The recurrent study's aim was to examine if HVIN was specific for retrocochlear pathology. To test this, the incidence of HVIN in 24 patients with confirmed acoustic neuroma was compared with its incidence in 38 patients with end-organ vestibular disease (defined as a greater than 25% reduction in caloric testing). Hyperventilation was carried out for 90 seconds. The results showed that 58% of the acoustic neuroma group were positive for HVIN versus 18% of the end-organ group. This difference was very significant on chi-square testing (p < .002). Hyperventilation-induced nystagmus appears to be much more prevalent in retrocochlear pathology than in end-organ pathology.     

Pathogenesis of airway inflammation in bronchial asthma

Bronchial asthma is a chronic disorder characterized by airway inflammation, reversible airway obstruction, and airway hyperresponsiveness. Eosinophils are believed to play important roles in the pathogenesis of asthma through the release of inflammatory mediators. In refractory eosinophilic asthma, anti-IL-5 mAb reduces exacerbations and steroid dose, indicating roles of eosinophils and IL-5 in the development of severe eosinophilic asthma. Even in the absence of IL-5, it is likely that the “Th2 network”, including a cascade of vascular cell adhesion molecule-1/CC chemokines/GM-CSF, can sufficiently maintain eosinophilic infiltration and degranulation. Cysteinyl leukotrienes can also directly provoke eosinophilic infiltration and activation in the airways of asthma. Therefore, various mechanisms would be involved in the eosinophilic airway inflammation of asthma.In the pathogenesis of severe asthma, not only eosinophils but also mast cells or neutrophils play important roles. Mast cells are much infiltrated to smooth muscle in severe asthma and induce airway remodeling by release of inflammatory mediators such as amphiregulin. Treatment with anti-IgE Ab, which neutralizes circulating IgE and suppresses mast cell functions, reduces asthma exacerbations in severe asthmatic patients. Furthermore, infiltration of neutrophils in the airway is also increased in severe asthma. IL-8 plays an important role in the accumulation of neutrophils and is indeed upregulated in severe asthma. In the absence of chemoattractant for eosinophils, neutrophils stimulated by IL-8 augment the trans-basement membrane migration of eosinophils, suggesting that IL-8-stimulated neutrophils could lead eosinophils to accumulate in the airways of asthma. In view of these mechanisms, an effective strategy for controlling asthma, especially severe asthma, should be considered.     

Changes in Nasal Airway Dimensions in Infancy

Thirty-nine infants, previously examined as neonates, were re-examined at 1 year of age with continuous wide-band noise acoustic rhinometry using a specific probe optimized for infants, to determine the dimensional growth and maturation of nasal airway geometry in otherwise healthy infants. During the first year of life, the acoustically determined dimensions of the nasal airways increased significantly. The total minimal cross-sectional area increased by 67% (0.21cm²     

Asthma,allergische Rhinitis,Sinusitis

Epidemiological studies indicate that allergic rhinoconjunctivitis (ARC) is an important risk factor for bronchial asthma. Both asthma and ARC have now been recognized as inflammatory diseases with similar manifestations in the mucous membranes of the upper (nose and paranasal sinuses) and lower respiratory tract (bronchi). Recent studies show that the deposition of allergen into the lower respiratory tract leads to increased inflammation of the upper respiratory tract, even if the patients are only suffering from ARC. These and other findings indicate that allergic diseases have a systemic component, which might be insufficiently targeted with local therapy.It is currently believed that the impaired function of the upper airways due to ARC causing nasal obstruction, retention of secretions, and disturbed conditioning of the inspired air plays an important role in the development of lower airway symptoms. Studies indicate that treatment of the upper respiratory tract inflammation not only reduces the manifestation of allergen-associated symptoms in the lower respiratory tract, but might also have preventive properties if applied early. ARC should no longer be viewed as a harmless disorder but as the early manifestation of a potentially progressive systemic disease and be treated as such.     

Asthma, allergic rhinitis, sinusitis. Concept of the "unified respiratory tracts"

Epidemiological studies indicate that allergic rhinoconjunctivitis (ARC) is an important risk factor for bronchial asthma. Both asthma and ARC have now been recognized as inflammatory diseases with similar manifestations in the mucous membranes of the upper (nose and paranasal sinuses) and lower respiratory tract (bronchi). Recent studies show that the deposition of allergen into the lower respiratory tract leads to increased inflammation of the upper respiratory tract, even if the patients are only suffering from ARC. These and other findings indicate that allergic diseases have a systemic component, which might be insufficiently targeted with local therapy. It is currently believed that the impaired function of the upper airways due to ARC causing nasal obstruction, retention of secretions, and disturbed conditioning of the inspired air plays an important role in the development of lower airway symptoms. Studies indicate that treatment of the upper respiratory tract inflammation not only reduces the manifestation of allergen-associated symptoms in the lower respiratory tract, but might also have preventive properties if applied early. ARC should no longer be viewed as a harmless disorder but as the early manifestation of a potentially progressive systemic disease and be treated as such.     

Does mucosal remodeling in chronic rhinosinusitis result in irreversible mucosal disease?

Mucosal remodeling in the sinuses is a recently described phenomenon in which the mucosa undergoes potentially irreversible changes as a result of ongoing underlying inflammatory processes. Research into remodeling that occurs in the bronchial airways in asthmatic patients has led to modification of asthma treatment guidelines. However, remodeling in the sinuses has still not led to changes in current medical or surgical management of chronic rhinosinusitis. Upper airway remodeling constitutes a new area of research that poses many unanswered clinical questions and may potentially alter the management of patients with severe chronic rhinosinusitis.