Methodological Aspects of Nasal Allergen Challenges Based on a Three-Year Tree Pollen Immunotherapy Study

During 3 years of immunotherapy with tree pollen extracts, 31 patients were provoked annually. Changes in nasal reactivity were followed by registration of expiratory nasal peak flow, number of sneezes, and amount of secretion. The reproducibility of the peak flow measurements was studied. The results from all three parameters were used to form a total nasal provocation score which, better than each parameter separately, could demonstrate the variation in sensitivity. Provocation with an allergen concentration of 1 HEP was the most effective means of showing changes in specific sensitivity of nasal mucosa.     

Distinct features of chronic rhinosinusitis with and without nasal polyps

BACKGROUND: Based on the presence of nasal polyps on endoscopy, chronic rhinosinusitis (CRS) may be clinically divided in CRS with nasal polyps and CRS without nasal polyps. It is unclear, whether CRS with nasal polyps and CRS without nasal polyps represent different disease entities or just different stages of one single disease. In case of one disease, only minor histopathological differences between CRS with small early-stage polyps (CRSNP((+))) and CRS without nasal polyps (CRSNP(-)) were expected. METHODS: Patients with CRSNP((+)) confined to the infundibular region or CRSNP(-) were selected. Histochemical and immunohistochemical characterization of ethmoidal mucosa was performed on formalin-fixed and paraffin-embedded tissue specimens. Frequency and distribution of eosinophils, neutrophils, mast cells, IgE(+) cells, macrophages, B- and T-cell subsets, natural killer cells, plasma cells and goblet cells were assessed. In addition, the thickness of the basal membrane was evaluated. RESULTS: Nine CRS patients without detectable polyps, and 11 patients with small early-stage polyps confined to the infundibular region were selected. Despite adjacent polyp stage, the amount of round cell infiltration (P < 0.05), number of eosinophils (P < 0.05), and plasma cells (P < 0.01) significantly differed in the ethmoidal specimens from patients of the two groups. CONCLUSION: Substantial histopathological differences were observed in ethmoidal mucosa of CRSNP((+)) and CRSNP(-) patients. Thus, the results of this investigation support the concept that CRS with nasal polyps and CRS without nasal polyps are two different disease entities rather than different stages of one single disease, but may also be interpreted as a higher degree of inflammation.     

Epithelial shedding is associated with nasal reactions to cold, dry air

BACKGROUND: Cold, dry air (CDA) can cause symptoms of rhinitis and obstructive airway responses. The pathophysiology of these reactions is not understood. One hypothesis is that the respiratory mucosa of individuals with CDA sensitivity cannot compensate for the loss of water that occurs on exposure to the stimulus, leading to epithelial damage. OBJECTIVE: To test for an association between nasal reactions to CDA and the number of epithelial cells recovered in nasal fluids. METHODS: Ten CDA-sensitive subjects received nasal provocations with CDA and warm, moist air; 10 CDA-insensitive subjects received CDA; and 10 subjects with allergic rhinitis received allergen and diluent challenges. Nasal lavage cytology was performed at baseline and after the challenge. Symptoms were recorded and histamine, [3H]-N-alpha-tosyl-L-arginine methyl ester-esterase activity, tryptase, and albumin were assayed in nasal lavages. RESULTS: A 6-fold increase in nasal lavage epithelial cells was found in the CDA-sensitive group after CDA (P < .01), but not after warm, moist air. No changes were observed in the CDA-insensitive group, or after allergen or diluent in allergic rhinitis. CONCLUSION: Epithelial cell shedding accompanies clinical responses to CDA in the human nose. This supports the hypothesis that the airway mucosa of CDA-sensitive individuals cannot compensate for the water loss that occurs under extreme conditions leading to epithelial damage. CLINICAL IMPLICATIONS: A defect in mucosal water homeostasis may need to be considered in individuals who get excessive nasal symptoms when exposed to cold and dry, windy environment.     

Nasal cytology in rhinitis children: comparison between brushing and blowing the nose

Allergic rhinitis is a common disease in childhood, but nasal cytology is rarely used by pediatricians. We compared two techniques of cell sampling, brushing and blowing the nose, among 77 children suffering from chronic rhinitis, of whom 59 were allergic. Staining by the May-Grünwald-Giemsa method enabled the evaluation of the density of cells and especially differential counting of the inflammatory cells. Staining by the Luna method was used as a control for the eosinophils. For the eosinophil count, we found a strong correlation between the two methods of collecting the nasal secretions ( r =0.96). Because blowing the nose is painless and easy to perform, it is more appropriate than brushing in routine use for the diagnosis of allergic rhinitis in children and in nasal challenge with allergens.     

An approach to the understanding of the nasal early-phase reaction induced by nasal allergen challenge

Quantitative determinations of the inflammatory mediators in nasal secretions were performed and correlated with the objective nasal symptoms within 1 h after nasal allergen challenge (NAC). Twenty-six patients with seasonal allergic rhinitis were enrolled outside the pollen season. All measurements were performed before (as a baseline control) and at 1, 5, 10, 30, and 60 min after NAC. This study aimed to clarify the pathogenic mechanism of the early-phase reaction (EPR) by monitoring the evolution of early-phase mediators in nasal secretions and the presence of nasal symptoms during this period. The results showed that, after NAC, the maximal mediator concentration was already reached after 1 min for histamine (124 ng/g), 5 min for tryptase (56 μU/g), and 5-10 min for leukotriene C₄ (40 ng/g). Itching and sneezing started as early as 20-30 s, and they were predominant symptoms within 5 min. Rhinorrhea and nasal obstruction started a few minutes after NAC and lasted until more than 1 h after NAC. There was no significant correlation between any single mediator and nasal symptoms during the sampling period. In conclusion, this study demonstrated that during the EPR the presence of nasal symptoms involves a complex mechanism, reflecting the interaction between the mediators released by inflammatory cells, and the receptors on different target organs. When evaluating symptoms during the EPR, one must consider not only the severity of these symptoms but also the time period within which these symptoms occur. For the symptoms of nasal obstruction and rhinorrhea, the early-phase reaction often lasted more than 1 h.     

Prevalence of non-allergic nasal complaints in an urban and a rural population in Sweden

By questionnaire, 1469 randomly selected persons between 16 and 82 years of age were asked whether they had suffered from such nasal complaints as obstruction, sneezing and discharge, at least during the previous 6 months. Seventy-five per cent answered the questionnaire, two thirds of whom were city dwellers and one third lived in a rural district. No difference was found between the urban and the rural populations regarding the prevalence of symptoms. Twenty-one per cent suffered from non-allergic nasal complaints, and 5% from allergic nasal complaints. The prevalence of non-allergic nasal complaints was highest in the 20-30-year age group, and lowest in the 50-60-year age group. Contributory factors were of greater importance among the younger individuals than among the more elderly.     

Bilateral nasal allergen provocation monitored with acoustic rhinometry. Assessment of both nasal passages and the side reacting with greater congestion: relation to the nasal cycle

BACKGROUND: The effect of bilateral nasal provocation on nasal mucosa measured with the use of acoustic rhinometry (AR) can be assessed for both nasal passages or for the side responding with greater congestion. Assessment of changes in nasal congestion during the nasal provocation test (NPT) can be affected by the nasal cycle (NC). The aim of this study was to find out the most accurate method to evaluate changes observed during bilateral nasal provocation. METHODS: Cross-sectional areas (CSA) at the level of inferior nasal turbinate (CSA-2) were recorded by AR in 26 volunteers with allergic rhinitis during the NC for 5-7 h and subsequently during NPT. The risk of spontaneous total and unilateral CSA-2 decrease was established. Sensitivity of the NPT assessment for the total CSA-2 and for the side responding with greater congestion was evaluated at chosen thresholds. These thresholds were selected in a way that the risk levels of spontaneous decrease of unilateral and total CSA-2 were equal. RESULTS: The assessment of the total CSA-2 was found to be more sensitive than the assessment of the side responding with greater congestion. The highest sensitivity and specificity of the test was achieved by using a combination of both assessments. Optimum thresholds of the CSA-2 decrease for assessment at 15 min after provocation, with this method, were 27% and 40% for the side responding with greater congestion and for the total CSA-2, respectively. CONCLUSIONS: Recognition of the risk of spontaneous unilateral and total CSA-2 decreases enables introduction of combined assessment of bilateral NPT. This assessment seems to be the most accurate method for evaluation of the test results.     

Regulation of glucocorticoid receptor in nasal polyps by systemic and intranasal glucocorticoids

Background: Poor response of nasal polyps to glucocorticoids (GCs) may be because of abnormal expression of GC receptors (GR) α and β or to downregulation of GRα. We aimed to evaluate the in vivo regulation of GR isoforms in GC‐treated nasal polyps and to assess the relationship between clinical response to GCs and GR levels. Methods: Patients with nasal polyps were randomly (3:1) treated (n = 51) or not (n = 14) with oral prednisone and intranasal budesonide for 2 weeks, plus intranasal budesonide for 10 additional weeks. Nasal symptoms were evaluated. Biopsies were obtained before (w0) and after 2 (w2) and 12 (w12) weeks of treatment, and analysed for their inflammatory content and GR mRNA (10² cDNA copies/μg total RNA) and protein (% immunoreactive inflammatory cells) expression. Healthy nasal mucosa (n = 11) was also investigated. Data are presented as median and 25–75th percentile. Results: At w0, nasal polyps expressed less GRα mRNA (1343;683–2263; P < 0.05) and GR protein (41;29–54; P < 0.05) than nasal mucosa (2474;1346–2933; 60;51–72, respectively). GRβ immunoreactivity was higher in nasal polyps (11;4–19; P < 0.05) than in nasal mucosa (5;2–5). At w2, increased GRα mRNA (2010;1037–2732; P < 0.01) and GR protein (56;27–71; P = 0.056) were found compared with w0 (1177;759–2058; 37;29–55, respectively). At w12, GRα mRNA and GR protein were similar to w0. GRβ expression was unaltered by treatment. Neither GRα nor GRβ correlated with nasal symptoms. GR immunoreactivity negatively correlated with eosinophils (r = ?0.478; P < 0.001). Conclusions: GRα is downregulated in nasal polyps and upregulated by GC treatment. Neither GRα nor GRβ appear to determine the sensitivity to GCs in nasal polyposis.     

Clinical significance of the sphenoidal process of the cartilaginous nasal septum: A preliminary morphological evaluation

The bony septum ossifies from cranial to caudal and from ventral to dorsal, thereby forming the perpendicular plate of ethmoid bone and vomer. A small strip of cartilage from the cartilaginous septum remains between these parts, the so‐called sphenoidal process of the cartilaginous septum. This sphenoidal process is usually seen at the top of a deviated nasal septum during septoplasty. This study evaluated the clinical significance of the sphenoidal process of the cartilaginous septum as a cause of nasal septal deviation. We studied 37 patients with septal deviation who underwent septoplasty. The complex consisting of the sphenoidal process of the cartilaginous septum, perpendicular plate of the ethmoid bone (PPE), and vomer was removed at surgery. The sphenoidal process was measured and the surgical specimen were evaluated histologically and compared to controls. The mean length of the sphenoidal process in patients with a deviated nasal septum was 26.05 ± 5.32 mm versus 11.95 ± 2.38 mm in controls. The sphenoidal process was significantly longer in the patients with a deviated nasal septum (P < 0.05). The sphenoidal process of the cartilaginous septum was connected to the PPE and vomer in the patients with a deviated nasal septum and differed histologically from that of the controls. The sphenoidal process of the cartilaginous septum was long and prominent in the patients with septal deviation, implying that delayed nasal septal ossification may be one cause of nasal septal deviation. Clin. Anat. 23:265–269, 2010. © 2010 Wiley‐Liss, Inc.     

鼻部外伤性骨折的诊断和修复（附500例分析报告）

目的 探讨鼻骨和鼻软骨骨折正确的诊断方法和最佳的诊断方法和最佳的复位方法。方法 对５００例鼻部外伤患者的鼻骨骨折Ｘ线侧位和轴位摄片（其中１６２例同时做ＣＴ水平扫描）等资料分析。其中３５０例诊断为双侧鼻骨骨折。单侧鼻骨骨折２３例,鼻软骨骨折２５例。单纯上颌骨额突骨折２１例,鼻骨,上颌骨额突复合骨折１６例。鼻骨,上颌窦、上颌骨额突和筛骨垂骨板复合骨折６例。鼻骨和鼻副窦复合４例。鼻眶骨折９例。均行手术和和手法复位。结果 ４９０例复位满意,１０例复位不佳。结论 Ｘ摄片鼻骨只能诊断双鼻骨同时骨折。而单例鼻骨骨折,上颌骨额突骨折,筛骨垂直板等复杂骨折ＣＴ扫描均能清楚显示。但鼻骨Ｘ拍片和鼻骨骨折ＣＴ扫描在诊断鼻骨骨折中二者不可缺一。鼻骨骨折和鼻软骨骨折同时要有两们耳科专科医师参与则诊断更加明确。     

Progressive bilateral nasal alar collapse: A dominantly inherited trait

We describe a 47-year-old woman with progressive bilateral collapse of the alae nasi first noted at age 16 years. Her dizygotic twin daughters have similar nasal collapse beginning at age 20 years. This condition appears to be inherited as a dominant trait. Although plastic surgical correction has been successful for a phenotypically similar condition due to trauma, surgical correction must be considered cautiously in individuals with an atraumative, possibly inherited, progressive form of the disorder.     

胎儿鼻中隔角及其粘膜的组织形态学研究

对８２例死亡的正常胎儿的鼻中隔角和鼻中隔呼吸区粘膜的发育及组织形态学特点作了观察,结果表明：（１）鼻中隔角的形态从上至下分别呈“Ｉ”或“Ｔ”型,“Ｙ”型,“Ｍ”型和“ｍ”型;（２）鼻中隔后部粘膜增厚,表面出现粘膜皱襞;（３）Ｌｉｔｔｌｅ区粘膜明显隔呼吸区粘膜对吸入空气起着重要的温湿作用;小儿外伤性鼻出血的主要原因是由于Ｌｉｔｔｌｅ区粘膜的增厚隆起,易被手指擦伤所致。     

Nasal conditioning in perennial allergic rhinitis after nasal allergen challenge

BACKGROUND: Antigen challenge in seasonal allergic rhinitis is considered to be associated with an increased ability of the nose to condition inspired air. In contrast, little is known about air conditioning after antigen challenge in perennial allergic rhinitis (PAR). OBJECTIVE: The aims of this study were to investigate whether antigen challenge in PAR changes nasal air conditioning and to assess the relationship between nasal conditioning and nasal patency and geometry. METHODS: Nineteen subjects with PAR were enrolled into this study. Measurement of nasal conditioning, active anterior rhinomanometry (AAR), acoustic rhinometry (AR), and clinical symptom evaluation were performed before and after nasal allergen challenge with allergen extracts from house dust mites. RESULTS: Ten and 20 min after nasal allergen challenge, the total water content of the air measured in the nasopharynx and the water gradient across the nose were significantly higher in the nasal cavity in which the allergen extract was sprayed. The temperature on both sides of the nose increased non-significantly after nasal allergen challenge. No correlation to data obtained by AAR, AR, and clinical symptom evaluation after nasal allergen challenge was found. CONCLUSION: We suggest that an increase in mucosal humidity due to the allergic provocation might be responsible for the increase in nasal conditioning capacity because no correlation to changes in nasal perimeter and patency was found.     

Unilateral nasal allergen challenge leads to bilateral release of prostaglandin D2

Background Multiple mediators including prostaglandin D₂ and leukotriene B₄ have been shown to increase in nasal secretions during the early response to nasal challenge with antigen. Objective Our objective was to investigate the time course of prostanoid and leukotriene B₄ release into nasal secretions on both the ipsilateral and contralateral side after a unilateral nasal allergen challenge. Methods We performed a controlled, randomized trial. Six volunteers were challenged unilaterally with antigen or diluent in a randomized order and discs were used to collect nasal secretions from both nostrils at 2 min intervals for 20 min after the challenge. Prostanoids and leukotriene B₄ (LTB₄) in recovered nasal secretions were measured by combined capillary gas chromatography-negative ion chemical ionization mass spectrometry (GC/MS). Results Nasal allergen challenge resulted in a significant and immediate increase in symptoms and sneezing. PGD₂ was significantly elevated above diluent values (0.6 ± 0.6pg) 30s after removal of the allergen disc (P<0.05), reached its peak (423.2 ± 182.4pg) at 2 min and then slowly decreased. PGD₂ also increased on the contralateral side after unilateral allergen challenge, reaching peak values about six times lower than on the ipsilateral side (70.8 ± 2l.7pg at 6 min). Levels of 9a, Ub-PGF₂ after antigen provocation became significantly higher than after diluent (0 ± 0pg) on the ipsilateral side at 2 min (17.2 ± 5.9 pg), and reached peak levels at 4 mm (25.1 ± 8.0 pg). LTB₄ also increased significantly on the side of ehallenge. For the other prostanoids measured (PGF₂, PGF_2α TxB₂, 6kPGF_1α), no significant changes in either ipsilateral or contralateral secretions were observed after allergen challenge. Conclusions Our study described the kinetics of PGD₂ and LTB₄ release as well as the contralaterai release of PGD₂.     

Gross morphological and morphometric study of the upper respiratory system of the African giant rat (Cricetomys gambianus,Waterhouse 1840)

The nose is a structurally and functionally complex organ in the upper respiratory tract. It not only serves as the principal organ for the sense of smell, but also functions to efficiently filter, warm, and humidify inhaled air before the air enters the more delicate distal tracheobronchial airways and alveolar parenchyma of the lungs. Despite the volume of published studies on the biology of rodents, there is no information on the gross upper respiratory morphology of the African giant rat (AGR) in the available literature. Hence, this study aimed to examine the anatomy of the turbinates, their meatuses, and the morphometry of the nasal cavity. The following were found and reported in this study: (a) There were three nasal conchae in AGR: the nasoturbinate, which was the largest; the ethmoturbinate, which was composed of one well-developed ectoturbinate and three well-developed endoturbinates; and the maxilloturbinate, which was fusiform, short, and branched. (b) Three major meatuses were observed: the dorsal nasal meatus, which was the longest and widest; the middle nasal meatus, which was without limbs but had a deep oval caudal recess; and the ventral nasal meatus, which directly continued caudally into the nasopharyngeal meatus. (c) Four ethmoturbinates with four slit-like meatuses were observed, each with dorsal and ventral limbs; the first contacted the middle nasal meatus but not the nasopharyngeal meatus. (d) There were three paranasal sinuses: one sphenoid, two frontal, and two palatine sinuses. The data obtained are relevant to pathologists and eco-morphologists, considering the burrowing habitat and behaviors of AGR, and provide baseline data for more investigative studies.     

Effects of intranasal fluticasone and salmeterol on allergen-induced nasal responses

BACKGROUND: Combination of inhaled steroid and long-acting beta-agonists has synergistic effects in asthma. OBJECTIVE: To investigate whether nasal corticosteroid and long-acting beta-agonists have synergistic effects on allergen-induced nasal responses. METHODS: The effects of intranasal treatment with fluticasone p-MDI (50 microg bid), salmeterol p-MDI (25 microg bid), their combination, and placebo, on nasal symptoms, eosinophil differential cell count and albumin in nasal lavage fluid (measures of inflammation and leakage respectively) and nasal electrical potential difference (measure of epithelial integrity) were studied in 11 atopic subjects with rhinitis, in a randomized, partially-blinded, 4-period, cross-over study. The measurements were made at baseline, at the end of 1 week of treatment, and immediately after a nasal allergen provocation. RESULTS: Allergen-induced sneeze, postnasal drip and nasal obstruction were significantly reduced by fluticasone, but not by salmeterol. Eosinophil count in postallergen nasal lavage fluid was significantly less after fluticasone (median 1.9%, IQR 4.6) and salmeterol treatment (median 2.5%, IQR 8.5) compared with placebo (median 12.5%, IQR 27.9). Compared with placebo, both fluticasone and salmeterol attenuated allergen-induced change in nasal potential (mean change from baseline -18.5, +0.4 and -7.2% respectively) and the increase in nasal albumin (median 154, 119 and 130 ng/ml respectively). Combination treatment did not have any additional benefits over the individual therapies. CONCLUSIONS: Although salmeterol has anti-inflammatory properties, intranasal salmeterol or its combination with fluticasone do not offer any added benefit over intranasal fluticasone alone for allergen-induced nasal responses.     

Measurements of nasal airflow and patency: a critical review with emphasis on the use of peak nasal inspiratory flow in daily practice

Objective measures can be used to assist the clinician to diagnose and treat nasal obstruction and also to quantify nasal obstruction in research. Objective measurements of nasal obstruction are as important as objective measurements of lung function. peak nasal inspiratory flow (PNIF), acoustic rhinometry (AR) and rhinomanometry (RM), with their specific peculiarity, assess different aspects of nasal obstruction. From the studies available in the literature, it seems that these methods roughly correlate with each other and that all of them can be alternatively utilized very well in research as well as in clinical practice. This review describes the various methods that can be used to measure nasal patency, airflow and resistance, mainly peak nasal inspiratory flow, rhinomanometry and acoustic rhinometry. PNIF has been demonstrated to be reproducible and as good an indication of objective nasal patency as formal rhinomanometry and has the advantage to be cheap, simple and suitable for serial measurements and for home use even in the paediatric population. PNIF normative data are available for children, adults and elderly subjects, and the availability of unilateral PNIF normal values allows evaluation of nasal sides separately. Just as in the lower airways, objective and subjective evaluation gives different information that together optimizes the diagnosis and the treatment of our patients. We argue that PNIF should be used regularly in every outpatient clinic that treats patients with nasal obstruction.