Consensus criteria for chronic rhinosinusitis disease control: an international Delphi Study.

BACKGROUND: Chronic rhinosinusitis (CRS) disease control is a global metric of disease status for CRS. While there is broad acceptance that it is an important treatment goal, there has been inconsistency in the criteria used to define CRS control. The objective of this study was to identify and develop consensus around essential criteria for assessment of CRS disease control. METHODS: Modified Delphi methodology consisting of three rounds to review a list of 24 possible CRS control criteria developed by a 12-person steering committee. The core authorship of the multidisciplinary EPOS 2020 guidelines was invited to participate. RESULTS: Thirty-two individuals accepted the invitation to participate and there was no dropout of participants throughout the entire study (3 rounds). Consensus essential criteria for assessment of CRS control were: overall symptom severity, need for CRS-related systemic corticosteroids in the prior 6 months, severity of nasal obstruction, and patient-reported CRS control. Near-consensus items were: nasal endoscopy findings, severity of smell loss, overall quality of life, impairment of normal activities and severity of nasal discharge. Participants’ comments provided insights into caveats of, and disagreements related to, near-consensus items. CONCLUSIONS: Overall symptom severity, use of CRS-related systemic corticosteroids, severity of nasal obstruction, and patient-reported CRS control are widely agreed upon essential criteria for assessment of CRS disease control. Consideration of near-consensus items to assess CRS control should be implemented with their intrinsic caveats in mind. These identified consensus CRS control criteria, together with evidence-based support, will provide a foundation upon which CRS control criteria with wide-spread acceptance can be developed.

The EUFOREA pocket guide for chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is known to affect around 5 % of the total population, with major impact on the quality of life of those severely affected (1). Despite a substantial burden on individuals, society and health economies, CRS often remains underdiagnosed, under-estimated and under-treated (2). International guidelines like the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) (3) and the International Consensus statement on Allergy and Rhinology: Rhinosinusitis 2021 (ICAR) (4) offer physicians insight into the recommended treatment options for CRS, with an overview of effective strategies and guidance of diagnosis and care throughout the disease journey of CRS.

European Position Paper on Rhinosinusitis and Nasal Polyps 2020.

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

EPOS2020: development strategy and goals for the latest European Position Paper on Rhinosinusitis.

BACKGROUND: The European Position Papers on Rhinosinusitis from 2005, 2007 and 2012 have had a measurable impact on the way this common condition with high impact on quality of life is managed around the world. EPOS2020 will be the latest iteration of the guideline, addressing new stakeholders and target users, presenting a summary of the latest literature and evolving treatment modalities, and formulating clear recommendations based on all available evidence. METHODOLOGY: Based on the AGREE II framework, this article demonstrates how the EPOS2020 steering group will address six key areas to ensure consistency in quality and presentation of information in the latest rhinosinusitis clinical practice guideline: scope and purpose; stakeholder involvement; rigour of development; clarity of presentation; recommendations and applicability; editorial independence. RESULTS: By analysing the guidance from AGREE II, we formulated a detailed development strategy for EPOS2020. We identify new stakeholders and target users and ratify the importance of patient involvement in the latest EPOS guideline. New and expanded areas of research to be addressed are highlighted. We confirm our intention to use mixed methodologies, combining evidence-based medicine with real life studies; when no evidence can be found, use Delphi rounds to achieve clear, inclusive recommendations. We also introduce new concepts for dissemination of the guideline, using Internet and social media to improve accessibility. CONCLUSION: This article is an introduction to the EPOS2020 project, and presents the key goals, core stakeholders, planned methodology and dissemination strategies for the latest version of this influential guideline.

A randomized, double-blind, placebo-controlled trial of anti-IgE for chronic rhinosinusitis.

Evidence suggests IgE may play a role in chronic rhinosinusitis (CRS). We sought to determine if treatment with a monoclonal antibody against IgE (omalizumab) is effective in reducing CRS inflammation. We performed a randomized, double blind, placebo controlled clinical trial in subjects with CRS despite treatment (including surgery). Subjects were randomized to receive omalizumab or placebo for 6 months. The primary outcome was quantitative measurement of sinus inflammation on imaging. Secondary outcome measures included quality of life, symptoms, and cellular inflammation, nasal airflow (NPIF) and olfactory testing (UPSIT). Subjects on omalizumab showed reduced inflammation on imaging after treatment, whereas those on placebo showed no change. The net difference, however, was not different between treatments. Treatment with omalizumab was associated with improvement in the Sino-Nasal Outcome Test (SNOT-20) at 3, 5, and 6 months compared to baseline with no significant changes in the control group. Remaining measures showed no significant differences across treatments. We conclude that IgE plays, at most, a small role in the mucosal inflammation of CRS and the symptoms. Placebo controlled, blinded studies with larger enrollment are needed to determine the clinical significance of any potential change.

Superiority of an intranasal corticosteroid compared with an oral antihistamine in the as-needed treatment of seasonal allergic rhinitis.

BACKGROUND: The daily use of either intranasal corticosteroids or histamine(1) (H(1)) receptor antagonists has proved to be efficacious in the treatment of seasonal allergic rhinitis. Most patients, however, use these medications as needed. Our objective was to compare the effectiveness of as-needed use of H(1) receptor antagonists with that of intranasal corticosteroids in the treatment of seasonal allergic rhinitis. METHODS: We performed a randomized, open-label, parallel-group study comparing the as-needed use of an H(1) receptor antagonist (loratadine) with that of an intranasal corticosteroid (fluticasone propionate) in the management of fall seasonal allergic rhinitis in the fall of 1999. Subjects kept a diary of their daily symptoms and were examined at enrollment into the study and biweekly for 4 weeks during treatment. Outcome measures were the Rhinoconjunctivitis Quality of Life Questionnaire score, daily symptom diary scores, and the number of eosinophils and the levels of eosinophilic cationic protein in nasal lavage samples. RESULTS: Patients in the fluticasone-treated group reported significantly better scores in the activity, sleep, practical, nasal, and overall domains (P<.05) of the Rhinoconjunctivitis Quality of Life Questionnaire. The median total symptom score in the fluticasone-treated group was significantly lower than that in the loratadine-treated group (4.0 vs 7.0; P<.01). After treatment, the number of eosinophils was significantly smaller in the fluticasone-treated group compared with the loratadine-treated group (P =.001). Eosinophilic cationic protein levels followed the same pattern, with a significant correlation between the levels of eosinophilic cationic protein and the number of eosinophils (r(s) = 0.70, P<.01). CONCLUSION: As-needed intranasal corticosteroids reduce allergic inflammation and are more effective than as-needed H(1) receptor antagonists in the treatment of seasonal allergic rhinitis.

Comparison of the secretory response of the nasal mucosa to methacholine and histamine.

To better understand the secretory response of the nasal mucosa, we must be able to accurately measure its physiological response. To this end, we developed a localized challenge technique using paper disks to stimulate the mucosa on one side and measure secretions from both sides to study both direct and reflex responses. Both methacholine and histamine induced a dose-dependent increase in secretion weights on the challenge side, whereas only histamine induced a contralateral reflex. Repeated stimulation with histamine, but not methacholine, resulted in tachyphylaxis. Pretreatment with atropine resulted in inhibition of the contralateral secretory response to histamine and the ipsilateral response to methacholine with only partial inhibition of the ipsilateral histamine response. Terfenadine pretreatment resulted in the complete inhibition of both the ipsilateral and contralateral responses to histamine with no effect on methacholine-induced secretions. Ipsilaterally applied lidocaine had no effect on the histamine response but, when applied contralaterally, partially inhibited that response. Topical diphenhydramine applied ipsilaterally led to significant inhibition of the ipsilateral and contralateral secretory responses to histamine but had no effect when applied contralaterally. We conclude that methacholine and histamine have different effects on the nasal mucosa. We speculate that methacholine stimulates glands directly, whereas histamine includes both direct and neurogenic stimulation.

Comparison of the response to histamine challenge of the nose and the maxillary sinus: effect of loratadine.

To study the response of the maxillary sinus to histamine provocation, we performed a double-blind, randomized, crossover trial during which nonallergic subjects without symptoms of rhinitis (n = 25) received either 10 mg loratadine or placebo once daily for a week and then underwent nasal challenge with histamine (3, 10, and 30 mg/ml) followed, 24 h later, by a maxillary sinus challenge while still receiving the medication. Nasal challenge with histamine led to significant increases in vascular permeability, reflex nasal secretions, sneezing, and other nasal symptoms. Sinus challenge resulted in significant increases in vascular permeability within the sinus cavity (P < 0.01) and some nasal symptoms but no significant change in reflex nasal secretions. The response of the sinus mucosa to histamine was lower in magnitude than that of the nose. Treatment with loratadine resulted in a significant inhibition of the histamine-induced changes in both nasal and sinus cavities. Our data suggest the lack of a sinonasal reflex response to histamine provocation of the maxillary sinus of nonallergic individuals.

A technique to measure the ability of the human nose to warm and humidify air.

To assess the ability of the nose to warm and humidify inhaled air, we developed a nasopharyngeal probe and measured the temperature and humidity of air exiting the nasal cavity. We delivered cold, dry air (19-1 degrees C, <10% relative humidity) or hot, humid air (37 degrees C, >90% relative humidity) to the nose via a nasal mask at flow rates of 5, 10, and 20 l/min. We used a water gradient across the nose (water content in nasopharynx minus water content of delivered air) to assess nasal function. We studied the characteristics of nasal air conditioning in 22 asymptomatic, seasonally allergic subjects (out of their allergy season) and 11 nonallergic normal subjects. Inhalation of hot, humid air at increasingly higher flow rates had little effect on both the relative humidity and the temperature of air in the nasopharynx. In both groups, increasing the flow of cold, dry air lowered both the temperature and the water content of the inspired air measured in the nasopharynx, although the relative humidity remained at 100%. Water gradient values obtained during cold dry air challenges on separate days showed reproducibility in both allergic and nonallergic subjects. After exposure to cold, dry air, the water gradient was significantly lower in allergic than in nonallergic subjects (1,430 +/- 45 vs. 1,718 +/- 141 mg; P = 0.02), suggesting an impairment in their ability to warm and humidify inhaled air.

Relationship between histamine and physiological changes during the early response to nasal antigen provocation.

To investigate the temporal relationships of mediator release and physiological changes during the early response to allergen, we challenged allergic individuals intranasally with antigen and followed their responses. This was done by using small filter paper disks to challenge one nostril and collect secretions from both the challenged and the contralateral nostril, thus enabling us to evaluate the nasonasal reflex. There was a significant increase in sneezing after allergen challenge that peaked within 2 min and returned to baseline. The weights of nasal secretions as well as nasal symptoms increased immediately and remained significantly elevated for 20 min in both nostrils. Nasal airway resistance increased slowly, reaching its peak at approximately 6 min after challenge on the ipsilateral side, but it did not change on the contralateral side. Histamine levels peaked 30 s after removal of the allergen disk on the side of challenge, whereas albumin levels peaked after those of histamine. Lactoferrin paralleled the increase in secretion weights and occurred in both nostrils. Increasing doses of antigen produced dose-dependent increases in all parameters, whereas control challenges produced no response. These studies describe a human model for the evaluation of the allergic response that is capable of simultaneously measuring mediator release and the physiological response, including the nasonasal reflex. This model should prove useful in studying the mechanism of allergic rhinitis in humans.

Supine position decreases the ability of the nose to warm and humidify air.

We tested the hypothesis that decreasing nasal air volume (i.e., increasing nasal turbinate blood volume) improves nasal air conditioning. We performed a randomized, two-way crossover study on the conditioning capacity of the nose in six healthy subjects in the supine and upright position. Cold, dry air (CDA) was delivered to the nose via a nasal mask, and the temperature and humidity of air were measured before it entered and after it exited the nasal cavity. The total water gradient (TWG) across the nose was calculated and represents the nasal conditioning capacity. Nasal volume decreased significantly from baseline without changing the mucosal temperature when subjects were placed in the supine position (P < 0.01). TWG in supine position was significantly lower than that in upright position (P < 0.001). In the supine position, nasal mucosal temperature after CDA exposure was significantly lower than that in upright position (P < 0.01). Our data show that placing subjects in the supine position decreased the ability of the nose to condition CDA compared with the upright position, in contrast to our hypothesis.

Coronal CT scan abnormalities in children with chronic sinusitis.

Coronal computed tomography (CT) scans are currently the optimal study to display the normal and abnormal anatomy in children with chronic and recurrent acute sinusitis after failure of medical therapy. To assess the extent and distribution of disease as well as associated anatomic abnormalities in this pediatric population, 74 coronal CT scans of children with continued symptoms of sinusitis after failure of extensive medical therapy were reviewed retrospectively. Twelve children with cystic fibrosis showed the characteristic features of medial displacement of the lateral nasal wall in the middle meatus and uncinate process demineralization, creating the appearance of a maxillary sinus mucocele. Nine of these 12 children had increased attenuation in the maxillary sinus on soft-tissue windows. In the remaining 62 children, a significantly greater frequency of disease, when compared with that reported for adults, was seen in the maxillary, anterior ethmoid, posterior ethmoid, and frontal sinuses. Children with asthma (n = 33) had more extensive disease. Bony anatomic abnormalities were similar to those reported for adults, except for a lower incidence of septal deformity.

Fine-needle aspiration biopsy of cervicofacial masses in children.

OBJECTIVE: To show the usefulness of fine-needle aspiration biopsy (FNAB) in the diagnosis of cervicofacial masses in children. DESIGN: Case series. SETTING: Pediatric otolaryngology referral center, ambulatory and hospitalized patients. PATIENTS: Seventeen pediatric (age, < 18 years) patients with cervicofacial masses. INTERVENTION: Fine-needle aspiration biopsy. OUTCOME MEASURES: Cytologic diagnosis, resolution of mass, and need for further surgical diagnosis or treatment. RESULTS: Following FNAB, 10 patients underwent open surgery; in seven, the surgery was indicated based on FNAB diagnosis; in three, surgery provided diagnoses where FNAB was insufficient. Based on FNAB data, seven patients were observed without surgery. CONCLUSIONS: Fine-needle aspiration biopsy is a useful early step in diagnosing cervicofacial masses in children.

Ragweed allergic rhinitis and the paranasal sinuses. A computed tomographic study.

OBJECTIVE: To explore the potential association of allergic rhinitis and sinusitis. DESIGN: Prospective clinical trial. SETTING: Academic tertiary referral center. PARTICIPANTS: Ten subjects with symptomatic ragweed allergy during the peak of the ragweed season. MAIN OUTCOME MEASURES: We obtained a paranasal sinus computed tomographic scan on all volunteers and had them complete a modified Rhinitis Quality of Life Questionnaire. All subjects were then treated with intranasal aqueous beclomethasone dipropionate (168 micrograms twice a day) and completed the Rhinitis Quality of Life Questionnaire weekly until the end of the study. RESULTS: Six of 10 of the subjects had sinus mucosal thickening on computed tomographic scan. All subjects improved symptomatically. A second computed tomographic scan was obtained after the pollen season in 5 patients with mucosal abnormalities, while the patients continued treatment with intranasal steroids and symptomatically improved. The sinus mucosal abnormalities persisted in all patients. CONCLUSION: Despite the 60% incidence of abnormalities on the computed tomographic scans of the subjects with ragweed allergy during the season, these abnormalities appear, at most, to contribute minimally to the patient's symptoms, since resolution of symptoms was not accompanied by a reduction in sinus mucosal abnormalities.

CD4+ lymphocytes are increased in the sinus mucosa of children with chronic sinusitis.

OBJECTIVES: To quantitate lymphocyte subtypes in sinus tissues harvested from children with chronic sinusitis and coexisting asthma, allergies, and cystic fibrosis during functional endoscopic sinus surgery and compare them with those in normal adult sphenoid sinus mucosa. DESIGN: Immunohistochemical staining of surgical specimens with monoclonal antibodies against CD4 and CD8 surface antigens. SETTING: Tertiary medical center. PATIENTS: Thirty-two children who underwent functional endoscopic sinus surgery for chronic sinusitis refractory to medical treatment (median age, 8 years; range, 2-13 years) were divided into 3 groups: 10 with asthma, 15 without asthma, and 7 with cystic fibrosis. Sphenoid sinus mucosa obtained from 10 adults (median age, 70 years) undergoing transsphenoidal hypophysectomy was used as control tissue. MAIN OUTCOME MEASURES: Numbers of CD4+ and CD8+ cells in the lamina propria and epithelium of surgical specimens. RESULTS: Significantly more CD4+ cells were in the sinus mucosa of patients with chronic sinusitis than in the normal sinus mucosa (P < .01), but there was no significant difference in the number of CD8+ cells (P = 4). Patients with chronic sinusitis with asthma, without asthma, and with cystic fibrosis all had increased numbers of CD4+ cells compared with sphenoid mucosa, with the difference reaching statistical significance only in the subgroup with chronic sinusitis without asthma (P < .001). The numbers of CD4+ cells were higher in patients with chronic sinusitis than in the sphenoid mucosa irrespective of allergic status. Significantly more CD4+ than CD8+ cells were in tissues from the patients with chronic sinusitis irrespective of concomitant diseases or allergic status. CD4+ and CD8+ cells were more numerous in the apical portion of the submucosa (immediately beneath the epithelium) than in the basal portion both in patients with chronic sinusitis and in normal sphenoid tissue. CONCLUSIONS: Children with chronic sinusitis have predominance of CD4+ cells in the sinus mucosa as compared with normal sphenoid tissue. This contrasts with published results in adults with chromic sinusitis, in whom CD8+ cells predominate in nasal polyps and the submucosa, possibly reflecting a difference in the immunologic response of children and adults.

Hot, humid air partially inhibits the nasal response to allergen provocation.

BACKGROUND: We have previously reported that preconditioning allergic subjects with hot, humid air (HHA) (temperature, 37 degrees C; relative humidity >95%) in an environmental chamber resulted in partial inhibition of the early response to nasal allergen challenge. OBJECTIVE: To investigate whether this inhibitory effect could be achieved by inhalation of HHA via a face mask. DESIGN: Randomized, 4-way crossover study. SUBJECTS: Eighteen subjects with seasonal allergic rhinitis participated in the study outside of their allergy season. INTERVENTIONS: Subjects underwent preconditioning with room air (RA) (temperature, 25 degrees C; relative humidity <20%) or HHA either in a chamber or delivered via a face mask for 1 hour prior to and during nasal challenge with diluent for the allergen extract followed by 2 increasing doses of allergen. RESULTS: Net changes from diluent challenge for all parameters were compared between HHA and RA in each delivery method. Hot, humid air delivered by mask significantly inhibited the mean+/-SEM number of allergen-induced sneezes (HHA, 2.7+/-0.6; RA, 6.6+/-2.1; P=.03), congestion score (HHA, 2.3+/-0.5; RA, 3.4+/-0.5; P=.01), and secretion weights (HHA, 26.9+/-4.4 mg; RA, 38.6+/-5.0 mg; P=.048). However, HHA inhaled in a chamber significantly inhibited only the mean+/-SEM allergen-induced congestion (HHA, 1.2+/-0.4; RA, 3.6+/-0.6; P=.002) and pruritus (HHA, 0.7+/-0.3; RA, 2.3+/-0.5; P=.002) scores. CONCLUSIONS: Preconditioning the nasal mucosa with HHA partially decreases the early response to nasal challenge with antigen irrespective of the administration technique. The secretory response, however, is only inhibited by localized delivery of HHA to the nose. The inhibitory effects of HHA are therefore probably related to local changes in the nasal mucosa and are not dependent on total body exposure to HHA.

The otolaryngology research paradox.

OBJECTIVE: To determine the attitude toward and the state of research within the field of otolaryngology-head and neck surgery. DESIGN: A questionnaire was sent to the chairpersons of departments of otolaryngology where residency training is provided. PARTICIPANTS AND SETTING: Program directors of academic otolaryngology training programs. MAIN OUTCOME MEASURE: Responses to questionnaire. RESULTS: Questionnaires were sent to 95 programs from which 86 responses were received. Respondents believed strongly that research was important to the specialty. Only two thirds of the full-time clinical faculty, however, do research, and on average they devote only 17% of their time to this activity. About a third of those doing research have funding, and the National Institutes of Health support only 12% of clinician-investigators. Although program directors believe that clinicians should do research, three fourths stated that clinicians were too busy to accomplish this goal. Surprisingly, half of the respondents were unaware of residency programs that offered 2 years of research training, aimed to develop clinician-investigators, who can become competitive for attainment of research funding. CONCLUSIONS: Although leaders within our specialty believe that research is important, clinicians are not provided with enough time to conduct research. Furthermore, pathways that would enhance their competitiveness to obtain research funding are not recommended to our future clinicians.

Eosinophilia in chronic childhood sinusitis.

OBJECTIVES: To quantify eosinophilia in sinus tissues obtained from children with chronic sinusitis and to correlate the degree of eosinophilia with history of asthma, allergy, cystic fibrosis, and preoperative computed tomographic (CT) scans. DESIGN: Examination of surgical specimens from children who underwent functional endoscopic sinus surgery and controls. SETTING: Tertiary care medical center. PATIENTS: Thirty-four children who underwent functional endoscopic sinus surgery for chronic sinusitis refractory to medical treatment were divided into three groups: 13 with asthma, 11 without asthma, and 10 with cystic fibrosis. Normal sphenoid sinus mucosa was also obtained from six adults undergoing transsphenoidal hypophysectomies. MAIN OUTCOME MEASURES: Number of lamina propria and intraepithelial eosinophils in surgical specimens, allergic status, presence or absence of asthma, and CT scans obtained preoperatively. RESULTS: There were significantly more lamina propria and intraepithelial eosinophils in the tissue of children with chronic sinusitis compared with normal sphenoid sinus mucosa. More eosinophils were counted in the tissues of patients with asthma and cystic fibrosis compared with patients without concomitant disease, but this did not reach statistical significance. Allergy status did not affect the degree of tissue eosinophilia. Eosinophilia did not correlate with severity of mucosal disease as assessed by CT scans. CONCLUSIONS: Tissue eosinophilia is a characteristic histologic feature of chronic sinusitis in children, especially those with asthma. The presence of allergy does not predict tissue eosinophilia. Furthermore, the degree of tissue eosinophilia does not correlate with the severity of mucosal thickening seen on CT scans.

A mouse model of acute bacterial rhinosinusitis.

OBJECTIVE: To develop a mouse model of acute bacterial rhinosinusitis. DESIGN: Study mice (C57BL6/J) were inoculated intranasally with Streptococcus pneumoniae, ATCC 49619 suspended in trypticase soy broth, and controls were inoculated with trypticase soy broth alone. After 2, 5, or 14 days, intranasal cultures were obtained and mice were killed. The sinuses were prepared for histological investigation. SETTING: Animal care facility at a tertiary, academic institution. METHOD: The histological sections of the sinuses were examined in a blinded manner for the percentage of sinus cavity occupied by neutrophil clusters, and for the number of neutrophils per square millimeter of sinus mucosa. RESULTS: Infected mice killed at 5 days had significantly more sinus area occupied by neutrophil clusters, significantly more neutrophils within the mucosa, and significantly more S pneumoniae growth in the intranasal cultures compared with controls (15/15 vs 0/6; P<.01). The amount of inflammation had decreased at 2 weeks. CONCLUSION: Streptococcus pneumoniae induces acute bacterial rhinosinusitis in C57BL6/4 mice as measured by culture and influx of neutrophils, and can be used as a model of acute bacterial rhinosinusitis.

Duration of action of intranasal atropine on methacholine-induced nasal secretions.

OBJECTIVE: To evaluate the duration of the inhibitory action of intranasal atropine on the secretory response to nasal challenge with methacholine. DESIGN: Double-blind, placebo-controlled, four-way crossover trial. SUBJECTS: Twelve volunteers with perennial allergic rhinitis. INTERVENTIONS: Subjects were treated intranasally with placebo or 100, 200, and 400 micrograms of atropine in each nostril. They were then challenged 30 minutes after administration of the nasal spray and hourly for 6 hours with 0.19 mg of methacholine. The weight of nasal secretions generated by methacholine challenge served as an indicator of the secretory response. The nasal challenges and the collection of nasal secretions were performed using filter paper disks. RESULTS: After placebo treatment, the response to methacholine was similar at each time point. In contrast, all doses of atropine significantly reduced the response to methacholine stimulation at the 30-minute, 1-hour, and 2-hour time points. CONCLUSIONS: Our data show that the anticholinergic activity of intranasal atropine lasts at least 2 hours with no significant difference in the duration of inhibitory action between the doses used. The results suggest that intranasal atropine could become a therapeutic modality for patients in whom glandular hypersecretion is a major symptom.