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.

Ruptured popliteal artery aneurysm.

BACKGROUND: Popliteal artery aneurysms (PAAs) are generally complicated by thrombosis and distal embolization, whereas rupture is rare. The aim of this study was to describe the clinical characteristics and outcome in a cohort of patients who had surgery for ruptured PAA (rPAA). METHODS: Operations for rPAA were identified from the Swedish Vascular Registry, Swedvasc, 1987-2012. Medical records and imaging were reviewed. Comparison was made with patients treated for PAA without rupture. RESULTS: Forty-five patients with rPAA were identified. The proportion with rupture among those operated on for PAA was 2·5 per cent. Patients with rPAA were 8 years older (77·7 versus 69·7 years; P < 0·001), had more lung and heart disease (P = 0·003 and P = 0·019 respectively), and a larger mean popliteal aneurysm diameter (63·7 versus 30·9 mm; P < 0·001) than patients with PAA treated for other indications. At time of surgery, 22 of 45 patients were already receiving anticoagulants, seven for concomitant deep venous thrombosis (DVT) in the affected leg. There was extensive swelling of the whole leg in 20 patients. In 27 patients, the initial diagnosis was DVT or a Baker's cyst. All patients underwent surgery, all but three by the open method. There were four amputations, all performed within 1 week of surgery. One year after surgery, 26 of the 45 patients were alive. Among these, the reconstructions were patent in 20 of 22 patients. CONCLUSION: The diagnosis of rPAA is difficult, and often delayed. The condition affects old patients, who often are on anticoagulation treatment and have large aneurysms. The immediate surgical results are acceptable, but the condition is associated with a high risk of death within the first year after surgery.

CHronic Rhinosinusitis Outcome MEasures (CHROME), developing a core outcome set for trials of interventions in chronic rhinosinusitis.

STATEMENT OF PROBLEM: Evaluating the effectiveness of treatments in chronic rhinosinusitis (CRS) have been limited by both a paucity of high quality randomised trials, and the heterogeneity of outcomes in those that have been reported. Core outcome sets (COS) are an agreed, standardized set of outcomes that should be measured and reported by future trials as a minimum and will facilitate future meta-analysis of trial results in systematic reviews (SRs). We set out to develop a core outcome set for interventions for adults with CRS. METHOD(S) OF STUDY: A long-list of potential outcomes was identified by a steering group utilising a literature review, thematic analysis of a wide range of stakeholders' views and systematic analysis of currently available Patient Reported Outcome Measures (PROMs). A subsequent e-Delphi process allowed 110 patients and healthcare practitioners to individually rate the outcomes in terms of importance, on a Likert scale. MAIN RESULTS: After 2 rounds of the iterative Delphi process, the 54 initial outcomes were distilled down to a final core-outcome set of 15 items, over 4 domains. PRINCIPAL CONCLUSIONS: The authors hope inclusion of these core outcomes in future trials will increase the value of research on interventions for CRS in adults. It was felt important to make recommendations regarding how these outcomes should be measured, although additional work is now required to further develop and revalidate existing outcome measures.

Treatment of Popliteal Aneurysm by Open and Endovascular Surgery: A Contemporary Study of 592 Procedures in Sweden.

BACKGROUND: Popliteal aneurysm (PA) is traditionally treated by open repair (OR). Endovascular repair (ER) has become more common. The aim was to describe time trends and compare results (OR/ER). METHODS: The Swedish vascular registry, Swedvasc, has a specific PA module. Data were collected (2008-2012) and supplemented with a specific protocol (response rate 99.1%). Data were compared with previously published data (1994-2002) from the same database. RESULTS: The number of operations for PA was 15.7/million person-years (8.3 during 1994-2001). Of 592 interventions for PA (499 patients), 174 (29.4%) were treated for acute ischaemia, 13 (2.2%) for rupture, 105 (17.7%) for other symptoms, and 300 (50.7%) were asymptomatic (31.5% were treated for acute ischaemia, 1994-2002, p = .58). There were no differences in background characteristics between OR and ER in the acute ischaemia group. The symptomatic and asymptomatic groups treated with ER were older (p = .006, p < .001). ER increased 3.6 fold (4.7% 1994-2002, 16.7% 2008-2012, p = .0001). Of those treated for acute ischaemia, a stent graft was used in 27 (16.4%). Secondary patency after ER was 70.4% at 30 days and 47.6% at 1 year, versus 93.1% and 86.8% after OR (p = .001, <.001). The amputation rate at 30 days was 14.8% after ER, 3.7% after OR (p = .022), and 17.4% and 6.8% at 1 year (p = .098). A stent graft was used in 18.3% for asymptomatic PA. Secondary patency after ER was 94.5% at 30 days and 83.7% at 1 year, compared with 98.8% and 93.5% after OR (p = .043 and 0.026). OR was performed with vein graft in 87.6% (395/451), with better primary and secondary patency at 1 year than prosthetic grafts (p = .002 and <.001), and with a posterior approach in 20.8% (121/581). CONCLUSIONS: The number of operations for PA doubled while the indications remained similar. ER patency was inferior to OR, especially after treatment for acute ischaemia, and the amputation risk tended to be higher, despite similar pre-operative characteristics.

Treatment with a topical glucocorticoid, budesonide, reduced the variability of rhinomanometric nasal airway resistance.

BACKGROUND: Previous rhinomanometry studies have shown significant long-term variability of the nasal airway resistance and questioned the clinical validity of rhinomanometry. RESEARCH QUESTION: Could treatment with a topical glucocorticoid, budesonide, influence the long-term variability of active anterior rhinomanometry? METHODS: Eight healthy volunteers participated in an unblinded controlled trial without, and later with, nasal budesonide once a day for 5 months. Their nasal airway resistance was measured every two weeks with active anterior rhinomanometry before and after decongestion with xylometazoline hydrochloride. In addition, subjective nasal obstruction was evaluated on a Visual Analogue Scale before each measurement. The participants had a year earlier been investigated with rhinomanometry every two weeks during 5 months but without budesonide treatment. We compared the variability of nasal airway resistance during the two periods with and without treatment with topical budesonide. RESULTS: Budesonide significantly reduced mean nasal airway resistance and the standard deviation of the mean after decongestion for 6 of 8 participants. The mean reduction of the nasal airway resistance was 40% for the decongested nasal cavity compared to the period without treatment with nasal budesonide. Subjective nasal obstruction assessed by Visual Analogue Scale was reduced in 3 of the 8 participants. CONCLUSION: The variability of nasal airway resistance was significantly reduced by treatment with topical budesonide for 6 out of 8 healthy volunteers participating in an unblinded repeated 5 month trial where the participants served as their own controls.

The importance of side difference in nasal obstruction and rhinomanometry: a retrospective correlation of symptoms and rhinomanometry in 1000 patients.

OBJECTIVES: The correlation between subjective and objective outcomes of nasal obstruction is still a matter of controversy. The aim of this study was to determine the minimal level of side difference in nasal airway resistance (NAR measured by Broms'v(2)) between the two nasal cavities, which could be discerned subjectively by the patient on a visual analogue scale (VAS). Nasal airway resistance was calculated from rhinomanometric measurements of nasal airflow and transnasal pressure after decongestion of the nasal mucosa. DESIGN: A retrospective study. SETTING: ENT department, Vaxjo Central Hospital, Sweden. PARTICIPANTS: We studied 1000 active anterior rhinomanometries from patients with nasal obstructions. MAIN OUTCOME MEASURES: We compared the side difference of nasal airway resistance with the side difference of VAS estimated immediately prior to the rhinomanometry. Each measurement was performed after nasal decongestion. RESULTS: When the difference in nasal airway resistance between the two nasal cavities was larger than 20° (Broms'v(2)) or R(2) > 0.36 Pa/cm(3) /s, we found a significant correlation between side differences of the objective measurement and the subjective assessment (VAS). With a nasal airway resistance side difference over 20°, an additional 20° difference corresponded to a 0.9 centimetre average VAS change. The more obstructed side of the nose could be determined by VAS in 823 (82.3%) of 1000 patients. Yet, 177 (17.7%) patients had a paradoxical sensation of nasal obstruction with the low resistance side of the nose experienced as the most congested side. CONCLUSION: A significant correlation between the side differences of nasal airway resistance and VAS can serve as a supplement to rhinoscopy in decisions about nasal surgery. This study also showed that in 17.7% of patients, there was a negative correlation between subjective and objective evaluations of nasal airway resistance. But in this group, the nasal airway resistance side difference was mostly under 20°.

NOD-like receptors in the human upper airways: a potential role in nasal polyposis.

BACKGROUND: Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are newly discovered cytosolic receptors belonging to the pattern-recognition receptor family. They detect various pathogen-associated molecular patterns, triggering an immune response. The knowledge about these receptors, and their role in health and disease, is limited. The aim of the present study was to characterize the expression of NOD1, NOD2, and NALP3 in the human upper airways. METHODS: Surgical samples were obtained from patients with tonsillar disease (n = 151), hypertrophic adenoids (n = 9), and nasal polyposis (n = 24). Nasal biopsies were obtained from healthy volunteers (n = 10). The expression of NOD1, NOD2, and NALP3 was analyzed using real-time PCR and immunohistochemistry. RESULTS: Expression of NOD1, NOD2, and NALP3 mRNA and protein were seen in all tissue specimens. The NLR mRNA was found to be higher in nasal polyps than in normal nasal mucosa, and local steroid treatment reduced the NLR expression in polyps. In contrast, tonsillar infection with Streptococcus pyogenes or Haemophilus influenzae did not affect the NLR expression. CONCLUSIONS: The present study demonstrates the presence of NLRs in several upper airway tissues and highlights a potential role of NLRs in chronic rhinosinusitis with polyps.

Allergic rhinitis and the common cold--high cost to society.

UNLABELLED: The common cold and allergic rhinitis constitute a global health problem that affects social life, sleep, school and work performance and is likely to impose a substantial economic burden on society because of absence from work and reduced working capacity. This study assesses the loss of productivity as a result of both allergic rhinitis and the common cold in the Swedish working population. METHODS: Four thousand questionnaires were sent to a randomized adult population, aged 18-65 years, in Sweden, stratified by gender and area of residence (metropolitan area vs rest of the country). The human capital approach was used to assign monetary value to lost productivity in terms of absenteeism (absence from work), presenteeism (reduced working capacity while at work) and caregiver absenteeism (absence from work to take care of a sick child). RESULTS: Thousand two hundred and thirteen individuals responded, response rate 32%. The mean productivity loss was estimated at 5.1 days or euro 653 per worker and year, yielding a total productivity loss in Sweden of euro 2.7 billion a year. Of the total costs, absenteeism (44%) was the dominant factor, followed by presenteeism (37%) and caregiver absenteeism (19%). Poisson regression analyses revealed that women, people in the 18-29 year age group, and respondents with 'doctor-diagnosed asthma' reported more lost days than the rest of the group. CONCLUSION: In Sweden, the cost of rhinitis is euro 2.7 billion a year in terms of lost productivity. A reduction in lost productivity of 1 day per individual and year would potentially save euro 528 million.

Genes regulating molecular and cellular functions in noninfectious nonallergic rhinitis.

BACKGROUND: Chronic noninfectious, nonallergic rhinitis (NINAR) is a complex syndrome with a principally unknown pathophysiology. New technology has made it possible to examine differentially expressed genes and according to network theory, genes connected by their function that might have key roles in the disease. METHODS: Connectivity analysis was used to identify NINAR key genes. mRNA was extracted from nasal biopsies from 12 NINAR patients and 12 healthy volunteers. Microarrays were performed using Affymetrix chips with 54 613 genes. Data were analysed with the Ingenuity Pathway System for organization of genes into annotated biological functions and, thereafter, linking genes into networks due to their connectivity. The regulation of key genes was confirmed with reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: In all, 43 genes were differentially expressed. The functional analysis showed that these genes were primarily involved in cellular movement, haematological system development and immune response. Merging these functions, 10 genes were found to be shared. Network analysis generated three networks and two of these 'shared genes' in key positions, c-fos and cell division cycle 42 (Cdc42). These genes were upregulated in both the array and the RT-PCR analysis. CONCLUSION: Ten genes were found to be of pathophysiological interest for NINAR and of these, c-fos and Cdc42 seemed to be of specific interest due to their ability to interact with other genes of interest within this context. Although the role of c-fos and Cdc42 in upper airway inflammation remains unknown, they might be used as potential disease markers.

The effects of nasal lavage with betamethasone cream post-endoscopic sinus surgery: clinical trial.

BACKGROUND: Steroid nasal irrigation for chronic rhinosinusitis patients following endoscopic sinus surgery reduces symptom recurrence. There are minimal safety data to recommend this treatment. This study evaluated the safety of betamethasone nasal irrigation by measuring its impact on endogenous cortisol levels. METHODS: Participants performed daily betamethasone nasal irrigation for six weeks. The impact on pre- and post-intervention serum and 24-hour urinary free cortisol was assessed. Efficacy was evaluated using the 22-item Sino-Nasal Outcome Test. RESULTS: Thirty participants completed the study (16 females and 14 males; mean age = 53.9 ± 15.6 years). Serum cortisol levels were unchanged (p = 0.28). However, 24-hour urinary free cortisol levels decreased (47.5 vs 41.5 nmol per 24 hours; p = 0.025). Sino-Nasal Outcome Test scores improved (41.13 ± 21.94 vs 23.4 ± 18.17; p < 0.001). The minimal clinical important difference was reached in 63 per cent of participants. CONCLUSION: Daily betamethasone nasal irrigation is an efficacious treatment modality not associated with changes in morning serum cortisol levels. The changes in 24-hour urinary free cortisol levels are considered clinically negligible. Hence, continued use of betamethasone nasal irrigation remains a viable and safe treatment option for chronic rhinosinusitis patients following functional endoscopic sinus surgery.

Rising incidence of head and neck mucosal melanoma in Australia.

OBJECTIVE: To establish Australian population-based incidence trends for mucosal melanoma of the head and neck. METHODS: Cases between 1985 and 2009 were identified in the Australian Cancer Database. Age-standardised incidence trends were established, including subgroup stratification by sex and site. RESULTS: A continuously progressive increase in incidence was evident in the 353 cases identified over the 25-year study period. This was particularly evident in sinonasal mucosal melanoma in men, despite the overall incidence remaining higher in women. CONCLUSION: There is such paucity in published global incidence trends of head and neck mucosal melanoma. Comparisons of incidence patterns between countries can provide insight into aetiological factors of this rare disease.

Melioidosis in a patient with chronic rhinosinusitis.

BACKGROUND: Melioidosis is a serious infection caused by soil-dwelling Gram-negative bacillus Burkholderia pseudomallei. It is most commonly reported in Northern Australia, Southeast and Southern Asia, China, and Taiwan. METHODS: A case report and short review of the literature are presented. Presentation, diagnosis including genomic sequencing, and acute and long-term management are discussed. RESULTS: A 58-year-old female presented with chronic rhinosinusitis secondary to melioidosis. This is the third reported incidence of sinusitis secondary to melioidosis, which occurred in an otherwise well female with no risk factors and no apparent cause of exposure. Treatment involved an acute phase in which meropenem was administered parenterally for two weeks, followed by a prolonged oral course of trimethoprim-sulfamethoxazole for three months, as per recommended guidelines. CONCLUSION: In patients presenting with refractory chronic rhinosinusitis, ENT surgeons should consider the presence of unusual causative pathogens such as B pseudomallei, particularly in those with recent travel history to Northern Queensland and/or Southeast Asia.

Healthcare provider contact for children with symptoms of sleep-disordered breathing: a population survey.

BACKGROUND: Symptoms of sleep-disordered breathing in children, such as frequent snoring, apnoea and choking, may lead to health problems if untreated. The caregiver's level of awareness of these symptoms has been poorly studied. This study aimed to study healthcare provider contact related to sleep-disordered breathing symptoms in a population of children aged 0-11 years. METHODS: A total of 1320 children were randomly selected from a national database that included all children living in Sweden. Caregivers answered a questionnaire about sleep-disordered breathing symptoms during the last month and healthcare provider contact related to these symptoms. RESULTS: A total of 754 answers were received. The prevalence of sleep-disordered breathing symptoms was 4.8 per cent. Of this subgroup, 69 per cent had not been in contact with a healthcare provider regarding their symptoms. CONCLUSION: This study shows that sleep-disordered breathing in children is underestimated and that there is a need to increase caregiver and healthcare provider awareness of sleep-disordered breathing in children.

Reducing the number of rigid bronchoscopies performed in suspected foreign body aspiration cases via the use of chest computed tomography: is it safe? A literature review.

BACKGROUND: Foreign body aspiration is common and potentially life threatening. Although rigid bronchoscopy has the potential for serious complications, it is the 'gold standard' of diagnosis. It is used frequently in light of the inaccuracy of clinical examination and chest radiography. Computed tomography is proposed as a non-invasive alternative to rigid bronchoscopy. OBJECTIVE: This study aimed to evaluate the accuracy and safety of computed tomography used in the diagnosis of suspected foreign body aspiration, and compare this with the current gold standard, in order to examine the possibility of using computed tomography to reduce the number of diagnostic rigid bronchoscopies performed. METHOD: The study comprised a review of literature published from 1970 to 2013, using the PubMed, Scopus, Web of Knowledge, Embase and Medline electronic databases. RESULTS: The sensitivity for computed tomography ranged between 90 and 100 per cent, with four studies demonstrating 100 per cent sensitivity. Specificity was between 75 and 100 per cent. Radiation exposure doses averaged 2.16 mSv. CONCLUSION: Computed tomography is a sensitive and specific modality in the diagnosis of foreign body aspiration, and its future use will reduce the number of unnecessary rigid bronchoscopies.

Cellular and molecular mechanisms of chronic rhinosinusitis and potential therapeutic strategies: review on cytokines, nuclear factor kappa B and transforming growth factor beta.

BACKGROUND: Chronic rhinosinusitis is characterised by persistent inflammation of the sinonasal mucosa. Multiple pathophysiological mechanisms are likely to exist. Previous research has focused predominantly on T-helper type cytokines to highlight the inflammatory mechanisms. However, proteins such as nuclear factor kappa B and transforming growth factor beta are increasingly recognised to have important roles in sinonasal inflammation and tissue remodelling. OBJECTIVE: This review article explores the roles of T-helper type cytokines, nuclear factor kappa B and transforming growth factor beta in the pathophysiological mechanisms of chronic rhinosinusitis. An understanding of these mechanisms will allow for better identification and classification of chronic rhinosinusitis endotypes, and, ultimately, improved therapeutic strategies.

Neuropeptide Y 16-36 inhibits mucociliary activity but does not affect blood flow in the rabbit maxillary sinus in vivo.

Recent investigations have shown neuropeptide Y (NPY) to be present in the rabbit maxillary sinus, and NPY is known to be released upon sympathetic nerve stimulation. To study, in vivo, the effect on mucociliary activity and blood flow, NPY 1-36 and some of its analogues were injected intra-arterially. The effects of the Y1/Y2 agonist NPY 1-36 was compared with the ones of the Y2 agonist NPY 16-36, the Y1-agonist [Leu31,Pro34]NPY and the Y1/Y2 agonist peptide YY. Mucociliary response was recorded photoelectrically and expressed as a percentage of the basal mucociliary activity immediately prior to challenge. The effect on blood flow was measured with laser Doppler flowmetry and expressed as a percentage of the mean blood flow during the 60 s preceding challenge. NPY 1-36 and NPY 16-36 both reduced mucociliary activity dose-dependently at equimolar dosages (0.024-1.2 nmol/kg). The greatest effect was seen after the highest dosage tested. NPY 1-36 reduced mucociliary activity by 14.6 +/- 1.8%, and NPY 16-36 by 13.2 +/- 1.4%. At the highest dosage tested the Y1 receptor agonist [Leu31,Pro34]NPY did not significantly reduce mucociliary activity, whereas PYY reduced mucociliary activity by 15.0 +/- 1.8%. Injections of NPY 16-36 had no effect on blood flow whereas NPY 1-36, [Leu31,Pro34]NPY and PYY all reduced blood flow dose-dependently. Maximal decrease was seen at the highest dosage tested and was 47.1 +/- 5.4%, 70.4 +/- 7.4% and 58.2 +/- 8.4%, respectively. These findings suggest the mucociliary effects to be mediated via Y2 receptors whereas blood flow is regulated via Y1 receptors.

Effects of halothane on mucociliary activity in vivo.

The effect of halothane on mucociliary activity in the rabbit maxillary sinus in vivo was recorded photoelectrically. Administration of halothane (1%, 2% or 4%) into the maxillary sinus induced a temporary acceleration of mucociliary activity. The peak increase (39.1% +/- 9.1%, p < 0.05, n = 5) was seen after the 4% concentration. Long-term exposure (60 minutes) of the maxillary sinus to halothane (2%) first induced an increase of 28.4% +/- 4.6% (p < 0.05, n = 6), lasting approximately four minutes, and followed after about 15 minutes by a decrease of mucociliary activity. The maximum decrease during the 60-minute period was 19.6% +/- 2.8% (p < 0.05, n = 6). Mucociliary activity returned to its baseline level approximately 25 minutes after withdrawal of halothane. Halothane delivered to the rabbit through a tracheal cannula at 1.1% for 60 minutes did not impair mucociliary activity in the maxillary sinus. On the contrary, it initially stimulated mucociliary activity, 19.9% +/- 2.7% (p < 0.05, n = 5). There was also an initial increase in respiratory rate from 62 +/- 7.3 to 89 +/- 12.9 breaths per minute (p < 0.05), which was noticeable after approximately 10 seconds and lasted 4 to 5 minutes. The dose-dependent increase in mucociliary activity seen after short-term exposure to halothane is probably due to stimulation of afferent C fibers, because halothane may be considered an airway irritant. The reversible depressant effect seen after 15 minutes of exposure is in accordance with findings in previous studies in vitro. The mechanism by which halothane impairs mucociliary activity is at present not known. However, halothane administered to the lower airways does not impair mucociliary activity in the maxillary sinus, indicating that halothane affects the ciliated epithelium directly and that the state of anesthesia itself has no effect on mucociliary activity.