Immunoglobulin deficiency in patients with chronic rhinosinusitis: Systematic review of the literature and meta-analysis.

BACKGROUND: Several studies have shown a high prevalence of immunoglobulin deficiencies in patients with chronic rhinosinusitis (CRS). OBJECTIVE: We sought to perform a systematic review and meta-analysis to estimate this prevalence more precisely and to identify patients who need substitution treatment. METHODS: All case series published after 1990 describing patients with CRS, which was defined as symptomatic rhinosinusitis for more than 12 weeks and documented immunoglobulin deficiencies (including deficiencies of IgG with subclasses, IgA, and IgM; specific antibody deficiencies; and potential common variable immunodeficiency), were retrieved. A meta-analysis of the proportion of any combination of common variable immunodeficiency, IgG deficiency, IgA deficiency, and IgM deficiency in patients with CRS was performed by using logit transformation of the prevalence. Recurrent CRS was defined as rhinosinusitis not controlled by appropriate conservative management for 4 months, and difficult-to-treat CRS was defined as noncontrollable rhinosinusitis despite successful sinus surgery and appropriate conservative management for at least 1 year. RESULTS: The meta-analysis revealed a prevalence of pooled IgG, IgA, and IgM deficiencies in 13% of patients with recurrent CRS and 23% of patients with difficult-to-treat CRS. The prevalence of IgG subclass deficiency (5% to 50%) and specific antibody deficiency (8% to 34%) was increased in patients with CRS, as was the prevalence of respiratory allergies in patients with recurrent CRS (31% to 72%). CONCLUSION: Immunoglobulin deficiency is a frequent condition in patients with CRS. An even higher prevalence of atopy was observed in patients with recurrent CRS. Therefore immunoglobulin titers and accurate allergy diagnostic workups are strongly recommended in these patients to provide specific treatments for symptom alleviation. However, there is a need for larger prospective studies addressing the effect of specific therapeutic interventions for CRS.

T lymphocytes promote the antiviral and inflammatory responses of airway epithelial cells.

HYPOTHESIS: T cells modulate the antiviral and inflammatory responses of airway epithelial cells to human rhinoviruses (HRV). METHODS: Differentiated primary human nasal epithelial cells (HNEC) grown on collagen-coated filters were exposed apically to HRV14 for 6 h, washed thoroughly and co-cultured with anti-CD3/CD28 activated T cells added in the basolateral compartment for 40 h. RESULTS: HRV14 did not induce IFNγ, NOS2, CXCL8 and IL-6 in HNEC, but enhanced expression of the T cell attractant CXCL10. On the other hand, HNEC co-cultured with activated T cells produced CXCL10 at a level several orders of magnitude higher than that induced by HRV14. Albeit to a much lower degree, activated T cells also induced CXCL8, IL-6 and NOS2. Anti-IFNγ antibodies and TNF soluble receptor completely blocked CXCL10 upregulation. Furthermore, a significant correlation was observed between epithelial CXCL10 mRNA expression and the amounts of IFNγ and TNF secreted by T cells. Likewise, increasing numbers of T cells to a constant number of HNEC in co-cultures resulted in increasing epithelial CXCL10 production, attaining a plateau at high IFNγ and TNF levels. Hence, HNEC activation by T cells is induced mainly by IFNγ and/or TNF. Activated T cells also markedly inhibited viral replication in HNEC, partially through activation of the nitric oxide pathway. CONCLUSION: Cross-talk between T cells and HNEC results in activation of the latter and increases their contribution to airway inflammation and virus clearance.

Olfactory function improves following hemodialysis.

Olfactory function has been shown to be affected in chronic kidney disease; however, studies are contradictory and little is known on the effects of dialysis. To resolve these issues we tested olfactory function in 24 healthy controls and in 28 patients with chronic kidney disease receiving hemodialysis (20 patients) or peritoneal dialysis (the other 8). As assays for olfactory function we measured smell identification, n-butanol and acetic acid thresholds, Kt/V urea, percentage reduced urea, and weights before and after dialysis. Olfactory function was also self-rated by the participants. Compared to healthy controls, predialysis olfactory function was moderately but significantly decreased in the two dialysis groups, with hemodialysis patients being more affected. Patients self-rated olfactory function similar to that of healthy controls, suggesting that patients are unaware of the olfactory decrease. Olfactory function was significantly improved by one hemodialysis session. Neither body mass index, total volume loss, nor any other dialysis parameter correlated with olfactory function or its restitution following hemodialysis. The observed pattern of improvement suggests underlying mixed peripheral and central mechanisms. Thus, olfactory dysfunction in patients with chronic kidney disease is readily reversible by hemodialysis.

Gustatory dysfunction after mandibular zoster.

Varicella zoster, limited to the mandibular nerve, is rare. Classical symptoms are pain, hypesthesia and vesicular eruption restricted to the third trigeminal segment (V3). Little is known on taste affection after mandibular nerve zoster. We report two cases of patients suffering from mandibular zoster associated with subjective taste disorder. In both cases, gustatory measures confirmed ipsilateral hemiageusia of the anterior two-thirds of the tongue. After 2 months, the symptoms regressed and psychophysical measures came back to normal values, whereas post-zoster neuralgia lasted for more than 1 year. Gustatory dysfunction is a possible symptom after mandibular nerve zoster. In contrast to post-zoster neuralgia, taste function seems to recover quickly.

Superantigens.

Superantigens (SAgs) are derived from diverse sources, including bacteria, viruses, and human hepatic tissue. SAgs initially cause lymphocyte activation but then result in clonal deletion and anergy, leading to immune tolerance. They can also act as superallergens by stimulating a broad spectrum of mast cells and basophils in patients with allergic conditions. The newly described staphylococcal SAg-like proteins subvert innate immune function by several mechanisms, which are distinct from SAgs' effects on lymphocytes and other acquired immune processes. There is mounting evidence to suggest that SAgs play a role in the pathophysiology of inflammatory airway disease. The pathophysiologic role of SAg-like proteins awaits clarification.

Screening for staphylococcal superantigen genes shows no correlation with the presence or the severity of chronic rhinosinusitis and nasal polyposis.

BACKGROUND: Staphylococcus aureus secretes numerous exotoxins which may exhibit superantigenic properties. Whereas the virulence of several of them is well documented, their exact biological effects are not fully understood. Exotoxins may influence the immune and inflammatory state of various organs, including the sinonasal mucosa: their possible involvement in chronic rhinosinusitis has been suggested and is one of the main trends in current research. The aim of this study was to investigate whether the presence of any of the 22 currently known staphylococcal exotoxin genes could be correlated with chronic rhinosinusitis. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a prospective, multi-centred European study, analysing 93 Staphylococcus aureus positive swabs taken from the middle meatus of patients suffering from chronic rhinosinusitis, with or without nasal polyposis, and controls. Strains were systematically tested for the presence of the 22 currently known exotoxin genes and genotyped according to their agr groups. No direct correlation was observed between chronic rhinosinusitis, with or without nasal polyposis, and either agr groups or the presence of the most studied exotoxins genes (egc, sea, seb, pvl, exfoliatins or tsst-1). However, genes for enterotoxins P and Q were frequently observed in nasal polyposis for the first time, but absent in the control group. The number of exotoxin genes detected was not statistically different among the 3 patient groups. CONCLUSIONS/SIGNIFICANCE: Unlike many previous studies have been suggesting, we did not find any evident correlation between staphylococcal exotoxin genes and the presence or severity of chronic rhinosinusitis with or without nasal polyposis.

Chemosensory function in Wegener's granulomatosis: a preliminary report.

Despite the fact that Wegener's granulomatosis affects the nasal and paranasal cavities and the cranial nerves regularly, chemosensory impairments have not been reported. The objective of this study is to test the three chemosensory systems, olfaction, taste, and intranasal trigeminal function in Wegener disease patients. We tested olfactory, gustatory, and intranasal trigeminal function in nine patients (5 women, 4 men, mean age 57 years) with confirmed Wegener's granulomatosis. Olfaction was tested with the Sniffin'Sticks, gustatory function with the "Taste strips" and intranasal trigeminal function with a lateralization task. One patient had anosmia (11%), four patients had hyposmia (44%) and four patients were normosmic (45%). Gustatory testing function showed pathological taste strip results in five patients (55%) and normal results in three patients (33%). One patient did not undergo taste testing. Intranasal trigeminal function was lowered in five patients (56%) and normal in four patients (44%). Neither previous nasal surgery status nor endoscopic status was associated to a higher frequency in pathological scores for any of the three chemical senses. In conclusion, these preliminary results suggest a consistent affection in chemosensory functions in Wegener's granulomatosis patients.

Nasal provocation test: how to maximize its clinical use?

In order to diagnose allergic rhinitis (AR), skin prick tests and serum specific IgE level are the most common used methods. But there are some conditions which the results of both methods do not correlate with the clinical presentation of AR. Nasal provocation test is the method of detecting local IgE at the shock organ. There are some variations of NPT in terms of dosage, allergen administration, evaluation and scoring system. This article summarized the usefulness of NPT, its indication and contraindication, dosage and instillation techniques for allergens and evaluation of outcome in the hope that if we can standardize the procedure and make it easier to perform, NPT will be applied more in clinical practice. In addition normal values among Asian ethnics are presented for appropriate interpretation of the test.

Olfactory disorders: the patients' view.

OBJECTIVE: To investigate the level of knowledge that patients had about their olfactory disorder at the time of presentation to a specialist Olfaction Clinic. DESIGN: Multi-centered, cohort study of consecutive patients presenting to specialist Olfaction Clinics surveyed using a standardized questionnaire. SETTING: Tertiary referral Olfactory Clinics in Geneva, Switzerland and Dresden, Germany. MAIN OUTCOME MEASURES: The number of prior medial consultations, the number and type of doctors they had consulted, a rating of the information they had received from these doctors, whether prognostic information had been given and whether they felt their problems had been well managed by the doctor were factors surveyed. Olfactory assessment was measured by the Sniffin' Sticks kit. RESULTS: Eighty percent of patients had sought previous medical advice, with a mean 2.1 past consultations. Of these patients, 60 % reported that they had received either no or unclear or unsatisfactory information about their diagnosis, 30% had received no information about their prognosis and 25 % felt they had not been managed well. CONCLUSION: The majority of patients with olfactory disorders seek medical advice before presenting to a specialist Olfaction Clinic. However, the majority reported receiving no or poor information about their diagnosis and prognosis. Considering the significant prevalence and potential consequences of olfactory disorders, it is our duty as specialists to improve the knowledge and communication of our medical colleagues about these diseases, so that patient education or referral can be improved.

Retronasal olfactory function in Parkinson's disease.

OBJECTIVES/HYPOTHESIS: Orthonasal olfaction is severely altered in PD patients. Retronasal olfactory function has been shown to be preserved under certain conditions even in the absence of orthonasal function. This study was undertaken to investigate retronasal versus orthonasal olfactory function in Parkinson's disease (PD). STUDY DESIGN: Prospective study. METHODS: A total of 45 PD patients (mean age, 61 years; range 26-82 years) underwent orthonasal olfactory testing with a standardized olfactory test (Sniffin' Sticks) and retronasal olfactory testing with a 10-item identification kit based on aromatized powders. RESULTS: Regarding orthonasal tests, all PD patients scored within the range of hyposmia and functional anosmia. The mean correct orthonasal identification score for PD patients was 56% +/- 2.6%, and the mean retronasal identification rate was 60% +/- 3%. There was no significant difference between ortho- and retronasal odor identification (P = .15). CONCLUSIONS: The present study shows that retronasal and orthonasal olfactory function are severely impaired in PD patients, and this impairment is of similar magnitude for both functions. The contribution of this finding to the food-intake behavior of PD patients is discussed.

Olfactory function and nasal nitric oxide.

PURPOSE OF REVIEW: To highlight two often forgotten nasal functions, olfaction and nasal nitric oxide production, which have both received more attention over the last two decades with consequent findings that are now entering the routine clinical setting. RECENT FINDINGS: Olfactory measurements have been optimized and normative data are available, giving clinicians the possibility of testing olfactory function quickly within a patient's workup. The results can lead to more thorough investigations if necessary. Olfactory disorders concern more than just a few people, and these disorders can be a very early sign of Parkinson's disease. Nasal nitric oxide is hypothesized to play a role as an airborne messenger and as an antiinfectious agent in the nose and sinuses and to contribute to the mucociliary clearance. Evidence is growing that the nasal nitric oxide level is a good parameter for diagnosis of ciliary beat impairments and a suitable parameter to monitor treatment success in chronic rhinosinusitis. SUMMARY: Both nasal nitric oxide and olfactory function are worth testing routinely in any rhinology workup. Valuable clinical information for diagnostic and follow-up purposes can be gained.

Gustatory function after microlaryngoscopy.

CONCLUSION: Quantitative gustatory alterations are rare after microlaryngoscopy (MLS), whereas transient qualitative taste distortions occur more often. Patients undergoing MLS should know that mild but transient qualitative taste disorders may occur. OBJECTIVE: Suspension MLS requires neck extension and tongue compression. Little is known about taste disorders following MLS. To investigate qualitative and quantitative gustatory function after MLS we tested and questioned patients before and several weeks after the MLS. SUBJECTS AND METHODS: This was a prospective controlled study carried out in a tertiary care centre. Forty-three patients participated, 33 of whom underwent MLS and 10 septoplasty. Tongue compression time was recorded during MLS. Patients received taste evaluation before and at 1 and 14 days after the intervention. Patients were asked to indicate subjectively changed taste perceptions. RESULTS: Psychophysical (quantitative) taste results showed no significant differences before and at 1 and 14 days after the intervention (p = 0.60). Tongue compression time (MLS group) had no influence on measured post-MLS taste scores. In the MLS group four patients reported distorted taste perception the day after the MLS, whereas no patient in the septoplasty group did so. In all, four patients distorted taste perception, had disappeared after 14 days.

Functional expression of connexin30 and connexin31 in the polarized human airway epithelium.

Gap junctions are documented in the human airway epithelium but the functional expression and molecular identity of their protein constituents (connexins, Cx) in the polarized epithelium is not known. To address this question, we documented the expression of a family of epithelial Cx (Cx26, Cx30, Cx30.3, Cx31, Cx31.1, Cx32, Cx37, Cx40, and Cx43) in primary human airway epithelial cells (AEC) grown on porous supports. Under submerged conditions, AEC formed a monolayer of airway cells whereas the air-liquid interface induced within 30-60 days AEC differentiation into a polarized epithelium for up to 6-9 months. Maturation of AEC was associated with the down-regulation of Cx26 and Cx43. The well-differentiated airway epithelium exhibited gap junctional communication between ciliated and between ciliated and basal cells. Interestingly, Cx30 was mostly present between ciliated cells whereas Cx31 was found between basal cells. These results are supportive of the establishment of signal-selective gap junctions with maturation of AEC, likely contributing to support airway epithelium function. These results lay the ground for studying the role of Cx-mediated cell-cell communication during repair following AEC injury and exploring Cx-targeted interventions to modulate the healing process.

Rhamnolipids are virulence factors that promote early infiltration of primary human airway epithelia by Pseudomonas aeruginosa.

The opportunistic bacterium Pseudomonas aeruginosa causes chronic respiratory infections in cystic fibrosis and immunocompromised individuals. Bacterial adherence to the basolateral domain of the host cells and internalization are thought to participate in P. aeruginosa pathogenicity. However, the mechanism by which the pathogen initially modulates the paracellular permeability of polarized respiratory epithelia remains to be understood. To investigate this mechanism, we have searched for virulence factors secreted by P. aeruginosa that affect the structure of human airway epithelium in the early stages of infection. We have found that only bacterial strains secreting rhamnolipids were efficient in modulating the barrier function of an in vitro-reconstituted human respiratory epithelium, irrespective of their release of elastase and lipopolysaccharide. In contrast to previous reports, we document that P. aeruginosa was not internalized by epithelial cells. We further report that purified rhamnolipids, applied on the surfaces of the epithelia, were sufficient to functionally disrupt the epithelia and to promote the paracellular invasion of rhamnolipid-deficient P. aeruginosa. The mechanism involves the incorporation of rhamnolipids within the host cell membrane, leading to tight-junction alterations. The study provides direct evidence for a hitherto unknown mechanism whereby the junction-dependent barrier of the respiratory epithelium is selectively altered by rhamnolipids.

Postoperative/posttraumatic gustatory dysfunction.

Clinical taste testing in humans is far from being routinely performed in ear, nose and throat (ENT) clinics. Consequently, most reports on posttraumatic and postoperative taste disorders are case reports and mainly consist of qualitative (e.g. dysgeusia, metallic taste) taste changes after either head injury or ENT surgery. Since quantitative taste deficiencies (ageusia, hypogeusia) often go unnoticed by the patients, the real incidence of ageusia and hypogeusia after head trauma and various surgical procedures remains largely unknown. This lack of reliable clinical data is partly due to the lack of easy, reproducible and rapid clinical taste testing devices. The present chapter tries to resume the current knowledge on postoperative and posttraumatic taste disorders. Despite the sparse literature, the chapter focuses on those ENT surgical procedures where at least some prospective and systematic studies on gustatory dysfunction exist. Accordingly, taste disorders after middle ear surgery, tonsillectomy and dental interventions are largely discussed.

Long-term cultures of polarized airway epithelial cells from patients with cystic fibrosis.

The poor ability of respiratory epithelial cells to proliferate and differentiate in vitro into a pseudostratified mucociliated epithelium limits the general use of primary airway epithelial cell (AEC) cultures generated from patients with rare diseases, such as cystic fibrosis (CF). Here, we describe a procedure to amplify AEC isolated from nasal polyps and generate long-term cultures of the respiratory epithelium. AEC were seeded onto microporous permeable supports that carried on their undersurface a preformed feeder layer of primary human airway fibroblasts. The use of fibroblast feeder layers strongly stimulated the proliferation of epithelial cells, allowing the expansion of the cell pool with successive passages. AEC at increasing passage were seeded onto supports undercoated with airway fibroblasts and exposed to air. Either freshly isolated or amplified AEC could differentiate into a pseudostratified mucociliated epithelium for at least 10 mo. Thus, CF epithelia cultures showed elevated Na+ transport, drastic hyperabsorption of surface liquid, and absence of cAMP-induced Cl- secretion as compared with non-CF cultures. They were also characterized by thick apical secretion that hampered the movement of cell surface debris by cilia. However, CF respiratory epithelia did not show increased production of mucins or IL-8. The method described here is now routinely used in our laboratory to establish long-term cultures of well differentiated respiratory epithelia from human airway biopsies.

Differences between orthonasal and retronasal olfactory functions in patients with loss of the sense of smell.

OBJECTIVE: To investigate differences between orthonasal and retronasal olfaction in patients with loss of the sense of smell without taste complaints. DESIGN: Electrophysiological and psychophysical testing of orthonasal and retronasal olfactory functions. SETTING: Outpatient clinics. PATIENTS: A series of 18 patients who had olfactory loss due to various reasons but no "taste" complaints. MAIN OUTCOME MEASURES: Orthonasal and retronasal olfactory functions assessed by olfactory event-related potentials and psychophysical smell tests. RESULTS: Psychophysical testing revealed retronasal olfaction to be normal or slightly altered, whereas orthonasal olfaction was either absent or severely compromised. Findings from nasal endoscopic examinations and computed tomographic scans were within the reference range in all subjects. In response to orthonasal stimulation there were neither detectable olfactory event-related potentials nor any with small amplitudes, whereas olfactory event-related potentials in response to retronasal stimulation were clearly present in some patients. CONCLUSION: These clinical observations, together with the psychophysical and electrophysiological findings, suggest that orthonasal and retronasal olfaction might be processed differently.

[Clinical aspects of dysosmia and presentation of European Olfactory Test of "sniffin sticks": a review]. / Prise en charge clinique des dysosmies et présentation du test d'olfaction Européen "Sniffin Sticks": une revue.

The medical community has neglected olfactory dysfunction for a long time. However, over the last two decades, remarkable progress has been made in terms of understanding the sense of smell and both the assessment and diagnosis of olfactory dysfunction. Currently, there are only a few validated olfactory tests. The most commonly used one is the University of Pennsylvania Smell Identification Test. Owing to its cultural biases, this test is mostly used in the United States. "Sniffin' Sticks" are one of the first European tests to be widely used. Since their development in 1996, they have been applied in numerous studies and have found increasing use in otolaryngology clinics. The goal of this article is to present Sniffin' Sticks and to provide a review of clinical olfactory research during recent years.

Evidence of an intracellular reservoir in the nasal mucosa of patients with recurrent Staphylococcus aureus rhinosinusitis.

Severe infections due to Staphylococcus aureus require prolonged therapy for cure, and relapse may occur even years after the first episode. Persistence of S. aureus may be explained, in part, by nasal carriage of S. aureus, which occurs in a large percentage of healthy humans and represents a major source of systemic infection. However, the persistence of internalized S. aureus within mucosal cells has not been evaluated in humans. Here, we provide the first in vivo evidence of intracellular reservoirs of S. aureus in humans, which were assessed in endonasal mucosa specimens from patients suffering from recurrent S. aureus rhinosinusitis due to unique, patient-specific bacterial clonotypes. Heavily infected foci of intracellular bacteria located in nasal epithelium, glandular, and myofibroblastic cells were revealed by inverted confocal laser scan fluorescence and electron microscopic examination of posttherapy intranasal biopsy specimens from symptom-free patients undergoing surgery on the sinuses. Intracellular residence may provide a sanctuary for pathogenic bacteria by protecting them from host defense mechanisms and antibiotic treatment during acute, recurrent S. aureus rhinosinusitis.