Management of chronic rhinosinusitis with nasal polyps in Samter triad by low-dose ASA desensitization or dupilumab

Samter triad is a chronic condition where patients suffer from intolerance to aspirin, recurring nasal polyposis and bronchial asthma. Causative treatment is often hard. Potential approaches are the daily intake of acetylsalicylic acid (ASA), shunting arachidonic acid into the lipoxygenase pathway, and a subsequent habituation to this constant inflammatory stimulus. Alternatively, the paramount interleukins 4 and 13 may be antagonized by the monoclonal antibody dupilumab. Hence, we evaluated the daily intake of 100 mg ASA and systemic dupilumab (300 mg s.c. every 2 weeks) therapy in refractory patients for its efficacy and compliance.We conducted a retrospective chart review for the efficacy and compliance of both continuous ASA desensitization and systemic dupilumab therapy for refractory patients.Thirty-one patients were included in this retrospective chart review, mean follow-up was 20.4 ± 15.7 months. All patients underwent ASA desensitization. Twenty-one patients had eventually discontinued therapy after 5.8 ± 4.5 months; 11 for its side effects, 12 for its inefficacy. Twenty patients developed sinunasal complaints soon thereafter. Ten patients were still undergoing desensitization (mean duration 15.3 ± 15.7 months). These patients had a higher prevalence of concomitant anti-asthmatic medication. Seventeen refractory patients underwent systemic dupilumab therapy. After 6.4 ± 2.7 months of treatment, sinunasal outcome test (68.1 ± 13.9 vs 20.1 ± 13.9) and visual analogue scales of overall complaints (8.7 ± 0.9 vs 2.2 ± 1.5) as well as endoscopic findings and olfactory function (brief smell identification test; 3.5 ± 2.6 vs 8.6 ± 2.4) all improved significantly.A considerable number of patients with Samter triad discontinued ASA desensitization, equally for ineffectiveness or side effects. If desensitization is to be effective, special care needs to be taken in respect to concomitant anti-asthmatic medication. Dupilumab is highly effective and safe in treating refractory patients.     

The price of pain in chronic rhinosinusitis

Background

Chronic rhinosinusitis (CRS) is associated with productivity losses exceeding US$13 billion annually. Although pain is well known to significantly affect patient productivity in other diseases, its economic impact on CRS‐related lost productivity has not been examined. The objective of this study was to determine whether CRS‐related facial pain correlates with lost productivity in patients with CRS.

Methods

Seventy patients with CRS were enrolled in a cross‐sectional investigation. Patients with a history of systemic inflammatory disease, ciliary dysfunction, chronic pain syndromes, migraines, and fibromyalgia were excluded. Pain was measured using the Brief Pain Inventory Short Form (BPI‐SF) and the Short‐Form McGill Pain Questionnaire (SF‐MPQ). Presenteeism, absenteeism and lost work, and household and overall productivity were assessed. Regression analysis was performed to assess potential confounders, including depression.

Results

Pain as measured with BPI‐SF and SF‐MPQ total scores correlated with all domains of productivity losses. Overall, lost productivity was significantly correlated with pain (R range, 0.354‐0.485; p < 0.001). Presenteeism (reduced work efficiency) had the highest correlation with all of the overall pain scores (R range, ?0.366 to ?0.515; p < 0.001). Lost household productivity time was the least affected by pain (R range, 0.267‐0.389; p < 0.05). These correlations remained statistically significant after regression analysis, which accounted for depression (p < 0.05).

Conclusion

A significant correlation exists between CRS‐related facial pain and productivity losses in patients with CRS that is independent of depression. Facial pain has the strongest correlation with presenteeism, which is the main driver of productivity losses and indirect costs associated with CRS.

     

The role of infection in chronic rhinosinusitis

Chronic rhinosinusitis is a common condition, yet little is understood about its pathogenesis. Chronic infection traditionally has been considered a significant factor in the etiology and manifestations of chronic rhinosinusitis. Bacteria can be recovered in most cases of chronic rhinosinusitis, most commonly consisting of Staphylococcus species, anaerobes, and in some cases, gram-negative bacteria. Increasing trends toward bacterial resistance have been identified in chronic rhinosinusitis. Recently, a potential role for fungal infection has emerged. A knowledge of the microbiology of chronic rhinosinusitis will help guide treatment, but more research is required to understand further the exact role of infection in the pathophysiology of chronic rhinosinusitis.     

The new histologic classification of chronic rhinosinusitis

Two histologic patterns of disease are found in chronic rhinosinusitis. The first is dominated by eosinophilia and polypoid changes. Glandular hyperplasia and hypertrophy characterize the second. We present the evidence supporting the existence of these two patterns of disease and link these histologic patterns to the larger pathophysiologic processes that drive them. This histologic classification should be acknowledged both in the clinical setting and in laboratory research of chronic rhinosinusitis.     

Eosinophilic chronic rhinosinusitis

Eosinophilic chronic rhinosinusitis (ECRS) is a subgroup of chronic rhinosinusitis with nasal polyps (CRSwNP), which is associated with severe eosinophilic infiltration and intractable. Its symptoms include dysosmia, nasal obstruction, and visous nasal discharge. The cause of ECRS is not clear, although it is thought that Staphylococcus aureus and its enterotoxins are involved in stimulating the Th2 system to promote IgE production and eosinophil infiltration through various pathways. While, the coagulation system is activated and the fibrinolytic system is suppressed, leading to deposition of fibrinous networks in nasal polyps. Therefore, a fibrin-degrading agent could be a new treatment for ECRS.Genetic analysis of nasal polyp cells using next-generation sequencing has identified some of the factors involved in ECRS, including periostin, which can be used as a biomarker of this condition. A protease inhibitor could be a therapeutic agent for ECRS. Regarding the role of eosinophils, many researchers have been interested in the mechanism of ETosis. However, the mechanism leading to development of nasal polyps is unknown.In Japan (as well as in East Asia), the incidence of non-ECRS is decreasing and that of ECRS is increasing, but the reason is also unknown. Thanks to the development of biologics therapy, it is thought that there will be a shift to precision medicine in the future.     

Impact of bitter taste receptor phenotype upon clinical presentation in chronic rhinosinusitis

Background

Genetic variation of the bitter taste receptor T2R38 has been associated with recalcitrant chronic rhinosinusitis (CRS). Specific T2R38 polymorphisms, correlating with bitter taste sensitivity to phenylthiocarbamide (PTC), have been identified as an independent risk factor for surgical intervention in CRS patients without polyps; however, the exact role of PTC tasting ability in clinical practice remains unknown. In this investigation we characterize PTC taste sensitivity in a tertiary care rhinology practice with pertinent clinical measures of disease and quality of life (QOL).

Methods

Adult CRS patients were prospectively assessed for their ability to taste PTC and categorized as nontasters, tasters, or supertasters. Objective taste was assessed with strips for bitter, sweet, sour, and salty, whereas olfactory testing was measured with Sniffin’ Sticks. Correlation was performed between PTC tasting ability and patient demographics, endoscopy scores, validated QOL surveys, and both subjective and objective measures of taste and olfaction.

Results

Sixty‐seven patients were enrolled. Fifty‐two percent were identified as nontasters, 34% as tasters, and 13% as supertasters. Nontasters were more likely to be non‐Hispanic (p = 0.018), white (p = 0.027), without nasal polyposis (p = 0.004), and nonasthmatics (p = 0.019). There were no other statistical differences in patients’ demographics, QOL measures, and subjective or objective olfactory and taste scores when compared with patients’ oral PTC‐sensing ability.

Conclusion

Oral PTC‐sensing ability may serve as a convenient marker of increased disease severity in white CRS patients without polyps and vary among regional populations. PTC tasting ability appears to provide unique phenotypic information not obtained using other subjective or objective measures of smell and taste.

     

Pathophysiology of chronic rhinosinusitis

Chronic rhinosinusitis (CRS), a disease presenting with chronic symptoms such as nasal obstruction, rhinorrhea, hyposmia and facial pain, is highly prevalent and has a considerable impact on quality of life and health care expenditures. The disease is characterized by chronic inflammation of the sinonasal mucosa and can present with nasal polyps. Current consensus classifies CRS into CRS with nasal polyps and CRS without nasal polyps. This review illustrates the diversity of pathophysiological observations in CRS and highlights selected etiological hypotheses. A wide spectrum of alterations is described regarding histopathology, pattern of T cells and inflammatory effector cells, remodeling, immunoglobulin production, chemokine and eicosanoid production, and the role of microorganisms. The pathophysiological diversity observed in CRS seems to stand in contrast to its nonspecific clinical presentation, but is of the utmost importance in the development and application of highly individualized treatments. Identification of specific disease subgroups and their etiologies is an important and challenging task for future research.     

Pathogenesis of chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is a heterogenous disorder and represents a major public health problem. Although insights into the pathophysiology of CRS have largely expanded over the last two decades, the exact etiology and mechanism of persistence is still unrevealed. CRS is a multifactorial disease, and, with variable evidence, impaired ostial patency, mucociliary impairment, allergy, bacterial or fungal infection (or triggering), immunocompromised state, and environmental and genetic factors have been suggested to be associated or risk factors. Pathomechanisms in CRS are better understood currently, allowing us to characterize and differentiate the heterogeneous pathology of chronic sinonasal inflammation based on histopathology, inflammatory pattern, cytokine profile, and remodeling processes. In nasal polyposis (NP), but not CRS without NP, an abundant eosinophilic inflammation and local immunoglobulin E production could be demonstrated, and Staphylococcus-derived superantigens may at least modulate disease severity and expression. These findings question the current assumption that NP is a subgroup of CRS, but suggest that CRS and NP should probably be considered as distinct disease entities.     

Antimicrobial therapy in chronic rhinosinusitis

Antimicrobial therapy has been a mainstay of treatment for chronic rhinosinusitis (CRS). The roles of bacterial and fungal infection in the primary pathogenesis of CRS recently have been called into question. Although many different bacteria and fungi can be isolated from CRS patients, antimicrobial treatment directed at their eradication has met with mixed clinical results. Overall, macrolide antibiotics hold the most promise before surgery. Topical antibiotics are safe, efficient, and effective for treating acute bacterial exacerbations of CRS after endoscopic sinus surgery and may prevent the development of subsequent bacterial resistance. Topical treatment of CRS with antifungal agents both before and after sinus surgery is of limited benefit and should not be considered as a primary treatment modality before surgery. Further research into the role of bacterial and fungal infection in the pathophysiology of CRS may offer better insights into appropriate antimicrobial choices, dosing, and treatment duration.     

The role of ubiquitous airborne fungi in chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is a confusing disease for both allergists and otorhinolaryngologists, partially due to its poorly understood pathophysiology and partially due to its limited treatment options. Several recent reports now provide evidence for a better understanding of the etiology and the relationship of CRS to airborne fungi, especially to Alternaria. First, the development of novel methods enables detection of certain fungi in mucus from the nasal and paranasal sinus cavities. Second, a non-immunoglobulin E-mediated immunologic mechanism for reactivity of CRS patients to certain common fungi has been described. Third, these fungi are surrounded by eosinophils in vivo, suggesting that they are targeted by eosinophils. Fourth, the preliminary results of studies using antifungal agents to treat patients with CRS are promising. Overall, these recent discoveries provide a logical mechanism for the pathophysiology of CRS, and they also suggest promising avenues for treatment of CRS with antifungal agents.