Background Current phenotyping of chronic rhinosinusitis (CRS) into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) might not adequately ...reflect the pathophysiologic diversity within patients with CRS. Objective We sought to identify inflammatory endotypes of CRS. Therefore we aimed to cluster patients with CRS based solely on immune markers in a phenotype-free approach. Secondarily, we aimed to match clusters to phenotypes. Methods In this multicenter case-control study patients with CRS and control subjects underwent surgery, and tissue was analyzed for IL-5, IFN-γ, IL-17A, TNF-α, IL-22, IL-1β, IL-6, IL-8, eosinophilic cationic protein, myeloperoxidase, TGF-β1, IgE, Staphylococcus aureus enterotoxin–specific IgE, and albumin. We used partition-based clustering. Results Clustering of 173 cases resulted in 10 clusters, of which 4 clusters with low or undetectable IL-5, eosinophilic cationic protein, IgE, and albumin concentrations, and 6 clusters with high concentrations of those markers. The group of IL-5–negative clusters, 3 clusters clinically resembled a predominant chronic rhinosinusitis without nasal polyps (CRSsNP) phenotype without increased asthma prevalence, and 1 cluster had a TH 17 profile and had mixed CRSsNP/CRSwNP. The IL-5–positive clusters were divided into a group with moderate IL-5 concentrations, a mixed CRSsNP/CRSwNP and increased asthma phenotype, and a group with high IL-5 levels, an almost exclusive nasal polyp phenotype with strongly increased asthma prevalence. In the latter group, 2 clusters demonstrated the highest concentrations of IgE and asthma prevalence, with all samples expressing Staphylococcus aureus enterotoxin–specific IgE. Conclusion Distinct CRS clusters with diverse inflammatory mechanisms largely correlated with phenotypes and further differentiated them and provided a more accurate description of the inflammatory mechanisms involved than phenotype information only.
Local allergic rhinitis (LAR) is a localized nasal allergic response in the absence of systemic atopy characterized by local production of specific IgE (sIgE) antibodies, a TH 2 pattern of mucosal ...cell infiltration during natural exposure to aeroallergens, and a positive nasal allergen provocation test response with release of inflammatory mediators (tryptase and eosinophil cationic protein). Although the prevalence remains to be established, a number of patients previously given a diagnosis of nonallergic rhinitis or idiopathic rhinitis are now being classified as having LAR. Culprit allergens responsible include house dust mite, grass and olive pollens, and many others. For the diagnosis of LAR, neither skin prick testing nor determination of the presence of serum sIgE antibodies is useful, and a nasal allergen provocation test is needed to identify the culprit allergen or allergens. In a certain proportion of cases, local sIgE can be detected, and conjunctivitis, asthma, or both can be associated. Whether patients with LAR will have systemic atopy in the future is a matter of debate. Further studies are needed for examine the prevalence of this phenomenon in different areas, to improve the diagnostic methods to better identify these patients, and to develop therapeutic approaches, including the use of immunotherapy.
Respiratory multimorbidities link allergic rhinitis with early allergic asthma and chronic rhinosinusitis with nasal polyps with late non-allergic asthma.
To investigate the association of asthma ...severity and control with specific upper airways phenotypes.
Asthma patients, were prospectively recruited from 23 pulmonology and ENT clinics. Asthma severity and control as well as upper airway comorbidities (allergic AR and non-allergic NAR rhinitis, and chronic rhinosinusitis with CRSwNP and without CRSsNP nasal polyps) were assessed according to international consensus guidelines definitions.
Four hundred ninety-two asthmatic patients were included. Half (49.6%) of asthmatics had associated rhinitis (37.0% AR, 12.6% NAR) or 36.2% CRS (16.7% CRSsNP and 19.5% CRSwNP) while 14.2% had no sinonasal symptoms. Most AR (78%) and NAR (84%) were present in mild-moderate asthmatics while CRSwNP was more frequent in severe asthma (35%, P<0.001) mainly nonatopic (44%; p<0.001). Severe asthma patients with CRSwNP had a worse asthma control which was correlated (r = 0.249; p=0.034) with sinus occupancy. Multiple logistic regression analysis showed that late onset asthma, intolerance to aspirin/NSAID and CRSwNP were independently associated with severe asthma.
Severe asthma is associated with CRSwNP which sinus occupancy affects asthma control. This study has identified two main different upper airways treatable traits, AR and CRSwNP which need further evaluation to improve management and control of asthma patients.
Background Allergic Rhinitis and its Impact on Asthma (ARIA) differentiates mild from moderate/severe patients on the basis of 4 severity items. The high prevalence of moderate/severe patients ...suggests the need to differentiate between them. Objectives To identify the categorization that maximizes discrimination between moderate and severe allergic rhinitis (AR) by using ARIA guidelines. Methods Observational, cross-sectional study. Clinical characteristics, nasal symptoms (Total Symptom Score 4), and health-related quality of life (HRQL; Rhinoconjunctivitis Quality of Life Questionnaire and Short Form 12) were assessed. The association of severity items ( sleep , daily activities/sport , work/school , and troublesome symptoms ) with symptoms and HRQL was analyzed using linear regression models. ANOVA and effect sizes were used to assess differences in symptoms and HRQL among groups defined by the number of affected ARIA items. Results Nontreated patients (N = 141) with moderate/severe AR were studied. All severity items showed a similar independent association with symptoms and HRQL scores, and there were no interaction effects, indicating that categorization of patients into moderate and severe could be based only on the number of items affected. Effect sizes were highest between patients with 4 affected ARIA items and those with 3, 2, or 1 affected item (effect sizes greater than 0.8 in all comparisons using Rhinoconjunctivitis Quality of Life Questionnaire and Short Form 12 Physical Composite Summary, and greater than 0.5 using the Total Symptom Score 4; P < .001). Conclusion Using ARIA severity items, the criterion that best discriminates AR severity is considering moderate those with 1 to 3 affected items and severe those with 4. Clinical implications Discrimination between patients with moderate and severe AR should help to obtain homogeneous populations for both research and clinical purposes.
Increasing evidence supports the united airway disease concept for the management of upper and lower respiratory tract diseases, particularly in patients with asthma and chronic rhinosinusitis with ...nasal polyps (CRSwNP). However, evidence for a combined approach in asthma and CRSwNP is scarce.
In this systematic review, we focused on the role of biologics in the lung function and quality of life in patients with severe asthma and CRSwNP.
We conducted a systematic search of 3 electronic databases using 2 search strategies to identify studies published from January 2010 to March 2022. Quality assessment was performed with the Critical Appraisal Skills Programme.
Of 1030 studies identified, 48 original studies reporting data of benralizumab (12), dupilumab (14), mepolizumab (10), omalizumab (13), and reslizumab (2) were analyzed. Primary diagnosis was mostly asthma or CRSwNP, with only 15 studies, mainly observational, performed in populations with united airway disease. In total, 18 studies reported data on quality of life (mostly 22-item Sino-Nasal Outcome Test score), 8 on lung function (mostly FEV1), and 22 on both outcomes. Significant FEV1 and 22-item Sino-Nasal Outcome Test score improvements were consistently observed after 24-week treatment, and thereafter, mostly in real-world studies that included variable proportions of patients with asthma/CRSwNP.
The use of biologics in patients with severe asthma and CRSwNP was overall associated with significant improvements in lung function and quality of life. However, we observed a high heterogeneity of populations and outcome measurements across studies. Notwithstanding the need of larger studies, our results reinforce the joint management of asthma and CRSwNP as united airway disease in clinical practice.
Background We hypothesized that the 2 reported alterations in aspirin-exacerbated respiratory disease (AERD), reduced expression/production of COX-2/prostaglandin (PG) E2 and diminished expression of ...E-prostanoid (EP) 2 receptor, are closely linked. Objective We sought to determine the mechanisms involved in the altered regulation of the COX pathway in patients with AERD. Methods Fibroblasts were obtained from nasal mucosa; samples of control subjects (NM-C, n = 8) and from nasal polyps from patients with aspirin-exacerbated respiratory disease (NP-AERD, n = 8). Expression of the autocrine loop components regulating PGE2 production and signaling, namely IL-1 type I receptor (IL-1RI), COX-2, microsomal prostaglandin E synthase 1 (mPGES-1), and EP receptors, was assessed at baseline and after stimulation with IL-1β, PGE2 , and specific EP receptor agonists. Results Compared with NM-C fibroblasts, basal expression levels of IL-1RI and EP2 receptor were lower in NP-AERD fibroblasts. IL-1β–induced IL-1RI, COX-2, and mPGES-1 expression levels were also lower in these cells. Levels of IL-1RI positively correlated with COX-2 and mPGES-1 expression in both NM-C and NP-AERD fibroblasts. Incubation with either exogenous PGE2 or selective EP2 agonist significantly increased expression of IL-1RI in NM-C fibroblasts and had hardly any effect on NP-AERD fibroblasts. Alterations in IL-1RI, COX-2, and mPGES-1 expression that were found in NP-AERD fibroblasts were corrected when EP2 receptor expression was normalized by transfection of NP-AERD fibroblasts. Conclusion Altered expression of EP2 in patients with AERD contributes to deficient induction of IL-1RI, reducing the capacity of IL-1β to increase COX-2 and mPGES-1 expression, which results in low PGE2 production. This impairment in the generation of PGE2 subsequently reduces its ability to induce IL-1RI.
The presence of aspirin-exacerbated respiratory disease (AERD) in a patient with chronic rhinosinusitis with nasal polyps and asthma is associated with severe eosinophilic upper and lower airway ...disease. This article deals with the inflammatory disease of the respiratory tract as it relates to the sinuses. Involvement of the sinuses in AERD is almost universal, depending on the stage of onset of the disease and evaluation by computed tomography. This article explores the clinical aspects, physiopathology, and treatment of rhinosinusitis as it relates to AERD.
Rationale Loss of smell is a major consequence for chronic sinusitis patients with nasal polyps and is a severity marker with significant impact on quality of life.
Chronic rhinosinusitis, including nasal polyps, is an inflammatory disease of the nose and sinuses. The medical treatment, mainly topical intranasal and oral corticosteroids, constitutes its first ...line of therapy. Long-term treatment with corticosteroid nasal spray reduces inflammation and nasal polyp size, and improves nasal symptoms such as nasal blockage, rhinorrea, and the loss of smell. Corticosteroid intranasal drops may be used when intranasal spray fails to demonstrate efficacy. Short courses of oral steroids are recommended in severe chronic rhinosinusitis with nasal polyps or when a rapid symptomatic improvement is needed. Endoscopic sinus surgery is only recommended when the medical treatment fails. Intranasal corticosteroids should be continued postoperatively. When using intranasal corticosteroids, care should be taken in selected populations such as children, pregnant women, and elderly patients; especially in those patients with comorbid conditions such as asthma, in which the overall steroid intake can be high due to the administration of both intranasal and inhaled corticosteroids.
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