Availability of Preoperative Systemic Steroids on Endoscopic Sinus Surgery for Chronic Rhinosinusitis with Nasal Polyposis

Purpose

To analyze the outcome of endoscopic sinus surgery (ESS) after preoperative systemic steroid (PSS) treatment for chronic rhinosinusitis (CRS) with nasal polyposis (NP) and to investigate and compare clinicopathological factors associated with the outcome.

Materials and Methods

We performed a retrospective chart review of 468 patients with CRS with NP who underwent primary ESS between January 2005 and October 2011. 124 patients who met the inclusion criteria were included. Beginning from 2008, our clinic administered steroid preoperatively in patients of CRS with NP, thus there were 84 patients with preoperative systemic steroid (PSS group) and another 40 patients without such regimen (no PSS group). To evaluate the outcome after ESS, poor outcome and complication were analyzed according to the following parameters: age, sex, follow-up duration, eosinophilic infiltration, atopy, asthma, Lund-Mackay score, and polyp grade.

Results

There was no significant difference in poor outcome rates between the PSS and no PSS group (35.0% vs. 47.6%, p=0.185). There was no significant difference in complication rates between the PSS and no PSS group (10% vs. 6%, p=0.468). As with the multivariate analysis of the clincopathological factors to the poor outcome rate, presence of asthma and eosinophilic infiltration were significantly related (odds ratio as 6.555 and 4.505, respectively), whereas PSS was confirmed as less likely related (odds ratio 0.611).

Conclusion

Low dose PSS administration does not seem to have an effect on the outcome after ESS in patients who have CRS with NP. Eosinophilic infiltration and presence of asthma are important predictors of surgical outcome.     

Risk Model Establishment of Endoscopic Sinus Surgery for Patients with Chronic Rhinosinusitis: a Multicenter Study in Korea

BackgroundEndoscopic sinus surgery (ESS) is the mainstay treatment for refractory chronic rhinosinusitis (CRS). Since various factors may contribute to the surgical outcome, it is challenging for physicians to predict surgical outcomes. The aim of study was to analyze the prognostic factors of postoperative outcomes and to establish the prediction model with the risk factors that impact the postoperative outcomes.MethodsMedical records of CRS patients who underwent ESS at 9 institutions in 2005, 2010, and 2016 were retrospectively reviewed. We classified the patients into 2 groups based on postoperative objective endoscopic outcomes. Demographics, nose-specific symptoms, olfactory function, eosinophil counts in blood (EoB) and nasal tissue (EoT), and Lund-Mackay CT score (LMS) were collected. Univariate and multivariate analyses were performed and established a prediction equation for postoperative endoscopic objective outcomes.ResultsIn total (n = 1,249), 27.0% were not satisfied under postoperative endoscopic examination. Of 10 variables, LMS (> 5), sinus dominancy (maxillary sinus and ethmoid sinus), EoB (> 210), and EoT (> 100) were statistically significant in univariate analysis (P < 0.05, all). In multivariate analysis, EoT (> 100) and LMS (> 5) were significantly associated with poor postoperative outcome. Furthermore, 5 significant variables were employed to establish the risk model of postoperative outcomes and P (the value of prediction probability) = 1 / (1 + exp [−0.392 + 1.088 × EoT (> 100) + 0.123 × mean LMS (> 5) − 0.366 × sinus dominancy (maxillary) + 0.064 × sinus dominancy (similar) + 0.200 × EoB (4%) + 0.344 × EoB (> 210)] was developed.ConclusionTissue eosinophil count and radiographic severity predispose to a poorer outcome of ESS and the risk model established may be helpful to predict postoperative outcomes of ESS.     

Long-term efficacy of dupilumab in asthma with or without chronic rhinosinusitis and nasal polyps

BackgroundCoexisting chronic rhinosinusitis and nasal polyps (CRS-NPs) substantially increases the disease burden of asthma. Dupilumab, a fully human monoclonal antibody, has established efficacy and an acceptable safety profile in asthma and CRS with NP.ObjectiveTo evaluate long-term dupilumab efficacy in TRAVERSE (NCT02134028) patients with uncontrolled, moderate-to-severe (QUEST) or oral corticosteroid (OCS)-dependent (VENTURE) asthma with or without coexisting CRS-NP.MethodsIn TRAVERSE, 317 of 1530 (21%) QUEST and 61 of 187 (48%) VENTURE patients had self-reported CRS-NP; they received subcutaneous 300 mg dupilumab every 2 weeks up to 96 weeks. Patients were categorized by parent study treatment group (placebo/dupilumab, dupilumab/dupilumab). End points included annualized asthma exacerbation rates and mean change from parent study baseline in prebronchodilator forced expiratory volume in 1 second, Asthma Control Questionnaire 5 score, Asthma Quality of Life Questionnaire score, and OCS dose.ResultsPatients with coexisting CRS-NP had higher OCS dose and a history of more exacerbations. Concluding TRAVERSE, exacerbation rates decreased from 2.39 to 0.32 and 2.32 to 0.35 in dupilumab/dupilumab and 2.36 to 0.41 and 2.36 to 0.45 in placebo/dupilumab by week 96 from QUEST and VENTURE baselines, respectively. Non-CRS-NP results were similar. Improvements in forced expiratory volume in 1 second, Asthma Control Questionnaire 5 score, and Asthma Quality of Life Questionnaire score during parent studies were maintained in TRAVERSE; placebo/dupilumab patients achieved similar improvements to dupilumab/dupilumab by week 48. By week 96, 71% and 39% of OCS-dependent patients with CRS-NP and 83% and 47% without CRS-NP treated with dupilumab/dupilumab and placebo/dupilumab, respectively, stopped OCS.ConclusionLong-term dupilumab efficacy was maintained in patients with asthma with or without self-reported coexisting CRS-NP, including OCS-sparing effects observed in OCS-dependent severe asthma.Clinical Trial RegistrationClinicalTrials.gov Identifiers: NCT02528214, NCT02414854, and NCT02134028.     

Benralizumab efficacy for patients with fixed airflow obstruction and severe,uncontrolled eosinophilic asthma

BackgroundFixed airflow obstruction (FAO) is associated with severe eosinophilic asthma. Benralizumab is an interleukin-5 receptor alpha–directed cytolytic monoclonal antibody for patients with severe, uncontrolled eosinophilic asthma.ObjectiveWe evaluated FAO influence on benralizumab treatment response.MethodsWe performed a post hoc analysis of pooled phase III SIROCCO (NCT01928771) and CALIMA (NCT01914757) data for patients with severe, uncontrolled asthma with baseline blood eosinophil counts of 300 or more cells/μL who received benralizumab 30 mg every 8 weeks or placebo. Demographics, baseline clinical characteristics, and treatment responses were evaluated by FAO status. FAO+ and FAO− were defined as ratios of postbronchodilator forced expiratory volume in 1 second (FEV₁) to forced vital capacity of less than 70% and 70% or more, respectively, at baseline.ResultsFAO+ prevalence was 63% (935/1493). With benralizumab, similar annual asthma exacerbation rate (AER) reductions vs placebo were achieved for FAO+ and FAO− patients (rate ratio [95% confidence interval (CI)] = 0.56 [0.44-0.71] and 0.58 [0.41-0.83], respectively), whereas annual AER reductions associated with emergency department visits or hospitalizations were greater for FAO+ vs FAO− patients (rate ratio [95% CI] = 0.55 [0.33-0.91] and 0.70 [0.33-1.48], respectively). Prebronchodilator FEV₁ (95% CI) increase from baseline to end of treatment was greater for FAO+ vs FAO− patients receiving benralizumab compared with placebo (0.159 L [0.082-0.236] vs 0.103 L [−0.008 to 0.215]). Other lung function measures, patient-reported outcomes, and symptom improvements were also numerically greater for FAO+ vs FAO− patients.ConclusionBenralizumab improved asthma control across several measures for patients with severe, uncontrolled eosinophilic asthma and FAO.Trial RegistrationSIROCCO trial: NCT01928771 (URL: https://clinicaltrials.gov/ct2/show/NCT01928771) CALIMA trial: NCT01914757 (URL: https://clinicaltrials.gov/ct2/show/NCT01914757)     

The spectrum of therapeutic activity of mepolizumab

ABSTRACT

Introduction: The basis of the development of the anti-interleukin-5 monoclonal antibody mepolizumab was the acknowledgment of the crucial importance of this cytokine in promoting eosinophils production, activation, and survival, which is associated with the eosinophilic asthma phenotype, as well as with other disorders characterized by high levels of eosinophils.

Areas covered: All the available literature on the outcomes treatment with mepolizumab in eosinophilic disorders are reviewed, including asthma, chronic rhinosinusitis, esophagitis, granulomatosis with polyangiitis, eosinophilic chronic obstructive pulmonary disease, hypereosinophilic syndrome, and allergic bronchopulmonary aspergillosis.

Expert opinion: The efficacy of mepolizumab in eosinophilic asthma is clearly demonstrated by a number of controlled trials and by meta-analyses. Among other eosinophilic disorders, controlled trials are available for chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, and eosinophilic chronic obstructive pulmonary disease. Allergic bronchopulmonary aspergillosis, as well as other minor eosinophilic disorders, are backed only by case reports and are waiting controlled trials to verify the therapeutic role of mepolizumab.     

Real-world Evaluation of Asthma Control and Treatment (REACT): findings from a national Web-based survey

BACKGROUND: Despite health initiatives for advancing the management of asthma, evidence suggests that many asthmatic subjects have uncontrolled disease. However, the prevalence of uncontrolled asthma in the United States is not known and has not been fully characterized. OBJECTIVE: We sought to assess the prevalence, morbidity, and factors associated with uncontrolled asthma in a nationally representative sample of patients with moderate-to-severe asthma using standard asthma medications. METHODS: A Web-based survey was administered to patients with diagnoses of asthma for at least 1 year who were receiving multiple controller medications. The Asthma Control Test score was used to stratify respondents into controlled and uncontrolled cohorts. RESULTS: A total of 1812 patients were assessed; 809 (45%) had controlled asthma, and 1003 (55%) had uncontrolled asthma. Most patients had health care coverage and received care from a general practitioner; a large proportion of patients with controlled asthma (74%) and patients with uncontrolled asthma (65%) reported never receiving an asthma action plan. Inhaled corticosteroid plus long-acting beta-agonist was the most common medication regimen in patients with controlled asthma (60%) and patients with uncontrolled asthma (48%) patients. Patients with uncontrolled asthma reported significantly higher rates of health care use. Several comorbidities were predictive of uncontrolled asthma. CONCLUSION: Uncontrolled asthma is highly prevalent (55%) in patients using standard asthma medications. There is need for improved asthma care in patients with moderate-to-severe asthma, including a global evaluation of asthma control, implementation of treatment plans and asthma control tests, and addressing comorbid conditions. CLINICAL IMPLICATIONS: Improved asthma care requires broader assessments of asthma control, including asthma-related health care and medication use, comorbidities, and the implementation of treatment plans and formal asthma control tests.     

Airway inflammation assessed by invasive and noninvasive means in severe asthma: eosinophilic and noneosinophilic phenotypes

BACKGROUND: Airway inflammation assessed by bronchial biopsies demonstrates distinct eosinophilic and noneosinophilic phenotypes in severe asthma, but their relationship to other biomarkers of disease (induced sputum and nitric oxide [NO]) is not clear. OBJECTIVES: We sought to compare airway inflammation using noninvasive (induced sputum, exhaled NO), and invasive (bronchial biopsies) methods in moderate and severe asthma and to assess whether induced sputum and exhaled NO would allow the identification of eosinophilic and noneosinophilic phenotypes in severe asthma. METHODS: We performed a cross-sectional study of 32 subjects with severe asthma and 35 subjects with moderate asthma, from whom we obtained bronchial biopsies, induced sputum, and exhaled NO measurements. RESULTS: Among subjects with severe asthma, we identified eosinophilic and noneosinophilic phenotypes using both bronchial biopsies and sputum cell counts. However, the vast majority of subjects with high sputum eosinophil counts did not have high mucosal eosinophil counts. Exhaled NO was increased in the eosinophilic phenotype as judged from bronchial biopsy findings, but not on the basis of induced sputum. Subjects with high sputum eosinophil counts experienced more asthma exacerbations than the subjects with low sputum eosinophil counts. In contrast, we did not find any differences in the clinical characteristics between eosinophilic and noneosinophilic phenotypes that were identified by bronchial biopsies. CONCLUSION: The use of sputum cell counts allowed the identification of a subgroup of subjects with severe asthma who were at risk of more frequent asthma exacerbations. CLINICAL IMPLICATIONS: Monitoring sputum eosinophil counts in subjects with severe asthma may allow identifying the subjects with the greatest disease activity.     

A clinical study of endoscopic sinus surgery for sinusitis in patients with bronchial asthma

BACKGROUND: An association between bronchial asthma and sinusitis has long been suspected. Our aim is to study the clinical features of chronic sinusitis associated with bronchial asthma as two manifestations of one airway disease. METHODS: We conducted a prospective analysis of the outcome of 88 patients, with or without bronchial asthma, who underwent endoscopic sinus surgery (ESS) for chronic sinusitis. Patients were divided into two groups by the presence or absence of asthma and were evaluated. One surgeon performed the ESS, and the same postoperative treatment was given to both groups. The postoperative outcomes of symptoms and objective findings related to sinusitis were evaluated numerically, with a maximum score of 2 points for each examination item. Twenty-eight patients with asthma symptoms were assessed before and after surgery, using peak flow (liter/second) and medication scores (according to US Food and Drug Administration) to determine whether bronchial asthma was improved by first-time ESS. RESULTS: The outcomes of ESS were significantly worse in the asthma group, especially the endonasal findings. Patients suffering from chronic sinusitis and bronchial asthma showed improvement following ESS in terms of their asthma symptoms, peak flow and medication score. Patients with a good ESS result tended to have the greatest improvement in their asthma. CONCLUSIONS: We conclude that sinusitis and asthma are closely related to each other, acting as two manifestations of one airway disease. We recommend treating cases of sinusitis complicated by asthma as a single disease of the entire respiratory tract.     

Features of airway remodeling and eosinophilic inflammation in chronic rhinosinusitis: is the histopathology similar to asthma?

BACKGROUND: Asthma and chronic rhinosinusitis (CRS) coexist clinically in >50% of patients with CRS. Although epithelial damage and basement membrane thickening are well-known features of airway remodeling in asthma, they have not been described in CRS. OBJECTIVE: In this study, we tested the hypothesis that histopathologic features of asthma, namely, the chronic eosinophilic inflammation, epithelial damage, and basement membrane thickening of the airway mucosa, are also present in sinonasal specimens from patients with CRS. METHODS: We examined histologic specimens from 22 randomly selected patients with refractory CRS undergoing endoscopic sinus surgery and 4 healthy control subjects. The shedding of the epithelium and basement membrane thickening were evaluated by 3 independent observers' scores of hematoxylin-and-eosin staining. Eosinophilic inflammation was monitored with immunohistochemistry for eosinophil major basic protein. A novel, computerized method objectively analyzed confocal microscopic images of major basic protein immunofluorescence to determine areas with the least and most inflammation per specimen. RESULTS: Specimens from all patients with CRS (22/22) revealed epithelial damage (shedding) and basement membrane thickening. Strikingly heterogeneous eosinophilic inflammation, which did not differ between allergic and nonallergic patients, was detected in all patients with CRS and was absent in all healthy control subjects. CONCLUSION: The histopathologic findings of asthma, namely, heterogeneous eosinophilic inflammation and features of airway remodeling, are also present in CRS. These findings, coupled with the common clinical coexistence of both diseases, suggest that the same pathologic disease process is manifest as CRS in the sinonasal tissue and as asthma in the lower airway.     

Noneosinophilic asthma: a distinct clinical and pathologic phenotype

The use of induced sputum to assess airway inflammation in large and diverse populations with asthma has led to the recognition that significant numbers of patients do not have evidence of eosinophilic airway inflammation. The absence of a sputum eosinophilia has been noted in patients across the range of asthma severity; it has also been reported in patients presenting with an asthma exacerbation. However, whether noneosinophilic asthma represents a pathologically distinct and clinically important asthma phenotype remains unclear. In this review, we present recent evidence suggesting that noneosinophilic asthma represents a stable phenotype associated with a distinct lower airway pathology and structure. We suggest that this lower airway inflammation develops in response to etiologic factors acting through the innate immune pathway and that elements of this immune response contribute to airway dysfunction. Finally, we argue that noneosinophilic asthma is associated with clinically important differences in natural history and treatment response. We particularly highlight evidence that noneosinophilic asthma is associated with a reduced short-term and long-term response to corticosteroid therapy.     

Efficacy of dupilumab in patients with moderate-to-severe asthma and persistent airflow obstruction

BackgroundThe 52-week, phase 3 LIBERTY ASTHMA QUEST study (NCT02414854) in patients aged above or equal to 12 years with uncontrolled, moderate-to-severe asthma demonstrated the efficacy and safety of dupilumab 200 mg and 300 mg every 2 weeks vs matched placebo.ObjectiveTo assess whether dupilumab improves clinical outcomes in QUEST patients with persistent airflow obstruction (PAO) defined as post-bronchodilator forced expiratory volume in 1 second/forced vital capacity ratio less than 0.7 at baseline.MethodsEnd points were annualized rate of severe exacerbations, pre and post-bronchodilator forced expiratory volume in 1 second over time, proportion achieving reversal of PAO, and quality of life. Efficacy was evaluated in patients with or without PAO at baseline in subpopulations with eosinophils ≥ 150 cells/µL or fractional exhaled nitric oxide (FeNO) ≥ 25 ppb or eosinophils ≥ 300 cells/µL and FeNO ≥ 25 ppb.ResultsOf 1902 patients enrolled in QUEST, 1039 (55%) had PAO at baseline. Dupilumab vs placebo rapidly and significantly improved lung function in patients with PAO and elevated type 2 inflammatory biomarkers at baseline. Dupilumab improved probability of reversing airflow obstruction (hazard ratio vs placebo 1.616 [95% confidence interval, 1.272-2.052] and 1.813 [1.291-2.546]; both P < .001) and significantly reduced severe exacerbations by 69% (relative risk, 0.411; 95% confidence interval [0.327-0.516]; P < .0001) and by 75% (0.252 [0.178-0.356]; P < .0001) in patients with PAO with eosinophils ≥ 150 cells/µL or FeNO ≥ 25 ppb and eosinophils ≥ 300 cells/µL and FeNO ≥ 25 ppb, respectively. Similar results were observed in patient subgroups without PAO.ConclusionIn patients with uncontrolled moderate-to-severe asthma, treatment with dupilumab facilitates reversal of PAO status and improves clinical outcomes.Trial Registration: ClinicalTrials.gov identifier: NCT02414854.     

Effect of omalizumab on lung function and eosinophil levels in adolescents with moderate-to-severe allergic asthma

BackgroundOmalizumab improves clinical outcomes in patients with asthma. Several studies have shown lung function improvements with omalizumab; however, this has not been examined exclusively in adolescents.ObjectiveTo assess the effect of omalizumab on lung function and eosinophil counts in adolescents with uncontrolled moderate-to-severe allergic asthma.MethodsIn this post hoc analysis, data from adolescents aged 12 to 17 years from 8 randomized trials of omalizumab were pooled (studies 008, 009, and 011, and SOLAR, INNOVATE, ALTO, ETOPA, and EXTRA). Changes from baseline to end of study in forced expiratory volume in 1 second (FEV₁), percent predicted FEV₁ (ppFEV₁), forced vital capacity (FVC), and blood eosinophil counts were assessed by fitting an analysis of covariance model and calculating least squares mean (LSM) difference for omalizumab vs placebo.ResultsA total of 340 adolescents were identified (omalizumab, n = 203 [59.7%]; placebo, n = 137 [40.3%]). Omalizumab increased all baseline lung function variables more than placebo by end of study: LSM treatment differences (95% confidence interval) were 3.0% (0.2%-5.7%; P = .035), 120.9 mL (30.6-211.2 mL; P = .009), and 101.5 mL (8.3-194.6 mL; P = .033) for ppFEV₁, absolute FEV₁, and FVC, respectively. The LSM difference demonstrated a greater reduction in eosinophil counts for omalizumab vs placebo: −85.9 cells/μL (−137.1 to −34.6 cells/μL; P = .001).ConclusionOmalizumab was associated with lung function improvements and circulating eosinophil counts reductions in adolescents with moderate-to-severe uncontrolled asthma. Findings emphasize the effect of omalizumab in young patients and the need to optimize treatment early in the disease course. https://clinicaltrials.gov/: NCT00314574, NCT00046748, NCT00401596     

Two inflammatory phenotypes of nasal polyps and comorbid asthma

Background

Nasal polyps and comorbid asthma (NPCA) is a common united airway disease. However, the inflammatory phenotyes of NPCA are not clear.

Rapid onset of effect of benralizumab on morning peak expiratory flow in severe,uncontrolled asthma

BackgroundBenralizumab is a unique eosinophil-depleting monoclonal antibody that significantly reduces asthma exacerbations, improves lung function and asthma symptoms, and permits the reduction of maintenance oral corticosteroid dosage for patients with severe, uncontrolled eosinophilic asthma.ObjectiveTo assess benralizumab's onset of action and efficacy by examining change in morning peak expiratory flow (PEF) after initiation of treatment in the phase 3 clinical trials SIROCCO, CALIMA, and ZONDA.MethodsMixed-model repeated-measures analysis was used to calculate PEF using daily least squares mean changes from baseline in morning PEF as well as differences between the benralizumab every 8 weeks (first 3 doses every 4 weeks) and placebo groups. A Bayesian nonlinear mixed-effects approach with an exponential relationship was used to model trial data to determine time to clinically meaningful improvement in morning PEF (defined as ≥25 L/min).ResultsLeast squares mean morning PEF improvement from baseline was numerically greater by Day 2 after initiation of benralizumab therapy in all 3 trials. The Bayesian nonlinear mixed-effects model indicated that PEF improvement reached the clinically meaningful threshold within 3 weeks in SIROCCO and CALIMA and 2 weeks in ZONDA.ConclusionIn 3 phase 3 randomized clinical trials, benralizumab provided notable improvement in morning PEF 2 days after initiation and clinically meaningful improvements within 3 weeks for patients with severe, uncontrolled eosinophilic asthma. The rapid improvement in PEF demonstrated in these trials suggests that benralizumab's unique mechanism of action rapidly improves lung function for patients with severe, eosinophilic asthma.Trial RegistrationClinicalTrials.gov Identifiers: NCT01928771 (SIROCCO), NCT01914757 (CALIMA), and NCT02075255 (ZONDA).     

Tezepelumab improves patient-reported outcomes in patients with severe,uncontrolled asthma in PATHWAY

BackgroundPatients with severe, uncontrolled asthma experience frequent exacerbations and hospitalization, leading to poor health-related quality of life. In the phase 2b PATHWAY study (NCT02054130), tezepelumab reduced exacerbations by up to 71% and improved lung function, asthma control, and health-related quality of life vs placebo.ObjectiveThis analysis further assessed the impact of tezepelumab on patient-reported outcomes (PROs) in PATHWAY.MethodsAdults with severe, uncontrolled asthma were randomized to subcutaneous tezepelumab (70 mg every 4 weeks, 210 mg every 4 weeks, or 280 mg every 2 weeks) or placebo for 52 weeks. PROs were assessed using the asthma control questionnaire–6 (ACQ-6) and the asthma quality of life questionnaire (standardized) for patients aged 12 years or older (AQLQ[S]+12). The proportions of responders (defined by improvements of ≥0.5 in ACQ-6 or AQLQ(S)+12 scores) and patients whose asthma was well-controlled, partially-controlled, or uncontrolled in the tezepelumab and placebo groups were identified. The Asthma Daily Diary questionnaire was used to assess changes in overall symptom severity.ResultsOverall, 550 patients were randomized. Up to 82% and 77% of tezepelumab-treated patients were ACQ-6 and AQLQ(S)+12 responders, respectively, compared with 70% and 64% of placebo-treated patients, respectively. The proportions of patients with well-controlled or partially-controlled asthma were higher in the tezepelumab-treated group than in the placebo group. In addition, tezepelumab improved the overall symptom severity.ConclusionTezepelumab treatment improved PROs vs placebo, as indicated by the higher proportion of ACQ-6 and AQLQ(S)+12 responders and improvements in symptom severity in the tezepelumab dose groups. These data further support the benefits of tezepelumab in patients with severe, uncontrolled asthma.     

Adult-onset eosinophilic airway diseases

Eosinophilic airway inflammation is one of the cardinal features of allergic airway diseases such as atopic asthma and allergic rhinitis. These childhood-onset conditions are mediated by allergen and allergen-specific IgE and often accompanied by other allergic diseases including food allergy and eczema. They can develop consecutively in the same patient, which is referred to as an allergic march. In contrast, some phenotypes of asthma, nonsteroidal anti-inflammatory drugs-exacerbated airway disease (N-ERD), chronic rhinosinusitis with nasal polyps (CRSwNP)/eosinophilic CRS and allergic bronchopulmonary aspergillosis/mycosis (ABPA/ABPM) are adult-onset airway diseases, which are characterized by prominent peripheral blood eosinophilia. Most of these conditions, except for ABPA/ABPM, are nonatopic, and the coexistence of multiple diseases, including an adult-onset eosinophilic systemic disease, eosinophilic granulomatosis with polyangiitis (EGPA), is common. In this review, we focus on eosinophil biology, genetics and clinical characteristics and the pathophysiology of adult-onset eosinophilic asthma, N-ERD, CRSwNP/eosinophilic CRS, ABPA/ABPM and EGPA, while exploring the common genetic, immunological and pathological conditions among these adult-onset eosinophilic diseases.     

Cysteinyl leukotriene expression in chronic hyperplastic sinusitis-nasal polyposis: importance to eosinophilia and asthma

BACKGROUND: Chronic hyperplastic eosinophilic sinusitis (CHS) results from the unregulated proliferation of eosinophils, T(H)2-like lymphocytes, goblet cells, mast cells, and fibroblasts and is present in most patients with asthma. The frequent coexpression of these disorders and their shared pathophysiology suggests that these are similar disorders affecting the upper and lower airways. OBJECTIVE: We evaluated the expression of cysteinyl leukotrienes (CysLTs) in sinus tissue from subjects with CHS compared with that seen in healthy sinus tissue. METHODS: Nasal polyp and sinus tissue was evaluated from 58 individuals undergoing elective functional endoscopic sinus surgery. The diagnosis of CHS was demonstrated through the presence of eosinophilia and activated (EG2(+)) eosinophils, as determined by means of tissue immunohistochemistry. Data were compared with those from both nasal polyp tissue without eosinophilic inflammation and healthy control sinus tissue obtained from the sinus ostiomeatal complex at the time of surgery for unrelated disorders. CysLTs were quantified by means of ELISA in lipid-extracted tissue. Activation of the metabolic pathway leading to CysLT synthesis was demonstrated by ribonuclease protection. Subjects were genotyped for leukotriene C(4) (LTC(4)) synthase C-to-A promoter polymorphism. RESULTS: CysLT concentrations were significantly higher in tissue obtained from subjects with CHS (776.7 +/- 201.9 pg/g tissue) compared with that seen in healthy sinus tissue (355.7 +/- 101.6 pg/g tissue, P <.03). CysLT concentrations within noneosinophilic nasal polyps (328.0 +/- 116.4 pg/g tissue) were similar to those in control tissue. The presence of CysLTs in CHS was associated with increased expression of LTC(4) synthase mRNA. The C-to-A promoter polymorphism was associated with trends toward the increased presence of CHS and CysLTs. CONCLUSIONS: CHS is characterized by the increased presence of CysLTs when compared with concentrations seen in tissue from patients with chronic inflammatory sinusitis or healthy sinus tissue. These studies support the use of LT modifiers as anti-inflammatory agents that might have clinical benefit in patients with these disorders.     

Validation of a single survey that can be used for case identification and assessment of asthma control: the Breathmobile Program.

BACKGROUND: Underdiagnosis of asthma and underrecognition of disease severity in lower socioeconomic populations continue to be significant health care concerns despite national efforts to better educate health care providers. OBJECTIVE: To validate a 1-page survey as a point-in-time tool identifying uncontrolled vs controlled asthma and moderate-to-severe disease activity in an urban, lower-socioeconomic pediatric population. METHODS: A previously validated survey (the Breathmobile Case Identification Survey) was evaluated as a point-in-time tool for identifying children with poorly controlled disease. Clinical validation was achieved in children (n = 1,826) presenting to a school-based asthma program for either an initial (n = 666) or a follow-up (n = 1,170) visit. Responses were compared with a comprehensive evaluation by a physician specialist as the gold standard. Response patterns were used to construct multimodel tiered scoring algorithms for baseline and follow-up visits that identify children with uncontrolled asthma, and children are likely to have moderate-to-severe disease activity at that time. RESULTS: Surveys scored using the developed algorithms identified children with uncontrolled asthma (sensitivity: baseline, 77.0%; follow-up, 71.6%; specificity: baseline, 72.7%; follow-up, 71.5%) and detected moderate-to-severe disease activity (sensitivity: baseline, 69.2%; follow-up, 77.4%; specificity: baseline, 70.2%; follow-up, 70.3%). CONCLUSIONS: The Breathmobile Case Identification Survey can be used in lower-socioeconomic, urban populations as a point-in-time tool for identifying children with uncontrolled vs controlled asthma and moderate-to-severe disease activity.