Defining the Efficacy of Omalizumab in Nasal Polyposis: A POLYP 1 and POLYP 2 Subgroup Analysis

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease with variable underlying pathophysiologies. Numerous patient factors have been linked to differences in disease severity, control, and response to treatment, including asthma status, aspirin sensitivity, previous sinonasal surgery, and blood eosinophil levels. Objective The present study examines the efficacy of the anti-immunoglobulin E therapy, omalizumab, versus placebo in patients with CRSwNP from the replicate POLYP 1 (NCT03280550) and POLYP 2 (NCT03280537) trials, grouped by inherent patient characteristics to determine the response to therapy. Methods Patients in prespecified subgroups from POLYP 1 and POLYP 2 (studies pooled for analysis) were examined. Subgroups included blood eosinophil count at baseline (>300 or ≤300 cells/μL), previous sinonasal surgery (yes or no), asthma status (yes or no), and aspirin sensitivity status (yes or no). Subgroups were examined for subgroup-specific adjusted mean difference (95% confidence interval [CI]) (omalizumab–placebo) in change from baseline at week 24 in Nasal Congestion Score (NCS), Nasal Polyp Score (NPS), Sino-Nasal Outcome Test-22 (SNOT-22), Total Nasal Symptom Score (TNSS), and University of Pennsylvania Smell Identification Test (UPSIT). Results Adjusted mean difference (95% CI) (omalizumab–placebo) in NCS, NPS, SNOT-22, TNSS, and UPSIT change from baseline at week 24 consistently favored omalizumab treatment over placebo in patients with blood eosinophil count >300 and ≤300 cells/μL, with or without previous sinonasal surgery, asthma, and aspirin sensitivity. Conclusion Together, these data suggest broad efficacy of omalizumab across clinical and patient-reported outcomes in patients with CRSwNP, independent of the underlying patient factors examined, including those with high eosinophil levels and those who have undergone previous surgery, which are associated with high recurrence. Clinical Trial Registration ClinicalTrials.gov identifiers: POLYP 1: ClinicalTrials.gov identifier NCT03280550 ( https://clinicaltrials.gov/ct2/show/NCT03280550 ); POLYP 2: ClinicalTrials.gov identifier NCT03280537 ( https://clinicaltrials.gov/ct2/show/NCT03280537 ).

Plasma Brain-Derived Neurotrophic Factor (BDNF) Concentration and BDNF/TrkB Gene Polymorphisms in Croatian Adults with Asthma

Brain-derived neurotrophic factor (BDNF) and its tropomyosin-related kinase B (TrkB) receptor might contribute to normal lung functioning and immune responses; however, their role in asthma remains unclear. Plasma BDNF concentrations, as well as BDNF and NTRK2 (TrkB gene) polymorphisms, were investigated in 120 asthma patients and 120 healthy individuals using enzyme-linked immunosorbent assay and polymerase chain reaction, respectively. The genotype and allele frequencies of BDNF Val66Met (rs6265) and NTRK2 rs1439050 polymorphisms did not differ between healthy individuals and asthma patients, nor between patients grouped according to severity or different asthma phenotypes. Although plasma BDNF concentrations were higher among healthy subjects carrying the BDNF Val66Met GG genotype compared to the A allele carriers, such differences were not detected in asthma patients, suggesting the influences of other factors. Plasma BDNF concentration was not affected by NTRK2 rs1439050 polymorphism. Asthma patients had higher plasma BDNF concentrations than control subjects; however, no differences were found between patients subdivided according to asthma severity, or Type-2, allergic, and eosinophilic asthma. Higher plasma BDNF levels were observed in asthma patients with aspirin sensitivity and aspirin-exacerbated respiratory disease. These results suggest that plasma BDNF may serve as a potential peripheral biomarker for asthma, particularly asthma with aspirin sensitivity.

Aspirin Sensitivity in Patients with Moderate to Severe Asthma

Asthma induced by ingestion of aspirin occurs when symptoms arise within 30 minutes to three hours after aspirin consumption. Previous data indicate that sensitivity to aspirin may be associated with poorly controlled asthma. This study aims to evaluate the frequency of aspirin sensitivity in patients with moderate to severe asthma receiving conventional asthma therapy. This clinical trial was conducted on 65 patients aged 18 to 65 years with moderate to severe asthma from February 2015 to February 2016 at the Allergy Department, Hazrat-e-Rasoul Hospital, Iran University of Medical Sciences, Tehran. To assess treatment responses in patients, forced expiratory volume in the first second (FEV1) and asthma control test (ACT) scores were measured at baseline and after 3 months. The results of the oral aspirin challenge revealed a prevalence of 35.38% for sensitivity to aspirin. Hypersensitivity reactions to aspirin were detected in 60.9% of the patients with moderate asthma and 39.1% of the patients with severe asthma. All patients with positive aspirin challenge tests suffered from rhinosinusitis and in 56.5% of cases, history of previous hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) was detected. No meaningful differences were found between those patients with aspirin sensitivity and those with aspirin tolerance neither in mean prebronchodilator FEV1 nor in ACT scores pre- and post-treatment. To conclude, aspirin sensitivity was not found to have an association with an unfavorable response to conventional treatment in patients with uncontrolled asthma.

Epithelial Squamous Metaplasia and Dysplasia in Inflammatory Nasal Polyps: An Observational Study

Nasal polyposis (NP) is characterized by polypoid outgrowths of chronically inflamed respiratory mucosa. The presence of squamous metaplasia and dysplasia on the mucosal surface of nasal polyps (NPs) represents different manifestations of epithelial atypia. The aim of this investigation was to evaluate the presence of epithelial squamous metaplasia and dysplasia in ethmoidal NPs. This retrospective analysis of prospectively collected data involved 212 patients with NP undergoing endoscopic ethmoidectomy. To evaluate possible etiological factors for epithelial atypia, the patients in whom we histopathologically detected the presence of epithelial atypia were compared with patients with “normal” NPs in accordance with the following characteristics as found in the patients’ medical records: gender, age, main symptoms, preoperative extent of sinus disease on computed tomography, atopic status, aspirin sensitivity, cigarette smoking, and occupational exposure to different noxious factors. Epithelial atypia were detected histopathologically in 44 (20.7%) NP patients, whereas features of “true” dysplasia were found in only 1 (0.5%) patient. The presence of atypia was more frequent in males than in females ( P = .008). The association with aspirin-exacerbated respiratory disease and with long-term occupational exposure to different noxious chemicals, especially in workers exposed to salts of heavy metals, was more frequent in NP patients with epithelial atypia than in patients without atypia ( P = .023; P = .006, respectively). Our results suggest epithelial atypia in NPs are associated with aspirin sensitivity and occupational exposure to different noxious chemicals. Although extremely rare, epithelial dysplasia may occasionally be noted in NPs, a fact potentially useful for both rhinologists and pathologists.