Immune endotyping and gene expression profile of patients with chronic rhinosinusitis with nasal polyps in the aspirin-exacerbated respiratory disease (AERD) and the non-AERD subgroups.

BACKGROUND: Chronic Rhinosinusitis (CRS) is a paranasal sinus inflammatory disease and is divided into two subgroups defined as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP displays a T helper (Th)2 biased phenotype, and based on sensitivity or tolerance to aspirin or non-steroidal anti-inflammatory drugs (NSAID), is further subdivided into Aspirin-exacerbated respiratory disease (AERD) and non-AERD groups. Considering the challenge of diagnosis and treatment in patients with CRSwNP, particularly the AERD subtype, and the significance of endotyping in these patients, we examined the immune profile and endotyping based on gene expression analysis in the AERD and the non-AERD groups of patients with CRSwNP. MATERIAL AND METHOD: In this study, 21 patients were enrolled and were categorized into AERD (N = 10) and non-AERD (N = 11) groups based on their sensitivity to aspirin. After the special washing period, nasal polyps were biopsied in both groups, and the infiltration of eosinophils, neutrophils, plasma cells, and lymphocytes was compared between the AERD and the non-AERD groups. Also, gene expression levels of transcription factors including Tbet, GATA3, RoRγt, and FoxP3 and inflammatory cytokines including interleukin (IL)1ß, IL1RAP (IL1 receptor accessory protein), IL2, IL4, IL5, IL10, IL13, IL17, TNFα, and IFNγ were investigated by quantitative Real-time PCR (qRT-PCR). Statistical analyses were performed using analytical tests including Kolmogorov-Smirnov, Mann-Whitney, and T-test. A P value less than 0.05 was considered statistically significant. RESULTS: The mean ± SD age of the studied groups was 37 ± 8.7 years old (21-50) for the AERD, and 40.4 ± 7.7 years old (31-52) for the non-AERD. LMS/EPOS/SNOT scores and pulmonary function tests showed no difference between the two groups. Serum immunoglobulin E (IgE) levels were found to be higher in patients with AERD (p = 0.04), however, the peripheral blood counts of eosinophils were comparable in the two groups. In the histopathologic analysis, the AERD group showed higher percentages of eosinophils (p = 0.04), neutrophils (p = 0.04), and plasma cells (p = 0.04) than the non-AERD group. Additionally, the gene expression levels of GATA3 (p = 0.001), IL4 (p = 0.04), IL5 (p = 0.007), and IL17 (p = 0.03) were significantly higher in the AERD than the non-AERD groups. CONCLUSION: Higher gene expression levels of GATA3, IL4, IL5, and IL17 were observed in the AERD group compared with the non-AERD group. These findings point to distinct patterns of inflammation in patients with AERD, with a predominance of Th2 inflammation.

Doxycycline Improves Quality of Life and Anosmia in Chronic Rhinosinusitis With Nasal Polyposis: A Randomized Controlled Trial.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex disorder and effective treatment remains a major challenge. Some antibiotics with anti-inflammatory properties are reported to have potential to be used as an adjunct therapy in the management of chronic airway inflammation. OBJECTIVE: The aim of this study was to evaluate the efficacy of doxycycline in CRSwNP. METHODS: In this randomized, double-blind, placebo-control study, we assessed the efficacy of doxycycline in patients with moderate to severe CRSwNP. A total of 100 patients were randomly assigned to receive either doxycycline (200 mg on the first day followed by 100 mg daily) or placebo for 6 weeks. All patients received baseline therapy with fluticasone, montelukast, and nasal irrigation during the study. The primary outcome was quality of life based on the sino-nasal outcome test (SNOT-22) questionnaire. We measured peak nasal inspiratory flow (PNIF) and severity of symptoms by visual analogue scale (VAS). Baseline blood eosinophil count, serum IgE level, eosinophil in nasal secretions, and Lund-Mackay score based on low dose paranasal CT scan were also recorded. RESULTS: Treatment with doxycycline significantly improved SNOT-22 (P = .037) and sense of smell (P = .048). The baseline SNOT-22 score had no effect on outcomes. The effect of doxycycline on quality of life in patients with or without nasal eosinophilia was not significantly different. Change in SNOT-22 score was also not correlated with serum IgE (P = .220, r = -0.186) and the eosinophil count (P = .190, r = -0.198). CONCLUSION: Doxycycline improves the quality of life in patients with CRSwNP. It also has temporarily beneficial effects in improving the sense of smell. The levels of eosinophil in the blood and nasal secretions do not affect the response to treatment. Hence, doxycycline can be used in both eosinophilic and non-eosinophilic nasal polyps.This study was registered at Iranian Registry of Clinical Trials. https://www.irct.ir/ IRCTID: IRCT20210403050817N1.

The Uncomplicated Course of COVID-19 in Primary Immunodeficiency Patients: A Report of 14 Common Variable Immunodeficiency Patients.

Coronavirus disease 2019 (COVID-19) affects millions of people worldwide. Clinical manifestations range from asymptomatic to severe viral pneumonia. CVID patients with COVID-19 infection are not adequately studied. In some studies, CVID patients had higher mortality rates, although other studies showed that CVID patients might have an uncomplicated COVID-19 infection. We describe 14 cases of COVID-19 infection in Iranian CVID patients in this study, including clinical manifestations, laboratory findings, and treatment strategies. There were 29% of patients with mild disease, 43% with moderate disease, and 29% with severe disease in this study. A critical case and a death occurred in none of our patients. There were six cases of infection more than two weeks after receiving the second dose of Sinopharm BIBP COVID-19 vaccine; all had mild to moderate disease. Among these patients, Remdesivir was the most frequently prescribed medication. According to this study, most of our patients presented with an uncomplicated disease course.

Immunodeficiency, Centromeric Region Instability, and Facial Anomalies Syndrome (ICF) in a Boy with Variable Clinical and Immunological Presentations.

Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare primary immunodeficiency disorder characterized by recurrent infections and low immunoglobulin levels due to variable combined immunodeficiency, and centromeric region instability, and facial dysmorphism. We describe a 12-year-old boy with recurrent respiratory tract infections, facial anomalies, scoliosis, and psychomotor retardation. He had recurrent pneumonia with low serum IgG and IgM levels during infancy and preschool age. Later at the age of 10, he developed recurrent ear infections. An IgA and IgM deficiency was found accompanied by a normal B-cell and T-cell count as well as an impaired candida-induced T-cell proliferation. Further evaluations revealed a missense mutation in the DNMT3B gene on chromosome 20. Chromosomal analysis showed a sunburst multi-radial feature on chromosome 1, which is a hallmark of ICF syndrome. The genetic mutation and chromosomal abnormality along with clinical findings are compatible with the diagnosis of ICF syndrome. To the best of our knowledge, this is the first time that scoliosis is observed in an ICF patient. The additional variable clinical symptoms in the case were the presence of spastic gait as well as hypogammaglobulinemia with immunoglobulin isotype switch at different ages.