Erythromycin reduces nasal inflammation by inhibiting immunoglobulin production, attenuating mucus secretion, and modulating cytokine expression

Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) share some similar pathological mechanisms. In current study, we intend to investigate the impact of AR on CRS. In addition, we explored the efficacy of erythromycin (EM) treatment on CRS mice with or without AR (CRSwoAR, CRSwAR). Study subjects were divided into control, CRSwoAR, and CRSwAR groups. Experimental mice were divided similarly into control, CRSwoAR, and CRSwAR groups. In addition, CRS mice were treated with EM at 0.75, 7.5, or 75 mg/kg or with dexamethasone (Dex) at 1 mg/kg. In our results, allergy exacerbates inflammation that was evident in nasal histology and cytokine expression both in patients and in mice with CRS. Dex 1 mg/kg, EM 7.5 or 75 mg/kg treatments significantly inhibited serum IgE and IgG2a in CRS mice. EM-treated CRS mice had significantly elevated IL-10 levels and had a reversal of Th-1/Th-2 cytokine expression in nasal-associated lymphoid tissue. MUC5AC expressions were significantly reduced in the 7.5 or 75 mg/kg EM-treated mice compared with untreated mice. EM showed inhibitions on immunoglobulin production and mucus secretion stronger than Dex. We concluded that comorbid AR enhanced inflammation of CRS. EM and Dex treatments showed similar anti-inflammatory effects on CRS but through partly different mechanisms.

COVID-19-related headache and sinonasal inflammation: A longitudinal study analysing the role of acute rhinosinusitis and ICHD-3 classification difficulties in SARS-CoV-2 infection

Background The genesis of headache in coronavirus disease 2019 (COVID-19) is currently unclear and the multitude of disease symptoms often further hinders locating the source of pain. Interestingly, many subjects with COVID-19 have symptoms of acute rhinosinusitis. The relation between nasal symptoms and headache in SARS-CoV-2 infection remains unknown. Methods This bi-center longitudinal study evaluated symptoms in consecutive COVID-19 patients in the participating practices. The first assessment was performed during the initial consultation after infection confirmation. That was followed up by a second consultation after a median 9 days. Results 130 patients were included in the study (80 women, 50 men; mean age 46.9 years). Headache was highly prevalent at the first visit (72%) and significantly associated with acute rhinosinusitis symptoms. The odds ratio for headache in subjects with rhinosinusitis was 3.5. Headache could be attributed to systemic viral infection in 96% and to acute rhinosinusitis in 51% of cases according to 3rd edition of the International Classification of Headache Disorders. Criterium C.3 (exacerbation of headache by pressure applied over paranasal sinuses) and C.4 (ipsilaterality of headache and sinusitis) had low sensitivity in headache attributed to acute rhinosinusitis. Conclusions Nasal inflammation is associated with headache in COVID-19, although the pain mechanism lies probably in a systemic reaction to the virus. 3rd edition of the International Classification of Headache Disorders criteria for headache attributed to acute rhinosinusitis need adjusting to the current understanding of acute sinonasal infection.

Cold bubble humidification of low-flow oxygen does not prevent acute changes in inflammation and oxidative stress at nasal mucosa

Some clinical situations require the use of oxygen therapy for a few hours without hypoxemia. However, there are no literature reports on the effects of acute oxygen therapy on the nasal mucosa. This study aimed to evaluate the acute effects of cold bubble humidification or dry oxygen on nasal Inflammation, oxidative stress, mucociliary clearance, and nasal symptoms. This is a randomized controlled cross-sectional study in which healthy subjects were randomly allocated into four groups: (1) CA + DRY (n = 8): individuals receiving dry compressed air; (2) OX + DRY (n = 8): individuals receiving dry oxygen therapy; (3) CA + HUMID (n = 7): individuals receiving cold bubbled humidified compressed air; (4) OX + HUMID (n = 8): individuals receiving cold bubbled humidified oxygen therapy. All groups received 3 L per minute (LPM) of the oxygen or compressed air for 1 h and were evaluated: total and differential cells in the nasal lavage fluid (NLF), exhaled nitric oxide (eNO), 8-iso-PGF2α levels, saccharin transit test, nasal symptoms, and humidity of nasal cannula and mucosa. Cold bubble humidification is not able to reduced nasal inflammation, eNO, oxidative stress, mucociliary clearance, and nasal mucosa moisture. However, subjects report improvement of nasal dryness symptoms (P < 0.05). In the conclusion, cold bubble humidification of low flow oxygen therapy via a nasal cannula did not produce any effect on the nasal mucosa and did not attenuate the oxidative stress caused by oxygen. However, it was able to improve nasal symptoms arising from the use of oxygen therapy.

Association Between Microbiota and Nasal Mucosal Diseases in terms of Immunity

The pathogenesis of nasal inflammatory diseases is related to various factors such as anatomical structure, heredity, and environment. The nasal microbiota play a key role in coordinating immune system functions. Dysfunction of the microbiota has a significant impact on the occurrence and development of nasal inflammation. This review will introduce the positive and negative roles of microbiota involved in immunity surrounding nasal mucosal diseases such as chronic sinusitis and allergic rhinitis. In addition, we will also introduce recent developments in DNA sequencing, metabolomics, and proteomics combined with computation-based bioinformatics.

Validity and Reliability of The Indonesian Modification of Score for Allergic Rhinitis

Allergic rhinitis (AR) is a nasal inflammation caused by IgE-mediated reacions after inhaled the allergens. It’s characterized as symptoms of sneezing, airflow obstruction, nasal pruritus, and often clear nasal discharge. The prevalence of AR is about 5-40% in the general population and still rising. Multiple non-instrumental tests for AR were reported though few were validated. Score for Allergic Rhinitis (SFAR) is a valid instrument to screening AR. The purpose of this study was to perform adaptation and cultural translation and validation of the SFAR questionnaire for the Indonesian language. This was a cross sectional study to assess the validity and reliability of the Indonesian modification of Score for Allergic Rhinitis. The study conduct in 59 subjects. The Indonesian modification of SFAR instrument is valid and reliable as an instrument for screening AR with r values ranging from 0.345 to 0.730. Internal consistency shows that Cronbach's alpha is 0.803. The validation and reliability test of Indonesian modification of Score for Allergic Rhinitis was performed and valid and reliable as an instrument for assessing allergic rhinitis. Keywords: Allergic Rhinitis, Score for Allergic Rhinitis, Validity, Indonesian Version.

The effect of coronaviruses on olfaction: systematic review

BACKGROUND: Unlike other respiratory viruses, SARS-CoV-2 causes anosmia without sinonasal inflammation. Here we systematically review the effects of the 7 known human coronaviruses on olfaction to determine if SARS-CoV-2 distinctly affects the olfactory system. METHOD: PubMed, EMBASE, Web of Science, bioRxiv, medRxiv and DOAJ were searched for studies describing pathophysiological, immunohistochemical, cytological and clinical data. RESULTS: 49 studies were included. Common cold coronaviruses lead to sinonasal inflammation which can cause transient and chronic loss of smell. MERS-CoV entry receptors were not found in the nasal mucosa and it did not impair olfaction. SARS-CoV-1 had low affinity for its receptor ACE2, limiting olfactory effects. Anosmia is frequent in SARS-CoV-2 infections. SARS-CoV-2’s entry factors ACE2 and TMPRSS2 are expressed in the nasal respiratory epithelium and olfactory supporting cells. SARS-CoV-2 appeared to target the olfactory cleft while diffuse nasal inflammation was not observed. Damage of the olfactory epithelium was observed in animal models. Alternative receptors such as furin and neuropilin-1 and the similarity of viral proteins to odourant receptors could amplify olfactory impairment in SARS-CoV-2 infection. CONCLUSIONS: The pathophysiology of anosmia in SARS-CoV-2 infection is distinct from other coronaviruses due to preferentially targeting olfactory supporting cells. However, SARS-CoV-2 does not cause sinonasal inflammation in spite of preferred entry factor expression in the nasal respiratory epithelium. This raises doubts about the attention given to ACE2. Alternative receptors, odourant receptor mimicry and other as yet unknown mechanisms may be crucial in the pathogenesis of anosmia in SARS-CoV-2 infection. Further studies are warranted to investigate infection mechanisms beyond ACE2.

Sex-dependent differences in the gut microbiota following chronic nasal inflammation in adult mice

A growing body of evidence suggests a relationship between olfactory dysfunction and the pathogenesis of mental disorders. Our previous studies indicated that chronic nasal inflammation caused loss of olfactory sensory neurons and gross atrophy of the olfactory bulb, which may lead to olfactory dysfunction. Simultaneously, increasing numbers of reports have elucidated the importance of gut microbiota to maintain brain function and that dysbiosis may be associated with neuropsychiatric disorders. Here we examined whether chronic nasal inflammation perturbed gut microbiota and whether there were sex differences in this pattern. Eight-week-old C57BL/6 mice repeatedly received bilateral nasal administration of lipopolysaccharide (LPS) 3 times/week to cause chronic nasal inflammation or saline as a control. At 9 weeks, cecal feces were used for 16S metagenomic analysis and whole blood and fresh tissue of spleen were used for ELISA analyses. Microbiome analysis demonstrated a remarkable change of the gut microbiota in male mice with chronic nasal inflammation which was different from that in female mice. In both mice, systemic inflammation did not occur. This has shown for the first time that chronic nasal inflammation correlates with sex-dependent changes in the gut microbiota. The detailed mechanism and potential alteration to brain functions await further studies.

Lung adenocarcinoma and sequential antineutrophil cytoplasmic antibody-associated vasculitis: a case report

The relationship between antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and lung cancer remains unclear. A 66-year-old man presented with pulmonary nodules. Histological examination of a specimen from computed tomography-guided percutaneous transthoracic biopsy revealed adenocarcinoma. The patient was treated using cryoablation and systemic chemotherapy. Sixteen months later, the patient presented with fever, nasal inflammation, recurrent lung lesions, elevated serum creatinine levels, and high levels of ANCA. Histological examination of a specimen from ultrasound-guided percutaneous renal biopsy revealed pauci-immune necrotizing crescentic glomerulonephritis. The patient responded to treatment, but granulomatosis with polyangiitis recurred and he later died. This case highlights the possibility of sequential AAV with lung cancer. Although this is relatively rare, further research is needed to better understand the association or pathophysiological link between lung cancer and AAV.