Inflammasome activation is one of the first steps in initiating innate immune responses. In this work, we studied the activation of inflammasomes in the airways of critically ill COVID-19 patients and the effects of N-acetylcysteine (NAC) on inflammasomes. Tracheal biopsies were obtained from critically ill patients without COVID-19 and no respiratory disease (control, n = 32), SARS-CoV-2 B.1 variant (n = 31), and B.1.1.7 VOC alpha variant (n = 20) patients. Gene expression and protein expression were measured by RT-qPCR and immunohistochemistry. Macrophages and bronchial epithelial cells were stimulated with different S, E, M, and N SARS-CoV-2 recombinant proteins in the presence or absence of NAC. NLRP3 inflammasome complex was over-expressed and activated in the COVID-19 B.1.1.7 VOC variant and associated with systemic inflammation and 28-day mortality. TLR2/MyD88 and redox NOX4/Nrf2 ratio were also over-expressed in the COVID-19 B.1.1.7 VOC variant. The combination of S-E-M SARS-CoV-2 recombinant proteins increased cytokine release in macrophages and bronchial epithelial cells through the activation of TLR2. NAC inhibited SARS-CoV-2 mosaic (S-E-M)-induced cytokine release and inflammasome activation. In summary, inflammasome is over-activated in severe COVID-19 and increased in B.1.1.7 VOC variant. In addition, NAC can reduce inflammasome activation induced by SARS-CoV-2 in vitro, which may be of potential translational value in COVID-19 patients.
Primary ciliary dyskinesia (PCD) is a rare disease resulting from a defect in ciliary function that generates, among other issues, chronic upper and lower respiratory tract infections. European guidelines recommend studying ciliary function (pattern (CBP) and frequency (CBF)), together with characteristic clinical symptoms, as one of the definitive tests. However, there is no “gold standard”. The present study aims to use high-speed video microscopy to describe how CBF and CBP alter over time and at different temperatures to reduce the error rate in the diagnosis of PCD. Samples of nasal epithelium from 27 healthy volunteers were studied to assess CBF and CBP at 0, 3, 24, 48, and 72 h, at room temperature and 4 °C. It was observed that CBF increased while CBP became dyskinetic, both at room temperature and at 4 °C, as time passed, especially after 3 h. In order to preserve all ciliary function parameters and to perform a reliable analysis to improve the diagnostic process of PCD, analysis should be performed within the first 3 h of sample collection, preferably in reference centers.
(1) Background: Factors influencing the quality of life (QoL) of patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) are poorly understood. We set out to determine the predictive factors on patients’ QoL using the Sino-Nasal Outcome Test-22 (SNOT-22); (2) Methods: An ambispective analysis of data from patients diagnosed with CRSwNP in our institution. All the patients underwent a nasal polyp biopsy and completed the SNOT-22 questionnaire. Demographic and molecular data as well as the SNOT-22 scores were collected. Patients were classified in six subgroups considering the presence of asthma, non-steroidal drugs (NSAID) intolerance and corticosteroid resistance; (3) Results: The mean SNOT-22 score was 39. Considering the clinical parameters, the SNOT-22 value was significantly associated with NSAID intolerance (p = 0.04) and the endoscopic polyp score (p = 0.04). A high SNOT-22 value was also correlated with high tissue eosinophilia (p = 0.01) and high IL-8 expression; (4) Conclusions: Eosinophilia, IL-8 expression and NSAID intolerance can be used as predictors of worse QoL in patients with CRSwNP.