COMPARISON OF DEXMEDETOMIDINE AND FENTANYL ON AIRWAY RESPONSE AND HEMODYNAMICS DURING TRACHEAL EXTUBATION

Background: Extubation is associated with various circulatory and airway responses. Various pharmacological measures including fentanyl and dexmedetomidine have been used to blunt the reflex without compromising the spontaneous respiration. In this study we wanted to compare dexmedetomidine and fentanyl on airway response, smoothness of extubation and hemodynamic changes. Methodology: A total of 68 patients undergoing surgery under general anesthesia with endotracheal intubation, were randomized into two groups. Group A received dexmedetomidine 0.5 mcg/kg and Group B received 1 mcg/kg of fentanyl with the start of skin suturing over a period of 10 minutes via syringe pump. Airway reflex during suction and smoothness of extubation were assessed. Level of sedation during suction, extubation and then every 5 minutes post extubation for 15 minutes were recorded. Hemodynamic parameters were assessed every 5 minutes with start of test solution till extubation and then every 5 minutes for 15 minutes. Results: A total of 68 patients were evaluated in the study. In dexmedetomidine group, 67.6% of patients had no cough on extubation while in fentanyl group 35.3% of patients had no cough on extubation which was statistically significant (p value 0.015). Mean heart rate during extubation increased in both the groups but the increase was 39% in Group B and 11% in Group A from baseline which was statistically significant (p value < 0.001). There was rise in mean systolic and mean arterial pressure during extubation in both the groups but the increase was significantly higher in fentanyl group. Patients in dexmedetomidine group were more sedated but there were no any adverse events. Conclusion: With the results obtained from the study, it is concluded that dexmedetomidine 0.5 mcg/kg over 10 minutes before extubation is effective in alleviating airway response and haemodynamics compared to fentanyl 1 mcg/kg.

Effect of dexmedetomidine on hemodynamic and recovery responses during tracheal extubation

Endotracheal extubation is associated with cardiovascular and airway responses leading to tachycardia, hypertension, arrhythmias, myocardial ischemia, coughing, agitation, bronchospasm, increased bleeding, raised intracranial and intraocular pressure which may be life threatening especially in vulnerable patients. Dexmedetomidine, a highly selective α2-adrenoreceptor agonist is found to attenuate these effects and provide a smooth extubation. To assess the effect of dexmedetomidine on hemodynamic and ventilatory recovery during tracheal extubation. This comparative study was done in 42 patients who fulfilled the inclusion and exclusion criteria between the age group of 20 to 45 years from both sexes were randomly allocated in to two groups of 21 each. One group received 0.5mg Dexmedetomidine and the other group received 100 ml NS. Both groups were compared for the hemodynamic parameters at different time intervals during the whole procedure and were compared for differences if any. In the study group, parameters like Mean arterial pressure, Systolic Blood Pressure, Diastolic Blood Pressure and Heart Rate were under control than the control group. The extubation quality score between controls and dexmedetomidine group (2.14 vs. 1.24) is statistically significant (P&#60;0.001). 14.28% of study group had cough compared to 52.39% in the control group. Bradycardia and Hypertension were significantly higher in the study population. Justbefore extubation, administration of dexmedetomidine ensures the smooth extubation of the trachea and reduces the cardiovascular responses. It also provides adequate sedation postoperatively.

Transient IL-33 upregulation in neonatal mouse lung promotes acute but not chronic type 2 immune responses induced by allergen later in life

Early life respiratory insults, such as viral infections or hyperoxia, often increase asthma susceptibility later in life. The mechanisms underlying this increased susceptibility are not fully understood. IL-33 has been shown to be critically involved in allergic airway diseases. IL-33 expression in the neonatal lung can be increased by various respiratory insults associated with asthma development. Therefore, we investigated whether and how early life increases in IL-33 impact allergic airway responses later in life. Using a novel IL-33 transgenic mouse model, in which full-length IL-33 was inducible overexpressed in lung epithelial cells, we transiently upregulated lung IL-33 expression in neonatal mice for one week. After resting for 4–6 weeks, mice were intranasally exposed to a single-dose of recombinant IL-33 or the airborne allergen Alternaria. Alternatively, mice were exposed to Alternaria and ovalbumin multiple times for one month. We found that a transient increase in IL-33 expression during the neonatal period promoted IL-5 and IL-13 production when mice were later exposed to a single-dose of IL-33 or Alternaria in adulthood. However, increased IL-33 expression during the neonatal period did not affect airway inflammation, type 2 cytokine production, lung mucus production, or antigen-specific antibody responses when adult mice were exposed to Alternaria and ovalbumin multiple times. These results suggest that transient increased IL-33 expression early in life may have differential effects on allergic airway responses in later life, preferentially affecting allergen-induced acute type 2 cytokine production.

Type 2 and interferon inflammation regulate SARS-CoV-2 entry factor expression in the airway epithelium

Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, an emerging virus that utilizes host proteins ACE2 and TMPRSS2 as entry factors. Understanding the factors affecting the pattern and levels of expression of these genes is important for deeper understanding of SARS-CoV-2 tropism and pathogenesis. Here we explore the role of genetics and co-expression networks in regulating these genes in the airway, through the analysis of nasal airway transcriptome data from 695 children. We identify expression quantitative trait loci for both ACE2 and TMPRSS2, that vary in frequency across world populations. We find TMPRSS2 is part of a mucus secretory network, highly upregulated by type 2 (T2) inflammation through the action of interleukin-13, and that the interferon response to respiratory viruses highly upregulates ACE2 expression. IL-13 and virus infection mediated effects on ACE2 expression were also observed at the protein level in the airway epithelium. Finally, we define airway responses to common coronavirus infections in children, finding that these infections generate host responses similar to other viral species, including upregulation of IL6 and ACE2. Our results reveal possible mechanisms influencing SARS-CoV-2 infectivity and COVID-19 clinical outcomes.

Commentary on: The potency of lncRNA MALAT1/miR-155 in altering asthmatic Th1/Th2 balance by modulation of CTLA4

Asthma is a common, allergic respiratory disorder affecting over 350 million people worldwide. One of the key features of asthma is skewing of CD4+ cells toward Th2 responses. This promotes the production of cytokines like IL-4 that induce IgE production resulting in the hypersecretion of mucus and airway smooth muscle contraction. Understanding the factors that favor Th2 expansion in asthma would provide important insights into the underlying pathogenesis of this disorder. Asthma research has focused on signaling pathways that control the transcription of key asthma-related genes. However, increasing evidence shows that post-transcriptional factors also determine CD4+ cell fate and the enhancement of allergic airway responses. A recent paper published by Liang et al. (Bioscience Reports (2020) 40, https://doi.org/10.1042/BSR20190397) highlights a novel role for the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in Th2 development in asthma. MALAT1 modulates several biological processes including alternative splicing, epigenetic modification and gene expression. It is one of the most highly expressed lncRNAs in normal tissues and MALAT1 levels correlate with poor clinical outcomes in cancer. The mechanisms of action of MALAT1 in tumor progression and metastasis remain unclear and even less is known about its effects in inflammatory disease states like asthma. The work of Liang et al. demonstrates heightened MALAT1 expression in asthma and further shows that this lncRNA targets miR-155 to promote Th2 differentiation in this disease. This insight sets the stage for future studies to examine how MALAT1 manipulation could deter allergic immune responses in asthmatic airways.

Type 2 and interferon inflammation strongly regulate SARS-CoV-2 related gene expression in the airway epithelium

Coronavirus disease 2019 (COVID-19) outcomes vary from asymptomatic infection to death. This disparity may reflect different airway levels of the SARS-CoV-2 receptor, ACE2, and the spike protein activator, TMPRSS2. Here we explore the role of genetics and co-expression networks in regulating these genes in the airway, through the analysis of nasal airway transcriptome data from 695 children. We identify expression quantitative trait loci (eQTL) for both ACE2 and TMPRSS2, that vary in frequency across world populations. Importantly, we find TMPRSS2 is part of a mucus secretory network, highly upregulated by T2 inflammation through the action of interleukin-13, and that interferon response to respiratory viruses highly upregulates ACE2 expression. Finally, we define airway responses to coronavirus infections in children, finding that these infections upregulate IL6 while also stimulating a more pronounced cytotoxic immune response relative to other respiratory viruses. Our results reveal mechanisms likely influencing SARS-CoV-2 infectivity and COVID-19 clinical outcomes.