Acute Airway Research Articles

The link between ferroptosis and airway inflammatory diseases: A novel target for treatment.

Ferroptosis is an iron-dependent mode of cell death characterized by intracellular lipid peroxide accumulation and a redox reaction imbalance. Compared with other modes of cell death, ferroptosis has specific biological and morphological features. The iron-dependent lipid peroxidation accumulation is manifested explicitly in the abnormal metabolism of intracellular lipid oxides catalyzed by excessive iron ions with the production of many reactive oxygen species and over-oxidization of polyunsaturated fatty acids. Recent studies have shown that various diseases, which include intestinal diseases and cancer, are associated with ferroptosis, but few studies are related to airway inflammatory diseases. This review provides a comprehensive analysis of the primary damage mechanisms of ferroptosis and summarizes the relationship between ferroptosis and airway inflammatory diseases. In addition to common acute and chronic airway inflammatory diseases, we also focus on the progress of research on COVID-19 in relation to ferroptosis. New therapeutic approaches and current issues to be addressed in the treatment of inflammatory airway diseases using ferroptosis are further proposed.

Targeting an Initiator Allergen Provides Durable and Expansive Protection against House Dust Mite Allergy.

Whereas treatment of allergic diseases such as asthma relies largely on the targeting of dysregulated effector pathways, the conceptually attractive alternative of preventing them by a pharmaceutical, at-source intervention has been stymied until now by uncertainties about suitable targets and the challenges facing drug design. House dust mites (HDMs) are globally significant triggers of allergy. Group 1 HDM allergens, exemplified by Der p 1, are cysteine proteases. Their degradome has a strong disease linkage that underlies their status as risk and initiator allergens acting directly and through bystander effects on other allergens. Our objective was to test whether target-selective inhibitors of group 1 HDM allergens might provide a viable route to novel therapies. Using structure-directed design to optimize a series of pyruvamides, we undertook the first examination of whether pharmaceutically developable inhibitors of group 1 allergens might offer protection against HDM exposure. Developability criteria included durable inhibition of clinically relevant signals after a single aerosolized dose of the drug. The compounds suppressed acute airway responses of rats and mice when challenged with an HDM extract representing the HDM allergome. Inhibitory effects operated through a miscellany of downstream pathways involving, among others, IL-33, thymic stromal lymphopoietin, chemokines, and dendritic cells. IL-13 and eosinophil recruitment, indices of Th2 pathway activation, were strongly attenuated. The surprisingly expansive benefits arising from a unique at-source intervention suggest a novel approach to multiple allergic diseases in which HDMs play prominent roles and encourage exploration of these pharmaceutically developable molecules in a clinical setting.

Interferon-β regulates proresolving lipids to promote the resolution of acute airway inflammation.

Aberrant immune responses, including hyperresponsiveness to Toll-like receptor (TLR) ligands, underlie acute respiratory distress syndrome (ARDS). Type I interferons confer antiviral activities and could also regulate the inflammatory response, whereas little is known about their actions to resolve aberrant inflammation. Here we report that interferon-β (IFN-β) exerts partially overlapping, but also cooperative actions with aspirin-triggered 15-epi-lipoxin A4 (15-epi-LXA4) and 17-epi-resolvin D1 to counter TLR9-generated cues to regulate neutrophil apoptosis and phagocytosis in human neutrophils. In mice, TLR9 activation impairs bacterial clearance, prolongs Escherichia coli-evoked lung injury, and suppresses production of IFN-β and the proresolving lipid mediators 15-epi-LXA4 and resolvin D1 (RvD1) in the lung. Neutralization of endogenous IFN-β delays pulmonary clearance of E. coli and aggravates mucosal injury. Conversely, treatment of mice with IFN-β accelerates clearance of bacteria, restores neutrophil phagocytosis, promotes neutrophil apoptosis and efferocytosis, and accelerates resolution of airway inflammation with concomitant increases in 15-epi-LXA4 and RvD1 production in the lungs. Pharmacological blockade of the lipoxin receptor ALX/FPR2 partially prevents IFN-β-mediated resolution. These findings point to a pivotal role of IFN-β in orchestrating timely resolution of neutrophil and TLR9 activation-driven airway inflammation and uncover an IFN-β-initiated resolution program, activation of an ALX/FPR2-centered, proresolving lipids-mediated circuit, for ARDS.

Nasal nitric oxide is decreased in acute mild COVID-19 and related to viral load

Gaseous nitric oxide levels from the lungs (FeNO) and from the nose (nNO) have been demonstrated to react to acute infection or influenza vaccination. There are no published data on nNO levels during acute COVID-19, but normal levels of FeNO have been reported in one study. Our aim was to assess if acute mild COVID-19 alters nasal or bronchial NO output at the time of acute infection and at a two-month follow up, and if this is related to symptoms or viral load. This study included 82 subjects with mild acute airway infection who did not need hospitalization: 43 cases (reverse transcription polymerase chain reaction (RT-PCR)-positive for SARS-CoV-2 in routine testing from nasopharynx) and 39 age- (±5 years) and gender-matched controls (RT-PCR-negative for SARS-CoV-2). During acute infection, the cases had lower nNO compared to controls (158 [104–206] vs. 232 [203–279] nl min−1; p < 0.001), but after two months, there was no significant difference between the groups (230 [179–290] vs. 268 [222–320] nl min−1; p = 0.162). There was no difference in FeNO between the groups at either of the visits. Nasal NO correlated with the cycle threshold (Ct) value of the nasopharyngeal RT-PCR test for SARS-CoV-2 (Spearman’s r s = 0.550; p < 0.001), that is, nNO was lower with a higher viral load. Nasal NO output was decreased in acute COVID-19 in relation to higher viral load, suggesting that the type and intensity of inflammatory response affects the release of NO from airway mucosa. In these subjects without significant lower airway involvement, there were no clinically relevant findings regarding FeNO.

Competency-Based Medical Training in Anesthesiology: Has It Delivered on the Promise of Better Education?

Competency-Based Medical Training in Anesthesiology: Has It Delivered on the Promise of Better Education?

Role of TRPA1/TRPV1 in acute ozone exposure induced murine model of airway inflammation and bronchial hyperresponsiveness.

BackgroundTransient receptor potential (TRP) ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) mediate the development of lung injury and inflammation. This study investigated the role and mechanism of the TRPA1/TRPV1 pathway in airway inflammation and bronchial hyperresponsiveness (BHR) induced by acute ozone exposure.MethodsC57BL/6 mice (8–10 weeks) were intraperitoneally injected with phosphate buffered saline (PBS), A967079 (TRPA1 inhibitor) or AMG9810 (TRPV1 inhibitor) 1 h before or after ozone exposure (2.5 ppm, 3 h). BHR, cell counts in bronchoalveolar lavage (BAL) fluid, oxidative stress biomarkers, inflammatory cytokines, TRPA1 and TPRV1 protein levels, mitochondrial dynamics- and mitophagy-related protein levels, and activities of mitochondrial respiratory chain (MRC) in lung were measured.ResultsThe preventive treatment effect was similar to the therapeutic treatment effect. Both A967079 and AMG9810 intervention suppressed BHR, inflammatory cytokines, total BAL fluid cells, malondialdehyde (MDA) levels and inflammatory cytokines mRNA including Substance P (SP), Keratinocyte-Derived Chemokine (KC), interleukin-18 (IL-18) and chemokine (C-X-C motif) ligand 8 (CXCL8) expression, and enhanced reduced glutathione (GSH)/oxidized glutathione (GSSG) levels compared with ozone-exposed mice. A967079 and AMG9810 intervention inhibited dynamin-related protein (DRP1), mitochondrial fission factor (MFF), Parkinson protein 2 E3 ubiquitin protein ligase (PARK2) and Sequestosome 1 (SQSTM1)/p62 expression, increased Optic atrophy 1 (OPA1), mitofusin 2 (MFN2) and PTEN-induced putative kinase 1 (PINK1) expression, and up-regulated the activities of MRC complex III and V in lung tissue.ConclusionsThe results show that both TRPA1 and TRPV1 pathways are involved in acute ozone exposure-induced airway inflammation and BHR and influence oxidative stress, mitochondrial quality control and MRC activity, which could be a potential target for clinical therapy of respiratory diseases.

Hypomagnesaemia in Acute Exacerbation Chronic Obstructive Airway Disease; Association with Anthonisen’s Levels of Exacerbation

Background: COPD is major public health issue causing morbidity and mortality. Lower serum magnesium levels are seen in patients with acute exacerbations compared to stable COPD patients. This study aims at identifying hypomagnesemia as predictor of COPD exacerbations that may help reduce the burden of readmissions and mortality.&#x0D; Material and Methods: The Descriptive cross-sectional study was conducted DHQ Hospital Rawalpindi from 16 July 2016 to 15 Jan 2017 after the ethical approval and informed consent. The indoor adult (&gt; 18 years) diagnosed cases of COPD exacerbation were included by consecutive sampling. Patients with malignancy, pregnancy and receiving magnesium supplements were excluded. Demographic details documented and after complete clinical evaluation, serum Magnesium levels of were assessed. Serum Magnesium &lt; 1.80 mg/dl labeled hypomagnesaemia. Data was analyzed by SPSS with significant p&lt; 0.05.&#x0D; Results: Amongst 176 patients; there were 93(52.8%) males and 83(47.2%) females. Mean age was 56+7 years. Mean duration of COPD was 6.56 + 5.24 years (2-10 years). Mean height in the study was 181 +12 cm and mean weight was 56.06 + 7.08 kg. The mean serum magnesium level was 1.5 + .49mg/dl. Low serum magnesium (&lt;1.8 mg/dl) observed in 103(58.5%), gender wasn’t associated with hypomagnesaemia (p=0.294). Hypomagnesaemia in accordance to types of Anthonisen’s criteria was observed in 19(44.2%) with Type I, 37(57.8%) with Type II and 47(68.1%) with Type III COPD exacerbation. Hypomagnesaemia had significant association with Anthinosen’s levels of exacerbation (p=0.043). The mean age in patients with hypomagnesaemia was 56.61+6.78 Vs. 55.30+7.47 in patients without hypomagnesaemia (p=0.228).&#x0D; Conclusion: The study concludes mean serum magnesium levels are significantly lower in patients with acute exacerbation of COPD (58.5%), particularly in type II and III. Magnesium levels should be performed in all COPD exacerbations irrespective of gender and age. Replacement of magnesium may be helpful in alleviating symptoms and reducing frequency of exacerbations.

Inhalation of Salvianolic Acid B Prevents Fine Particulate Matter-Induced Acute Airway Inflammation and Oxidative Stress by Downregulating the LTR4/MyD88/NLRP3 Pathway.

Air pollution is a serious threat to human health. Inhaled fine particulate matter (PM2.5) can cause inflammation and oxidative stress in the airway; however, the mechanisms responsible for this effect have yet to be elucidated and there are no specific drugs that can prevent and treat this condition. In the present study, we investigated the effects and mechanisms underlying the inhalation of salvianolic acid B (SalB) on PM2.5-induced airway inflammation and oxidative stress. We used a PM2.5-induced mouse model of airway inflammation and oxidative stress, along with a human epithelial cell model, to study the action and mechanisms of SalB by histopathology, real-time PCR, enzyme-linked immunosorbent assays, flow cytometry, and western blotting. SalB treatment markedly inhibited the PM2.5-induced increase in the number of neutrophils and macrophages in bronchoalveolar lavage fluid, improved the infiltration of inflammatory cells in lung tissue, and reduced injury in the alveolar septum. Furthermore, SalB reduced the mRNA and protein levels of interleukin- (IL-) 1β, tumor necrosis factor- (TNF-) α, keratinocyte (KC), and transforming growth factor- (TGF-) β1 in lung tissues and the protein levels of IL-1β, TNF-α, IL-8, IL-6, and TGF-β1 in human epithelial cells. SalB treatment also significantly prevented the reduction of levels of superoxide dismutase, catalase, glutathione, and glutathione peroxidase in lung tissue and reduced the levels of reactive oxygen species in human epithelial cells induced by PM2.5. Furthermore, SalB and the myeloid differentiation primary response 88 (MyD88) inhibitor ST2825 inhibited the expression levels of toll-like receptor 4 (TLR4), MyD88, tumor necrosis factor receptor associated factor 6 (TRAF-6), and NOD-like receptor protein 3 (NLRP3), as well as the phosphorylation of downstream Erk1/2 and P38 in lung tissue and epithelial cells. SalB protects against PM2.5-induced airway inflammation and oxidative stress in a manner that is associated with the inhibition of the TLR4/MyD88/TRAF-6/NLRP3 pathway and downstream signals ERK1/2 and P38.

Targeting the DNA repair enzymes MTH1 and OGG1 as a novel approach to treat inflammatory diseases.

Autoimmune diseases and acute inflammation like sepsis cause significant morbidity and disability globally, and new targeted therapies are urgently needed. DNA repair and reactive oxygen species (ROS) pathways have long been investigated as targets for cancer treatment, but their role in immunological research has been limited. In this MiniReview, we discuss the DNA repair enzymes MTH1 and OGG1 as targets to treat both T cell‐driven diseases and acute inflammation. The MiniReview is based on a PhD thesis where both enzymes were investigated with cell and animal models. For MTH1, we found that its inhibition selectively kills activated T cells without being toxic to resting cells or other tissues. MTH1 inhibition also had an alleviating role in disease models of psoriasis and multiple sclerosis. We further identified a novel MTH1lowROSlow phenotype among activated T cells. Regarding OGG1, we demonstrated a mechanism of action of the OGG1 inhibitor TH5487, which prevents the assembly of pro‐inflammatory transcription factors and mitigates acute airway infection in mouse models of pneumonia. Hence, we propose both enzymes to be promising novel targets to treat inflammation and suggest that redox and DNA repair pathways could be useful targets for future immunomodulating therapies.

Extracellular ST6GAL1 regulates monocyte-macrophage development and survival.

Interaction of immune cells with the systemic environment is necessary for the coordinated development and execution of immune responses. Monocyte-macrophage lineage cells reside at the junction of innate and adaptive immunity. Previously we reported that the sialyltransferase ST6GAL1 in the extracellular milieu modulates B cell development and IgG production, granulocyte production, and attenuates acute airway inflammation to bacterial challenge in mouse models. Here, we report that extracellular ST6GAL1 also elicits profound responses in monocyte-macrophage lineage cells. We show that recombinant ST6GAL1 adheres to subsets of thioglycolate-elicited inflammatory cells in the mouse peritoneum and to cultured human monocyte THP-1 cells. Exposure of the inflammatory cells to recombinant ST6GAL1 elicited wholesale changes in the gene expression profile of primary mouse myeloid cells; most notable was the striking up-regulation of monocyte-macrophage and monocyte-derived dendritic cell development pathway signature genes and transcription factors PU.1, NFκB and their target genes, driving increased monocyte-macrophage population and survival ex vivo. In the cultured human monocyte cells, the essential cell surface receptor of the monocyte-macrophage lineage, the M-CSF receptor (M-CSF-R, Csfr1) was a target of extracellular ST6GAL1 catalytic activity. Extracellular ST6GAL1 activated the M-CSF-R and initiated intracellular signaling events, namely, the nuclear translocation of NFκB subunit p65, and phosphorylation of ERK 1/2 and AKT. The findings implicate extracellular ST6GAL1 in monocyte development by a mechanism initiated at the cell surface and support an emerging paradigm of an extracellular glycan-modifying enzyme as a central regulator coordinating immune hematopoietic cell development and function.

Macrophage-intrinsic DUOX1 contributes to type 2 inflammation and mucus metaplasia during allergic airway disease.

The NADPH oxidase DUOX1 contributes to epithelial production of alarmins, including interleukin (IL)-33, in response to injurious triggers such as airborne protease allergens, and mediates development of mucus metaplasia and airway remodeling in chronic allergic airways diseases. DUOX1 is also expressed in non-epithelial lung cell types, including macrophages that play an important role in airway remodeling during chronic lung disease. We therefore conditionally deleted DUOX1 in either lung epithelial or monocyte/macrophage lineages to address its cell-specific actions in innate airway responses to acute airway challenge with house dust mite (HDM) allergen, and in chronic HDM-driven allergic airway inflammation. As expected, acute responses to airway challenge with HDM, as well as type 2 inflammation and related features of airway remodeling during chronic HDM-induced allergic inflammation, were largely driven by DUOX1 with the respiratory epithelium. However, in the context of chronic HDM-driven inflammation, DUOX1 deletion in macrophages also significantly impaired type 2 cytokine production and indices of mucus metaplasia. Further studies revealed a contribution of macrophage-intrinsic DUOX1 in macrophage recruitment upon chronic HDM challenge, as well as features of macrophage activation that impact on type 2 inflammation and remodeling.

N-methyl-D-aspartate receptor blockers attenuate bleomycin-induced pulmonary fibrosis by inhibiting endogenous mesenchymal stem cells senescence

BackgroundA large number of our previous studies showed that endogenous glutamate and N-methyl-D-aspartate receptor (NMDAR) activation may be involved in various types of acute lung injury, airway inflammation, asthma, and pulmonary fibrosis. In animal models, the transplantation of exogenous bone marrow mesenchymal stem cells (BM-MSCs) is the most promising treatment for idiopathic pulmonary fibrosis. However, there are limited reports on the status of endogenous BM-MSCs in the process of bleomycin-induced pulmonary fibrosis in animals.MethodsWe constructed a mouse model of bleomycin-induced pulmonary fibrosis. In vitro, the senescence model of BM-MSCs was constructed with hydrogen peroxide and high concentration of N-methyl-D-aspartate (NDMA). The changes in aging-related indexes were detected by senescence associated beta-galactosidase (SA-β-gal) staining, western blot, flow cytometry and real time-PCR. The epithelial-mesenchymal transformation (EMT) changes of mouse lung epithelial cells (MLE-12) co-cultured with senescent BM-MSCs were detected by immunofluorescence and western blotting.ResultsWe observed that endogenous BM-MSCs senescence occurs during bleomycin-induced pulmonary fibrosis in mice, and the model group had a higher expression level of the NMDAR subunit than the control group. We observed a significant increase in NMDAR subunit expression in a hydrogen peroxide-induced senescent cell model in vitro. BM-MSCs showed senescence-related phenotype and cell cycle arrest after high concentration of NMDA treatment. At the same time, the expression levels of the classic Wingless and int-1 (Wnt) pathway protein β-cantenin and downstream cyclin D1 also changed. In the co-culture of aged BM-MSCs and MLE-12 cells, EMT can be promoted in MLE-12 cells, and MK-801 can partially antagonize the occurrence of EMT. The NMDAR antagonist can partially prevent the above phenomenon.ConclusionsHigh concentrations of NMDA can promote senescence of BM-MSCs. NMDAR blockers may inhibit endogenous BM-MSCs aging through the WNT signaling pathway, thereby reducing the effect of bleomycin-induced pulmonary fibrosis.

Immunoproteasome Inhibition Reduces the T Helper 2 Response in Mouse Models of Allergic Airway Inflammation.

BackgroundAllergic asthma is a chronic disease and medical treatment often fails to fully control the disease in the long term, leading to a great need for new therapeutic approaches. Immunoproteasome inhibition impairs T helper cell function and is effective in many (auto-) inflammatory settings but its effect on allergic airway inflammation is unknown.MethodsImmunoproteasome expression was analyzed in in vitro polarized T helper cell subsets. To study Th2 cells in vivo acute allergic airway inflammation was induced in GATIR (GATA-3-vYFP reporter) mice using ovalbumin and house dust mite extract. Mice were treated with the immunoproteasome inhibitor ONX 0914 or vehicle during the challenge phase and the induction of airway inflammation was analyzed.Results In vitro polarized T helper cell subsets (Th1, Th2, Th17, and Treg) express high levels of immunoproteasome subunits. GATIR mice proved to be a useful tool for identification of Th2 cells. Immunoproteasome inhibition reduced the Th2 response in both airway inflammation models. Furthermore, T cell activation and antigen-specific cytokine secretion was impaired and a reduced infiltration of eosinophils and professional antigen-presenting cells into the lung and the bronchoalveolar space was observed in the ovalbumin model.ConclusionThese results show the importance of the immunoproteasome in Th2 cells and airway inflammation. Our data provides first insight into the potential of using immunoproteasome inhibition to target the aberrant Th2 response, e.g. in allergic airway inflammation.

Bilateral Vocal Cord Paralysis in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects the synovial membrane, causing joint damage and bone destruction. Symptoms of cricoid arytenoid joint (CJ) arthritis often include a voice change and a feeling of fullness in the throat and pharynx. In some cases, bilateral CJ invasion may require an emergency tracheostomy due to acute airway closure. This report describes a 45-year-old man who suffers from voice changes and aspiration due to a vocal cord palsy caused by RA, along with bilateral CJ invasion. One month after receiving drug treatment for rheumatoid arthritis, the patient regained normal voice.

Therapeutic Effects of Human Pluripotent Stem Cell-Derived Mesenchymal Stem Cells on a Murine Model of Acute Type-2-Dominated Airway Inflammation

Allergic rhinitis and allergic asthma are the most common type-2 inflammatory diseases, which are hardly curable and cause heavy burden to general well-being. Mesenchymal stem cells (MSCs) are multipotent nonhematopoietic cells with potential immunomodulatory effects that have been showning to have a therapeutic effect on allergic diseases. Here, we investigated the effects of human induced pluripotent stem cell (iPSC)-derived MSCs on airway hyperresponsiveness and acute type-2-dominated inflammation throughout the upper and lower airways. In this study, human MSCs, MSC cell culture supernatant, and culture medium (control) was injected into the acute airway inflammatory model via the tail vein. Mouse behavioristics were recorded immediately and mouse lung function was measured 24hours after the last ovalbumin (OVA) challenge. Histological staining, Luminex, Elisa and flow cytometry were employed to evaluate the effects on the production of total/OVA-specific IgG1 and IgE, cytokines expression in lung tissues, and inflammatory cells infiltration in the lung and spleen of the experimental mice. Expressions of eotaxin, IL-4, IL-5, IL-13, IL-33 in nasal and lung lavage were evaluated by Luminex and Elisa. We found that for this acute inflammatory mouse model, human MSC transplantation significantly mitigated the decreased motoring time and the increased lung function Rrs caused by OVA challenge. Serum OVA-IgG1, OVA-IgE, and eosinophil percentages in the splenocytes were significantly decreased. Injection of the MSC supernatant also showed the same trend, but not significantly changed. After treatment, IL-4 and IL-13 were significantly decreased in the lung tissue, and IL-5 and IL-13 were significantly decreased in lung lavage. In conclusion, both human MSC culture supernatant and cell transplantation could alleviate AHR and inflammation in acute inflammatory experimental animals, which demonstrated their potential for clinical therapeutics. Human iPSC-MSCs, MSC cell culture supernatant, or culture medium (control) was injected into the OVA-induced acute airway inflammatory model via the tail vein. Behavioral changes, AHR, serum OVA-specific IgG1 and IgE concentrations, and type-2 inflammations were alleviated.

The Probiotics in Pediatric Asthma Management (PROPAM) study: A Post Hoc analysis in allergic children

Type 2 inflammation is prevalent in children with asthma and increases susceptibility to respiratory infections.1 Furthermore, acute airway infections usually precede asthma exacerbations in children.2 Consequently, an ideal therapeutic strategy should be targeted to dampen inflammation and prevent infections. There is also evidence to suggest that children with asthma have intestinal and respiratory dysbiosis that promotes airway inflammation and allergy.3 It is speculated that probiotics could restore “eubiosis,” dampen inflammation, and prevent infections.

T cell‐intrinsic miR‐155 is required for Th2 and Th17‐biased responses in acute and chronic airway inflammation by targeting several different transcription factors

Asthmatic airway inflammation is divided into two typical endotypes: Th2-mediated eosinophilic and Th1- or Th17-mediated neutrophilic airway inflammation. The miRNA miR-155 has well-documented roles in the regulation of adaptive T-cell responses and innate immunity. However, no specific cell-intrinsic role has yet been elucidated for miR-155 in T cells in the course of Th2-eosinophilic and Th17-neutrophilic airway inflammation using actual in vivo asthma models. Here, using conditional KO (miR155ΔCD4 cKO) mice that have the specific deficiency of miR-155 in T cells, we found that the specific deficiency of miR-155 in T cells resulted in fully suppressed Th2-type eosinophilic airway inflammation following acute allergen exposure, as well as greatly attenuated the Th17-type neutrophilic airway inflammation induced by repeated allergen exposure. Furthermore, miR-155 in T cells appeared to regulate the expression of several different target genes in the functional activation of CD4+ Th2 and Th17 cells. To be more precise, the deficiency of miR-155 in T cells enhanced the expression of c-Maf, SOCS1, Fosl2 and Jarid2 in the course of CD4+ Th2 cell activation, while C/EBPβ was highly enhanced in CD4+ Th17 cell activation in the absence of miR-155 expression. Conclusively, our data revealed that miR-155 could promote Th2 and Th17-mediated airway inflammation via the regulation of several different target genes, depending on the context of asthmatic diseases. Therefore, these results provide valuable insights into actual understanding of specific cell-intrinsic role of miR-155 in eosinophilic and neutrophilic airway inflammation for the development of fine-tune therapeutic strategies.

Acute Upper Airway Disease in Children With the Omicron (B.1.1.529) Variant of SARS-CoV-2—A Report From the US National COVID Cohort Collaborative

This cohort study uses data from the US National COVID Cohort Collaborative to evaluate upper airway infections in children during the surge of the Omicron (B.1.1.529) variant of SARS-CoV-2 in the US.

Dual migration of organic foreign body in bronchus

The foreign body in the bronchus is one of the most fatal emergencies in the Otorhinolaryngology. Delay in the appropriate treatment may result in acute airway diseases and fatal complications. The aim of this manuscript is to report a clinical case of dual migration of an organic foreign body from left to right and then back to the left bronchus in a 13 months old child. The case was initially diagnosed as left sided severe pneumonia which recurred after initial partial response to medical management and thus raised the suspicion of a foreign body. Computed tomography of the chest revealed a foreign body in the right bronchus contrary to clinical findings on the left side suggesting the first migration. The foreign body was visualized and removed from the left bronchus during bronchoscopy; which was contrary to radiological findings, suggesting the second migration.

Percutaneous Tracheostomy: A Bedside Procedure.

Percutaneous tracheostomy is a bedside surgical procedure that creates an opening in the anterior tracheal wall. Tracheostomy is performed in patients expected to require mechanical ventilation for longer than seven to 10 days. This bedside percutaneous tracheostomy has been used since the late 1990s. Tracheotomy tubes are of various kinds like cuffed vs. uncuffed, fenestrated vs. unfenestrated, single lumen vs. double lumen, and metal vs. plastic. Its indications are categorized into emergency vs. elective. The most common emergency indication is acute airway obstruction, and the elective indication is prolonged intubation. There is no absolute contraindication, but a physician should consider severe hypoxia requiring high oxygen and coagulopathy. Percutaneous tracheostomy is a new technique requiring different skills. Advantages of percutaneous tracheostomy are as follows - it is performed at the bedside, procedural time is less, the cost is less, does not need operating schedule time. Percutaneous tracheostomy is generally performed by otolaryngologists, general surgeons, interventional pulmonologists, thoracic surgeons, or intensivists.