Acute Airway Research Articles

Pseudomonas aeruginosa modulates neutrophil granule exocytosis in an in vitro model of airway infection.

A population of neutrophils recruited into cystic fibrosis (CF) airways is associated with proteolytic lung damage, exhibiting high expression of primary granule exocytosis marker CD63 and reduced phagocytic receptor CD16. Causative factors for this population are unknown, limiting intervention. Here we present a laboratory model to characterize responses of differentiated airway epithelium and neutrophils following respiratory infection. Pediatric primary airway epithelial cells were cultured at the air–liquid interface, challenged individually or in combination with rhinovirus (RV) and Pseudomonas aeruginosa, then apically washed with medical saline to sample epithelial infection milieus. Cytokine multiplex analysis revealed epithelial antiviral signals, including IP‐10 and RANTES, increased with exclusive RV infection but were diminished if P. aeruginosa was also present. Proinflammatory signals interleukin‐1α and β were dominant in P. aeruginosa infection milieus. Infection washes were also applied to a published model of neutrophil transmigration into the airways. Neutrophils migrating into bacterial and viral–bacterial co‐infection milieus exhibited the in vivo CF phenotype of increased CD63 expression and reduced CD16 expression, while neutrophils migrating into milieus of RV‐infected or uninfected cultures did not. Individually, bacterial products lipopolysaccharide and N‐formylmethionyl‐leucyl‐phenylalanine and isolated cytokine signals only partially activated this phenotype, suggesting that additional soluble factors in the infection microenvironment trigger primary granule release. Findings identify P. aeruginosa as a trigger of acute airway inflammation and neutrophil primary granule exocytosis, underscoring potential roles of airway microbes in prompting this neutrophil subset. Further studies are required to characterize microbes implicated in primary granule release, and identify potential therapeutic targets.

Utility of nasal mucus inflammatory profile as a biomarker of nasal polyp regrowth in aspirin-exacerbated respiratory disease

Aspirin-exacerbated respiratory disease (AERD) is a disease of the upper and lower airways characterized by asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), and acute upper and/or lower airway symptoms triggered by cyclooxygenase-1 inhibitors. Individuals with AERD have more severe upper and lower airway disease, poorer quality of life (QoL), and increased medication utilization than their aspirin-tolerant asthma and CRSwNP counterparts.1 The high rate of nasal polyp recurrence despite adequate surgical excision in patients with AERD is major driver of health care utilization and impaired QoL.

A breathing mask attenuates acute airway responses to exercise in sub-zero environment in healthy subjects

PurposeCold air exposure is associated with increased respiratory morbidity and mortality. Repeated inhalation of cold and dry air is considered the cause of the high prevalence of asthma among winter endurance athletes. This study assessed whether a heat- and moisture-exchanging breathing device (HME) attenuates airway responses to high-intensity exercise in sub-zero temperatures among healthy subjects.MethodsUsing a randomized cross-over design, 23 healthy trained participants performed a 30-min warm-up followed by a 4-min maximal, self-paced running time trial in − 15 °C, with and without HME. Lung function was assessed pre- and immediately post-trials. Club cell protein (CC-16), 8-isoprostane, and cytokine concentrations were measured in plasma and urine pre- and 60 min post trials. Symptoms were assessed prior to, during, and immediately after each trial in the chamber.ResultsHME use attenuated the decrease in forced expiratory volume in 1 s (FEV1) post trials (∆FEV1: mean (SD) HME − 0.5 (1.9) % vs. no-HME − 2.7 (2.7) %, p = 0.002). HME also substantially attenuated the median relative increase in plasma-CC16 concentrations (with HME + 27% (interquartile range 9–38) vs no-HME + 121% (55–162), p < 0.001) and reduced airway and general symptom intensity, compared to the trial without HME. No significant changes between trials were detected in urine CC16, 8-isoprostane, or cytokine concentrations.ConclusionThe HME attenuated acute airway responses induced by moderate-to-maximal-intensity exercise in − 15 °C in healthy subjects. Further studies are needed to examine whether this HMEs could constitute primary prevention against asthma in winter endurance athletes.

Successful airway management in a patient with left parapharyngeal and retropharyngeal abscess with mediastinal extension during COVID-19 pandemic

Acute airway compromise caused by a deep neck space abscess significantly contributes to the morbidity and mortality, and it requires quick identification and rapid treatment.1 Parapharyngeal and retropharyngeal abscesses affect 2.64 persons out of 100,000 population. The incidence in males and females is 3.34 and 1.94 per 100,000 people, respectively.2 Of note, the abscess might increase the patient’s susceptibility to COVID-19 infection. In order to limit COVID-19 transmission in such patients, an advanced treatment plan is required.3 We share the anesthetic airway management of a high-risk airway case during the current COVID-19 pandemic.&#x0D; Key words: airway management; COVID-19; abscess, parapharyngeal; abscess, retropharyngeal; video-assisted thoracoscopy; Surgery, thoracic&#x0D; Citation: Hehsan MR, Shukeri WFWM, Chettiar RSRMS, Abidin HZ. Successful airway management in a patient with left parapharyngeal and retropharyngeal abscess with mediastinal extension during COVID-19 pandemic. Anaesth. pain intensive care 2021;26(1):128-129.&#x0D; DOI: 10.35975/apic.v26i1.1784

Microbiome Modulation as a Novel Strategy to Treat and Prevent Respiratory Infections

Acute and chronic lower airway disease still represent a major cause of morbidity and mortality on a global scale. With the steady rise of multidrug-resistant respiratory pathogens, such as Pseudomonas aeruginosa and Klebsiella pneumoniae, we are rapidly approaching the advent of a post-antibiotic era. In addition, potentially detrimental novel variants of respiratory viruses continuously emerge with the most prominent recent example being severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To this end, alternative preventive and therapeutic intervention strategies will be critical to combat airway infections in the future. Chronic respiratory diseases are associated with alterations in the lung and gut microbiome, which is thought to contribute to disease progression and increased susceptibility to infection with respiratory pathogens. In this review we will focus on how modulating and harnessing the microbiome may pose a novel strategy to prevent and treat pulmonary infections as well as chronic respiratory disease.

Study effect of probiotics and prebiotics on treatment of OVA-LPS-induced of allergic asthma inflammation and pneumonia by regulating the TLR4/NF-kB signaling pathway

Asthma is a common respiratory disease, and immune system dysregulation has direct relevance to asthma pathogenesis. Probiotics and prebiotics have immunomodulatory effects and can regulate immune responses and may attenuate allergic reactions. Therefore, in this study, we explored the role of probiotics and prebiotics in regulating acute airway inflammation and the TLR4/NF-kB pathway. Allergic asthma model of BALB/c mice was produced and treated with probiotics (LA-5, GG, and BB-12) and prebiotics (FOS and GOS). Then AHR, BALF cells count, EPO activity, IL-4, 5, 13, 17, 25, 33, as well as IFN-γ, total and OVA-specific IgE, IgG1, Cys-LT, LTB4, LTC4, and TSLP levels were measured. Also, the GTP/GOT assay was performed and gene expression of Akt, NLR3, NF-kB, PI3K, MyD88, TLR4, CCL11, CCL24, MUC5a, Eotaxin, IL-38, and IL-8 were determined. Finally, lung histopathological features were evaluated. Treatment with probiotics could control AHR, eosinophil infiltration to the BALF and reduce the levels of immunoglobulins, IL-17, GTP and also decrease mucus secretion, goblet cell hyperplasia, peribronchial and perivascular inflammation and also, EPO activity. It could reduce gene expression of TLR4 and CCL11. On the other hand, IL-38 gene expression was increased by both probiotic and prebiotic treatment. Treatment with probiotics and prebiotics could control levels of IL-4, 5, 13, 25, 33, leukotrienes, the gene expression of AKT, NLR3, NF-κB, MyD88, MUC5a. The prebiotic treatment could control peribronchial inflammation and PI3K gene expression. Both of the treatments had no significant effect on the GOT, TSLP and IL-8, eotaxin and CCL24 gene expression. Probiotics and prebiotics could induce tolerance in allegro-inflammatory reactions and alter immune responses in allergic conditions. Probiotics could also modulate cellular and humoral immune responses and prevent allergic disorders.

Statement of Retraction: Endoplasmic reticulum stress potentiates the autophagy of alveolar macrophage to attenuate acute lung injury and airway inflammation

Statement of Retraction: Endoplasmic reticulum stress potentiates the autophagy of alveolar macrophage to attenuate acute lung injury and airway inflammation

Complete Airway Obstruction and Massive Hemorrhage from Post-Thyroidectomy Neck Hematoma: A Case Report and Management Algorithm

Postoperative Neck Hematoma (PONH) is a potentially life-threatening complication of neck/thyroid procedures due to massive hemorrhage and/or acute airway compromise (often associated with difficult airway management) requiring immediate surgical re-intervention. Patient survival often relies on optimal crisis resource management skills of the care team. We describe the case of a PONH in an elderly patient in the immediate post-thyroidectomy period, presenting with acute respiratory failure/arrest and massive hemorrhage with hemodynamic instability. We outline the approach taken to successfully manage this emergency and highlight critical management steps including the leadership role of the anesthesiologist that ultimately resulted in a positive outcome.

An international survey on nasal nitric oxide measurement practices for the diagnosis of primary ciliary dyskinesia.

Nasal nitric oxide (nNO) measurements are used in the assessment of patients suspected of having primary ciliary dyskinesia (PCD), but recommendations for performing such measurements have not focused on children and do not include all current practices. To guide the development of a European Respiratory Society-supported technical standard for nNO measurement in children, an international online survey was conducted to better understand current measurement practices among providers involved in PCD diagnostics.78 professionals responded, representing 65 centres across 18 countries, mainly in Europe and North America. Nearly all centres measured nNO in children and more than half performed measurements before 5 years of age. The test was often postponed in children with signs of acute airway infection. In Europe, the electrochemical technique was more frequently used than chemiluminescence. A similar proportion of centres performed measurements during exhalation against a resistance (49 out of 65) or during tidal breathing (50 out of 65); 15 centres used only exhalation against a resistance and 15 used only tidal breathing. The cut-off values used to discriminate PCD were consistent across centres using chemiluminescence analysers; these centres reported results as an output (nL·min−1). Cut-off values were highly variable across centres using electrochemical devices, and nNO concentrations were typically reported as ppb.This survey is the first to determine real-world use of nNO measurements globally and revealed remarkable variability in methodology, equipment and interpretation. These findings will help standardise methods and training.

Emergency physician-performed emergency bronchoscopy in cardiac arrest patient due to acute foreign body airway obstruction.

As foreign body airway obstruction (FBAO) can be life-threatening, it has to be promptly diagnosed and treated. We report a case series of three patients presenting to the emergency department with cardiac arrest due to FBAO. In each case, ventilation was difficult due to high airway resistance. As FBAO was suspected, the emergency physician did a prompt flexible bronchoscopy to confirm the diagnosis and retrieve the foreign body. Flexible bronchoscopy is an important diagnostic and therapeutic tool for emergency airway management, and is a relatively safe procedure if performed by a trained personnel. The life-saving benefits of bronchoscopy outweigh the small risks of complications such as bleeding, desaturation and pneumothorax. In the three cases, the removal of the obstructing material led to immediate improvements in oxygenation and ventilation. The patients had return of spontaneous circulation after cardiopulmonary resuscitation and definite airway control.

Effects of TORS-OSA Surgery on Lower Urinary Tract Symptoms, Overactive Bladder Symptoms, and Nocturia in Male Patients with Obstructive Sleep Apnea/Hypopnea Syndrome

ObjectiveTo determine the presence of lower urinary tract symptoms (LUTS), and overactive bladder (OAB) symptoms in men with obstructive sleep apnea/hypopnea syndrome (OSA) and the effects of transoral robotic surgery (TORS) for the treatment of OSA on these conditions.Materials and MethodsOne hundred twenty-three patients with a diagnosis of OSA were prospectively enrolled. The evaluations of LUTS and OAB symptoms were based on self-administered questionnaires containing international prostate symptom score (IPSS) and OAB symptom score (OABSS), respectively. Men with an OABSS urgency score of ≥2 and sum score of ≥3 were considered to have OAB. The therapeutic outcomes were assessed at baseline, and 12 weeks after TORS-OSA Surgery.ResultsThere were significant differences in IPSS, and OABSS according to OSA severity. After TORS-OSA surgery, significant improvements on OSA severity, daytime quality of life (QoL) and nighttime sleep quality were observed. TORS-OSA surgery was also associated with a statistically significant improvement of LUTS, LUTS QoL score, and OAB symptoms (IPSS 22.1% decrease; IPSS QoL score 21.1% decrease; OABSS17.4% decrease) at post-operative 3 months’ follow-up. The presence of OAB, and severe nocturia was significantly reduced from 22.8% to 11.4% (p=0.001), 5.7% to 0.8% (p=0.031) after TORS-OSA surgery. There were no patients who had acute airway compromise or massive bleeding peri- or post-operatively.ConclusionTORS upper airway surgery could improve LUTS and OAB symptoms on male patients with OSA in addition to improvement of major parameters of sleep study and sleep-related QoL.

Age-Related Differences in Structure and Function of Nasal Epithelial Cultures From Healthy Children and Elderly People.

The nasal epithelium represents the first line of defense against inhaled pathogens, allergens, and irritants and plays a key role in the pathogenesis of a spectrum of acute and chronic airways diseases. Despite age-dependent clinical phenotypes triggered by these noxious stimuli, little is known about how aging affects the structure and function of the airway epithelium that is crucial for lung homeostasis and host defense. The aim of this study was therefore to determine age-related differences in structural and functional properties of primary nasal epithelial cultures from healthy children and non-smoking elderly people. To achieve this goal, highly differentiated nasal epithelial cultures were established from nasal brushes at air–liquid interface and used to study epithelial cell type composition, mucin (MUC5AC and MUC5B) expression, and ion transport properties. Furthermore, we determined age-dependent molecular signatures using global proteomic analysis. We found lower numeric densities of ciliated cells and higher levels of MUC5AC expression in cultures from children vs. elderly people. Bioelectric studies showed no differences in basal ion transport properties, ENaC-mediated sodium absorption, or CFTR-mediated chloride transport, but detected decreased calcium-activated TMEM16A-mediated chloride secretory responses in cultures from children vs. elderly people. Proteome analysis identified distinct age-dependent molecular signatures associated with ciliation and mucin biosynthesis, as well as other pathways implicated in aging. Our data identified intrinsic, age-related differences in structure and function of the nasal epithelium and provide a basis for further studies on the role of these findings in age-dependent airways disease phenotypes observed with a spectrum of respiratory infections and other noxious stimuli.

Retropharyngeal haematoma following thrombolytic therapy with Tenecteplase for acute myocardial infarction: a case report

Retropharyngeal haematomas (RPHs) are rare but can give rise to life threatening acute airway obstruction andrequire prompt diagnosis and management. Its clinical presentation is not always straight forward. Majority of RPHs are managed conservatively while few need surgical evacuation. We present a case of a 41-year-old male who needed surgical evacuation of RPH following single dose of Tenecteplase (rt-PA) for acute ST elevation myocardial infarction. We present this case because of its rarity with thrombolytic therapy.

Anaphylaxis to Ciprofloxacin Requiring Emergent Surgical Cricothyrotomy.

Although allergies to antibiotics are commonly stated, anaphylactic reactions are uncommonly reported. This is especially the case with reactions to fluoroquinolone antibiotics. Furthermore, airway emergencies are rare. We present a case of ciprofloxacin-induced acute airway obstruction and anaphylaxis, necessitating emergent surgical cricothyrotomy following respiratory distress.LEARNING POINTSAnaphylactic reactions to fluoroquinolone antibiotics are extremely rare.There are currently no standardized diagnostic tests, making the diagnosis of anaphylaxis challenging and largely based on history alone.Treating clinicians should be aware of this rare, but potentially rapidly fatal adverse drug reaction.

Emergency Use of Extracorporeal Membrane Oxygenation for Pediatric Acute Airway Obstruction Caused by an Anterior Mediastinal Mass

Emergency Use of Extracorporeal Membrane Oxygenation for Pediatric Acute Airway Obstruction Caused by an Anterior Mediastinal Mass

Interfering with alternatively activated macrophages by CSF-1R inhibition exerts therapeutic capacity on allergic airway inflammation

PurposeAllergic asthma is a chronic inflammatory disorder with airway hyperresponsiveness and tissue remodeling as the main pathological characteristics. The etiology of asthma is relatively complicated, involving genetic susceptibility, epigenetic regulation, environmental factors, and immune imbalance. Colony stimulating factor 1 receptor (CSF-1R), highly expressed in myeloid monocytes, plays an important role in regulating inflammation. However, the pathological role of CSF-1R and the therapeutic effects of CSF-1R inhibitor in allergic airway inflammation remain indistinct. MethodsThe house dust mite (HDM)-triggered allergic airway inflammation model was conducted to fully uncover the efficacies of CSF-1R inhibition, as illustrated by histopathological examinations, biochemical analysis, ELISA, RT-PCR, Western blotting assay, immunofluorescence, and flow cytometry. Furthermore, bone marrow-derived macrophages (BMDMs) were differentiated and polarized upon IL-4/IL-13 induction to clarify the underlying mechanisms of CSF-1R inhibition. ResultsHerein, we presented that the expression of CSF-1R was increased in HDM-induced experimental asthma and inhibition of CSF-1R displayed dramatic effects on the disease severity of asthma, referring to suppressing the secretion of allergic mediators, dysfunction of airway epithelium, and infiltration of inflammatory cells. Furthermore, CSF-1R inhibitor could markedly restrain the polarization and expression of transcriptional factors of alternatively activated macrophages (AAMs) in the presence of IL-4/IL-13 and reduce the recruitment of CSF-1R-dominant macrophages, both in acute and chronic allergic airway inflammation model. ConclusionCollectively, our findings demonstrated the molecular pathological mechanism of CSF-1R in allergic airway diseases and suggested that targeting CSF-1R might be an alternative intervention strategy on the homeostasis of airway immune microenvironment in asthma.

Exercise capacity, lung and respiratory muscle function in substance use disorders

BackgroundSubstance use disorder (SUD) causes conditions such as cognitive and behavioral disorders, anxiety, depression, and social isolation it also causes acute airway inflammation by affecting airway bronchial dynamics. The current study aimed to investigate the lung function, respiratory muscle strength, and exercise capacity in patients with SUD. MethodsOne hundred-eighty three patients with SUD, a total of 119 healthy controls, 54 of whom were cigarette smokers and 65 of whom were non-smokers were included in the study. Spirometric tests, respiratory muscle strength (MIP and MEP), and the 6-Minute Walk Test (6-MWT) were assessed. The III National Health and Nutrition Examination Survey were used to evaluate respiratory symptoms in patients with SUD and cigarette smokers. Results86.3% of the SUD patients included in the study were using heroin, 9.2% were cannabis, and 5.5% were spice. The most common symptom in both SUD patients and cigarette smokers was shortness of breath, wheezing, and sputum production. After post-hoc tests, the FVC (p = 0.002), FVC (%predicted) (p < 0.0001), FEV1 (p = 0.002), FEV1 (%predicted) (p < 0.0001), FEV1/FVC (%) (p < 0.0001), PEF (p < 0.0001) and FEF%25-75 (p < 0.0001) lung function parameters were significantly lower in SUD patients than non-smokers. In addition, it was found that MIP (p < 0.0001), MIP (%predicted) (p < 0.0001), MEP (p < 0.0001), and MEP (%predicted) (p < 0.0001) values of SUD patients were significantly lower than non-smokers. ConclusionThe study findings indicate that substance use has an effect on lung functions and the most commonly reported symptoms are shortness of breath, wheezing, and sputum production. In addition, respiratory muscle strength and exercise capacity were decreased in SUD patients compared to non-smokers.

In Situ Simulation as a Tool to Longitudinally Identify and Track Latent Safety Threats in a Structured Quality Improvement Initiative for SARS-CoV-2 Airway Management: A Single-Center Study.

In situ simulation has emerged as a powerful tool for identifying latent safety threats (LSTs). After the first wave of the SARS-CoV-2 pandemic, an urban community emergency department (ED) identified opportunities for improvement surrounding acute airway management and particularly focused on infection control precautions, equipment availability, and interprofessional communication during acute resuscitation. Using the Model for Improvement, a hybrid in situ/quality improvement initiative was implemented using Plan-Do-Study-Act (PDSA) cycles to enhance systems for intubating patients with SARS-CoV-2. Three PDSA cycles consisting of 10 simulations each were conducted from June 2020 through February 2021. Latent safety threats (LST) were identified through an in situ simulation scenario involving a patient with SARS-CoV-2 in acute respiratory failure. LSTs were collected through structured debriefs focused on (1) infection control, (2) equipment availability, and (3) communication. The SAFER-Matrix was used to score LSTs according to frequency and likelihood of harm by members of the ED QI team (SAFER score). The research team worked with the same QI leaders to implement action plans based on scored threats using cause-and-effect and driver diagrams. The Donabedian model was used to conceptually evaluate the quality of interventions upon conclusion of the third PDSA cycle. The median SAFER score decreased from 10.94 in PDSA cycle 1 to 6.77 in PDSA cycle 2 to 4.71 in PDSA cycle 3. Across all identified LSTs, the SAFER score decreased by 3.114 for every additional PDSA cycle ( P = 0.0167). When evaluating for threats identified as being primarily structure based, there was a decrease in SAFER score of 1.28 per every additional PDSA cycle ( P = 0.001). There was a decrease in total count of LST of 0.20 per additional simulation run ( P = 0.02) after controlling for shift type, census, perceived workload, team size, and prior attendance in simulations across all PDSA cycles. This study presents a blueprint for the utilization of in situ simulation through multiple waves of the SARS-CoV-2 pandemic to identify LSTs and use the SAFER score as a surrogate marker to monitor the impact of interventions for a safer environment for both medical staff and patients.

Rhinovirus Infections and Their Roles in Asthma: Etiology and Exacerbations

Rhinovirus infections can cause wheezing illnesses in all age groups. In preschool children, rhinovirus infections frequently initiate acute wheezing illnesses. Children who wheeze with rhinoviruses are at increased risk to go on to develop asthma. Once asthma is established, rhinovirus infections are potent triggers for acute airway obstruction and exacerbations in children and adults. Paradoxically, for most individuals, rhinovirus infections commonly cause cold symptoms with little or no involvement of the lower airways. This paradox has led investigators to identify specific risk factors and mechanisms for rhinovirus wheezing, and this review will outline progress in 3 main areas. First, the 3 species of rhinoviruses have different patterns of infection and virulence. Second, personal factors such as lung function and immunity influence lower respiratory outcomes of rhinovirus infection. The mucosal immune response is critical, and the quality of the interferon response and allergic inflammation interacts to determine the risk for rhinovirus wheezing. Finally, rhinovirus infections can promote pathogen-dominated airway microbiota that increase the risk for wheezing. Although specific antivirals for rhinovirus are still not available, identifying risk factors for wheezing illnesses has provided several other potential targets and strategies for reducing the risk of rhinovirus-induced wheezing and exacerbations of asthma.

Altered secretome by diesel exhaust particles and lipopolysaccharide in primary human nasal epithelium

Airway epithelial cells can actively participate in the defense against environmental pathogens to elicit local or systemic inflammation. Diesel exhaust particles (DEP), a main component of urban air pollution with particulate matter, are associated with the occurrence of acute and chronic upper airway inflammatory diseases. We sought to investigate the effect of DEP alone or in combination with lipopolysaccharide on the secretome in the primary human nasal epithelium (PHNE) and to find potential biomarkers to relate DEP exposure to upper airway inflammatory diseases. PHNE was cultured at an air-liquid interface to create a differentiated invivo-like model. Secreted proteins (secretome) on the bottom media of the PHNE were analyzed by mass spectrometry-based label-free quantitative proteomics and ELISA. Considerably more differentially expressed secreted proteins were identified in response to DEP plus lipopolysaccharide than to DEP alone. Some canonical pathways related to inflammation and cancer such as the p53, β-catenin, and extracellular signal-regulated kinase 1/2 pathways were involved. Among differentially expressed secreted proteins, leukemia inhibitory factor was also detected at a high level in the middle ear effusions of otitis media patients, and the leukemia inhibitory factor level was significantly correlated with daily mean mass concentrations of atmospheric particulate matter averaged over 8 days before sample collection. Apical stimulation with DEP and lipopolysaccharide can significantly alter the basal secretome in PHNE, and this alteration can be reflected by surrounding inflammation with effusion of fluids invivo such as middle ear effusions in otitis media patients.