Fatal Airway Research Articles

Safety and clinical activity of PD-L1 blockade in patients with aggressive recurrent respiratory papillomatosis

BackgroundRecurrent respiratory papillomatosis (RRP) is a human papillomavirus (HPV)-driven disorder that causes substantial morbidity and can lead to fatal distal airway obstruction and post-obstructive pneumonias. Patients require frequent surgical debridement of disease, and no approved systemic adjuvant therapies exist.MethodsA phase II study was conducted to investigate the clinical activity and safety of programmed death-ligand 1 (PD-L1) blockade with avelumab in patients with RRP.ResultsTwelve patients were treated. All patients with laryngeal RRP displayed improvement in disease burden, and 5 of 9 (56%) displayed partial responses. None of 4 patients with pulmonary RRP displayed a response. Using each patient’s surgical history as their own control, patients required fewer surgical interventions after avelumab treatment (p = 0.008). A subset of partial responders developed HPV-specific reactivity in papilloma-infiltrating T-cells that correlated with reduced HPV viral load and an increased Tissue Inflammation Signature.ConclusionsAvelumab demonstrated safety and clinical activity in patients with laryngeal RRP. Further study of immune checkpoint blockade for RRP, possibly with longer treatment duration or in combination with other immunotherapies aimed at activating antiviral immunity, is warranted.Trial registrationNCT, number NCT02859454, registered August 9, 2016.

Cost analysis of intraoperative neural monitoring

The recurrent laryngeal nerve (RLN) injury represents one of the most feared complications during thyroidectomy (1). These injuries may cause a temporary or permanent palsy of the RLN and occur, more frequently, monolaterally. If only one side is involved, the palsy results in voice changes, hoarseness, or breathing trouble; in bilateral cases, instead, patients can undergo a potentially fatal airway obstruction needing an urgent tracheostomy (1). This complication, affects the quality of life of the patients, increases the charges for health care, and is the most frequent plea of lawsuits against thyroid surgeons.

Targeted Treatments for Chronic Obstructive Pulmonary Disease (COPD) Using Low-Molecular-Weight Drugs (LMWDs).

Chronic obstructive pulmonary disease (COPD) is a very common and frequently fatal airway disease. Current therapies for COPD depend mainly on long-acting bronchodilators, which cannot target the pathogenic mechanisms of chronic inflammation in COPD. New pharmaceutical therapies for the inflammatory processes of COPD are urgently needed. Several anti-inflammatory targets have been identified based on increased understanding of the pathogenesis of COPD, which raises new hopes for targeted treatment of this fatal respiratory disease. In this review, we discuss the recent advances in bioactive low-molecular-weight drugs (LMWDs) for the treatment of COPD and, in addition to the first-line drug bronchodilators, focus particularly on low-molecular-weight anti-inflammatory agents, including modulators of inflammatory mediators, inflammasome inhibitors, protease inhibitors, antioxidants, PDE4 inhibitors, kinase inhibitors, and other agents. We also provide new insights into targeted COPD treatments using LMWDs, particularly small-molecule agents.

Acute epiglottitis: An uncommon cause of fatal upper airway obstruction in adults

Acute epiglottitis is an uncommon cause of fatal upper airway obstruction in adults. We present a case of a 61-year-old who died from acute epiglottitis whom was initially thought to die from anaphylaxis by ambulance staff. On gross examination, the epiglottis and laryngeal mucosa was grossly oedematous and erythematous. Microscopy showed necrosis, oedema, and exuberant acute inflammation in the mucosal lining confirming acute epiglottitis. Comparisons of clinical and pathological features with other reported cases and case series of adult acute epiglottitis are presented. Similarities and differences with two other common upper airway pathologies that may mimic acute epiglottitis (anaphylaxis and intubation related injury) are also discussed.

Fatal airway complication during root canal treatment

Foreign body (FB) in the tracheobronchial tree is not uncommon, especially in infants and children. They often present with respiratory obstruction, which can lead to death if not removed in time. Despite public awareness and education, FB aspiration continues to be a problem among patients. We report a case of tracheobronchial FB in a 13-year-old boy who had accidentally aspirated a sharp metallic needle, used during root canal treatment by a dental surgeon. The FB was removed successfully without any complication. FB inhalation is possible while conducting a surgical procedure in the oral cavity. This situation is a life-threatening condition, affecting the patient, and may also create a legal issue to the concerned caregivers. Every clinician should be aware of this type of mishappening during oral cavity procedure.

Pediatric airway surgery.

Pediatric airway surgery is a challenging field in pediatric surgery. Laryngotracheal stenosis has a variety of congenital and acquired conditions that require precise assessment and tailored treatment for each individual patient. About 90% of acquired conditions are represented by subglottic stenosis (SGS) resulting as a complication of tracheal intubation. Congenital tracheal stenosis (CTS) is a rare and life-threatening malformation, usually associated with complete tracheal rings along a variable length of the trachea. Tracheomalacia (TM) is a process characterized by flaccidity of the supporting tracheal cartilage, widening of the posterior membranous wall, and reduced anterior-posterior airway caliber. The clinical presentation can vary from almost asymptomatic patients to near fatal airway obstruction. There is considerable variation in both the morphologic subtypes and the prognosis of pediatric airway. The patients are divided into three clinical groups (mild, moderate, and severe). A further division was proposed according to the presence or absence of associated anomalies. The definitive diagnosis of pediatric airway was made by means of rigid bronchoscope and computed tomography scan with three-dimensional reconstruction (3D-CT). Rigid bronchoscopy and 3D-CT confirmed the diagnosis in all the cases. Other associated anomalies include congenital heart disease, vascular anomalies, and BPFM (maldevelopment of aerodigestive tract). After definitive diagnosis of pediatric airway lesions, surgical intervention should be considered. Surgical strategy was presented on each lesion.

Stenting of critical tracheal stenosis with adjuvant cardio-pulmonary bypass.

Severe and critical central airway obstruction causing impaired ventilation and/or oxygenation can impose tremendous challenges on the interventional pulmonologist. Near total airway obstruction can rapidly evolve into potentially fatal complete airway occlusion during bronchoscopic airway manipulation under moderate sedation; as well as during the induction of the general anesthesia. Although there are currently interventional pulmonary procedures available to tackle the critical airway obstruction in extreme situations, cardio-pulmonary bypass should be considered prior to the intervention to maintain the adequate gas exchange during the procedure. Orotracheal intubation with mechanical ventilation in this situation can be fatal itself if the obstructing airway lesion functions as a “one way valve” allowing air to follow distally during inspiration but impeding expiratory flow leading to gas trapping, high intrathoracic pressure, tension pneumothorax, and ultimately a cardiac arrest.

Accumulation of Ubiquitin and Sequestosome-1 Implicate Protein Damage in Diacetyl-Induced Cytotoxicity

Inhaled diacetyl vapors are associated with flavorings-related lung disease, a potentially fatal airway disease. The reactive α-dicarbonyl group in diacetyl causes protein damage invitro. Dicarbonyl/l-xylulose reductase (DCXR) metabolizes diacetyl into acetoin, which lacks this α-dicarbonyl group. To investigate the hypothesis that flavorings-related lung disease is caused by invivo protein damage, we correlated diacetyl-induced airway damage in mice with immunofluorescence for markers of protein turnover and autophagy. Western immunoblots identified shifts in ubiquitin pools. Diacetyl inhalation caused dose-dependent increases in bronchial epithelial cells with puncta of both total ubiquitin and K63-ubiquitin, central mediators of protein turnover. This response was greater in Dcxr-knockout mice than in wild-type controls inhaling 200 ppm diacetyl, further implicating the α-dicarbonyl group in protein damage. Western immunoblots demonstrated decreased free ubiquitin in airway-enriched fractions. Transmission electron microscopy and colocalization of ubiquitin-positive puncta with lysosomal-associated membrane proteins 1 and 2 and with the multifunctional scaffolding protein sequestosome-1 (SQSTM1/p62) confirmed autophagy. Surprisingly, immunoreactive SQSTM1 also accumulated in the olfactory bulb of the brain. Olfactory bulb SQSTM1 often congregated in activated microglial cells that also contained olfactory marker protein, indicating neuronophagia within the olfactory bulb. This suggests the possibility that SQSTM1 or damaged proteins may be transported from the nose to the brain. Together, these findings strongly implicate widespread protein damage in the etiology of flavorings-related lung disease.

From tooth extraction to fatal airway complication in a child – A case report

Exogenous foreign body (FB) in the tracheobronchial tree is not uncommon especially in infants and children often present with respiratory obstruction that can lead to death if not removed in time. Despite public awareness and education, prevention of FB aspiration continues to a problem among children. FB inhalation is quite uncommon during conducting a surgical procedure in the oral cavity. This situation is a life threatening condition, affecting the patient and also may create a legal issue to the concerned care givers. We report a case of an endogenous bronchial foreign body in an 8year old boy who had accidentally aspirated a tooth which occurred during tooth extraction done by a medical quack. The FB was removed successfully without any complications.

Unexpected delayed death after manual strangulation: need for careful examination in the emergency room

The aim of this case report was to demonstrate the importance of detailed clinical assessment in victims of attempted manual strangulation, to prevent the occurrence of delayed death due to an airway collapse; and to provide an update on clinical management of these patients. An elderly male patient presented with a sore throat and speech impairment after attempting manual strangulation. Physical examination showed reddish skin of the neck, an extensive haematoma of the hard palate and anterior tongue. Flexible laryngoscopy failed to show any swelling of the hypopharynx or larynx. A few hours after presentation, the patient developed acute dyspnoea and died. Autopsy and post-mortem CT scan showed a haematoma in the thyro-epiglottal space. In conclusion, victims of manual strangulation can survive despite internal neck injury which can lead to delayed fatal airway collapse. This is because often there are few or no signs of assault, therefore medical evaluation should be thorough and timely. Sometimes immediate tracheotomy can be life saving.

A novel case of adult, acute epiglottitis successfully treated with noninvasive ventilation.

Acute adult epiglottitis is a rare and potentially fatal upper airway condition, requiring prompt recognition, resuscitation, stabilization, and transfer to definitive care. Treatment centers on skilled airway management and early antimicrobial therapy. We describe a patient with acute adult epiglottitis in whom airway management using noninvasive positive pressure ventilation was successful allowing avoidance of tracheal intubation.

Incidence of Fatal Airway Obstruction in Police Officers Feloniously Killed in the Line of Duty: A 10-Year Retrospective Analysis

According to US military data, airway obstruction is the third leading cause of possibly preventable death in combat. In the absence of law enforcement-specific medical training, military experience has been translated to the law enforcement sector. The purpose of this study was to determine whether airway obstruction represents a significant cause of possibly preventable death in police officers, and whether current military combat lifesaver training programs might have prevented these fatalities. De-identified, open-source US Federal Bureau of Investigation (FBI) Uniform Crime Report Law Enforcement Officers Killed and Assaulted (LEOKA) data for the years 1998-2007 were reviewed. Cases were included if officers were on duty at the time of fatal injury and died within one hour from time of wounding from penetrating face or neck trauma. After case identification, letters requesting autopsy reports were sent to the departments of victim officers. Reports were abstracted into a Microsoft Excel database. During the study period, 42 of 533 victim officers met inclusion criteria. Departmental response rate was 85.7%. Autopsy reports were provided for 29 officers; 23 (54.8%) cases remained in the final analysis. All officers died from gunshot wounds. No coroner specifically identified airway obstruction as either a direct cause of death or contributing factor. Based upon autopsy findings, three of 341 officers possibly succumbed to airway trauma (0.9%; 95% CI, 0.0%-1.9%). Endotracheal intubation was the most common advanced airway management technique utilized during attempted resuscitation. The limited LEOKA data suggests that acute airway obstruction secondary to penetrating trauma appears to be a rare cause of possibly preventable death in police officers. Based upon the nature of airway trauma, nasopharyngeal airways would not be expected to be an effective lifesaving intervention. This study highlights the requirement for a comprehensive mortality and "near miss" database for law enforcement officers.

Anaesthesia Management of a Patient with Hereditary Angioedema with Prophylactic Administration of C1 Esterase Inhibitor : Case Report and Literature Review

Hereditary angioedema (HAE) is a rare disorder caused by a deficiency of C1 esterase inhibitor. Minor trauma and emotional stress are the most common initiating events leading to contact system activation and excessive uncontrolled bradykinin release. This manifests as angioedema, a vascular reaction of the deeper layers of the skin and mucous membranes, with vasodilatation and increased permeability resulting in tissue swelling. Severe angioedema can occur in the perioperative period, leading to fatal airway obstruction. We describe the anaesthetic management of a child with HAE for dental rehabilitation and provide an review of the relevant literature.

Foreign body airway obstruction causing a ball valve effect

Foreign body airway obstruction (FBAO) in adults is a rare but potentially fatal anaesthetic airway emergency.1

Choking on a grape: an unusual type of upper airway obstruction

ForewordBradwell, a London doctor, stated in 1663 ‘‘Of things thatendanger stopping of the breath in swallowing, some aresharp, and some blunt… I have heard of a child inWoodstreet strangled with a grape.’’ [1, 2]Case reportAfter a mother had fed a 4-year-old boy a grape he sud-denly became ‘‘blue in the face’’ and started to ‘‘wheeze.’’The boy died about 1 h from the original onset of symp-toms, on his way to hospital. During the autopsy the nextday the non-chewed grape was found wedged between theanterior side of the epiglottis and the upper side of the rootof the tongue, caught between the median glosso-epiglotticfold and the tonsils (Figs. 1, 2). In this position the grapepressed on the epiglottis, pushing it backwards toward thelaryngeal inlet, obstructing it completely. There were noinjuries to the oral, pharyngeal, or laryngeal mucosae.Pleural petechial hemorrhages, congestion, and tissueswelling, as well the fluidity of the blood were noted duringthe autopsy. The cause of death was choking by obstructionof the upper airway by a non-chewed grape.DiscussionChoking refers to blockage of the internal airways, usuallybetween the pharynx and the bifurcation of the trachea.Causes of choking include metallic, plastic, or other for-eign bodies, food material, as well as acute obstructivelesions—edema of the glottis or larynx [3]. Long-standingbenign tumors or other conditions could also compromisethe upper respiratory tract, causing choking [4–6].In adult cases, the most common cause of laryngealobstruction is by a bolus of food, that is, a ‘‘cafe coronary.’’The term was first used by Haugen in 1963 for sudden andunexpected death occurring during a meal because of theaccidental occlusion of the airway by a bolus of food [7].Choking and obstruction of the trachea or main bronchi byaspiration of a foreign body is a common cause of acci-dental death in children aged from 1 to 5 years, that is, a‘‘creche coronary’’ [1, 2, 8]: more than 90 % of cases occurin infants and children younger than 5 years, with 65 % ininfants younger than 2 years [1]. Round foods are the mostfrequently aspirated foreign objects causing death [2]. Thephases of acute fatal airway obstruction are entrance of theobject into the airway, obstruction of the airway, andfailure to expel once obstruction has occurred [8].The case presented in this paper could indicate anotherpossible mechanism of upper airway obstruction in cases ofchoking, beside penetration of the object into the airway.During the first oropharyngeal phase of swallowing, thefood-bolus is forced by the tongue posteriorly toward thepharynx, as the tongue pushes upward against the hardpalate. The superior constrictor muscle of the pharynx thencontracts, preventing the movement of bolus into thenasopharynx. At the same time, the epiglottis slidesdownward to prevent the bolus from entering the larynxand the trachea [9]. Hence, it is easy to presume that a

CPC-123 Risperidone and Suspected Angioneurotic Oedema: Contribution of Multidisciplinary Care

BackgroundPsychotropic drugs may cause cutaneous eruptions with various degrees of severity ranging from urticaria to ‘angioedema’ (AE). Respiratory tract obstruction needs emergency care.Purpose To report on a patient who developed...

Epiglottic and arytenoid cyst in a preterm infant: Case report and review of the literature

Abstract Supraglottic cysts are rare laryngeal lesions that can cause stridor, dysphagia, and fatal airway occlusion in infancy. Treatment is usually surgical with favorable prognosis. In this report, we present a case of a premature infant with supraglottic cyst in an unusual location that was successfully treated with endoscopic marsupialization.

Prompt Reversal of Airway Obstruction Secondary to Angiotensin Converting Enzyme Inhibitor (ACEI) Induced Angioedema by Ecallantide: A Case Report

Fatal airway obstruction from ACEI angioedema has been described but effective therapy has not been established. Intubation is sometimes required for progressive airway compromise. Ecallantide is a kallikrein pathway blocker and may offer benefit in reversing ACEI induced angioedema.

A case of congenital high airway obstruction syndrome caused by complete tracheal obstruction with associated anomalies

An obstruction of the fetal upper airway in utero due to various reasons may cause a fatal condition congenital high airway obstruction syndrome (CHAOS). The prenatal ultrasound fi ndings of CHAOS include large echogenic lungs, fl attened or inverted diaphragms, dilated airways distal to the obstruction, and fetal ascites and/or hydrops [1]. If it is associated with severe hydrops and/ or associated anomalies, its prognosis is fatal. Here we present a case of antenatally diagnosed CHAOS with associated anomalies and a literature review.

디프테리아 백신의 진화와 물리화학적, 분자생물학적, 면역학적 지식의 진보에 따른 새로운 백신의 개발에 관한 고찰연구

This review article provides an overview of the evolution of diphtheria vaccine, its value and its future. Diphtheria is an infectious illness caused by diphtheria toxin produced by pathogenic strains of Corynebacterium diphtheriae. It is characterized by a sore throat with membrane formation due to local tissue necrosis, which can lead to fatal airway obstruction; neural and cardiac damage are other common complications. Diphtheria vaccine was first brought to market in the 1920s, following the discovery that diphtheria toxin can be detoxified using formalin. However, conventional formalin-inactivated toxoid vaccines have some fundamental limitations. Innovative technologies and approaches with the potential to overcome these limitations are discussed in this paper. These include genetic inactivation of diphtheria toxoid, innovative vaccine delivery systems, new adjuvants (both TLRindependent and TLR-dependent adjuvants), and heat- and freeze-stable agents, as well as novel platforms for producing improved conventional vaccine, DNA vaccine, transcutaneous (microneedle-mediated) vaccine, oral vaccine and edible vaccine expressed in transgenic plants. These innovations target improvements in vaccine quality (efficacy, safety, stability and consistency), ease of use and/or thermal stability. Their successful development and use should help to increase global diphtheria vaccine coverage.