Delay in diagnosis is the most important proximate reason for mortality in hereditary angio-oedema: our experience at Chandigarh, India.

BACKGROUND: Hereditary angio-oedema (HAE) is a rare autosomal dominant disorder characterized clinically by recurrent episodes of nonpruritic subcutaneous and/or submucosal oedema. Laryngeal oedema is the commonest cause of mortality in patients with HAE. Prior to the availability of first-line treatment options for the management of HAE, mortality was as high as 30%. Mortality has significantly declined in countries where first-line treatment options are available and patients can access these therapies. There is a paucity of literature on the outcomes of patients with HAE in developing countries where availability of and access to first-line treatment options are still a challenge. OBJECTIVES: To report our experience on mortality in patients with HAE and to report factors associated with the death of these patients. METHODS: We carried out a record review of all patients diagnosed with HAE between January 1996 and August 2022. Families with HAE who had reported the death of at least one family member/relative from laryngeal oedema were studied in detail. RESULTS: Of the 65 families (170 patients) registered in the clinic, 16 families reported the death of at least one family member/relative from laryngeal oedema (total of 36 deaths). Of these 16 families, 14 reported that 1 or more family members had experienced at least 1 attack of laryngeal oedema. One patient died during follow-up when she was taking long-term prophylaxis with stanozolol and tranexamic acid, while the remaining 35 patients were not diagnosed with HAE at the time of their death. At the time of death of all 36 patients, at least 1 other family member had symptoms suggestive of HAE, but the diagnosis was not established for the family. CONCLUSIONS: To our knowledge, this is the largest single-centre cohort of patients with HAE in India reporting mortality data and factors associated with death in these families. The delay in diagnosis is the most important reason for mortality.

Incidental Laryngeal Findings in Routine Laryngopharyngeal Reflux Diagnosis.

BACKGROUND: Laryngopharyngeal reflux (LPR) refers to the backflow of acidic stomach content into the larynx, pharynx, and upper aerodigestive tract. The diagnosis of LPR is based on the patient's history and findings of the laryngoscopy associated with LPR. Other possible manifestations consistent with LPR symptoms include laryngeal cancer, vocal fold granulomas, Reinke's space edema, and vocal polyps. In this study, we compared the characteristics of patients with LPR symptoms and incidental laryngeal findings (ILF) in the laryngoscopic evaluation to those without ILF (WILF). OBJECTIVES: Determine the characteristics of LPR-symptomatic patients with ILF versus WILF. METHODS: In this retrospective study, we examined 160 medical charts from patients referred to the otolaryngology clinic at Galilee Medical Center for LPR evaluation 2016-2018. The reflux symptoms index (RSI), reflux finding score (RFS), and demographics of the patient were collected. All patients with a positive RSI score for LPR (RSI > 9) were included, and the profiles of patients with versus without ILF on laryngoscopy examination were compared. RESULTS: Of the 160 patients, 20 (12.5%) had ILF during laryngoscopy. Most had vocal cord findings such as leukoplakia (20%), polyps (15%), and nodules (20%). Hoarseness, throat clearing, swallowing difficulty, breathing difficulties, and total RSI score were significantly higher in patients with ILF. CONCLUSIONS: Evaluation of LPR symptoms may provide otolaryngologists with a tool to identify patients with other findings on fiberoptic laryngoscopy. A laryngoscopic examination should be part of the examination of every patient with LPR to enable diagnosis of incidental findings.

A novel system that continuously visualizes and analyzes respiratory sounds to promptly evaluate upper airway abnormalities: a pilot study.

Although respiratory sounds are useful indicators for evaluating abnormalities of the upper airway and lungs, the accuracy of their evaluation may be limited. The continuous evaluation and visualization of respiratory sounds has so far been impossible. To resolve these problems, we developed a novel continuous visualization system for assessing respiratory sounds. Our novel system was used to evaluate respiratory abnormalities in two patients. The results were not known until later. The first patient was a 23-year-old man with chronic granulomatous disease and persistent anorexia. During his hospital stay, he exhibited a consciousness disorder, bradypnea, and hypercapnia requiring tracheal intubation. After the administration of muscle relaxant, he suddenly developed acute airway stenosis. Because we could not intubate and ventilate, we performed cricothyroidotomy. Subsequent review of our novel system revealed mild stridor before the onset of acute airway stenosis, which had not been recognized clinically. The second patient was a 74-year-old woman who had been intubated several days earlier for tracheal burn injury, and was extubated after alleviation of her laryngeal edema. After extubation, she gradually developed inspiratory stridor. We re-intubated her after diagnosing post-extubation laryngeal edema. Subsequent review of our novel system revealed serially increased stridor after the extubation, at an earlier time than was recognized by healthcare providers. This unique continuous monitoring and visualization system for respiratory sounds could be an objective tool for improving patient safety regarding airway complications.

Emergency videoendoscopic endonasal tracheal intubation for severe upper airway stenosis.

PURPOSE: Upper airway stenosis is one of the most formidable situations in medicine and is frequently encountered in the ENT clinic. We introduce here our method of emergency endonasal endotracheal intubation under videoendoscopic observation. METHODS: Transnasal endoscopic observation was done, and the region of airway stenosis was detected. Then, the endotracheal tube was prepared and the endoscope was inserted into the tube. The endoscope with tube was inserted up to the larynx. Immediately after the administration of lidocaine to the larynx, the endoscope with tube was inserted to the endolarynx and then to the trachea. The endotracheal tube was tightly held in the nostril, and the endoscope was removed. RESULTS: We have encountered four cases this year. The primary disease developing airway stenosis was acute epiglottitis due to pharyngeal and deep neck abscesses in three cases and laryngeal edema due to Ludwig's angina. All patients underwent uneventful intubation, and dyspnea was immediately ceased. CONCLUSION: In cases showing severe suffocation, the clinician should perform airway maintenance even in an outpatient setting apart from a more monitored setting like the operation room. This technique resembles the usual nasal endoscopic laryngeal observation and is done even in the usual ENT office and/or emergency room. The supine position tends to worsen airway stenosis in patients with upper airway stenosis; however, this technique can be performed in a sitting or semi-sitting position. This method is less invasive for patients and also reduces the risk to the medical staff, especially in this COVID-19 era.

Evaluating Risk Factors for Pediatric Post-extubation Upper Airway Obstruction Using a Physiology-based Tool.

RATIONALE: Subglottic edema is the most common cause of pediatric extubation failure, but few studies have confirmed risk factors or prevention strategies. This may be due to subjective assessment of stridor or inability to differentiate supraglottic from subglottic disease. OBJECTIVES: Objective 1 was to assess the utility of calibrated respiratory inductance plethysmography (RIP) and esophageal manometry to identify clinically significant post-extubation upper airway obstruction (UAO) and differentiate subglottic from supraglottic UAO. Objective 2 was to identify risk factors for subglottic UAO, stratified by cuffed versus uncuffed endotracheal tubes (ETTs). METHODS: We conducted a single-center prospective study of children receiving mechanical ventilation. UAO was defined by inspiratory flow limitation (measured by RIP and esophageal manometry) and classified as subglottic or supraglottic based on airway maneuver response. Clinicians performed simultaneous blinded clinical UAO assessment at the bedside. MEASUREMENTS AND MAIN RESULTS: A total of 409 children were included, 98 of whom had post-extubation UAO and 49 (12%) of whom were subglottic. The reintubation rate was 34 (8.3%) of 409, with 14 (41%) of these 34 attributable to subglottic UAO. Five minutes after extubation, RIP and esophageal manometry better identified patients who subsequently received UAO treatment than clinical UAO assessment (P < 0.006). Risk factors independently associated with subglottic UAO included low cuff leak volume or high preextubation leak pressure, poor sedation, and preexisting UAO (P < 0.04) for cuffed ETTs; and age (range, 1 mo to 5 yr) for uncuffed ETTs (P < 0.04). For uncuffed ETTs, the presence or absence of preextubation leak was not associated with subglottic UAO. CONCLUSIONS: RIP and esophageal manometry can objectively identify subglottic UAO after extubation. Using this technique, preextubation leak pressures or cuff leak volumes predict subglottic UAO in children, but only if the ETT is cuffed.

Postextubation laryngeal edema and stridor resulting in respiratory failure in critically ill adult patients: updated review.

Endotracheal intubation is frequently complicated by laryngeal edema, which may present as postextubation stridor or respiratory difficulty or both. Ultimately, postextubation laryngeal edema may result in respiratory failure with subsequent reintubation. Risk factors for postextubation laryngeal edema include female gender, large tube size, and prolonged intubation. Although patients at low risk for postextubation respiratory insufficiency due to laryngeal edema can be identified by the cuff leak test or laryngeal ultrasound, no reliable test for the identification of high-risk patients is currently available. If applied in a timely manner, intravenous or nebulized corticosteroids can prevent postextubation laryngeal edema; however, the inability to identify high-risk patients prevents the targeted pretreatment of these patients. Therefore, the decision to start corticosteroids should be made on an individual basis and on the basis of the outcome of the cuff leak test and additional risk factors. The preferential treatment of postextubation laryngeal edema consists of intravenous or nebulized corticosteroids combined with nebulized epinephrine, although no data on the optimal treatment algorithm are available. In the presence of respiratory failure, reintubation should be performed without delay. Application of noninvasive ventilation or inhalation of a helium/oxygen mixture is not indicated since it does not improve outcome and increases the delay to intubation.

Dysphagia Caused by Chronic Laryngeal Edema.

A rare case of a young female with chronic diffuse laryngeal edema causing severe swallowing difficulty is presented. The patient was previously treated with antibiotics and steroids with no improvement. Diagnosis was made with biopsy of the epiglottis under local anesthesia in the office.

[PROGNOSTICATION OF "HARD" TRACHEAL INTUBATION IN PATIENTS, SUFFERING PURULENT-INFLAMMATORY DISEASES OF THE JAW-FACIAL REGION].

Clinical follow-up was conducted in 75 patients, to whom the operation and intensive therapy were performed in 2006-2015 yrs for phlegmon of the neck. Difficulties while providing passability of respiratory ways have occurred in 73.3% patients. It was established, that the predictors of "hard" tracheal intubation in patients, operated on for cervical phlegmon, are follows: the cervical tissues oedema, restriction of the mouth opening lesser than 3 cm, odontogenous phlegmon of oral cavity and the neck, rigid epiglottis, the larynx oedema. Presence of these factors demands application of endoscopic methods for tracheal intubation in such patients.

Upper airway edema in 43 patients with hereditary angioedema.

BACKGROUND: Upper airway edema (UAE) occurs infrequently in hereditary angioedema (HAE), but still results in significant morbidity and mortality. OBJECTIVE: To assess patients with HAE and UAE to determine whether unique features exist that can predict the risk of UAE. METHODS: Clinical, laboratory, and genetic data were compared between 43 patients with HAE and 743 UAE attacks and those without UAE and normal controls after ethics committee approval. RESULTS: Most patients had their first episode of UAE in the second (25.6%), third (27.9%), and fourth (23.3%) decades of life, and the mean age at onset was 27.3 years. Evolution of UAE from initial to maximum symptoms was 4.6 hours on average, and most cases (69.8%) progressed within 4 hours. Dyspnea was the most frequent manifestation in per-episode (92.2%) and per-patient (97.7%) analyses. Men developed more asphyxiation attacks (19 vs 2) and underwent more tracheotomies (12 vs 2) than did women. UAE was associated with facial edema in half the studied patients. Patients with a positive family history of UAE had a high risk of UAE attacks. CONCLUSION: Symptoms limited to the upper airway should be taken seriously. Dyspnea may be the only manifestation of UAE. UAE attacks most commonly start spontaneously and usually progress rapidly, as quickly as 30 minutes, from awareness of symptoms to maximum airway involvement. Patients with a positive UAE family history are predisposed to UAE attacks, and men appear to be more apt to develop asphyxiation than women.

Two cases of pharyngolaryngeal zoster advanced to multiple cranial neuropathy.

Varicella zoster virus (VZV) infection of the head and neck region may present with various symptoms. I present two cases of VZV infection of the pharynx and larynx with multiple cranial nerve neuropathies. Their initial symptoms such as sore throat, odynophagia, and dysphasia were complicated by otalgia, dizziness, hearing loss, or ipsilateral facial nerve paralysis. All of these lesions tended to lateralize to the ipsilateral side and endoscopic findings suggested VZV infections, which were confirmed by serial serologic examinations.

DNA rare copy number alterations in Reinke's Edema.

INTRODUCTION: Reinke's Edema (RE) is a laryngeal lesion related to excessive tobacco smoking, voice overuse, and laryngopharyngeal reflux. Although the risk of malignancy has been considered low in literature, RE is classified among precancerous lesions. OBJECTIVES: We investigated DNA Copy Number Alterations (CNAs) in specimens of RE and its potential association with malignant progression. METHODS: We used array-based comparative genomic hybridization (aCGH, Agilent 4 × 180 K platform) to study eight RE cases. All patients were heavy tobacco users for at least 30 years, and none of them progressed to cancer in the follow-up (>8 years). Two RE presented mild dysplasia, one moderate dysplasia, and no histological alterations were found in the remaining five cases. CNAs were compared with the Database of Genomic Variants (DGV) and genes mapped on altered regions had their functions annotated. RESULTS: Six of eight patients showed different rare copy number alterations on chromosomes 2q37.3, 4q13.1, 4q13.3, 7q11.22, 10p14, and 13q34. A gain of the whole chromosome 8 were detected in one case. Of interest, four of eight RE cases showed copy number imbalances involving genes previously described in several tumor types (RASA3, COL6A3, LINC00707, LINP1, SMR3A, and SMR3B). CONCLUSION: The genomic imbalances herein found in RE have the potential to contribute to the phenotype but with limited or no risk of cancer. A long-term follow-up in a large series of patients could clarify the mechanisms involved in the malignant progression of RE.

Intra-individual variation of the cuff-leak test as a predictor of post-extubation stridor.

BACKGROUND: This was an evaluation of intra-individual variation of the cuff-leak test (ΔCLT) immediately post-intubation and pre-extubation, as a predictor of post-extubation stridor. METHODS: Prospective, clinical investigation in the ICU of a non-university hospital. CLTs were performed immediately after intubation (T0) and before extubation (T1) to evaluate the differences in cuff leak (ΔCLT = CL(T1) - CL(T0)). RESULTS: We included 104 mechanically ventilated subjects in the study over a 12-month period. The incidence of post-extubation stridor was 6.7%. Stridor was more common in females of short stature. ΔCLT was considered as significant when CL(T1) - CL(T0) was negative. The sensitivity and the specificity of the test were 86% and 48%, respectively. When we tested the pre-extubation CLT alone with a threshold of 130 mL as a predictor of post-extubation stridor, the sensitivity and the specificity of the test were 86% and 76%, respectively. CONCLUSIONS: The intra-individual variation of CLT immediately post-intubation and pre-extubation does not improve the accuracy of a standard pre-extubation CLT to predict post-extubation stridor. Moreover, the standard pre-extubation CLT did not appear in our study to be an ideal test to detect post-extubation stridor. Larger studies should be performed before generalizing these preliminary results.

Cuff leak volume as a clinical predictor for identifying post-extubation stridor.

BACKGROUND: Post-extubation stridor occurs after translaryngeal intubation results to re-intubation in a number of patients. OBJECTIVE: To determine the cut-off value of the cuff leak volume test among Thai patients as a predictor for post-extubation stridor MATERIAL AND METHOD: Demographic data and cuff leak volume were collected from patients who had been intubated with planned extubation. Clinical stridor was observed and identified after extubation. RESULTS: Among 115 patients, the cuff leak volume of less than 114 ml was used to predict post-extubation stridor with the sensitivity of 89%, specificity of 90%, positive predictive value of 65%, and negative predictive value of 98%, respectively. Among the stridor group, 12 of 19 cases (63.2%) needed re-intubation. CONCLUSION: The cuff leak volume of less than 114 ml can be used as a clinical predictor for identifying post-extubation stridor

Chronic pharyngitis is associated with severe acidic laryngopharyngeal reflux in patients with Reinke's edema.

OBJECTIVES: We evaluated the association between pathological acidic laryngopharyngeal reflux (LPR) events and chronic pharyngitis in patients with Reinke's edema. METHODS: We performed a prospective controlled study in 20 consecutive patients with Reinke's edema without pathological acidic LPR events (group A) and 40 consecutive patients with Reinke's edema with both clinical symptoms and 24-hour pH-metry suggesting acidic LPR (group B). The severity of acidic LPR was assessed by use of the Reflux Finding Score (RFS), the Reflux Symptom Index (RSI), and dual antimony probe 24-hour pH-metry. The patients were evaluated for the presence of chronic pharyngitis by clinical examination and biopsy specimens taken from the posterior pharyngeal wall. The Chi2 test was used to compare the groups for the presence of pharyngitis. In group B, the RSI, the RFS, and the total duration and number of acidic LPR events on 24-hour pH-metry were compared between patients with and without concomitant pharyngitis by use of the Mann-Whitney test. RESULTS: Five patients of group A and 20 patients of group B had chronic pharyngitis. Therefore, more patients with Reinke's edema and clinical signs of LPR tended to have chronic pharyngitis than did those with Reinke's edema and no clinical signs of LPR, but the difference was not statistically significant (p = 0.064; odds ratio, 3.0; 95% confidence interval, 0.9 to 9.8). Among group B patients, those with pharyngitis had significantly more acidic LPR events (p < 0.001) and a greater exposure time to gastric fluid (p = 0.008) than did those without pharyngitis. Their RFS and RSI did not differ significantly (p = 0.692 and p = 0.914, respectively). CONCLUSIONS: Only in the subgroup of patients with Reinke's edema and LPR was there a statistically significant correlation between the pH probe results and the incidence of clinical pharyngitis. Awareness should increase among physicians about addressing chronic pharyngitis in therapy for acidic LPR and/or Reinke's edema.

Pre-tracheotomy for Potentially Emergent Airway Scenarios: Indications and Outcomes.

OBJECTIVES/HYPOTHESIS: Airway access in the setting of unsuccessful ventilation and intubation typically involves emergent cricothyrotomy or tracheotomy, procedures with associated significant risk. The potential for such emergent scenarios can often be predicted based on patient and disease factors. Planned tracheotomy can be performed in these cases but is not without its own risks. We previously described a technique of pre-tracheotomy or exposing the tracheal framework without entering the trachea, as an alternative to planned tracheostomy in such cases. In this way, a tracheotomy can be easily completed if needed, or the wound can be closed if it is not needed. This procedure has since been used in an array of indications. We describe the clinical situations where pre-tracheotomy was performed as well as subsequent patient outcomes. METHODS: Retrospective series of patients undergoing a pre-tracheotomy from 2015 to 2020. Records were reviewed for patient characteristics, indication, whether the procedure was converted to tracheotomy or closed at the bedside, and any post-procedural complications. RESULTS: Pre-tracheotomy was performed in 18 patients. Indications included failed extubation after head and neck reconstruction, subglottic stenosis, laryngeal masses, laryngeal edema, thyroid masses, and an oropharyngeal bleed requiring operative intervention. Tracheotomy was avoided in 10 patients with wound closed at the bedside; procedure was converted to tracheotomy in the remaining eight. There were no complications. Indications for conversion included failed extubation, intraoperative hemorrhage, significant stridor with dyspnea, and inability to ventilate. CONCLUSION: Pre-tracheotomy offers simplified airway access and provides a valuable option in scenarios where tracheotomy may, but not necessarily, be needed. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2802-E2809, 2021.

The influence of laryngopharyngeal reflux in the healing of laryngeal trauma.

The aim of this clinical study was to evaluate the effect of laryngopharyngeal reflux (LPR) on the healing process of surgical laryngeal trauma. A total of 112 consecutive patients, who suffered from LPR and were scheduled for operation of Reinke edema or laryngeal polyps/nodules (40 and 72 patients, respectively) during a period of 5 years, were included. Diagnosis of LPR was made on the basis of both history and dual pH probe recording during 24 h in the inferior esophagus and the hypopharynx. The reflux finding score (RFS) and the reflux symptom index (RSI) were used to estimate the clinical severity of LPR. In patients with LPR, proton pump inhibitors (PPI) were initiated in half of them, randomly chosen. Fifty LPR-free subjects operated for Reinke edema or laryngeal polyps during the same time period (19 and 31 patients, respectively) were used as controls. In six patients who had been administered PPI, resolution of the disease was observed and no surgical treatment was undertaken. The remaining patients were operated on under general anesthesia by a single surgeon. All patients had 1-year postoperative follow-up. Epithelization was complete in all vocal cords of both the control group and the group of patients who had been administered PPI. Within the group of patients who had not taken PPI, six patients presented granulation tissue or recurrence of the polyps and in two of them revision surgery was needed. RFS and RSI scores showed significant improvement postoperatively, across all the three groups of patients, with major differences observed in the group treated by PPI. Comparison of the postoperative RFS and RSI scores between the two groups of patients with LPR showed statistically significant differences in both, indicating better treatment outcome in those patients who had received PPI. It may be thus concluded that LPR influences epithelization and recurrence of laryngeal polyps or Reinke edema in vocal cords, after partial or total decortication. Surgical outcome is superior in patients with LPR with preoperative and postoperative anti-reflux treatment.