BACKGROUND: Patients with airway stenosis (AS) are associated with considerable morbidity and mortality after lung transplantation (LTx). This study aims to develop and validate machine learning (ML) models to predict AS requiring clinical intervention in patients after LTx.
METHODS: Patients who underwent LTx between January 2017 and December 2019 were reviewed. The conventional logistic regression (LR) model was fitted by the independent risk factors which were determined by multivariate LR. The optimal ML model was determined based on 7 feature selection methods and 8 ML algorithms. Model performance was assessed by the area under the curve (AUC) and brier score, which were internally validated by the bootstrap method.
RESULTS: A total of 381 LTx patients were included, and 40 (10.5%) patients developed AS. Multivariate analysis indicated that male, pulmonary arterial hypertension, and postoperative 6-min walking test were significantly associated with AS (all P < 0.001). The conventional LR model showed performance with an AUC of 0.689 and brier score of 0.091. In total, 56 ML models were developed and the optimal ML model was the model fitted using a random forest algorithm with a determination coefficient feature selection method. The optimal model exhibited the highest AUC and brier score values of 0.760 (95% confidence interval [CI], 0.666-0.864) and 0.085 (95% CI, 0.058-0.117) among all ML models, which was superior to the conventional LR model.
CONCLUSIONS: The optimal ML model, which was developed by clinical characteristics, allows for the satisfactory prediction of AS in patients after LTx.

OBJECTIVE: Occurrence of post-intubation laryngotracheal stenosis (LTS) with respect to COVID-19 status.
METHODS: Retrospective cross-sectional inpatient database.
METHODS: Eleven Midwest academic and community hospitals, United States.
METHODS: Adults, mechanically ventilated, from January 2020 to August 2022, who were subsequently readmitted within 6 months with a new diagnosis of LTS.
METHODS: None.
RESULTS: Six thousand eight hundred fifty-one COVID-19 negative and 1316 COVID-19 positive patients were intubated and had similar distribution by age (median 63.77 vs. 63.16 yr old), sex (male, 60.8%; n = 4173 vs. 60%; n = 789), endotracheal tube size (≥ 7.5, 75.8%; n = 5192 vs. 75.5%; n = 994), and comorbidities. The ICU length of stay (median [interquartile range (IQR)], 7.23 d [2.13-16.67 d] vs. 3.95 d [1.91-8.88 d]) and mechanical ventilation days (median [IQR], 5.57 d [1.01-14.18 d] vs. 1.37 d [0.35-4.72 d]) were longer in the COVID-19 positive group. The occurrence of LTS was double in the COVID-19 positive group (12.7%, n = 168 vs. 6.4%, n = 440; p < 0.001) and was most commonly diagnosed within 60 days of intubation. In multivariate analysis, the risk of LTS increased by 2% with each additional ICU day (hazard ratio [HR], 1.02; 95% CI, 1.02-1.03; p < 0.001), by 3% with each additional day of ventilation (HR, 1.03; 95% CI, 1.02-1.04; p < 0.001), and by 52% for each additional reintubation (HR, 1.52; 95% CI, 1.36-1.71; p < 0.001). We observed no significant association COVID-19 status and risk of LTS.
CONCLUSIONS: The occurrence of post-intubation LTS was double in a COVID-19 positive cohort, with higher risk with increasing number of days intubated, days in the ICU and especially with the number of reintubations. COVID-19 status was not an independent risk factor for LTS.

UNASSIGNED: Pediatric patients with certain rare diseases are at increased risk of severe respiratory syncytial virus (RSV) infection. However, the prophylactic use of anti-RSV antibody (palivizumab) in these patients is not indicated at present in Japan.
UNASSIGNED: This first-in-the-world multicenter, uncontrolled, open-label, phase II clinical trial was carried out between 28 July 2019 and 24 September 2021 at seven medical institutions in Japan to investigate the efficacy, safety, and pharmacokinetics of palivizumab in 23 subjects recruited from among neonates, infants, or children aged 24 months or younger who had any of the following conditions: pulmonary hypoplasia, airway stenosis, congenital esophageal atresia, inherited metabolic disease, or neuromuscular disease. At least four continuous doses of palivizumab were administered intramuscularly at 15 mg/kg at intervals of 30 days.
UNASSIGNED: Twenty-three enrolled subjects completed the study. No subject required hospitalization for RSV. Adverse events (AE) did not notably differ from the event terms described in the latest interview form. Five severe AEs required unplanned hospitalization, but resolved without RSV infection. Therapeutically effective concentrations of palivizumab were maintained throughout the study period.
UNASSIGNED: Palivizumab might be well tolerated and effective in preventing serious respiratory symptoms and hospitalization due to severe RSV infection, indicating the prophylactic use in the pediatric patients included in this study.
UNASSIGNED: Japan Agency for Medical Research and Development (AMED), grant numbers 19lk0201097h0001 (to MM), 20lk0201097h0002 (to MM), 21lk0201097h0003 (to MM), and 22lk0201097h0004 (to MM). AMED did not have any role in the execution of this study, analysis and interpretation of the data, or the decision to submit the results.

Photodynamic therapy (PDT) has been shown to be effective and safe in the treatment of malignant central airway stenosis. However, the laser dose for talaporfin PDT is unclear. We herein review cases where talaporfin PDT was used to treat malignant central airway stenosis. A total of 17 lesions were treated with talaporfin PDT at laser doses of 50-150 J/cm2. Improvement of airway stenosis was observed in all cases except for 1 lesion treated with a dose of 50 J/cm2. The results show that talaporfin PDT with 100 J/cm2 of laser dose is a feasible treatment for malignant central airway stenosis. (This is a secondary publication from the Journal of Japan Society for Laser Surgery and Medicine 2022; 43(1): 9-12.).

The prophylactic use of anti-respiratory syncytial virus (RSV) antibody (palivizumab) for severe RSV infection is not approved in Japan in specified groups of infants with neuromuscular diseases or other rare diseases associated with reduced ventilation competence or difficulty in expectoration, which increase the risk of exacerbation of severe RSV infection. The objective of this study is to investigate the efficacy, safety, and pharmacokinetics of palivizumab in pediatric patients with those rare diseases for which palivizumab is not indicated at present.
This study is a multicenter, uncontrolled, open-label study planned to be carried out between July 1, 2019 and June 30, 2022 at 7 medical institutions in Japan. The study population will be recruited from among neonates, infants, or children aged 24 months or younger with a condition falling under any of the following 5 disease groups: pulmonary hypoplasia, airway stenosis, congenital esophageal atresia, inherited metabolic disease, or neuromuscular disease. The planned sample size is 18 subjects, including at least 3 subjects per disease group. Throughout the RSV season, at least 4 continuous doses of palivizumab will be administered intramuscularly at 15 mg/kg at intervals of 30 days. The efficacy and safety of palivizumab will be comprehensively evaluated based on the incidence of RSV-related hospitalization, and serum palivizumab concentration, serum anti-palivizumab antibody concentration, and the occurrence of adverse events/reactions after the start of palivizumab treatment.
This study will evaluate the efficacy and safety of palivizumab in pediatric patients with rare diseases which place them at high risk of severe RSV infection, but which fall outside the current indications for palivizumab prophylaxis. The generated data will have implications for the regulatory approval of prophylactic palivizumab treatment in this patient group.
This study has been prospectively registered in Japic Clinical Trials Information, which is managed and administered by the Japan Pharmaceutical Information Center (registration number: JapicCTI-194946 , registration date: September 10, 2019).

The COVID-19 pandemic has led to unprecedented demands on healthcare with many requiring intubation. Tracheostomy insertion has often been delayed and the enduring effects of this on voice, swallow, and airway outcomes in COVID-19 tracheostomy patients are unknown. The aim of this study was to prospectively assess these outcomes in this patient cohort following hospital discharge.
All COVID-19 patients who had undergone tracheostomy insertion, and were subsequently decannulated, were identified at our institution and followed up 2 months post-discharge. Patient-reported (PROMS) and clinician-reported outcome measures, endoscopic examination, and spirometry were used to assess voice, swallow, and airway outcomes.
Forty-one patients were included in the study with a mean age of 56 years and male:female ratio of 28:13. Average duration of endotracheal intubation was 24 days and 63.4% of tracheostomies were performed at day 21 to 35 of intubation. 53.7% had an abnormal GRBAS score and 30% reported abnormal swallow on EAT-10 questionnaire. 81.1% had normal endoscopic examination of the larynx, however, positive endoscopic findings correlated with the patient self-reported VHI-10 (P = .036) and EAT-10 scores (P = .027). 22.5% had spirometric evidence of fixed upper airway obstruction using the Expiratory-Disproportion Index (EDI) and Spearman correlation analysis showed a positive trend between abnormal endoscopic findings and EDI scores over 50 (P < .0001).
The preliminary results of this study reveal a high incidence of laryngeal injury among patients who underwent intubation and tracheostomy insertion during the COVID-19 pandemic. As these patients continue to be followed up, the evolution of these complications will be studied.
3 Laryngoscope, 131:E1918-E1925, 2021.

OBJECTIVE: Tracheal reconstruction is a rare surgical procedure and the actual incidence of or indications for this procedure have not been thoroughly elucidated. We performed the nationwide database analysis to clarify the real-world situation of laryngotracheal surgery requiring cervical tracheal reconstruction.
METHODS: Patients who underwent surgical treatment for laryngotracheal stenosis or defect from 2008 to 2016 were identified from the Diagnosis Procedure Combination inpatient database, collected from 270 acute care hospitals in Japan. Patients were divided into two groups based on presence/absence of malignancy, and T-tube or tracheotomy dependence at 6 months after surgery was compared between the two groups.
RESULTS: One hundred and thirty-four patients (75 males) were identified. The median age at surgery was 65.5 years. The most common indication for surgery was malignancy (n = 60, 44.8%), followed by iatrogenic (n = 25, 18.6%), trauma (n = 6, 4.5%), malformation of the larynx and trachea (n = 6, 4.5%), and chronic inflammatory disease (n = 4, 2.8%). Thyroid cancer was the most common malignancy (n = 38). Thirty patients (22.4%) failed to decannulate within 6 months and malignancy was associated with a lower dependence on T-tube or tracheotomy at 6 months after surgery (adjusted odds ratio: 0.25, 95% confidence interval: 0.08-0.79).
CONCLUSIONS: A Japanese health insurance claims database provided a useful overview of the clinical features and outcomes of patients who underwent cervical tracheal reconstruction surgery for laryngotracheal stenosis or defect.

Topical mitomycin-C (MMC) application is a commonly accepted adjuvant therapy in the surgical treatment for laryngotracheal stenosis (LTS). However, the efficacy of MMC has not been examined in a prospective, randomized clinical trial in humans. We aimed to examine the efficacy of MMC in the treatment of LTS patients as compared to a placebo-controlled group.
Prospective, randomized, double-blind, placebo-controlled clinical trial.
Fifteen patients with LTS were enrolled in a 24-month trial and randomized into one of two groups: 1) endoscopic surgical treatment with topical application of MMC or 2) endoscopic surgical treatment with topical application of saline. Postoperatively, patients were evaluated at standardized intervals with a symptom questionnaire and spirometry. Subsequent surgery was performed as needed based on relapse of stenosis on exam and patient-reported symptom severity.
The average interval between surgical treatments was 17.9 months in the placebo group and 17.4 months in the MMC group (P = .95). There was no difference in magnitude of peak inspiratory flow (PIF) improvement between groups. The average magnitude of PIF change was 1.3 L/sec and 1.1 L/sec for the placebo and MMC groups, respectively (P = .64). Similarly, there was no difference in magnitude of symptom improvement or duration of symptom improvement between the two groups.
This prospective, randomized. double-blind. placebo-controlled trial suggests that the use of MMC as a topical adjuvant therapy has no additional benefit in the endoscopic surgical management of LTS. Further study is needed.
1b Laryngoscope, 130:706-711, 2020.

BACKGROUND: Endoscopic estimation of the degree of stenosis in central airway obstruction is subjective and highly variable.
OBJECTIVE: To determine the benefits of using SENSA (System for Endoscopic Stenosis Assessment), an image-based computational software, for obtaining objective stenosis index (SI) measurements among a group of expert bronchoscopists and general pulmonologists.
METHODS: A total of 7 expert bronchoscopists and 7 general pulmonologists were enrolled to validate SENSA usage. The SI obtained by the physicians and by SENSA were compared with a reference SI to set their precision in SI computation. We used SENSA to efficiently obtain this reference SI in 11 selected cases of benign stenosis. A Web platform with three user-friendly microtasks was designed to gather the data. The users had to visually estimate the SI from videos with and without contours of the normal and the obstructed area provided by SENSA. The users were able to modify the SENSA contours to define the reference SI using morphometric bronchoscopy.
RESULTS: Visual SI estimation accuracy was associated with neither bronchoscopic experience (p = 0.71) nor the contours of the normal and the obstructed area provided by the system (p = 0.13). The precision of the SI by SENSA was 97.7% (95% CI: 92.4-103.7), which is significantly better than the precision of the SI by visual estimation (p < 0.001), with an improvement by at least 15%.
CONCLUSIONS: SENSA provides objective SI measurements with a precision of up to 99.5%, which can be calculated from any bronchoscope using an affordable scalable interface. Providing normal and obstructed contours on bronchoscopic videos does not improve physicians\' visual estimation of the SI.

Cricoid fracture is a serious concern for balloon dilatation in airway stenosis. Furthermore, there are no studies examining tracheal rupture in balloon dilatation of stenotic segments. The aim of this study was to evaluate the effect of supramaximal pressures of balloons on the cricoid and tracheal rings.
Prospective cadaveric study.
Seven cadaveric laryngotracheal complexes of normal adults with intact cricothyroid membranes were acquired. Noncompliant vascular angioplasty balloons (BARD-VIDA) were used for dilatation. The subglottis and trachea were subjected to supramaximal dilatation pressures graduated to nominal burst pressure (NBP) and, if necessary, rated burst pressure (RBP). Larger-diameter balloons, starting from 18 mm size to 24 mm, were used. Dilatations were maintained for 3 minutes.
The cricoid ring was disrupted by larger-diameter balloons (22 mm and 24 mm) even at lower pressures (less than NBP) in six cases. Tracheal cartilages were very distensible, and external examination after supramaximal dilatation (24 mm close to RBP) revealed no obvious cartilage fractures or trachealis tears. Histopathological examination revealed sloughing of mucosa in the areas corresponding to balloon placement, but no microfractures or disruption of the perichondrium of tracheal ring cartilages.
These results indicate that the cricoid is vulnerable to injury from larger balloons even at lower dilatation pressures. The tracheal cartilages and the membranous wall of the trachea remained resilient to supramaximal dilatation and larger balloons.
NA. Laryngoscope, 128:1304-1309, 2018.