Development and validation of the Exercise-Induced Laryngeal Obstruction Dyspnea Index (EILODI).

BACKGROUND: Exercise-induced laryngeal obstruction (EILO) causes exertional dyspnea and is important for its effect on quality of life, diagnostic confusion with exercise-induced asthma, and health care resource utilization. There is no validated patient-reported outcome measure specific to EILO. OBJECTIVE: We sought to develop, validate, and define a minimal clinically important difference for a patient-reported outcome measure to be used with adolescents and young adults with EILO. METHODS: A multidisciplinary group created a preliminary measure, modified by a 10-member participant focus group, with 20 items scored along a 5-point Likert scale. A subsequent cohort of participants recruited from a clinic, aged 12 to 21 years, with confirmed EILO by continuous laryngoscopy during exercise testing (1) completed the measure at 3 points in time over 28 days and (2) provided anchoring data in the form of a daily exercise log and categorical self-assessments of clinical improvement. Thirty additional participants without exertional dyspnea served as controls. RESULTS: Two hundred nineteen subjects with mild to severe EILO participated in the exploratory factor analysis, which identified 7 factors within the preliminary outcome measure. After a process of item reduction, a 12-item metric with a total score ranging from 0 to 48 was developed. Mean scores of patients with EILO and healthy controls at baseline were 28.8 ± 7.4 and 4.5 ± 7.4, respectively. A minimal clinically important difference of 6 was determined by comparison of index change with changes in categorical self-assessments of improvement. CONCLUSIONS: This is the first patient-reported outcome measure specifically designed for adolescents and young adults with EILO.

Continuous laryngoscopy quantitates laryngeal behaviour in exercise and recovery.

Exercise-induced laryngeal obstruction (E-ILO) causes exertional dyspnoea. There is no standardised methodology which characterises laryngeal obstruction in relation to exercise or links laryngeal obstruction and dyspnoea severity. Continuous laryngoscopy during exercise (CLE) may improve diagnostic sensitivity by enabling laryngeal visualisation at peak work capacity in patients with rapidly resolving obstruction. The time course of laryngeal obstruction across exercise and recovery has not been quantitated until this report.Adolescents and young adults referred for CLE were laryngoscopically monitored across rest, maximal cycle ergometry exercise, and recovery. Three reviewers, blinded to time sequencing, rated inspiratory glottic and supraglottic obstruction during 10 windows of 15-s corresponding to rest, 25%, 50%, 75%, 90% and 100% of individual symptom-limited peak work capacity (expressed in Watts), and four consecutive recovery windows.85 patients were screened and 71 included. Over 96% of time windows were interpretable. Laryngeal obstruction severity reached observed maximal levels at peak work capacity, and rapidly resolved. A spectrum of observed maximal obstruction was measured.CLE provides interpretable data demonstrating laryngeal obstruction in patients with suspected E-ILO that is more severe at peak work capacity than during rest, submaximal exercise, or recovery. Observed maximal obstruction was infrequently severe and rapidly resolved.

Cord Blood-Derived Endothelial Progenitor Cells Promote In Vivo Regeneration of Human Hematopoietic Bone Marrow.

PURPOSE: Victims of acute radiation exposure are susceptible to hematopoietic toxicity due to bone marrow damage and loss of mature blood elements. Here, we evaluated cord blood-derived endothelial progenitor cells (CB-EPCs) as a potential cellular therapy for mitigation of hematologic acute radiation syndrome. CB-EPCs express endothelial cell markers and maintain their growth characteristics beyond 10+ passages without diminishing their doubling capacity. Further, CB-EPCs can be cryopreserved in vapor-phase liquid nitrogen and easily recovered for propagation, making them an attractive nonimmunogenic cellular therapy for off-the-shelf use. Importantly, we show CB-EPCs have the capacity to potently expand adult human bone marrow hematopoietic progenitor cells both in vitro and in vivo. METHODS AND MATERIALS: To demonstrate the role of CB-EPCs in promoting in vivo human immune reconstitution after irradiation, we employed a novel humanized mouse model established by transplant of CD34+ bone marrow cells from 9 unique adult organ donors into immunocompromised NSG-SGM3 mice. The response of the humanized immune system to ionizing irradiation was then tested by exposure to 1 Gy followed by subcutaneous treatment of CB-EPCs, Food and Drug Administration-approved growth factor pegfilgrastim (0.3 mg/kg), or saline. RESULTS: At day 7, total human bone marrow was decreased by 80% in irradiated controls. However, treatment with either growth factor pegfilgrastim or CB-EPCs increased recovery of total human bone marrow by 2.5-fold compared with saline. Notably, CB-EPCs also increased recovery of both human CD34+ progenitors by 5-fold and colony-forming capacity by 3-fold versus saline. Additionally, CB-EPCs promoted recovery of endogenous bone marrow endothelial cells as observed by both increased vessel area and length compared with saline. CONCLUSIONS: These findings indicate the feasibility of using humanized mice engrafted with adult bone marrow for radiation research and the development of CB-EPCs as an off-the-shelf cellular therapy for mitigation of hematologic acute radiation syndrome.

Therapeutic laryngoscopy during exercise: A novel non-surgical therapy for refractory EILO.

BACKGROUND: Exercise-induced laryngeal obstruction (EILO) may affect as many as 6% of the adolescent population, with some patients experiencing symptoms refractory to conservative interventions. OBJECTIVES: This report describes therapeutic laryngoscopy during exercise, a novel, non-surgical intervention that harnesses real-time laryngoscopy video as biofeedback to control laryngeal aperture during high-intensity exercise. Additionally, we quantitate patient-reported perceptions of procedure safety, tolerability, learning value, and effectiveness. METHODS: Clinical EILO patients with symptoms refractory to conventional respiratory retraining and other therapies were referred for the procedure which features laryngoscopy video as biofeedback during serial physician-guided 1-min exercise sprints. We quantify perceptions of procedure safety, tolerability, learning value, and effectiveness through questionnaires offered to all patients as well as observers of the procedure. RESULTS: Forty-one patients and 37 parent observers were approached for feedback; 88% of patients and 95% of observers consented to participation. Patients and observers reported perceptions of safety and tolerability (81% and 86%, respectively), learning value (78% and 91%, respectively), and effectiveness (58% and 80%, respectively) with patient age predicting some responses. Seventy-five percent of patients noted that "Since the procedure, my breathing during exercise has improved," and 85% of this group noted that therapeutic laryngoscopy during exercise was "the most important therapy leading to my breathing improvement." The procedure also provided insight into the psychological experience of patients, a domain not clinically apparent prior to the procedure. CONCLUSIONS: Our data support further study of therapeutic laryngoscopy during exercise as a possible intervention for patients with refractory EILO. Pediatr Pulmonol. 2017;52:813-819. © 2016 Wiley Periodicals, Inc.