A longitudinal study of exercise-induced bronchoconstriction and laryngeal obstruction in high school athletes.

BACKGROUND: Exercise-induced bronchoconstriction (EIB) and exercise-induced laryngeal obstruction (EILO) are common in elite athletes. Knowledge of which factors are related to incident EIB and EILO is limited. The aim of this study was to explore the course of EIB and EILO in adolescent athletes over a 2 years period and baseline characteristics related to incident EIB. METHODS: Questionnaire data on respiratory symptoms, asthma, and aeroallergy and results of objective EIB and EILO tests were collected from 58 participants (27 tested for EILO) at baseline and after 2 years (follow-up). Associations between incident EIB and baseline asthma-like symptoms, exercise-induced symptoms, fractional exhaled nitric oxide (FeNO), aeroallergy, and sex were assessed using logistic regression models. RESULTS: Ten participants had incident EIB, and eight participants had persistent EIB. Five were EIB positive at baseline but negative at follow-up, while 35 participants were EIB negative at both time points. Having incident EIB was associated with reporting waking up with chest tightness (OR = 4.38; 95% CI: 1.06, 22.09). Reporting an increased number of asthma-like symptoms increased the likelihood of incident EIB (OR = 2.78; 95% CI: 1.16, 6.58). No associations were found between exercise-induced symptoms, FeNO, aeroallergy, or sex and incident EIB. Incident EILO was found in three and persistent EILO in two of the 27 participants tested. CONCLUSION: Two in nine had incident EIB and one eighth had incident EILO, suggesting that recurrent testing for EIB and EILO may be relevant in young athletes. Particularly, EIB-negative athletes reporting multiple asthma-like symptoms could benefit from recurrent EIB testing.

Self-reported exercise-induced dyspnea and airways obstruction assessed by oscillometry and spirometry in adolescents.

BACKGROUND: Self-reported exercise-induced dyspnea (EID) is common among adolescents. Possible underlying pathologies are exercise-induced bronchoconstriction (EIB) and laryngeal obstruction (EILO). The forced oscillation technique (FOT) may evaluate exercise-induced changes in airway caliber. AIM: To investigate in adolescents the relationship between EID, EIB (post-exercise fall in forced expiratory volume in 1s (FEV1 )≥10%), EILO, and post-exercise challenge changes in FOT parameters. METHODS: One hundred and forty-three subjects (97 with EID) of 13-15 years old underwent a standardized exercise challenge with FOT measurement and spirometry repeatedly performed between 2 and 30 min post-exercise. EILO was studied in a subset of 123 adolescents. Subjects showing greater changes than the healthy subgroup in the modulus of the inspiratory impedance were considered FOT responders. RESULTS: EID-nonEIB subjects presented similar post-exercise changes in all FOT parameters to nonEID-nonEIB adolescents. Changes in all FOT parameters correlated with FEV1 fall. 45 of 97 EID subjects responded neither by FEV1 nor FOT to exercise. 19 and 18 subjects responded only by FEV1 (onlyFEV1 responders) or FOT (onlyFOTresponders), respectively. Only a lower baseline forced vital capacity (FVC)%predicted and a higher FEV1 /FVC distinguished the onlyFEV1 responders from onlyFOTresponders. FOT parameters did not present specific post-exercise patterns in EILO subjects. CONCLUSION: FOT can be used to identify post-exercise changes in lower airway function. However, EID has a modest relation with both FEV1 and FOT responses, highlighting the need for objective testing. More research is needed to understand whether onlyFEV1 responders and onlyFOTresponders represent different endotypes.

High Prevalence of Exercise-induced Laryngeal Obstruction in a Cohort of Elite Cross-country Skiers.

INTRODUCTION: Exercise-induced laryngeal obstruction (EILO) is a differential diagnosis for asthma and prevalent in athletes referred for exercise-induced dyspnea. The aim of this study was to estimate the prevalence of EILO in elite cross-country skiers, known for a high prevalence of asthma. METHOD: Elite cross-country skiers were invited for screening of EILO. Screening consisted of clinical assessment, questionnaires, skin prick test, spirometry, eucapnic voluntary hyperventilation test, and continuous laryngoscopy during exercise test. Current asthma was defined as physician-diagnosed asthma and use of asthma medication during the last 12 months. EILO was defined as ≥2 points at the supraglottic or glottic level during exercise at maximal effort, using a visual grade score system. RESULT: A total of 89 (51% female) cross-country skiers completed the study. EILO was identified in 27% of the skiers, 83% of whom were female. All skiers with EILO had supraglottic EILO, and there was no glottic EILO. Current asthma was present in 34 (38%) of the skiers, 10 (29%) of whom had concomitant EILO. In the skiers with EILO, a higher proportion reported wheeze or shortness of breath after exercise, compared with skiers without EILO. In skiers with EILO and current asthma, compared with skiers with asthma only, a higher proportion reported wheeze or shortness of breath after exercise. Asthma medication usage did not differ between these groups. CONCLUSION: EILO is common in elite cross-country skiers, especially females. Asthma and EILO may coexist, and the prevalence of respiratory symptoms is higher in skiers with both. Testing for EILO should be considered in cross-country skiers with respiratory symptoms.

The course of specific self-reported exercise-induced airway symptoms in adolescents with and without asthma.

In a general population, the prevalence of exercise-induced cough, dyspnoea, throat and chest tightness, wheeze, and stridor increases from adolescence to young adulthood among individuals without asthma in contrast to individuals with asthma https://bit.ly/3hR57OX.

Prevalence of exercise-induced bronchoconstriction and laryngeal obstruction in adolescent athletes.

OBJECTIVES: To study the prevalence of exercise-induced bronchoconstriction (EIB) and exercise-induced laryngeal obstruction (EILO) in adolescent athletes. METHODS: All adolescents (n = 549) attending first year at a sports high school in 2016 and 2017, were invited to answer a questionnaire on respiratory symptoms. The 367 responding participants were divided into two groups based on whether they reported exercise-induced dyspnea (dyspnea group) or not (nondyspnea group). Randomly selected participants in each group were invited to undergo two standardized exercise tests, an EIB test and a continuous laryngoscopy exercise (CLE) test, to investigate EILO. RESULTS: In total, 98 participants completed an EIB test, 75 of whom also completed a CLE test. Positive EIB tests: eight of 41 in the dyspnea group and 16 of 57 in the nondyspnea group. Positive CLE tests: 5 of 34 in the dyspnea group and three of 41 in the nondyspnea group. The estimated prevalence of EIB was 23.1% (95% confidence interval [CI]: 14.5-33.8) and of EILO 8.1% (95% CI: 2.5-18.5) in the whole study population. No differences in prevalence of EIB or EILO were found between the dyspnea and the nondyspnea groups. CONCLUSION: EIB was highly prevalent in this cohort of adolescent athletes. EILO was less prevalent, but represents an important differential diagnosis to EIB. Self-reported exercise-induced dyspnea is a weak indicator for both EIB and EILO and standardized testing should be provided.

Differences in laryngeal movements during exercise in healthy and dyspnoeic adolescents.

OBJECTIVES: To compare glottic and supraglottic movements in healthy adolescents and adolescents experiencing dyspnoea during strenuous exercise. METHODS: Using the continuous laryngoscopy exercise (CLE)-test laryngeal movements during exercise were analysed in healthy controls (n = 28) and compared to subjects with exercise induced bronchoconstriction (EIB) (n = 10), exercise induced laryngeal obstruction (EILO) (n = 10) and subjects experiencing exercise-induced dyspnoea without having any of these diagnoses (n = 31). Images from the video recordings were assessed regarding glottic angle, glottic area and supraglottic area using the software measuring tool EILOMEA. RESULTS: No significant differences were detected between controls, the dyspnoea group without a diagnosis of EIB or EILO and the EIB group regarding glottis angle, glottis area or supraglottic area at maximum effort. All three parameters differed significantly in the EILO group compared to the other groups (p=<0.001). In the group with EILO all but one had supraglottic obstruction (corresponding to a CLE-test score ≥2). Movement of the laryngeal structures, corresponding to a CLE-test score of 1, at glottic and/or supraglottic level was seen in 26 of 35 (74%) of controls, 34 out of 41 (83%) of patients in the dyspnoea group, and in 25 of 38 (66%) of EIB-subjects. CONCLUSION: Minor movements at both glottic and supraglottic level are equally common in healthy controls as among adolescents with exercise induced dyspnoea without EIB or EILO and adolescents with EIB. Adolescents with EILO had a statistically significant more pronounced supraglottic obstruction than the other groups.

Exercise-Induced Laryngeal Obstruction-An Overview.

Exertional dyspnea is common in health and disease. Despite having known for centuries that breathlessness can arise from the larynx, exercise-induced laryngeal obstruction is a more prevalent condition than previously assumed. This article provides a brief overview of the history, epidemiology, and pathophysiology of exercise-induced laryngeal obstruction.

Surgical Intervention for Exercise-Induced Laryngeal Obstruction.

Respiratory distress during exercise can be caused by exercise-induced laryngeal obstruction (EILO). The obstruction may appear at the level of the laryngeal inlet (supraglottic), similar to supraglottic collapse observed in infants with congenital laryngomalacia (CLM). This observation has encouraged surgeons to treat supraglottic EILO with procedures proven efficient for severe CLM. This article summarizes key features of the published experience related to surgical treatment of EILO. Supraglottoplasty is an irreversible procedure with potential complications. Surgery should be restricted to cases where the supraglottic laryngeal obstruction significantly affects the quality of life in patients for whom conservative treatment modalities have failed.

Inducible laryngeal obstruction: an official joint European Respiratory Society and European Laryngological Society statement.

Inducible laryngeal obstruction (ILO) describes an inappropriate, transient, reversible narrowing of the larynx in response to external triggers. ILO is an important cause of a variety of respiratory symptoms and can mimic asthma. Current understanding of ILO has been hampered by imprecise nomenclature and variable approaches to assessment and management. A task force of the European Respiratory Society (ERS) and European Laryngological Society (ELS) was thus set up to address this, and to identify research priorities.A literature search identified relevant articles published until June 2016, using all identifiable terms for ILO, although including only articles using laryngoscopy. In total, 172 out of 252 articles met the inclusion criteria, summarised in sections on diagnostic approach, aetiology, comorbidities, epidemiology and treatment. The consensus taxonomy published by ERS, ELS and the American College of Chest Physicians (ACCP) in 2015 is used throughout this statement.We highlight the high prevalence of ILO and the clinical impact for those affected. Despite recent advances, most aspects of this condition unfortunately remain incompletely understood, precluding firm guidance. Specifically, validated diagnostic and treatment algorithms are yet to be established, and no randomised control studies were identified in this search; hence we also make recommendations for future research.

Comparison of Clinical Factors Between Patients With Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema and Cough.

BACKGROUND: Angioedema is a rare and serious adverse drug reaction (ADR) to angiotensin-converting enzyme (ACE) inhibitor treatment. Dry cough is a common side effect of ACE inhibitors and has been identified as a possible risk factor for angioedema. OBJECTIVE: We compared characteristics between patients with ACE inhibitor-induced angioedema and cough with the aim of identifying risk factors that differ between these adverse events. METHODS: Data on patients with angioedema or cough induced by ACE inhibitors were collected from the Swedish database of spontaneously reported ADRs or from collaborating clinicians. Wilcoxon rank sum test, Fisher's exact test, and odds ratios (ORs) with 95% CIs were used to test for between-group differences. The significance threshold was set to P <0.00128 to correct for multiple comparisons. RESULTS: Clinical characteristics were compared between 168 patients with angioedema and 121 with cough only. Smoking and concomitant selective calcium channel blocker treatment were more frequent among patients with angioedema than cough: OR = 4.3, 95% CI = 2.1-8.9, P = 2.2 × 10-5, and OR = 3.7, 95% CI = 2.0-7.0, P = 1.7 × 10-5. Angioedema cases were seen more often in male patients (OR = 2.2, 95% CI = 1.4-3.6, P = 1.3 × 10-4) and had longer time to onset and higher doses than those with cough ( P = 3.2 × 10-10 and P = 2.6 × 10-4). A multiple model containing the variables smoking, concurrent calcium channel blocker treatment, male sex, and time to onset accounted for 26% of the variance between the groups. CONCLUSION: Smoking, comedication with selective calcium channel blockers, male sex, and longer treatment time were associated with ACE inhibitor-induced angioedema rather than cough.

The relationship between exercise induced bronchial obstruction and health related quality of life in female and male adolescents from a general population.

BACKGROUND: Previous studies have observed that exercise-induced bronchoconstriction (EIB) is more common and more strongly related to exercise related breathing problems in female adolescents than male adolescents. However, few studies have investigated the association between EIB and health related quality of life (HRQoL) from a gender perspective. The aim of this study was to examine the association between EIB and HRQoL and physical activity level in female and male adolescents with and without EIB. METHODS: From a population based study on exercise-induced breathing problems among adolescents (13-15 years, n = 3838) a cross sectional study with prospective data collection was carried out in a random subsample of 140 adolescents. The subjects in the sample were tested for EIB with a standardised exercise test, of which 49 adolescents were tested positive. HRQoL was assessed with the Pediatric Quality of Life Inventory (PedsQL) and the adolescents' physical activity levels were measured objectively with accelerometer. RESULTS: The female subjects with EIB reported a lower HRQoL, both in total score (p = 0.03) and physical functioning score (p = 0.009) and had a lower baseline FEV1 compared to females without EIB (88 vs. 94 % predicted, p = 0.001). No differences were found in HRQoL or baseline lung function between males with or without EIB. There were no differences in minutes of moderate to vigorous physical activity per day between females or males with and without EIB. CONCLUSION: In a general population, the female adolescents with EIB had lower HRQoL and poorer baseline lung function compared to counterparts without EIB. These differences were not observed in males. EIB does not appear to affect the level of daily physical activity neither in females nor males.

Definition of nocturnal gastroesophageal reflux for studies on respiratory diseases.

OBJECTIVE: Nocturnal gastroesophageal reflux (nGER) has been associated with respiratory diseases. Our aim was to study a questionnaire method to identify nGER subjects with respiratory involvement in a general population. MATERIAL AND METHODS: A subgroup of Icelandic participants in the European Community Respiratory Health Survey III (ECRHS III) reporting symptoms of nGER (n = 48) as well as age and gender paired controls (n = 42) were studied further by a structured interview, questionnaires, laryngeal fibrescopy, and exhaled breath condensate. A subgroup underwent 24-h oesophageal pH impedance (24-h MII-pH) measurements. Symptoms of nGER were assessed with a modified version of the reflux disease questionnaire (RDQ), where symptoms were divided into daytime and nocturnal. A report of nGER both at baseline and at follow-up was defined as persistent nGER. RESULTS: Participants reporting persistent nGER had significantly more signs of laryngopharyngeal reflux according to the reflux finding score than those without nGER (Mean ± SD: 5.1 ± 2.3 vs. 3.9 ± 2.2, p = 0.02). Of the 16 persistent nGER subjects that underwent 24-h MII-pH, 11 had abnormal gastroesophageal reflux, but none of three control subjects (69% vs. 0%). Pepsin was more commonly found in exhaled breath condensate in the nGER group (67% vs. 45%, p = 0.04). CONCLUSIONS: Participants with nGER symptoms at least once a month, reported on two occasions, had a high level of positive 24-h MII-pH measurements, laryngeal inflammation and pepsin in exhaled breath condensate. This nGER definition identified a representable group for studies on nGER and respiratory diseases in a general population.

Early laryngeal outcome of prolonged intubation using an anatomical tube: a double blind, randomised study.

The objective of this study was to study the short-term impact on larynx by a newly designed anatomical tube. A prospective randomised trial of a newly designed anatomical tube versus a standard endotracheal tube in patients operated under general anaesthesia for at least 12 h. Seventy adults were included and randomised to either type of tube. The patients were evaluated by means of fibre-optic laryngoscopy and VAS-rating of symptoms on two occasions in the first post-operative week. The evaluating investigators and the patients were blinded to the type of tube used. 27 cases and 23 controls had complete data for evaluation. Age, gender and intubation times were comparable. Symptoms such as hoarseness, coughing, and pain were rated above 30 % of maximum during at least one of the first post-operative days by 21 and 19 patients, respectively. At the first examination (within 24 h), 38 % of patients in the anatomical tube group stated no hoarseness; compared to 13 % of the controls (p = 0.057). Fibre-optic laryngoscopy showed some kind of pathology in all the patients examined within 24 h of extubation. After 3-6 days, seven patients with the anatomical tube and four patients in the control group showed complete resolution of the lesions, and the changes were limited to redness in the vocal process area in another seven and four, respectively. The differences between the groups did not attain statistical significance. The study shows considerable short-term laryngeal morbidity after prolonged intubation, and the anatomical tube only showed an advantage concerning hoarseness. Further improvement of the endotracheal tubes and intubation routines are still needed.

Comparison between two assessment methods for exercise-induced laryngeal obstructions.

Exercise-induced laryngeal obstructions (E-ILOs) are important differential diagnoses to exercise-induced asthma and are diagnosed by the continuous laryngoscopy exercise (CLE) test. There are two different methods for evaluating the severity of E-ILOs using recordings from the CLE test; the CLE score and EILOMEA. The aim of this study was to investigate the consistency between these methods. Using their respective method, the developers of each method evaluated 60 laryngoscopic recordings from patients with different subtypes and various levels of severity of E-ILOs. The CLE score evaluates glottic and supraglottic obstructions on a 4-grade scale. EILOMEA uses software to calculate the obstruction severity on continuous scales from a still frame of the larynx during maximal obstruction giving three parameters reflecting glottic and supraglottic obstruction. The means of the EILOMEA measures differed significantly for CLE score 1 vs. 2 and 2 vs. 3, but not for 0 vs. 1 for glottic as well as supraglottic obstructions. The EILOMEA method does not distinguish between CLE score 0 and 1, but otherwise the methods correlate. Since previous studies have suggested that only CLE scores of 2 and 3 reflect a severity of E-ILOs of clinical importance, this lack of the EILOMEA method is not crucial for a correct medical evaluation.

Exercise test using dry air in random adolescents: Temporal profile and predictors of bronchoconstriction.

BACKGROUND AND OBJECTIVE: Guidelines recommend exercise tests using dry air to diagnose exercise-induced bronchoconstriction (EIB). Lung function changes subsequent to these tests have not been investigated in a general adolescent population, and it remains unknown whether signs of airway inflammation, measured using exhaled nitric oxide (FeNO), can predict a positive response. The aim of this study was to investigate the temporal aspect of decline in forced expiratory volume in 1 s (FEV1 ) after an exercise test using dry air, and to investigate predictors of EIB. METHODS: From a cross-sectional study on adolescents aged 13-15 years (n = 3838), a random subsample of 146 adolescents (99 with and 47 without self-reported exercise-induced dyspnoea) underwent standardized treadmill exercise tests for EIB while breathing dry air. RESULTS: Of the adolescents, 34% had a positive EIB test (decline of ≥10% in FEV1 from baseline) within 30 min. Of the subjects with EIB, 53% showed the greatest decline in FEV1 at 5 to 10 min (mean decline 18.5%), and the remaining 47% of the subjects showed the greatest decline at 15 to 30 min (mean decline 18.9%) after exercise. Increased FeNO (>20 ppb), female gender and self-reported exercise-induced dyspnoea were independently associated with a positive EIB test. CONCLUSION: When assessing general adolescents for EIB with exercise test using dry air, there is a temporal variation in the greatest FEV1 decline after exercise. Therefore, lung function should be measured for at least 30 min after the exercise. Increased FeNO, female gender and self-reported exercise-induced dyspnoea can be predictors of a positive EIB test.

Surgical treatment is effective in severe cases of exercise-induced laryngeal obstruction: A follow-up study.

CONCLUSIONS: Surgery is an effective treatment in severe cases of supraglottic exercise-induced laryngeal obstruction (E-ILO). Conservatively treated subjects and subjects tested negative for E-ILO, who still experience breathing problems 1-3 years after diagnosis, tend to adjust their physical activity to a greater extent than surgically treated subjects. OBJECTIVE: To investigate how symptoms and level of physical activity change over time in patients with E-ILO who have undergone surgery, patients with E-ILO treated conservatively and patients who tested negative for laryngeal obstruction at continuous laryngoscopy exercise-test (CLE-test). METHODS: Patients referred for exercise-induced breathing difficulties answered questionnaires at diagnostic CLE-test and at follow-up. Questions regarded exercise-induced breathing problems, current physical activity level, and medical history of asthma and perennial allergy. RESULTS: Out of 84 invited subjects, 59 (70%) answered both questionnaires. Surgically treated subjects had less breathing problems at follow-up compared with conservatively treated subjects and subjects who tested negative (p < 0.001). None of the surgically treated subjects were less physically active or had changed sport due to exercise-induced dyspnoea, whereas 41.7% of the conservatively treated subjects had made such adjustments (p < 0.001).

Prevalence of exercise-induced bronchoconstriction and exercise-induced laryngeal obstruction in a general adolescent population.

BACKGROUND: Exercise-induced respiratory symptoms are common among adolescents. Exercise is a known stimulus for transient narrowing of the airways, such as exercise-induced bronchoconstriction (EIB) and exercise-induced laryngeal obstruction (EILO). Our aim was to investigate the prevalence of EIB and EILO in a general population of adolescents. METHODS: In this cross-sectional study, a questionnaire on exercise-induced dyspnoea was sent to all adolescents born in 1997 and 1998 in Uppsala, Sweden (n=3838). A random subsample of 146 adolescents (99 with self-reported exercise-induced dyspnoea and 47 without this condition) underwent standardised treadmill exercise tests for EIB and EILO. The exercise test for EIB was performed while breathing dry air; a positive test was defined as a decrease of ≥10% in FEV1 from baseline. EILO was investigated using continuous laryngoscopy during exercise. RESULTS: The estimated prevalence of EIB and EILO in the total population was 19.2% and 5.7%, respectively. No gender differences were found. In adolescents with exercise-induced dyspnoea, 39.8% had EIB, 6% had EILO and 4.8% had both conditions. In this group, significantly more boys than girls had neither EIB nor EILO (64.7% vs 38.8%; p=0.026). There were no significant differences in body mass index, lung function, diagnosed asthma or medication between the participants with exercise-induced dyspnoea who had or did not have a positive EIB or EILO test result. CONCLUSIONS: Both EIB and EILO are common causes of exercise-induced dyspnoea in adolescents. EILO is equally common among girls and boys and can coexist with EIB.

BDNF as otoprotectant in toxin-induced hearing loss.

CONCLUSION: Brain-derived neurotrophic factor (BDNF) can prevent auditory brainstem response (ABR) threshold shift changes caused by Pseudomonas aeruginosa exotoxin A (PaExoA). OBJECTIVE: Peptides of the neurotrophin family are known to prevent neuronal death during embryonic development by interacting with specific membrane receptors. The purpose of this study was to investigate whether a single dose of BDNF is an effective protectant against toxic effects of PaExoA-induced ABR threshold shifts. MATERIALS AND METHODS: Eight groups of Sprague-Dawley rats were used. There were five control groups (n = 20) as follows. Group A (n = 4) received NaCl solution; group B (n = 3) received 4 µg BDNF; group C (n = 4) received 1 µg/20 µl PaExoA; group D (n = 4) received 2 µg/20 µl PaExoA; group E (n = 5) received 10 µg/20 µl PaExoA injected into the round window niche. Three treatment groups (n = 13) received a single dose of PaExoA and 4 µg of BDNF simultaneously. Group 1 (n = 3) received 1 µg/20 µl PaExoA + 4 µg of BDNF; group 2 (n = 5) received 2 µg/20 µl PaExoA + 4 µg BDNF; group 3 (n = 5) received 10 µg/20 µl PaExoA + 4 µg BDNF. ABR was used to measure efficacy by analyzing threshold shifts before and after injections. RESULTS: A single dose of BDNF prevented changes in ABR thresholds following exposure to increasing concentrations of PaExoA injected into the middle ear.

Early hearing protection by brain-derived neurotrophic factor.

CONCLUSION: Brain-derived neurotrophic factor (BDNF) protects the inner ear from PaExoA (exotoxin A from Pseudomonas aeruginosa)-induced sensory neural hearing loss when administered 12 h after exotoxin, but not after 72 h. OBJECTIVE: BDNF is a peptide in the neurotrophin family with protective effects against noise-induced hair cell loss and toxic inner ear damage following exposure to cisplatin. The exotoxin A (PaExoA) from P. aeruginosa, the most common microorganism in chronic suppurative otitis media, induces sensorineural hearing loss in rats. Previous study showed that, when given simultaneously with the exotoxin, BDNF protected the inner ear from damage. The aim of this study was to determine if BDNF has a protective effect when given 12-72 h after PaExoA. MATERIALS AND METHODS: Five groups of Sprague-Dawley rats were used. The three control groups (n = 16) were as follows. Group 1 (n = 8) received 15 µg/20 µl PaExoA; group 2 (n = 5) received 20 µg/20 µl PaExoA; and group 3 (n = 3) received 25 µg/20 µl PaExoA injected into the round window niche. There were two treatment groups (n = 12): group A (n = 6) received 15 µg/20 µl PaExoA and 4 µg/20 µl BDNF 12 h later; group B (n = 6) received 15 µg/20 µl PaExoA and 4 µg/20 µl BDNF 72 h later. Brainstem response audiometry (ABR) was performed on day 0 (control), and repeated on days 7, 14, 21, 28, and 35 to analyze the thresholds shifts. RESULTS: Exposure to 15 µg/20 µl PaExoA caused persistent and significant ABR impairment in controls when measured after 35 days. A single dose of BDNF given 12 h after PaExoA reduced hearing loss significantly, but when BDNF was given 72 h after PaExoA no protective effect was evident.