Search

Objective: To provide family physicians with a practical evidence-based approach to management of otitis externa., Sources of Information: The approach described is based on MEDLINE and PubMed literature published between 1993 and 2023., Main Message: Otitis externa is diffuse inflammation of the external auditory canal and typically occurs from moisture exposure and trauma. Management focuses on eliminating infection, pain management, education, and preventing recurrence. The primary treatment of uncomplicated otitis externa is topical. Complicated presentations may require additional systemic therapy., Conclusion: History taking and physical examination can help differentiate among acute, chronic, and necrotizing otitis externa. At-risk populations, typically those who are immunosuppressed, are more likely to develop necrotizing otitis externa and should be carefully monitored., (Copyright © 2024 the College of Family Physicians of Canada.)

Background: Hearing loss is one of the most common sensory impairments and hearing aids are the most common unmet assistive device need among individuals with a disability. The benefits of hearing interventions are well-documented as they are known to deter the sequalae of hearing loss including social isolation, poor mental health, falls and cognitive decline. Identifying trends in hearing aid users can provide valuable information for improving access to hearing loss interventions., Methods: Data were retrieved from ICES databases that were used to generate a cohort of 372,448 individuals in Ontario, Canada, who first claimed hearing aids between April 2007 and March 2018 through the Assistive Devices Program., Results: The data indicated that the frequency distribution of hearing aids has steadily inclined since 2007. The mean age of hearing aid users was 70.25 ± 14.70 years and higher neighbourhood income quintile was associated with greater hearing aid use ( p  < 0.001). Most first claims occurred after visiting primary care physicians (70.60%) compared with otolaryngology (13.39%). An examination of clinical comorbidities revealed hypertension (63.41%), and diabetes (24.93%) to be the most common. Regression analysis demonstrated a positive associated between age and most comorbidities. Furthermore, higher neighbourhood income quintiles were associated with a reduced risk of having the examined comorbidities., Conclusions: This study examines patient demographics and clinical comorbidities in a cohort of hearing aid users in Ontario. The results identify associations between demographics and comorbidities that provide information relevant for improving access to hearing interventions and clinical decision-making in primary care.Implications for RehabilitationScreening for hearing loss (using an audiogram) in elderly individuals that manage multiple comorbidities, and any patient with significant risk factors for hearing loss (e.g., noise exposure history, prior ototoxic medications, prior head injury, history of ear surgery, family history of hearing loss) will identify deficits and direct appropriate hearing interventions.Improving access to care in low-income communities should include community-based education around expectation management and communication strategies to reinforce proper use and care of hearing devices.Geographic proximity to hearing testing facilities and hearing aid dispensaries is a significant barrier to hearing rehabilitation strategies.

Introduction: The prevalence of hearing loss in Canada is high, with many patients requiring implantable hearing devices (IHDs) as treatment for their disease severity. Despite this need, many eligible patients do not pursue these interventions. The objective of this study was to examine rates of IHD based on geographic location to understand locoregional variation in access to care., Study Design: This was a retrospective population-based cohort study., Setting: All hospitals in the Canadian province of Ontario., Methods: Of all patients with IHD between April 1, 1992, and March 31, 2021, cochlear implants (CIs) (4,720) and bone-anchored hearing aids (BAHA) (1,125) cohorts were constructed. Place of residence was categorized based on Local Health Integrated Network (LHIN). Summary statistics for place of surgical institution based on LHIN at first surgery, name of institution of first surgery and "as the crow flies" distance (in km) between place of residence and surgical institution were calculated. Rate of implantations was calculated for LHIN regions based on number of surgeries per 1,000,000 persons/years., Results: Toronto Central, Central, Central East, and Champlain regions had &gt;10% of patients undergoing BAHA and CI. 1,019 (90.6%) and 4,232 (89.7%) of patients receiving BAHA and CI, respectively, resided in urban/suburban regions and 94 patients (8.4%) and 436 (9.2%) resided in rural regions. The median distance between residential location and the institution was 46.4 km (interquartile range [IQR], 18.9-103.6) and 44.7 km (IQR, 15.7-96.9) for BAHA and CI, respectively. From 1992 to 2021, the number of CI and BAHA performed across Ontario increased by 17 folds and 6 folds, respectively., Conclusion: This large comprehensive population study provides longitudinal insight into the access to care of IHD based on geographic factors. Our findings of the present population-based study indicate an overall increase in access to devices with disproportionate access to care based on geographic locations. Further work is needed to characterize barriers to IHD access to align with demands., (© 2023 S. Karger AG, Basel.)

Objective: To provide family physicians with a practical evidence-based approach to the management of patients with sialadenitis., Sources of Information: MEDLINE and PubMed databases were searched for English-language research on sialadenitis and other salivary gland disorders, as well as for relevant review articles and guidelines published between 1981 and 2021., Main Message: Sialadenitis refers to inflammation or infection of the salivary glands and is a condition that can be caused by a broad range of processes including infectious, obstructive, and autoimmune. History and physical examination play important roles in directing management, while imaging is often useful to establish a diagnosis. Red flags such as suspected abscess formation, signs of respiratory obstruction, facial paresis, and fixation of a mass to underlying tissue should prompt urgent referral to head and neck surgery or a visit to the emergency department., Conclusion: Family physicians can play an important role in the diagnosis and management of sialadenitis. Prompt recognition and treatment of the condition can prevent the development of complications., (Copyright © 2023 the College of Family Physicians of Canada.)

Introduction: Hearing loss (HL) is considered a potentially modifiable risk factor for dementia. We aimed to examine the relationship between HL and incident dementia diagnosis in a province-wide population-based cohort study with matched controls., Methods: Administrative healthcare databases were linked to generate a cohort of patients who were aged ≥40 years at their first claimed hearing amplification devices (HAD) between April 2007 and March 2016 through the Assistive Devices Program (ADP) (257,285 with claims and 1,005,010 controls). The main outcome was incident dementia diagnosis, ascertained using validated algorithms. Dementia incidence was compared between cases and controls using Cox regression. Patient, disease, and other risk factors were examined., Results: Dementia incidence rates (per 1,000 person-years) were 19.51 (95% confidence interval [CI]: 19.26-19.77) and 14.15 (95% CI: 14.04-14.26) for the ADP claimants and matched controls, respectively. In adjusted analyses, risk of dementia was higher in ADP claimants compared with controls (hazard ratio [HR]: 1.10 [95% CI: 1.09-1.12, p &lt; 0.001]). Subgroup analyses showed a dose-response gradient, with risk of dementia higher among patients with bilateral HADs (HR: 1.12 [95% CI: 1.10-1.14, p &lt; 0.001]), and an exposure-response gradient, with increasing risk over time from April 2007-March 2010 (HR: 1.03 [95% CI: 1.01-1.06, p = 0.014]), April 2010-March 2013 (HR: 1.12 [95% CI: 1.09-1.15, p &lt; 0.001]), and April 2013-March 2016 (HR: 1.19 [95% CI: 1.16-1.23, p &lt; 0.001])., Conclusion: In this population-based study, adults with HL had an increased risk of being diagnosed with dementia. Given the implications of HL on dementia risk, understanding the effect of hearing interventions merits further investigation., (© 2023 S. Karger AG, Basel.)

Objective: To examine postoperative opioid-prescribing patterns following otologic surgery., Study Design: Retrospective population-based descriptive study., Setting: All hospitals in the Canadian province of Ontario., Methods: Of all patients with advanced ear surgery between July 1, 2012, and March 31, 2019, 7 cohorts were constructed: tympanoplasty with or without ossiculoplasty (n = 7812), atticotomy/limited mastoidectomy (n = 1371), mastoidectomy (n = 3717), semicircular canal occlusion (SCO; n = 179), stapedectomy (n = 2735), bone-implanted hearing aid insertion (n = 280), and cochlear implant (n = 2169). Prescriptions filled for narcotics postoperatively were calculated per morphine milligram equivalent (MME) opioid dose. Multivariable regression was used to determine predictors of higher opioid doses., Results: The mean ± SD MMEs prescribed were as follows: tympanoplasty with or without ossiculoplasty, 246.77 ± 1380.78; atticotomy/limited mastoidectomy, 283.32 ± 956.10; mastoidectomy, 280.56 ± 1018.50; SCO, 328.61 ± 1090.86; stapedectomy, 164.64 ± 657.18; bone-implanted hearing aid insertion, 326.11 ± 1054.66; and cochlear implant, 200.87 ± 639.93. SCO (odds ratio [OR], 1.69 [95% CI, 1.16-2.48]) and mastoidectomy (OR, 1.50 [95% CI, 1.36-1.66]) were associated with higher opioid doses than tympanoplasty-ossiculoplasty. Asthma (OR, 1.24 [95% CI, 1.12-1.38]), chronic obstructive pulmonary disease (OR, 1.29 [95% CI, 1.12-1.47]), myocardial infarction (OR, 1.33 [95% CI, 1.05-1.68]), diabetes (OR, 1.22 [95% CI, 1.08-1.39]), and substance-related and addictive disorders (OR, 2.59 [95% CI, 1.67-4.00]) were associated with higher opioid doses prescribed. Overall MME prescribed by year demonstrates a sharp drop from 2017-2018 to 2018-2019., Conclusion: This large comprehensive population study provides insight into the prescribing patterns following otologic surgery. The large amounts prescribed and substantial variation require further study to determine barriers that limit good opioid-prescribing stewardship in the postoperative period.

Background: Falls are the leading cause of fatal and nonfatal injuries among adults over 65 years old. The increase in fall mortality rates is likely multifactorial. With a lack of key drivers identified to explain rising rates of death from falls, accurate predictive modelling can be challenging, hindering evidence-based health resource and policy efforts. The objective of this work is to examine the predictive power of geographic utilization and longitudinal trends in mortality from unintentional falls amongst different demographic and geographic strata., Methods: This is a nationwide, retrospective cohort study using the United States Centers for Disease Control (CDC) Web-based Injury Statistics Query and Reporting System (WISQARS) database. The exposure was death from an unintentional fall as determined by the CDC. Outcomes included aggregate and trend crude and age-adjusted death rates. Health care utilization, reimbursement, and cost metrics were also compared., Results: Over 2001 to 2018, 465,486 total deaths due to unintentional falls were recorded with crude and age-adjusted rates of 8.42 and 7.76 per 100,000 population respectively. Comparing age-adjusted rates, males had a significantly higher age-adjusted death rate (9.89 vs. 6.17; p <  0.00001), but both male and female annual age-adjusted mortality rates are expected to rise (Male: + 0.25 rate/year, R 2 = 0.98; Female: + 0.22 rate/year, R 2 = 0.99). There were significant increases in death rates commensurate with increasing age, with the adults aged 85 years or older having the highest aggregate (201.1 per 100,000) and trending death rates (+ 8.75 deaths per 100,000/year, R 2 = 0.99). Machine learning algorithms using health care utilization data were accurate in predicting geographic age-adjusted death rates., Conclusions: Machine learning models have high accuracy in predicting geographic age-adjusted mortality rates from health care utilization data. In the United States from 2001 through 2018, adults aged 85+ years carried the highest death rate from unintentional falls and this rate is forecasted to accelerate., (© 2022. The Author(s).)

Rationale, Aims and Objectives: Physician consultations are a limited resource. Anesthesiologists provide anaesthesia during surgery and procedures, prepare patients for surgery in preoperative clinics, and provide postoperative care. This study sought to evaluate current consultation usage patterns, with an aim to determine possible opportunities for efficiency., Method: A retrospective comprehensive population-based cohort study was performed, evaluating all hospitals in the Canadian province of Ontario from 2002 to 2018. The main outcome measures were American Society of Anesthesiologists (ASA) classification of the patients, and whether the patients underwent surgery within 3 months following the anaesthesia consultation., Results: A cohort of 2,023,499 patients, and a total of 2,920,100 preoperative anaesthesia consultations was obtained. The number of consults per year doubled between 2003 (112,983/year) and 2017 (246,427/year), despite a less than 40% increase in practicing Canadian Anesthesiologists over this same timeframe. Each year, an average of 19.3% of the consults (range: 17.7-20.5%) were for patients that did not progress to having surgery. Of those that did have surgery following the anaesthesia consult, 37.2% were ASA Classification I or II. The most common surgical procedures (percent of total) following anaesthesia consult were: Knee arthroplasty (9.5%), hip arthroplasty (5.8%), cataract extraction (4.1%), repair of muscle of chest/abdomen (3.3%), hysterectomy (2.8%), and cholecystectomy (2.7%)., Conclusions: This study reveals data on utilization and trends over time of preoperative anaesthesia consultations. Potential opportunities for optimization were found, including patients who did not proceed to surgery, and healthier patients undergoing low to moderate risk surgery., (© 2021 John Wiley & Sons Ltd.)

A multifactorial risk assessment, correction of hearing impairment, exercise, and an optimized home environment can help prevent imbalance-related falls.

Competing Interests: The authors disclose no conflicts of interest.

Objective: To investigate preoperative patient demographics and comorbidities in relation with postsurgical complications following vestibular schwannoma surgery., Study Design: Retrospective population-based cohort study., Setting: All hospitals in the Canadian province of Ontario., Patients: This study includes 1,456 patients who underwent vestibular schwannoma surgery from April 1, 2002 to March 31, 2018 in Ontario, Canada., Intervention/outcome Measures: For all surgical patients, the demographic data, preoperative comorbidities, and postoperative complications were evaluated. Postoperative complications were examined immediately following surgery in the hospital as well as 1 year following the hospital discharge., Results: The most common comorbidities in this cohort were hypertension (30.22%), diabetes (9.48%), asthma (13.53%), and chronic obstructive pulmonary disease (6.73%). Diabetes was the most impactful comorbidity and was associated with higher risk of myocardial infarction (RR = 4.58, p < 0.01), pneumonia (RR = 1.80, p = 0.02), dysphagia (RR = 1.58, p < 0.01), and meningitis (RR = 3.62, p < 0.01). Analysis of surgical approaches revealed that the translabyrinthine approach, compared with the open craniotomy approach, was negatively associated with postoperative complications including pneumonia (RR = 0.43, p < 0.01), urinary tract infection (RR = 0.55, p = 0.01), dysphagia (RR = 0.66, p < 0.01), and readmission (RR = 0.45, p < 0.01)., Conclusion: This study examines patient demographics, preoperative comorbidities, and postoperative complications in patients who have undergone vestibular schwannoma surgery. The results highlight associations between patient characteristics and postoperative outcomes that can aid in preoperative decision-making and counselling., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2021, Otology & Neurotology, Inc.)

This study aims to test whether the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) differs between patients who developed tinnitus following a traumatic brain injury (TBI), and those without a history of TBI. This was a parallel pilot, open-label, non-randomized, clinical trial to compare the efficacy of low frequency rTMS on tinnitus symptoms in patients with and without a TBI history. Patients with moderate to severe tinnitus symptoms based on the Tinnitus Handicap Inventory (THI) and the Tinnitus Functional Index (TFI) were enrolled in the study. Validated questionnaires (THI and TFI) were used to quantify the severity of tinnitus symptoms and hearing impairment (Hearing Handicap Index - HHI) before and after ten sessions of rTMS of the left primary auditory cortex. Hearing threshold levels as well as speech reception and speech discrimination thresholds were also compared. The number of patients who experienced a reduction in their subjective tinnitus symptoms was greater and sustained longer in patients without a history of TBI. The same was seen with subjective symptoms of hearing impairment. In conclusion, our preliminary results suggest tinnitus patients without a history of TBI respond better to low frequency rTMS than those with a history of TBI, suggesting that treatments could be more effective if tailored to tinnitus etiology.

Objective: To provide family physicians with a practical evidence-based approach to the management of patients with hearing loss., Sources of Information: MEDLINE and PubMed databases were searched for English-language hearing loss research, review articles, and guidelines published between 1980 and 2020. Most of the retrieved articles provided level II or III evidence., Main Message: Hearing loss is one of the most common sensory impairments worldwide and causes great detriment to a patient's overall well-being by affecting physical health, finances, social inclusion, and mental health. A robust clinical assessment of hearing loss includes a history and physical examination that effectively characterizes the deficit as conductive, sensorineural, or mixed. Patients presenting with red flags (such as sudden unilateral sensorineural hearing loss) must be urgently referred to otolaryngology-head and neck surgery or immediately assessed in the emergency department. Many nonurgent presentations of hearing loss will also require referral for further audiological assessment, diagnosis, and management., Conclusion: As primary care providers, family physicians are well equipped to manage the psychological concerns associated with hearing loss and to reinforce conservative treatment strategies. Frequently, referral or urgent workup, including imaging, is necessary to confirm a patient's diagnosis and initiate management in order to prevent further complications., (Copyright© the College of Family Physicians of Canada.)

Background: Computer-assisted learning has been shown to be an effective means of teaching anatomy, with 3-D visualization technology more successfully improving participants' factual and spatial knowledge in comparison to traditional methods. To date, however, the effectiveness of teaching ear anatomy using 3-D holographic technology has not been studied. The present study aimed to evaluate the feasibility and effectiveness of learning ear anatomy using a holographic (HG) anatomic model in comparison to didactic lecture (DL) and a computer module (CM)., Methods: A 3-D anatomic model of the middle and inner ear was created and displayed using presentation slides in a lecture, computer module, or via the Microsoft HoloLens. Twenty-nine medical students were randomized to one of the three interventions. All participants underwent assessment of baseline knowledge of ear anatomy. Immediately following each intervention, testing was repeated along with completion of a satisfaction survey., Results: Baseline test scores did not differ across intervention groups. All groups showed an improvement in anatomic knowledge post-intervention (p < 0.001); the improvement was equal across all interventions (p = 0.06). Participants rated the interventions equally for delivery of factual content (p = 0.96), but rated the HG higher than the DL and CM for overall effectiveness, ability to convey spatial relationships, and for learner engagement and motivation (p < 0.001)., Conclusions: These results suggest that 3-D holographic technology is an effective method of teaching ear anatomy as compared to DLs and CMs. Furthermore, it is better at engaging and motivating learners compared to traditional methods, meriting its inclusion as a tool in undergraduate medical education curriculum.

Purpose: Hearing loss is a significant late effect among childhood cancer survivors. Recent guidelines note insufficient evidence to quantify its natural history or risk associated with specific exposures. We examined the long-term incidence and predictors of hearing loss requiring hearing amplification devices (HADs) using population-based health care data., Methods: In Ontario, Canada, HAD costs are subsidized by the Assistive Devices Program (ADP). Ontario children < 18 years of age at cancer diagnosis between 1987 and 2016 were identified and linked to ADP claims. Cumulative HAD incidence was compared between cases and matched controls. Patient, disease, and treatment predictors of HAD were examined., Results: We identified 11,842 cases and 59,210 controls. Cases were at higher risk for HAD (hazard ratio [HR], 12.8; 95% CI, 9.8 to 16.7; P < .001). The cumulative incidence of HAD among survivors was 2.1% (95% CI, 1.7% to 2.5%) at 20 years and 6.4% (95% CI, 2.8% to 12.1%) at 30 years post-diagnosis. The 30-year incidence was highest in neuroblastoma (10.7%; 95% CI, 3.8% to 21.7%) and hepatoblastoma (16.2%; 95% CI, 8.6% to 26.0%) survivors. Predictors of HAD in multivariable analyses included age 0-4 years at diagnosis ( v 5-9 years; HR, 2.2; 95% CI, 1.4-3.3; P < .001). Relative to no cisplatin exposure, patients receiving < 200 mg/m 2 were not at greater risk, unlike those receiving higher cumulative doses. Relative to no cranial or facial radiation, those who had received ≤ 32.00 Gy were at no higher risk, unlike those who had received > 32.00 Gy. Carboplatin exposure was not associated with HAD., Conclusion: Childhood cancer survivors are at elevated risk for requiring HAD, which continues to increase between 20 and 30 years after diagnosis. Thresholds of cisplatin and radiation exposure exist, above which risk substantially increases. Prolonged monitoring and trials of otoprotective agents are warranted in high-risk populations.

Competing Interests: Competing interests: None declared.

Objective: To provide family physicians with an updated approach to diagnosis and treatment of pharyngitis, detailing key symptoms, methods of investigation, and a summary of common causes., Sources of Information: The approach described is based on the authors' clinical practice and peer-reviewed literature from 1989 to 2018., Main Message: Sore throat caused by pharyngitis is commonly seen in family medicine clinics and is caused by inflammation of the pharynx and surrounding tissues. Pharyngitis can be caused by viral, bacterial, or fungal infections. Viral causes are often self-limiting, while bacterial and fungal infections typically require antimicrobial therapy. Rapid antigen detection tests and throat cultures can be used with clinical findings to identify the inciting organism. Pharyngitis caused by Streptococcus pyogenes is among the most concerning owing to its associated severe complications such as acute rheumatic fever and glomerulonephritis. Hence, careful diagnosis of pharyngitis is necessary to provide targeted treatment., Conclusion: A thorough history is key to diagnosing pharyngitis. Rapid antigen detection tests should be reserved for concerns about antibiotic initiation. Physicians should exercise restraint in antibiotic initiation for pharyngitis, as restraint does not delay recovery or increase the risk of S pyogenes infections., (Copyright© the College of Family Physicians of Canada.)

Background: Ear (tympanostomy) tube (TT) placement is a common ambulatory surgery in children. Despite the commonality of this treatment, the long-term effects are unknown. The objective of this study was to determine the rate of permanent hearing loss, as measured by use of a rehabilitative hearing device., Methods: A retrospective comprehensive population-based cohort study was performed, evaluating all hospitals in the Canadian province of Ontario. Three cohorts of children were constructed: TT - at least one ear tube procedure (n = 193,880), No-TT -recurrent visits to a physician for middle ear disease, did not undergo ear tubes (n = 203,283), and Control - an age/sex matched group who had not undergone ear tubes and who didn't have repeat physician visits for middle ear disease (n = 961,168). The main outcome measures were risk and odds ratio (OR) of rehabilitative hearing devices., Results: The TT cohort had a higher risk of obtaining a hearing aid (OR 4.53 vs. No-TT, p < 0.001; OR 10.81 vs. Control, p < 0.001), an FM system (OR 3.84 vs. No-TT, p < 0.001; OR 15.13 vs. Control, p < 0.001), and an implanted bone conduction device (OR 5.08 vs. No-TT, p < 0.001; OR 15.67 vs. Control, p < 0.001)., Conclusions: An association between ear tube placement and long-term need for a rehabilitative hearing device was found. This association warrants future prospective research in this area.

Objective: To provide family physicians with a practical, evidence-based approach to managing patients with cerumen impaction. Methods: MEDLINE, The Cochrane Library, and the Turning Research Into Practice (TRIP) database were searched for English-language cerumen impaction guidelines and reviews. All such articles published between 1992 and 2018 were reviewed, with most providing level II and III evidence. Results: Cerumen impaction is a common presentation seen in primary care and cerumen removal is one of the most common otolaryngologic procedures performed in general practice. Cerumen impaction is often harmless but can be accompanied by more serious symptoms. Cerumenolytics and irrigation of the ear canal are reasonable first-line therapies and can be used in conjunction or isolation. If irrigation and cerumenolytics are contraindicated, manual removal is appropriate, but the tools necessary are not commonplace in primary care clinics and specialized training may be required to prevent adverse outcomes. Conclusion: Family physicians play a key role in the assessment and management of cerumen impaction and are well equipped to do so. Knowledge of the available techniques for cerumen removal as well as their contraindications ensures that cerumen is removed safely and effectively. When cerumen removal cannot be removed safely in a primary care setting, referral to Otolaryngology-Head and Neck Surgery is appropriate.

Objective: To provide family physicians with an updated approach to the diagnosis and management of Ménière disease (MD), detailing the natural course of MD and describing how to initiate medical therapy while awaiting consultation with otolaryngology-head and neck surgery., Sources of Information: The approach is based on the authors' clinical practices and review articles from 1989 to 2018. Most of the cited studies provided level II or III evidence., Main Message: Ménière disease is an uncommon disorder of the inner ear causing vertigo attacks with associated unilateral hearing loss, tinnitus, and aural fullness. It has a degenerative course that often results in permanent sensorineural hearing loss. On average, MD stabilizes with no further vestibular attacks by about 8 years after the onset of symptoms; however, this is highly variable. Vertigo symptoms can be controlled through a combination of dietary salt restriction, stress reduction, and medical therapy (betahistine, diuretics, or both). These can be initiated by family physicians before consultation with otolaryngology-head and neck surgery. Symptoms refractory to such strategies can be treated using nonablative, and occasionally ablative, therapies., Conclusion: A thorough history is key to the approach to and management of MD and permits differentiating MD from other vestibular and nonvestibular conditions., (Copyright© the College of Family Physicians of Canada.)

Objective: To investigate future surgery for chronic ear disease in children who underwent tympanostomy tube (TT) placement, compared with non-surgically treated patients and healthy controls., Study Design: Retrospective population-based cohort study., Setting: All hospitals in the Canadian province of Ontario., Patients/intervention: Of children aged 18 years and younger, three cohorts were constructed: 1) TT: patients who had undergone at least one TT procedure (n = 193,880), 2) No-TT: patients with recurrent physician visits for middle ear concerns who did not undergo TT (n = 203,283), and 3) Control: an age-sex matched control group who had not had TT or physician visits for recurrent middle ear concerns (n = 961,168)., Main Outcome Measures: Risk, and odds ratios (ORs) of surgery for chronic ear disease., Results: The TT cohort had a higher risk of tympanoplasty (OR 9.50 versus No-TT, p < 0.001; OR 207.90 versus Control, p < 0.001), ossiculoplasty (OR 3.22 versus No-TT, p < 0.001; OR 84.13 versus Control, p < 0.001), atticotomy (OR 4.41 versus No-TT, p < 0.001; OR 44.78 versus Control, p < 0.001), and mastoidectomy (OR 3.22 versus No-TT, p < 0.001; OR 89.12 versus control, p < 0.001)., Conclusion: This study describes the population risk of subsequent ear surgeries in TT patients. These TT patients have a significantly higher risk of surgery for chronic ear disease versus those patients with recurrent middle ear disease that did not undergo TT, and age-sex matched controls.

First, determine whether the sensation the patient is experiencing is dizziness or true vertigo. Then eliminate ominous causes from the array of benign ones.

Objective: To provide family physicians with an evidence-based and practical approach to managing patients with tinnitus., Sources of Information: MEDLINE was searched for English-language tinnitus guidelines and reviews. All such articles published between 1980 and 2016 were reviewed, with most providing level II and III evidence., Main Message: Tinnitus affects more than 40% of Canadians at least once in their lifetimes, most commonly older adults. Tinnitus is the perception of sound without external stimulation. It can greatly affect a patient's physical and psychological quality of life. Clinical history taking is directed at eliciting whether symptoms have a pulsatile or nonpulsatile quality, whether symptoms are unilateral or bilateral, and whether there is associated hearing loss. For tinnitus that is pulsatile or unilateral, referral to an otolaryngologist is recommended, as these qualities might be associated with more serious underlying conditions. Most patients with tinnitus can be managed with reassurance, conservative measures, and hearing aids if substantial hearing loss exists., Conclusion: Family physicians play the primary role in managing patients with tinnitus and are well situated to address both the physiologic and the psychological manifestations. As tinnitus is very common, helping patients cope with the symptoms through conservative measures and reassurance can prove to have the best outcomes., (Copyright© the College of Family Physicians of Canada.)

Objective: To determine which teaching method-otoscopy simulation (OS), web-based module (WM), or standard classroom instruction (SI)-produced greater translation of knowledge and otoscopy examination skills to real patients., Design: In a prospective randomized controlled nonclinical trial, medical students were randomized to 1 of 3 interventional arms: (1) OS, (2) WM, or (3) SI. Students were assessed at baseline for diagnostic accuracy and otoscopy skills on 5 volunteer patients (total of 10 ears), followed by the intervention. Testing was repeated immediately after intervention on the same patients. Student reported confidence in diagnostic accuracy and otoscopy examination were also captured. Assessors were blinded to the intervention group, and whether students were pre- or post-intervention., Setting: Clinical Teaching Centre, Queen's University., Participants: Twenty-nine participants were initially randomized. Two students were unable to attend their specific intervention sessions and withdrew. Final group sizes were: OS-10, WM-9, SI-8. Five patients with external/middle ear pathologies were voluntarily recruited to participate as testing subjects., Results: Baseline diagnostic accuracy and otoscopy clinical skills did not differ across the groups. Post-intervention, there were improvements in diagnostic accuracy from all groups: OS (127.78%, 2.30 ± 1.42, p = 0.0006), WM (76.40%, 1.44 ± 1.88, p = 0.0499), and SI (100.00%, 1.50 ± 1.20, p = 0.0093). For otoscopy skills, post-intervention improvements were noted from OS (77.00%, 3.85 ± 2.55, p < 0.0001) and SI (22.20%, 1.25 ± 1.20, p = 0.0011), with no significant improvement from WM (13.46%, 0.78 ± 1.92, p = 0.1050). Students across all groups reported significantly improved confidence in diagnostic accuracy (p < 0.0001) and otoscopy skill (p < 0.0001) after the intervention., Conclusion: All 3 teaching modalities showed an improvement in diagnostic accuracy immediately post-intervention. Otoscopy clinical skills were found to have increased only in OS and SI, with the OS group demonstrating the largest improvement. Simulation-based medical education in Otolaryngology may provide the greatest transfer of medical knowledge and technical skills when evaluated with real patients., (Copyright © 2018 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Objective Tympanostomy tube (TT) insertion is the most common ambulatory surgery performed on children. American Academy of Otolaryngology-Head and Neck Surgery Founda-tion (AAO-HNSF) Clinical Practice Guidelines (CPGs) recommend hearing testing for all pediatric TT candidates. The aim of this study was to assess audiometric testing in this population. Study Design Retrospective population-based cohort study. Setting All hospitals in the Canadian province of Ontario. Subjects and Methods All patients 12 years of age and younger who underwent at least 1 TT procedure between January 1993 and June 2016. The primary outcomes were the percentage of patients who underwent a hearing test within 1 year before and/or 1 year after surgery. Results A total of 316,599 bilateral TT procedures were performed during the study period (1993 to 2016). Presurgical hearing tests increased from 55.7% to 74.9%, and postsurgical hearing tests increased from 42.2% to 68.9%. Younger surgeons demonstrated a greater adherence to the CPGs (relative risk [RR], 1.22; 95% CI, 1.08-1.38; P = .001). Remarkably, there was not a spike in preoperative hearing tests following the introduction of the CPGs in 2013 (RR, 1.12; 95% CI, 0.85-1.47; P = .432). Presurgical hearing testing ranged from 26.1% to 83.5% across health regions. Conclusion In this cohort of children who underwent TT placement, the trends of preoperative and postoperative audiometric testing are increasing but are still lower than recommended by the CPGs, despite a tripling of practicing audiologists. This study describes the current state of testing in Ontario and highlights issues of access to audiology services, possible parent preferences, and the importance of ongoing continuing medical education for all health care practitioners.

Objectives: To characterize risk factors that predict the need for multiple tympanostomy tube (TT) procedures., Study Design: Retrospective population-based cohort study of children aged 18 years and younger in Ontario, Canada, who underwent at least one TT placement between January 1, 1994, and October 31, 2013., Methods: The relative risk (RR) of need for multiple TT procedures was determined using log-binomial regression., Results: There were 193,880 children who underwent TT insertion included in this cohort. Of these, 28.58% underwent at least two separate TT procedures. Over time, the RR of undergoing multiple TT procedures is decreasing for all children. In general, the younger the child was at the first TT procedure, the more likely the child was to undergo multiple TT procedures. Significantly higher RR for multiple TT procedures also was associated with male sex, the second-highest neighborhood income quintile, asthma or reactive airways, gastrointestinal disease, prematurity, or cleft lip and/or palate. Significantly lower RR for multiple TT procedures was associated with adenoidectomy or tonsillectomy (with or without adenoidectomy) at first TT placement or within 3 years prior. Furthermore, the benefit of adjuvant adenoidectomy or tonsillectomy was present for children aged under 4 years, in addition to those aged 4 years and older., Conclusion: Among Ontario children who have had TT placement, more than one in four will have multiple sets placed. These identified risk factors permit improved preoperative counseling and enable identification of children who need closer follow-up., Level of Evidence: 2b. Laryngoscope, 128:991-997, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To assess the efficacy and safety of two different intratympanic dexamethasone (IT Dex) injection protocols for intractable unilateral Ménière's disease., Study Design: Prospective case series., Setting: Tertiary neurotology clinic., Patients: One hundred six consecutive adult patients with definite unilateral Ménière's disease who had failed medical management were studied for an average of 1,061 days. None had previous oral steroid, IT steroid, or ablative treatment., Interventions: Two different IT Dex regimes, either a single injection or a series of four injections, that were subsequently repeated as indicated., Main Outcome Measure: Requirement for subsequent ablative therapy in the form of intratympanic gentamicin, vestibular nerve section, or labyrinthectomy. Hearing outcomes were measured using pure-tone average of 0.5, 1, 2, and 3 kHz on standard audiometry., Results: The number of intratympanic dexamethasone injections per patient ranged from 1 to 29 (median = 4). Using the Kaplan-Meier method, predicted survival (patients not requiring ablative therapy) at 2 and 4 years after initial treatment was 83.9 and 79.3%, respectively. The injection series protocol ultimately yielded 5% better survival than the single injection protocol, but this was not statistically significant. Injections did not protect against hearing loss, and the most recent pure-tone averages declined compared with pretreatment values by an average of 8.27 dB (p < 0.05). The treatments did not result in any acute hearing losses, permanent tympanic membrane perforations, or other significant adverse events., Conclusion: Intratympanic dexamethasone injections were successful in controlling vertigo insofar as they were able to obviate ablative therapy in the majority of Ménière's disease patients in this study. The injection series protocol may have been more beneficial compared with the single injection, although the difference between the two protocols was nonsignificant. Hearing mildly declined over the treatment course, which likely represents natural disease progression. The lack of adverse events suggests that IT Dex may be a nonablative option for patients with bilateral disease or only hearing/vestibular ears.

Airway management in trauma is a crucial skill, because patients are at risk of aspiration, hypoxia, and hypoventilation, all of which may be fatal in the setting of increased intracranial pressure. The King Laryngeal Tube reusable supraglottic airway (King Systems, Noblesville, IN) allows for temporary management of a difficult airway but poses a challenge when an attempt is made to exchange the device for an endotracheal tube, often managed by emergency tracheostomy. We describe a novel fiberoptic, video laryngoscope-assisted approach to intubation in a difficult trauma airway with an in situ King Laryngeal Tube.

Objective To determine which teaching method-otoscopy simulation (OS), web-based module (WM), or standard classroom instruction (SI)-produced the best improvement in the diagnosis of middle/external ear pathologies and the development of otoscopy clinical skills. Study Design Prospective randomized controlled nonclinical trial. Setting Preclerkship undergraduate medical education. Subjects and Methods Fifty-four medical students (first year, 26; second year, 28) were randomized to receive 1 of the 3 interventions: OS, WM, or SI. All students underwent baseline testing of diagnostic accuracy (25 ear pathologies) and otoscopy skills. Immediately following each intervention and 3 months later, testing was repeated. Results Baseline scores for diagnostic accuracy and otoscopy skills did not differ across intervention groups. Immediately postintervention, all groups showed an improvement in diagnostic accuracy ( P < .001). OS scored significantly higher than SI ( P < .001), as did WM ( P = .003). At 3-month follow-up, all groups continued to demonstrate improved diagnostic accuracy as compared with baseline. Again, OS showed improvement over SI ( P = .031). For otoscopy clinical skills, only OS improved immediately postintervention ( P < .001). OS had significantly higher scores than WM and SI ( P < .001). At 3-month follow-up, OS again showed improvement over WM ( P < .001) and SI ( P = .009). Conclusion All groups showed an improvement in diagnostic accuracy immediately postintervention, with the largest increases coming from OS and WM. Otoscopy clinical skills increased and were retained only in OS. Preclerkship medical student acquisition and retention of otolaryngology diagnostic skills can be greatly improved through web-based teaching modules and otoscopy simulation.

Objective: Unexplained outcome variability exists among adults with cochlear implants (CIs). Two significant predictors are age and duration of deafness, with older patients and those with longer durations of deafness generally demonstrating poorer speech recognition. However, these factors are often highly correlated. Thus, it is unclear whether poorer outcomes should be attributed primarily to age-related declines or to the experience of auditory deprivation. Our aim was to examine the effects of aging and duration of hearing loss on outcomes for postlingually deaf adults with CIs., Study Design: Retrospective review of adults who received CIs from 1983 to 2014., Setting: Tertiary adult CI program., Patients: Sixty-four adult patients with postlingual hearing loss beginning after age 12 years, full electrode insertion, normal cochlear anatomy, and availability of postoperative outcome measures., Intervention: Cochlear implantation with 12 months or greater of device use., Main Outcome Measures: Postoperative pure-tone averages (0.5, 1, 2, and 3 kHz) and recognition of words in sentences (Hearing in Noise Test and AzBio)., Results: Age at postoperative testing had a negative partial correlation with AzBio scores, when controlling for duration of deafness, whereas duration of deafness had a positive partial correlation with AzBio scores, when controlling for age. No other effects were identified., Conclusion: Older age at testing was associated with poorer recognition of words in difficult sentences, suggesting that cognitive aging may negatively impact CI outcomes. Further studies are needed to examine how a long duration of auditory deprivation affects CI outcomes.

Temporal bone malignancy presents a significant clinical challenge for the otolaryngologist. This article provides an overview of squamous cell carcinoma of the temporal bone, including clinical presentation, diagnosis, staging, treatment, and prognosis. As demonstrated in this case study, the prognosis for patients with advanced-stage temporal bone malignancy is poor, even with maximal therapy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To determine the feasibility of measuring tympanic membrane (TM) vibrations at multiple locations on the TM to differentiate normal eardrums from those with associated ossicular pathologies., Design: Cadaveric human temporal bone study., Setting: Basic science laboratory., Methods: A mastoidectomy and facial recess approach was performed on four cadaveric temporal bones to obtain access to the ossicles without disrupting the TM. Ossicles were palpated to ensure normal mobility and an intact ossicular chain. Laser Doppler Vibrometry (LDV) measurements were then taken on all four TMs. LDV measurements were repeated on each TM following stapes footplate fixation, incudo-stapedial joint dislocation, and malleus head fixation., Main Outcome Measures: LDV measurements of TM vibration at the umbo, the lateral process of the malleus, and in each of the four quadrants of the TM., Results: The best signal-to-noise ratios were found between 2 and 4 kHz, at the umbo, the anterior superior quadrant, the anterior inferior quadrant, and the posterior inferior quadrant. Since our goal was to assess the ossicular chain, we selected the TM locations closest to the ossicular chain (the umbo and lateral process of the malleus) for further analysis. Differences could be seen between normals and the simulated ossicular pathologies, but values were not statistically significant., Conclusions: LDV measurements are technically challenging and require optimization to obtain consistent measurements. This study demonstrates the potential of LDV to differentiate ossicular pathologies behind an intact tympanic membrane. Future studies will further characterize the clinical role of this diagnostic modality.

Purpose of Review: To highlight the recent advances in the understanding of the diagnosis and management of viral inner ear disorders. Congenital sensorineural hearing loss (cSNHL), sudden sensorineural hearing loss (SSNHL), Ménière's disease, and vestibular neuritis/viral labyrinthitis are discussed., Recent Findings: Cytomegalovirus infection during pregnancy is an under-recognized cause of hearing loss and central nervous system disease amongst the general population. Prevention of maternal infection and treatment of affected newborns with ganciclovir are promising interventions. Recent evidence in SSNHL patients has resulted in recommendations against viral serology or the use of antivirals. There appears to be an increased risk of SSNHL in patients with comorbid hypertension and diabetes. The viral hypothesis of Ménière's disease remains unproven. In patients with an acute episode of vestibular neuritis, there is presently not sufficient evidence to support the routine use of corticosteroids or antiviral medications., Summary: cSNHL remains the most clearly defined of the viral inner ear disorders. The evidence for viral involvement in SSNHL, Ménière's disease, and vestibular neuritis is indirect and equivocal. This review highlights the recent advancements in the diagnosis and management of these disorders.

Objectives/hypothesis: Transmastoid occlusion of the superior semicircular canal in superior semicircular canal dehiscence (SSCD) syndrome and the posterior semicircular canal in intractable benign paroxysmal positional vertigo (BPPV) will produce resolution of preoperative symptoms., Study Design: Retrospective review, quality assurance., Methods: Sixteen patients with SSCD and 61 patients (65 ears) with intractable BPPV who underwent canal occlusion were reviewed. All patients underwent occlusion of the affected semicircular canal through a transmastoid approach., Results: Preoperative symptoms (vestibular, 13 patients; pulsatile tinnitus, 2 patients; or hyperacusis, 1 patient) were greatly improved or completely resolved in 15 of the 16 SSCD patients who underwent transmastoid occlusion of the superior canal. Hearing was preserved in 14 patients and improved in two patients. Vestibular symptoms were resolved in all intractable BPPV patients who underwent transmastoid occlusion of the posterior canal. One patient had a late recurrence of atypical BPPV. Almost all BPPV patients with normal preoperative hearing have an initial transient postoperative hearing loss, which when tested for is usually a mild to moderate mixed loss. Delayed sensorineural hearing loss was noted in three patients; one loss was profound whereas two were mild., Conclusions: The transmastoid approach to canal plugging is successful in the treatment of symptoms in both SSCD and intractable BPPV, and is a familiar approach for the otologist. This is a viable alternative to the middle fossa approach for SSCD, thereby avoiding a craniotomy. Transmastoid is the definitive approach for posterior canal occlusion., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objectives: Purified plant polysaccharide (HemoStase) is a plant-derived hemostatic agent that has not previously been used in sinus surgery. This study was conducted to evaluate the effectiveness of this novel agent in the control of nasal bleeding during endoscopic sinus surgery. The volume of bleeding during endoscopic sinus surgery was hypothesized to not be statistically significantly different between a control group (gelatin-thrombin matrix; FloSeal) and an experimental group (purified plant polysaccharide; HemoStase)., Methods: Eighteen patients with a history of chronic rhinosinusitis in whom maximal medical therapy failed who underwent endoscopic sinus surgery were randomized into one of two groups (control FloSeal group or experimental HemoStase group). In the control group, sites in the nose that were actively bleeding during the operation were controlled with FloSeal. In the experimental group, sites in the nose that were actively bleeding during the operation were controlled with HemoStase. The main outcome measure was total operative blood loss. Blood loss was the sum of blood removed by suction during the surgery (recorded in milliliters) and blood on surgical sponges (weighed and converted to milliliters). Statistical analysis was performed with the t-test and the Mann-Whitney U test., Results: The amounts of blood loss (mean +/- SEM) were not significantly different between the FloSeal (262 +/- 15 mL) and HemoStase (265 +/- 33 mL) groups (p = 0.93)., Conclusions: The results of this study demonstrate the use of a novel product for the control of intraoperative bleeding during endoscopic sinus surgery.

Objective: To evaluate vestibular evoked myogenic potentials (VEMPs) in Meniere disease and vestibular schwannoma. Given that the saccule and inferior vestibular nerve may be damaged in Meniere disease and vestibular schwannoma, respectively, VEMP latency may be prolonged in the patient's affected ear., Design: Prospective study., Setting: Urban otolaryngology practice., Methods: Ten Meniere disease and 12 vestibular schwannoma patients. Subjects were tested with the VEMP head rotation protocol., Main Outcome Measure: VEMP latency., Results: In Meniere disease patients, the pI latencies (mean +/- SEM, milliseconds) were 12.26 +/- 0.75 (healthy ear) and 14.20 +/- 0.73 (affected ear) (p = .041). The nI latencies were 20.29 +/- 1.06 (healthy ear) and 25.06 +/- 1.64 (affected ear) (p = .013). In vestibular schwannoma patients, the pI latencies were 12.02 +/- 0.93 (healthy ear) and 15.88 +/- 1.35 (affected ear) (p = .016). The nI latencies were 20.98 +/- 1.59 (healthy ear) and 24.84 +/- 1.08 (affected ear) (p = .031)., Conclusion: VEMP pI and nI latencies were prolonged in the affected ear of Meniere disease and vestibular schwannoma patients. We propose classifying VEMP as abnormal if both the pI latency is > 1 ms longer and the nI latency is > 2 ms longer (sensitivity 66.7%, specificity 86.4%) compared with the other ear. This study suggests a role for VEMP in the clinical testing of these patients.

Vertical nystagmus occurs in patients with central vestibular system pathology. Lesions of the pons, medulla, and cerebellum lead to vertical nystagmus. Given this association, vertical nystagmus is considered pathognomonic in nature. We present a case of benign paroxysmal positional vertigo (BPPV) with positive Dix-Hallpike bilaterally, but also with upbeat purely vertical nystagmus in the straight back head hanging position. Computed tomography imaging of the typically pathologic structures in vertical nystagmus (brainstem/posterior fossa) revealed normal anatomy. We propose this case as an instance of peripheral-associated purely vertical nystagmus without central pathology, while building on our previous understanding of BPPV physiology.

Growth hormone (GH) mRNA and protein have recently been demonstrated in the rat lung throughout the period of alveolarization (day 4-14 postnatally). The functional significance of this finding was therefore assessed, by determining the effects of GH mRNA knockout using aerosolized antisense oligodeoxynucleotides (ODN) directed against the GH gene. In a preliminary experiment, the effectiveness of the antisense GH ODN was demonstrated in a lung Type II epithelial cell line (L2 cells), in which constitutive GH mRNA expression was completely abolished by GH ODN transfection. Administration of the aerosolized GH ODN to 4-day-old rats for 10 days was accompanied by a widespread presence of its delivery liposomes within lung cells. Aerosolized GH ODN treatment decreased lung concentrations of IGF (insulin-like growth factor)-1 and increased concentrations of albumin, calcyclin binding protein, superoxide dismutase, RNA binding protein motif 3, and the alpha- and beta-subunits of ATP synthase and electron transfer flavoprotein. At least 32 other proteins (identified by 2D gel electrophoresis) were also significantly affected by the antisense GH ODN treatment. By changing the lung proteome, these results indicate hitherto unsuspected autocrine/paracrine actions of GH in developmental lung function.

Objective: To evaluate the methodology for vestibular evoked myogenic potential (VEMP) testing, with a focus on the usefulness of the head rotation as a means to tense the sternocleidomastoid (SCM) muscles. Our goal was to obtain normative data for our site and methodology., Design: Prospective study., Setting: Outpatient otolaryngology clinic., Methods: P rospective study. Volunteers without an otologic history were selected. While sitting, the volunteer rotated his or her head away from the tested ear so as to tense the ipsilateral SCM. While the SCM was tensed, the volunteer was presented with loud clicks. Responses were averaged., Main Outcome Measures: VEMP positive (pI) wave latency and amplitude, VEMP negative (nI) wave latency and amplitude, and volunteer ability to perform the head rotation method., Results: In healthy controls, average P1 latencies (milliseconds) were 12.58 +/- 0.39 and N1 latencies were 21.88 +/- 0.40. Average P1 amplitudes (microvolts) were 20.48 +/- 1.94 and N1 amplitudes were -25.56 +/- 2.21. VEMP amplitudes were less consistent in patients with limited neck strength., Conclusions: VEMPs can be elicited from the majority of volunteers. The test is easy to perform, and it is only mildly uncomfortable for most patients using the head rotation method.

The presence of growth hormone (GH) and GH receptors (GHRs) in the lung suggests it is an autocrine/paracrine target site for pulmonary GH action and/or an endocrine site of pituitary GH action. Roles for GH in lung growth or pulmonary function are, however, uncertain. The possibility that pituitary and/or pulmonary GH have physiological roles in lung development has therefore been investigated in GHR knockout (KO or -/-) mice, using a proteomics approach to determine if an absence of GH-signaling affects the proteome of the developing lung. More than 600 proteins were detected by 2-DE in the lungs of control [GHR (+/+)] and GHR (-/-) mice at the end of the alveolarization period (at day 14 postnatally). Of these, 39 differed significantly in protein content at the p>0.05 level [6 were of higher abundance in the GHR (-/-) group, 33 were of lower abundance] and 17 differed at the p>0.02 level [5 of higher abundance in the GHR (-/-) group, 12 of lower abundance] and 7 were definitively identified by MS. Vimentin, a protein involved in cellular proliferation, was reduced in content by approximately 75% in the lungs of the GHR (-/-) mice. Three proteins involved in oxidative protection [SH3 domain-binding glutamic acid-rich-like protein, peroxiredoxin 6 (Prdx6), and isocitrate dehydrogenase 1] were also of lower content in the GHR (-/-) lungs (by approximately 88%, 81% and 70%, respectively). Prdx6 is also involved in lipid and surfactant metabolism, as is apolipoprotein A-IV, the lung content of which was reduced by approximately 73% in these mice. Proteasome 26S ATPase subunit 4, a protein involved in the non-lysosomal degradation of intracellular proteins, and electron flavoprotein alpha subunit , involved in intracellular metabolism, were also reduced in content in the lungs of the GHR (-/-) mice (by approximately 70% and 49%, respectively). These results therefore suggest that these proteins are normally dependent upon GH signaling, and that GH is normally involved in early lung growth, oxidative protection, lipid and energy metabolism and in proteasomal activity. These roles may reflect endocrine actions of pituitary GH and/or local autocrine/paracrine actions of GH produced within the lung.

The lung is well established as being a postnatal target site for growth hormone (GH) action, since pathophysiological states of GH excess and deficiency are both associated with impaired pulmonary function. Pituitary GH is therefore probably involved in normal lung growth or development, although perinatal lung development occurs prior to the differentiation of pituitary somatotrophs and the ontogeny of pituitary GH secretion. The lung itself may, however, be a site of GH production during prenatal development, since a specific GH-response gene (a marker of GH activity) is expressed in the lungs of early chick embryos, in which GH immunoreactivity is widespread in many other peripheral tissues. We have assessed this possibility in embryonic chicks. A 690-bp cDNA, identical in size and nucleotide sequence to the full-length pituitary GH transcript, was amplified by reverse transcription/polymerase chain reaction from total RNA extracted from the lungs of embryos at 11, 13, 15, and 18 days of the 21-day incubation period. This transcript was localized by in situ hybridization to mesenchymal and epithelial cells of the developing lungs, in which specific GH immunoreactivity was similarly located. Intense GH immunoreactivity was also present after embryonic day 15 (ED15) in the smooth muscle surrounding blood vessels in the lung and surrounding the bronchioles. Lung GH immunoreactivity was primarily associated with a 15-kDa protein, rather than the 26-kDa protein in the pituitary gland. After the onset of pituitary GH secretion (at ED17), GH mRNA was barely detectable in the lungs of ED20 embryos, at the start of lung breathing. GH immunoreactivity was, however, still present in some cells in the lungs of ED20 embryos. GH-receptor mRNA and immunoreactivity were also widespread and abundant within the embryonic lung. Lung GH may thus have autocrine or paracrine roles in lung development or in pulmonary function prior to the ontogeny of the pituitary gland and the appearance of GH in peripheral plasma.

Growth hormone (GH) recently has been shown to be expressed in the neonatal rat lung during alveolarization. The possible functional importance of lung GH in lung function, therefore, has been assessed by determining changes in GH-responsive proteins in the developing rat lung after the overexpression of the GH gene in this tissue. GH overexpression was achieved using an adenovirus that expressed the mouse GH gene. This adenovirus was effective in inducing mouse GH expression in cultured rat lung L2 epithelial cells. It was also shown to be strongly expressed in the alveoli of 14-day-old rat pup lungs 10 days after it was administered by intratracheal injection, during a period of rapid lung development. Expression of the transgene in these pups was accompanied by changes in lung protein concentrations determined by two-dimensional gel electrophoresis and mass spectrometry. The lung concentrations of specific enzymes (nucleotide diphosphate kinase B, Cu/Zn superoxide dismutase, glutathione-S-transferase, and aldehyde reductase-1) were increased by the adenoviral expression of mouse GH, as were the concentrations of beta subunit G-protein calponin 2, beta-5 tubulin, retinoblastoma binding protein 4, and fetuin A. In contrast, the lung concentrations of haptoglobin and major acute phase alpha-1 protein were reduced by adenoviral expression of mouse GH. Although most of these proteins have not previously been identified as GH-responsive proteins, these results demonstrate actions of GH in the rat lung and support the possibility that GH acts as an autocrine/paracrine during early lung development., ((c) 2005 Wiley-Liss, Inc.)