William J Doyle

University of Pittsburgh | Pitt · Department of Otolaryngology

Introduction: Middle ear (ME) pressure-regulation (MEPR) is a homeostatic mechanism that maintains the ME-environment pressure-gradient (MEEPG) within a range optimized for "normal" hearing. Objective: Describe MEPR using equations applicable to passive, inter-compartmental gas-exchange and determine if the predictions of that description includ...

Exposure to parental separation or divorce during childhood has been associated with an increased risk for physical morbidity during adulthood. Here we tested the hypothesis that this association is primarily attributable to separated parents who do not communicate with each other. We also examined whether early exposure to separated parents in con...

Objective: Determine if the middle ear transmucosal nitrous oxide (N2O) exchange rate is affected by nasal inflammation caused by topical application of histamine. Methods: In a randomized, double-blind, crossover study, 20 adults were challenged intranasally with histamine (5 mg) and placebo on separate occasions. At each session, the subjects...

Objective: To describe the temporal pattern of otitis media with effusion (OME) resolution for a cohort of nonsyndromic cleft palate children enrolled before palatoplasty and followed through 5 years of age. Design: This is a prospective, longitudinal study of the time course for OME resolution in infants and children with palatal clefts. Setti...

Objective: To examine whether trait positive and negative affect (PA, NA) moderate the stress-buffering effect of perceived social support on risk for developing a cold subsequent to being exposed to a virus that causes mild upper respiratory illness. Method: Analyses were based on archival data from 694 healthy adults (mean age = 31.0±10.7 year...

Objectives Determine if a 2-Step multivariate analysis of historical symptom/sign data for comorbid diseases can abstract high-level constructs useful in assigning a child's “risk” for different Otitis Media expressions. Methods Seventeen items related to the symptom/sign expression of hypothesized Otitis Media comorbidities were collected by hist...

The immunosuppressive effects of glucocorticoids (GCs) are well-established. However, whether the net effect of GC-elicited alterations in immune function is sufficient to influence a clinically relevant outcome in healthy adults has yet to be shown. The aim of the present study was to investigate whether inter-individual differences in basal saliv...

Objective: To test the hypothesis that eustachian tube opening efficiency, measured as the fractional gradient equilibrated (FGE), is lower in 6-year-old children with no middle ear disease but a well-documented history of recurrent acute otitis media, as compared with children with a negative disease history (control). Study design: Cross-secti...

Objective: Determine if the middle ear (ME) trans-mucosal nitrous oxide (N2O) gas exchange rate can be pharmacologically modulated by the nasal application of a vasoconstrictor. Methods: In a randomized, double-blind, crossover study, 20 adults received a nasal spray challenge containing either oxymetazoline or saline (placebo). At each session,...

Objectives: To explore the association of self-rated health (SRH) with host resistance to illness after exposure to a common cold virus and identify mechanisms linking SRH to future health status. Methods: We analyzed archival data from 360 healthy adults (mean [standard deviation] age = 33.07 [10.69] years, 45.6% women). Each completed validate...

Determine if oral treatment with a vasoconstrictor decreases the blood to middle ear exchange rate of the perfusion-limited gas, nitrous oxide (N2 O). Randomized, double-blind, crossover study. Ten adult subjects with and 10 without past middle ear disease completed paired experimental sessions, identical except for oral treatment with either pseud...

Perceived social support has been hypothesized to protect against the pathogenic effects of stress. How such protection might be conferred, however, is not well understood. Using a sample of 404 healthy adults, we examined the roles of perceived social support and received hugs in buffering against interpersonal stress-induced susceptibility to inf...

Eustachian tube (ET) dysfunction predisposes ears to otitis media, tympanic membrane retraction, retraction pocket and perforation, or cholesteatoma. To develop a method to quantitatively measure the eustachian tube (ET) component movements and their interactions captured by transnasal videoendoscopy of the ET during swallowing. A blinded analysis...

Objectives/HypothesisTest the hypothesis that the eustachian tube (ET) function measured using standard manometric test methods is different between groups of ears with tympanostomy tubes inserted for recurrent acute otitis media (RAOM) and for chronic otitis media with effusion (COME). Study DesignA cross-sectional study of ET function in populati...

Objectives (1) Image the Eustachian tube (ET) lumen by computed tomography (CT) scanning during ET function (ETF) testing, (2) characterize the differences in image quality for different scanning protocols, and (3) establish a novel research methodology for studying ET anatomy and physiology. Methods In a cadaver head without craniofacial or otolo...

Childhood adversity, defined in terms of material hardship or physical or emotional maltreatment has been associated with risk for infection with cytomegalovirus (CMV) among children and adolescents, and with CMV reactivation in children and adults. The present study examined whether different dimensions of childhood experience—those pertaining to...

Conclusions: Protocol limitations were identified and accounted for in the analysis. Percent gradient equilibrated (PGE) was affected by driving gradient direction in a similar manner to other efficiency measures. A finer resolution of possible age-related changes in eustachian tube opening efficiency is expected with the application of more sophi...

Conclusions: Fractional gradient equilibrated (FGE) for ears with applied positive but not negative middle ear (ME)-ambient pressure gradients is highly sensitive to a cold-like illness (CLI). Objective: The sequential development of eustachian tube (ET) dysfunction, ME under-pressure, and otitis media (OM) characterizes many children during a C...

Sonotubometry is a simple test for Eustachian tube (ET) opening during a maneuver. Different sonotubometry configurations were suggested to maximize test accuracy, but no method has been described for comparing sonotubometry test results with those for a definitive measure of ET opening. Here, we present such a method and exemplify is use by an acc...

Objective Test the hypothesis that active Eustachian tube opening efficiency as measured by sonotubometry is higher in adults with no extant middle-ear disease and no history of previous otitis media (Group-1) when compared to adults with no middle-ear disease but a positive history for otitis media (Group-2). Methods Eustachian tube function for...

Childhood adversity, defined in terms of material hardship or physical or emotional maltreatment has been associated with risk for infection with cytomegalovirus (CMV) among children and adolescents, and with CMV reactivation in children and adults. The present study examined whether different dimensions of childhood experience—those pertaining to...

Objectives/hypothesis: In children with ventilation tubes (VTs) inserted for chronic otitis media with effusion (COME), the authors sought to determine whether any parameter of Eustachian tube (ET) function measured by the forced response test (FRT) predicts disease recurrence after the VT becomes nonfunctional. Study design: Prospective study o...

Low socioeconomic status (SES) during childhood and adolescence has been found to predict greater susceptibility to common cold viruses in adults. Here, we test whether low childhood SES is associated with shorter leukocyte telomere length in adulthood, and whether telomere length mediates the association between childhood SES and susceptibility to...

Importance: The study demonstrates the utility of eustachian tube (ET) function (ETF) test results for accurately assigning ears to disease state. Objectives: To determine if ETF tests can identify ears with physician-diagnosed ET dysfunction (ETD) in a mixed population at high sensitivity and specificity and to define the interrelatedness of ET...

Objective: This report reviews the literature to identify the advances in our understanding of the middle ear (ME)-Eustachian tube (ET) system during the past 4 years and, on that basis, to determine whether the short-term goals elaborated in the last report were achieved and propose updated goals to guide future otitis media (OM) research. Data...

Eustachian tube function is stable over time in children with ventilation tubes for chronic otitis media with effusion. Clinical studies report that Eustachian tube function tests in patients with a persistent tympanic membrane perforation predict the success of myringoplasty, and those in patients with ventilation tubes for chronic otitis media pr...

Objectives: The Cephalic Index, an anthropometric measure of head shape, was reported to be different between individuals with and without signs of past or concurrent otitis media (OM). In this study, we compared the Cephalic Index and other measures of head shape among groups of children aged 36-48 months with a documented history of chronic OM w...

To determine the role played by the tensor veli palatini and levator veli palatini muscles (mTVP and mLVP, respectively) in eustachian tube (ET) opening. Prospective study. Research laboratories at a tertiary care hospital. Fifteen healthy adults with normal middle ears and documented ET openings. Submental and ground surface electrodes were placed...

To determine whether parenthood predicts host resistance to the common cold among healthy volunteers experimentally exposed to a common cold virus. Participants were 795 healthy volunteers (age range = 18-55 years) enrolled in one of three viral-challenge studies conducted from 1993 to 2004. After reporting parenthood status, participants were quar...

We propose a model wherein chronic stress results in glucocorticoid receptor resistance (GCR) that, in turn, results in failure to down-regulate inflammatory response. Here we test the model in two viral-challenge studies. In study 1, we assessed stressful life events, GCR, and control variables including baseline antibody to the challenge virus, a...

One past study conducted in 1986 reported Eustachian tube dilation with swallowing during the forced response test (FRT) in a very high percentage (>80%) of cleft palate patients both before and after palatoplasty. The present study was designed to determine the reproducibility of those results. The FRT was used to evaluate Eustachian tube function...

This study assessed the normal growth and development of mastoid air-cell system (MACS) geometry from infancy through adolescence. Cross-sectional study. This cross-sectional study evaluated the change with age in MACS volume, surface area, and surface area/volume ratio in 36 (72 ears) individuals aged 1.6 to 18 years with no history of middle ear...

This study describes the changes in mastoid air cell system (MACS) geometry with age in ears with a history of otitis media (OM), without (GR-I) or with (GR-II) middle ear fluid on the CT scan. Thirty-seven (74 MACSs) CT scans were selected to approximate 4 MACSs/year between 1 and 18 years. For each MACS, the volume, surface area and surface area/...

Objective: Evaluate normal human Eustachian tube (ET) function during swallowing and other maneuvers that open the ET using a variety of modalities including EMG of the Tensor veli palatini (mTVP), Levator veli palatini (mLVP), and submental muscles, videoendoscopy, and sonotubometry; and compare these results with ET function tests in a pressure c...

When used to test 3-year-old children within 3 months of tympanostomy tube placement for recurrent acute otitis media (rAOM) or chronic otitis media with effusion (cOME) the forced response test (FRT) showed relatively minor differences in the active and passive functions of the eustachian tube. While the sample size was small, the high variability...

Objective: To characterize Eustachian tube function using the forced response test in young children with cleft palate with or without cleft lip after palatoplasty with tympanostomy tubes inserted prepalatoplasty and compare these results with those of a 1986 study that evaluated a similar population using identical methods. Setting: Outpatient...

The geometry of the adult human mastoid air cell system has not previously been described over a large range of mastoid air cell volumes. Twenty subjects with a wide range of mastoid air cell pneumatised areas, as determined by X-ray, underwent computed tomography scanning of the middle ear. Mastoid air cell surface areas and volumes were then reco...

We sought to develop normative values for 5 eustachian tube function (ETF) test protocols in adults without otitis media (OM). Twenty adults (19 to 48 years of age) without a recent history of OM (5 had OM in childhood) underwent unilateral myringotomy and were evaluated for ETF by use of the forced response, inflation, deflation, forcible "sniff",...

Past in vivo studies in humans showed that the tympanic membrane (TM) is permeable to physiological gases. Animal studies show that transTM CO(2) conductance is increased by TM pathology. The objective of the study was to determine if transTM CO(2) exchange in humans is affected by atrophic and sclerotic pathologies. The study used an ear canal (EC...

Determine the role of mastoid volume in middle ear pressure (MEP) regulation. The hypothesis was that inert gas exchange between blood and middle ear (ME) is slower for larger mastoid volumes. Prospective. For 21 enrolled subjects, the bilateral surface areas and volumes of the mastoid and tympanum were measured from computed tomography scans in 20...

Estimate the transmucosal CO(2) and O(2) rate-constants for adult middle ears (MEs). Ten adults with healthy MEs had a unilateral myringotomy. A custom-fitted acrylic mold with a valved line to a mass spectrometer (MS) and central tube coupled to a 3-way valve and connected to a pressure transducer (the probe) was sealed with adhesive glue within t...

The vector relationships between the Eustachian tube, Tensor veli palatini muscle and cranial base constrain the efficiency of middle ear pressure-regulation and are required parameters for computational modeling of Eustachian tube function. Here, those relationships were reconstructed from skulls and compared between children and adults. Reconstru...

The middle ear (ME) surface area/volume ratio (SA/V) is greater than that of the tympanum. The rate of ME pressure decrease is proportional to the ME SA/V. The mastoid air-cell system (MACS) will not function as an ME gas reserve unless the blood perfusion/surface area is much greater for the tympanum than the MACS and decreases as MACS volume incr...

To determine if levels of interleukin (IL) 5, IL-6, and IL-10 or their ratios in nasal secretion are diagnostic of viral upper respiratory tract infections (vURTIs) and coldlike illnesses (CLIs) in children. Longitudinal study of children for vURTIs, CLIs, and concentrations and ratios of nasal cytokines. Outpatient assessments of children. A total...

Hostility has been associated with heightened proinflammatory activity. However, it is not known whether greater hostility contributes to greater inflammation by promoting higher Th1 activity, lower Th2 activity, or both. The present study examines the relation of hostility to mitogen-stimulated Th1 and Th2 cytokine production in vitro. Participant...

In adults and children with respiratory syncytial virus (RSV) infection, a polymorphism in the interleukin 6 (IL-6) promoter at position -174 predicts illness magnitude. In addition, polymorphisms in the interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma) genes are associated with immune responsiveness...

The development of a “cold-like illness” (CLI) usually requires infection with an upper respiratory virus such as rhinovirus, influenza virus, respiratory syncytial virus, parainfuluenza virus, coronavirus or adenovirus, among others, and the development of sufficient signs, symptoms and pathophysiologies to qualify as being ill based on personal a...

Objectives: Upper respiratory virus infection is associated with the expression of symptoms and signs of illness, and with the development of complications in anatomically contiguous structures. In most epidemiological studies, the frequency of the various complications is expressed as a fraction of the total population judged to be ill by report,...

The effect of changing body position on the Eustachian tube opening time (TOT) and nasal conductance (NC) was investigated in 5 subjects. Eustachian tube function was evaluated using a sonotubometric technique and NC was determined by anterior or posterior rhinomanometry. The results showed that both the TOT and NC were decreased by changing the bo...

In an effort to study the effects of experimental paralysis of tensor veli palatini (TVP) muscle on Eustachian tube (ET) function and middle-ear (ME) status, botulinum toxin A (Oculinum) was injected into the TVP muscles of 8 Rhesus monkeys. Tubal function was tested longitudinally in 2 animals with tympanostomy tubes using the forced-response test...

Sleep quality is thought to be an important predictor of immunity and, in turn, susceptibility to the common cold. This article examines whether sleep duration and efficiency in the weeks preceding viral exposure are associated with cold susceptibility. A total of 153 healthy men and women (age range, 21-55 years) volunteered to participate in the...

To estimate the coincidence of new otitis media (OM) for first nasopharyngeal detections of the more common viruses by polymerase chain reaction (PCR). New OM episodes are usually coincident with a viral upper respiratory tract infection (vURTI), but there are conflicting data regarding the association between specific viruses and OM. Longitudinal...

Guidelines recommend treatment with intranasal corticosteroids for patients with allergic rhinitis (AR), but concerns remain about possible adverse effects. To present the 1- and 2-year growth results for children with AR treated with triamcinolone acetonide aqueous nasal spray. Thirty-nine children (aged 6.1-14.3 years at study entry) were treated...

The hypothesis that the human tympanic membrane (TM) is permeable to CO(2) and O(2) at physiologic pressure gradients is supported but additional experiments need to be done to validate this methodology. Gas exchange between the middle ear and adjacent compartments determines the trajectory of middle ear pressure change. Little information is avail...

Streptococcus pneumoniae, a leading cause of otitis media (OM), undergoes spontaneous intra-strain variations in colony morphology. Transparent (T) variant is more efficient in colonizing the nasopharynx while the opaque (O) variant exhibits greater virulence during systemic infections. We hypothesized that changes in middle ear (ME) gas pressure/c...

Viral upper respiratory tract infection (vURI) may or may not present with a cold/flu-like illness (CFLI). For common upper respiratory viruses that cause vURIs, to determine the relative frequencies of virus detection by PCR in subjects with and without CFLIs. Prospective follow-up of 170 children aged 1-8.6 years through the CFLI season by daily...

Previous studies suggested that the otitis media (OM) complication rate of viral upper respiratory infection (vURI) is conditioned by genes affecting cytokine production. Two hundred and thirty children (114 male; 187 White, 25 Black; aged 1-9.3 years, average=3.6+/-1.6 years) were prospectively followed over the typical cold season for cold-like i...

Tympanometry is a relatively simple method to assess middle ear (ME) status and pressure. Daily, serial tympanometric measurements may contain information on the constitutional efficiency of Eustachian tube function (ETF). A study was conducted to determine family compliance with an effort-intensive protocol that requires daily tympanometry done on...

Tympanometry is a simple method to assess middle ear pressure (MEP) and the presence of middle ear effusion (MEE), a marker of otitis media (OM). To determine whether daily parental tympanometry and illness sign recording in their children can be used to define the time between onsets of cold-like illness (CLI) and MEE at high resolution. Prospecti...

We ask whether subjective socioeconomic status (SES) predicts who develops a common cold when exposed to a cold virus. 193 healthy men and women ages 21-55 years were assessed for subjective (perceived rank) and objective SES, cognitive, affective and social dispositions, and health practices. Subsequently, they were exposed by nasal drops to a rhi...

There is a continuing interest in defining the incidence, prevalence and burden of otitis media (OM) in the individual and population for purposes of assigning "risk factors". Often overlooked in past studies are the contributions of cold-like illnesses (CLIs) and sampling interval to those estimates. Describe the incidence of symptomatic (AOM) and...

New otitis media (OM) episodes are most frequently a complication of cold-like illnesses (CLIs) which are often virus infections that can be exchanged within the family unit. Interference with intrafamily CLI transmission may present a strategy for OM prophylaxis in high risk children. This study estimated factors relevant to strategy efficiency. T...

Otitis media is a frequent complication of a viral upper respiratory tract infection, and the reported co-incidence of those diseases increases with assay sensitivity and sampling density. We determined the incidence of otitis-media complications in young children when referenced to cold-like illnesses and to concurrent virus recovery from the naso...

The physiological function of the mastoid air cell system (MACS) with respect to middle ear (ME) pressure-regulation remains controversial because predictive mathematical models and experimental data to formulate and test hypotheses are lacking. A mathematical description of MACS volume effects on the rate of ME pressure change is presented; the ag...

Infection commonly triggers nonspecific psychological and behavioral changes including fatigue and malaise, anhedonia, inability to concentrate, and disturbed sleep that collectively are termed "sickness behaviors". Converging evidence from several lines of research implicate the activities of proinflammatory cytokines as a cause of sickness behavi...

Most studies on the natural history of viral upper respiratory tract infections and their complications rely for ascertainment on self-assessed cold/flu illness or the identification of presumed complications. The criteria for cold/flu definition, however, are variable within and between individuals and illness is not prerequisite for a viral upper...

The mechanisms that control Streptococcus pneumoniae's ability to colonize the nasopharynx or to invade the middle ear and cause acute otitis media are not understood. Focused study of these mechanisms requires efficient methods for the extraction of microbial RNA from minute clinical samples. Several lysis/extraction methods were tested and compar...

Simple, 2-compartment mathematical models of middle ear (ME) transmucosal gas exchange reproduce observed ME pressure behavior. These models require input of an experimentally determined, lumped-parameter exchange constant for each represented gas species. Previous model applications assumed directional asymmetry for those parameters, which has not...

In contradistinction to the poetically inspired disjunction between the name and quality of a rose recited by Juliet in the famous quote from Shakespeare's play, disease labels used in the medical sciences need to have exact meaning to ensure that they communicate an accurate diagnosis and a valid treatment approach. Above, we presented a consisten...

These results hold promise that morphometric analysis can be used to generate transMEM (middle ear mucosa) gas conductance estimates for MEM geometries representative of the shift from healthy to pathologic states (e.g. increased MEM thickness and capillary density). Novel strategies to treat otitis media with effusion require a better understandin...

In an earlier study, positive emotional style (PES) was associated with resistance to the common cold and a bias to underreport (relative to objective disease markers) symptom severity. This work did not control for social and cognitive factors closely associated with PES. We replicate the original study using a different virus and controls for the...

Past studies suggest that the majority of new otitis media (OM) diagnoses is a complication of a colds/flu. A prospective format was used to determine the coincidence of otitis media and parent diagnosed cold/flu episodes in young children followed over a typical cold/flu season. Eighteen families with children aged 1-8 years were followed from Oct...

Allergy skin testing is one of the most frequently performed physician office procedures. Many factors can affect the results of those tests, including the well-defined suppressive effect of systemic antihistamines. False-positive allergen skin test results are known to occur; however, contributing factors are not well understood. To determine whet...

We assess whether socioeconomic status (SES) is associated with basal levels of cortisol and catecholamines and determine if any association between SES and these hormones can be explained (is mediated) by behavioral, social, and emotional differences across the SES gradient. One hundred ninety-three adult subjects, including men and women and whit...

Psychosocial factors moderate the expression of illness during upper respiratory virus infections but past attempts to define mediational pathways were not successful. Here, we used a model of experimental rhinovirus infection in humans to evaluate three proinflammatory cytokines for their potential role in mediating the previously documented assoc...

Identification of a pharmacologically targeted mediator of the common cold is a desirable, but, to date, elusive goal of current research. The roles of various mediators, such as histamine, leukotrienes, bradykinin, and, more recently, chemokines and cytokines, in the pathophysiology and development of complications of the common cold are the subje...

Middle ear barotrauma during flight is a painful disorder experienced by passengers who cannot properly regulate their middle ear pressure in response to the changing cabin pressures during ascent and descent. Previous reports emphasized the important role of poor eustachian tube function in disease pathogenesis but paid little attention to other m...

We measured affect in 334 healthy adults on each of 7 days over a 3-week period. On the last day, salivary cortisol was assessed 14 times yielding scores for total concentration, morning rise amplitude, and slope of the time function. Trait negative affect (NA) was associated with higher total cortisol concentrations and greater morning rise in men...

Nasal inflammation (NI) resulting from allergy or virus infection is causally associated with otitis media. Impaired Eustachian tube (ET) function consequent to NI may mediate this relationship. Moreover, the functional demand placed upon the ET for gas supply may be increased by NI, a hypothesis tested here. A total of five experiments were done a...

An accurate mathematical model of transmucosal gas exchange is prerequisite to understanding middle ear (ME) physiology. Current models require experimentally measured gas species time constants for all extant conditions as input parameters. However, studies on pulmonary gas exchange have shown that a morphometric model that incorporates more funda...

Earlier studies documented a slow diffusion of gas across the tympanic membrane (TM) in humans and animals. However, structural changes caused by repeated TM perforations could affect gas diffusion rates. This possibility was evaluated using a chinchilla model. In six chinchillas, the right TM was perforated four times at 2-week intervals; the left...

Low childhood socioeconomic status (SES) is a risk factor for adult morbidity and mortality primarily attributable to cardiovascular disease. Here, we examine whether childhood SES is associated with adult host resistance to infectious illness, and whether the effect is limited to a critical period of low SES exposure, can be undone by changes in c...

Objectives/hypothesis: Acute otitis media, often caused by infection with Streptococcus pneumoniae, is characterized by inflammation of the middle ear mucosa. A prominent feature of the host response to bacterial infection of the middle ear mucosa is an influx of inflammatory cells that contributes to the local pool of inflammatory mediators by re...

The development and expression of allergic rhinitis and asthma may be influenced by the elaboration of specific cytokines. Cytokine genotypes moderate illness severity in a variety of inflammatory disorders. Cytokine genotyping was performed on 124 infants (85% white, 57% male) to determine whether specific cytokine genotypes are associated with a...

RationaleThe development and expression of allergic rhinitis and asthma may be influenced by the elaboration of specific cytokines. Cytokine gene polymorphisms moderate illness severity in a variety of inflammatory disorders.

RationaleElevations of exhaled NO have been reported in patients with asthma. Laboratory studies suggest that levalbuterol possesses anti-inflammatory properties. The objective of this study was to evaluate the effect of levalbuterol versus placebo on exhaled NO levels in subjects with asthma.

RationaleThe general population can be divided into groups that report either frequent (>3/year) or infrequent episodes (<1/year) of the common cold. The factors influencing this are unknown; however, recent data implicate immunologic factors, including cytokine responses. The objective of this study was to determine whether certain cytokine respon...

Tympanometry is useful for evaluating middle ear (ME) status, but its accuracy in estimating true ME pressure has been questioned. We evaluated the accuracy of tympanometry in 6 monkeys. Direct application and measurement of ME pressure were achieved with a probe introduced into the mastoid antrum, and tympanometry was done over a large range of ap...