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Objective: To determine the effect of changes from nasal to tracheal respiration on maxillary sinus mucosal blood flow in rabbits with unobstructed sinus ostia. Design: Animals underwent tracheotomy with a T tube, and then a small window of intact maxillary sinus mucosa was exposed. Mucosal blood flow was recorded during normal nasal respiration using laser-Doppler velocimetry. At hourly intervals, respiration was changed from the nasal to the tracheal route and then back again. Subjects: Ten anesthetized rabbits were used: 5 underwent single and 4 underwent multiple shifts in the respiratory route, while 1 was monitored continuously during long-term nasal breathing only. Results: A significant decrease in maxillary sinus blood flow occurred on switching from nasal to tracheal respiration and a significant increase in blood flow occurred on return to nasal respiration. Where multiple switches were made, blood flow changes diminished in magnitude, but significant decreases (nasal to tracheal) or increases (tracheal to nasal) were evident in all cases. Conclusions: It is proposed that the maxillary sinus may act in an accessory capacity to the nose for humidification of inspired air via secretions liberated from the sinus ostium. Furthermore, we suggest that nasal airflow is involved with the reflex regulation of sinus blood flow, probably via stimulation of sensory receptors in the nasal cavity. Reduced maxillary sinus mucosal blood flow may thus contribute to supra-systemic levels of antral carbon dioxide. Since elevated carbon dioxide levels have been shown to reduce maxillary sinus mucociliary activity in vitro, nasal airflow compromise may contribute to the initiation of a cascade of pathophysiological events leading to acute sinusitis. Arch Otolaryngol Head Neck Surg. 1997;123:1336-1340

Objective: To estimate the rate of exchange of selected gases across the middle ear (ME) mucosa and define the exchange limitations. Design: At separate sessions, the ME was inflated via the eustachian tube with a bolus of pure nitrogen, carbon dioxide, oxygen, or nitrous oxide, and ME pressures were recorded by tympanometry at selected intervals for up to 4 hours. The slope of the function relating pressure change to pressure was calculated by least squares regression and used as an estimate of the rate constant for exchange of that gas (experiment 1). Because of the slow rate of nitrogen exchange, a second experiment was performed in which the tensor veli palatini muscle was unilaterally paralyzed. The ME was inflated with nitrogen, and the slope of the rate-pressure function for measurements at 24-hour intervals was used to estimate the rate constant. Subjects: Ten juvenile cynomolgus monkeys, six for experiment 1 and four for experiment 2. Results: The relative, average rate constants for carbon dioxide, nitrous oxide, oxygen, and nitrogen were 1, 10.7, 18.6, and greater than 700, respectively. Comparisons of these rates with those predicted by theory show that oxygen and carbon dioxide exchange is diffusion limited, and nitrous oxide and nitrogen is perfusion limited. Conclusions: The perfusion limitation for nitrogen suggests that its exchange rate is notably increased by inflammation from increased mucosal blood flow. Targeting inflammation for therapy of persistent ME effusions may decrease the rate of nitrogen exchange and reestablish normal ME pressure regulation. (Arch Otolaryngol Head Neck Surg. 1995;121:887-892)

To elucidate the role of cytokines, immunoglobulins, and bacterial pathogens in the middle ear effusions (MEEs) of children with otitis media (OM).Paired MEEs and serum samples collected from consecutive patients were assayed for immunoglobulins. Middle ear effusions were cultured for bacterial pathogens and assayed for interleukin-1 beta, interleukin-6, tumor necrosis factor alpha, and interferon gamma. The medical charts of the patients were retrospectively reviewed to define the history of OM.Seventy-five patients with a history of recurrent acute OM, persistent OM with effusion, or both. Exclusion criteria included the presence of a major coexisting condition, or an unclear or atypical history of OM.A private practice at a tertiary care children's hospital.At the time of tympanostomy tube placement, with the patient under general anesthesia, one MEE and a serum sample were collected.Interleukin-1 beta was detected in 58% (44/75) MEEs; interleukin-6, 83% (60/72); tumor necrosis factor alpha, 37% (28/75) [corrected]; and interferon gamma, 61% (45/74). Concentrations of interleukin-1 beta, interleukin-6 and tumor necrosis factor alpha in MEEs were highly correlated with each other (P.01 for each association) suggesting increased local production and the expected effects of cytokines stimulating their own production during OM. High concentrations of tumor necrosis factor alpha in MEEs were also associated with a history of multiple placements of tympanostomy tubes (r = .63).These data suggest a regulatory role for cytokines in inflammation during OM, and suggest that high concentrations of tumor necrosis factor alpha in MEEs may be a marker for OM chronicity.

• To evaluate the efficacy and otologic effects of recombinant interferon beta serine for experimental rhinovirus colds, 38 healthy adults received nasal drops of recombinant interferon beta serine, 12×10 6 U, or placebo three times daily for 4.3 days beginning 36 hours after infection. Illness rates and severity did not differ between the groups, but the frequency of virus shedding was reduced on the fourth (37% vs 74%) and sixth (11% vs 42%) postchallenge days in recipients of recombinant interferon beta serine. Abnormal eustachian tube function in at least one ear was identified by the inflation-deflation test during 44% of observations in 13 infected recipients of recombinant interferon beta serine compared with 62% of observations in five placebo recipients. Tympanometry revealed middle-ear pressure abnormalities ( 20 mm H 2 O) in at least one ear during 18% of observations in recipients of recombinant interferon beta serine compared with 38% of observations in placebo recipients. These results suggest that antiviral therapy may alter the course of middle-ear dysfunction associated with experimental colds. ( Arch Otolaryngol Head Neck Surg. 1992;118:933-936)

• In this study, experimental otitis media was created in the chinchilla by direct middle ear challenge with Escherichia coli endotoxin, Streptococcus pneumoniae, Haemophilus influenzae , or Pseudomonas aeruginosa . The effusions recovered from the chinchillas in all four challenge groups were shown to inhibit the lymphoproliferative response of chinchilla peripheral blood lymphocytes to stimulation with phytohemagglutinin. The effect was dose dependent, and for effusions of infectious origin, the degree of inhibition was directly related to the duration of infection. Presence of the inhibitor in plasma was undocumented, suggesting a local production within the middle ear. Lymphocytes from middle ears infected with bacteria but not middle ears challenged with endotoxin were hyporesponsive or nonresponsive to stimulation with phytohemagglutinin. These results confirm the presence of an inhibitor of the lymphoproliferative response in experimental otitis media of different etiologies. ( Arch Otolaryngol Head Neck Surg . 1992;118:749-752)

• There is concern that third-generation cephalosporins may not be effective in the treatment of acute otitis media due to Streptococcus pneumoniae . Using the chinchilla animal model, we compared two third-generation cephalosporins, cefixime (Suprax) and ceftibuten (investigational), with ampicillin and saline controls in an investigatorblinded, randomized trial. Whereas the saline controls performed worse than all other groups, no significant differences were detected among the three antibiotics regarding the time required to sterilize the middle ear cleft, or the prevalence of positive cultures after 10 days of therapy. The statistical power of the comparisons of cefixime and ceftibuten with ampicillin were 98% and 67%, respectively. The results of this in vivo animal study fail to support the contention that the two third-generation cephalosporins investigated are not effective in the treatment of pneumococcal acute otitis media. Caution is advised when extrapolating these results to the general clinical setting. ( Arch Otolaryngol Head Neck Surg. 1992;118:49-52)

Importance Eustachian tube (ET) dysfunction predisposes ears to otitis media, tympanic membrane retraction, retraction pocket and perforation, or cholesteatoma. Objective 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. Design, Setting, and Participants A blinded analysis of ET mechanics in 33 adults, aged 18 to 54 years, with no middle ear disease at present but without (group 1 [n = 16]) or with (group 2 [n = 17]) history of disease, conducted at a clinical research laboratory. Interventions Videoendoscopy of the ET orifice at the nasopharynx. Main Outcomes and Measures Eustachian tube component translations and structural interactions during a swallow and the between-group differences in those variables. After topical anesthesia of the nose, a 45° telescope was introduced unilaterally and focused on the ipsilateral ET orifice. A video recording of ET component movements was made during 3 swallows. Swallow and ET opening durations and times to selected events were calculated. Images at 3 time points were analyzed by measuring the apex angle, the medial-lateral luminal width, and the medial angles between a frame-normal horizontal line through the apex and fixed points on the torus and medial and lateral luminal walls. Linear and angular variables during a swallow were expressed as change from baseline. Results Luminal opening was driven by soft palate elevation–related medial rotation of the torus and medial wall, coupled with lateral wall fixedness. The magnitude of the change from baseline for most variables was statistically greater than 0. Swallow time, palatal elevation time, time interval between maximum palatal elevation, and maximum eustachian tube opening time were not different between groups 1 and 2. Opening time was longer (mean [SD], 0.49 [0.28] vs 0.67 [0.51] seconds; P = .03) in group 2. Higher magnitude of torus rotation (mean [SD], 36.05° [12.96°] vs 27.72° [9.45°]; P = .002) with maximum soft palate elevation in group 1 resulted in greater degree of eustachian tube orifice widening (mean [SD], 0.34% [0.47%] vs −0.02% [0.49%]; P = .001) compared with the resting position in that group. Conclusions and Relevance This methodology has application in developing quantitative descriptions of ET mechanics in groups of persons without and with history or suspected ET dysfunction. A lesser degree of soft palate elevation during swallow that derives the ET medial lamina rotation and widening of the ET orifice may be associated with poor ET function and higher risk for otitis media. Videoendoscopic evaluation of the ET orifice may assist in diagnosing presence and mechanism of ET dysfunction.

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 ETF test parameters. Design, Setting, and Participants Through use of the forced-response, inflation-deflation, Valsalva, and sniffing tests, ETF was evaluated in 15 control ears of adult subjects after unilateral myringotomy (group 1) and in 23 ears of 19 adult subjects with ventilation tubes inserted for ETD (group 2). Data were analyzed using logistic regression including each parameter independently and then a step-down discriminant analysis including all ETF test parameters to predict group assignment. Factor analysis operating over all parameters was used to explore relatedness. Exposures ETF testing. Main Outcomes and Measures ETF parameters for the forced response, inflation-deflation, Valsalva, and sniffing tests measured in 15 control ears of adult subjects after unilateral myringotomy (group 1) and in 23 ears of 19 adult subjects with ventilation tubes inserted for ETD (group 2). Results The discriminant analysis identified 4 ETF test parameters (Valsalva, ET opening pressure, dilatory efficiency, and percentage of positive pressure equilibrated) that together correctly assigned ears to group 2 at a sensitivity of 95% and a specificity of 83%. Individual parameters representing the efficiency of ET opening during swallowing showed moderately accurate assignments of ears to their respective groups. Three factors captured approximately 98% of the variance among parameters: the first had negative loadings of the ETF structural parameters; the second had positive loadings of the muscle-assisted ET opening parameters; and the third had negative loadings of the muscle-assisted ET opening parameters and positive loadings of the structural parameters. Conclusions and Relevance These results show that ETF tests can correctly assign individual ears to physician-diagnosed ETD with high sensitivity and specificity and that ETF test parameters can be grouped into structural-functional categories.

IMPORTANCE: Although leukocyte telomere length is associated with mortality and many chronic diseases thought to be manifestations of age-related functional decline, it is not known whether it relates to acute disease in younger healthy populations. OBJECTIVE: To determine whether shorter telomeres in leukocytes, especially CD8CD28- T cells, are associated with decreased resistance to upper respiratory infection and clinical illness in young to midlife adults. DESIGN, SETTING, AND PARTICIPANTS: Between 2008 and 2011, telomere length was assessed in peripheral blood mononuclear cells (PBMCs) and T-cell subsets (CD4, CD8CD28+, CD8CD28-) from 152 healthy 18- to 55-year-old residents of Pittsburgh, Pennsylvania. Participants were subsequently quarantined (single rooms), administered nasal drops containing a common cold virus (rhinovirus 39), and monitored for 5 days for development of infection and clinical illness. MAIN OUTCOME MEASURES: Infection (virus shedding or 4-fold increase in virus-specific antibody titer) and clinical illness (verified infection plus objective signs of illness). RESULTS: Rates of infections and clinical illness were 69% (n = 105) and 22% (n = 33), respectively. Shorter telomeres were associated with greater odds of infection, independent of prechallenge virus-specific antibody, demographics, contraceptive use, season, and body mass index (PBMC: odds ratio [OR] per 1-SD decrease in telomere length, 1.71 [95% CI, 1.08-2.72]; n = 128 [shortest tertile 77% infected; middle, 66%; longest, 57%]; CD4: OR, 1.76 [95% CI, 1.15-2.70]; n = 146 [shortest tertile 80% infected; middle, 71%; longest, 54%]; CD8CD28+: OR, 1.93 [95% CI, 1.21-3.09], n = 132 [shortest tertile 84% infected; middle, 64%; longest, 58%]; CD8CD28-: OR, 2.02 [95% CI, 1.29-3.16]; n = 144 [shortest tertile 77% infected; middle, 75%; longest, 50%]). CD8CD28- was the only cell population in which shorter telomeres were associated with greater risk of clinical illness (OR, 1.69 [95% CI, 1.01-2.84]; n = 144 [shortest tertile, 26%; middle, 22%; longest, 13%]). The association between CD8CD28- telomere length and infection increased with age (CD8CD28- telomere length × age interaction, b = 0.09 [95% CI, 0.02-0.16], P = .01, n = 144). CONCLUSION AND RELEVANCE: In this preliminary study among a cohort of healthy 18- to 55-year-olds, shorter CD8CD28- T-cell telomere length was associated with increased risk for experimentally induced acute upper respiratory infection and clinical illness.

Objective 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. Design Longitudinal (October-March), prospective follow-up of children for coldlike illness (CLI) by diary, middle ear status by pneumatic otoscopy, and vURTI by PCR. Setting Academic medical centers. Participants A total of 102 families with at least 2 children aged between 1 and 5 years (213 children; mean [SD] age, 3.7 [1.5] years; 110 male; and 176 white) were recruited from the local communities at 2 study sites by advertisement. Main Outcome Measures New OM and CLI episodes and nasopharyngeal virus detections. Results A total of 176 children (81%) had isolated PCR detection of at least 1 virus. The OM coincidence rates were 62 of 144 (44%) for rhinovirus, 15 of 27 (56%) for respiratory syncytial virus, 8 of 11 (73%) and 1 of 5 (20%) for influenza A and B, respectively, 6 of 12 (50%) for adenovirus, 7 of 18 (39%) for coronavirus, and 4 of 11 (36%) for parainfluenza virus detections ( P = .37). For rhinovirus, new OM occurred in 50% of children with and 32% without a concurrent CLI ( P = .15), and OM risk was predicted by OM and breastfeeding histories and by daily environment outside the home. Conclusions New OM was associated with nasopharyngeal detection of all assayed viruses irrespective of the presence or absence of a concurrent CLI. Differences among viruses were noted, but statistical significance was not achieved, possibly because of the low power associated with the small number of nonrhinovirus detections.

In Reply. —Drs Edmunds, Medley, and O'Callaghan suggest that gregarious adults have more contacts with others and therefore would be exposed more often to rhinoviruses resulting in the development of protective immunity. They further argue that in our study, we only measure specific antibody to the challenge strains and that increased exposure to related strains may afford a degree of antibody protection that accounts for why those with diverse networks are less susceptible to rhinovirus-induced colds. However, our data are not consistent with their hypothesis. This is because the neutralizing test detects any antibody (virus specific or nonspecific) that binds to the virus. Even so, we agree with their concern that some aspect of specific immunity that we have not assessed (eg, IgA antibody, cytotoxic T-cell response) could be influenced by social contact across different social domains. However, this possibility is tempered by the fact that social diversity predicts the incidence of

We present a case of an inferior orbital blow-out fracture that is unusual in both the nature of the severe ocular injury and the surprising lack of findings that would suggest such an injury to a nonophthalmologist. Report of a Case. —A 22-year-old white man was struck with a fist in his right eye. He did not seek medical attention initially and when his lid swelling decreased he began to notice diplopia along with floaters and photopsia. On examination, the patient's best visual acuity was 20/30+. He was unable to either supraduct or infraduct the globe and there was numbness in the distribution of the infraorbital nerve. Results of the anterior segment examination were normal with no evidence of blunt trauma. However, the funduscopic examination revealed a 2-disc-diameter tear in the inferior retina just posterior to the equator. Beneath the tear the choroid was ruptured, with bare sclera visible (Figure).

• To explain an allergic basis for the development of otitis media with effusion (OME), it was suggested that the middle ear mucosa can act as an allergic "shock organ." To evaluate this possibility, 16 juvenile rhesus monkeys were passively sensitized to pollen by intravenous injection of allergic human serum. All ears were then challenged by insufflation of pollen via the nose and eustachian tube (ET), twice daily, for four to five days. Daily tympanometry and otomicroscopy were performed, and on the last day of challenge, tympanocentesis was done to recover effusions. Five animals were killed and the middle ears were processed for histologic study. The results showed that none of the ears developed a middle ear effusion or OME. It is concluded that middle ear challenge with an appropriate pollen antigen in passively sensitized rhesus monkeys does not initiate an inflammatory reaction in the middle ear or induce OME. (Arch Otolaryngol1985;111:502-506)

• This study measured the changes in 64 ears of 32 adult volunteers in eustachian tube function by the nine-step test, middle ear pressure by tympanometry, and nasal patency by active posterior rhinomanometry for 18 days following type 39 or Hanks rhinovirus infection. Abnormal measures were limited to the 75% of subjects (24) with clinical illness (colds) defined by symptom scores. Two days after infection, tubal function was present in only 50% of ears (48) and 20% of persons (5), middle ear underpressures of less than −50 mm H 2 O were measured in 50% of volunteers (12), and decreased nasal patency was observed in 54% of those with colds (13). These changes resolved 6 to 10 days after challenge. These results support a causal relationship between viral upper respiratory tract infection eustachian tube obstruction and abnormal middle ear pressure. ( Arch Otolaryngol Head Neck Surg. 1989;115:1054-1059)

We developed a canine animal model of subglottic stenosis following prolonged intubation with modified non-cuffed endotracheal tubes. None of the puppies intubated for seven days had an irreversible stenosing subglottic lesion, whereas all animals intubated for 14 days or more had at least a 40% to 50% reduction of the subglottic lumen secondary to maturing fibrotic stenosis. The model described is more congruent with the known and suspected pathogenesis in those infants and children who require prolonged endotracheal intubation and subsequently acquire subglottic stenosis, and can be used in evaluating the efficacy of medical therapy or surgical therapy, or both, in the prevention or management of this disease.

• The efficacy of sulbactam sodium (CP45,899-2) was investigated using the chinchilla animal model of acute otitis media with effusion (AOME). Both ears of 78 chinchillas were inoculated with β-lactamase-producing nontypable Hemophilus influenzae . Half of the animals were treated with ampicillin sodium alone (group A) and the remaining animals received ampicillin plus sulbactam (group B). On day 14, all of the ears in group B were culture-negative whereas H influenzae was recoverable in over 70% of the effusions in group A. Similarly, the course of middle ear effusion was significantly abbreviated in group B during the two-week study period. These findings suggest that sulbactam in combination with ampicillin is effective in treating AOME secondary to infection with β-lactamase–producing nontypable H influenzae in the chinchilla animal model. ( Arch Otolaryngol 1983;109:533-535)

• The effect of topical timolol maleate on exercise performance was investigated in a randomized double-blind study. Healthy young subjects underwent two graded maximal exercise evaluations on a treadmill. The evaluations were given one week apart. Before each trial, the subjects were given a single drop of either placebo or 0.5% timolol maleate in each eye. The results indicate that topical timolol has a statistically significant effect on both maximal heart rate and time to exhaustion. However, we found that the drug had no effect on the physiologic parameters of Vo 2 , respiratory rate, Vco 2 , or respiratory quotient.

In Reply .—Dr Wilson neglects to consider a most promising upper respiratory mechanism by which an IgE-mediated allergic reaction could result in otitis media with effusion (OME). This hypothesis suggests the development of eustachian tube obstruction secondary to allergic rhinitis. A number of recent studies in our laboratories have shown that provocative intranasal challenge with either allergens or histamine in allergic subjects induces a severe functional obstruction of the eustachian tube, 1-6 which has been previously shown to underly the pathogenesis of OME. 7 We propose that continued study of this phenomenon should better define the role of respiratory allergy in the pathogenesis of OME. These studies may obviate the enthusiasm with which Dr Wilson and others rush to implicate gastrointestinal tract allergy in the pathogenesis of OME.