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Research Article

Chronic Conductive Hearing Loss Is Associated With Speech Intelligibility Deficits in Patients With Normal Bone Conduction Thresholds

Okada, Masahiro1,2; Welling, D. Bradley2; Liberman, M. Charles2; Maison, Stéphane F.2

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doi: 10.1097/AUD.0000000000000787
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Abstract

INTRODUCTION

Otitis media (OM) is the most common group of inflammatory diseases of the middle ear encountered in pediatric populations, many of which result from bacterial infection (Klein 1994). Up to 75% of children will experience one or more bouts before they reach 5 years of age, making it the most common cause for physician visits and antibiotic prescriptions in pediatric outpatients (Pennie 1998). These bouts can reoccur with a cumulative incidence of 42% by 2 years of age and 60% by age 3 years of age (Kaur et al. 2017). Several studies of patients presenting with a unilateral chronic OM (COM) showed that bone conduction (BC) thresholds were significantly poorer on the affected side, suggesting that a sensorineural component had developed as well (da Costa et al. 2009; Jesic et al. 2012; Joglekar et al. 2010; Kolo et al. 2012; Luntz et al. 2013; Redaelli de Zinis et al. 2005; Yehudai et al. 2015; Yoshida et al. 2014). Others have shown long-lasting deficits in spatial hearing as well as receptive language skills that persist after the middle ear pathology has resolved (for review, see Deggouj et al. 2012).

Sensorineural damage associated with cholesteatomas in addition to conductive hearing loss (CHL) is well documented (Rosito et al. 2016). Histopathologic studies of both human and animal temporal bones suggested that penetration of bacterial toxins and inflammatory mediators into the inner ear compartment via the round window membrane can be the cause of hair cell damage and related sensorineural loss (Paparella et al. 1984; Joglekar et al. 2010; Katano et al. 2005; MacArthur et al. 2013a,2013b). Sensorineural damage is further increased when a fistula of the inner ear has been created by the erosive properties of the cholesteatoma. The use of ototoxic topical aminoglycosides is an additional potential cause of damage, and a surgical intervention can also contribute to sensorineural loss as cholesteatomas necessitate removal. The finding that some pathologies with a conductive component can lead to sensorineural damage, however, cannot explain why patients with single-sided congenital ear malformation (and therefore presenting CHL) have poorer speech recognition scores in quiet and in noise on the malformed side, despite having similar BC thresholds in the normal and the affected ear (Priwin et al. 2007; Snik et al. 1994).

Animal studies on the effects of sound deprivation have shown long-lasting impact on brain and behavior. However, most studies disrupted the middle ear during the neonatal period (e.g., Smith et al. 1983; Tucci et al. 1985,1987) and most have evaluated its effects on the higher centers of the auditory pathways rather than in the cochlea (Clarkson et al. 2016; Dahmen & King 2007; Grande et al. 2014; Harrison & Negandhi 2012; Hutson et al. 2008; Kandler & Gillespie 2005; Wang et al. 2011; Zhuang et al. 2017). Recently, we showed in mice that a chronic (1-year duration) CHL from eardrum resection in the mature animal led to a reduction in cochlear efferent innervation and a loss of up to 30% of the afferent synapses between the cochlear nerve and the sensory cells (Liberman et al. 2015). This surprising finding revealed signs of plasticity of cochlear innervation in the fully developed ear. This type of subtotal cochlear synaptopathy will not elevate behavioral or electrophysiologic thresholds until it becomes extreme (Lobarinas et al. 2013; Woellner & Schuknecht 1955) because the most vulnerable cochlear neurons in other forms of cochlear synaptopathy tend to be those with high thresholds and low spontaneous rates (Furman et al. 2013; Schmiedt et al. 1996). However, it should degrade the signal-coding abilities of the auditory nerve and might impair performance on more complex tasks such as speech recognition.

The present study aims to determine whether patients with chronic reduction in sound transmission through the middle ear show increased difficulty with word recognition (WR) tasks as predicted by the synaptopathic effects of chronic CHL in animal models.

MATERIALS AND METHODS

We collected audiologic data from patients seen at the Massachusetts Eye & Ear Infirmary between 1993 and 2017 for otologic evaluation. To be included, patient must have presented with normal (≤25 dB HL) and symmetrical BC thresholds bilaterally (interaural difference ≤10 dB from 250 to 4 kHz) and a unilateral CHL at the first visit. A CHL was defined as ≥15 dB difference between the mean pure-tone average (PTA) for air conduction (AC) and BC thresholds (air-bone gap). The CHL was defined as chronic when the air-bone gap remained ≥15 dB between the first and the last visit. It was defined as acute when the air-bone gap was <15 dB at the second visit and remained so on follow-up appointments. Records spanning <2 years and patients with fewer than three hearing evaluations were excluded. Patients <10 years of age were not considered because hearing assessment differs in the pediatric setting. Further characteristics of patient’s profile including age, observation spans, and visit intervals are described in Figure 1. With the exception of 1 patient, who was excluded, none of the study population wore traditional or bone-anchored hearing aids. This research study was reviewed and approved by the Institutional Review Board of the Massachusetts Eye & Ear.

Fig. 1.
Fig. 1.:
Ages, observation spans, and visit intervals for subjects in the five groups. Means (± SEMs) are shown for each parameter. AC indicates air conduction; AOM, acute otitis media; Chole., cholesteatoma; COM, chronic otitis media; Cong., congenital malformations of the external/middle ear; OME, otitis media with effusion; SEM, standard error of the mean.

Audiometric thresholds were obtained using a number of different audiometers including Grason-Stadler (GS-10, GS-16), Interacoustics AC-30, Virtual 320, and Interacoustics Equinox, running under the same Harvard Audiometer Operating System (AOS; Thornton et al. 1994). Pure-tone AC thresholds were measured at standard audiometric frequencies from 0.25 to 8 kHz, in octave steps using TDH39 headphones or ER-3A insert earphones. BC thresholds were acquired from 250 to 4000 Hz with a Radioear B-71 vibrator over the mastoid. The PTA was defined as the average threshold at 500, 1000, and 2000 Hz. Hearing loss configurations were divided into 3 groups: (1) upward sloping when mean AC thresholds at 250 and 500 Hz were 10 dB worse than mean thresholds at 4 and 8 kHz; (2) downward sloping for patients with mean AC thresholds at 250 and 500 Hz 10 dB better than mean thresholds at 4 and 8 kHz; and (3) flat for all other hearing loss profiles.

Speech recognition performance was assessed using a recorded Central Institute for the Deaf W-22 phonetically balanced test, consisting of 50 consonant-vowel nucleus-consonant word lists presented with a contralateral speech-shaped noise. The Articulation Index was used to predict the performance/intensity function for speech (Pavlovic et al. 1986; Wilde & Humes 1990) based on the audiogram, using a transfer function for Central Institute for the Deaf W-22 (ANSI 1997; Sherbecoe & Studebaker 1990). This procedure was automatically generated by the Harvard AOS software as described in Halpin et al. (1994). The level at which maximal intelligibility was predicted was chosen as presentation level. If this value, however, fell below 70 dB HL, presentation level remained at 70 dB HL. All WR scores were obtained from native speakers of English. The scores reported here are those at the time of the initial visit, for patients with acute CHL, and at the time of the final visit for patients with chronic conditions.

All statistical analyses were performed under the JMP statistical data analysis software (SAS Institute Inc., Cary, NC). The threshold for statistical significance was p = 0.05. Equivalent testing using the “two-one-sided t-tests” procedure was considered to examine whether interaural changes in threshold differed among groups. The nonparametric Steel-Dwass test was used to perform multiple group comparisons. A two-way analysis of variance (ANOVA) followed by a Mann-Whitney U test were performed to compare WR scores across groups. Finally, the relationship between AC and BC thresholds as a function of WR score was tested using a Spearman rank correlation coefficient method.

RESULTS

Out of 240 cases meeting our inclusion criteria, 169 cases were chronic conditions with one of three etiologies: 15 with atresia and/or a congenital middle ear malformation, 71 with COM, and 83 with cholesteatoma. An additional 71 cases were acute conditions: 20 with acute OM (AOM) and 51 with OM with effusion (OME). Figure 2 shows the mean AC and BC thresholds of each cohort on the side of the conductive impairment. Note that whatever small intergroup differences there are, the mean BC thresholds are slightly worse in the acute groups than in the chronic groups, especially at 4 kHz where the difference was statistically significant (ANOVA: F = 2.15; p = 0.04).

Fig. 2.
Fig. 2.:
Mean hearing sensitivity in the affected ear for each cohort. Mean AC and BC thresholds on the CHL side of each cohort, color-coded according to etiologies: three chronic types of CHL (Cong., COM, and Chole.) and two acute types of CHL group (AOM and OME). Error bars are for SEMs. AC indicates air conduction; AOM, acute otitis media; BC, bone conduction; CHL, conductive hearing loss; Chole., cholesteatoma; COM, chronic otitis media; Cong., congenital malformations of the external/middle ear; OME, otitis media with effusion; SEM, standard error of the mean.

Whereas all patients presented with a mild to moderately severe CHL in one ear, in the contralateral ear, there was no significant air-bone gap, and PTAs for AC and BC thresholds were within normal limits (Fig. 3). Patients were separated into two PTA groups, as color coded in Figure 3: mild CHL when AC threshold was ≤40 dB HL and moderate to moderately severe CHL for AC thresholds were between 40 and 70 dB HL.

Fig. 3.
Fig. 3.:
Individual PTAs, by AC and BC, for the affected sides vs. contralateral ears. Box and whiskers plots of AC and BC threshold PTAs (500, 1000, and 200 Hz) for each subject from each group. As defined in key, two degrees of hearing loss were considered for the CHL ears: this color coding convention will be carried forward in the remaining figures. AC indicates air conduction; AOM, acute otitis media; BC, bone conduction; CHL, conductive hearing loss; Chole., cholesteatoma; COM, chronic otitis media; Cong., congenital malformations of the external/middle ear; Contra., contralateral; OME, otitis media with effusion; PTA, pure-tone average.

To quantify interaural differences in BC thresholds over the observation period (Fig. 1) and track signs of progressive hair cell damage on the CHL side, changes in BC thresholds as a function of time were calculated for each chronic condition group in each ear (Fig. 4). There were no statistically significant differences in the rate of threshold deterioration (dB/year) between the CHL ear and the contralateral ear in either PTA group, as examined with an equivalence testing approach using the two-one-sided t-tests procedure (congenital, p = 0.53; COM, p = 0.37; cholesteatoma, p = 0.59; Fig. 3).

Fig. 4.
Fig. 4.:
Change in BC thresholds over the observation span. Rate of PTA shift in each ear was computed over the entire observation period from first to last visit. As shown in the key, an ensemble average was computed for each group (black circles) as well as separate averages for each PTA group on the affected sides. Error bars are for SEMs. AC indicates air conduction; BC, bone conduction; Chole., cholesteatoma; COM, chronic otitis media; Cong., congenital malformations of the external/middle ear; Contra., contralateral; PTA, pure-tone average; SEM, standard error of the mean.

However, as shown in Figure 5, WR scores were significantly poorer on the CHL side, when the PTA was >40 dB HL and when the condition was chronic, whether assessed by ANOVA (congenital: F = 4.70, p = 0.01; COM: F = 13.91, p < 0.001; cholesteatoma: F = 6.21, p < 0.001; AOM: F = 0.54, p > 0.05; OME: F = 6.86, p = 0.01) or by a post hoc Steel-Dwass test for multiple comparisons (congenital: AC ≤ 40, Z = 1.57, p > 0.05/AC > 40, Z = 3.03, p = 0.04; COM: AC ≤ 40, Z = 0.16, p > 0.05/AC > 40, Z = 3.64, p = 0.04; cholesteatoma: AC ≤ 40, Z = 1.31, p > 0.05/AC > 40, Z = 3.72, p = 0.04). Another statistical approach was to use a two-way ANOVA to show that duration (acute versus chronic) and degree of hearing loss had significant effects on the difference in WR scores between the affected and the unaffected ear (acute versus chronic: F = 49.7, p < 0.001; degree of hearing loss: F = 16.7, p < 0.001), with no interaction between diagnosis and degree (p = 0.48). Finally, post hoc analysis showed a statistically significant effect of the degree of hearing loss in chronic conditions (p < 0.001), but not in acute conditions (p = 0.68). Similarly, we found no statistically significant difference between chronic and acute conditions in patients with mild hearing loss (p = 0.99), while these differences became significant in patients with a moderate to moder ately severe loss (p = 0.03). Finally, there was no statistically significant effect of sex in any of the chronic groups (Table 1).

TABLE 1.
TABLE 1.:
Demographic and audiometric characteristics of chronic CHL groups
Fig. 5.
Fig. 5.:
WR scores as a function of CHL and etiology. For all conditions, WR scores were averaged, and error bars are for SEMs. Statistical significance of the post hoc analysis (Steel-Dwass test for multiple comparisons) is indicated (*p < 0.05). AC indicates air conduction; AOM, acute otitis media; CHL, conductive hearing loss; Chole., cholesteatoma; COM, chronic otitis media; Cong., congenital malformations of the external/middle ear; Contra., contralateral; OME, otitis media with effusion; SEM, standard error of the mean; WR, word recognition.

The results suggest that both degree and duration of hearing loss are relevant to the decrement in WR score. This relationship is further supported by (1) the statistically significant correlations obtained between WR score and AC-PTA thresholds in chronic conditions, as shown in Figure 6D–E (congenital: ρ = −0.59, p = 0.02; COM-cholesteatoma: ρ = −0.24, p = 0.001) and (2) by the absence of correlation between BC-PTA thresholds and word scores (Fig. 6A–C) in the same group of patients (congenital: ρ = −0.12, p = 0.66; COM-cholesteatoma: ρ = 0.03, p = 0.81; AOM-OME: ρ = −0.24, p = 0.09). Thus, inner ear threshold sensitivity, as measured with BC, is not significantly associated with WR score in these patients. Note that a higher Spearman rank correlation coefficient was seen for the congenital group compared with groups that included patients who experienced repeated middle ear infections and/or cholesteatoma.

Fig. 6.
Fig. 6.:
Predictability of WR scores as a function of degree of CHL and etiology. No statistically significant relationship was found between BC thresholds and WR score in any cohort (A–C). However, significant correlations were observed in the affected ear between AC PTAs and WR scores for all chronic CHL groups [congenital malformations of the external/middle ear (D), COM and Chole. (E)]. The same relationship did not reach statistical significance in CHL (F). The linear regression is shown when the coefficient correlation was significant. For all conditions, scores were obtained at the last visit. Statistical significance is indicated: *p < 0.05; ***p < 0.001. AC indicates air conduction; AOM, acute otitis media; BC, bone conduction; CHL, conductive hearing loss; Chole., cholesteatoma; COM, chronic otitis media; OME, otitis media with effusion; PTA, pure-tone average; WR, word recognition.

DISCUSSION

This study shows that patients with chronic conditions associated with at least a moderate unilateral CHL have poorer word recognition scores (WRS) on the affected side compared with the unaffected side, even if BC thresholds remain symmetrical and within normal limits bilaterally.

A number of methodologic limitations intrinsic to retrospective studies need to be acknowledged. First, as a result of our inclusion criteria, cohorts with acute CHL were significantly older than patients with chronic conditions (Fig. 1). Indeed, audiometric data were collected from patients with AOM who did not repeat the condition, excluding therefore younger patients who tend to repeat ear infections (Tos 1984; Williamson et al. 1994). Similarly, we excluded patients with poor BC thresholds (>25 dB HL). Given that BC thresholds decline with age, patients with COM and/or a cholesteatoma were relatively younger. Poorer WRS were observed in chronic CHL cohorts; thus, age is unlikely to be a significant factor detrimental to WRS in this study population.

A second limitation lies with how WR performance was assessed: speech material was delivered at a single presentation level, obtained from an estimate of the speech intelligibility index curve (see Methods). It is possible that the level at which maximum performance was predicted by this procedure was not optimal. However, this is unlikely, as the predicted presentation level would have to be off by >14 dB to produce WRS as poor as those observed in the chronic condition groups, as determined using the Harvard AOS software.

It is also possible that hearing loss configuration could alter speech perception performance by filtering out energy from the speech signal. While a majority of these chronic CHL produced “flat” audiograms as defined in Methods (74 out of 169), 41 patients presented with an upward-sloping and 54 presented with a downward-sloping configuration (Fig. 7). Although the speech material was not spectrally adjusted to compensate for audiometric losses, we found no evidence that hearing loss configuration had a significant impact on WR scores (ANOVA: congenital: F = 0.63, p = 0.48; COM: F = 0.53, p = 0.65; cholesteatoma: F = 2.47, p = 0.10).

Fig. 7.
Fig. 7.:
Effect of hearing loss configuration on WR scores in patients presenting a chronic CHL. No statistically significant difference in WR scores was found from patient presenting a chronic CHL with different hearing loss configurations. CHL indicates conductive hearing loss; Chole., cholesteatoma; COM, chronic otitis media; WR, word recognition.

It is worth noting as well that a great majority of the chronic-CHL cohort had cholesteatoma or COM, both of which can cause inner ear damage, as documented in many investigations. Histopathologic studies point at the cochlear basal turn as a target for middle ear infections (Cook et al. 1999; Cureoglu et al. 2004; Paparella et al. 1972), and children with a history of OM have poorer extended high-frequency thresholds compared with controls (Hunter et al. 1996; Margolis et al. 2000). The byproducts of bacterial infections and inflammatory mediators can alter gene expression in the inner ear (Ghaheri et al. 2007; MacArthur et al. 2013a), including those for ion channels and transporters in the stria vascularis and spiral ligament (MacArthur et al. 2013b). Such alterations could result in sensorineural hearing loss. However, here, we excluded patients with elevated BC thresholds (>25 dB HL) to minimize the contributions of hair cell damage, strial damage, or other non-neural cells in the cochlear duct to any observed degradation in speech-recognition performance on the affected side. It is possible that inflammatory byproducts of infection reach the inner ear and cause damage that is not captured by BC thresholds. Nevertheless, the WR score obtained in all group of patients with chronic etiologies and moderate to moderately severe hearing losses were significantly lower than that predicted from the speech intelligibility curve (>98%), and no significant correlation was observed between BC thresholds and WR score (Fig. 6A–C). Thus, even if there is damage to the most basal regions of the cochlea, it should not affect speech recognition scores to the extent observed here, when words are presented at comfortable levels to patients with bilaterally normal BC thresholds. In addition, as shown in Figure 2, acute cohorts (with the worse WR scores) actually had slightly poorer BC thresholds at 4 kHz compared with chronic cohorts. Therefore, a different mechanism likely underlies the decrement in WR score.

Evidence for a noninflammatory etiology is provided by patients with congenital malformations (e.g., atretic canal). These patients showed the strongest correlation between AC thresholds and WR score (Fig. 6). This result is consistent with the idea that a reduced acoustic drive to the inner ear is the root cause of the impairment in speech-recognition performance. Such CHL is a common form of auditory deprivation that has long-lasting deleterious effects on hearing when occurring during critical periods of development (for review, see Whitton & Polley 2011). Unilateral CHLs also alter interaural time and level differences of acoustic signals arriving at the two ears (Hall & Derlacki 1988; Thornton et al. 2012), and therefore affect spatial hearing, particularly in the horizontal plane. The resulting degraded afferent signals when carried to brain areas during critical periods of development will impact the formation of neural circuits that mediate perception, as evidenced at the cellular level by significantly reduced cell-body diameter and dendritic arborization in regions of the cochlear nucleus and superior olivary complex (Webster & Webster 1977,1979; Conlee et al. 1984,1986). CHL has also been found to disrupt temporal response properties of auditory cortical neurons in animal studies (e.g., Polley et al. 2013; Teichert & Bolz 2017) and, more recently, in increased neural response amplitudes in humans with a chronic unilateral CHL (Parry et al. 2019). Furthermore, several studies report that sound deprivation can alter the normal development of the central auditory system even after hearing thresholds return to normal by disrupting binaural integration, by impoverishing hearing in noise (Knudsen et al. 1984,Popescu & Polley 2010; Gay et al. 2014) and by disrupting normal binaural balance between the representation of sounds delivered to each ear (Clopton & Silverman 1977; Silverman & Clopton 1977,Moore & Irvine 1981; Popescu & Polley 2010). However, normal-hearing thresholds do not guarantee an absence of peripheral damage, and none of these studies looking at central effects of sound deprivation provided evidence of peripheral integrity at the neuronal level. Therefore, a peripheral involvement in the persistent perceptual impairments associated with chronic CHL in any of these prior studies cannot be ruled out.

In prior animal work, our group showed that prolonged unilateral CHL, due to resection of the eardrum, caused up to 30% loss of synapses between cochlear nerve fibers and their peripheral targets, the inner hair cells (Liberman et al. 2015). This type of cochlear synaptopathy could cause hearing impairments, especially in noisy environments (Liberman 2017) because the most vulnerable cochlear neurons to both noise and aging are those with high thresholds and low spontaneous rates (Furman et al. 2013; Schmiedt et al. 1996). These high-threshold fibers are key contributors to the coding of transient stimuli in noisy environments (Costalupes et al. 1984) despite the fact that their loss remained undetected because neural degeneration per se does not elevate behavioral or electrophysiologic thresholds until it becomes extreme (Lobarinas et al. 2013; Woellner & Schuknecht 1955). Because WR score in this study was obtained in quiet, the impairment experienced by these patients may be underestimated.

As discussed earlier, a number of studies have documented changes in central auditory nuclei as a result of a chronic conductive impairment. Of particular interest are the changes in the superior olivary complex in animal models of neonatal CHL, where a significant abnormalities have been observed in rats (Myers et al. 2012), gerbils (Tucci et al. 2001), and guinea pigs (Potashner et al. 1997). For example, levels of oxidative enzymes, thought to reflect overall electrical activity (Wong-Riley et al. 1981), changed significantly within the lateral superior olive of adult gerbils as a result of unilateral malleus removal or cochlear ablation (Tucci et al. 2002). Given the importance of the lateral superior olive as the origin of olivocochlear feedback to the cochlea, these central changes may also lead to changes at the periphery. Our prior animal study of CHL also showed a reduction in the density of cochlear efferent fibers originating in the lateral superior olive and projecting to the dendrites of cochlear nerve fibers in the inner hair cell area (Liberman et al. 2015). The further observation that cochlear de-efferentation, per se, by surgical interruption of the fiber bundle, also leads to cochlear synaptopathy (Liberman et al. 2014), suggests that the cochlear neurodegeneration associated with CHL may be mediated by changes in the efferent feedback pathways to the inner ear. Together, these results from animal studies suggest that cochlear synaptopathy may be a contributing factor to the reduced WR scores observed in our cohort of human subjects with chronic CHL of a moderate to moderately severe degree.

This study also supports the idea that amplification should be considered in the management of unilateral CHL: if hearing cannot be medically improved, patients may benefit from either conventional amplification or from an osseointegrated device. In absence of amplification, our data suggest that speech recognition, particularly in adverse environments, may worsen on the side of the pathology, possibly also including deficits in sound localization. This speculation is further supported by a study of patients with bilateral symmetric CHL who received monaural versus binaural amplification: speech recognition in unaided ears was poorer than that in aided ears (Dieroff 1993). Lack of treatment for unilateral or asymmetric hearing loss can be based on the belief that the contralateral ear can compensate for the loss. Yet, children with asymmetric hearing loss have higher rates of academic, social, and behavioral difficulties (Lieu et al. 2012; Wie et al. 2010). Given that cochlear synaptopathy appears to be irreversible, peripheral deficits related to cochlear neural degeneration should be considered as well, when patients report lingering deficits in auditory processing after persistent middle ear issues are resolved.

ACKNOWLEDGMENTS

The authors are grateful to William Goedicke and Dr. Barbara Herrmann for their technical help and logistic support.

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Keywords:

Conductive hearing loss; Cochlear synaptopathy; Hidden hearing loss; Word recognition; Middle ear; Otitis media; Sound deprivation; Auditory processing disorder; Amplification

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