Asymmetry of Occupational Noise Induced Hearing Loss: An Electrophysiological Approach

Abstract Introduction The question as to whether occupational noise exposure causes symmetrical or asymmetrical hearing loss is still controversial and incompletely understood. Objective Two electrophysiological methods (cortical evoked response audiometry: CERA and auditory steady state responses: ASSR) were used to address this issue. Method 156 subjects with a well-documented history of noise exposure, a wide range of noise induced hearing loss (NIHL) and without middle ear pathology underwent both a CERA and an ASSR examination in the context of an exhaustive medicolegal expert assessment intended for possible compensation. Results Whatever the method (CERA or ASSR), the average electrophysiological hearing thresholds (1-2-3 kHz) are significantly worse in the left ear. The right - left differences in CERA and ASSR thresholds are strongly correlated with each other. No significant effect of frequency is found. No correlation is observed between right - left differences in hearing thresholds and either age or degree of hearing loss. Conclusion In NIHL, there is an actual average right - left difference of about 2.23 dB, i.e., 3.2%, the left ear being more impaired.

Asymmetry of Occupational Noise Induced Hearing Loss: An Electrophysiological Approach.

Introduction The question as to whether occupational noise exposure causes symmetrical or asymmetrical hearing loss is still controversial and incompletely understood. Objective Two electrophysiological methods (cortical evoked response audiometry: CERA and auditory steady state responses: ASSR) were used to address this issue. Method 156 subjects with a well-documented history of noise exposure, a wide range of noise induced hearing loss (NIHL) and without middle ear pathology underwent both a CERA and an ASSR examination in the context of an exhaustive medicolegal expert assessment intended for possible compensation. Results Whatever the method (CERA or ASSR), the average electrophysiological hearing thresholds (1-2-3 kHz) are significantly worse in the left ear. The right - left differences in CERA and ASSR thresholds are strongly correlated with each other. No significant effect of frequency is found. No correlation is observed between right - left differences in hearing thresholds and either age or degree of hearing loss. Conclusion In NIHL, there is an actual average right - left difference of about 2.23 dB, i.e., 3.2%, the left ear being more impaired.

Beneficial Effects of Zoledronic Acid on Tendons of the Osteogenesis Imperfecta Mouse (Oim).

Osteogenesis imperfecta (OI) is a genetic disorder of connective tissue characterized by spontaneous fractures, bone deformities, impaired growth and posture, as well as extra-skeletal manifestations. Recent studies have underlined an impairment of the osteotendinous complex in mice models of OI. The first objective of the present work was to further investigate the properties of tendons in the osteogenesis imperfecta mouse (oim), a model characterized by a mutation in the COL1A2 gene. The second objective was to identify the possible beneficial effects of zoledronic acid on tendons. Oim received a single intravenous injection of zoledronic acid (ZA group) at 5 weeks and were euthanized at 14 weeks. Their tendons were compared with those of untreated oim (oim group) and control mice (WT group) by histology, mechanical tests, western blotting and Raman spectroscopy. The ulnar epiphysis had a significantly lower relative bone surface (BV/TV) in oim than WT mice. The tendon of the triceps brachii was also significantly less birefringent and displayed numerous chondrocytes aligned along the fibers. ZA mice showed an increase in BV/TV of the ulnar epiphysis and in tendon birefringence. The tendon of the flexor digitorum longus was significantly less viscous in oim than WT mice; in ZA-treated mice, there was an improvement of viscoelastic properties, especially in the toe region of stress-strain curve, which corresponds to collagen crimp. The tendons of both oim and ZA groups did not show any significant change in the expression of decorin or tenomodulin. Finally, Raman spectroscopy highlighted differences in material properties between ZA and WT tendons. There was also a significant increase in the rate of hydroxyproline in the tendons of ZA mice compared with oim ones. This study highlighted changes in matrix organization and an alteration of mechanical properties in oim tendons; zoledronic acid treatment had beneficial effects on these parameters. In the future, it will be interesting to better understand the underlying mechanisms which are possibly linked to a greater solicitation of the musculoskeletal system.

Vocal Fold Collision Speed in vivo: The Effect of Loudness.

Mechanical impact stress on the vocal fold surface, particularly when excessive, has been postulated to cause the so-called phonotraumatic tissue lesions, such as nodules and polyps. The collision stress between the vocal folds depends on the vocal fold velocity at the time of impact. Hence this vocal fold collision speed is a relevant parameter when considering biomechanical economy of phonation, especially in voice professionals needing a louder voice than normal. Combining a precise photometric measurement of glottal area and simultaneous measurements of translaryngeal impedance (electroglottogram) for identifying the time of the maximum rate of increase of vocal fold contact allows computing the vocal fold collision speed in a wide range of loudnesses. The vocal fold collision speed is - for modal voicing - always smaller than the maximum vocal fold velocity during the closing phase, but it strongly increases with intensity. Moreover, this increase shows a biphasic pattern, with a significant enhancement from a certain value of dB on. Understanding physiological variables that influence vocal fold collision forces provides relevant insight into the pathophysiology and the prevention of voice disorders associated with phonotraumatic vocal hyperfunction.

Intraglottal Aerodynamics at Vocal Fold Vibration Onset.

The most frequently observed type of voice onset in spontaneous speech in normal subjects is the soft onset, and it may be considered as the "physiological" onset. It starts from an immobile narrow glottal slit crossed by a continuous airflow, and then a few oscillations (even a single one in some cases) precede the first glottal closure. It is a transient event, during which the acting forces, lung pressure, intraglottal pressure, myoelastic tension of the vocal fold (VF) oscillator and inertance of the supraglottal vocal tract, interact to progressively reach the steady state of a sustained oscillation. Combined measurements of flow, area, and pressure provide a detailed qualitative and quantitative analysis of the intraglottal mechanical events at the precise moment of starting oscillation in a physiological (soft or soft/breathy) onset. Our in vivo measurements of airflow and glottal area show that the very first oscillation occurs exactly at the time when turbulence appears at the level of the glottal narrowing, ie, when the Reynolds number reaches its critical value. The turbulence may be assumed to trigger an oscillator consisting in the ensemble of the VFs and the air of the vocal tract, which is known to be weakly damped. Turbulence can act here as an aspecific flick, triggering the oscillator, the frequency of oscillation being determined by its mechanical properties. Furthermore, the first noticeable glottal oscillations are sinusoidal: the VFs are neither steeply sucked together by a negative Bernoulli pressure, nor burst apart by the lung pressure. Our measurements show that, at the critical time, the rising positive lung pressure is balanced by the rising negative Bernoulli pressure generated by the transglottal flow.

In Vivo Quantification of the Intraglottal Pressure: Modal Phonation and Voice Onset.

Intraglottal pressure is the driving force of vocal fold vibration. Its time course during the open phase of the vibratory cycle is essential in the mechanics of phonation, but measuring it directly is difficult and may hinder spontaneous voicing. However, it can be computed from the in vivo measured transglottal flow and glottal area (hence the air particle velocity) on the basis of the Bernoulli energy law and the interaction with the inertance of the vocal tract. As to sustained modal phonation, calculations are presented for the two possible shapes of glottal duct: convergent and divergent, including absolute calibration in order to obtain quantitative physical values. Whatever the glottal duct configuration, the calculations based on measured values of glottal area and air flow show that the integrated intraglottal pressure during the opening phase systematically exceeds that during the closing phase, which is the basic condition for sustaining vocal fold oscillation. The key point is that the airflow curve is skewed to the right relative to the glottal area curve. The skewing results from air compressibility and vocal tract inertance. The intraglottal pressure becomes negative during the closing phase. As to the soft (or physiological) voice onset, a similar approach shows that the integrated pressure differences (opening phase - closing phase) actually increase as the onset progresses, and this applies to the results based on Bernoulli's energy law as well as to those based on the interaction with the inertance of the vocal tract. Furthermore and similarly, the phase lead of the pressure wave with respect to the glottal opening progressively increases. The underlying explanation lies in the progressively increasing skewing of the airflow curve to the right with respect to the glottal area curve.

Dynamics of the Driving Force During the Normal Vocal Fold Vibration Cycle.

Intraglottal pressure is the driving force of vocal fold vibration. Theoretically, simultaneous quantification of glottal area and transglottal airflow allows the calculation of the intraglottal pressure waveform during a single vibration cycle. In this study, we show that, by combining photoglottography (transglottal light transmission) and airflow (Rothenberg mask) measurements during sustained vocal emissions in vivo, the intraglottal pressure wave can be approximated in a way similar to what has been done in models. The results confirm in vivo that the intraglottal pressure is systematically larger during the opening phase than during the closing phase, so that over one whole cycle, the driving force performs net positive work, accounting for sustained vocal fold motion. A component of this driving force asymmetry is related to vocal tract inertance, which also accounts for the skewing of the airflow waveform compared with the area waveform. Furthermore, the intraglottal pressure ratio (opening:closing) increases with voicing intensity, reaches a maximum around 76 dB, and significantly decreases at higher intensities. This rise and fall suggests that there is a range of intensity values in which, mechanically, a maximum of the driving force is imparted to the vocal fold mass. This finding could have implications for voice economy in professional speakers.

Maximal Ambient Noise Levels and Type of Voice Material Required for Valid Use of Smartphones in Clinical Voice Research.

PURPOSE: Smartphone technology provides new opportunities for recording standardized voice samples of patients and transmitting the audio files to the voice laboratory. This drastically improves the achievement of baseline designs, used in research on efficiency of voice treatments. However, the basic requirement is the suitability of smartphones for recording and digitizing pathologic voices (mainly characterized by period perturbations and noise) without significant distortion. In a previous article, this was tested using realistic synthesized deviant voice samples (/a:/) with three precisely known levels of jitter and of noise in all combinations. High correlations were found between jitter and noise to harmonics ratio measured in (1) recordings via smartphones, (2) direct microphone recordings, and (3) sound files generated by the synthesizer. In the present work, similar experiments were performed (1) in the presence of increasing levels of ambient noise and (2) using synthetic deviant voice samples (/a:/) as well as synthetic voice material simulating a deviant short voiced utterance (/aiuaiuaiu/). RESULTS: Ambient noise levels up to 50 dBA are acceptable. However, signal processing occurs in some smartphones, and this significantly affects estimates of jitter and noise to harmonics ratio when formant changes are introduced in analogy with running speech. The conclusion is that voice material must provisionally be limited to a sustained /a/.

Physiology and Acoustics of Inspiratory Phonation.

INTRODUCTION: Inspiratory phonation (IP) means phonating with inspiratory airflow. Some vocalists remarkably master this technique, to such an extent that it offers new dramatic, aesthetic, and functional possibilities in singing specific contemporary music. The present study aims to a better understanding of the physiological backgrounds of IP. MATERIAL AND METHODS: A total of 51 inhaling utterances were compared with 61 exhaling utterances in a professional soprano highly skilled in inhaling singing, by means of high-speed single-line scanning and advanced acoustic analysis. Ranges of intensity and Fo were kept similar. RESULTS: The main differences are: (1) an inversion of the mucosal wave, (2) a smaller closed quotient in IP, (3) a larger opening/closing quotient in IP with the additional difference that in IP, the quotient is larger than 1 (opening slower than closing), whereas it is less than 1 in expiratory mode (opening faster than closing), (4) a larger vocal-fold excursion in IP, (5) higher values of adaptive normalized noise energy in IP, and (6) a steeper slope of harmonic peaks in IP. However, jitter values are similar (within normal range), as well as damping ratios and central formant frequencies. The two voicing modes cannot be differentiated by blind listening. CONCLUSION: The basic physiological mechanisms are comparable in both voicing modes, although with specific differences. IP is actually to be considered as an "extended vocal technique," a term applied to vocalization in art music, which falls outside of traditional classical singing styles, but with remarkable possibilities in skilled vocalists.

Automated tracking of quantitative parameters from single line scanning of vocal folds: a case study of the 'messa di voce' exercise.

This article presents a novel application of the 'single line scanning' of the vocal fold vibrations (kymography) in singing pedagogy, particularly in a specific technical voice exercise: the 'messa di voce'. It aims at giving the singer relevant and valid short-term feedback. A user-friendly automatic analysis program makes possible a precise, immediate quantification of the essential physiological parameters characterizing the changes in glottal impedance, concomitant with the progressive increase and decrease of the lung pressure. The data provided by the program show a strong correlation with the hand-made measurements. Additional measurements such as subglottic pressure and flow glottography by inverse filtering can be meaningfully correlated with the data obtained from the kymographic images.

Immunomodulatory activity of vardenafil on induced lung inflammation in cystic fibrosis mice.

BACKGROUND: We tested the hypothesis that vardenafil, a common drug used for improving erectile dysfunction and able to partially normalize transepithelial chloride transport in cystic fibrosis (CF), modulates CF lung inflammation. METHODS: Inflammatory markers in lungs of F508del-CF and wild-type mice were monitored in response to lipopolysaccharide from Pseudomonas aeruginosa (LPS). The effect of pretreatment with vardenafil (0.14 mg/kg) was evaluated. RESULTS: A latent inflammatory status, characterized by neutrophil infiltrate, mouse macrophage inflammatory protein (MIP)-2 and tumor necrosis factor (TNF)-α, was found in baseline conditions in F508del-CF mice. Inflammatory markers were increased after LPS with higher responses in CF. Vardenafil globally attenuated inflammatory responses in both genotypes however reduction of macrophage infiltration, macrophage chemoattractant chemokine and interleukin-1ß was observed in the CF group only. CONCLUSION: Vardenafil reduces lung inflammation with a more pronounced effect in F508del-CF mice, particularly on macrophage cell markers.

Role of TRPC1 channel in skeletal muscle function.

Skeletal muscle contraction is reputed not to depend on extracellular Ca2+. Indeed, stricto sensu, excitation-contraction coupling does not necessitate entry of Ca2+. However, we previously observed that, during sustained activity (repeated contractions), entry of Ca2+ is needed to maintain force production. In the present study, we evaluated the possible involvement of the canonical transient receptor potential (TRPC)1 ion channel in this entry of Ca2+ and investigated its possible role in muscle function. Patch-clamp experiments reveal the presence of a small-conductance channel (13 pS) that is completely lost in adult fibers from TRPC1(-/-) mice. The influx of Ca2+ through TRPC1 channels represents a minor part of the entry of Ca(2+) into muscle fibers at rest, and the activity of the channel is not store dependent. The lack of TRPC1 does not affect intracellular Ca2+ concentration ([Ca2+](i)) transients reached during a single isometric contraction. However, the involvement of TRPC1-related Ca2+ entry is clearly emphasized in muscle fatigue. Indeed, muscles from TRPC1(-/-) mice stimulated repeatedly progressively display lower [Ca2+](i) transients than those observed in TRPC1(+/+) fibers, and they also present an accentuated progressive loss of force. Interestingly, muscles from TRPC1(-/-) mice display a smaller fiber cross-sectional area, generate less force per cross-sectional area, and contain less myofibrillar proteins than their controls. They do not present other signs of myopathy. In agreement with in vitro experiments, TRPC1(-/-) mice present an important decrease of endurance of physical activity. We conclude that TRPC1 ion channels modulate the entry of Ca(2+) during repeated contractions and help muscles to maintain their force during sustained repeated contractions.

Increased tissue arachidonic acid and reduced linoleic acid in a mouse model of cystic fibrosis are reversed by supplemental glycerophospholipids enriched in docosahexaenoic acid.

An imbalance in (n-6)/(n-3) PUFA has been reported in cystic fibrosis (CF) patients. Glycerophospholipids enriched in docosahexaenoic acid (GPL-DHA) have been shown to regulate the (n-6)/(n-3) fatty acid ratio in the elderly. Here, we tested the effect of GPL-DHA supplementation on PUFA status in F508del homozygous CF mice. GPL-DHA liposomes were administrated by gavage (60 mg DHA/kg daily, i.e. at maximum 1.4 mg DHA/d) to 1.5-mo-old CF mice (CF+DHA) and their corresponding wild-type (WT) homozygous littermates (WT+DHA) for 6 wk. The PUFA status of different tissues was determined by GC and compared with control groups (CF and WT). There was an alteration in the (n-6) PUFA pathway in several CF-target organs in CF compared with WT mice, as evidenced by a higher level of arachidonic acid (AA) in membrane phospholipids or whole tissue (21 and 39% in duodenum-jejunum, 32 and 38% in ileum, and 19 and 43% in pancreas). Elevated AA levels were associated with lower linoleic acid (LA) and higher dihomo-gamma-linolenic acid levels. No DHA deficiency was observed. GPL-DHA treatment resulted in different PUFA composition changes depending on the tissue (increase in LA, decrease in elevated AA, DHA increase, increase in (n-6)/(n-3) fatty acid ratio). However, the DHA/AA ratio consistently increased in all tissues in CF+DHA and WT+DHA mice. Our study demonstrates the effectiveness of an original oral DHA formulation in counter-balancing the abnormal (n-6) fatty acid metabolism in organs of CF mice when administrated at a low dose and highlights the potential of the use of GPL-DHA as nutritherapy for CF patients.

Essential role of TRPV2 ion channel in the sensitivity of dystrophic muscle to eccentric contractions.

Duchenne myopathy is a lethal disease due to the absence of dystrophin, a cytoskeletal protein. Muscles from dystrophin-deficient mice (mdx) typically present an exaggerated susceptibility to eccentric work characterized by an important force drop and an increased membrane permeability consecutive to repeated lengthening contractions. The present study shows that mdx muscles are largely protected from eccentric work-induced damage by overexpressing a dominant negative mutant of TRPV2 ion channel. This observation points out the role of TRPV2 channel in the physiopathology of Duchenne muscular dystrophy.

Airway delivery of low-dose miglustat normalizes nasal potential difference in F508del cystic fibrosis mice.

RATIONALE: N-butyldeoxynojyrimicin (NB-DNJ, miglustat [Zavesca]) an approved drug for treating Gaucher disease, was reported to be able to correct the defective trafficking of the F508del-CFTR protein. OBJECTIVES: To evaluate the efficacy of in vivo airway delivery of miglustat for restoring ion transport in cystic fibrosis (CF). METHODS: We used nasal transepithelial potential difference (PD) as a measure of sodium and chloride transport. The effect of nasal instillation of a single dose of miglustat was investigated in F508del, cftr knockout and normal homozygous mice. The galactose iminosugar analog N-butyldeoxygalactonojirimycin (NB-DGJ) was used as a placebo. MEASUREMENTS AND MAIN RESULTS: In F508del mice, sodium conductance (evaluated by basal hyperpolarization) and chloride conductance (evaluated by perfusing the nasal mucosa with chloride-free solution in the presence of amiloride and forskolin) were normalized 1 hour after an intranasal dose of 50 picomoles of miglustat. Chloride conductance in the presence of 200 microM 4-4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS), an inhibitor of alternative chloride channels, was much higher after miglustat than after placebo. In cftr knockout mice, a normalizing effect was observed on sodium but not on chloride conductance. CONCLUSIONS: Our results provide clear evidence that nasal delivery of miglustat, at picomolar doses, normalizes sodium and Cftr-dependent chloride transport in F508del transgenic mice; they highlight the potential of topical miglustat as a therapy for CF.

Experience with a medicolegal decision-making system for occupational hearing loss-related tinnitus.

Owing to an increasing number of requests for compensation, a medicolegal decision-making system for tinnitus related to noise-induced hearing loss (NIHL) has been elaborated at the Federal Belgian Institute of Occupational Diseases. Experience with 113 patients, all of them claiming compensation for NIHL and tinnitus, is now available. The patients underwent an exhaustive audiological investigation, and their professional career and noise exposure were carefully and objectively documented. We reviewed the group of 35 "accepted" cases (i.e., with chronic tinnitus recognized as related to NIHL and financially compensated as an occupational disease) and analyzed the medicolegal arguments for acceptance or rejection. In these patients, tinnitus was mostly bilateral, was perceived on average at a frequency of 4 KHz and with a supraliminal intensity of 7.2 dB, and lasted on average for 7.3 years. To gain better insight into the relationship between cochlear damage and chronic tinnitus, we compared our group to a control group of 35 patients with similar hearing thresholds at 3 and 4 KHz but free of tinnitus. The main difference is a significantly steeper slope of the audiometric curve between 2 and 3 KHz in the tinnitus group. Furthermore, a notch in the distortion product-gram is noticed in 60% of the ears affected by tinnitus versus 9% of the ears in the control group. This abrupt discontinuity in the activity along the tonotopic axis of the auditory system-the main characteristic of NIHL-could be a factor eliciting tinnitus, as a correspondence between the audiometric notch and tinnitus frequency appears to exist.

Airway ion transport impacts on disease presentation and severity in cystic fibrosis.

OBJECTIVES: Abnormal airway ion transport is a feature of cystic fibrosis. The aim of this study was to investigate whether distinct components of ion transport are associated with the clinical expression and severity of the disease. DESIGN AND METHODS: Univariate and multivariate analyses were used to study interaction effects between nasal potential difference parameters and clinical status, recorded at stable conditions, in 75 F508del homozygous young adults. RESULTS: All patients demonstrated increased sodium and reduced chloride conductances. Less sodium transport abnormalities were related to better respiratory function and nutrition. Presentation with digestive symptoms at diagnosis was associated with lower chloride conductance. With an accuracy of 85% good nutritional status was linked to more preserved lung function, increasing age and more preserved chloride conductance. CONCLUSIONS: Ion transport abnormalities have distinct clinical outcomes. Sodium conductance relates to respiratory function and nutrition; chloride conductance to nutrition and presentation with digestive symptoms at diagnosis.

Preclinical evidence that sildenafil and vardenafil activate chloride transport in cystic fibrosis.

RATIONALE: Sildenafil has been implicated in the activation of cystic fibrosis transmembrane conductance regulator (CFTR) protein. The effect was observed in vitro and in the presence of doses roughly 300 times larger than those commonly used for treating erectile dysfunction. OBJECTIVES: To evaluate in vivo the therapeutic efficacy of clinical doses of sildenafil and vardenafil, two clinically approved phosphodiesterase 5 inhibitors, for activating ion transport in cystic fibrosis. METHODS: We used transepithelial potential difference in vivo across the nasal mucosa as a measure of sodium and chloride transport. The effect of a single intraperitoneal injection of sildenafil (0.7 mg/kg) or vardenafil (0.14 mg/kg) was investigated in F508del, cftr knockout and normal homozygous mice. MEASUREMENTS AND MAIN RESULTS: In F508del mice, but not in cftr knockout mice, the chloride conductance, evaluated by perfusing the nasal mucosa with a chloride-free solution in the presence of amiloride and with forskolin, was corrected 1 hour after sildenafil administration. A more prolonged effect, persisting for at least 24 hours, was observed with vardenafil. The forskolin response was increased after sildenafil and vardenafil in both normal and F508del mutant animals. In F508del mice, the chloride conductance in the presence of 200 microM 4-4'-diisothiocyanostilbene-2,2'-disulphonic acid, an inhibitor of alternative chloride channels, was much higher after sildenafil injection than after placebo treatment. No effect on the sodium conductance was detected in any group of animals. CONCLUSIONS: Our results provide preclinical evidence that both drugs stimulate chloride transport activity of F508del-CFTR protein.

An overview of monitoring and supplementation of omega 3 fatty acids in cystic fibrosis.

Essential fatty acid deficiency has been increasingly reported in patients with cystic fibrosis. The purpose of this work is to critically summarize previous data on fatty acid status and omega3 supplementation in cystic fibrosis. Although the reported abnormalities differ from study to study, the two most consistent features appeared to be reduced circulating levels of linoleic acid and docosahexaenoic acid (DHA). On the assumption that the fatty acid composition of erythrocyte cell membranes may be similar to that of other organs, it seems appropriate to monitor the phospholipid profile from erythrocyte membranes together with circulating blood levels. Formulations containing widely variable DHA doses, ranging from 300 mg to 5 g per day, have been administered to patients with cystic fibrosis with discrepant outcomes. Randomized controlled trials are needed in order to draw firm conclusions on the therapeutic effect of omega3 fatty acid supplementation in cystic fibrosis.