Respiratory pathology in vibroacoustic disease: 25 years of research.

BACKGROUND: Respiratory pathology induced by low frequency noise (LFN, < 500 Hz, including infrasound) is not a novel subject given that in the 1960's, within the context of U.S. and U.S.S.R. Space Programs, other authors have already reported its existence. Within the scope of vibroacoustic disease (VAD), a whole-body pathology caused by excessive exposure to LFN, respiratory pathology takes on specific features. Initially, respiratory pathology was not considered a con- sequence of LFN exposure; but today, LFN can be regarded as a major agent of disease that targets the respiratory system. The goal of this report is to put forth what is known to date on the clinical signs of respiratory pathology seen in VAD patients. METHODS: Data from the past 25 years of research will be taken together and presented. RESULTS: In persons exposed to LFN on the job, respiratory complaints appear af- ter the first 4 years of professional activity. At this stage, they disappear during vacation periods or when the person is removed form his /her workstation for other reasons. With long-term exposure, more serious situations can arise, such as, atypical pleural effusion, respiratory insufficiency, fibrosis and tumours. There is no correlation with smoking habits. In LFN-exposed animal models, morphological changes of the pleura, and loss of the phagocytic ability of pleural mesothelial cells (explaining the atypical pleural effusions). Fibrotic lesions and neo-vascularization were observed along the entire respiratory tract. Fibrosis lesions and neovascularisation were observed through- out the respiratory tract of the animals seen. Pre-malignant lesions, metaplasia e displasia, were also identified. DISCUSSION: LFN is an agent of disease and the respiratory tract is one of its preferential targets. The respiratory pathology associated with VAD needs further in-depth studies in order to achieve a greater understanding, and develop methods of pharmaco- logical intervention.

Vibroacoustic disease: biological effects of infrasound and low-frequency noise explained by mechanotransduction cellular signalling.

At present, infrasound (0-20 Hz) and low-frequency noise (20-500 Hz) (ILFN, 0-500 Hz) are agents of disease that go unchecked. Vibroacoustic disease (VAD) is a whole-body pathology that develops in individuals excessively exposed to ILFN. VAD has been diagnosed within several professional groups employed within the aeronautical industry, and in other heavy industries. However, given the ubiquitous nature of ILFN and the absence of legislation concerning ILFN, VAD is increasingly being diagnosed among members of the general population, including children. VAD is associated with the abnormal growth of extra-cellular matrices (collagen and elastin), in the absence of an inflammatory process. In VAD, the end-product of collagen and elastin growth is reinforcement of structural integrity. This is seen in blood vessels, cardiac structures, trachea, lung, and kidney of both VAD patients and ILFN-exposed animals. VAD is, essentially, a mechanotransduction disease. Inter- and intra-cellular communication is achieved through both biochemical and mechanotranduction signalling. When the structural components of tissue are altered, as is seen in ILFN-exposed specimens, the mechanically mediated signalling is, at best, impaired. Common medical diagnostic tests, such as EKG, EEG, as well as many blood chemistry analyses, are based on the mal-function of biochemical signalling processes. VAD patients typically present normal values for these tests. However, when echocardiography, brain MRI or histological studies are performed, where structural changes can be identified, all consistently show significant changes in VAD patients and ILFN-exposed animals. Frequency-specific effects are not yet known, valid dose-responses have been difficult to identify, and large-scale epidemiological studies are still lacking.

Respiratory squamous cell carcinomas in vibroacoustic disease.

BACKGROUND: In 1987, the autopsy of a vibroacoustic disease (VAD) patient disclosed two tumours: a renal cell carcinoma and a malignant glioma in the brain. Since 1987, malignancy in VAD patients has been under close surveillance. To date, in a universe of 945 individuals, there are 46 cases of malignancies, of which 11 are multiple. Of the 11 cases of respiratory tract tumours, all were squamous cell carcinomas (SqCC). This report focuses on the morphological features of these tumours. METHODS: Tumour fragments were collected (endoscopic biopsy or surgery) from 11 male VAD patients (ave. age: 58+/-9 years, 3 non-smokers): 2 in glottis and 9 in the lung. In the 3 non-smokers, 2 had lung tumours and 1 had a glottis tumour. All were employed as or retired aircraft technicians, military or commercial pilots. Fragments were fixed either for light and electron microscopy. Immunohistochemistry studies used chromagranine and synaptophysine staining. RESULTS: All lung tumours were located in the upper right lobe bronchi and were histologically poorly differentiated SqCC (Figs. 1, 2). The search with neuroendocrine markers was negative. The average age of tumour onset in helicopter pilots was below 50 years old while for the other professional groups it was above 50. Nine patients are deceased. The 2 surviving patients are heavy smokers (> 2 packs/day). Smoking habits had no influence on tumour outcome and progression. DISCUSSION: Epidemiological studies indicate that squamous cell carcinomas account for approximately 40% of all lung tumours in men. It seems to be highly relevant that all VAD patient respiratory tract tumours are squamous cell carcinomas. It is not surprising that helicopter pilots are the ones who are affected the earliest because previous studies have shown that helicopter pilots exhibited the highest values for the frequency of sister chromatid exchanges. Generally, epidemiological tumor studies do not take histological tumor type into account, but given the results herein, it would seem of the utmost importance to begin specifiying the exact histological type of tumor in all statistical studies.

Voice acoustic patterns of patients diagnosed with vibroacoustic disease.

BACKGROUND: Long-term low frequency noise exposure (LFN) (< or = 500 Hz, including infrasound) may lead to the development of vibroacoustic disease (VAD), a systemic pathology characterized by the abnormal growth of extra-cellular matrices. The respiratory system is a target for LFN. Fibrosis of the respiratory tract epithelia was observed in VAD patients through biopsy, and confirmed in animal models exposed to LFN. Voice acoustic analysis can detect vocal fold variations of mass, tension, muscular and neural activity. Frequency perturbation (jitter), amplitude perturbation (shimmer) and harmonic-to-noise ratio (HNR) are used in the evaluation of the vocal function, and can be indicators of the presence and degree of severity of vocal pathology. Since the respiratory system is the energy source of the phonation process, this raises questions about the effects of VAD on voice production. The purpose of this study was to determine if voice acoustic parameters of VAD patients are different from normative data. METHODS: Nine individuals (5 males and 4 females) diagnosed with VAD were recorded performing spoken and sung tasks. The spoken tasks included sustaining vowels and fricatives. The sung tasks consisted of maximum phonational frequency range (MPFR). Voice acoustic parameters ana- lysed were: fundamental frequency (F0), jitter, shimmer, HNR and temporal measures. RESULTS: Compared with normative data, both males and females diagnosed with VAD exhibited increased F0, shimmer and HNR. Jitter, MPFR and one temporal measure were reduced. CONCLUSIONS: VAD individuals presented voice acoustic parameter differences in spectral, temporal and perturbation measures, which may be indicative of small morphological changes in the phonatory system.

Abnormal respiratory drive in vibroacoustic disease.

INTRODUCTION: Central nervous system disorders in workers exposed to low frequency noise (LFN, < 500 Hz, including infrasound) were first observed 25 years ago among aircraft technicians. Concurrently, respiratory pathology was identified in these workers, and later reproduced in LFN-exposed animal models. Today vibroacoustic disease (VAD) is defined as the systemic pathology caused by excessive exposure to LFN. The respiratory tract continues to be under heavy scrutiny in both LFN-exposed humans and animal models and has been confirmed as a major target for LFN-induced damage. Given that both the respiratory and central nervous systems were compromised in these workers, it became pertinent to investigate the status of the neurological control of breathing in VAD patients. METHODS: The P- 0.1 value, a measure of the suction pressure developed at the mouth 0.1 seconds after the start of inspiration, depends on the respiratory centres and the autonomic nervous system pathway of the neural control of respiratory function. By rebreathing CO2, (6% in air) normal individuals present an average seven-fold increase in P0.1 (CO2) as compared to basal P- 0.1. Twenty-two male VAD patients (ave. age 50.5 +/- 8.5 years, range: 36-66 years) underwent the P0.1(CO2) index respiratory drive tests, as well as standard pulmonary function tests. Seven individuals (ave. age 42.4 +/-14 years, range: 25- 61 years) with reduced LFN exposure served as controls. RESULTS: Pulmonary function tests were normal in both VAD patients and controls. The P0.1 (CO2) in- dex was below average value in VAD patients (average: 22.9%) while it presented normal values in the control group (average > 60%). DISCUSSION: In the involuntary response to increased PCO2 levels, central chemoreceptors are responsible for 70% of the ventilatory stimulus. In VAD patients, this dysfunction may originate in the brainstem. This is corroborated by the fact that VAD patients register abnormal values for auditory brainstem evoked potentials, and disclose lesions with magnetic resonance imaging. The neurological control of breathing is compromised in VAD patients. The P0.1 (CO2) index may be a useful clinical indicator for VAD diagnosis and follow-up.

Involvement of central airways in vibroacoustic disease patients.

INTRODUCTION: Vibroacoustic disease (VAD) is the whole-body pathology caused by excessive exposure to LFN. For the past 25 years, it has been know that low frequency noise (LFN, < 500 Hz, including infrasound) targets the respiratory system. In LFN-exposed rodents, the morphological changes of respiratory tract tissue partially explained some respiratory symptoms reported by VAD patients. However, many questions remain unanswered. Recently, some volunteer VAD patients underwent bronchoscopy in order to ascertain possible damage that could be associated with their respiratory complaints. METHODS: Fourteen fully-informed and volunteer VAD patients were submitted to bronchoscopy, and biopsies were removed for analysis. RESULTS: All patients exhibited small submucosal vascular-like lesions near the spurs, consisting of increased collagen and elastin fibres. Histology disclosed cilliary abnormalities, basal membrane hyperplasia, and thickening of vessel walls. In five patients, collagen bundles appeared degenerative and disrupted. No inflammatory process was ever identified, and no differences were seen between smokers and non-smokers. DISCUSSION: Data is in accordance with what was observed in LFN-exposed animal models and also in 8 VAD patients who developed lung tumours. Collagen disruption and degeneration was also observed in electron microscopy images of the respiratory tract of LFN-exposed rodents. Thickened blood and lymphatic vessel walls have been consistently seen in images of VAD patients and of LFN-exposed rodents. During bronchoscopy performed by other reasons, this sort of structural aspects is not frequently seen. Taken together, it is strongly suggested that these findings could be VAD-specific.

Noise-induced gastric lesions: a light and scanning electron microscopy study of the alterations of the rat gastric mucosa induced by low frequency noise.

INTRODUCTION: Exposure to low frequency noise (LFN) can lead to vibroacoustic disease (VAD), recognized as a systemic disease with lesions in a broad spectrum of organs. Although gastrointestinal complaints are common among individuals exposed to noise, only few studies tried to evaluate the digestive lesions. The authors performed this study in order to investigate gastric lesions in an animal model of VAD. MATERIAL AND METHODS: Adult Wistar rats were exposed to continuous LFN. After five weeks they were sacrificed. The stomachs were studied by light microscopy and scanning electron microscopy, and compared with stomachs of animals kept in silence. RESULTS: Superficial erosions were present in the noise-exposed animals. Massive cell death of the gastric epithelium was observed, both by light and electron microscopy. DISCUSSION: The erosions, reflecting cellular degeneration and death, occurred without inflammation, similar to what has been observed in other LFN-exposed organs.

Noise and the respiratory system.

Noise-induced pulmonary pathology is still an issue that is regarded with much suspicion despite the significant body of evidence demonstrating that acoustic phenomena target the respiratory tract. The goal of this review paper is threefold: a) to describe acoustic phenomena as an agent of disease, and the inadequacies of current legislation regarding noise-induced, non-auditory pathology; b) to trace how the interest in noise-induced pulmonary pathology emerged within the scope of studies on vibroacoustic disease; and c) to bring to light other studies denouncing noise as an agent of disease that impinges on the respiratory tract. As concluding remarks, future perspectives in LFN-related research will be discussed. The need for animal models will be emphasized.

Respiratory epithelia in Wistar rats.

Morphofunctional changes of respiratory epithelia became the object of intense study in Wistar rats after previous research showed that occupationally-simulated exposure to low frequency noise (500 Hz, including infrasound) induced irreversible lesions in these tissues. Aspects of normal respiratory epithelia in rats are lacking in the literature, and are the object of this report. Ten Wistar rats were kept in silence, fed standard rat food, and had unrestrained access to water (treated in accordance with 86/609/CE). The animals were sacrificed at 3.5 months of age, and respiratory epithelial fragments were excised and prepared for scanning (SEM) and transmission (TEM) electron microscopy. Brush cells (BC) were frequently observed with TEM, but with SEM they were often covered by the cilia of neighbouring cells. BC were always observed at the center of a ring of secretory cells (SC), in a rosetta-shaped formation. In TEM, the microvilli of SC surrounding the BC were uniform, and had the same density and shape in all cells. Multivesicular bodies were identified in areas within the BC. Formation and budding of vesicles from ciliary plasma membranes and from BC microvilli were frequently observed in both TEM and SEM. These data contribute to the understanding of the BC function.

[Respiratory epithelia in Wistar rats after 48 hours of continuous exposure to low frequency noise]. / O epitélio respiratório em ratos Wistar após 48 horas de exposição contínua ao ruído de baixa frequência.

Previous studies show that exposure to low frequency noise (LFN) (< or =500 Hz, including infrasound) produces irreversible lesions in Wistar rat respiratory epithelia. Recovery periods for LFN-induced lesions have thus become an object of interest. Changes in the respiratory epithelia of Wistar rats after continuous short-term exposure to LFN are described. Twelve rats were exposed to continuous LFN for 48 hrs, and 10 age-matched rats were kept in silence. Animals were treated in accordance with 86/609/CE. After exposure ceased, two rodents were sacrificed immediately, and another two after 6, 12, 24, 48 hrs, and 7 days of post-exposure silence. Respiratory epithelial fragments were prepared for light and scanning/transmission electron microscopy. Six hours after exposure, intense and irregular cellular tumefaction was visible and rosetta structures, formed by secretory cells (SC) centered on a brush cell (BC), were identifiable. Cilia were shorter and shaggy. BC microvilli tended to group, losing the uniform distribution seen in controls. Twelve hours after exposure, cell ballooning was still present, BC shape was highly irregular and microvilli were grouped. SC microvilli were still shorter than controls. Seven days after exposure, controls and exposed were indistinguishable. LFN-induced epithelial lesions seem to be reversible if recovery periods are respected.

[Respiratory epithelia in Wistar rats born in low frequency noise plus varying amounts of additional exposure]. / O epitélio respiratório em ratos Wistar nascidos em ruído de baixa frequência e expostos a ruído adicional.

Earlier studies of Wistar rat respiratory epithelia exposed to low frequency noise (LFN) (< or =500 Hz, including infrasound) showed that LFN effects trauma on the respiratory tract. In rats gestated and born in LFN environments, trauma was still treated in accordance with 86/609/EC. Respiratory epithelial fragments were prepared for light and scanning/transmission electron microscopy. Group A brush cell (BC) microvilli tended to group together; in Group B they were clearly clustered together, and in Groups C-F they became fused. Rosetta structures (rings of secretory cells centered on a BC) were visible in Groups A-D and difficult to identify in Groups E,F. The amount of sheared cilia increased with exposure time, as did the images of cellular de-differentiation. LFN exposure induces severe trauma on the respiratory epithelial cells in these rats.