Effects of radiotherapy on olfaction and nasal function in head and neck cancer patients.

PURPOSE: Radiotherapy (RT) is a major component of treatment in head and neck malignancies and often the radiation field includes the nasal cavity and olfactory cleft region. We aimed to assess olfaction, mucociliary clearance time and quality of life (QOL) before RT and during the course of radiotherapy. METHODS: This prospective, observational, cohort study was conducted over a period of 1 year. The olfactory function, mucociliary clearance and QOL of patients with primary head and neck cancers undergoing radiation therapy as part of treatment were assessed prior to radiotherapy and followed up serially up to 3 months after radiotherapy. A total of 21 patients were enrolled. Assessment was done using noninvasive tests for better compliance and ease of examination. RESULTS: Among the 21 patients recruited, 18 completed radiotherapy and 13 were assessed 3 months post radiotherapy. Mean olfactory scores (including olfactory threshold and odor identification), using Connecticut Chemosensory Clinical Research Center (CCCRC) test, deteriorated significantly at the end of radiotherapy (p < 0.001) as compared to scores before irradiation. Subjective assessment of olfaction by Appetite, Hunger and Sensory perception (AHSP) questionnaire did not demonstrate significant impairment in nasal function (p < 0.319) although overall QOL significantly deteriorated (p 0.004). The mucociliary clearance time was prolonged in 72% of the patients at the end of radiotherapy. CONCLUSION: Deterioration in olfactory function was found to occur during the course of radiotherapy with gradual improvement after 3 months. However, patients did not notice olfactory dysfunction subjectively. Mucociliary dysfunction persisted even after 3 months following radiation.

Irradiation as a hazard for mucociliary clearance.

OBJECTIVES: In this paper we study effects of irradiation to pulmonary tissue on a micro and ultrastructural level to get insights into the dynamics of morphological changes and associated post-radiative physiological conditions. METHODS: Animal and human pulmonary tissue with and without radiation damage was subject to light, transmission, scanning and polarization microscopy and morphometric evaluation. RESULTS: The present investigations on the influence of irradiation on experimental and human lung tissue demonstrate that complex changes are induced in the cells which are essential for mucociliary clearance. These changes are a shortage of alveolar macrophages, cell apoptosis, proliferation of collagen ligament in the barrier of gaseous exchange, retraction of endothelial lining of capillaries and significant broadening of the gaseous exchange barrier, resulting in serious damage for the O2 and CO2 exchange. CONCLUSIONS: These changes at microscopic, cellular, and ciliary level trigger conditions for various diseases of the respiratory system, which is further assessed by a simultaneous computer aided estimation of ciliary function. With the concurrent world-wide increase of respiratory diseases, these findings are important knowledge for the clinical practice.

The effects of 2100-MHz radiofrequency radiation on nasal mucosa and mucociliary clearance in rats.

BACKGROUND: Nasal mucociliary clearance has an important role in voiding the airways from inhaled foreign substances. This activity could be disturbed by environmental factors such as radiofrequency radiation. The aim of the present study was to investigate short-term and relatively long-term effects of 2100-MHz radiofrequency radiation emitted by a generator, simulating a 3G-mobile phone, on the nasal septal mucosa and mucociliary clearance in rats. METHODS: Thirty Wistar albino rats were divided into 4 groups. There were 6 rats in Group A and Group B, which served as the control groups (10-day and 40-day groups, respectively). Groups C (10-day exposure) and D (40-day exposure) were both composed of 9 rats; they comprised the radiofrequency radiation exposure groups. The rats in groups C and D were exposed to 2100-MHz radiofrequency radiation emitted by a generator, simulating a 3G-mobile phone, 6 hours/day, for 10 or 40 days, respectively. After exposure, nasal mucociliary clearance was measured by rhinoscintigraphy. After euthanization, the nasal septa of the animals were removed, and tissue samples of the nasal mucosa were examined using a transmission electron microscope. RESULTS: The differences in mucociliary clearances between groups A and C, groups B and D, and groups C and D were found to be statistically significant (p = 0.005, p < 0.001, p < 0.001, respectively). Although there were no histopathological abnormalities in the control groups, the exposure groups showed a number of degenerated and apoptotic cells, ciliary disorganization and ciliary loss in the epithelial cells, epithelial metaplasia, alteration of normal chromatin distribution and karyolysis in nuclei, changes in the basal cells, and lymphocytic infiltration. The histopathological changes were more severe in group D. CONCLUSION: Radiofrequency radiation at 2100 MHz damaged the nasal septal mucosa, and disturbed the mucociliary clearance. Ciliary disorganization and ciliary loss in the epithelial cells resulted in deterioration of nasal mucociliary clearance.

The effect of radiotherapy on mucociliary clearance in patients with laryngeal and nasopharyngeal cancer.

The present study aimed to demonstrate how the nasal mucociliary transport times are affected in the patients receiving radiotherapy for head-neck tumor in two different anatomic localizations. The study included 44 patients receiving radiotherapy under the diagnoses of the nasopharyngeal and laryngeal cancer. The mucociliary transport times of both groups were measured via saccharine tablets before radiotherapy, and at months 3 and 6 after radiotherapy. The difference between the groups was statistically evaluated. The pre-irradiation (pre-RT) mean transport times of NPC and LC patients were 9.7 and 9.1 min, respectively. The difference in the mucociliary transport times between these two groups was not statistically significant (p = 0.49). The mean transport time was 26.1 min at post-RT month 3, 23.9 min, at month 6; the change from pre-RT to month 3 was significant (p < 0.05) and the change from month 3 to 6 was not statistically significant (p = 0.182). The mean transport time of the LC patients was 16.8 min. At post-RT month 3, 12.4 min. at month 6; the change from pre-RT to month 3 (p < 0.05) and the change from month 3 to 6 were statistically significant (p = 0.007). It was found that radiotherapy affected the physiological conditions of the patients with nasopharyngeal cancer in a more severe and sustained way compared to the LC patients, which negatively affects the patient's response to the treatment by the resulting organic and psychological effects.

The effects of a 1.8 GHz continuous electromagnetic fields on mucociliary transport of human nasal mucosa.

OBJECTIVES/HYPOTHESIS: The aim of this study was to investigate the effects of a 1.8 GHz continuous electromagnetic fields (EMF) on human nasal mucociliary transport, and to determine the pathophysiology of ciliary beat frequency (CBF) during an EMF-induced change. METHODS: Human nasal mucosa cells were exposed to a 1.8 GHz EMF (SAR=1.0 W/kg), and CBF was analyzed using an optical flow technique with the peak detection method. RESULTS: The 1.8 GHz-exposed group showed a decreased CBF when compared to the control group. In the cytotoxicity assay, difference in survival rates was not found between the two groups. In the EMF-exposed group, protein kinase C (PKC) activity was increased during a PKC activity assay. The broad PKC inhibitor, Calphostin C abolished the EMF-induced decrease of CBF. The EMF-induced decrease of CBF was abolished by GF 109203X, a novel PKC (nPKC) isoform inhibitor, whereas the decrease was not attenuated by Gö-6976, a specific inhibitor of conventional PKC (cPKC) isoform. CONCLUSIONS: EMF may inhibit CBF via an nPKC-dependent mechanism. Therefore, we have confirmed that EMF could decrease CBF by increasing PKC activity.

Choanal fungus ball mimicking a tumour.

We report the first case of an isolated choanal fungus ball in a 28-year-old man with a previous history of nasopharyngeal carcinoma, who was treated with radiotherapy 14 years ago. The initial diagnosis was a recurrent tumour or a secondary neoplasm. Histopathological examination confirmed a fungal infection. There are no previous reports of a fungus ball located at the posterior choanal region. Although it has been reported that bacteriology of sinonasal region would be different in irradiated patients, there is no study reporting fungal infections in irradiated patients in English literature. In this report, the clinical presentation, relevant radiologic findings and management of sinonasal fungus ball and its relationship with previous radiotherapy were discussed with the literature knowledge.

Damage of nasal mucociliary movement after intensity-modulated radiation therapy of nasopharyngeal carcinoma.

BACKGROUND AND OBJECTIVE: Radiation usually results in paranasal sinusitis in patients with nasopharyngeal carcinoma (NPC), which influences patients' quality of life. This study aimed to determine the relationships between dose distribution in the nasal cavity and nasal mucous injury in patients with NPC treated by intensity-modulated radiation therapy (IMRT), and to find the tolerable radiation dose for the nasal mucous. METHODS: Sixty-six patients with NPC treated by IMRT between October 2006 and November 2008 were enrolled. The irradiation dose in the nasal cavity was determined by the computer with the IMRT work platform. Mucociliary transport rate (MTR) was detected by modified saccharine test before IMRT, at the end of IMRT, and at 3, 6, and 12 months after IMRT. RESULTS: The data were available for 129 nasal cavities. The cavities receiving a mean dose below or equal to 37 Gy showed substantial preservation of nasal mucous after IMRT. The MRT decreased to (62.82 ± 38.59)%, (56.78 ± 37.79)%, (64.05 ± 39.37)%, and (71.13 ± 39.55)% of pre-IMRT value at 4 time points after IMRT, with significant differences among the data (P < 0.05). In contrast, when the cavities received a mean dose higher than 37 Gy, no significant differences in MTR among the time points were observed. At 3 months after IMRT, the MTR was the lowest (38.27% of pre-RT value). CONCLUSIONS: A mean radiation dose of ≤ 37 Gy for the nasal cavity is an optimal dose to protect the nasal cavity function.

[Affects of transmission capability of nose mucociliary in radiotherapy].

OBJECTIVE: To investigate the effects of radioactive ray on transmission capability of nose mucociliary. METHOD: Forty-six patients with NPC were selected and saccharin clearance time (SCT) for 7 phases were detected in both pre- and post-radiotherapy respectively. RESULT: Among 46 patients with NPC, the shortest SCT was 247 seconds and the longest 601 seconds in pre-radiotherapy phases; from 4th week of introradiotherapy to 18 months of postradiotherapy, the longest SCT was in 12 months after radiotherapy, which was 903 seconds. There were no significant differences in SCT before radiotherapy and 18 months after radiotherapy. There were significant differences in SCT of preradiotherapy and introdiotherapy, post radiotherapy, after radiotherapy 3 months, 6 months, 12 months after radiotherapy. CONCLUSION: Radiotherapy is the important factors in influencing transmission capability of nose cavity and sinus mucociliary and hints that gender and nasal cavity side don't affect SCT. Detection of SCT in different stages of NPC patients can be helpful to protect nasal mucous membrane effectively, and to reduce incidence rate of RNS.

Nasal and paranasal sinus changes after radiotherapy for nasopharyngeal carcinoma.

OBJECTIVE: To study sinonasal side-effects after radiotherapy (RT) in nasopharyngeal carcinoma (NPC) patients. MATERIAL AND METHODS: The study subjects comprised 32 cases of NPC (23 new cases, 9 old cases) who had been treated with RT with no recurrence. They were subjected to a saccharine test, nasal endoscopy and CT. RESULTS: There was a gradual and persistent increase in the saccharine delay time after RT. Endoscopy showed that, early post-RT, edema and discharge were replaced by delayed crusting and adhesions. CT showed that the maxillary sinus, anterior ethmoid sinus and ostiomeatal complex were the areas most affected. CONCLUSIONS: Rhinosinusitis is a common post-RT side-effect in NPC patients. A pre-RT saccharine test is a good predictor of those patients who are more likely to develop sinonasal side-effects. Functional endoscopic sinus surgery should be considered with caution in post-RT rhinosinusitis.

Impairment of nasal mucociliary clearance after radiotherapy for childhood head cancer.

BACKGROUND: Radiotherapy of the head region in children is known to cause long-term sequelae, such as facial, dental, and ocular abnormalities. We investigated whether a decreased nasal mucociliary function occurs after radiotherapy of the head in children. METHODS: A saccharin/charcoal test was performed in 20 children treated with radiotherapy of the head and in 20 controls, age-matched and gender-matched. RESULTS: We found a decreased nasal mucociliary clearance (lower percentage of responses (p = 0083) and longer mucociliary transport times (p =.0001) in the patients compared with the controls. The radiotherapy dosage influenced the response to the test (p =.0046). CONCLUSIONS: Irradiation of the head in children may cause impairment of mucociliary function, even permanently, which may predispose children to upper respiratory infections. We would suggest careful monitoring of such patients to detect as early as possible the clinical effects of the functional changes and to prevent the evolution to chronic diseases.

Nasal mucociliary clearance after radiation therapy.

Irradiation has been demonstrated to cause decreased mucociliary clearance in animal models. We sought to verify this effect clinically by using the saccharin transport test to evaluate nasal mucociliary clearance in 9 patients previously treated with radiation therapy to the nasal cavity. The patients also completed a questionnaire examining the prevalence of nasal symptoms before and after radiation therapy. Patients who received radiation therapy had no clearance of saccharin from the nasal cavity at a minimum of 20 minutes. The controls had a median clearance time of 5 minutes. The patients noted a higher prevalence of nasal congestion, drainage, and facial pain after radiation therapy. This study demonstrates that radiation therapy to the nasal cavity causes a decrease in nasal mucociliary clearance. This alteration should be considered when selecting therapy for malignancies in the nasal area.

Effects of irradiation on the rat middle ear mucosa. A scanning electron microscopic study.

Adult Sprague-Dawley rats (n = 64) were used in this study to replicate in an animal model tissue change formed clinically during radiotherapy for the treatment of head and neck malignancy. Gamma irradiation was administered to both ears of each rat, using a cobalt-60 machine. A total dose of 30 Gy was administered, with 500 cGy/fraction given on 6 consecutive days to a time-dose fractionation value of 81. Animals were then sacrificed at sequential intervals. The tympanic bullae were removed and the mucosa was processed for scanning electron microscopy. Tissue findings indicated that irradiation might initially have no influence on the clearance activity of the middle ear. However, ultrastructural changes showed stagnation of secretion between cilia, falling off and different directions of the cilia, fused or collapsed cilia, and eustachian tube dysfunction (with mucosal edema). These findings possibly account for the occurrence of middle ear effusions in patients during and after radiotherapy for head and neck malignancy. It is our concept that insertion of a ventilation tube is necessary if abnormal mucociliary function appears, in order to clear and prevent the accumulation of any middle ear effusions and prevent further mucociliary dysfunction.

Effect of the radioprotector WR2721 on irradiation-induced injury to ciliated cells of eustachian tube.

Our previous studies revealed that injury to the ciliated cells of the eustachian tube may be the primary cause of irradiation-induced serous otitis media. The purpose of this study was to investigate the effects of the radioprotector WR2721 on irradiation-induced injury to ciliated cells of the eustachian tube (ET) in chinchillas. Twelve chinchillas were divided into two groups: the control group and the experimental group, which was pretreated with a single intraperitoneal dose of the radioprotector S-2-[3-aminopropylamino]ethylphosphorothioic acid (WR2721) 400 mg/kg. The two groups were exposed to 30 Gy of 13-MeV electrons in a single fraction to the area of the bullae and nasopharynx. Ciliary dysfunction was tested and ciliated cells of the ET were examined by scanning and transmission electron microscopy. Pretreatment with WR2721 was found to protect ciliated cells of the ET from irradiation injury.

[Study of the mucociliary transport rate in evaluating the effectiveness of the treatment of suppurative endobronchitis by CO2 laser]. / Skorost' mukotsiliarnogo transporta v otsenke éffektivnosti lecheniia gnoinogo éndobronkhita CO2-lazerom.

The rate of mucociliary transport (MCT) in dogs with an experimental pulmonary tuberculosis and concurrent suppurative endobronchitis (SEB) and just with the latter was measured. The treatment effect was achieved by an endobronchial radiation with a CO2-laser unfocused beam of 3.56 and 5.3 w/cm2 power density, and the dogs in the control group were subjected to an endobronchial introduction of furagin. A comparison of the endoscopic picture and MCT rate findings made it possible to believe that the latter index appeared to be more reliable than a visual inspection of the bronchial mucous membrane. An active specific process in the lungs brings about MCT rate inhibition while the concurrent SEB aggravates these changes to a great extent. The radiation of the bronchial mucous membrane with the CO2-laser unfocused beam produces an immediate positive effect on MCT rate normalization. Better results were observed at a power density of 3.56 w/cm2.

Functional and morphological pathology of the nasal mucosa after x-ray irradiation.

In our present study we examined the pathology of the nasal mucociliary system after x-ray irradiation in an animal model namely the rabbit. A reduced ciliary activity was observed immediately after the irradiation and did not show any recovery during our observation. No ciliary activity was seen in the nasal mucosa 8 weeks after the irradiation. Morphologically, hypersecretion of goblet cells was observed immediately after irradiation. Cytoplasmic vacuolation and nuclear pyknosis of ciliated cells started after irradiation, and sloughing of ciliated cells was observed for up to 3 weeks. Epithelial metaplasia started from 4 weeks, and no cilia were seen in the nasal mucosa and the surface of the epithelium was covered with flat squamous cells. Our present study shows that x-ray irradiation has serious influence on the function and structure of the nasal mucociliary system and that recovery from degeneration due to x-ray irradiation cannot be expected within several weeks.