BRONCHUS AND LUNG CANCER INCIDENCE IN POPULATION LIVING AROUND THE FORMER URANIUM MAINING AND MILING SITES.

The indoor radon concentrations and lung cancer incidence in Eleshnitza village and Blagoevgrad district of Bulgaria were examined in the study reported here. The Eleshnitza was the second largest uranium mining and milling region of the country. The geometric mean of indoor radon concentration in Eleshnitza (465 Bq/m3) was higher than the geometric mean of Blagoevgrad district (78 Bq/m3). Retrospective analyses on lung cancer incidence, covering the period 1995-2012 have been shown the same trend. The results were suggestive of an existing relationship between the two variables. Possible effects attributable to age and gender on lung cancer incidence were examined and found to be significant.

Effectiveness of bronchial thermoplasty in patients with severe refractory asthma: Clinical and histopathologic correlations.

BACKGROUND: The effectiveness of bronchial thermoplasty (BT) has been reported in patients with severe asthma, yet its effect on different bronchial structures remains unknown. OBJECTIVE: We sought to examine the effect of BT on bronchial structures and to explore the association with clinical outcome in patients with severe refractory asthma. METHODS: Bronchial biopsy specimens (n = 300) were collected from 15 patients with severe uncontrolled asthma before and 3 months after BT. Immunostained sections were assessed for airway smooth muscle (ASM) area, subepithelial basement membrane thickness, nerve fibers, and epithelial neuroendocrine cells. Histopathologic findings were correlated with clinical parameters. RESULTS: BT significantly improved asthma control and quality of life at both 3 and 12 months and decreased the numbers of severe exacerbations and the dose of oral corticosteroids. At 3 months, this clinical benefit was accompanied by a reduction in ASM area (median values before and after BT, respectively: 19.7% [25th-75th interquartile range (IQR), 15.9% to 22.4%] and 5.3% [25th-75th IQR], 3.5% to 10.1%, P < .001), subepithelial basement membrane thickening (4.4 µm [25th-75th IQR, 4.0-4.7 µm] and 3.9 µm [25th-75th IQR, 3.7-4.6 µm], P = 0.02), submucosal nerves (1.0 ‰ [25th-75th IQR, 0.7-1.3 ‰] immunoreactivity and 0.3 ‰ [25th-75th IQR, 0.1-0.5 ‰] immunoreactivity, P < .001), ASM-associated nerves (452.6 [25th-75th IQR, 196.0-811.2] immunoreactive pixels per mm2 and 62.7 [25th-75th IQR, 0.0-230.3] immunoreactive pixels per mm2, P = .02), and epithelial neuroendocrine cells (4.9/mm2 [25th-75th IQR, 0-16.4/mm2] and 0.0/mm2 [25th-75th IQR, 0-0/mm2], P = .02). Histopathologic parameters were associated based on Asthma Control Test scores, numbers of exacerbations, and visits to the emergency department (all P ≤ .02) 3 and 12 months after BT. CONCLUSION: BT is a treatment option in patients with severe therapy-refractory asthma that downregulates selectively structural abnormalities involved in airway narrowing and bronchial reactivity, particularly ASM, neuroendocrine epithelial cells, and bronchial nerve endings.

Low-level laser therapy inhibits bronchoconstriction, Th2 inflammation and airway remodeling in allergic asthma.

Low-level laser therapy (LLLT) controls bronchial hyperresponsiveness (BHR) associated with increased RhoA expression as well as pro-inflammatory mediators associated with NF-kB in acute lung inflammation. Herein, we explore if LLLT can reduce both BHR and Th2 cytokines in allergic asthma. Mice were studied for bronchial reactivity and lung inflammation after antigen challenge. BHR was measured through dose-response curves to acetylcholine. Some animals were pretreated with a RhoA inhibitor before the antigen. LLLT (660 nm, 30 mW and 5.4 J) was applied on the skin over the right upper bronchus and two irradiation protocols were used. Reduction of BHR post LLLT coincided with lower RhoA expression in bronchial muscle as well as reduction in eosinophils and eotaxin. LLLT also diminished ICAM expression and Th2 cytokines as well as signal transducer and activator of transduction 6 (STAT6) levels in lungs from challenged mice. Our results demonstrated that LLLT reduced BHR via RhoA and lessened allergic lung inflammation via STAT6.

3D-modelling of radon-induced cellular radiobiological effects in bronchial airway bifurcations: direct versus bystander effects.

PURPOSE: The primary objective of this paper was to investigate the distribution of radiation doses and the related biological responses in cells of a central airway bifurcation of the human lung of a hypothetical worker of the New Mexico uranium mines during approximately 12 hours of exposure to short-lived radon progenies. MATERIALS AND METHODS: State-of-the-art computational modelling techniques were applied to simulate the relevant biophysical and biological processes in a central human airway bifurcation. RESULTS: The non-uniform deposition pattern of inhaled radon daughters caused a non-uniform distribution of energy deposition among cells, and of related cell inactivation and cell transformation probabilities. When damage propagation via bystander signalling was assessed, it produced more cell killing and cell transformation events than did direct effects. If bystander signalling was considered, variations of the average probabilities of cell killing and cell transformation were supra-linear over time. CONCLUSIONS: Our results are very sensitive to the radiobiological parameters, derived from in vitro experiments (e.g., range of bystander signalling), applied in this work and suggest that these parameters may not be directly applicable to realistic three-dimensional (3D) epithelium models.

Meta-analysis of the efficacy and safety of bronchial thermoplasty in patients with moderate-to-severe persistent asthma.

This meta-analysis assessed the efficacy and safety of a novel intervention for asthma, bronchial thermoplasty (BT), in patients with moderate-to-severe persistent asthma. An electronic literature search identified three randomized controlled trials (RCT) of BT that recruited 421 patients in total. Outcomes of interest were the Asthma Quality of Life Questionnaire (AQLQ) score, morning peak expiratory flow (PEF), tolerability and safety. Compared with standard medications and sham BT treatment, BT significantly improved AQLQ scores and PEF from baseline to the end of the trials. There were more respiratory adverse events and hospitalizations for adverse respiratory events with BT than with medications or sham treatment during the treatment period, but most events resolved, on average, within a week. This effect of BT treatment was not seen during the posttreatment period. Additional long-term RCT are required to confirm whether BT provides benefit to patients with moderate-to-severe persistent asthma.

Effect of site-specific bronchial radon progeny deposition on the spatial and temporal distributions of cellular responses.

Inhaled short-lived radon progenies may deposit in bronchial airways and interact with the epithelium by the emission of alpha particles. Simulation of the related radiobiological effects requires the knowledge of space and time distributions of alpha particle hits and biological endpoints. Present modelling efforts include simulation of radioaerosol deposition patterns in a central bronchial airway bifurcation, modelling of human bronchial epithelium, generation of alpha particle tracks, and computation of spatio-temporal distributions of cell nucleus hits, cell killing and cell transformation events. Simulation results indicate that the preferential radionuclide deposition at carinal ridges plays an important role in the space and time evolution of the biological events. While multiple hits are generally rare for low cumulative exposures, their probability may be quite high at the carinal ridges of the airway bifurcations. Likewise, cell killing and transformation events also occur with higher probability in this area. In the case of uniform surface activities, successive hits as well as cell killing and transformation events within a restricted area (say 0.5 mm(2)) are well separated in time. However, in the case of realistic inhomogeneous deposition, they occur more frequently within the mean cycle time of cells located at the carinal ridge even at low cumulative doses. The site-specificity of radionuclide deposition impacts not only on direct, but also on non-targeted radiobiological effects due to intercellular communication. Incorporation of present results into mechanistic models of carcinogenesis may provide useful information concerning the dose-effect relationship in the low-dose range.

Low-level laser therapy (LLLT) attenuates RhoA mRNA expression in the rat bronchi smooth muscle exposed to tumor necrosis factor-alpha.

Low-level laser therapy (LLLT) has been found to produce anti-inflammatory effects in a variety of disorders. Bronchial smooth muscle (BSM) hyperreactivity is associated with increased Ca+2 sensitivity and increased RhoA mRNA expression. In the current study, we investigated if LLLT could reduce BSM contraction force and RhoA mRNA expression in tumor necrosis factor-alpha (TNF-alpha)-induced BSM hyperreactivity. In the study, 112 male Wistar rats were divided randomly into 16 groups, and BSM was harvested and suspended in TNF-alpha baths for 6 and 24 h, respectively. Irradiation with LLLT was performed with a wavelength of 660 nm for 42 s with a dose of 1.3 J/cm2. This LLLT dose was administered once in the 6-h group and twice in the 24-h group. LLLT significantly decreased contraction force in BSM at 6 h (TNF-alpha + LLLT: 11.65+/-1.10 g/100 mg of tissue) (F=3115) and at 24 h (TNF-alpha+ LLLT: 14.15+/-1.1 g/100 mg of tissue) (F=3245, p<0.05) after TNF-alpha, respectively, when compared to vehicle-bathed groups (control). LLLT also significantly decreased the expression of RhoA mRNA in BSM segments at 6 h (1.22+/-0.20) (F=2820, p<0.05) and 24 h (2.13+/-0.20) (F=3324, p<0.05) when compared to BSM segments incubated with TNF-alpha without LLLT irradiation. We conclude that LLLT administered with this protocol, reduces RhoA mRNA expression and BSM contraction force in TNF-alpha-induced BSM hyperreactivity.

Low level laser therapy (LLLT): attenuation of cholinergic hyperreactivity, beta(2)-adrenergic hyporesponsiveness and TNF-alpha mRNA expression in rat bronchi segments in E. coli lipopolysaccharide-induced airway inflammation by a NF-kappaB dependent mechanism.

BACKGROUND AND OBJECTIVES: It is unknown if the decreased ability to relax airways smooth muscles in asthma and other inflammatory disorders, such as acute respiratory distress syndrome (ARDS), can be influenced by low level laser therapy (LLLT) irradiation. In this context, the present work was developed in order to investigate if LLLT could reduce dysfunction in inflamed bronchi smooth muscles (BSM) in rats. STUDY DESIGN/MATERIALS AND METHODS: A controlled ex vivo study was developed where bronchi from Wistar rat were dissected and mounted in an organ bath apparatus with or without a TNF-alpha. RESULTS: LLLT administered perpendicularly to a point in the middle of the dissected bronchi with a wavelength of 655 nm and a dose of 2.6 J/cm(2), partially decreased BSM hyperreactivity to cholinergic agonist, restored BSM relaxation to isoproterenol and reduced the TNF-alpha mRNA expression. An NF-kappaB antagonist (BMS205820) blocked the LLLT effect on dysfunction in inflamed BSM. CONCLUSION: The results obtained in this work indicate that the LLLT effect on alterations in responsiveness of airway smooth muscles observed in TNF-alpha-induced experimental acute lung inflammation seems to be dependent of NF-kappaB activation.

[Efficiency of a combination of haloaerosols and helium-neon laser in the multimodality treatment of patients with bronchial asthma].

A hundred and thirty-eight patients with infection-dependent bronchial asthma, including 73 with moderate persistent asthma and 65 with severe persistent one, were examined. Four modes of a combination of traditional (drug) therapy (DT) and untraditional (halotherapy (HT) and endobronchial helium-neon laser irradiation (ELI) one were used. The efficiency of the treatment performed was evaluated, by determining the time course of clinical symptoms of the disease on the basis of scores of their magnitude and the patients' condition. The findings indicated that in moderate persistent asthma, both HT and ELI in combination with DT exerted an equal therapeutic effect, which provided a good and excellent condition in 83.3% of cases. In severe persistent asthma, such a condition was achieved in 93.75% of cases only when multimodality treatment involving DT, HT, and ELI had been performed.

[Morphological diagnosis of the inhalation trauma and criteria of efficacy of the endobronchial laser therapy based on the biopsy material]. / Morfologicheskaia diagnostika ingaliatsionnoi travmy i kriterii éffektivnosti éndobronkhial'noi lazernoi terapii po biopsiinomu materialu.

The results of 424 biopsies obtained at fibrobronchoscopy (FBS) from 45 patients with inhalation trauma (IT) are presented. The standard and endoscopic laser treatment (ELT) have been used (24 and 21 patients, respectively). It is demonstrated that precise visual assessment of IT severity is possible under dynamic endoscopic observation only. Healing of mucous defects of the tracheo-bronchial tree was shorter in the ELT group. Morphologically, early and continuous ELT was not associated with signs of severe purulent inflammation and, therefore, produced no early additional, damage to the wall. This may explain accelerated formation of the granulation tissue at the ulcer bottom and epithelization at the margin areas.

The distribution and clearance of inhaled UO2 particles on the first bifurcation and trachea of rats.

The distribution of inhaled UO2 particles is described in the upper respiratory tract of rats up to 14 d after inhalation. Delayed neutron analysis was used to determine accurately nanogram quantities of UO2 present in excised tissues. The mass of UO2 in the extrapulmonary bronchi and first bifurcation decreased more slowly over 0--8 d after inhalation than the corresponding mass on the trachea. Between 8 and 14 d neither amount altered significantly. Small but significant quantities of UO2 deposited on the trachea during inhalation, remained until at least 14 d after inhalation.