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BACKGROUND: Diesel exhaust fumes represent one of the most common toxic pollutants. The prolonged effects of acute exposure to this pollutant on inflammatory status and vascular properties are unknown. METHODS: During a 2-h session, 40 healthy subjects were exposed to diesel exhaust fumes and/or filtered air. Endothelial function was assessed with flow mediated dilation, arterial stiffness with pulse wave velocity and reflected waves with augmentation index. C-reactive protein, fibrinogen, protein C levels and protein S activity were also measured. Standard deviation of normal to normal R-R intervals (SDNN) was used to assess heart rate variability. Measurements were assessed before exposure and 2 and 24 h after diesel exposure. RESULTS: Compared with filtered air, exposure to diesel exhaust fumes decreased flow mediated dilation and increased pulse wave velocity and augmentation index up to 24 h after the exposure (p < 0.001 for all). Similarly, compared with filtered air, diesel exhaust exposure impaired SDNN during the 24-h study period (p = 0.007). C-reactive protein and fibrinogen levels were significantly increased after diesel exhaust exposure while protein C levels and protein S activity decreased (p < 0.01 for all). Exposure to diesel exhaust fumes resulted in higher C-reactive protein concentration in smokers compared with non-smokers (p < 0.001). CONCLUSION: Short-term exposure to diesel exhaust fumes has a prolonged adverse impact on endothelial function and vascular wall properties, along with impaired heart rate variability, abnormal fibrinolytic activity and increased markers of inflammation. These findings give insights into the mechanisms underlining the increased cardiovascular risk of subjects regularly exposed to diesel exhaust fumes.

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In this study we investigated the implication of NLRP3 inflammasomes in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and rheumatoid arthritis-usual interstitial pneumonia (RA-UIP).NLRP3 inflammasome activation at baseline and following stimulation with lipopolysaccharide/ATP was evaluated by measuring interleukin (IL)-1ß and IL-18 levels released in the bronchoalveolar lavage fluid (BALF) fluid and by cultures of BALF cells. IL-1ß and IL-18 levels were significantly elevated in the BALF and BALF macrophage cultures from RA-UIP patients, consistent with pre-existing inflammasome activation in these patients. In contrast, in IPF, BALF levels of IL-1ß were significantly less elevated relative to RA-UIP and IL-18 was lower than controls. Furthermore, upon inflammasome stimulation, IPF BALF macrophage cultures failed to upregulate IL-1ß and partly IL-18 secretion, in contrast to controls, which showed robust IL-1ß and IL-18 upregulation. Interestingly, RA-UIP BALF cell cultures treated with lipopolysaccharide/ATP showed a potent stimulation of IL-18 secretion but not IL-1ß, the latter being already elevated in the unstimulated cultures, while examination of the intracellular IL-1ß levels in RA-UIP BALF cells upon NLRP3 inflammasome stimulation showed a significant upregulation of IL-1ß suggesting the NLRP3 pathway could be further activated.Taken together, our results suggest distinct inflammasome activation profiles between autoimmune and idiopathic lung fibrosis.

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Present generations are being repeatedly exposed to different types and doses of non-ionizing radiation (NIR) from wireless technologies (FM radio, TETRA and TV stations, GSM and UMTS phones/base stations, Wi-Fi networks, DECT phones). Although there is controversy on the published data regarding the non-thermal effects of NIR, studies have convincingly demonstrated bioeffects. Their results indicate that modulation, intensity, exposure duration and model system are important factors determining the biological response to irradiation. Attempting to address the dependence of NIR bioeffectiveness on these factors, apoptosis in the model biological system Drosophila melanogaster was studied under different exposure protocols. A signal generator was used operating alternatively under Continuous Wave (CW) or Frequency Modulation (FM) emission modes, at three power output values (10 dB, 0, -10 dB), under four carrier frequencies (100, 395, 682, 900 MHz). Newly emerged flies were exposed either acutely (6 min or 60 min on the 6th day), or repeatedly (6 min or 60 min daily for the first 6 days of their life). All exposure protocols resulted in an increase of apoptotic cell death (ACD) observed in egg chambers, even at very low electric field strengths. FM waves seem to have a stronger effect in ACD than continuous waves. Regarding intensity and temporal exposure pattern, EMF-biological tissue interaction is not linear in response. Intensity threshold for the induction of biological effects depends on frequency, modulation and temporal exposure pattern with unknown so far mechanisms. Given this complexity, translating such experimental data into possible human exposure guidelines is yet arbitrary.

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STUDY OBJECTIVES: The most recent idiopathic pulmonary fibrosis (IPF) guidelines include obstructive sleep apnea (OSA) among the IPF-associated comorbidities. Furthermore, they recognize the paucity of studies related to continuous positive airway pressure(CPAP) treatment in this patient group and call for intensive research in this field. Our aim was to assess the effect of CPAP treatment on sleep and overall life quality parameters, morbidity, and mortality in IPF patients with OSA. METHODS: Ninety-two treatment-naive, newly diagnosed, consecutive IPF patients underwent overnight-attended polysomnography (PSG). In those patients with an apnea-hypopnea index (AHI) of ≥15, therapy with CPAP was initiated. Patients were divided into poor and good CPAP compliance groups. All subjects completed multiple quality-of-life and sleep instruments before CPAP initiation and at 1 year after the start of CPAP treatment. RESULTS: The good CPAP compliance group (37 patients) showed statistically significant improvement in all quality-of-life and sleep instruments after 1 year's CPAP treatment. The poor CPAP compliance group (18 patients) showed significant changes of smaller strength only in a minority of the used instruments. During the 24-month follow-up period after CPAP initiation, three patients from the CPAP poor compliance group died, whereas all patients from the good CPAP compliance group remained alive. CONCLUSION: Early OSA recognition and treatment is crucial in a fatal disease such as IPF. Effective CPAP treatment in IPF patients with OSA results in a significant improvement in daily living activities and quality of sleep and life. Good CPAP compliance appears to improve mortality.

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Adult-onset Still's disease is an inflammatory multisystemic disease of unknown etiology. Pleuritis is the most common pulmonary manifestation and pleural effusions are usually exudates with a predominance of neutrophils. We report a case of an eosinophilic pleural effusion as a novel and hitherto unrecognized manifestation of active adult-onset Still's disease. We also observed a marked NLRP3 inflammasome activation with increased production of IL-1ß which coincided with the development and resolved upon remission of the pleural effusion suggesting a possible novel pathogenetic pathway for the development of pleural effusions in the context of the auto-inflammatory disorders.

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BACKGROUND: The recent literature shows an increased incidence of obstructive sleep apnea (OSA) in patients with idiopathic pulmonary fibrosis (IPF). On the other hand, there are no published studies related to continuous positive airway pressure (CPAP) treatment in this patient group. Our aim was to assess the effect of CPAP on sleep and overall life quality parameters in IPF patients with OSA and to recognize and overcome possible difficulties in CPAP initiation and acceptance by these patients. METHODS: Twelve patients (ten males and two females, age 67.1 ± 7.2 years) with newly diagnosed IPF and moderate to severe OSA, confirmed by overnight attended polysomnography, were included. Therapy with CPAP was initiated after a formal in-lab CPAP titration study. The patients completed the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI), the Functional Outcomes in Sleep Questionnaire (FOSQ), the Fatigue Severity Scale (FSS), the SF-36 quality of life questionnaire, and the Beck Depression Inventory (BDI) at CPAP initiation and after 1, 3, and 6 months of effective CPAP therapy. RESULTS: A statistically significant improvement was observed in the FOSQ at 1, 3, and 6 months after CPAP initiation (baseline 12.9 ± 2.9 vs. 14.7 ± 2.6 vs. 15.8 ± 2.1 vs. 16.9 ± 1.9, respectively, p = 0.02). Improvement, although not statistically significant, was noted in ESS score (9.2 ± 5.6 vs. 7.6 ± 4.9 vs. 7.5 ± 5.3 vs. 7.7 ± 5.2, p = 0.84), PSQI (10.7 ± 4.4 vs. 10.1 ± 4.3 vs. 9.4 ± 4.7 vs. 8.6 ± 5.2, p = 0.66), FSS (39.5 ± 10.2 vs. 34.8 ± 8.5 vs. 33.6 ± 10.7 vs. 33.4 ± 10.9, p = 0.44), SF-36 (63.2 ± 13.9 vs. 68.9 ± 13.5 vs. 72.1 ± 12.9 vs. 74.4 ± 11.3, p = 0.27), and BDI (12.9 ± 5.5 vs. 10.7 ± 4.3 vs. 9.4 ± 4.8 vs. 9.6 ± 4.5, p = 0.40). Two patients had difficulty complying with CPAP for a variety of reasons (nocturnal cough, claustrophobia, insomnia) and stopped CPAP use after the first month, despite intense follow-up by the CPAP clinic staff. Heated humidification was added for all patients in order to improve the common complaint of disabling nocturnal cough. CONCLUSION: Effective CPAP treatment in IPF patients with OSA results in a significant improvement in daily living activities based on the FOSQ, namely an OSA-specific follow-up instrument. Improvement was also noted in other questionnaires assessing quality of life, though not to a statistically significant degree, probably because of the multifactorial influences of IPF on physical and mental health. The probability of poor CPAP compliance was high and could only be eliminated with intense follow-up by the CPAP clinic staff.

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