Human Protoparvovirus DNA and IgG in Children and Adults with and without Respiratory or Gastrointestinal Infections.

Three human protoparvoviruses, bufavirus (BuV), tusavirus (TuV) and cutavirus (CuV), have recently been discovered in diarrheal stool. BuV has been associated with diarrhea and CuV with cutaneous T-cell lymphoma, but there are hardly any data for TuV or CuV in stool or respiratory samples. Hence, using qPCR and IgG enzyme immunoassays, we analyzed 1072 stool, 316 respiratory and 445 serum or plasma samples from 1098 patients with and without gastroenteritis (GE) or respiratory-tract infections (RTI) from Finland, Latvia and Malawi. The overall CuV-DNA prevalences in stool samples ranged between 0-6.1% among our six patient cohorts. In Finland, CuV DNA was significantly more prevalent in GE patients above rather than below 60 years of age (5.1% vs 0.2%). CuV DNA was more prevalent in stools among Latvian and Malawian children compared with Finnish children. In 10/11 CuV DNA-positive adults and 4/6 CuV DNA-positive children with GE, no known causal pathogens were detected. Interestingly, for the first time, CuV DNA was observed in two nasopharyngeal aspirates from children with RTI and the rare TuV in diarrheal stools of two adults. Our results provide new insights on the occurrence of human protoparvoviruses in GE and RTI in different countries.

Smoke exposure from chronic biomass burning induces distinct accumulative systemic inflammatory cytokine alterations compared to tobacco smoking in healthy women.

Long-term exposure to biomass-burning smoke (BS) is associated with chronic obstructive pulmonary disease (COPD), asthma, and other chronic inflammatory lung diseases. BS results from such processes as the burning of wood for indoor cooking and heating, with women and children having the highest exposure rate. This study aimed to analyze the accumulative alterations in cytokine levels associated with BS (from wood) compared to tobacco smoke (TS) in healthy adult women. The levels of 27 cytokines were analyzed in the serum of 100 women, including 40 tobacco smokers/non-exposed to BS (TS+/BS-), 30 never-smokers/exposed to BS (TS-/BS+) and 30 never-smokers/non-exposed to BS (TS-/BS-) as controls, using 27-Plex immunoassay. The chronic BS exposure index was rated at ≥100 h-years, and the tobacco-smoking index was ≥10 pack-years. Compared to TS-/BS-, TS+/BS- had higher levels of IL-2, IL-9, MCP-1, MIP-1ß, and VEGF, while TS-/BS+ showed higher levels of IL-1ra, IL-6, IL-8, Eotaxin, IP-10, RANTES, and VEGF, presenting a distinct inflammatory profile that may favor an eosinophil-derived inflammatory response to BS exposure. Compared to TS+/BS-, TS-/BS+ expressed higher levels of IP-10 and IL-8, but lower levels of IL-2 and MIP-1ß. Gene-disease database analysis showed that altered cytokines in both TS+/BS- and TS-/BS+ are associated with asthma, COPD, lung fibrosis, and lung cancer. In conclusion, chronic BS exposure induces distinct systemic inflammatory cytokine alterations compared to tobacco smokers in healthy women. These findings provide new insights into how long-term exposure to BS affects the inflammatory response-and potentially the health-of adult women.

Circulating 25-hydroxyvitamin D concentration and cause-specific mortality in the Melbourne Collaborative Cohort Study.

Vitamin D deficiency is associated with higher all-cause mortality, but associations with specific causes of death are unclear. We investigated the association between circulating 25-hydroxyvitamin D (25(OH)D) concentration and cause-specific mortality using a case-cohort study within the Melbourne Collaborative Cohort Study (MCCS). Eligibility for the case-cohort study was restricted to participants with baseline dried blood spot samples and no pre-baseline diagnosis of cancer. These analyses included participants who died (n = 2307) during a mean follow-up of 14 years and a sex-stratified random sample of eligible cohort participants ('subcohort', n = 2923). Concentration of 25(OH)D was measured using liquid chromatography-tandem mass spectrometry. Cox regression, with Barlow weights and robust standard errors to account for the case-cohort design, was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for cause-specific mortality in relation to 25(OH)D concentration with adjustment for confounders. Circulating 25(OH)D concentration was inversely associated with risk of death due to cancer (HR per 25 nmol/L increment = 0.88, 95 % CI 0.78-0.99), particularly colorectal cancer (HR = 0.75, 95 % CI 0.57-0.99). Higher 25(OH)D concentrations were also associated with a lower risk of death due to diseases of the respiratory system (HR = 0.62, 95 % CI 0.43-0.88), particularly chronic obstructive pulmonary disease (HR = 0.53, 95 % CI 0.30-0.94), and diseases of the digestive system (HR = 0.44, 95 % CI 0.26-0.76). Estimates for diabetes mortality (HR = 0.64, 95 % CI 0.33-1.26) and cardiovascular disease mortality (HR = 0.90, 95 % CI 0.76-1.07) lacked precision. The findings suggest that vitamin D might be important for preventing death due to some cancers, respiratory diseases, and digestive diseases.

Use of procalcitonin, neopterin, haptoglobin, serum amyloid A and proinflammatory cytokines in diagnosis and prognosis of bovine respiratory disease in feedlot calves under field conditions.

Bovine respiratory diseases (BRD) have long been considered a serious problem that causes major economic losses in feedlot calves (FC). This study aimed to determine the diagnostic and prognostic effect of selected biological markers including, procalcitonin (PCT), neopterin (NP), proinflammatory cytokines (IL-1ß, IL-8, TNF-α, IF-γ), haptoglobin (HP) and serum amyloid A (SAA) on FC with BRD under field conditions. Sixty-nine FC that were identified to be infected with Mannheimia haemolytica and Histophilus somni and had different clinical respiratory signs (diseased group) were selected for this study. In addition, 20 healthy FC have been selected as a control group. We have detected higher serum levels of PCT, NP, HP, SAA, IL-1ß, IL-8, TNF-α and IF-γ in diseased FC group compared with the control group. All tested markers revealed a high level of discrimination between BRD infected FC and healthy ones (AUC > 0.90). Moreover, the obtained data showed a high degree of prognostic accuracy for PCT, NP, IL-8, HP, IF-γ and IL-1ß in predicting treatment response of FC with BRD at the selected thresholds (AUC = 0.99, 0.99, 0.97, 0.93, 0.88 and 0.82, respectively). Significant inhibition was observed for the selected biochemical markers in treated FC 7 days post-treatment. In conclusion, this study showed that BRD in FC was associated with significant alterations in serum APPs, proinflammatory cytokines, PCT and NPT levels. Furthermore, it demonstrated that these serum biomarkers are much higher in FC with BRD compared to recovered ones. Our data suggest that the measurement of PCT, NPT, APPs and cytokines together with the clinical examination may be a useful diagnostic and prognostic tool for assessment of FC naturally infected with M. haemolytica and H. somni.

Exhaled nitric oxide in pediatric patients with respiratory disease.

Measurement of nitric oxide (NO) levels in exhaled air from the upper and lower airways is currently used as a non-invasive marker of inflammation in respiratory diseases. Assessment of NO exhaled from the lower air respiratory tract is considered to be a quick method for confirmation and control of asthma in patients as well as an estimation of treatment efficiency. The main aim of this study was to determine differences between levels of exhaled nitric oxide (fractional exhaled NO; FeNO) in patients with respiratory disease as measured by an electrochemical analyzer. Measurements were taken in 352 pediatric patients aged 4-17 with cystic fibrosis (CF) (n = 43), asthma (n = 69), allergic rhinitis (AR) (n = 70), asthma and AR (n = 128) and non-diseased children (n = 42) recruited from the Allergology Outpatient Department, Provincial Hospital No 2, Rzeszów. The second objective of this study was to assess any correlations between FeNO and clinical parameters of patients. The level of FeNO in patients with CF was normal when compared with control subjects (10.8 ± 2.9 versus 11.4 ± 6 ppb). We found significantly higher FeNO in patients with asthma (26.6 ± 15.3 ppb, p < 0.001), AR (18.4 ± 9.6 ppb, p < 0.01) as well as in patients with both asthma and AR (43.3 ± 31.1 ppb, p < 0.001) when compared to healthy children. Statistical analysis revealed a positive correlation between FeNO and age, height and weight of control subjects, and height in children with AR. FeNO was independent of sex, BMI, spirometry and blood results as well as the type of residence in control children and subjects with CF, asthma, AR and combined asthma and AR. In conclusion, we found normal levels of FeNO in children with CF and elevated levels in patients with asthma, AR and combined asthma and AR as compared to control subjects. Due to conflicting data, there is still a need for additional research, especially related to regarding factors that affect FeNO levels in respiratory disease.

Low interferon-gamma release in response to phytohemagglutinin predicts the high severity of diseases.

A clinically useful immune biomarker could potentially assist clinicians in their decision making. We stimulated T-cell proliferation to secret interferon gamma (IFN-γ) by phytohemagglutinin, and then measured the production of IFN-γ (mitogen value [M value]). We aimed to determine the relationship between the M value, clinical severity, and outcomes of diseases.In all, 484 patients admitted to intensive care units were enrolled in this retrospective study. The Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were collected within the first 24 hours. M value, C-reaction protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR), and routine blood tests were analyzed and collected during the study.When APACHE II scores were greater than 15 and M values were less than 6, the hospital mortality rose in a straight line. There was an inverse correlation between APACHE II score and M value (rs = -0.212, P < .001). There was a positive correlation between M value and lymphocyte numbers (b' = 0.249, P < .001); however, there was an inverse correlation between M value and WBC (b' = -0.230, P < .001), and ESR (b' = -0.100, P = .029). Neurological diseases had the greatest influence on APACHE II scores (b' = 10.356, P < .001), whereas respiratory diseases had the greatest influence on M value (b' = 1.933, P < .001). Furthermore, in the respiratory system, severe pneumonia had a greater influence on M value. Taking the APACHE II score as the gold standard, the area under the curve of M was 0.632 (95% confidence interval [CI] 0.575-0.690, P < .001), PCT was 0.647 (95% CI 0.589-0.705, P < .001), CRP was 0.570 (95% CI 0.511-0.629, P = .022), and ESR was 0.553 (95% CI 0.494-0.612, P = .078). Divided by M value = 5, the positive predictive value of the M value is 37.22% (115/309) and negative predictive value is 75.43% (132/175).The results show that the M values, PCT, and CRP were better than ESR to predict the severity of diseases. The number and proportion of lymphocytes also affected the result of the M value. To a certain extent, the M value may be a clinically useful immune biomarker, which may help clinicians objectively evaluate the severity of diseases, especially in the respiratory system.

Plasma vitamin C concentrations and risk of incident respiratory diseases and mortality in the European Prospective Investigation into Cancer-Norfolk population-based cohort study.

BACKGROUND/OBJECTIVES: Cancerous and non-cancerous respiratory diseases are common and contribute significantly to global disease burden. We aim to quantify the association between plasma vitamin C concentrations as an indicator of high fruit and vegetable consumption and the risk of incident respiratory diseases and associated mortality in a general population. SUBJECTS/METHODS: Nineteen thousand three hundred and fifty-seven men and women aged 40-79 years without prevalent respiratory diseases at the baseline (1993-1997) and participating in the European Prospective Investigation into Cancer (EPIC)-Norfolk study in the United Kingdom were followed through March 2015 for both incidence and mortality from respiratory diseases. RESULTS: There were a total of 3914 incident events and 407 deaths due to any respiratory diseases (excluding lung cancers), 367 incident lung cancers and 280 lung cancer deaths during the follow-up (total person-years >300,000 years). Cox's proportional hazards models showed that persons in the top quartiles of baseline plasma vitamin C concentrations had a 43% lower risk of lung cancer (hazard ratio (HR) 0.57; 95% confidence interval (CI): 0.41-0.81) than did those in the bottom quartile, independently of potential confounders. The results are similar for any non-cancerous respiratory diseases (HR 0.85; 0.77-0.95), including chronic respiratory diseases (HR 0.81; 0.69-0.96) and pneumonia (HR 0.70; 0.59-0.83). The corresponding values for mortality were 0.54 (0.35-0.81), 0.81 (0.59-1.12), 0.85 (0.44-1.66) and 0.61 (0.37-1.01), respectively. Confining analyses to non-smokers showed 42% and 53% risk reduction of non-smoking-related lung cancer incidence and death. CONCLUSIONS: Higher levels of vitamin C concentrations as a marker of high fruit and vegetable consumption reduces the risk of cancerous and non-cancerous respiratory illnesses including non-smoking-related cancer incidence and deaths.

Tuberculose em População Indígena Autodeclarada no Estado do Paraná / Tuberculosis in Self-declares Indigenous People in the State of Parana

Objetivo: Descrever o perfil epidemiológico e o percentual de cura da tuberculose (TB) na população indígena no Estado do Paraná. Metodologia: Trata-se de um estudo epidemiológico retrospectivo realizado a partir de 36.889 casos de tuberculose obtidos por meio do Sistema de Informação de Agravos de Notificação do Estado do Paraná, no período de 2001 a 2012. Foram selecionadas variáveis clínicas contemplando dados da população indígena notificada com tuberculose no Estado do Paraná, forma clínica da tuberculose, situação de encerramento e variáveis sociodemográficas (sexo, idade, escolaridade e zona de domicílio). Utilizou-se análise exploratória das variáveis por meio da distribuição de frequência absoluta e relativas. Resultados: Considerando a população total do estudo, 174 eram indígenas com predomínio de tuberculose na forma pulmonar (85%), apresentando coeficiente de incidência elevado principalmente no sexo masculino (58,6%), em residentes na zona rural (67,2%), sendo que, 72,4% obtiveram a cura. A faixa etária com idade entre 31-40 anos (20,1%) apresentou o maior número de casos notificados. Conclusão: A população que se declarou indígena apresentou características sociodemográficas similares à população geral com tuberculose, entretanto, evidenciou-se vulnerabilidade na população declarada indígena para incidência e cura da doença. (AU)

Objective: To describe the epidemiological profile and cure rate of tuberculosis (TB) in the indigenous population in the state of Paraná. Methodology: This is a retrospective epidemiological study based on 36.889 cases of tuberculosis obtained through the Paraná Notification of Injury Information System from 2001 to 2012. Clinical variables were selected contemplating data from the indigenous population reported with tuberculosis in the State of Paraná, clinical form of tuberculosis, closure and sociodemographic variables (sex, age, schooling and domicile area. An exploratory analysis of the data was used through the absolute and relative frequency distribution. Results: Considering the total population of the study, 174 were indigenous with a predominance of tuberculosis in the pulmonary form (85%), with a high incidence rate, mainly in males (58,6%), in rural residents (67,2%), being that 72,4% obtained a cure. The age group between 31-40 years (20,1%) had the highest number of reported cases. Conclusion: The population that declared themselves indigenous had sociodemographic characteristics similar to the general population with tuberculosis. However, it showed a vulnerability in the population declared indigenous for incidence and cure of the disease. (AU)

Serum Beta Carotene and Overall and Cause-Specific Mortality.

RATIONALE: Although the health effects of beta carotene have been studied extensively, a systematic examination of serum concentrations and long-term mortality, including cardiovascular disease mortality, has not been reported. OBJECTIVE: Explore whether serum beta carotene is associated with overall and cause-specific mortality and to elucidate the strength and dose-response of the association. METHODS AND RESULTS: We conducted a prospective serological analysis of 29 103 men in the ATBC study (Alpha-Tocopherol, Beta-Carotene Cancer Prevention). During 31 years of follow-up, 23 796 deaths occurred, including deaths because of cardiovascular disease (9869), cancer (7692), respiratory disease (2161), diabetes mellitus (119), injuries and accidents (1255), and other causes (2700). Serum beta carotene was assayed using high-performance liquid chromatography. Adjusting for major risk factors measured, men with higher serum beta carotene had significantly lower all-cause mortality (hazard ratios=0.81, 0.71, 0.69, and 0.64 for quintile 2 (Q2)-Q5 versus Q1, respectively; Ptrend<0.0001). Serum beta carotene was significantly associated with risk of death from cardiovascular disease, heart disease, stroke, cancer, respiratory disease, diabetes mellitus, injuries and accidents, and other causes (Q5 versus Q1, hazard ratio=0.21-0.73, all Ptrend<0.0001). The all-cause mortality association was not materially impacted by adjustment for fruit and vegetable consumption (albeit, estimated with some measurement error) and was generally similar across subgroups of smoking intensity, alcohol consumption, trial supplementation, and duration of follow-up, but was significantly modified by age, years of smoking, and body mass index, with stronger inverse associations among men who were younger, smoked fewer years, and had a lower body mass index (all Pinteraction≤0.0025). CONCLUSIONS: This study provides evidence that higher beta carotene biochemical status is associated with lower overall, cardiovascular disease, heart disease, stroke, cancer, and other causes of mortality. The dose-response associations over a 30-year period were not attenuated by adjustment for other important risk factors and support greater fruit and vegetable consumption as a means to increase beta carotene status and promote longevity.

Minimally invasive esophagectomy in the prone position improves postoperative outcomes: role of C-reactive protein as an indicator of surgical invasiveness.

BACKGROUND: The aim of the study was to assess serum C-reactive protein (CRP) level immediately after minimally invasive esophagectomy (MIE) as a surrogate of surgical invasiveness in patients who underwent esophagectomy. METHODS: In total, 104 patients were enrolled in the study: 37 patients underwent MIE in the left lateral decubitus position (MIE-LP) and 67 patients underwent MIE in the prone position (MIE-PP). Serum CRP levels were assessed on POD 1, 3, 5, and 7 after MIE, and were compared with surgical outcomes and duration of systemic inflammatory response syndrome (SIRS) to investigate less invasiveness of the MIE. RESULTS: Reduced serum CRP level on POD 1 was associated with PP during MIE (P < 0.001) and decreased blood loss (P = 0.03). MIE-PP was identified as a significant independent predictor of reduced CRP level on POD 1 (odds ratio 3.65, P = 0.042). CRP level on POD 7 was associated with gender (P = 0.02), position of MIE (P = 0.011), blood loss (P = 0.02), and respiratory complications and/or anastomotic leakage (P < 0.001). Postoperative respiratory and/or anastomotic complication was identified as a significant predictor of elevated serum CRP level on POD 7 (odds ratio 3.44, P = 0.048). Shorter duration of SIRS was shown in the patients with reduced serum CRP level on POD 1 and 7 (P = 0.03 and P < 0.001, respectively). CONCLUSION: Serial assessments of serum CRP level immediately after MIE may be a possible indicator that can reflect surgical invasiveness and postoperative complications.

Health Effects of Airline Cabin Environments in Simulated 8-Hour Flights.

INTRODUCTION: Commercial air travel is usually without health incidents. However, there is a view that cabin environments may be detrimental to health, especially flights of 8 h or more. Concerns have been raised about deep vein thrombosis, upper respiratory tract infections, altitude sickness, and toxins from the engines. METHODS: Passenger cabin simulators were used to achieve a comparative observational study with 8-h flights at pressures equivalent to terrestrial altitudes of ground, 4000, 6000, and 8000 ft. Biomarkers of thrombosis (D-Dimer), inflammation (interleukin-6), and respiratory dysfunction (FEV1) and oxygen saturation (Spo2) were measured, as well as pulse and blood pressure. The wellbeing of the passengers was also monitored. RESULTS: During 36 flights, 1260 healthy subjects [626 women (F) and 634 men (M) (mean age = 43, SD = 16)] were assessed. Additionally, 72 subjects with chronic obstructive pulmonary disease (F = 32, M = 40, mean age = 48, SD = 17) and 74 with heart failure (F = 50, M = 24, mean age = 54, SD = 14) contributed to 11 flights. Additionally, 76 normal controls were observed while engaged in a usual day's work (F = 38, M = 38, mean age = 39, SD = 15). There were no health-significant changes in D-Dimer, interleukin-6, or FEV1. Spo2 varied as expected, with lowest values at 8000 ft and in patients with cardiopulmonary disease. The only differences from the controls were the loss of the normal diurnal variations in interleukin-6 and D-Dimer. DISCUSSION: This very large, comparative, controlled study provides much reassurance for the traveling public, who use airline flights of up to 8 h. We did not show evidence of the development of venous thrombosis, inflammation, respiratory embarrassment, nor passenger distress. No significant symptoms or adverse effects were reported.Ideal Cabin Environment (ICE) Research Consortium of the European Community 6th Framework Programme. Health effects of airline cabin environments in simulated 8-hour flights. Aerosp Med Hum Perform. 2017; 88(7):651-656.

Long-Term Impact of Postoperative Complications on Cancer Recurrence Following Lung Cancer Surgery.

BACKGROUND: Postoperative complications are associated with poor cancer-specific survival in various types of cancer surgery. Recent studies suggest that systemic inflammation induced by surgical trauma can accelerate the adhesion of circulating tumor cells to the vascular endothelium of distant organs, resulting in early cancer recurrence. We investigated the impact of postoperative cardiopulmonary complications on cancer recurrence following lung cancer surgery. METHODS: From a prospective database of 675 consecutive patients who underwent curative surgery for lung cancer between 2007 and 2012, the incidence of postoperative cardiopulmonary complications, white blood cell counts, and C-reactive protein levels were evaluated in the acute phase after surgery. Four patients had both cardiovascular and respiratory complications. The remaining 671 patients were divided into 3 groups: patients without cardiopulmonary complications; those with cardiovascular complications; and those with respiratory complications. The incidence of cancer recurrence was compared among the three groups. RESULTS: Postoperative cardiovascular or respiratory complications were identified in 94 (14%) or 25 (4%) patients, respectively. Postoperative white blood cell counts and C-reactive protein levels were significantly higher in those with postoperative respiratory complications than in those without. There was a significantly higher incidence of cancer recurrence in those with postoperative respiratory complications than in those without (48.0 vs. 16.8%; p < 0.0001). Multiple regression analysis adjusted for age, sex, and pathological staging showed that the incidence of postoperative respiratory complications was a significant predictor of cancer recurrence. CONCLUSIONS: The presence of respiratory complications following lung cancer surgery was a significant predictor of cancer recurrence.

Procalcitonin as a biomarker in equine chronic pneumopathies.

BACKGROUND: Procalcitonin (PCT), a precursor protein of the hormone calcitonin, is a sensitive inflammatory marker in human medicine, which is primarily used for diagnosis of bacterial sepsis, but is also useful in diagnosis of exacerbation of asthma and COPD. In this study, PCT was evaluated as a potential biomarker for different chronic pneumopathies in the horse using an equine specific ELISA in comparison to established clinical markers and different interleukins. Sixty-four horses were classified as free of respiratory disease, recurrent airway obstruction (RAO), inflammatory airway disease (IAD) or chronic interstitial pneumopathy (CIP) using a scoring system. PCT concentrations were measured in plasma (n = 17) and in the cell-free supernatant of bronchoalveolar lavage (n = 64). PCT concentrations were correlated to interleukins IL-1ß and IL-6 in BALF, clinical findings and BALF cytology. RESULTS: The median PCT concentrations in plasma were increased in respiratory disease (174.46 ng/ml, n = 7) compared to controls (13.94 ng/ml, n = 10, P = 0.05) and correlated to PCT in BALF supernatant (rs = 0.48). Compared to controls (5.49 ng/ml, n = 15), median PCT concentrations in BALF supernatant correlated to the overall clinical score (rs = 0.32, P = 0.007) and were significantly increased in RAO (13.40 ng/ml, n = 21) and IAD (16.89 ng/ml, n = 16), while no differences were found for CIP (12.02 ng/ml, n = 12). No significant increases were found for IL-1 and IL-6 between controls and respiratory disease in general as well as different disease groups. CONCLUSIONS: Although some correlations were found between PCT in plasma, BALF supernatant and clinical scores, PCT in BALF does not seem to be a superior marker compared to established clinical markers. PCT in plasma seems to be more promising and a greater number of samples should be evaluated in further studies.

Biomarkers of patient intrinsic risk for upper and lower airway injury after exposure to the World Trade Center atrocity.

BACKGROUND: High rates of upper and lower airways disease have occurred in Fire Department of the City of New York (FDNY) workers exposed to the World Trade Center (WTC) disaster site. Most experienced acute declines in pulmonary function, and some continued to experience decline over 14 years of follow-up. Similarly, some with rhinosinusitis had symptoms requiring sinus surgery. AIM: To increase generalizability of biomarker investigation, we describe biomarkers of risk for upper and lower airway injury that do not require stored serum. METHODS: We review WTC biomarker literature. RESULTS: Cytokines expressed in stored serum from the first 6 months post-9/11 can identify individuals at higher risk for future abnormal pulmonary function. CONCLUSION: This research will help identify individuals at high risk of lung and sinus disease that develop after these, or future, irritant exposures for intensive monitoring and treatment. It may also identify targets for effective therapeutic interventions. Am. J. Ind. Med. 59:788-794, 2016. © 2016 Wiley Periodicals, Inc.

High prevalence of cardiovascular and respiratory abnormalities in advanced, intensively treated (transplanted) myeloma: The case for 'late effects' screening and preventive strategies.

OBJECTIVES: Modern management of myeloma has significantly improved survival, with increasing numbers of patients living beyond a decade. However, little is known about the long-term cardiovascular and respiratory status of intensively treated and multiply relapsed survivors. METHODS: We performed detailed cardiovascular and respiratory evaluations in patients with intensively treated, advanced but stable myeloma. All patients had received at least two lines of treatment, including at least one haematopoietic stem cell transplantation procedure, but had stable, controlled disease and were off active treatment at the time of evaluation. RESULTS: Thirty-two patients with a median duration of 6 years (range 2-12) from original diagnosis of myeloma and three lines (range 2-6) of treatment were evaluated. Despite normal physical examination in the majority, there was a high prevalence of sub-clinical cardiac and respiratory dysfunction, reflected by abnormalities of electrocardiography (45%), echocardiography (50%), serum N-terminal pro-B-type natriuretic peptide level (NT-pro-BNP, 50%), and pulmonary function testing (45%). NT-pro-BNP level correlated negatively with quality of life (P = 0.012) and positively with serum ferritin (P = 0.027). Dyspnoea score correlated with BMI (P = 0.001). Risk factors for cardiovascular disease (obesity, hypertension, hyperlipidaemia, and hyperinsulinaemia) were common. DISCUSSION: Even in the absence of overt clinical features, the majority of intensively treated long-term survivors of myeloma have established cardiovascular and/or respiratory dysfunction, above levels expected in the general population of a similar age. CONCLUSION: This study supports routine screening and lifestyle modification combined with primary and secondary preventive strategies to reduce cardiovascular and respiratory disease and to preserve quality of life in transplanted myeloma patients.

Dietary supplementation with radionuclide free food improves children's health following community exposure to (137)Cesium: a prospective study.

BACKGROUND: Following the Chernobyl nuclear disaster of 1986, vast areas of Ukraine became contaminated with radionuclides. We examined health effects of school-based food intervention for children in a rural region Narodichi, Ukraine, exposed to low-level radiation through diet of locally produced foods. Until 1995, children received three daily meals with low content of artificial radionuclides which were subsequently reduced to two. METHODS: Annual health screening data (1993-1998) were examined using a quasi-experimental regression discontinuity analysis (n = 947 children; 3,573 repeated measurements). Generalized Estimating Equation models evaluated effect of the food supplementation reduction on hematologic measures and prevalence of anemia, acute respiratory illnesses and diseases of immune system. RESULTS: Prior improvement of several hematologic parameters diminished after food supplementation was reduced. From 1995 to 1996, levels of hemoglobin and erythrocytes decreased from 12.63 (95% CI: 12.56-12.71) to 12.46 g/dL (% CI: 12.39-12.52) and from 4.10 (95% CI: 4.07-4.12) to 4.02 (95% CI: 4.00-4.04) × 10(12)/L, respectively. In agreement, the prevalence ratio (PR) of previously declining anemia increased from 0.57 to 1.31 per year (p(interaction )< .0001). The relation between food supplementation and hemoglobin levels was modified by residential (137)Cs soil levels. After food supply reduction, PR of common cold and bronchitis increased from 1.27 to 2.32 per year (p(interaction) = 0.01) and from 1.09 to 1.24 per year (p(interaction) = 0.43), respectively. CONCLUSIONS: Food supplementation provided by the Ukrainian government likely prevented development of anemia in many of the children residing in the contaminated district. Food supplementation after the community exposure to radioactivity through a diet of locally grown foods should be considered as an effective approach to reduce adverse health effects of radiation.

Lifestyle-Related Factors and Atopy in Seven Danish Population-Based Studies from Different Time Periods.

BACKGROUND: The prevalence of allergic respiratory disease tends to increase in populations that adopt the so-called Westernized lifestyle. We investigated the association between atopy and several possible lifestyle-related factors in seven Danish population-based studies. METHODS: A total of 20048 persons participated in the seven studies. We used logistic regression to analyse the associations between possible determinants and atopy defined as serum specific IgE or skin prick test positivity against inhalant allergens. Associations were expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs). In addition, individual participant data meta-analyses were performed. RESULTS: Atopy was significantly associated with younger age (OR per 1 year increase in age: 0.97; 95% CI: 0.97, 0.98); male sex (OR for males versus females: 1.34; 95% CI: 1.24, 1.45), heavy drinking (OR for heavy drinkers versus light drinkers: 1.15; 95% CI: 1.04, 1.27), never smoking (OR for current versus never smokers: 0.73; 95% CI: 0.67, 0.80), and higher educational level (OR for educated versus uneducated: 1.27; 95% CI: 1.15, 1.41). Atopy was not associated with blood pressure, serum total cholesterol, physical activity or body mass except in women only, where we found a positive association (OR for obese vs. normal weight: 1.18; 95% CI: 1.00, 1.39) with ptrend = 0.032. CONCLUSIONS: Of interest for preventive purposes, we found that atopy was associated with some of the reversible lifestyle-related factors that characterize a Westernized lifestyle.

The intake of maqui (Aristotelia chilensis) berry extract normalizes H2O2 and IL-6 concentrations in exhaled breath condensate from healthy smokers - an explorative study.

BACKGROUND: Respiratory diseases are associated with pulmonary oxidative stress and inflammatory processes. Though studies in animal models suggest that dietary polyphenols improve lung injury, no intervention studies were carried out in humans. The aim of this study was to determine whether the intake of an anthocyanin-rich maqui extract improved H2O2 and IL-6 concentrations in exhaled breath condensates (EBCs) from asymptomatic smokers. FINDINGS: 15 asymptomatic smokers with mild cigarette smoking (3 pack-year [2.4 - 7.7]) (mean [CI95%]) were recruited in this exploratory longitudinal study. They ingested 2 g of maqui extract (polyphenol content = 5.18 ± 2.00 g GAE/100 g; FRAP value = 27.1 ± 2.0 mmol Fe(++)/100 g), twice daily for two weeks. EBCs were collected before and after treatment and the changes in H2O2 and IL-6 concentrations were determined by fluorimetry and Elisa, respectively. The EBC contents of H2O2 and IL-6 H2O2 before and after treatment in smokers were also compared with those determined in single EBC samples from 8 healthy non-smokers subjects. At baseline, the H2O2 concentrations were higher and those of IL-6 lower in the smokers than in the non-smokers. Maqui extract significantly decreased H2O2 (p < 0.0002) and increased IL-6 (p < 0.004) in the EBC from smokers. The EBC concentrations of H2O2 and IL-6 after maqui administration did not differ between smokers and non-smokers. CONCLUSIONS: Maqui extract normalizes IL-6 and H2O2 concentrations in EBC from humans with mild smoking habits. If confirmed, these results suggest that dietary polyphenols might be considered as an interesting alternative for the dietary management of respiratory disorders.

Serum 25-hydroxyvitamin D, mortality, and incident cardiovascular disease, respiratory disease, cancers, and fractures: a 13-y prospective population study.

BACKGROUND: Vitamin D is associated with many health conditions, but optimal blood concentrations are still uncertain. OBJECTIVES: We examined the prospective relation between serum 25-hydroxyvitamin D [25(OH)D] concentrations [which comprised 25(OH)D3 and 25(OH)D2] and subsequent mortality by the cause and incident diseases in a prospective population study. DESIGN: Serum vitamin D concentrations were measured in 14,641 men and women aged 42-82 y in 1997-2000 who were living in Norfolk, United Kingdom, and were followed up to 2012. Participants were categorized into 5 groups according to baseline serum concentrations of total 25(OH)D <30, 30 to <50, 50 to <70, 70 to <90, and ≥ 90 nmol/L. RESULTS: The mean serum total 25(OH)D was 56.6 nmol/L, which consisted predominantly of 25(OH)D3 (mean: 56.2 nmol/L; 99% of total). The age-, sex-, and month-adjusted HRs (95% CIs) for all-cause mortality (2776 deaths) for men and women by increasing vitamin D category were 1, 0.84 (0.74, 0.94), 0.72 (0.63, 0.81), 0.71 (0.62, 0.82), and 0.66 (0.55, 0.79) (P-trend < 0.0001). When analyzed as a continuous variable and with additional adjustment for body mass index, smoking, social class, education, physical activity, alcohol intake, plasma vitamin C, history of cardiovascular disease, diabetes, or cancer, HRs for a 20-nmol/L increase in 25(OH)D were 0.92 (0.88, 0.96) (P < 0.001) for total mortality, 0.96 (0.93, 0.99) (P = 0.014) (4469 events) for cardiovascular disease, 0.89 (0.85, 0.93) (P < 0.0001) (2132 events) for respiratory disease, 0.89 (0.81, 0.98) (P = 0.012) (563 events) for fractures, and 1.02 (0.99, 1.06) (P = 0.21) (3121 events) for incident total cancers. CONCLUSIONS: Plasma 25(OH)D concentrations predict subsequent lower 13-y total mortality and incident cardiovascular disease, respiratory disease, and fractures but not total incident cancers. For mortality, lowest risks were in subjects with concentrations >90 nmol/L, and there was no evidence of increased mortality at high concentrations, suggesting that a moderate increase in population mean concentrations may have potential health benefit, but <1% of the population had concentrations >120 nmol/L.