Study protocol of the GRoningen early-PD Ambroxol treatment (GREAT) trial: a randomized, double-blind, placebo-controlled, single center trial with ambroxol in Parkinson patients with a GBA mutation.

BACKGROUND: To date, no disease modifying therapies are available for Parkinson's disease (PD). Since PD is the second most prevalent neurodegenerative disorder, there is a high demand for such therapies. Both environmental and genetic risk factors play an important role in the etiology and progression of PD. The most common genetic risk factor for PD is a mutation in the GBA1(GBA)-gene, encoding the lysosomal enzyme glucocerebrosidase (GCase). The mucolytic ambroxol is a repurposed drug, which has shown the property to upregulate GCase activity in-vitro and in-vivo. Ambroxol therefore has the potency to become a disease modifying therapy in PD, which was the reason to design this randomized controlled trial with ambroxol in PD patients. METHODS: This trial is a single-center, double-blind, randomized, placebo-controlled study, including 80 PD patients with a GBA mutation, receiving either ambroxol 1800 mg/day or placebo for 48 weeks. The primary outcome measure is the Unified Parkinson's Disease Rating Scale motor subscore (part III) of the Movement Disorder Society (MDS-UPDRSIII) in the practically defined off-state at 60 weeks (after a 12-week washout period). Secondary outcomes include a 3,4-dihydroxy-6-18F-fluoro-I-phenylalanine ([18F]FDOPA) PET-scan of the brain, Magnetic Resonance Imaging (with resting state f-MRI and Diffusion Tensor Imaging), GCase activity, both intra- and extracellularly, sphingolipid profiles in plasma, Montreal Cognitive Assessment (MoCA), quality of life (QoL) measured by the Parkinson's Disease Questionnaire (PDQ-39) and the Non-Motor Symptom Scale (NMSS) questionnaire. DISCUSSION: Ambroxol up to 1200 mg/day has shown effects on human cerebrospinal fluid endpoints, which supports at least passage of the blood-brain-barrier. The dose titration in this trial up to 1800 mg/day will reveal if this dose level is safe and also effective in modifying the course of the disease. TRIAL REGISTRATION: NCT05830396. Registration date: March 20, 2023.

Climatic controls of ecohydrological responses in the highlands of northern Ethiopia.

Climate variability and recurrent droughts have a strong negative impact on agricultural production and hydrology in the highlands northern Ethiopia. Since the 1980s, numerous mitigation and land rehabilitation measures have been implemented by local and national authorities to reduce these impacts, are often poorly effective. As underlying reason may be that controlling relationships between climate and ecohydrology at medium-sized catchments (10-10,000km2) of semi-arid highlands are not well known. We investigated trends and relationships in precipitation, temperature, streamflow, and net primary productivity (NPP). The results were mixed, with both significant increasing and decreasing trends for temperature and streamflow. Precipitation time series did not show a significant trend for the majority of stations, both over the years and over each season, except for a few stations. A time series indicated a significant abrupt increase of NPP in annual, seasonal and monthly timescale. Cross-correlation and regression analysis indicate precipitation and maximum temperature were the dominant climatic variables in the Geba catchment for streamflow and NPP. In view of these results, also land use and land cover change over the past three decades was analysed as a possible factor of importance, as human intervention, may affect streamflow and NPP. Factors that mainly correlate with streamflow and NPP are precipitation and maximum temperature. Important interventions that appear beneficial for these responses are construction of micro-dams, soil and water conservation and ecological restoration measures. The awareness that interactions can be quite different in semi-arid and semi-humid regions, as well as in upstream and downstream areas, should be reflected in management aimed at sustainable water and land resources use.

The impact of particle filtration on indoor air quality in a classroom near a highway.

A pilot study was performed to investigate whether the application of a new mechanical ventilation system with a fine F8 (MERV14) filter could improve indoor air quality in a high school near the Amsterdam ring road. PM10, PM2.5, and black carbon (BC) concentrations were measured continuously inside an occupied intervention classroom and outside the school during three sampling periods in the winter of 2013/2014. Initially, 3 weeks of baseline measurements were performed, with the existing ventilation system and normal ventilation habits. Next, an intervention study was performed. A new ventilation system was installed in the classroom, and measurements were performed during 8 school weeks, in alternating 2-week periods with and without the filter in the ventilation system under otherwise identical ventilation conditions. Indoor/outdoor ratios measured during the weeks with filter were compared with those measured without filter to evaluate the ability of the F8 filter to improve indoor air quality. During teaching hours, the filter reduced BC exposure by, on average, 36%. For PM10 and PM2.5, a reduction of 34% and 30% was found, respectively. This implies that application of a fine filter can reduce the exposure of schoolchildren to traffic exhaust at hot spot locations by about one-third.

Cadmium re-distribution from pod and root zones and accumulation by peanut (Arachis hypogaea L.).

Peanut (Arachis hypogaea L.) genotypes may differ greatly with regard to cadmium (Cd) accumulation, but the underlying mechanisms remain unclear. To determine the key factors that may contribute to Cd re-distribution and accumulation in peanut genotypes with different Cd accumulating patterns, a split-pot soil experiment was conducted with three common Chinese peanut cultivars (Fenghua-6, Huayu-20, and Huayu-23). The growth medium was separated into pod and root zones with varied Cd concentrations in each zone to determine the re-distribution of Cd after it is taken up via different routes. The peanut cultivars were divided into two groups based on Cd translocation efficiency as follows: (1) high internal Cd translocation efficiency cultivar (Fenghua-6) and (2) low internal Cd translocation efficiency cultivars (Huayu-20 and Huayu-23). Compared with Fenghua-6, low Cd translocation cultivars Huayu-20 and Huayu-23 showed higher biomass production, especially in stems and leaves, leading to dilution of metal concentrations. Results also showed that Cd concentration in roots increased significantly with increasing Cd concentrations in soils when Cd was applied in the root zone. However, there were no significant differences in the root Cd concentrations between different pod zone Cd treatments and the control, suggesting that root uptake, rather than pod uptake, is responsible for Cd accumulation in the roots of peanuts. Significant differences of Cd distribution were observed between pod and root zone Cd exposure treatments. The three peanut cultivars revealed higher kernel over total Cd fractions for pod than for root zone Cd exposure if only extra applied Cd was considered. This suggests that uptake through peg and pod shell might, at least partially, be responsible for the variation in Cd re-distribution and accumulation among peanut cultivars. Cd uptake by plants via two routes (i.e., via roots and via pegs and pods, respectively) and internal Cd translocation appear to be important mechanisms in determining Cd accumulation in the kernels of peanuts.

Low-Resolution Modeling of Dense Drainage Networks in Confining Layers.

Groundwater-surface water (GW-SW) interaction in numerical groundwater flow models is generally simulated using a Cauchy boundary condition, which relates the flow between the surface water and the groundwater to the product of the head difference between the node and the surface water level, and a coefficient, often referred to as the "conductance." Previous studies have shown that in models with a low grid resolution, the resistance to GW-SW interaction below the surface water bed should often be accounted for in the parameterization of the conductance, in addition to the resistance across the surface water bed. Three conductance expressions that take this resistance into account were investigated: two that were presented by Mehl and Hill (2010) and the one that was presented by De Lange (1999). Their accuracy in low-resolution models regarding salt and water fluxes to a dense drainage network in a confined aquifer system was determined. For a wide range of hydrogeological conditions, the influence of (1) variable groundwater density; (2) vertical grid discretization; and (3) simulation of both ditches and tile drains in a single model cell was investigated. The results indicate that the conductance expression of De Lange (1999) should be used in similar hydrogeological conditions as considered in this paper, as it is better taking into account the resistance to flow below the surface water bed. For the cases that were considered, the influence of variable groundwater density and vertical grid discretization on the accuracy of the conductance expression of De Lange (1999) is small.

Transport and degradation of propylene glycol in the vadose zone: model development and sensitivity analysis.

Transport and degradation of de-icing chemical (containing propylene glycol, PG) in the vadose zone were studied with a lysimeter experiment and a model, in which transient water flow, kinetic degradation of PG and soil chemistry were combined. The lysimeter experiment indicated that aerobic as well as anaerobic degradation occurs in the vadose zone. Therefore, the model included both types of degradation, which was made possible by assuming advection-controlled (mobile) and diffusion-controlled (immobile) zones. In the mobile zone, oxygen can be transported by diffusion in the gas phase. The immobile zone is always water-saturated, and oxygen only diffuses slowly in the water phase. Therefore, the model is designed in a way that the redox potential can decrease when PG is degraded, and thus, anaerobic degradation can occur. In our model, manganese oxide (MnO2, which is present in the soil) and NO3- (applied to enhance biodegradation) can be used as electron acceptors for anaerobic degradation. The application of NO3- does not result in a lower leaching of PG nor in a slower depletion of MnO2. The thickness of the snowcover influences the leached fraction of PG, as with a high infiltration rate, transport is fast, there is less time for degradation and thus more PG will leach. The model showed that, in this soil, the effect of the water flow dominates over the effect of the degradation parameters on the leaching at a 1-m depth.

Comparative performance of gene-based warfarin dosing algorithms in a multiethnic population.

SUMMARY BACKGROUND: Gene-based warfarin dosing algorithms have largely been developed in homogeneous populations, and their generalizability has not been established. OBJECTIVES: We sought to assess the performance of published algorithms in a racially diverse and multiethnic sample, and determine if additional clinical variables or genetic variants associated with dose could enhance algorithm performance. PATIENTS AND METHODS: In 145 compliant patients on warfarin with a goal international normalized ratio (INR) of 2-3, stable, therapeutic doses were compared with predicted doses using 12 reported algorithms that incorporated CYP2C9 and VKORC1 variants. Additional covariates tested with each model included race, concurrent medications, medications known to interact with warfarin and previously described CYP4F2, CALU and GGCX variants. RESULTS: The mean patient age was 67 +/- 14 years; 90 (62%) were male. Eighty-two (57%) were Caucasian, 28 (19%) African-American, 20 (14%) Hispanic and 15 (10%) Asian. The median warfarin dose was 35 mg per week (interquartile range 23-53 mg per week). Gene-based dosing algorithms explained 37-55% of the variation in warfarin dose requirements. Neither the addition of race, number of concurrent medications nor the number of concurrent medications interacting with warfarin enhanced algorithm performance. Similarly, consideration of CYP4F2, CALU or GGCX variant genotypes did not improve algorithms. CONCLUSIONS: Existing gene-based dosing algorithms explained between approximately one-third and one-half of the variability in warfarin dose requirements in this racially and ethnically diverse cohort. Additional clinical and recently described genetic variants associated with warfarin dose did not enhance prediction in our patient population.

[Cardiovascular disease and chronic kidney disease: from treatment to promoting health]. / Enfermedades cardiovasculares y nefropatía crónica: del tratamiento al fomento de la salud.

Chronic kidney disease is associated with poor cardiovascular outcomes and should be screened for in all patients with cardiovascular disease or risk factors such as hypertension and diabetes mellitus using estimate of glomerular filtration rate and a random urine albumin-to creatinine ratio. Strategies to identify and prevent chronic kidney disease must be part of a comprehensive program of disease prevention, that include evaluation of tobacco use, diet and exercise patterns, body mass index, blood pressure, lipid profile, blood glucose and patient-appropriate cancer screening. The global increase in patients with chronic kidney disease is threatening to reach epidemic proportions over the next decade, and few countries will be able to meet the economic challenges posed. A change in global approach from treatment of renal failure to aggressive primary and secondary prevention is essential. We propose that the United Nations Millennium Developments Goals for 2000-2015 should be expanded to include combatting infectious diseases as well as chronic diseases such as cardiovascular disease, diabetes, renal disease and cancer, using an integrated approach.

Enfermedades cardiovasculares y nefropatía crónica: del tratamiento al fomento de la salud / Cardiovascular disease and chronic kidney disease: from treatment to promoting health

La nefropatía crónica está asociada con un mal desenlace cardiovascular, y debería investigarse de forma sistemática en todos los pacientes con enfermedades cardiovasculares o factores de riesgo, tales como la hipertensión y la diabetes mellitus, mediante la determinación de la tasa de filtración glomerular y la razón albúmina/creatinina en muestras aleatorias de orina. Las estrategias para identificar y prevenir la nefropatía crónica deben formar parte de los programas integrales de prevención de enfermedades. Dichas estrategias deben incluir determinación del tabaquismo, del régimen alimentario y las pautas de ejercicio, el índice de masa corporal, la presión arterial, el perfil lipídico, la glucemia y la detección precoz del cáncer de la forma más adecuada para el paciente. El aumento mundial de pacientes con nefropatía crónica amenaza con alcanzar proporciones epidémicas durante la próxima década, y pocos países podrán afrontar los retos económicos que ello supone. Es esencial realizar un cambio de enfoque global y pasar del tratamiento de la insuficiencia renal a una prevención primaria y secundaria agresivas. Proponemos que los objetivos de Desarrollo del Milenio de las Naciones Unidas para 2000-2015 se amplíen y, además de la lucha contra las enfermedades infecciosas, incluyan las enfermedades crónicas (enfermedades cardiovasculares, diabetes mellitus, nefropatía y cáncer) mediante una estrategia integral (AU)

Chronic kidney disease is associated with poor cardiovascular outcomes and should be screened for in all patients with cardiovascular disease or risk factors such as hypertension and diabetes mellitus using estimate of glomerular filtration rate and a random urine albumin-tocreatinine ratio. Strategies to identify and prevent chronic kidney di - sea se must be part of a comprehensive program of disease prevention, that include evaluation of tobacco use, diet and exercise patterns, body mass index, blood pressure, lipid profile, blood glucose and patient-appropriate cancer screening. The global increase in patients with chronic kidney disease is threatening to reach epidemic proportions over the next decade, and few countries will be able to meet the economic challenges posed. A change in global approach from treatment of renal failure to aggressive primary and secondary prevention is essential. We propose that the United Nations Millenium Developments Goals for 2000-2015 should be expanded to include combatting infectious diseases as well as chronic diseases such as cardiovascular disease, diabetes, renal disease and cancer, using an integrated approach (AU)

Vasopressin administration facilitates fluid removal during hemodialysis.

Inadequate secretion of vasopressin during fluid removal by hemodialysis may contribute to the cardiovascular instability that complicates this therapy and administration of exogenous hormone, by supporting arterial pressure, may facilitate volume removal. To test this, we measured plasma vasopressin in patients with end-stage renal disease (ESRD) during hemodialysis and found that despite significant fluid removal, plasma vasopressin concentration did not increase. We further found that ESRD did not alter the endogenous removal rate of plasma vasopressin and that plasma hormone is not dialyzed. Finally, in a randomized, double-blinded, placebo-controlled trial in 22 hypertensive patients, we examined the effect of a constant infusion of a non-pressor dose of vasopressin on the arterial pressure response during a hemodialysis in which the target fluid loss was increased by 0.5 kg over the baseline prescription. We found that arterial pressure was more stable in the patients receiving vasopressin and that while only one patient (9%) in the vasopressin group had a symptomatic hypotensive episode, 64% of the patients receiving placebo had such an episode (P=0.024). Moreover, increased fluid removal was achieved only in the vasopressin group (520+/-90 ml vs 64+/-130 ml, P=0.01). Thus, administration of non-pressor doses of vasopressin to hypertensive subjects improves cardiovascular stability during hemodialysis and allows increased removal of excess extracellular fluid. Inadequate vasopressin secretion during hemodialysis-induced fluid removal is a likely contributor to the intradialytic hypotension that limits fluid removal.

Susceptibility to air pollution in elderly males and females.

It is important to know which individuals in the general population have increased susceptibility to air pollution. The aim of this study was to identify susceptible subgroups by studying airways hyperresponsiveness (AHR), high total immunoglobulin (Ig)E and sex. Diary data on lower and upper respiratory symptoms (LRS and URS, respectively), cough, and morning and evening peak expiratory flow (PEF) were collected in 327 elderly patients (50-70 yrs) for a period of 3 months. Acute effects of particulate matter with a diameter <10 microm, black smoke, sulphur dioxide and nitrogen dioxide on symptoms and PEF were estimated using logistic regression. In total, 48 (14.7%) subjects had AHR+/IgE+, 112 (34.3%) had AHR-/IgE+, 42 (12.8%) had AHR+/IgE- and 125 (38.2%) had AHR-/IgE-. In the AHR+/IgE+ group, each 10 microg x m(-3) increase in air pollution was associated with a significant increase in prevalence of URS (odds ratio ranging 1.03-1.19), cough (1.03-1.08) and fall in morning PEF (1.04-1.26). In the AHR+/IgE+ group, males responded predominantly with symptoms and females with a fall in morning PEF. In conclusion, elderly individuals with both airway hyperresponsiveness and high total immunoglobulin E are especially susceptible to air pollution. Identifying susceptible subgroups might enlarge insight into the actual mechanisms by which air pollution evokes specific modes of response.

Heavy metal concentrations in soil and earthworms in a floodplain grassland.

We determined accumulated heavy metal concentrations (Cd, Pb, Cu, Zn) of earthworms in moderately contaminated floodplain soils. Both soil and mature earthworms were sampled before and after flooding and earthworm species were identified to understand species specific differences in bioconcentration. Accumulated metal concentrations in floodplain earthworms differed before and after flooding. Differences in uptake and elimination mechanisms, in food choice and living habitat of the different earthworm species and changes in speciation of the heavy metals are possible causes for this observation. Regression equations taken from literature, that relate metal accumulation by earthworms in floodplains as a function of metal concentration in soil, performed well when all species specific data were combined in an average accumulation, but did not address differences in accumulation between earthworm species.

Infiltration and redistribution of LNAPL into unsaturated layered porous media.

Enhanced understanding of light non-aqueous phase liquid (LNAPL) infiltration into heterogeneous porous media is important for the effective design of remediation strategies. We used a 2-D experimental facility that allows for visual observation of LNAPL contours in order to study LNAPL redistribution in a layered porous medium. The layers are situated in the unsaturated zone near the watertable and they are inclined to be able to observe the effect of discontinuities in capillary forces and relative permeabilities. Two experiments were performed. The first experiment consisted of LNAPL infiltration into a fine sand matrix with a coarse sand layer, and the second experiment consisted of a coarse sand matrix and a fine sand layer. The numerical multi-phase flow model STOMP was validated with regard to the experimental results. This model is able to adequately reproduce the experimental LNAPL contours. Numerical sensitivity analysis was also performed. The capillarity contrast between sands was found to be the main controlling factor determining the final LNAPL distribution.

A set of constitutive relationships accounting for residual NAPL in the unsaturated zone.

Although laboratory experiments show that non-aqueous phase liquid (NAPL) is retained in the unsaturated zone, no existing multiphase flow model has been developed to account for residual NAPL after NAPL drainage in the unsaturated zone. We developed a static constitutive set of saturation-capillary pressure relationships for water, NAPL and air that accounts for both this residual NAPL and entrapped NAPL. The set of constitutive relationships is formulated similarly to the set of scaled relationships that is frequently applied in continuum models. The new set consists of three fluid-phase systems: a three-phase system and a two-phase system, that both comply with the original constitutive model, and a newly introduced residual NAPL system. The new system can be added relatively easily to the original two- and three-phase systems. Entrapment is included in the model. The constitutive relationships of the non-drainable residual NAPL system are based on qualitative fluid behavior derived from a pore scale model. The pore scale model reveals that the amount of residual NAPL depends on the spreading coefficient and the water saturation. Furthermore, residual NAPL is history-dependent. At the continuum scale, a critical NAPL pressure head defines the transition from free, mobile NAPL to residual NAPL. Although the Pc-S relationships for water and total liquid are not independent in case of residual NAPL, two two-phase Pc-S relations can represent a three-phase residual system of Pc-S relations. A newly introduced parameter, referred to as the residual oil pressure head, reflects the mutual dependency of water and oil. Example calculations show consistent behavior of the constitutive model. Entrapment and retention in the unsaturated zone cooperate to retain NAPL. Moreover, the results of our constitutive model are in agreement with experimental observations.

Transport and degradation of propyleneglycol and potassium acetate in the unsaturated zone.

De-icing chemicals used during the winter season are potential pollutants for the groundwater underneath the new main airport of Norway. Several field experiments examining the transport and degradation of propyleneglycol (PG), potassium acetate (KAc) and non-reactive tracers were performed in a lysimeter trench under natural snowmelting conditions. Chemicals were applied underneath the snow cover and the transport in a heterogeneous coarse sandy soil was examined by extracting soil water from 30 or 40 suction cups placed at five depths between 0.4 and 2.4 m depth. Transport and degradation was analysed by spatial moment calculations. The de-icing chemicals showed the same basic displacement as chemically inactive tracers, an initial fast transport during the melting period followed by a period of stagnation throughout the summer season. PG seemed to be displaced to greater depths compared to non-reactive tracer after the first application. However, computer simulations of transport and degradation in a heterogeneous unsaturated soil showed that decreasing degradation constants with depth can generate a downward movement of the centre of mass without any flow occurring in the system. Potassium acetate showed some adsorption, with calculated retardation factors of approximately 1.3 and 1.2. The degradation rate constant for PG was calculated to be 0.015 day-1 in 1994 and increased to 0.047 day-1 in the second application made in 1995. The degradation rate constant for acetate was estimated to be 0.02 day-1. Increased manganese concentrations seem to be a good indicator of degradation of PG and Ac.

A stochastic empirical model for regional heavy-metal balances in agroecosystems.

Mass flux balancing provides essential information for preventive strategies against heavy-metal accumulation in agricultural soils that may result from atmospheric deposition and application of fertilizers and pesticides. In this paper we present the empirical stochastic balance model, PROTERRA-S, that estimates heavy-metal and phosphorus accumulation in agricultural soils on the regional level. The basic units of these balances are land use systems defined by livestock production and cultivated crops. The model is designed to use available databases, such as regional agricultural statistics and soil information systems. In a case study, we assessed the phosphorus, cadmium, and zinc balances for the Sundgau region, Switzerland. The regional P requirements of crops were mainly supplied by animal manure (56%) and commercial fertilizers (40%). Net cadmium fluxes of the land use systems ranged from 1.0 g ha(-1) yr(-1) (dairy and mixed farm types) to 17.8 g ha(-1) yr(-1) (animal husbandry systems), whereas the regional net cadmium flux was only 1.4 g ha(-1) yr(-1). The regional net zinc flux was 605 g ha(-1) yr(-1). The smallest net zinc flux of 101 g ha(-1) yr(-1) was found for an arable farm type, whereas for animal husbandry systems fluxes up to 39.8 kg ha(-1) yr(-1) were estimated. Comparison of model results with reported metal balances of experimental farms shows that identification of agricultural land with high risks of heavy-metal accumulation benefits from stratification of heavy-metal balances according to land use systems while accounting for their P fertilization plans. Consequently, the model may support sustainable management of heavy-metal cycles in agricultural soils.

(1-->3)-beta-D-glucan and endotoxin in house dust and peak flow variability in children.

House dust-associated bacterial endotoxins have been shown to be associated with asthma severity, and a similar role has been suggested for fungal (1-->3)-beta-D-glucans. In this study the relation between these agents and peak expiratory flow (PEF) variability was investigated in 148 children 7 to 11 yr of age of whom 50% had self- or parent-reported chronic respiratory symptoms. All children self-monitored twice daily their PEF for a period of 16 wk. Dust samples were collected from mattresses and from living room and bedroom floors, and endotoxin and (1-->3)-beta-D-glucan were measured in dust extracts. The relations with mean daily PEF variability (Ampl%mean) were investigated by linear regression analysis, adjusting for dust mite allergen levels, presence of pets, and type of floor cover. In unadjusted analyses the levels of both endotoxin and (1--> 3)-beta-D-glucan per square meter of living room floor were significantly associated with PEF-variability (but not when expressed per gram of sampled dust), particularly in atopic children with asthma symptoms. Adjusted analyses showed the same association for (1--> 3)-beta-D-glucan but not for endotoxin. Although no associations were found with microbial agent levels in bedroom floor or mattress dust, high levels of (1-->3)-beta-D-glucan in living room floor dust apparently increase PEF variability in asthmatic children.

Incidence of influenza-like illness, measured by a general practitioner sentinel system, is associated with day-to-day variations in respiratory health in panel studies.

During three consecutive winters beginning in 1992-1993, the association between the incidence of influenza and influenza-like illness (ILI), measured by a general practitioner sentinel system, and respiratory health was investigated in an air pollution panel study. Data from 22 panels of children (7-11 years old) and adults (50-70 years old) in the Netherlands were used. ILI incidence was associated with peak expiratory flow, respiratory symptoms, and bronchodilator use. Peak ILI incidence of 122 cases/10,000 subjects was associated with a decrement in peak expiratory flow of 6% and a 3- to 4.5-fold increase in symptom reporting and bronchodilator use. In panel studies, ILI incidence might be used to adjust for confounding by acute respiratory infections.

Acute effects of air pollution on respiratory health of 50-70 yr old adults.

The aim of this study was to investigate the association between daily changes in respiratory health and air pollution in 489 adults, aged 50-70 yrs, with and without chronic respiratory symptoms, living in urban and nonurban areas in the Netherlands. Subjects were selected from the general population with a screening questionnaire. During three consecutive winters starting in 1992/1993, peak expiratory flow (PEF) and respiratory symptoms were registered in a daily diary. Daily measurements of particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10), black smoke (BS), sulphate, sulphur dioxide (SO2) and nitrogen dioxide (NO2) were conducted. The difference in PM10, BS and sulphate concentrations between urban and nonurban areas was small, but there was more contrast in the concentrations of SO2 and NO2. In symptomatic subjects from urban areas, PM10, BS, sulphate and SO2 concentrations were associated with the prevalence of large decrements in morning PEF (>20% below the median). BS in particular was also associated with upper respiratory symptoms (URS). The magnitude of the effect estimates was in the order of an 80% increase in PEF decrements and a 20% increase in URS for a 40 microg x m-3 increase of the same day BS concentration. In symptomatic subjects from nonurban areas, no consistent associations between air pollution and health indicators were observed. However, the differences in effect estimates between urban and nonurban symptomatic panels were small and nonsignificant. In nonsymptomatic adults from both areas, no consistent pattern of associations with air pollution was found. In conclusion, air pollution effects were only found in symptomatic adults in the urban areas.

Modulation of the acute respiratory effects of winter air pollution by serum and dietary antioxidants: a panel study.

This study investigated whether a high dietary intake or serum concentration of antioxidant (pro-) vitamins could attenuate the acute respiratory effects of air pollution in panels of adults (n = 227) aged 50-70 yrs with chronic respiratory symptoms in two winters starting in 1993/1994. Subjects performed daily peak expiratory flow (PEF) measurements in the morning and evening and reported the occurrence of respiratory symptoms in two regions (urban and nonurban) each winter. Logistic regression analysis was used with the prevalences of large PEF decrements as dependent variables and air pollution levels as independent variables. Analyses were performed separately for subjects below and above the median levels of serum beta-carotene and the intake of dietary vitamin C and beta-carotene. Subjects with low levels of serum beta-carotene more often had large PEF decrements when particles <10 microm in diameter or black smoke levels which were higher compared to subjects with high levels of serum beta-carotene. The same results tended to be observed for dietary vitamin C or beta-carotene, but there were less significant air pollution effects in the low dietary antioxidant group. The results suggest that serum beta-carotene and to a lesser extent dietary vitamin C and beta-carotene may attenuate peak expiratory flow decrements due to air pollution in subjects with chronic respiratory symptoms.