High resolution exposure modelling of heat and air pollution and the impact on mortality

Background Elevated temperature and air pollution have been associated with increased mortality. Exposure to heat and air pollution, as well as the density of vulnerable groups varies within cities. The objective was to investigate the extent of neighbourhood differences in mortality risk due to heat and air pollution in a city with a temperate maritime climate. Methods A case-crossover design was used to study associations between heat, air pollution and mortality. Different thermal indicators and air pollutants (PM10, NO2, O3) were reconstructed at high spatial resolution to improve exposure classification. Daily exposures were linked to individual mortality cases over a 15 year period. Results Significant interaction between maximum air temperature (Tamax) and PM10 was observed. During “summer smog” days (Tamax > 25 °C and PM10 > 50 μg/m3), the mortality risk at lag 2 was 7% higher compared to the reference (Tamax 15 °C and PM10 15 μg/m3). Persons above age 85 living alone were at highest risk. Conclusion We found significant synergistic effects of high temperatures and air pollution on mortality. Single living elderly were the most vulnerable group. Due to spatial differences in temperature and air pollution, mortality risks varied substantially between neighbourhoods, with a difference up to 7%

Different potencies of topical corticosteroids for a better treatment strategy in children with atopic dermatitis (The Rotterdam Eczema study): Protocol for an observational cohort study with an embedded randomised open-label controlled trial

Introduction Topical corticosteroids (TCS) of different potencies are the main treatment to control atopic dermatitis (AD). The Dutch guideline on AD for general practitioners (GPs) recommends a stepwise approach in which treatment steps are tailored to the severity of the disease, starting with the lowest possible potency of TCS. However, it remains unclear whether the recommended stepwise approach is most efficient. This randomised open-label controlled trial aims to determine whether a potent TCS is more effective than a low-potency TCS in the initial treatment of children with a moderate flare-up of AD in primary care. In the observational cohort, the overall aim is to determine the frequency, burden and determinants of flare-ups of AD during follow-up. Methods and analysis The study is an observational cohort study with an embedded pragmatic randomised controlled, open-label trial. Eligible are patients diagnosed with AD (aged 12 weeks to 18 years) who visited the GP for AD or received repeated prescriptions for AD in the previous 12 months; follow-up of the cohort is 1 year. Children are enrolled in the trial if they have a flare-up of AD during follow-up in the cohort. Eligible children are randomised to the intervention group (with a potent TCS once daily) or to the GP guideline group (with a low potency TCS once daily). Primary outcome is the difference in average subjective disease severity over 24 weeks follow-up in the trial, measured with the patient-oriented eczema measure. As secondary outcome, the Eczema Area and Severity Index is measured. Ethics and dissemination This study tests the hypothesis that immediate treatment with a potent TCS during a flare-up of AD leads to faster and more efficacious results as compared with starting with a TCS with low potency with less overall use of TCS. The study protocol is approved by the Medical Ethics Committee (MEC) of the Erasmus Medical Center Rotterdam, the Netherlands (MEC-2017-328). The results of the study will be published in international peer-reviewed journals and presented at national and international conferences. Trial registration number NTR: 6679; Pre-results

Nasal gene expression differentiates COPD from controls and overlaps bronchial gene expression

© 2017 The Author(s). Background: Nasal gene expression profiling is a promising method to characterize COPD non-invasively. We aimed to identify a nasal gene expression profile to distinguish COPD patients from healthy controls. We investigated whether this COPD-associated gene expression profile in nasal epithelium is comparable with the profile observed in bronchial epithelium. Methods: Genome wide gene expression analysis was performed on nasal epithelial brushes of 31 severe COPD patients and 22 controls, all current smokers, using Affymetrix Human Gene 1.0 ST Arrays. We repeated the gene expression analysis on bronchial epithelial brushes in 2 independent cohorts of mild-to-moderate COPD patients and controls. Results: In nasal epithelium, 135 genes were significantly differentially expressed between severe COPD patients and controls, 21 being up- and 114 downregulated in COPD (false discovery rate < 0.01). Gene Set Enrichment Analysis (GSEA) showed significant concordant enrichment of COPD-associated nasal and bronchial gene expression in both independent cohorts (FDRGSEA < 0.001). Conclusion: We identified a nasal gene expression profile that differentiates severe COPD patients from controls. Of interest, part of the nasal gene expression changes in COPD mimics differentially expressed genes in the bronchus. These findings indicate that nasal gene expression profiling is potentially useful as a non-invasive biomarker in COPD. Trial registration:ClinicalTrials.govregistration number NCT01351792(registration date May 10, 2011), ClinicalTrials.govregistration number NCT00848406(registration date February 19, 2009), ClinicalTrials.govregistration number NCT00807469(registration date December 11, 2008)

Discontinuation of furosemide decreases PaCO(2) in patients with COPD.

Item does not contain fulltextSTUDY OBJECTIVE: To evaluate whether the discontinuation of furosemide treatment resulted in a decrease in PaCO(2) and an increase in daytime and nocturnal oxygenation. BACKGROUND: Furosemide is widely prescribed in patients with COPD for the treatment of peripheral edema. It is known that furosemide causes a metabolic alkalosis. A diminished chemoreceptor stimulation may cause a decreased alveolar ventilation. DESIGN: Randomized, double-blind, placebo-controlled, crossover trial. SETTING: Department of Pulmonology, Rijnstate Hospital Arnhem, the Netherlands. PATIENTS: Twenty patients with stable COPD (10 men; median age, 70 years [range, 58 to 81 years]; FEV(1) 35% predicted [range, 19 to 70% predicted]). Subjects were included if they had received furosemide, 40 mg/d, for the treatment of peripheral edema for at least a month and if they had a mean nocturnal arterial oxygen saturation (SaO(2)) < 92%. Patients with cardiac left and/or right ventricular dysfunction, sleep apneas, and patients receiving other diuretics, angiotensin-converting enzyme inhibitors, potassium or chloride replacement therapy, or long-term oxygen treatment were excluded. INTERVENTION: Furosemide was discontinued for 1 week and replaced by placebo treatment in the first or the second week. MEASUREMENTS AND RESULTS: Ventilation, daytime arterial blood gas levels, and nocturnal SaO(2) were measured at baseline, after 1, and after 2 weeks. Sixteen subjects completed the study. Ventilation increased from 10.4 L/min (range, 6.7 to 15.4 L/min) at baseline to 11.6 L/min (range, 8.7 to 14.0 L/min) after discontinuation of furosemide (p < 0.05). PaCO(2) decreased from 45 mm Hg (range, 35 to 64 mm Hg) to 41 mm Hg (range, 32 to 61 mm Hg; p < 0.01). Daytime and nocturnal oxygenation did not improve. CONCLUSIONS: Although it does not improve oxygenation, the discontinuation of furosemide decreases PaCO(2) in patients with COPD

Underestimation of nocturnal hypoxemia due to monitoring conditions in patients with COPD.

Item does not contain fulltextSTUDY OBJECTIVES: COPD patients run a risk of developing nocturnal oxygen desaturation. When evaluating patients with nocturnal hypoxemia, an unfamiliar hospital environment and the monitoring equipment may cause sleep disturbances. It was hypothesized that increased sleep disruption will lead to fewer instances of desaturation during a night of monitoring. DESIGN:The following forms of monitoring were evaluated prospectively on 3 nights for each patient: oximetry at home; polysomnography (PSG) at home; and PSG in the hospital. SETTING: Department of Pulmonology, Rijnstate Hospital Arnhem, The Netherlands. PATIENTS: Fourteen stable COPD patients (7 men; median age, 71.5 years; age range, 59 to 81 years; FEV(1), 32.5% predicted; FEV(1) range, 19 to 70% predicted) participated in the study. All subjects had significant instances of nocturnal arterial oxygen desaturation. Those patients with a sleep-related breathing disorder or cardiac failure were excluded from the study. MEASUREMENTS AND RESULTS: The mean nocturnal arterial oxygen saturation (SaO(2)) level was higher during PSG monitoring at home (89.7%; range, 77 to 93%) than during oximetry monitoring (88.5%; range, 80 to 92%) [p 4%) was lower during PSG monitoring at home (22.1%; range, 3 to 63%) during PSG monitoring at home than during oximetry monitoring (50.4%; range, 4 to 91%) [p < 0.01]. A correction for actual sleep during PSG monitoring reduced the differences between PSG monitoring at home and oximetry monitoring, although a difference in the desaturation time remained (PSG monitoring at home, 31.9% [range, 2 to 75%]; oximetry monitoring, 50.4% [range, 4 to 91%]) [p = 0.041]. A comparison of sleep architectures for nights when PSG was being monitored showed a higher arousal index in the hospital than at home (PSG monitoring in the hospital, 5.6 arousals per hour [range, 2 to 16 arousals per hour]; PSG monitoring at home, 2.5 arousals per hour [range, 1 to 6 arousals per hour]) [p < 0.025], but no differences in SaO(2) levels were found between PSG monitoring at home and PSG monitoring in the hospital. CONCLUSION: The artifacts due to sleep-monitoring equipment may cause an underestimation of the degree of nocturnal hypoxemia in COPD patients. The addition of an unfamiliar environment causes more sleep disruption, but this does not affect nocturnal SaO(2) levels further

Metabolic acidosis improves airway conductance in patients with asthma.

Contains fulltext : 79556.pdf (publisher's version ) (Closed access)The objective was to investigate whether acute metabolic acidosis could cause bronchodilation in patients with asthma. Twelve patients with asthma (8 females, mean age 39 (+/- SD 12) years, forced expiratory volume in 1 second [FEV(1)] 93 [+/-9] % predicted, PC(20) 1.9 (+/-1.0) mg/mL) participated in a double-blind, placebo-controlled trial. Subjects ingested calculated amounts of ammonium chloride to induce acidosis or saline as placebo, in random order, each on a separate day. Airway resistance (R(aw)), specific airway conductance (sG(aw)), FEV(1), and PEF were measured as primary variables. To evaluate the consequences of alterations in bronchial contractility on the airway responsiveness, the histamine provocation test (PC(20)) was measured as secondary variable. The intervention resulted in a mean (SD) decrease in base excess from -0.5 (+/-1.4) to -3.9 (+/-1.1) mmol/L (p < 0.01) and a decrease in pH from 7.41 (+/-0.02) to 7.36 (+/-0.02) (p < 0.01). This caused a statistically significant increase in sG(aw) from 1.15 (+/-0.16) to 1.26 (+/-0.13) 1/kPa.s) (p < 0.05). Tendencies towards increase were found in PEF (7.79 (+/-2.2) versus 8.09 (+/-1.9) (NS, p = 0.10) and in FEV(1) (2.98 (+/-0.9) versus 3.06 (+/-0.9) (NS, p = 0.15). PC(20) did not change significantly. It was concluded that acute metabolic acidosis has a modest bronchodilating effect in patients with asthma

Obesity in COPD: Revealed and Unrevealed Issues

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Volumetric measurements of peripheral edema in clinical conditions.

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