Desiree Jansen

No effects of probiotics on atopic dermatitis in infancy: a randomized placebo‐controlled trial

Background Studies have been performed suggesting that administration of probiotics may have therapeutic and/or preventive benefits in the development of sensitization and atopic disease, particularly in infants with atopic dermatitis (AD).

Effect of Fluticasone With and Without Salmeterol on Pulmonary Outcomes in Chronic Obstructive Pulmonary Disease: A Randomized Trial

BACKGROUND Inhaled corticosteroids (ICSs) and long-acting beta(2)-agonists (LABAs) are used to treat moderate to severe chronic obstructive pulmonary disease (COPD). OBJECTIVE To determine whether long-term ICS therapy, with and without LABAs, reduces inflammation and improves pulmonary function in COPD. DESIGN Randomized, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00158847) SETTING 2 university medical centers in The Netherlands. PATIENTS 114 steroid-naive current or former smokers with moderate to severe COPD. MEASUREMENTS Cell counts in bronchial biopsies and sputum (primary outcome); methacholine responsiveness at baseline, 6, and 30 months; and clinical outcomes every 3 months. INTERVENTION Random assignment by minimization method to receive fluticasone propionate, 500 microg twice daily, for 6 months (n = 31) or 30 months (n = 26); fluticasone, 500 microg twice daily, and salmeterol, 50 microg twice daily, for 30 months (single inhaler; n = 28); or placebo twice daily (n = 29). RESULTS 101 patients were greater than 70% adherent to therapy. Fluticasone therapy decreased counts of mucosal CD3(+) cells (-55% [95% CI, -74% to -22%]; P = 0.004), CD4(+) cells (-78% [CI, -88% to 60%]; P < 0.001), CD8(+) cells (-57% [CI, -77% to -18%]; P = 0.010), and mast cells (-38% [CI, -60% to -2%]; P = 0.039) and reduced hyperresponsiveness (P = 0.036) versus placebo at 6 months, with effects maintained after 30 months. Fluticasone therapy for 30 months reduced mast cell count and increased eosinophil count and percentage of intact epithelium, with accompanying reductions in sputum neutrophil, macrophage, and lymphocyte counts and improvements in FEV(1) decline, dyspnea, and quality of life. Reductions in inflammatory cells correlated with clinical improvements. Discontinuing fluticasone therapy at 6 months increased counts of CD3(+) cells (120% [CI, 24% to 289%]; P = 0.007), mast cells (218% [CI, 99% to 407%]; P < 0.001), and plasma cells (118% [CI, 9% to 336%]; P = 0.028) and worsened clinical outcome. Adding salmeterol improved FEV(1) level. LIMITATIONS The study was not designed to evaluate clinical outcomes. Measurement of primary outcome was not available for 24% of patients at 30 months. CONCLUSION ICS therapy decreases inflammation and can attenuate decline in lung function in steroid-naive patients with moderate to severe COPD. Adding LABAs does not enhance these effects. .

Nocturnal non-invasive ventilation in addition to rehabilitation in hypercapnic patients with COPD

Background: Long-term non-invasive positive pressure ventilation (NIPPV) might improve the outcomes of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD) with chronic respiratory failure. A study was undertaken to investigate whether nocturnal NIPPV in addition to pulmonary rehabilitation improves health-related quality of life, functional status and gas exchange compared with pulmonary rehabilitation alone in patients with COPD with chronic hypercapnic respiratory failure. Methods: 72 patients with COPD were randomly assigned to nocturnal NIPPV in addition to rehabilitation (n = 37) or rehabilitation alone (n = 35). Outcome measures were assessed before and after the 3-month intervention period. Results: The Chronic Respiratory Questionnaire total score improved 15.1 points with NIPPV + rehabilitation compared with 8.7 points with rehabilitation alone. The difference of 7.5 points was not significant (p = 0.08). However, compared with rehabilitation alone, the difference in the fatigue domain was greater with NIPPV + rehabilitation (mean difference 3.3 points, p<0.01), as was the improvement in the Maugeri Respiratory Failure questionnaire total score (mean difference −10%, p<0.03) and its cognition domain (mean difference −22%, p<0.01). Furthermore, the addition of NIPPV improved daytime arterial carbon dioxide pressure (mean difference −0.3 kPa; p<0.01) and daily step count (mean difference 1269 steps/day, p<0.01). This was accompanied by an increased daytime minute ventilation (mean difference 1.4 l; p<0.001). Conclusion: Non-invasive ventilation augments the benefits of pulmonary rehabilitation in patients with COPD with chronic hypercapnic respiratory failure as it improves several measures of health-related quality of life, functional status and gas exchange. Trial registration number: NCT00135538.

Gender differences in predictors of the decline of renal function in the general population

We sought to identify predictors of the decline in renal function, especially those that are modifiable, in the 5488 participants of the prospective, community-based cohort study PREVEND who completed three visits during a mean follow-up of 6.5 years. The change in renal function was used as the outcome and this was calculated as the linear regression of three estimated GFR measurements obtained during follow-up. Risk factors, known to influence renal outcome in patients with primary renal diseases, were used as potential predictors in multivariate regression analyses. High systolic blood pressure and plasma glucose were found to be independent predictors for an accelerated decline in function for both genders. In males, albuminuria was the strongest independent predictor for renal function decline, whereas in females albuminuria was univariately associated only after adjustment for age. The direction of the association between cholesterol/HDL ratio and decline of renal function differed by gender. Surprisingly, in males, waist circumference was an independent predictor and positively associated with renal function outcome. These studies show that there are gender differences in the standard predictors of the decline in renal function.

Increased number of B-cells in bronchial biopsies in COPD

Recently, it has been shown that the accumulated volume of B-cells in small airways is increased in chronic obstructive pulmonary disease (COPD) Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 3 and 4. Little is known about the number of B-cells in central airways in COPD. The present authors hypothesised that the number of B-cells in bronchial biopsies of large airways is higher in patients with COPD than in controls without airflow limitation and higher in more severe COPD. Therefore, bronchial biopsies were collected from 114 COPD patients (postbronchodilator forced expiratory volume in one second (FEV1) 63±9 % predicted value, FEV1/inspiratory vital capacity (IVC) 48±9%) and 28 controls (postbronchodilator FEV1 108±12 % predicted value, FEV1/IVC 78±4%). Paraffin sections were stained for B-cells (CD20+) and their number was determined in the subepithelial area (excluding muscle, glands and vessels). B-cell numbers were higher in patients with COPD versus controls (8.5 versus 3.9 cells·mm−2, respectively) and higher in patients with GOLD severity stage 3 (n = 11) than stage 2 (n = 103; 22.3 versus 7.8 cells·mm−2). No relationship was found between the number of B-cells and clinical characteristics within the chronic obstructive pulmonary disease group. The authors suggest that these increased B-cell numbers may have an important contribution to the pathogenesis of chronic obstructive pulmonary disease.

(A)Symptomatic bronchial hyper-responsiveness and asthma

Bronchial responsiveness constitutes the phenomenon of the occurrence of airways obstruction upon physical, chemical and pharmacological stimuli (l-3). The clinical presentation in asthmatic individuals includes wheeze, cough and/or dyspnoea upon exercise and inhalation of e.g. cold air, fog and perfume. The prevalence of bronchial hyper-responsiveness (BHR) in the population varies from 6 to 35% (4-14) and is strongly associated with the presence of respiratory symptoms. Even though BHR is generally accompanied by respiratory symptoms, population studies have shown that it may also occur in subjects without any respiratory symptom, so-called asymptomatic hyper-responsiveness (69,12,15). There is increasing evidence that an inflammatory process in the airway wall is one of the underlying pathophysiologic mechanisms of BHR in asthma. This inflammatory process may directly or indirectly cause smooth muscle contraction, airway wall oedema, and stimulation of the nervous system, leading to symptoms of cough, wheeze and dyspnoea. It is still unclear whether an inflammatory process is also present in asymptomatic individuals, and if so, whether it has similar cellular components. Furthermore, it is important to assess whether asymptomatic hyper-responsiveness has any prognostic importance as an early sign of disease development.

High Protein Intake Associates with Cardiovascular Events but not with Loss of Renal Function

The long-term effects of higher dietary protein intake on cardiovascular and renal outcomes in the general population are not clear. We analyzed data from 8461 individuals who did not have renal disease and participated in two or three subsequent screenings (6.4-yr follow-up) in a prospective, community-based cohort study (Prevention of Renal and Vascular ENd-stage Disease [PREVEND]). We calculated daily protein intake from 24-h urinary urea excretion (Maroni formula) and used Cox proportional hazard models to analyze the associations between protein intake, cardiovascular events, and mortality. We used mixed-effects models to investigate the association between protein intake and change in renal function over time. The mean +/- SD daily protein intake was 1.20 +/- 0.27 g/kg. Protein intake was significantly associated with cardiovascular events during follow-up. The associations seemed U-shaped; compared with intermediate protein intake, individuals with either higher or lower protein intake had higher event rates. All-cause mortality and noncardiovascular mortality also were significantly associated with protein intake; individuals with low protein intake had the highest event rates. We found no association between baseline protein intake and rate of renal function decline during follow-up. In summary, in the general population, high protein intake does not promote accelerated decline of renal function but does associate with an increased risk for cardiovascular events.

Airway inflammation contributes to health status in COPD: a cross-sectional study.

BackgroundChronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow limitation and airway inflammation, accompanied by decreased health status. It is still unknown which factors are responsible for the impaired health status in COPD. We postulated that airway inflammation negatively contributes to health status in COPD.MethodsIn 114 COPD patients (99 male, age: 62 ± 8 yr, 41 [31–55] pack-years, no inhaled or oral corticosteroids, postbronchodilator FEV1: 63 ± 9% pred, FEV1/IVC: 48 ± 9%) we obtained induced sputum and measured health status (St. Georges respiratory questionnaire (SGRQ)), postbronchodilator FEV1, hyperinflation (RV/TLC), and airway hyperresponsiveness to methacholine (PC20). Sputum was induced by hypertonic saline and differential cell counts were obtained in 102 patients.ResultsUnivariate analysis showed that SGRQ total and symptom score were positively associated with % sputum macrophages (r = 0.20, p = 0.05; and r = 0.20, p = 0.04, respectively). Multiple regression analysis confirmed these relationships, providing significant contributions of % sputum macrophages (B = 0.25, p = 0.021) and RV/TLC (B = 0.60, p = 0.002) to SGRQ total score. Furthermore, SGRQ symptom score was associated with % sputum macrophages (B = 0.30, p = 0.03) and RV/TLC (B = 0.48, p = 0.044), whilst SGRQ activity score was associated with % sputum macrophages (B = 0.46, p = 0.002), RV/TLC (B = 0.61, p = 0.015), and PC20 (B = -9.3, p = 0.024). Current smoking and FEV1 were not significantly associated with health status in the multiple regression analysis.ConclusionWe conclude that worse health status in COPD patients is associated with higher inflammatory cell counts in induced sputum. Our findings suggest that airway inflammation and hyperinflation independently contribute to impaired health status in COPD. This may provide a rationale for anti-inflammatory therapy in this disease.

Respiratory muscle activity and dyspnea during exercise in chronic obstructive pulmonary disease

We aimed to determine by non-invasive EMG, whether during exercise: (1) COPD patients increase scalene and intercostal EMG activity, (2) increased EMG activity is associated with increased dyspnea, and (3) the ratio between EMG activity and volume displacement is increased in COPD compared to healthy subjects (HS). During a maximal incremental cycle test, scalene and intercostal EMG was derived transcutaneously in 17 COPD patients and 10 HS. Dyspnea was quantified using a Borg scale, ranging from zero to 10 (maximal dyspnea). For analyses the ratio between inspiratory muscle activity during exercise and activity during quiet breathing was used (logEMGAR). In COPD patients, scalene and intercostal activity increased at greater rate early in exercise compared to that of the HS. With a doubling of the logEMGAR, in COPD, dyspnea increased with 2.8/3.8 points, while in the HS, dyspnea increased less with 1.1/1.4 points. In COPD, there was a larger increase in EMG activity relatively to tidal volume increases.

Sibling effect on atopy in children of patients with asthma

Background Multiple population studies have shown the presence of a sibling effect on atopic disease. However, it is unclear if the sibling effect is also of importance in subjects who are genetically at high risk for the development of atopy.