Forskolin-induced Organoid Swelling is Associated with Long-term CF Disease Progression

RATIONALE: Cystic fibrosis (CF) is a monogenic life-shortening disease associated with highly variable individual disease progression which is difficult to predict. Here we assessed the association of forskolin-induced swelling (FIS) of patient-derived organoids (PDO) with long-term CF disease progression in multiple organs and compared FIS with the golden standard biomarker sweat chloride concentration (SCC). METHODS: We retrieved 9-year longitudinal clinical data from the Dutch CF Registry of 173 people with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Individual CFTR function was defined by FIS, measured as the relative size increase of intestinal organoids after stimulation with 0.8 µM forskolin, quantified as area under the curve (AUC). We used linear mixed effect models and multivariable logistic regression to estimate the association of FIS with long-term FEV1pp decline and development of pancreatic insufficiency, CF-related liver disease and diabetes. Within these models, FIS was compared with SCC. RESULTS: FIS was strongly associated with longitudinal changes of lung function, with an estimated difference in annual FEV1pp decline of 0.32% (95%CI: 0.11%-0.54%; p=0.004) per 1000-points change in AUC. Moreover, increasing FIS levels were associated with lower odds of developing pancreatic insufficiency (adjusted OR: 0.18, 95%CI: 0.07-0.46, p<0.001), CF-related liver disease (adjusted OR: 0.18, 95%CI: 0.06-0.54, p=0.002) and diabetes (adjusted OR: 0.34, 95%CI: 0.12-0.97, p=0.044). These associations were absent for SCC. CONCLUSION: This study exemplifies the prognostic value of a PDO-based biomarker within a clinical setting, which is especially important for people carrying rare CFTR mutations with unclear clinical consequences

ANALYSIS OF LIFE INSURANCE INVESTMENT COMPOSITION

Economic recession and global mettle down have brought the question of insurance company investment to the forefront. Growing attention has shifted to the pattern of investments by the insurance and question of how to evaluate such investments. The aim of this research is to evaluate investment compositions which are made by life insurance companies in Indonesia, as well as to know the effects on the performance of Insurance companies

Invloed van inhalatiecorticosteroïden op de kwaliteit van leven bij patiënten met astma en chronisch obstructieve longziekte

Contains fulltext : 24178___.PDF (publisher's version ) (Open Access

Kunnen patiënten met licht astma stoppen met inhalatiecorticosteroïden in een stabiele fase van de ziekte?

Contains fulltext : 24218___.PDF (publisher's version ) (Open Access

Asthma and chronic bronchitis. Can family physicians predict rates of progression?

OBJECTIVE: To investigate whether the progression rate of asthma or chronic bronchitis can be predicted from a cross-sectional assessment of features that can be measured by family physicians. DESIGN: Secondary analysis of data from a 2-year randomized, controlled bronchodilator intervention study in family practice. SETTING: Twenty-nine general practices in the eastern part of The Netherlands. PATIENTS: One hundred sixty patients (101 with chronic bronchitis, 59 with asthma) from the 29 general practices. INTERVENTIONS: Predictors were related to the annual decline in lung function (the forced expiratory volume in one second) by means of multiple analysis of variance, controlling for age, sex, smoking habits, initial FEV1 level, bronchial hyperresponsiveness, reversibility of obstruction, and medication during the study. MAIN OUTCOME MEASURES: Predictors of the annual decline in lung function (FEV1), which is believed to be the most important measure for progression. RESULTS: Only three variables predicted the decline in lung function: having a barrel-shaped chest, experiencing wheezing, and an unusual diurnal peak-flow rate index. Wheezing was the best predictor of the annual decline in lung function. In chronic bronchitis, the decline in FEV1 of wheezing patients was 133 mL/y compared with 62 mL/y for non-wheezing patients (P < 0.05). In asthma with more severe symptoms, wheezing patients had a tendency to decline 156 mL/y compared with 57 mL/y among non-wheezing patients (P = 0.08). CONCLUSIONS: It is nearly impossible to predict the progression rate of asthma or chronic bronchitis from symptoms, physical signs of the chest, and the PEFR. Therefore, patients with a rapid progression rate can probably be detected only by monitoring progression of the disease through repeated lung function testing

Preventie van astma

Primary prevention of asthma is not easy to achieve. - Preventive measures which are useful in all children are prevention of passive smoking exposure in utero and/or in childhood and the use of breast-feeding during at least the first six months of life. - Single interventions towards reduction of house dust mite allergens are not effective in preventing asthma; only a combined intervention with breast feeding, stopping of passive smoking, and reduction of allergens of pets and house dust mite appeared to be effective in young children at risk for asthma. - In children with already existing asthma, a combination of (secondary) preventive measures with sanitation of the house, reduction of allergens of pets and house dust mite, and optimal ventilation is useful. - Removal of pets from homes of children in the general population before the onset of atopy and allergic disorders is not effective. - Children visiting day-care report more airway infections and respiratory complaints in the first years of life. However, the chance on asthma or atopy development in later life is not influenced. Therefore, there is no reason to avoid day-care attendance in the first years of life. - There is no evidence for the use of probiotics in order to prevent asthma. Their use is not advised. - The Dutch vaccination program does not increase the risk on atopy or asthma. - There is no evidence for the benefit of influenza vaccination in children with asthma. - Exposure to a dog or cat in already sensitised children with asthma is associated with more severe asthma. Therefore, pets are not advised with these children

Randomised controlled study of clinical efficacy of spacer therapy in asthma with regard to electrostatic charge

BACKGROUND—Inhalation therapy using a pressured metered dose inhaler (pMDI) and a spacer is frequently used in the treatment of airway disease in children. Several laboratory studies found a clear negative influence of electrostatic charge (ESC) on plastic spacers on the delivery of aerosol.
AIMS—To investigate whether ESC on plastic spacers could diminish bronchodilating responses to salbutamol.
METHODS—Ninety asthmatic children (aged 4-8 years) were randomised into three groups: metal Nebuchamber, plastic Volumatic, and plastic Aerochamber. The bronchodilating response was measured by the change in peak expiratory flow rate (PEF) after 100 µg and 400µg salbutamol. Within the Volumatic and Aerochamber groups, a crossover comparison was made between electrostatic and non-electrostatic spacers.
RESULTS—We found no significant effect of ESC on the bronchodilating response to salbutamol with any of the doses in the Aerochamber and Volumatic groups. For the plastic spacers, the mean difference of the change in PEF after 100 µg salbutamol between non-electrostatic and electrostatic spacers was only +1.7% (95% CI −1.3% to 4.7%). After 400 µg salbutamol this was +1.9% (95% CI −1.4% to 5.1%). A comparable efficacy was found for the Nebuchamber, the Aerochamber, and Volumatic with respect to the change in PEF after 100 and 400 µg salbutamol.
CONCLUSION—This study showed no negative influence of ESC on plastic spacers with regard to clinical efficacy of a β(2) agonist (salbutamol) in children with asthma. The metal Nebuchamber, plastic Aerochamber, and plastic Volumatic were equally effective.