Sonographic pancreas echogenicity in cystic fibrosis compared to exocrine pancreatic function and pancreas fat content at Dixon-MRI.

OBJECTIVE: Fatty infiltration of the pancreas is a dominating feature in cystic fibrosis (CF). We evaluate the association between pancreatic fat content assessed by Dixon magnetic resonance imaging (MRI), pancreatic echogenicity at ultrasonography (US) and exocrine function in CF patients and healthy controls (HC). MATERIAL AND METHODS: Transabdominal US, pancreatic Dixon-MRI and diffusion-weighted imaging (DWI) were performed in 21 CF patients and 15 HCs. Exocrine function was assessed by endoscopic secretin test and fecal elastase. RESULTS: CF patients were grouped according to exocrine pancreatic function as subjects with normal (CFS: n = 11) or reduced (CFI: n = 10) function. Among CFI 90% (9/10) had visual hyperechogenicity. CFI also had increased echo-level values (p<0.05 vs others). All CFI (10/10) had markedly increased pancreatic fat content estimated by MRI compared to sufficient groups, p<0.001). Among CFS patients and HC, 27% (3/11) and 33% (5/15), respectively, had hyperechoic pancreas. However, all these had low pancreatic fat-content at MRI compared to CFI. In CFI, pancreatic fat content was correlated to ADC (r = -0.93, p<0.001). CONCLUSION: Pancreas insufficient CF patients exhibit severe pancreatic fatty-infiltration at MRI and hyperechoic pancreas at US. Pancreas hyperechogenicity in pancreatic sufficient subjects does not co-exist with fatty infiltration at MRI. MRI evaluates pancreatic fatty infiltration more accurately than US and fat infiltration estimated by MRI outperforms sonographic hyper-echogenicity as a marker for exocrine pancreatic failure in CF.

Maternal age at delivery, lung function and asthma in offspring: a population-based survey.

There is limited information about potential impact of maternal age on the respiratory health of offspring. We investigated the association of maternal age at delivery with adult offspring's lung function, respiratory symptoms and asthma, and potential differences according to offspring sex.10 692 adults from 13 countries participating in the European Community Respiratory Health Survey (ECRHS) II responded to standardised interviews and provided lung function measurements and serum for IgE measurements at age 25-55 years. In logistic and linear multilevel mixed models we adjusted for participants' characteristics (age, education, centre, number of older siblings) and maternal characteristics (smoking in pregnancy, education) while investigating for differential effects by sex. Maternal age was validated in a subsample using data from the Norwegian birth registry.Increasing maternal age was associated with increasing forced expiratory volume in 1 s (2.33 mL per year, 95% CI 0.34-4.32 mL per year), more consistent in females (ptrend 0.025) than in males (ptrend 0.14). Asthma (OR 0.85, 95% CI 0.79-0.92) and respiratory symptoms (OR 0.87, 95% CI 0.82-0.92) decreased with increasing maternal age (per 5 years) in females, but not in males (pinteraction 0.05 and 0.001, respectively). The results were consistent across centres and not explained by confounding factors.Maternal ageing was related to higher adult lung function and less asthma/symptoms in females. Biological characteristics in offspring related to maternal ageing are plausible and need further investigation.

Contrast-enhanced ultrasonography of the pancreas shows impaired perfusion in pancreas insufficient cystic fibrosis patients.

BACKGROUND: Perfusion assessment of the pancreas is challenging and poorly evaluated. Pancreatic affection is a prevalent feature of cystic fibrosis (CF). Little is known about pancreatic perfusion in CF. We aimed to assess pancreatic perfusion by contrast-enhanced ultrasound (CEUS) analysed in the bolus-and-burst model and software. METHODS: We performed contrast enhanced ultrasound of the pancreas in 25 CF patients and 20 healthy controls. Perfusion data was analysed using a dedicated perfusion model providing the mean capillary transit-time (MTT), blood flow (BF) and blood-volume (BV). CF patients were divided according to exocrine function. RESULTS: The pancreas insufficient CF patients had longer MTT (p ≤ 0.002), lower BF (p < 0.001) and lower BV (p < 0.05) compared to the healthy controls and sufficient CF patients. Interrater analysis showed substantial agreement for the analysis of mean transit time. CONCLUSION: The bolus-and-burst method used on pancreatic CEUS-examinations demonstrates reduced perfusion in CF patients with pancreas affection. The perfusion model and software requires further optimization and standardization to be clinical applicable for the assessment of pancreatic perfusion.

Nordic consensus statement on the systematic assessment and management of possible severe asthma in adults.

Although a minority of asthma patients suffer from severe asthma, they represent a major clinical challenge in terms of poor symptom control despite high-dose treatment, risk of exacerbations, and side effects. Novel biological treatments may benefit patients with severe asthma, but are expensive, and are only effective in appropriately targeted patients. In some patients, symptoms are driven by other factors than asthma, and all patients with suspected severe asthma ('difficult asthma') should undergo systematic assessment, in order to differentiate between true severe asthma, and 'difficult-to-treat' patients, in whom poor control is related to factors such as poor adherence or co-morbidities. The Nordic Consensus Statement on severe asthma was developed by the Nordic Severe Asthma Network, consisting of members from Norway, Sweden, Finland, Denmark, Iceland and Estonia, including representatives from the respective national respiratory scientific societies with the aim to provide an overview and recommendations regarding the diagnosis, systematic assessment and management of severe asthma. Furthermore, the Consensus Statement proposes recommendations for the organization of severe asthma management in primary, secondary, and tertiary care.

Secretin-stimulated ultrasound estimation of pancreatic secretion in cystic fibrosis validated by magnetic resonance imaging.

OBJECTIVES: Secretin-stimulated magnetic resonance imaging (s-MRI) is the best validated radiological modality assessing pancreatic secretion. The purpose of this study was to compare volume output measures from secretin-stimulated transabdominal ultrasonography (s-US) to s-MRI for the diagnosis of exocrine pancreatic failure in cystic fibrosis (CF). METHODS: We performed transabdominal ultrasonography and MRI before and at timed intervals during 15 minutes after secretin stimulation in 21 CF patients and 13 healthy controls. To clearly identify the subjects with reduced exocrine pancreatic function, we classified CF patients as pancreas-sufficient or -insufficient by secretin-stimulated endoscopic short test and faecal elastase. RESULTS: Pancreas-insufficient CF patients had reduced pancreatic secretions compared to pancreas-sufficient subjects based on both imaging modalities (p < 0.001). Volume output estimates assessed by s-US correlated to that of s-MRI (r = 0.56-0.62; p < 0.001). Both s-US (AUC: 0.88) and s-MRI (AUC: 0.99) demonstrated good diagnostic accuracy for exocrine pancreatic failure. CONCLUSIONS: Pancreatic volume-output estimated by s-US corresponds well to exocrine pancreatic function in CF patients and yields comparable results to that of s-MRI. s-US provides a simple and feasible tool in the assessment of pancreatic secretion. KEY POINTS: • Cystic fibrosis patients with affected pancreas have reduced pancreatic secretions. • Secretin-stimulated sonography is a simple and feasible method to assess pancreatic output. • Secretin-simulated MRI is a more precise method to assess pancreatic secretions. • The sonographic and MRI methods yielded comparable pancreatic secretory output estimates.

Secretin-stimulated MRI assessment of exocrine pancreatic function in patients with cystic fibrosis and healthy controls.

PURPOSE: Secretin-stimulated magnetic resonance imaging (s-MRI) and pancreatic diffusion weighted imaging (DWI) are novel non-invasive imaging techniques for assessment of exocrine pancreatic insufficiency (EPI). The aim was to validate s-MRI assessed pancreatic secreted volume using novel semi-automatic quantification software, and to assess the ability of s-MRI with DWI to diagnose EPI in patients with cystic fibrosis (CF). METHODS: s-MRI and DWI was performed in 19 patients with CF (median age 21 years; range 16-56; eight men) and in 10 healthy controls (HC) (median age 46 years; range 20-65; four men). Sequential coronal T2-weighted images covering the duodenum and small bowel and axial DWI were acquired before and 1, 5, 9, and 13 min after secretin stimulation. A short endoscopic secretin test was used as reference method for EPI. RESULTS: CF patients with EPI had lower apparent diffusion coefficient before secretin in the pancreatic head (P < 0.001) and lower secreted bowel fluid volumes (P = 0.035) compared to HC and CF patients without EPI. ROC curve analyses identified that secreted fluid volume after 13 min yielded the highest diagnostic accuracy for diagnosing EPI (AUC 0.93; 95% CI [0.80-1.00]). CONCLUSION: Pancreatic s-MRI is useful for the assessment of exocrine pancreatic function with high diagnostic accuracy for the diagnosis of EPI in CF.

Need of education for dry powder inhaler storage and retention - a patient-reported survey.

BACKGROUND: Dry powder inhalers (DPIs) are the most commonly used devices in asthma treatment in the Nordic countries. As new DPIs become available, patients are likely to be exposed to more than one type of device, with variable optimal handling. The aim was to examine real life storage and retention of multidose DPIs in patients with asthma. METHODS: This patient-reported survey on real life storage and retention of DPIs included asthma patients using multidose DPIs. Basic patient characteristics, information on inhaler use and storage, check of expiry date, and concurrent inhaler use was examined using an on line questionnaire. RESULTS: A total of 738 patients were included with a median age of 41 years, out of which 83 % were women. Sixty-three per cent reported storage conditions pre-defined as risk locations for their maintenance inhaler and 38 % of the responding patients had more than one maintenance inhaler in use at the same time. Two thirds of the study population checked inhaler expiry date less than monthly or not at all. Use after expiry date was frequently reported. Two thirds of the patients had not received information on DPI storage, either from their doctor and/or nurse or at the pharmacy. CONCLUSIONS: This patient reported survey indicates that two thirds of the patients store their inhaler devices in suboptimal conditions, and only a minority had received instruction regarding inhaler handling. Non awareness of inhalers' expiry dates and use of more than one maintenance inhaler simultaneously was common. As inhaler mishandling may impact device functionality, improved communication and patient education is needed.

Diagnostic Accuracy of a Short Endoscopic Secretin Test in Patients With Cystic Fibrosis.

OBJECTIVE: Short endoscopic secretin tests for exocrine pancreatic function are not properly evaluated in cystic fibrosis (CF). METHODS: Patients with CF and healthy controls (HCs) underwent endoscopic collection of duodenal juice between 30 and 45 minutes after secretin stimulation. Duodenal juice was analyzed for HCO3 concentration and pancreatic enzyme activities. Stool was analyzed for fecal elastase. RESULTS: Thirty-one patients with CF and 25 HCs were tested. Patients were classified as exocrine pancreatic sufficient (n = 13) or insufficient (n = 18). Both bicarbonate concentrations and enzyme activities in duodenal juice differentiated patients with CFI from patients with CFS and HC (P < 0.001). The population displays strong correlation between severe CF genotype in both alleles and pancreatic insufficient phenotype (P < 0.001). CONCLUSIONS: Pancreatic exocrine insufficient CF patients could be differentiated from exocrine sufficient patients and HCs using short endoscopic secretin test.

Ultrasound echo-intensity predicts severe pancreatic affection in cystic fibrosis patients.

BACKGROUND: Pancreatic destruction affects the majority of patients with cystic fibrosis. We aimed to relate ultrasound findings to exocrine pancreatic function and cystic fibrosis genotype. METHODS: Patients with cystic fibrosis and a matched group of healthy controls were included. We performed transabdominal ultrasound, and recorded echo intensities of the pancreas and parenchymal characteristics according to endoscopic ultrasound based Rosemont criteria. RESULTS: We included 39 patients and 29 healthy controls. The cystic fibrosis patients were grouped according to exocrine pancreatic function; Cystic fibrosis, insufficient (n = 20) and sufficient (n = 19). Echo intensity measures and visual score demonstrated hyper-echogenicity in the pancreas insufficient group compared to the pancreas sufficient groups (p<0.001). Ductal and parenchymal changes were not prevalent in any of the groups. CONCLUSION: The hyper-echoic pancreas was the most frequent ultrasonographic finding in exocrine pancreas insufficient cystic fibrosis patients. Pancreatic echo levels correlated to pancreatic phenotype.

Diagnostic accuracy of secretin-stimulated ultrasonography of the pancreas assessing exocrine pancreatic failure in cystic fibrosis and chronic pancreatitis.

OBJECTIVE: Volume output failure is a feature of decreasing exocrine pancreatic function. This parameter is assessed by secretin-stimulated MRI in several studies. Our purpose was to evaluate ultrasonography of the fluid in the descending duodenum and Wirsung duct (WD) after secretin stimulation as a measure of pancreatic fluid flow in patients expected to have severe output failure. MATERIAL AND METHODS: We included subjects with chronic pancreatitis (CP), cystic fibrosis (CF) and a group of healthy controls in a prospective observation study. Transabdominal ultrasonography was performed before and during 15 min after secretin i.v. duodenal juice was collected by endoscopic short test (EST), and bicarbonate concentration measured. Patient groups were classified according to exocrine pancreatic function. RESULTS: Pancreatic insufficient CF (CFI) patients and CP insufficient (CPI) patients showed less duodenal fluid filling compared to other groups (p < 0.001). Measures of the WD diameter could only identify the most severe failure in the CFI group (p < 0.001). CONCLUSION: Secretin-stimulated ultrasonography can be used to assess pancreatic fluid flow and may be combined with EST in the evaluation of exocrine pancreatic function. Fluid filling in the descending part of duodenum was the most accurate predictor of pancreatic insufficiency in both patient groups. The test demonstrated better diagnostic accuracy diagnosing exocrine pancreatic failure in the CF patients than in CP patients.

Gender differences in the Scandinavian cystic fibrosis population.

AIMS: To explore whether gender differences in the Scandinavian Cystic Fibrosis (CF) patients exist in the areas of key clinical parameters, complications, and medication. METHODS: Cross-sectional data on 890 (416 female) pancreatic insufficient CF patients were evaluated regarding chronic infection, body mass index, lung function, medication, and diabetes, as well as data of Pseudomonas infection status, antibiotic treatment and hospitalization from 1-year follow-up. RESULTS: We found no differences in lung function, body mass index, or frequency of diabetes. The adult group consisted of more males than females (208:168). We found no significant difference in prevalence of chronic Pseudomonas aeruginosa infection, but during the follow-up the incidence of new chronic infection was higher in adult females (10/33 vs. 4/56). Females had higher prevalence of Burkholderia infection (21/416 vs. 11/474). Adult females had more days on intravenous antibiotics (median 39 vs. 26 days/year), and days in hospital (median 2 vs. 0 days/year). More adult females received inhaled and oral steroids. In the pediatric cohort, females were treated more often with macrolides as an anti-inflammatory agent. CONCLUSION: We found no gender difference in key clinical parameters in our CF population. However, our study showed a higher risk of Pseudomonas and Burkholderia infection among the female patients. Additionally, we found that female patients require more intensified treatment regarding antibiotics, macrolides, steroids and days of hospitalization, indicating a true female disadvantage even with modern aggressive treatment. The finding of more males than females in the adult population suggesting a male advantage, warrants a mortality study.

Differences in prevalence and treatment of Pseudomonas aeruginosa in cystic fibrosis centres in Denmark, Norway and Sweden.

BACKGROUND: Chronic Pseudomonas aeruginosa (PA) infection causes increased morbidity and mortality in cystic fibrosis (CF). This study aimed to answer the following questions: Does the prevalence of chronic infection with PA differ between the CF centres in Scandinavia? Which differences exist concerning segregation and treatment of PA? METHODS: 989 patients (86%) from all eight CF-centres in Scandinavia were included. Demographic and clinical data, including PA colonisation status based on cultures and serology, were recorded at inclusion. The patients were followed prospectively for 1 year, recording number of days with anti-PA antibiotic treatment. RESULTS: In all pancreatic insufficient (PI) patients (n=890) the prevalence of chronic PA infection at each centre ranged from 25.8% to 48.9%, but were not significantly different. In PI patients <19 years the prevalence was 14.5% in Copenhagen compared to 30.9% in the Swedish centres pooled (p=0.001). In intermittently colonised PI patients <19 years the median number of days per year on anti-PA antibiotics was almost 6 times higher in Copenhagen (mean 86 (110), median 61 days) compared to the Swedish centres pooled (mean 27 (52), median 11 days) (p=0.037). The pulmonary function was similar. CONCLUSIONS: It is possible to maintain a very low prevalence of chronic PA infection in CF patients <19 years. We speculate that this was most likely due to a very intensive treatment of intermittently colonised patients with inhaled anti-PA antibiotics over prolonged periods of time in some centres. Since lung function was similar in centres with less intensive use of inhaled antibiotics, studies comparing different treatment modalities and other parts of CF care are needed to define the best clinical practice, including how to use antibiotics in the most rational way.

Early life environment and snoring in adulthood.

BACKGROUND: To our knowledge, no studies of the possible association of early life environment with snoring in adulthood have been published. We aimed to investigate whether early life environment is associated with snoring later in life. METHODS: A questionnaire including snoring frequency in adulthood and environmental factors in early life was obtained from 16,190 randomly selected men and women, aged 25-54 years, in Sweden, Norway, Iceland, Denmark and Estonia (response rate 74%). RESULTS: A total of 15,556 subjects answered the questions on snoring. Habitual snoring, defined as loud and disturbing snoring at least 3 nights a week, was reported by 18%. Being hospitalized for a respiratory infection before the age of two years (adjusted odds ratio (OR) = 1.27; 95% confidence interval (CI) 1.01-1.59), suffering from recurrent otitis as a child (OR = 1.18; 95%CI 1.05-1.33), growing up in a large family (OR = 1.04; 95%CI 1.002-1.07) and being exposed to a dog at home as a newborn (OR = 1.26; 95%CI 1.12-1.42) were independently related to snoring later in life and independent of a number of possible confounders in adulthood. The same childhood environmental factors except household size were also related with snoring and daytime sleepiness combined. CONCLUSION: The predisposition for adult snoring may be partly established early in life. Having had severe airway infections or recurrent otitis in childhood, being exposed to a dog as a newborn and growing up in a large family are environmental factors associated with snoring in adulthood.

Young maternal age at delivery is associated with asthma in adult offspring.

OBJECTIVE: Some studies have shown an association between lower maternal age at delivery and increased asthma in children and young adults. It is unclear whether this represents an effect of maternal ageing or a protective effect of siblings. In a North-European population based study, we investigated whether mother's age at delivery was associated with risk for asthma and hay fever in adult offspring, taking into account relevant confounders. METHODS: A total of 16,190 subjects (74%) aged 23-54 yr answered a postal questionnaire in a follow-up of the European Community Respiratory Health Survey (ECRHS I). RESULTS: The associations of maternal age at delivery with hay fever, respiratory symptoms and diagnosed asthma were analysed using logistic regression, adjusting for household size, dwelling, parental education, centre, gender, adult hay fever, smoking, age and body mass index (BMI). The adjusted odds ratios (95% CI) for wheeze with breathlessness, wheeze without a cold and asthma in the offspring were 0.94 (0.90-0.99), 0.89 (0.86-0.94) and 0.92 (0.88-0.97), respectively, per 5 yr increase in maternal age. No heterogeneity between centres was found (p=0.84). The estimates remained similar in sub-sample analyses when adjusting for siblings, maternal smoking (n=3109) and for birth weight (n=1686). Hay fever was more common among those with the youngest and oldest mothers. CONCLUSIONS: In this large North-European multi-centre study, asthma was less common with increasing maternal age. This effect was consistent between centres and persisted with adjustment for several potential confounders, suggesting that the association may possibly be explained by biological changes related to maternal ageing.

The influence of active and passive smoking on habitual snoring.

The impact of active smoking, passive smoking, and obesity on habitual snoring in the population is mainly unknown. We aimed to study the relationship of habitual snoring with active and passive tobacco smoking in a population-based sample. A total of 15,555 of 21,802 (71%) randomly selected men and women aged 25-54 years from Iceland, Estonia, Denmark, Norway, and Sweden answered a postal questionnaire. Habitual snoring, defined as loud and disturbing snoring at least 3 nights a week, was more prevalent among current smokers (24.0%, p < 0.0001) and ex-smokers (20.3%, p < 0.0001) than in never-smokers (13.7%). Snoring was also more prevalent in never-smokers exposed to passive smoking at home on a daily basis than in never-smokers without this exposure (19.8% vs. 13.3%, p < 0.0001). The frequency of habitual snoring increased with the amount of tobacco smoked. Active smoking and passive smoking were related to snoring, independent of obesity, sex, center, and age. Ever smoking accounted for 17.1% of the attributable risk of habitual snoring, obesity (body mass index > or = 30 kg/m(2)) for 4.3%, and passive smoking for 2.2%. Smoking, both current and ex-smoking, is a major contributor to habitual snoring in the general population. Passive smoking is a previously unrecognized risk factor for snoring among adults.