Elisabeth Maurer

Factors influencing age at diagnosis of primary ciliary dyskinesia in European children.

Primary ciliary dyskinesia (PCD) is a hereditary disorder of mucociliary clearance causing chronic upper and lower airways disease. We determined the number of patients with diagnosed PCD across Europe, described age at diagnosis and determined risk factors for late diagnosis. Centres treating children with PCD in Europe answered questionnaires and provided anonymous patient lists. In total, 223 centres from 26 countries reported 1,009 patients aged <20 yrs. Reported cases per million children (for 5–14 yr olds) were highest in Cyprus (111), Switzerland (47) and Denmark (46). Overall, 57% were males and 48% had situs inversus. Median age at diagnosis was 5.3 yrs, lower in children with situs inversus (3.5 versus 5.8 yrs; p<0.001) and in children treated in large centres (4.1 versus 4.8 yrs; p = 0.002). Adjusted age at diagnosis was 5.0 yrs in Western Europe, 4.8 yrs in the British Isles, 5.5 yrs in Northern Europe, 6.8 yrs in Eastern Europe and 6.5 yrs in Southern Europe (p<0.001). This strongly correlated with general government expenditures on health (p<0.001). This European survey suggests that PCD in children is under-diagnosed and diagnosed late, particularly in countries with low health expenditures. Prospective studies should assess the impact this delay might have on patient prognosis and on health economic costs across Europe.

Development and Validation of a Symptom-Based Activity Index for Adults With Eosinophilic Esophagitis

BACKGROUND & AIMS Standardized instruments are needed to assess the activity of eosinophilic esophagitis (EoE) and to provide end points for clinical trials and observational studies. We aimed to develop and validate a patient-reported outcome (PRO) instrument and score, based on items that could account for variations in patient assessments of disease severity. We also evaluated relationships between patient assessment of disease severity and EoE-associated endoscopic, histologic, and laboratory findings. METHODS We collected information from 186 patients with EoE in Switzerland and the United States (69.4% male; median age, 43 y) via surveys (n = 135), focus groups (n = 27), and semistructured interviews (n = 24). Items were generated for the instruments to assess biologic activity based on physician input. Linear regression was used to quantify the extent to which variations in patient-reported disease characteristics could account for variations in patient assessment of EoE severity. The PRO instrument was used prospectively in 153 adult patients with EoE (72.5% male; median age, 38 y), and validated in an independent group of 120 patients with EoE (60.8% male; median age, 40.5 y). RESULTS Seven PRO factors that are used to assess characteristics of dysphagia, behavioral adaptations to living with dysphagia, and pain while swallowing accounted for 67% of the variation in patient assessment of disease severity. Based on statistical consideration and patient input, a 7-day recall period was selected. Highly active EoE, based on endoscopic and histologic findings, was associated with an increase in patient-assessed disease severity. In the validation study, the mean difference between patient assessment of EoE severity (range, 0-10) and PRO score (range, 0-8.52) was 0.15. CONCLUSIONS We developed and validated an EoE scoring system based on 7 PRO items that assess symptoms over a 7-day recall period. Clinicaltrials.gov number: NCT00939263.

Management of primary ciliary dyskinesia in European children: recommendations and clinical practice

The European Respiratory Society Task Force on primary ciliary dyskinesia (PCD) in children recently published recommendations for diagnosis and management. This paper compares these recommendations with current clinical practice in Europe. Questionnaires were returned by 194 paediatric respiratory centres caring for PCD patients in 26 countries. In most countries, PCD care was not centralised, with a median (interquartile range) of 4 (2–9) patients treated per centre. Overall, 90% of centres had access to nasal or bronchial mucosal biopsy. Samples were analysed by electron microscopy (77%) and ciliary function tests (57%). Nasal nitric oxide was used for screening in 46% of centres and saccharine tests in 36%. Treatment approaches varied widely, both within and between countries. European region, size of centre and the country’s general government expenditure on health partly defined availability of advanced diagnostic tests and choice of treatments. In conclusion, we found substantial heterogeneity in management of PCD within and between countries, and poor concordance with current recommendations. This demonstrates how essential it is to standardise management and decrease inequality between countries. Our results also demonstrate the urgent need for research: to simplify PCD diagnosis, to understand the natural history and to test the effectiveness of interventions.

Clinical manifestations in primary ciliary dyskinesia: systematic review and meta-analysis

Few original studies have described the prevalence and severity of clinical symptoms of primary ciliary dyskinesia (PCD). This systematic review and meta-analysis aimed to identify all published studies on clinical manifestations of PCD patients, and to describe their prevalence and severity stratified by age and sex. We searched PubMed, Embase and Scopus for studies describing clinical symptoms of ≥10 patients with PCD. We performed meta-analyses and meta-regression to explain heterogeneity. We included 52 studies describing a total of 1970 patients (range 10–168 per study). We found a prevalence of 5% for congenital heart disease. For the rest of reported characteristics, we found considerable heterogeneity (I2 range 68–93.8%) when calculating the weighted mean prevalence. Even after taking into account the explanatory factors, the largest part of the between-studies variance in symptom prevalence remained unexplained for all symptoms. Sensitivity analysis including only studies with test-proven diagnosis showed similar results in prevalence and heterogeneity. Large differences in study design, selection of study populations and definition of symptoms could explain the heterogeneity in symptom prevalence. To better characterise the disease, we need larger, multicentre, multidisciplinary, prospective studies that include all age groups, use uniform diagnostics and report on all symptoms. Review of the clinical manifestations of PCD found between-study variation; large prospective studies needed http://ow.ly/Y5GC300Sw73

How Do Gastroenterologists Assess Overall Activity of Eosinophilic Esophagitis in Adult Patients

OBJECTIVES:There is no “gold standard” for assessing disease activity in patients with eosinophilic esophagitis (EoE). We aimed to compare physicians’ judgment of EoE activity with patients’ judgment of symptom severity. We also aimed to examine the relative contribution of symptoms as well as endoscopic and histologic findings in shaping physicians’ judgment of EoE activity.METHODS:Six gastroenterologists (all EoE experts) assessed EoE-associated symptoms in adult patients. Patients completed a symptom instrument and provided global assessment of EoE symptom severity (PatGA) (Likert scale: 0 (inactive) to 10 (most active)). Following esophagogastroduodenoscopy with biopsy sampling, gastroenterologists provided a global assessment of EoE activity (PhysGA) (Likert scale from 0 to 10) based on patient history and endoscopic and histologic findings. Linear regression and analysis of variance was used to quantify the extent to which variations in severity of EoE symptoms and endoscopic and histologic findings explain variations in PhysGA.RESULTS:A total of 149 EoE patients were prospectively included (71.8% male, median age at inclusion 38 years, 71.8% with concomitant allergies). A moderate positive correlation between PhysGA and PatGA (rho=0.442, P<0.001) was observed and the mean difference in the Bland–Altman plot was 1.77. Variations in severity of endoscopic findings, symptoms, and histologic findings alone explained 53%, 49%, and 30%, of the variability in PhysGA, respectively. Together, these findings explained 75% of variability in PhysGA.CONCLUSIONS:Gastroenterologists rate EoE activity mainly on the basis of endoscopic findings and symptoms and, to a lesser extent, on histologic findings.

The international primary ciliary dyskinesia cohort (iPCD Cohort): methods and first results

Data on primary ciliary dyskinesia (PCD) epidemiology is scarce and published studies are characterised by low numbers. In the framework of the European Union project BESTCILIA we aimed to combine all available datasets in a retrospective international PCD cohort (iPCD Cohort). We identified eligible datasets by performing a systematic review of published studies containing clinical information on PCD, and by contacting members of past and current European Respiratory Society Task Forces on PCD. We compared the contents of the datasets, clarified definitions and pooled them in a standardised format. As of April 2016 the iPCD Cohort includes data on 3013 patients from 18 countries. It includes data on diagnostic evaluations, symptoms, lung function, growth and treatments. Longitudinal data are currently available for 542 patients. The extent of clinical details per patient varies between centres. More than 50% of patients have a definite PCD diagnosis based on recent guidelines. Children aged 10–19 years are the largest age group, followed by younger children (≤9 years) and young adults (20–29 years). This is the largest observational PCD dataset available to date. It will allow us to answer pertinent questions on clinical phenotype, disease severity, prognosis and effect of treatments, and to investigate genotype–phenotype correlations. The iPCD Cohort offers a unique opportunity to study PCD in an international retrospective cohort of >3000 patients http://ow.ly/rn0m304Jgsu

Disparities in treatment rates of paediatric end-stage renal disease across Europe: insights from the ESPN/ERA-EDTA registry

BACKGROUND Considerable disparities exist in the provision of paediatric renal replacement therapy (RRT) across Europe. This study aims to determine whether these disparities arise from geographical differences in the occurrence of renal disease, or whether country-level access-to-care factors may be responsible. METHODS Incidence was defined as the number of new patients aged 0-14 years starting RRT per year, between 2007 and 2011, per million children (pmc), and was extracted from the ESPN/ERA-EDTA registry database for 35 European countries. Country-level indicators on macroeconomics, perinatal care and physical access to treatment were collected through an online survey and from the World Bank database. The estimated effect is presented per 1SD increase for each indicator. RESULTS The incidence of paediatric RRT in Europe was 5.4 cases pmc. Incidence decreased from Western to Eastern Europe (-1.91 pmc/1321 km, P < 0.0001), and increased from Southern to Northern Europe (0.93 pmc/838 km, P = 0.002). Regional differences in the occurrence of specific renal diseases were marginal. Higher RRT treatment rates were found in wealthier countries (2.47 pmc/€10 378 GDP per capita, P < 0.0001), among those that tend to spend more on healthcare (1.45 pmc/1.7% public health expenditure, P < 0.0001), and among countries where patients pay less out-of-pocket for healthcare (-1.29 pmc/11.7% out-of-pocket health expenditure, P < 0.0001). Country neonatal mortality was inversely related with incidence in the youngest patients (ages 0-4, -1.1 pmc/2.1 deaths per 1000 births, P = 0.10). Countries with a higher incidence had a lower average age at RRT start, which was fully explained by country GDP per capita. CONCLUSIONS Inequalities exist in the provision of paediatric RRT throughout Europe, most of which are explained by differences in country macroeconomics, which limit the provision of treatment particularly in the youngest patients. This poses a challenge for healthcare policy makers in their aim to ensure universal and equal access to high-quality healthcare services across Europe.

Primary ciliary dyskinesia (Pcd) in Austria

SummaryINTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare hereditary recessive disease with symptoms of recurrent pneumonia, chronic bronchitis, bronchiectasis, and chronic sinusitis. Chronic rhinitis is often the presenting symptom in newborns and infants. Approximately half of the patients show visceral mirror image arrangements (situs inversus). In this study, we aimed 1) to determine the number of paediatric PCD patients in Austria, 2) to show the diagnostic and therapeutic modalities used in the clinical centres and 3) to describe symptoms of children with PCD. PATIENTS, MATERIAL AND METHODS: For the first two aims, we analysed data from a questionnaire survey of the European Respiratory Society (ERS) task force on Primary Ciliary Dyskinesia in children. All paediatric respiratory units in Austria received a questionnaire. Symptoms of PCD patients from Vienna Childrens University Hospital (aim 3) were extracted from case histories. RESULTS: In 13 Austrian clinics 48 patients with PCD (36 aged from 0–19 years) were identified. The prevalence of reported cases (aged 0–19 yrs) in Austria was 1:48000. Median age at diagnosis was 4.8 years (IQR 0.3–8.2), lower in children with situs inversus compared to those without (3.1 vs. 8.1 yrs, p = 0.067). In 2005–2006, the saccharine test was still the most commonly used screening test for PCD in Austria (45%). Confirmation of the diagnosis was usually by electron microscopy (73%). All clinics treated exacerbations immediately with antibiotics, 73% prescribed airway clearance therapy routinely to all patients. Other therapies and diagnostic tests were applied very inconsistently across Austrian hospitals. All PCD patients from Vienna (n = 13) had increased upper and lower respiratory secretions, most had recurring airway infections (n = 12), bronchiectasis (n = 7) and bronchitis (n = 7). CONCLUSION: Diagnosis and therapy of PCD in Austria are inhomogeneous. Prospective studies are needed to learn more about the course of the disease and to evaluate benefits and harms of different treatment strategies.ZusammenfassungEINLEITUNG: Die primäre Ziliendyskinesie (Primary Ciliary Dykinesia, PCD) ist eine seltene, meist autosomal-rezessiv vererbte Erkrankung, mit den typischen Manifestationen rezidivierende Pneumonien, chronische Bronchitis, Bronchiektasien, chronische Sinusitis und, insbesondere bei Neugeborenen und Säuglingen, chronischer Rhinitis. Die Hälfte der Patienten haben einen Situs inversus. Die Ziele dieser Studie waren, 1) die Anzahl pädiatrischer PCD-Patienten in Österreich zu erfassen, 2) die diagnostischen und therapeutischen Modalitäten der behandelnden Zentren darzustellen und 3) die Symptomatik der Patienten zu beschreiben. PATIENTEN, MATERIAL UND METHODEN: Zur Beantwortung der ersten zwei Fragen analysierten wir die österreichischen Resultate einer Fragebogenuntersuchung der pädiatrischen PCD Taskforce der European Respiratory Society (ERS). Die klinischen Charakteristika der PCD-Patienten an der Universitätsklinik für Kinder- und Jugendheilkunde in Wien stellten wir anhand der Krankengeschichten zusammen. ERGEBNISSE: In 13 österreichischen Krankenhäusern wurden 48 Patienten identifiziert (36 im Alter von 0–19 Jahre). Dies ergibt für Österreich eine Prävalenz diagnostizierter PCD-Patienten (0–19 Jahre) von 1:48000. Das mediane Alter bei Diagnose war 4,8 Jahre (IQR 0,3–8,2 Jahre). Patienten mit Situs inversus wurden früher diagsnotiziert (3,1 Jahre versus 8,1 Jahre; p = 0,067). Das gebräuchlichste screening-Verfahren (2005–2006) war der Saccharintest (45%), zur Diagnosesicherung wurde meist die Elektronenmikroskopie eingesetzt (73%). Alle Kliniken behandelten Exazerbationen sofort antibiotisch, Atemphysiotherapie wurde in 73% der Zentren eingesetzt. Insgesamt waren Diagnostik und Therapie der PCD in Österreich uneinheitlich. Alle Patienten der Universitätsklinik Wien (n = 13) hatten eine verstärkte Sekretproduktion, die meisten rezidivierende Atemwegsinfekte (n = 12), Bronchiektasen (n = 7) und Bronchitis (n = 7). KONKLUSION: Diagnostik und Therapie der PCD in Österreich sind uneinheitlich. Prospektive Studien sind notwendig, den Verlauf der Erkrankung zu erforschen sowie Nutzen und Schaden unterschiedlicher Therapie-konzepte darzustellen.INTRODUCTION Primary ciliary dyskinesia (PCD) is a rare hereditary recessive disease with symptoms of recurrent pneumonia, chronic bronchitis, bronchiectasis, and chronic sinusitis. Chronic rhinitis is often the presenting symptom in newborns and infants. Approximately half of the patients show visceral mirror image arrangements (situs inversus). In this study, we aimed 1) to determine the number of paediatric PCD patients in Austria, 2) to show the diagnostic and therapeutic modalities used in the clinical centres and 3) to describe symptoms of children with PCD. PATIENTS, MATERIAL AND METHODS For the first two aims, we analysed data from a questionnaire survey of the European Respiratory Society (ERS) task force on Primary Ciliary Dyskinesia in children. All paediatric respiratory units in Austria received a questionnaire. Symptoms of PCD patients from Vienna Childrens University Hospital (aim 3) were extracted from case histories. RESULTS In 13 Austrian clinics 48 patients with PCD (36 aged from 0-19 years) were identified. The prevalence of reported cases (aged 0-19 yrs) in Austria was 1:48000. Median age at diagnosis was 4.8 years (IQR 0.3-8.2), lower in children with situs inversus compared to those without (3.1 vs. 8.1 yrs, p = 0.067). In 2005-2006, the saccharine test was still the most commonly used screening test for PCD in Austria (45%). Confirmation of the diagnosis was usually by electron microscopy (73%). All clinics treated exacerbations immediately with antibiotics, 73% prescribed airway clearance therapy routinely to all patients. Other therapies and diagnostic tests were applied very inconsistently across Austrian hospitals. All PCD patients from Vienna (n = 13) had increased upper and lower respiratory secretions, most had recurring airway infections (n = 12), bronchiectasis (n = 7) and bronchitis (n = 7). CONCLUSION Diagnosis and therapy of PCD in Austria are inhomogeneous. Prospective studies are needed to learn more about the course of the disease and to evaluate benefits and harms of different treatment strategies.

Growth and nutritional status, and their association with lung function: a study from the international Primary Ciliary Dyskinesia Cohort

Chronic respiratory disease can affect growth and nutrition, which can influence lung function. We investigated height, body mass index (BMI), and lung function in patients with primary ciliary dyskinesia (PCD). In this study, based on the international PCD (iPCD) Cohort, we calculated z-scores for height and BMI using World Health Organization (WHO) and national growth references, and assessed associations with age, sex, country, diagnostic certainty, age at diagnosis, organ laterality and lung function in multilevel regression models that accounted for repeated measurements. We analysed 6402 measurements from 1609 iPCD Cohort patients. Height was reduced compared to WHO (z-score −0.12, 95% CI −0.17 to −0.06) and national references (z-score −0.27, 95% CI −0.33 to −0.21) in male and female patients in all age groups, with variation between countries. Height and BMI were higher in patients diagnosed earlier in life (p=0.026 and p<0.001, respectively) and closely associated with forced expiratory volume in 1 s and forced vital capacity z-scores (p<0.001). Our study indicates that both growth and nutrition are affected adversely in PCD patients from early life and are both strongly associated with lung function. If supported by longitudinal studies, these findings suggest that early diagnosis with multidisciplinary management and nutritional advice could improve growth and delay disease progression and lung function impairment in PCD. Multidisciplinary management and nutritional advice could improve growth and delay lung function impairment in PCD http://ow.ly/5iQz30gB4Mo

Primäre Ziliendyskinesie in Österreich

SummaryINTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare hereditary recessive disease with symptoms of recurrent pneumonia, chronic bronchitis, bronchiectasis, and chronic sinusitis. Chronic rhinitis is often the presenting symptom in newborns and infants. Approximately half of the patients show visceral mirror image arrangements (situs inversus). In this study, we aimed 1) to determine the number of paediatric PCD patients in Austria, 2) to show the diagnostic and therapeutic modalities used in the clinical centres and 3) to describe symptoms of children with PCD. PATIENTS, MATERIAL AND METHODS: For the first two aims, we analysed data from a questionnaire survey of the European Respiratory Society (ERS) task force on Primary Ciliary Dyskinesia in children. All paediatric respiratory units in Austria received a questionnaire. Symptoms of PCD patients from Vienna Childrens University Hospital (aim 3) were extracted from case histories. RESULTS: In 13 Austrian clinics 48 patients with PCD (36 aged from 0–19 years) were identified. The prevalence of reported cases (aged 0–19 yrs) in Austria was 1:48000. Median age at diagnosis was 4.8 years (IQR 0.3–8.2), lower in children with situs inversus compared to those without (3.1 vs. 8.1 yrs, p = 0.067). In 2005–2006, the saccharine test was still the most commonly used screening test for PCD in Austria (45%). Confirmation of the diagnosis was usually by electron microscopy (73%). All clinics treated exacerbations immediately with antibiotics, 73% prescribed airway clearance therapy routinely to all patients. Other therapies and diagnostic tests were applied very inconsistently across Austrian hospitals. All PCD patients from Vienna (n = 13) had increased upper and lower respiratory secretions, most had recurring airway infections (n = 12), bronchiectasis (n = 7) and bronchitis (n = 7). CONCLUSION: Diagnosis and therapy of PCD in Austria are inhomogeneous. Prospective studies are needed to learn more about the course of the disease and to evaluate benefits and harms of different treatment strategies.ZusammenfassungEINLEITUNG: Die primäre Ziliendyskinesie (Primary Ciliary Dykinesia, PCD) ist eine seltene, meist autosomal-rezessiv vererbte Erkrankung, mit den typischen Manifestationen rezidivierende Pneumonien, chronische Bronchitis, Bronchiektasien, chronische Sinusitis und, insbesondere bei Neugeborenen und Säuglingen, chronischer Rhinitis. Die Hälfte der Patienten haben einen Situs inversus. Die Ziele dieser Studie waren, 1) die Anzahl pädiatrischer PCD-Patienten in Österreich zu erfassen, 2) die diagnostischen und therapeutischen Modalitäten der behandelnden Zentren darzustellen und 3) die Symptomatik der Patienten zu beschreiben. PATIENTEN, MATERIAL UND METHODEN: Zur Beantwortung der ersten zwei Fragen analysierten wir die österreichischen Resultate einer Fragebogenuntersuchung der pädiatrischen PCD Taskforce der European Respiratory Society (ERS). Die klinischen Charakteristika der PCD-Patienten an der Universitätsklinik für Kinder- und Jugendheilkunde in Wien stellten wir anhand der Krankengeschichten zusammen. ERGEBNISSE: In 13 österreichischen Krankenhäusern wurden 48 Patienten identifiziert (36 im Alter von 0–19 Jahre). Dies ergibt für Österreich eine Prävalenz diagnostizierter PCD-Patienten (0–19 Jahre) von 1:48000. Das mediane Alter bei Diagnose war 4,8 Jahre (IQR 0,3–8,2 Jahre). Patienten mit Situs inversus wurden früher diagsnotiziert (3,1 Jahre versus 8,1 Jahre; p = 0,067). Das gebräuchlichste screening-Verfahren (2005–2006) war der Saccharintest (45%), zur Diagnosesicherung wurde meist die Elektronenmikroskopie eingesetzt (73%). Alle Kliniken behandelten Exazerbationen sofort antibiotisch, Atemphysiotherapie wurde in 73% der Zentren eingesetzt. Insgesamt waren Diagnostik und Therapie der PCD in Österreich uneinheitlich. Alle Patienten der Universitätsklinik Wien (n = 13) hatten eine verstärkte Sekretproduktion, die meisten rezidivierende Atemwegsinfekte (n = 12), Bronchiektasen (n = 7) und Bronchitis (n = 7). KONKLUSION: Diagnostik und Therapie der PCD in Österreich sind uneinheitlich. Prospektive Studien sind notwendig, den Verlauf der Erkrankung zu erforschen sowie Nutzen und Schaden unterschiedlicher Therapie-konzepte darzustellen.INTRODUCTION Primary ciliary dyskinesia (PCD) is a rare hereditary recessive disease with symptoms of recurrent pneumonia, chronic bronchitis, bronchiectasis, and chronic sinusitis. Chronic rhinitis is often the presenting symptom in newborns and infants. Approximately half of the patients show visceral mirror image arrangements (situs inversus). In this study, we aimed 1) to determine the number of paediatric PCD patients in Austria, 2) to show the diagnostic and therapeutic modalities used in the clinical centres and 3) to describe symptoms of children with PCD. PATIENTS, MATERIAL AND METHODS For the first two aims, we analysed data from a questionnaire survey of the European Respiratory Society (ERS) task force on Primary Ciliary Dyskinesia in children. All paediatric respiratory units in Austria received a questionnaire. Symptoms of PCD patients from Vienna Childrens University Hospital (aim 3) were extracted from case histories. RESULTS In 13 Austrian clinics 48 patients with PCD (36 aged from 0-19 years) were identified. The prevalence of reported cases (aged 0-19 yrs) in Austria was 1:48000. Median age at diagnosis was 4.8 years (IQR 0.3-8.2), lower in children with situs inversus compared to those without (3.1 vs. 8.1 yrs, p = 0.067). In 2005-2006, the saccharine test was still the most commonly used screening test for PCD in Austria (45%). Confirmation of the diagnosis was usually by electron microscopy (73%). All clinics treated exacerbations immediately with antibiotics, 73% prescribed airway clearance therapy routinely to all patients. Other therapies and diagnostic tests were applied very inconsistently across Austrian hospitals. All PCD patients from Vienna (n = 13) had increased upper and lower respiratory secretions, most had recurring airway infections (n = 12), bronchiectasis (n = 7) and bronchitis (n = 7). CONCLUSION Diagnosis and therapy of PCD in Austria are inhomogeneous. Prospective studies are needed to learn more about the course of the disease and to evaluate benefits and harms of different treatment strategies.