Myrofora Goutaki

European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia

The diagnosis of primary ciliary dyskinesia is often confirmed with standard, albeit complex and expensive, tests. In many cases, however, the diagnosis remains difficult despite the array of sophisticated diagnostic tests. There is no “gold standard” reference test. Hence, a Task Force supported by the European Respiratory Society has developed this guideline to provide evidence-based recommendations on diagnostic testing, especially in light of new developments in such tests, and the need for robust diagnoses of patients who might enter randomised controlled trials of treatments. The guideline is based on pre-defined questions relevant for clinical care, a systematic review of the literature, and assessment of the evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. It focuses on clinical presentation, nasal nitric oxide, analysis of ciliary beat frequency and pattern by high-speed video-microscopy analysis, transmission electron microscopy, genotyping and immunofluorescence. It then used a modified Delphi survey to develop an algorithm for the use of diagnostic tests to definitively confirm and exclude the diagnosis of primary ciliary dyskinesia; and to provide advice when the diagnosis was not conclusive. Finally, this guideline proposes a set of quality criteria for future research on the validity of diagnostic methods for primary ciliary dyskinesia. International ERS guidelines recommend a combination of tests to diagnose primary ciliary dyskinesia http://ow.ly/sJhH304InBN

PICADAR: a diagnostic predictive tool for primary ciliary dyskinesia

Symptoms of primary ciliary dyskinesia (PCD) are nonspecific and guidance on whom to refer for testing is limited. Diagnostic tests for PCD are highly specialised, requiring expensive equipment and experienced PCD scientists. This study aims to develop a practical clinical diagnostic tool to identify patients requiring testing. Patients consecutively referred for testing were studied. Information readily obtained from patient history was correlated with diagnostic outcome. Using logistic regression, the predictive performance of the best model was tested by receiver operating characteristic curve analyses. The model was simplified into a practical tool (PICADAR) and externally validated in a second diagnostic centre. Of 641 referrals with a definitive diagnostic outcome, 75 (12%) were positive. PICADAR applies to patients with persistent wet cough and has seven predictive parameters: full-term gestation, neonatal chest symptoms, neonatal intensive care admittance, chronic rhinitis, ear symptoms, situs inversus and congenital cardiac defect. Sensitivity and specificity of the tool were 0.90 and 0.75 for a cut-off score of 5 points. Area under the curve for the internally and externally validated tool was 0.91 and 0.87, respectively. PICADAR represents a simple diagnostic clinical prediction rule with good accuracy and validity, ready for testing in respiratory centres referring to PCD centres. PICADAR is a simple diagnostic prediction tool for PCD with good accuracy and validity that is now ready for testing http://ow.ly/X6y9s

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

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

The role of TLR4 and CD14 polymorphisms in the pathogenesis of respiratory syncytial virus bronchiolitis in greek infants.

Clinical manifestations of respiratory syncytial virus (RSV) infection vary from minimal disease to severe acute bronchiolitis. The structural complex of TLR4/CD14 participates in the virus recognition as a component of natural immune response. Genetic variations of TLR4/CD14 may explain great variations in disease severity. The aim of this study was to investigate the possible role of polymorphisms of TLR4, Asp299Gly and Thr399Ile and CD14, C-159T and C-550T in the development of RSV bronchiolitis. Our study included two groups of Greek infants and young children (A and B). Group A consisted of 50 infants ≤2 years of age hospitalised with bronchiolitis and group B of 99 previously healthy children aged 4–14 years (control group) with a free past medical history. RSV was indentified by PCR of genetic material that was extracted from nasopharyngeal samples collected from all patients. Blood samples were used to extract DNA and by using the PCR-RFLP method we performed TLR4 and CD14 genotyping. We found no association between TLR4 polymorphisms (Asp299Gly and Thr399Ile) and the development of acute bronchiolitis. For CD14 polymorphisms, a positive association was found between the C-159T and the development of bronchiolitis (p=0.05) but not for the other loci. There were no differences detected in the frequencies of the four polymorphisms studied among infants with RSV and non-RSV bronchiolitis. It is concluded that protein CD14 may have a functional role in the viral conjunction to the structural complex TLR4/CD14. The association between the polymorphism C-159T and the manifestation of disease found in our study points out that the severity in the development of acute bronchiolitis is not specified exclusively by the pathogen, but the immune response of the host also plays a significant role. More extensive multicentric studies need to take place, in order to lead to safer conclusions.

Proceedings of the COST action BM1407 inaugural conference BEAT-PCD: translational research in primary ciliary dyskinesia - bench, bedside, and population perspectives

Primary ciliary dyskinesia (PCD) is a rare heterogenous condition that causes progressive suppurative lung disease, chronic rhinosinusitis, chronic otitis media, infertility and abnormal situs. ‘Better Experimental Approaches to Treat Primary Ciliary Dyskinesia’ (BEAT-PCD) is a network of scientists and clinicians coordinating research from basic science through to clinical care with the intention of developing treatments and diagnostics that lead to improved long-term outcomes for patients. BEAT-PCD activities are supported by EU Framework Programme Horizon 2020 funded COST Action (BM1407). The Inaugural Conference of BEAT-PCD was held in December 2015 in Southampton, UK. The conference attracted ninety-six scientists, clinicians, allied health professionals, industrial partners and patient representatives from twenty countries. We aimed to identify the needs for PCD research and clinical care, particularly focussing on basic science, epidemiology, diagnostic testing, clinical management and clinical trials. The multidisciplinary conference provided an interactive platform for exchanging ideas through a program of lectures, poster presentations, breakout sessions and workshops. This allowed us to develop plans for collaborative studies. In this report, we summarize the meeting, highlight developments, and discuss open questions thereby documenting ongoing developments in the field of PCD research.

Human bocavirus infections in hospitalized Greek children.

Introduction The epidemiology of human bocavirus (HBoV) infections has not been described in Greece, a south-eastern European country. To define the epidemiological profile and the clinical characteristics associated with HBoV infection in a population of children hospitalized with respiratory tract infection. Material and methods During a one-year period throat swab samples were collected from 370 previously healthy children, aged 14 days to 13 years, admitted to two different paediatric wards because of respiratory tract infection. Samples were tested for HBoV by PCR amplifying a part of the NS1 gene. Results Human bocavirus was detected in 12 children (3.2%). Four of the 12 cases were co-infections, 3 of them with influenza A and 1 with coronavirus OC43. Cases were observed only during the cold months. The mean age of children was 1.8 years (range 2 months to 4 years). The most common symptoms were fever, cough and various degrees of respiratory distress. All children were clinically diagnosed as having lower respiratory tract infections, mainly pneumonia and acute laryngotracheobronchitis, and recovered uneventfully. Conclusions HBoV infections occur in Greece mostly among very young children. They accounted for 3.2% of children hospitalized with acute respiratory disease. Cases were observed only in late autumn to early spring.

Alternative inert gas washout outcomes in patients with primary ciliary dyskinesia

The lung clearance index (LCI) derived from a nitrogen multiple breath washout test (N2-MBW) is a promising tool to assess small airways disease in primary ciliary dyskinesia, but it is difficult to apply in routine clinical settings because of its long measuring time. In this study, we aimed to assess alternative indices derived from shorter washout protocols. 49 patients with primary ciliary dyskinesia (mean age 14.7±6.6 years) and 37 controls (mean age 14.3±1.4 years) performed N2-MBW and double-tracer gas (DTG) single-breath washout tests. Global (LCI and moment ratio (M2/M0)), conductive (Scond) and acinar ventilation inhomogeneity (DTG Slope III (SIII-DTG)) were determined for each individual. The main outcomes were 1) the ability to detect abnormal lung function from washout indices (>1.64 z-scores) and 2) measurement duration. The prevalence of abnormal values for LCI2.5% was 37 out of 47 (79%), for LCI5% was 34 out of 47 (72%), for M2/M0 was 34 out of 47 (72%), for Scond was 36 out of 46 (78%) and for SIII-DTG was 12 out of 35 (34%). Mean±sd duration of measurement was 19.8±11.2 min for LCI2.5%, 10.8±4.6 min for LCI5% and 8.6±2.3 min for Scond. Compared to standard LCI2.5%, ventilation inhomogeneity was detected by LCI5%, moment ratio and Scond with comparable sensitivity while measurement duration was significantly shorter. Longitudinal studies will show which outcome is most suitable and practical in terms of sensitivity, duration and variability within the course of primary ciliary dyskinesia lung disease. Alternative washout outcomes of shorter test duration detect ventilation inhomogeneity in patients with PCD http://ow.ly/ffnL307OzWX

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

Age‐related changes in childhood wheezing characteristics: A whole population study

Wheezing illnesses are characterized by phenotypic variability, which changes with age, but few studies report on a wide age range of children. We studied how prevalence, severity, and triggers of wheeze vary throughout childhood.