Association between upper and lower respiratory disease among patients with primary ciliary dyskinesia: an international study.

Introduction: Nearly all patients with primary ciliary dyskinesia (PCD) report ear-nose-throat (ENT) symptoms. However, scarce evidence exists about how ENT symptoms relate to pulmonary disease in PCD. We explored possible associations between upper and lower respiratory disease among patients with PCD in a multicentre study. Methods: We included patients from the ENT Prospective International Cohort (EPIC-PCD). We studied associations of several reported ENT symptoms and chronic rhinosinusitis (defined using patient-reported information and examination findings) with reported sputum production and shortness of breath, using ordinal logistic regression. In a subgroup with available lung function results, we used linear regression to study associations of chronic rhinosinusitis and forced expiratory volume in 1 s (FEV1) accounting for relevant factors. Results: We included 457 patients (median age 15 years, interquartile range 10-24 years; 54% males). Shortness of breath associated with reported nasal symptoms and ear pain of any frequency, often or daily hearing problems, headache when bending down (OR 2.1, 95% CI 1.29-3.54) and chronic rhinosinusitis (OR 2.3, 95% CI 1.57-3.38) regardless of polyp presence. Sputum production associated with daily reported nasal (OR 2.2, 95% CI 1.20-4.09) and hearing (OR 2.0, 95% CI 1.10-3.64) problems and chronic rhinosinusitis (OR 2.1, 95% CI 1.48-3.07). We did not find any association between chronic rhinosinusitis and FEV1. Conclusion: Reported upper airway symptoms and signs of chronic rhinosinusitis associated with reported pulmonary symptoms, but not with lung function. Our results emphasise the assessment and management of upper and lower respiratory disease as a common, interdependent entity among patients with PCD.

Improved childhood asthma control after exposure reduction interventions for desert dust and anthropogenic air pollution: the MEDEA randomised controlled trial.

INTRODUCTION: Elevated particulate matter (PM) concentrations of anthropogenic and/or desert dust origin are associated with increased morbidity among children with asthma. OBJECTIVE: The Mitigating the Health Effects of Desert Dust Storms Using Exposure-Reduction Approaches randomised controlled trial assessed the impact of exposure reduction recommendations, including indoor air filtration, on childhood asthma control during high desert dust storms (DDS) season in Cyprus and Greece. DESIGN, PARTICIPANTS, INTERVENTIONS AND SETTING: Primary school children with asthma were randomised into three parallel groups: (a) no intervention (controls); (b) outdoor intervention (early alerts notifications, recommendations to stay indoors and limit outdoor physical activity during DDS) and (c) combined intervention (same as (b) combined with indoor air purification with high efficiency particulate air filters in children's homes and school classrooms. Asthma symptom control was assessed using the childhood Asthma Control Test (c-ACT), spirometry (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC)) and fractional exhaled nitric oxide (FeNO). RESULTS: In total, 182 children with asthma (age; mean=9.5, SD=1.63) were evaluated during 2019 and 2021. After three follow-up months, the combined intervention group demonstrated a significant improvement in c-ACT in comparison to controls (ß=2.63, 95% CI 0.72 to 4.54, p=0.007), which was more profound among atopic children (ß=3.56, 95% CI 0.04 to 7.07, p=0.047). Similarly, FEV1% predicted (ß=4.26, 95% CI 0.54 to 7.99, p=0.025), the need for any asthma medication and unscheduled clinician visits, but not FVC% and FeNO, were significantly improved in the combined intervention compared with controls. CONCLUSION: Recommendations to reduce exposure and use of indoor air filtration in areas with high PM pollution may improve symptom control and lung function in children with asthma. TRIAL REGISTRATION NUMBER: NCT03503812.

Epidemiology, risk factors, clinical presentation and complications of late-onset neonatal sepsis among preterm neonates in Cyprus: a prospective case-control study.

BACKGROUND: Late-onset neonatal sepsis (LOS) is common in preterm neonates, with increasing incidence in recent years. In the present study, we examined the epidemiology, clinical presentation, and complications of LOS in Cyprus and quantified possible risk factors for the development of this condition. METHODS: The study subjects were preterm neonates admitted in the Neonatal Intensive Care Unit (NICU) of Archbishop Makarios III Hospital, the only neonatal tertiary centre in Cyprus. A prospective, case-control study was designed, and carried out between April 2017-October 2018. Depending on blood culture results, preterm neonates were classified as "Confirmed LOS": positive blood culture - microorganism isolated and LOS symptoms, "Unconfirmed LOS": negative blood culture and LOS symptoms, and "Controls" group: negative blood culture and absence of LOS symptoms. Comparisons between the 3 groups were performed and the associations between demographic, clinical and treatment characteristics with the likelihood of LOS were assessed using univariate and multivariate logistic regression. RESULTS: A total of 350 preterm neonates were included in the study and the incidence of LOS was 41.1%. 79 (22.6%) and 65 (18.6%) neonates were classified as "Confirmed LOS", and "unconfirmed LOS" cases respectively while 206 (58.9%) served as controls. The rate of confirmed LOS ranged from 12.2% in moderate to late preterm neonates to 78.6% in extremely preterm neonates. In the multivariate model, we demonstrated an independent association between LOS and duration of hospitalization (OR: 1.06, 95%CI: 1.01-1.10), duration of ventilation (OR: 1.23, 95%CI: 1.07-1.43) and necrotising enterocolitis (OR: 3.41, 95%CI: 1.13-10.25). CONCLUSIONS: The present study highlights the epidemiology of LOS in preterm neonates in Cyprus and its association with the duration of ventilation and hospitalization as well as with necrotizing enterocolitis. Establishment of protocols for the prevention of nosocomial infections during hospitalization in the NICUs and mechanical ventilation of preterm neonates is recommended.

The impact of COVID-19 lockdown measures on symptoms control in children with asthma: A systematic review and meta-analysis of observational cohort studies.

OBJECTIVES: Reported reductions in emergency department visits and hospitalizations for asthma in previous studies have suggested a beneficial effect of the coronavirus disease of 2019 (COVID-19) lockdown measures on asthma morbidity. Nevertheless, studies relying on administrative data may overestimate the true impact of lockdowns due to changes in health-seeking behavior and reduced availability of pediatric asthma services during the pandemic. In this study, we systematically reviewed the literature and identified observational cohort studies that focused on nonadministrative data to assess the true impact of COVID-19 lockdowns on symptom control in children with asthma. METHODS: A systematic literature search was conducted between January 2020 and August 2022 (International Prospective Register of Systematic Reviews ID: CRD42022354369). The impact of COVID-19 lockdowns across studies was expressed as a standardized mean difference (SMD) for continuous outcomes and as a summary relative risk (RR) for binary outcomes. RESULTS: During the lockdown periods, the pooled asthma symptoms control test score (SMD: 1.99, 95% confidence interval [CI]: 0.75, 3.24, I2 : 98.4%) and the proportion of children with well-controlled asthma (RR: 1.35, 95% CI: 1.06, 1.71, I2 : 77.6%) were significantly increased. On the other hand, the pooled proportion of children with poorly controlled asthma (RR: 0.47, 95% CI: 0.38, 0.57, I2 : 0.0%) was significantly decreased. CONCLUSIONS: During COVID-19 lockdowns, asthma symptoms and breakthrough disease exacerbations were significantly reduced in children with asthma. Further research is warranted on potential interventions aiming to enhance asthma control after the pandemic while taking into consideration their acceptability and potential tradeoffs.

Ambient climatic factors and term birthweight: A study of critical windows of exposure in the Republic of Cyprus.

BACKGROUND: Reduced birthweight is associated with adverse perinatal and long-term outcomes. A few studies examined the association between climatic factors and birthweight with inconsistent results probably due to differences in exposure assessment, statistical models, climatic parameters, and study populations. METHODS: We obtained data from the Republic of Cyprus birth registry from 2007 to 2020, and matched climatic exposures (i.e., temperature, relative humidity, temperature variability, humidity variability) by the hospital district at birth. We used distributed lag models to examine the association between term birthweight, temperature, humidity, and their variability to identify critical windows. Our models were adjusted for coarse particulate matter level (≤10 µm [PM10), and individual-level covariates. Subgroup analysis was conducted to examine effect modification by maternal age and education. RESULTS: We identified two critical windows of exposure to ambient temperature at early and late pregnancy. The cumulative change of birthweight per 5 °C increases in mean weekly temperature was -57.27 (2%) (95% Confidence Interval [CI]: 99.62 (3.1%), -14.92 (0.5%)) and -79.2 (2.5%) (95%CI: 117.03 (3.5%), -41.52 (1.3%)) grams during weeks 1-8 and weeks 28-37, respectively. There was no significant effect of humidity, temperature variability, or humidity variability on birthweight. Based on subgroup analysis, mothers with post-secondary education were more sensitive to temperature, but the marginal significance of differences in effect estimates may be linked with differences in sample size. CONCLUSION: Our study suggests that higher ambient temperature exposure during early and late pregnancy is associated with lower birthweight in main and subgroup analysis. The findings demonstrate in a country highly impacted by climate change like Cyprus that rising temperatures may be associated with perinatal outcomes in susceptible populations during sensitive windows of exposure.

Characteristics of Otologic Disease Among Patients With Primary Ciliary Dyskinesia.

Importance: Otologic disease is common among people with primary ciliary dyskinesia (PCD), yet little is known about its spectrum and severity. Objective: To characterize otologic disease among participants with PCD using data from the Ear-Nose-Throat Prospective International Cohort. Design, Setting, and Participants: This cross-sectional analysis of baseline cohort data from February 2020 through July 2022 included participants from 12 specialized centers in 10 countries. Children and adults with PCD diagnoses; routine ear, nose, and throat examinations; and completed symptom questionnaires at the same visit or within 2 weeks were prospectively included. Exposures: Potential risk factors associated with increased risk of ear disease. Main Outcomes and Measures: The prevalence and characteristics of patient-reported otologic symptoms and findings from otologic examinations, including potential factors associated with increased risk of ear inflammation and hearing impairment. Results: A total of 397 individuals were eligible to participate in this study (median [range] age, 15.2 [0.2-72.4] years; 186 (47%) female). Of the included participants, 204 (51%) reported ear pain, 110 (28%) reported ear discharge, and 183 (46%) reported hearing problems. Adults reported ear pain and hearing problems more frequently when compared with children. Otitis media with effusion-usually bilateral-was the most common otoscopic finding among 121 of 384 (32%) participants. Retracted tympanic membrane and tympanic sclerosis were more commonly seen among adults. Tympanometry was performed for 216 participants and showed pathologic type B results for 114 (53%). Audiometry was performed for 273 participants and showed hearing impairment in at least 1 ear, most commonly mild. Season of visit was the strongest risk factor for problems associated with ear inflammation (autumn vs spring: odds ratio, 2.40; 95% CI, 1.51-3.81) and age 30 years and older for hearing impairment (41-50 years vs ≤10 years: odds ratio, 3.33; 95% CI, 1.12-9.91). Conclusion and Relevance: In this cross-sectional study, many people with PCD experienced ear problems, yet frequency varied, highlighting disease expression differences and possible clinical phenotypes. Understanding differences in otologic disease expression and progression during lifetime may inform clinical decisions about follow-up and medical care. Multidisciplinary PCD management should be recommended, including regular otologic assessments for all ages, even without specific complaints.

Sinonasal disease among patients with primary ciliary dyskinesia: an international study.

Background: Sinonasal symptoms are a common feature of primary ciliary dyskinesia (PCD); however, literature about their severity and frequency, particularly during the life course, is scarce. Using baseline data from the Ear, nose and throat (ENT) Prospective International Cohort of PCD patients, we describe sinonasal disease in PCD. Methods: We included participants who had a routine sinonasal examination during which they completed a symptoms questionnaire. We compared frequency of reported symptoms and examination findings among children and adults, and identified characteristics potentially associated with higher risk of sinonasal disease using ordinal regression. Results: 12 centres contributed 384 participants; median age was 16 years (IQR 9-22), and 54% were male. Chronic nasal problems were the most common feature, reported by 341 (89%). More adults (33; 24%) than children (10; 4%) described hyposmia. Quality of life was moderately affected by rhinosinusitis among 136 participants with completed SNOT-22 questionnaires (median score 31; IQR 23-45). Examinations revealed nasal polyps among 51 of 345 participants (15%) and hypertrophic inferior nasal turbinates among 127 of 341 participants (37%). Facial pain was detected in 50 of 342 participants (15%). Nasal polyps, hypertrophic turbinates, deviated septum and facial pain were found more commonly in adults than children. The only characteristic associated with higher risk of sinonasal disease was age 10 years and older. Conclusions: Based on our findings, regular sinonasal examinations are relevant for patients with PCD of all ages. There is a need for improved management of sinonasal disease supported by evidence-based guidelines.

MEDEA randomised intervention study protocol in Cyprus, Greece and Israel for mitigation of desert dust health effects in adults with atrial fibrillation.

INTRODUCTION: Mediterranean countries experience frequent desert dust storm (DDS) events originating from neighbouring Sahara and Arabian deserts, which are associated with significant increase in mortality and hospital admissions, mostly from cardiovascular and respiratory diseases. Short-term exposure to ambient air pollution is considered as a trigger for symptomatic exacerbations of pre-existing paroxysmal atrial fibrillation (AF) and other types of heart arrhythmia. The Mitigating the Health Effects of Desert Dust Storms Using Exposure-Reduction Approaches clinical randomised intervention study in adults with AF is funded by EU LIFE+programme to evaluate the efficacy of recommendations aiming to reduce exposure to desert dust and related heart arrhythmia effects. METHODS AND ANALYSIS: The study is performed in three heavily exposed to desert dust regions of the Eastern Mediterranean: Cyprus, Israel and Crete-Greece. Adults with paroxysmal AF and implanted pacemaker are recruited and randomised to three parallel groups: (a) no intervention, (b) interventions to reduce outdoor exposure to desert dust, (c) interventions to reduce both outdoor and indoor exposure to particulate matter during desert dust episodes. Eligible participants are enrolled on a web-based platform which communicates, alerts and makes exposure reduction recommendations during DDS events. Exposure changes are assessed by novel tools (smartwatches with Global Positioning System and physical activity sensors, air pollution samplers assessing air quality inside and outside participant's homes, etc). Clinical outcomes include the AF burden expressed as the percentage of time with paroxysmal AF over the total study period, the incidence of ventricular arrhythmia episodes as recorded by the participants' pacemakers or cardioverters/defibrillators and the disease-specific Atrial Fibrillation Effect on QualiTy-of-Life questionnaire. ETHICS AND DISSEMINATION: Local bioethics' authorities approved the study at all sites, according to national legislations (Cyprus: National Bioethics Committee, Data Protection Commissioner and Ministry of Health; Greece, Scientific Committee and Governing Board of the University General Hospital of Heraklion; Israel: Institutional Review Board ('Helsinki committee') of the Soroka University Medical Center). The findings will be publicised in peer-reviewed scientific journals, in international conferences and in professional websites and newsletters. A summary of the results and participants' interviews will be included in a documentary in English, Greek and Hebrew. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier; NCT03503812.

Setup of Consumer Wearable Devices for Exposure and Health Monitoring in Population Studies.

Wearable sensors, which are often embedded in commercial smartwatches, allow for continuous and non-invasive health measurements and exposure assessments in clinical studies. Nevertheless, the real-life application of these technologies in studies involving a large number of participants for a significant observation period may be hindered by several practical challenges. In this study, we present a modified protocol from a previous intervention study for the mitigation of health effects from desert dust storms. The study involved two distinct population groups: asthmatic children aged 6-11 years and elderly patients with atrial fibrillation (AF). Both groups were equipped with a smartwatch for the assessment of physical activity (using a heart rate monitor, pedometer, and accelerometer) and location (using GPS signals to locate individuals in indoor "at home" or outdoor microenvironments). The participants were required to wear the smartwatch equipped with a data collection application on a daily basis, and data were transmitted via a wireless network to a centrally administered data collection platform for the near real-time assessment of compliance. Over a period of 26 months, more than 250 children and 50 patients with AF participated in the aforementioned study. The main technical challenges identified included restricting access to standard smartwatch features, such as gaming, internet browser, camera, and audio recording applications, technical issues, such as loss of GPS signal, especially in indoor environments, and the internal smartwatch settings interfering with the data collection application. The aim of this protocol is to demonstrate how the use of publicly available application lockers and device automation applications made it possible to address most of these challenges in a simple and cost-effective way. In addition, the inclusion of a Wi-Fi received signal strength indicator significantly improved indoor localization and largely minimized GPS signal misclassification. The implementation of these protocols during the roll-out of this intervention study in the spring of 2020 led to significantly improved results in terms of data completeness and data quality.

Improved indoor air quality during desert dust storms: The impact of the MEDEA exposure-reduction strategies.

Desert dust storms (DDS) are natural events that impact not only populations close to the emission sources but also populations many kilometers away. Countries located across the main dust sources, including countries in the Eastern Mediterranean, are highly affected by DDS. In addition, climate change is expanding arid areas exacerbating DDS events. Currently, there are no intervention measures with proven, quantified exposure reduction to desert dust particles. As part of the wider "MEDEA" project, co-funded by LIFE 2016 Programme, we examined the effectiveness of an indoor exposure-reduction intervention (i.e., decrease home ventilation during DDS events and continuous use of air purifier during DDS and non-DDS days) across homes and/or classrooms of schoolchildren with asthma and adults with atrial fibrillation in Cyprus and Crete-Greece. Participants were randomized to a control or intervention groups, including an indoor intervention group with exposure reduction measures and the use of air purifiers. Particle sampling, PM10 and PM2.5, was conducted in participants' homes and/or classrooms, between 2019 and 2022, during DDS-free weeks and during DDS days for as long as the event lasted. In indoor and outdoor PM10 and PM2.5 samples, mass and content in main and trace elements was determined. Indoor PM2.5 and PM10 mass concentrations, adjusting for premise type and dust conditions, were significantly lower in the indoor intervention group compared to the control group (PM2.5-intervention/PM2.5-control = 0.57, 95% CI: 0.47, 0.70; PM10-intervention/PM10-control = 0.59, 95% CI: 0.49, 0.71). In addition, the PM2.5 and PM10 particles of outdoor origin were significantly lower in the intervention vs. the control group (PM2.5 infiltration intervention-to-control ratio: 0.49, 95% CI: 0.42, 0.58; PM10 infiltration intervention-to-control ratio: 0.68, 95% CI: 0.52, 0.89). Our findings suggest that the use of air purifiers alongside decreased ventilation measures is an effective protective measure that reduces significantly indoor exposure to particles during DDS and non-DDS in high-risk population groups.

Responses of schoolchildren with asthma to recommendations to reduce desert dust exposure: Results from the LIFE-MEDEA intervention project using wearable technology.

Current public health recommendations for desert dust storms (DDS) events focus on vulnerable population groups, such as children with asthma, and include advice to stay indoors and limit outdoor physical activity. To date, no scientific evidence exists on the efficacy of these recommendations in reducing DDS exposure. We aimed to objectively assess the behavioral responses of children with asthma to recommendations for reduction of DDS exposure. In two heavily affected by DDS Mediterranean regions (Cyprus & Crete, Greece), schoolchildren with asthma (6-11 years) were recruited from primary schools and were randomized to control (business as usual scenario) and intervention groups. All children were equipped with pedometer and GPS sensors embedded in smartwatches for objective real-time data collection from inside and outside their classroom and household settings. Interventions included the timely communication of personal DDS alerts accompanied by exposure reduction recommendations to both the parents and school-teachers of children in the intervention group. A mixed effect model was used to assess changes in daily levels of time spent, and steps performed outside classrooms and households, between non-DDS and DDS days across the study groups. The change in the time spent outside classrooms and homes, between non-DDS and DDS days, was 37.2 min (pvalue = 0.098) in the control group and -62.4 min (pvalue < 0.001) in the intervention group. The difference in the effects between the two groups was statistically significant (interaction pvalue < 0.001). The change in daily steps performed outside classrooms and homes, was -495.1 steps (pvalue = 0.350) in the control group and -1039.5 (pvalue = 0.003) in the intervention group (interaction pvalue = 0.575). The effects on both the time and steps performed outside were more profound during after-school hours. To summarize, among children with asthma, we demonstrated that timely personal DDS alerts and detailed recommendations lead to significant behavioral changes in contrast to the usual public health recommendations.

The disease-specific clinical trial network for primary ciliary dyskinesia: PCD-CTN.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by impaired mucociliary clearance leading to irreversible lung damage. In contrast to other rare lung diseases like cystic fibrosis (CF), there are only few clinical trials and limited evidence-based treatments. Management is mainly based on expert opinions and treatment is challenging due to a wide range of clinical manifestations and disease severity. To improve clinical and translational research and facilitate development of new treatments, the clinical trial network for PCD (PCD-CTN) was founded in 2020 under the framework of the European Reference Network (ERN)-LUNG PCD Core. Applications from European PCD sites interested in participating in the PCD-CTN were requested. Inclusion criteria consisted of patient numbers, membership of ERN-LUNG PCD Core, use of associated standards of care, experience in PCD and/or CF clinical research, resources to run clinical trials, good clinical practice (GCP) certifications and institutional support. So far, applications from 22 trial sites in 18 European countries have been approved, including >1400 adult and >1600 paediatric individuals with PCD. The PCD-CTN is headed by a coordinating centre and consists of a steering and executive committee, a data safety monitoring board and committees for protocol review, training and standardisation. A strong association with patient organisations and industrial companies are further cornerstones. All participating trial sites agreed on a code of conduct. As CTNs from other diseases have demonstrated successfully, this newly formed PCD-CTN operates to establish evidence-based treatments for this orphan disease and to bring new personalised treatment approaches to patients.

Lung function from school age to adulthood in primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) presents with symptoms early in life and the disease course may be progressive, but longitudinal data on lung function are scarce. This multinational cohort study describes lung function trajectories in children, adolescents and young adults with PCD. We analysed data from 486 patients with repeated lung function measurements obtained between the age of 6 and 24 years from the International PCD Cohort and calculated z-scores for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio using the Global Lung Function Initiative 2012 references. We described baseline lung function and change of lung function over time and described their associations with possible determinants in mixed-effects linear regression models. Overall, FEV1, FVC and FEV1/FVC z-scores declined over time (average crude annual FEV1 decline was -0.07 z-scores), but not at the same rate for all patients. FEV1 z-scores improved over time in 21% of patients, remained stable in 40% and declined in 39%. Low body mass index was associated with poor baseline lung function and with further decline. Results differed by country and ultrastructural defect, but we found no evidence of differences by sex, calendar year of diagnosis, age at diagnosis, diagnostic certainty or laterality defect. Our study shows that on average lung function in PCD declines throughout the entire period of lung growth, from childhood to young adult age, even among patients treated in specialised centres. It is essential to develop strategies to reverse this tendency and improve prognosis.

Pediatric asthma symptom control during lockdown for the COVID-19 pandemic in Spring 2020: A prospective community-based study in Cyprus and Greece.

OBJECTIVES: To prospectively quantify at the community level changes in asthma symptom control and other morbidity indices, among asthmatic schoolchildren in response to coronavirus disease 2019 (COVID-19) lockdown measures. METHODS: In Spring 2019 and Spring 2020, we prospectively assessed monthly changes in pediatric asthma control test (c-ACT), asthma medication usage, infections and unscheduled visits for asthma among schoolchildren with active asthma in Cyprus and Greece. We compared asthma symptom control and other morbidity indices before and during lockdown measures, while participants' time spent at home was objectively assessed by wearable sensors. RESULTS: A total of 119 asthmatic children participated in the study during Spring 2020. Compared to a mean baseline (pre-COVID-19 lockdown) c-ACT score of 22.70, adjusted mean increases of 2.58 (95% confidence interval [CI]: 1.91, 3.26, p < 0.001) and 3.57 (95% CI: 2.88, 4.27, p < 0.001) in the 2nd and 3rd monthly assessments were observed after implementation of lockdown measures. A mean increase in c-ACT score of 0.32 (95% CI: 0.17, 0.47, p < 0.001) was noted per 10% increase in the time spent at home. Improvement was more profound in children with severe asthma, while significant reductions in infections, asthma medication usage and unscheduled visits for asthma were also observed. During Spring 2019, 39 children participated in the study in the absence of lockdown measures and no changes in c-ACT or other indices of disease severity were observed. CONCLUSIONS: Clinically meaningful improvements in asthma symptom control, among asthmatic schoolchildren were observed during the COVID-19 lockdown measures in Spring 2020. Improvements were independently associated with time spent at home and were more profound in the children with severe asthma.

Observational study of health utilities in adult primary ciliary dyskinesia patients: preliminary data on associations with molecular diagnosis, clinical phenotype and HRQOL measures.

Background: Primary ciliary dyskinesia (PCD) is a congenital disorder characterized by chronic respiratory morbidity. To date, there is no information on PCD-specific preference-based quality of life measures such as health utilities (HU). We cross-sectionally assessed HU in adult PCD patients and explored relationships with genotype, phenotype and quality of life (QOL)-PCD scales. Methods: Diagnostic testing was performed according to international guidelines, while participants completed the visual analog scale (VAS), time trade off (TTO), standard gamble (SG), and EuroQol 5 dimensions (EQ5D) HU instruments, as well as the QOL-PCD questionnaire. Hierarchical regression was used to identify the QOL-PCD scales that are most predictive of HU. Results: Among 31 patients, median HU are 0.75 (VAS), 0.86 (EQ5D), 0.91 (TTO) and 0.99 (SG). The underlying genotype is not associated with HU measures. VAS and EQ5D are associated with lung function, while TTO and SG values are not sensitive to any of the examined factors. Among the QOL-PCD scales, physical functioning and lower respiratory symptoms explained much of VAS (R2= 0.419) and EQ5D (R2= 0.538) variability. Conclusions: Our study demonstrates that HU elicitation in PCD is feasible using both direct and indirect methods. Overall, HU scores are relatively high among adult patients, with higher scores observed in SG and TTO, followed by EQ5D and VAS. VAS and EQ5D HU values are sensitive to lung function as well as to QOL-PCD physical functioning and lower respiratory symptom scores.

Health effects of desert dust storm events in the south-eastern Mediterranean: perceptions and practices of local stakeholders.

BACKGROUND: The south-eastern Mediterranean experiences frequent desert dust storm events (DDS) that have been shown to be associated with adverse health effects. AIMS: This study assessed the perceptions and practices towards DDS of local authorities and stakeholders from 3 countries in the region, Cyprus, Greece and Israel. METHODS: Between October 2017 and April 2018, we administered a semi-structured questionnaire to regulatory authorities involved in public protection from DDS as well as social stakeholders in the 3 countries. The questionnaire addressed their knowledge regarding DDS, perceptions on the relationship between DDS and health effects and relevant actions taken towards public protection. RESULTS: Out of 58 stakeholders contacted, 49 participated in the study (84.5% response rate). Fourteen (28.6%) were regulatory authorities and 35 (71.4%) were social stakeholders. All responders were familiar with DDS but several underestimated the frequency of events while the majority (73%) instinctively reported that elders, children and respiratory patients are susceptible subpopulations. Nevertheless, 71% were unaware of a national policy on DDS, or considered that this was lacking in their country. Although several stakeholders reportedly receive questions from the public regarding DDS effects, only few reply according to a pre-determined action plan. CONCLUSIONS: Regulatory authorities and social stakeholders in Cyprus, Greece and Israel are characterized by good knowledge of DDS and associated health effects, although implementation of pre-determined action plans for public protection is limited. Future efforts should concentrate on increasing awareness among stakeholders and the public and developing national policies, including effective measures to minimize DDS exposure.

Demographic characteristics, clinical and laboratory features, and the distribution of pathogenic variants in the CFTR gene in the Cypriot cystic fibrosis (CF) population demonstrate the utility of a national CF patient registry.

BACKGROUND: Specialized clinical care for cystic fibrosis (CF) in Cyprus, a small island country, has been implemented since the 1990s. However, only recently, a national CF patient registry has been established for the systematic recording of patients' data. In this study, we aim to present data on the epidemiological, genotypic and phenotypic features of CF patients in the country from the most recent data collection in 2019, with particular emphasis on notable rare or unique cases. RESULTS: Overall, data from 52 patients are presented, 5 of whom have deceased and 13 have been lost to follow-up in previous years. The mean age at diagnosis was 7.2 ± 12.3 years, and the mean age of 34 alive patients by the end of 2019 was 22.6 ± 13.2 years. Patients most commonly presented at diagnosis with acute or persistent respiratory symptoms (46.2%), failure to thrive or malnutrition (40.4%), and dehydration or electrolyte imbalance (32.7%). Sweat chloride levels were diagnostic (above 60 mmol/L) in 81.8% of examined patients. The most common identified mutation was p.Phe508del (F508del) (45.2%), followed by p.Leu346Pro (L346P) (6.7%), a mutation detected solely in individuals of Cypriot descent. The mean BMI and FEV1 z-scores were 0.2 ± 1.3 and - 2.1 ± 1.7 across all age groups, respectively, whereas chronic Pseudomonas aeruginosa colonization was noted in 26.9% of patients. The majority of patients (74.5%) were eligible to receive at least one of the available CFTR modulator therapies. In 25% of patients we recovered rare or unique genotypic profiles, including the endemic p.Leu346Pro (L346P), the rare CFTR-dup2, the co-segregated c.4200_4201delTG/c.489 + 3A > G, and the polymorphism p.Ser877Ala. CONCLUSIONS: CF patient registries are particularly important in small or isolated populations, such as in Cyprus, with rare or unique disease cases. Their operation is necessary for the optimization of clinical care provided to CF patients, enabling their majority to benefit from evolving advances in precision medicine.

Study protocol: the ear-nose-throat (ENT) prospective international cohort of patients with primary ciliary dyskinesia (EPIC-PCD).

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare, genetic, multiorgan disease with an estimated prevalence of 1 in 10 000. It affects mainly the upper and lower airways due to impaired mucociliary clearance. Almost all patients have sinonasal or otologic (ear-nose-throat, ENT) problems, although the ENT clinical phenotype may present great variability. Despite that, data on PCD ENT manifestations are scarce and based on small single-centre studies. To date, we know little about the spectrum and severity of PCD ENT disease, its association with lung disease, its course over life and its determinants of prognosis.This study protocol describes the aims and methods of the first prospective, observational, multinational cohort study focusing on ENT disease in patients with PCD. METHODS AND ANALYSIS: The ENT prospective international cohort of patients with PCD (EPIC-PCD) is a prospective standardised observational clinical cohort set up as a multinational multicentre study, embedded into routine patient care. It aims to longitudinally characterise ENT disease in patients with PCD and its association with lung disease, and to identify determinants of its prognosis. Patients of all ages, diagnosed with PCD who undergo an ENT clinical assessment at least once a year at one of the participating centres will be invited to participate. Collected data include diagnostic test results, results of ENT examinations, lung function measurements, information on management of ENT disease and patient-reported data on clinical symptoms and health-related quality of life (QoL). Data are collected using the standardised PCD-specific FOLLOW-PCD form and the validated QoL-PCD questionnaire. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the Human Research Ethics Committees at all participating centres, based on local legislation. The results of the study will be published in scientific journals, presented at scientific conferences and disseminated to participants and national patient organisations. TRIAL REGISTRATION: NCT04611516.

International BEAT-PCD consensus statement for infection prevention and control for primary ciliary dyskinesia in collaboration with ERN-LUNG PCD Core Network and patient representatives.

INTRODUCTION: In primary ciliary dyskinesia (PCD) impaired mucociliary clearance leads to recurrent airway infections and progressive lung destruction, and concern over chronic airway infection and patient-to-patient transmission is considerable. So far, there has been no defined consensus on how to control infection across centres caring for patients with PCD. Within the BEAT-PCD network, COST Action and ERS CRC together with the ERN-Lung PCD core a first initiative has now been taken towards creating such a consensus statement. METHODS: A multidisciplinary international PCD expert panel was set up to create a consensus statement for infection prevention and control (IP&C) for PCD, covering diagnostic microbiology, infection prevention for specific pathogens considered indicated for treatment and segregation aspects. Using a modified Delphi process, consensus to a statement demanded at least 80% agreement within the PCD expert panel group. Patient organisation representatives were involved throughout the process. RESULTS: We present a consensus statement on 20 IP&C statements for PCD including suggested actions for microbiological identification, indications for treatment of Pseudomonas aeruginosa, Burkholderia cepacia and nontuberculous mycobacteria and suggested segregation aspects aimed to minimise patient-to-patient transmission of infections whether in-hospital, in PCD clinics or wards, or out of hospital at meetings between people with PCD. The statement also includes segregation aspects adapted to the current coronavirus disease 2019 (COVID-19) pandemic. CONCLUSION: The first ever international consensus statement on IP&C intended specifically for PCD is presented and is targeted at clinicians managing paediatric and adult patients with PCD, microbiologists, patient organisations and not least the patients and their families.