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.

Implementation of multigene panel NGS diagnosis in the national primary ciliary dyskinesia cohort of Cyprus: An island with a high disease prevalence.

We aimed to determine a genetic diagnosis in the national primary ciliary dyskinesia (PCD) cohort of Cyprus, an island with a high disease prevalence. We used targeted next-generation sequencing (NGS) of 39 PCD genes in 48 patients of Greek-Cypriot and other ancestries. We achieved a molecular diagnosis in 74% of the unrelated families tested. We identified 24 different mutations in 11 genes, 12 of which are novel. Homozygosity was more common in Greek-Cypriot than non-Greek-Cypriot patients (88% vs. 46.2%, p = .016). Four mutations (DNAH11:c.5095-2A>G, CFAP300:c.95_103delGCCGGCTCC, TTC25:c.716G>A, RSPH9:c.670+2T>C) were found in 74% of the diagnosed Greek-Cypriot families. Patients with RSPH9 mutations demonstrated higher nasal nitric oxide (57 vs. 15 nl/min, p <.001), higher forced expiratory volume in 1 s (-0.89 vs. -2.37, p = .018) and forced vital capacity (-1.00 vs. -2.16, p = .029) z scores than the rest of the cohort. Targeted multigene-panel NGS is an efficient tool for early diagnosis of PCD, providing insight into genetic disease epidemiology and improved patient stratification.

The MEDEA childhood asthma study design for mitigation of desert dust health effects: implementation of novel methods for assessment of air pollution exposure and lessons learned.

BACKGROUND: Desert dust events in Mediterranean countries, originating mostly from the Sahara and Arabian deserts, have been linked to climate change and are associated with significant increase in mortality and hospital admissions from respiratory causes. The MEDEA clinical intervention study in children with asthma is funded by EU LIFE+ program to evaluate the efficacy of recommendations aiming to reduce exposure to desert dust and related health effects. METHODS: This paper describes the design, methods, and challenges of the MEDEA childhood asthma study, which is performed in two highly exposed regions of the Eastern Mediterranean: Cyprus and Greece-Crete. Eligible children are recruited using screening surveys performed at primary schools and are randomized to three parallel intervention groups: a) no intervention for desert dust events, b) interventions for outdoor exposure reduction, and c) interventions for both outdoor and indoor exposure reduction. At baseline visits, participants are enrolled on MEDena® Health-Hub, which communicates, alerts and provides exposure reduction recommendations in anticipation of desert dust events. MEDEA employs novel environmental epidemiology and telemedicine methods including wearable GPS, actigraphy, health parameters sensors as well as indoor and outdoor air pollution samplers to assess study participants' compliance to recommendations, air pollutant exposures in homes and schools, and disease related clinical outcomes. DISCUSSION: The MEDEA study evaluates, for the first time, interventions aiming to reduce desert dust exposure and implement novel telemedicine methods in assessing clinical outcomes and personal compliance to recommendations. In Cyprus and Crete, during the first study period (February-May 2019), a total of 91 children participated in the trial while for the second study period (February-May 2020), another 120 children completed data collection. Recruitment for the third study period (February-May 2021) is underway. In this paper, we also present the unique challenges faced during the implementation of novel methodologies to reduce air pollution exposure in children. Engagement of families of asthmatic children, schools and local communities, is critical. Successful study completion will provide the knowledge for informed decision-making both at national and international level for mitigating the health effects of desert dust events in South-Eastern Europe. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03503812 , April 20, 2018.

Health related quality of life in adult primary Ciliary dyskinesia patients in Cyprus: development and validation of the Greek version of the QOL-PCD questionnaire.

BACKGROUND: The QOL-PCD questionnaire is a recently developed Health Related Quality of Life (HRQoL) instrument for Primary Ciliary Dyskinesia. The aim of this study was to translate the adult QOL-PCD questionnaire into Greek language and to conduct psychometric validation to assess its performance. METHODS: Forward translations to Greek and backward translation to English were performed, followed by cognitive interviews in 12 adult PCD patients. The finalized translated version was administered to a consecutive sample of 31 adult, Greek speaking PCD patients in Cyprus for psychometric validation, which included assessment of internal consistency, test-retest reliability, construct and convergent validity. Internal consistency was assessed by Cronbach's alpha test in terms of the overall and sub-scales. Test-retest reliability was assessed by repeat administration of the questionnaire within 2 weeks and calculation of the intra-class correlation (ICC). Construct validity was assessed by comparing different groups of patients based on a-priori hypotheses and convergent validity was evaluated by examining associations between the QOL-PCD and SF-36 questionnaires. RESULTS: Moderate to good internal consistency was observed (Cronbach's α: 0.46-0.88 across sub-scales) and test-retest reliability assessment demonstrated good repeatability for most scales (ICC: 0.67-0.91 across subscales). Patients of female gender, older age and lower lung function exhibited lower QOL-PCD scores in general, while high correlations for most QOL-PCD scales with corresponding SF-36 scales were observed, in particular for physical functioning (r = 0.78, p < 0.05). CONCLUSION: The adult version of QoL-PCD questionnaire has been translated according to international guidelines resulting to a cross-culturally validated Greek version which exhibited moderate to good metric properties in terms of internal consistency, stability, known-group and convergent validity.

Prevalence and course of disease after lung resection in primary ciliary dyskinesia: a cohort & nested case-control study.

BACKGROUND: Lung resection is a controversial and understudied therapeutic modality in Primary Ciliary Dyskinesia (PCD). We assessed the prevalence of lung resection in PCD across countries and compared disease course in lobectomised and non-lobectomised patients. METHODS: In the international iPCD cohort, we identified lobectomised and non-lobectomised age and sex-matched PCD patients and compared their characteristics, lung function and BMI cross-sectionally and longitudinally. RESULTS: Among 2896 patients in the iPCD cohort, 163 from 20 centers (15 countries) underwent lung resection (5.6%). Among adult patients, prevalence of lung resection was 8.9%, demonstrating wide variation among countries. Compared to the rest of the iPCD cohort, lobectomised patients were more often females, older at diagnosis, and more often had situs solitus. In about half of the cases (45.6%) lung resection was performed before presentation to specialized PCD centers for diagnostic work-up. Compared to controls (n = 197), lobectomised patients had lower FVC z-scores (- 2.41 vs - 1.35, p = 0.0001) and FEV1 z-scores (- 2.79 vs - 1.99, p = 0.003) at their first post-lung resection assessment. After surgery, lung function continued to decline at a faster rate in lobectomised patients compared to controls (FVC z-score slope: - 0.037/year Vs - 0.009/year, p = 0.047 and FEV1 z-score slope: - 0.052/year Vs - 0.033/year, p = 0.235), although difference did not reach statistical significance for FEV1. Within cases, females and patients with multiple lobe resections had lower lung function. CONCLUSIONS: Prevalence of lung resection in PCD varies widely between countries, is often performed before PCD diagnosis and overall is more frequent in patients with delayed diagnosis. After lung resection, compared to controls most lobectomised patients have poorer and continuing decline of lung function despite lung resection. Further studies benefiting from prospective data collection are needed to confirm these findings.

The effect of l-Arginine on Ciliary Beat Frequency in PCD patients, non-PCD respiratory patients and healthy controls.

OBJECTIVES: Few studies have examined the potentially therapeutic effect of increasing the production of endogenous nitric oxide (NO) in Primary Ciliary Dyskinesia (PCD) and other chronic respiratory conditions. Nasal NO is low in PCD and has been found to correlate with compromised Ciliary Beat Frequency (CBF). In this study we assessed the effect of increasing l-Arginine, as the substrate of NO synthases, on CBF in biopsies of human respiratory ciliated epithelium. METHODOLOGY: A total of 28 suspect cases with chronic respiratory manifestations referred for PCD diagnostic testing and 8 healthy controls underwent nasal brushing. Obtained epithelial cells were divided between three culture medium 199 solutions, containing different levels of l-Arginine (0.33 mM as baseline, 1 mM and 10 Mm as increased levels). CBF measurements were obtained at 37 °C and 25 °C at 1, 3 and 24 h after sample acquisition. RESULTS: Among a total of 36 recruited subjects, 8 had PCD confirmed (PCD n = 8), 20 had PCD excluded (non-PCD n = 20) and 8 were healthy controls (Healthy Controls = 8). Among PCD subjects, ciliary motility was characterized by rotational (n = 5) or dyskinetic (n = 3) beating. At 37 °C, compared to baseline, higher levels of l-Arginine resulted in up to 9% CBF increase at 1 h (p = 0.007), up to 9% CBF increase at 3 h (p < 0.001) and up to 12% CBF increase at 24 h (p = 0.002). Similar although smaller scale increases were recorded at 25 °C. The effect of l-Arginine was time dependent (interaction p = 0.002) and was similar in PCD patients, non-PCD chronic respiratory patients and healthy controls (interaction p = 0.800). CONCLUSIONS: l-Arginine increases CBF and merits to be evaluated as a potential stimulator of mucociliary clearance in chronic respiratory conditions and congenital ciliary disorders with residual motility. Larger human studies are needed to confirm these findings.

Maternal socioeconomic factors and the risk of premature birth and low birth weight in Cyprus: a case-control study.

BACKGROUND: Prematurity and low birth weight are significant predictors of perinatal morbidity and mortality and are influenced by the overall health and socioeconomic status of the pregnant mother. Although Cyprus is characterized by the highest prematurity rate in Europe (13.1% in 2014), the relationship between maternal health and socioeconomic characteristics with prematurity and low birth weight has never been investigated. We aimed to investigate the association of maternal demographic, clinical and socioeconomic characteristics with premature delivery and low neonatal birth weight in Cyprus. METHODS: In a case-control design, questionnaire data were collected from 348 women who gave birth prematurely (cases) and 349 women who gave birth at term (controls). Information was obtained on gestation duration and birth weight as well as maternal demographic, socioeconomic and clinical profiles, including parameters such as smoking, body mass index, alcohol consumption, presence of gestational diabetes and mental health factors. RESULTS: Premature delivery was associated with greater maternal age (OR: 1.12, 95% CI: 1.06-1.18), absence of gestational diabetes (OR: 0.53, 95% CI: 0.30-0.97), long working hours (OR: 3.77, 95% CI: 2.08-6.84) and emotional stress (OR: 8.5, 95% CI: 3.03-23.89). Within the cases group, emotional stress was also associated with lower birth-weight (ß: -323.68 (95% CI: -570.36, - 77.00). CONCLUSIONS: The findings of this study demonstrate the positive association of maternal psychological factors, working conditions as well as maternal age with prematurity and low birth weight in Cyprus. Additional, prospective, studies are needed in the country to further investigate these associations and inform public health intervention measures.

Prevalence of primary ciliary dyskinesia in consecutive referrals of suspect cases and the transmission electron microscopy detection rate: a systematic review and meta-analysis.

Diagnostic testing for primary ciliary dyskinesia (PCD) usually includes transmission electron microscopy (TEM), nasal nitric oxide, high-speed video microscopy, and genetics. Diagnostic performance of each test should be assessed toward the development of PCD diagnostic algorithms. We systematically reviewed the literature and quantified PCD prevalence among referrals and TEM detection rate in confirmed PCD patients. Major electronic databases were searched until December 2015 using appropriate terms. Included studies described cohorts of consecutive PCD referrals in which PCD was confirmed by at least TEM and one additional test, in order to compare the index test performance with other test(s). Meta-analyses of pooled PCD prevalence and TEM detection rate across studies were performed. PCD prevalence among referrals was 32% (95% CI: 25-39%, I2 = 92%). TEM detection rate among PCD patients was 83% (95% CI: 75-90%, I2 = 90%). Exclusion of studies reporting isolated inner dynein arm defects as PCD, reduced TEM detection rate and explained an important fraction of observed heterogeneity (74%, 95% CI: 66-83%, I2 = 66%). Approximately, one third of referrals, are diagnosed with PCD. Among PCD patients, a significant percentage, at least as high as 26%, is missed by TEM, a limitation that should be accounted toward the development of an efficacious PCD diagnostic algorithm.

Association of vitamin D with adiposity measures and other determinants in a cross-sectional study of Cypriot adolescents.

OBJECTIVE: To assess vitamin D status among Cypriot adolescents and investigate potential determinants including BMI and body fat percentage (BF%). DESIGN: Participants had cross-sectional assessments of serum vitamin D, physical activity, dietary vitamin D intake and sun exposure. Linear and logistic regression models were used to explore the associations of vitamin D with potential predictors. SETTING: Hospitals, Cyprus, November 2007-May 2008. SUBJECTS: Adolescents (n 671) aged 16-18 years. RESULTS: Mean serum vitamin D was 22·90 (sd 6·41) ng/ml. Only one in ten children had sufficient levels of vitamin D (≥30 ng/ml), while the prevalence of vitamin D deficiency (12-20 ng/ml) and severe deficiency (<12 ng/ml) was 31·7 % and 4·0 %, respectively. Lower vitamin D was associated with winter and spring season, female gender, reduced sun exposure in winter and darker skin. Participants with highest BMI and BF% when compared with a middle reference group had increased adjusted odds of vitamin D insufficiency (OR = 3·00; 95 % CI 1·21, 7·45 and OR = 5·02; 95 % CI 1·80, 13·97, respectively). A similar pattern, although not as strong, was shown for vitamin D deficiency with BF% (OR = 1·81; 95 % CI 1·04, 3·16) and BMI (OR = 1·51; 95 % CI 0·85, 2·67). Participants in the lowest BMI and BF% groups also displayed compromised vitamin D status, suggesting a U-shaped association. CONCLUSIONS: Vitamin D deficiency in adolescence is very prevalent in sunny Cyprus, particularly among females, those with darker skin and those with reduced sun exposure in winter. Furthermore, vitamin D status appears to have a U-shaped association with adiposity measures.

Diagnostic accuracy of nasal nitric oxide for establishing diagnosis of primary ciliary dyskinesia: a meta-analysis.

BACKGROUND: To date, diagnosis of Primary Ciliary Dyskinesia (PCD) remains difficult and challenging. We systematically evaluated the diagnostic performance of nasal Nitric Oxide (nNO) measurement for the detection of PCD, using either velum-closure (VC) or non-velum-closure (non-VC) techniques. METHODS: All major electronic databases were searched from inception until March 2015 using appropriate terms. The sensitivity and specificity of nNO measurement was calculated in PCD patients diagnosed by transmission electron microscopy, high speed video-microscopy or genetic testing. Summary receiver operating characteristic (HSROC) curves were drawn using the parameters of the fitted models. RESULTS: Twelve studies provided data for 13 different populations, including nine case-control (n = 793) and four prospective cohorts (n = 392). The overall sensitivity of nNO measured by VC techniques was 0.95 (95 % CI 0.91-0.97), while specificity was 0.94 (95 % CI 0.88-0.97). The positive likelihood ratio (LR+) of the test was 15.8 (95 % CI 8.1-30.6), whereas the negative likelihood ratio (LR-) was 0.06 (95 % CI 0.04-0.09). For non-VC techniques, the overall sensitivity of nNO measurement was 0.93 (95 % CI 0.89-0.96) whereas specificity was 0.95 (95 % CI 0.82-0.99). The LR+ of the test was 18.5 (95 % CI 4.6-73.8) whereas the LR- was 0.07 (95 % CI 0.04-0.12). CONCLUSIONS: Diagnostic accuracy of nNO measurement both with VC and non-VC maneuvers is high and can be effectively employed in the clinical setting to detect PCD even in young children, thus potentiating early diagnosis. Measurement of nNO merits to be part of a revised diagnostic algorithm with the most efficacious combination of tests to achieve PCD diagnosis.

Vitamin D levels and status amongst asthmatic and non-asthmatic adolescents in Cyprus: a comparative cross-sectional study.

BACKGROUND: Emerging evidence suggests that vitamin D might be implicated in asthma pathophysiology. This study aims to compare Vitamin D mean serum levels and status between asthmatic and non-asthmatic adolescents and investigate the association of vitamin D with asthma severity. METHODS: In a cohort of adolescents aged 16-17 years, those reporting wheezing in the past 12 months and Ever asthma on the ISAAC questionnaire were invited to participate and formed the Active Asthmatics group. Controls were selected amongst Never Wheezers/Never Asthmatics (NWNA). Differences in mean 25(OH)D serum levels and vitamin D status between AA and NWNA were examined in multivariate linear and logistic regression models respectively, adjusting for potential confounders. Within AA, differences in vitamin D levels were assessed across asthma severity indicators. RESULTS: A total of 69 AA and 671 NWNA participated in the study. Unadjusted mean 25(OH)D serum levels were 22.90 (SD 6.41), and 21.15 (SD 5.59) ng/mL in NWNA and AA respectively (p = 0.03). In adjusted models, mean 25(OH)D levels remained significantly lower amongst AA compared to NWNA (adjusted beta coefficient -1.68, 95% CI -3.24, -0.13). Severe (<12 ng/mL), moderate (<25 ng/mL) or insufficient (<30 ng/mL) vitamin D status was more prevalent among AA who were 1.6 times (95% CI 1.01, 2.53) more likely to belong to a lower vitamin D category compared to NWNA. Within AA, there was a negative trend between vitamin D levels and the number of reported asthma severity indicators. CONCLUSIONS: Levels of vitamin D tend to be lower among asthmatic compared to non-asthmatic children and in those with severe asthma independent of important confounders.

Asthma: the role of low high-density-lipoprotein cholesterol in childhood and adolescence.

BACKGROUND: Several studies have examined the relationship of asthma with serum dyslipidemia and reported positive, negative or no association. Most studies were limited by their cross-sectional design and the wide age range of the participants. In a cohort of children in Cyprus, we explored the association of asthma with serum high-density-lipoprotein cholesterol (HDL-C) at age 16-18 years (follow-up) independently of and in relation to HDL-C at age 11-12 years (baseline). METHODS: In a case-control design, we recruited active asthmatics (AA; n = 68), current wheezers only (CWO; n = 123) and non-asthmatic controls (n = 660). Logistic regression models were used to evaluate associations of asthma with follow-up serum HDL-C and the role of baseline HDL-C. RESULTS: At follow-up, mean HDL-C levels in AA and CWO patients were significantly lower than in the controls (47.9 and 49.7 vs. 53.4 mg/dl; p = 0.001 and p = 0.011). We observed significant associations of AA patients with low HDL-C (<15th percentile; OR 2.32, 95% CI 1.16-4.47) that remained significant after further adjustment for baseline HDL-C (OR 2.14, 95% CI 1.06-4.14). Stratification by baseline HDL-C indicated that the association was significant only in those with high baseline HDL-C (OR 2.40, 95% CI 1.03-5.20). Stratification by IgE sensitization showed that the association was pronounced only in subjects who were sensitized (OR 3.41, 95% CI 1.12-9.88). CONCLUSIONS: Adolescent asthma is associated with low serum HDL-C independent of previous HDL-C levels in childhood. The association appears pronounced in those with a drop in HDL-C levels between childhood and adolescence and in those who have IgE sensitization.

PM10 concentration levels at an urban and background site in Cyprus: the impact of urban sources and dust storms.

Air quality in Cyprus is influenced by both local and transported pollution, including desert dust storms. We examined PM10 concentration data collected in Nicosia (urban representative) from April 1, 1993, through December 11, 2008, and in Ayia Marina (rural background representative) from January 1, 1999, through December 31, 2008. Measurements were conducted using a Tapered Element Oscillating Micro-balance (TEOM). PM10 concentrations, meteorological records, and satellite data were used to identify dust storm days. We investigated long-term trends using a Generalized Additive Model (GAM) after controlling for day of week, month, temperature, wind speed, and relative humidity. In Nicosia, annual PM10 concentrations ranged from 50.4 to 63.8 µg/m3 and exceeded the EU annual standard limit enacted in 2005 of 40 µg/m3 every year A large, statistically significant impact of urban sources (defined as the difference between urban and background levels) was seen in Nicosia over the period 2000-2008, and was highest during traffic hours, weekdays, cold months, and low wind conditions. Our estimate of the mean (standard error) contribution of urban sources to the daily ambient PM10 was 24.0 (0.4) µg/m3. The study of yearly trends showed that PM10 levels in Nicosia decreased from 59.4 µg/m3 in 1993 to 49.0 µg/m3 in 2008, probably in part as a result of traffic emission control policies in Cyprus. In Ayia Marina, annual concentrations ranged from 27.3 to 35.6 µg/m3, and no obvious time trends were observed. The levels measured at the Cyprus background site are comparable to background concentrations reported in other Eastern Mediterranean countries. Average daily PM10 concentrations during desert dust storms were around 100 µg/m3 since 2000 and much higher in earlier years. Despite the large impact ofdust storms and their increasing frequency over time, dust storms were responsible for a small fraction of the exceedances of the daily PM10 limit. Implications: This paper examines PM10 concentrations in Nicosia, Cyprus, from 1993 to 2008. The decrease in PM10 levels in Nicosia suggests that the implementation of traffic emission control policies in Cyprus has been effective. However, particle levels still exceeded the European Uion annual standard, and dust storms were responsible for a small fraction of the daily PM10 limit exceedances. Other natural particles that are not assessed in this study, such as resuspended soil and sea salt, may be responsible in part for the hig particle levels.

Temporal trends in temperature-related mortality and evidence for maladaptation to heat and cold in the Eastern Mediterranean region.

The eastern Mediterranean region is characterized by rising temperature trends exceeding the corresponding global averages and is considered a climate change hot-spot. Although previous studies have thoroughly investigated the impact of extreme heat and cold on human mortality and morbidity, both for the current and future climate change scenarios, the temporal trends in temperature-related mortality or the potential historical adaptation to heat and cold extremes has never been studied in this region. This study focuses on cardiovascular mortality and assesses the temporal evolution of the Minimum Mortality Temperature (MMT), as well as the disease-specific cold- and heat-attributable fraction of mortality in three typical eastern Mediterranean environments (Athens, Thessaloniki and Cyprus). Data on daily cardiovascular mortality (ICD-10 code: I00-I99) and meteorological parameters were available between 1999 and 2019 for Athens, 1999 to 2018 for Thessaloniki and 2004 to 2019 for Cyprus. Estimation of cardiovascular MMT and mortality fractions relied on time-series Poisson regressions with distributed lag nonlinear models (DLNM) controlling for seasonal and long-term trends, performed over a series of rolling sub-periods at each site. The results indicated that in Athens, the MMT decreased from 23 °C (67.5th percentile) in 1999-2007 to 21.8 °C (62nd percentile) in 2011-2019, while in Cyprus the MMT decreased from 26.3 °C (79th percentile) in 2004-2012 to 23.9 °C (66.5th percentile) in 2011-2019. In Thessaloniki, the decrease in MMT was rather negligible. In all regions under study, the fractions of mortality attributed to both cold and heat followed an upward trend throughout the years. In conclusion, the demonstrated increase in cold attributable fraction and the decreasing temporal trend of MMT across the examined sites are suggestive of maladaptation to extreme temperatures in regions with warm climate and highlight the need for relevant public health policies and interventions.

Airborne particle radioactivity during desert dust days in Cyprus.

Mediterranean countries are often affected by desert dust storms, which have significant effects on the environment and public health. We compared airborne particle radioactivity levels during desert dust and non-dust days in Cyprus. Gross α- and ß-radioactivity from Total Suspended Particle (TSP) samples, collected at two urban routine monitoring stations in Limassol and Nicosia, were available for the period 2017-2020 and 2008-2020, respectively. Radionuclides 137Cs and 40K, from TSP samples, were also available from a semi-industrial monitoring station in Nicosia during 2008-2020. Information on desert dust presence, dust origin, particulate matter (PM) levels, and solar activity (KP index and solar sunspot numbers - SSN) were also obtained. We used linear regression models adjusting for seasonality and long-term trends, and solar activity to assess the effect of dust storms on TSP gross α- and ß-, and 137Cs and 40K radioactivity levels. Gross α- and ß-radioactivity, and 137Cs and 40K radioactivity levels were significantly higher on days with desert dust compared to days characterized with no influence of desert dust. Levels of gross α- and ß-radioactivity during dust days were higher when dust originated from the Middle East deserts than from the Sahara Desert. The same trend was observed for the ratios 137Cs to 40K and 137Cs to PM10. Conversely, ratios of TSP gross α- and ß-radioactivity to PM10 were significantly lower during desert dust days in comparison to days without dust influence. This study suggests that desert dust increase both TSP gross α- and ß-radioactivity, as well as 137Cs and 40K radioactivity levels. Further studies should clarify the contribution of anthropogenic and other natural sources to the emission or transportation of particles radioactivity, to better mitigate future exposures.

First outbreak of nosocomial Legionella infection in term neonates caused by a cold mist ultrasonic humidifier.

BACKGROUND: To date, all descriptions of legionellosis in neonates have emerged from a small number of isolated case reports in newborns with unusually severe pneumonia. In December 2008, a large outbreak of Legionella infection occurred in term neonates in Cyprus, providing new information on the epidemiological and clinical features of Legionellosis in this age group. METHODS: An environmental investigation was performed at a small private hospital where the infected neonates were delivered. The medical records of the infected neonates were retrospectively reviewed to obtain clinical data on presentation, complications, and course of disease. RESULTS: Nine of the 32 (28%) newborns who were exposed to the contaminated source at the private nursery were infected with Legionella. Six subjects had pulmonary infiltrates, but in 3 cases there were no abnormal radiological findings and clinical presentation was mild. In 4 neonates, pulmonary infiltrates at presentation were bilateral and extensive and 3 died, conferring a mortality rate of 50% in subjects with pulmonary infiltrates and an overall mortality of 33.3%. Legionella pneumophila serogroup 3 was recovered in neonatal biological samples, although in some patients there was implication of a second strain, serogroup 1. It was determined that the neonates were infected while in the nursery at the private hospital by aerosol produced by a recently installed cold-mist humidifier that was filled with contaminated water. CONCLUSIONS: Use of humidifiers in nursery units must be avoided as the risk of disseminating Legionella in neonates is very high. In neonates legionellosis should be suspected when signs of infection first appear and take an unusual course, even when no pulmonary infiltrates appear.

Prevalence of asthma and allergies in children from the Greek-Cypriot and Turkish-Cypriot communities in Cyprus: a bi-communal cross-sectional study.

BACKGROUND: The Greek-Cypriot (G/C) and Turkish-Cypriot (T/C) communities have lived apart since 1974, with the former presumably adopting a more westernized way of life. We estimated the prevalence of asthma and allergies among children in the two communities and investigated differences in socio-demographic and lifestyle risk factors. METHODS: The ISAAC questionnaire was completed by 10156 children aged 7-8 and 13-14 years. Relative differences in asthma and allergic symptoms between the two communities were expressed as odds ratios (OR), estimated in multivariable logistic regression models before and after adjusting for participants' risk characteristics. RESULTS: In contrast to our original speculation, consistently lower prevalence rates were observed for respiratory outcomes (but not eczema) among G/C compared to T/C children in both age-groups. For instance, the prevalence of current wheeze among 7-8 year-olds was 8.7% vs 11.4% (OR = 0.74, 95%, CI: 0.61, 0.90) and of current rhinoconjuctivitis 2.6% vs 4.9% (OR = 0.52, 95% CI: 0.37, 0.71). Surprisingly, the proportion reporting family history of allergy was almost double in the G/C community. With the exception of early life nursery attendance, several protective factors were more prevalent amongst T/C, such as bedroom sharing, less urbanized environment and exposure to farm animals. In contrast, exposure to tobacco smoke was more frequent in the T/C community. Controlling for risk factors did not account for the observed lower prevalence of current wheeze (in the younger age-group) and rhinoconjuctivitis (in both age-groups) among G/C children while differences in the prevalence of eczema between the two communities were no longer statistically significant. CONCLUSIONS: A mixed picture of potential risk factors was observed in the two communities of Cyprus, not consistently favoring one over the other community since, for example, bedroom sharing and rural living but also exposure to tobacco smoke were more common among T/C children. Investigated risk factors do not fully account for the lower prevalence of asthma and allergies among G/C children, especially against a background of higher family history of allergy in this community.

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.

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.