Publications by authors named "John Tsanakas"

28 Publications

  • Page 1 of 1

Toward the Establishment of New Clinical Endpoints for Cystic Fibrosis: The Role of Lung Clearance Index and Cardiopulmonary Exercise Testing.

Front Pediatr 2021 25;9:635719. Epub 2021 Feb 25.

Pediatric Pulmonology and Cystic Fibrosis Unit, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

As Cystic Fibrosis (CF) treatment advances, research evidence has highlighted the value and applicability of Lung Clearance Index and Cardiopulmonary Exercise Testing as endpoints for clinical trials. In the context of these new endpoints for CF trials, we have explored the use of these two test outcomes for routine CF care. In this review we have presented the use of these methods in assessing disease severity, disease progression, and the efficacy of new interventions with considerations for future research.
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http://dx.doi.org/10.3389/fped.2021.635719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946844PMC
February 2021

Cardiorespiratory Fitness Predicted by Fibrinogen and Leptin Concentrations in Children with Obesity and Risk for Diabetes: A Cross-Sectional Study and a ROC Curve Analysis.

Nutrients 2021 Feb 19;13(2). Epub 2021 Feb 19.

Paediatric Endocrine Research Laboratory, Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics, School of Medicine, University of Patras, University Campus, GR-26504 Patras, Greece.

Obesity is defined as abnormal or excessive fat accumulation that presents a risk to health. The ability to exercise is affected by adiposity, and this mechanism involves low-grade chronic inflammation and homeostatic stress produced mainly in adipocytes, which can result in abnormal adipokine secretion. To date, the gold standard for cardiorespiratory fitness assessment is considered to be the maximum oxygen uptake (VO). The aim of the present study was to assess the prognostic value of hematological parameters of childhood obesity, as potential predictors of cardiorespiratory fitness (VO), using a sample of children and adolescents with obesity and risk for diabetes. A total of 84 clinically healthy children and adolescents were recruited, of which 21 were considered lean, 22 overweight and 41 obese, with a mean age of 12.0 ± 1.9, 11.4 ± 2.0, and 11.2 ± 2.1 years old, in each weight status category, respectively. Age and sex did not differ between groups. Hematologic testing was performed after 12 h of fasting including glucose, serum lipids, insulin, hc-CRP, adiponectin, leptin and fibrinogen levels. Cardiorespiratory capacity for exercise was assessed to determine VO, using a cycle ergometer. The VO was negatively correlated with progressive strength to the BMIz (-0.656, ≤ 0.001), hs-CRP (r = -0.341, ≤ 0.002), glucose (r = -0.404, ≤ 0.001) and insulin levels (r = -0.348, ≤ 0.001), the homeostasis model assessment of insulin resistance (HOMA-IR) (r = -0.345, ≤ 0.002), as well as to the leptin (r = -0.639, ≤ 0.001) and fibrinogen concentrations (r = -0.520, ≤ 0.001). The multivariate analysis revealed that only leptin and fibrinogen concentrations could predict the VO adjusted for the BMIz of participants. The receiver operating characteristic (ROC) curve for the diagnostic accuracy of leptin, hs-CRP and fibrinogen concentrations for the prediction of VO revealed a good diagnostic ability for all parameters, with leptin being the most promising one (area under the curve (AUC): 99%). The results verify that in children with obesity, VO may be predicted from hematological parameters (leptin and fibrinogen), possibly bypassing more invasive methods.
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http://dx.doi.org/10.3390/nu13020674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923274PMC
February 2021

Does Colonization Affect Exercise Capacity in CF?

Pulm Med 2019 9;2019:3786245. Epub 2019 Dec 9.

Pediatric Pulmonology and CF Unit, 3 Department of Pediatrics, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Introduction: Cardio-Pulmonary Exercise Testing (CPET) has been recognized as a valuable method in assessing disease burden and exercise capacity among CF patients.

Aim: To evaluate whether colonization status affects Exercise Capacity, LCI and High-Resolution Computed Tomography (HRCT) indices among patients with CF; to check if colonization can predict exercise intolerance.

Subjects: Seventy-eight (78) children and adults with CF (31 males) mean (range) age 17.08 (6.75; 24.25) performed spirometry, Multiple Breath Washout (MBW) and CPET along with HRCT on the same day during their admission or follow up visit.

Results: 78 CF patients (mean FEV1: 83.3% mean LCI: 10.9 and mean VO peak: 79.1%) were evaluated: 33 were chronically colonized with , 24 were intermittently colonized whereas 21 were free. Statistically significant differences were observed among the three groups in: peak oxygen uptake % predicted (VO peak% ( < 0.001), LCI ( < 0.001), as well as FEV1% ( < 0.001) and FVC% ( < 0.001). colonization could predict VO peak% ( < 0.001, : -0.395).

Conclusion: Exercise capacity as reflected by peak oxygen uptake is reduced in colonized patients and reflects lung structural damages as shown on HRCT. colonization could predict exercise limitation among CF patients.
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http://dx.doi.org/10.1155/2019/3786245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942891PMC
June 2020

Ventilation efficiency to exercise in patients with cystic fibrosis.

Pediatr Pulmonol 2019 10 5;54(10):1584-1590. Epub 2019 Jul 5.

Pediatric Pulmonology and Cystic Fibrosis Unit, Aristotle University of Thessaloniki School of Health Sciences, Hippokration Hospital of Thessaloniki, Thessaloniki, Greece.

Introduction: Exercise ventilation efficiency index in cardiopulmonary exercise testing (CPET) is elevated in patients with heart failure providing useful information on disease progression and prognosis. Few data, however, exist for ventilation efficiency index among cystic fibrosis (CF) patients.

Aims: To assess ventilation efficiency index (ΔVE/ΔVCO or V'E/V'CO slope) and intercept of ventilation (VE-intercept) in CF patients with mild, moderate, and severe cystic fibrosis (CF) lung disease. To assess possible correlations with ventilation inhomogeneity and structural damages as seen on high resolution computed tomography (HRCT).

Methods: CF patients with mild (FEV  > 80%, n = 47), moderate (60% < FEV  < 80%, n = 21), and severe (FEV  < 60%, n = 9) lung disease, mean age 14.9 years participated. Peak oxygen uptake (VO peak), pulmonary ventilation at peak exercise (VE), respiratory equivalent ratios for oxygen and carbon dioxide at peak exercise (VE/VO , VE/VCO ), end-tidal CO (PetCO ), and ΔVE/ΔVCO , ΔVE/ΔVO in a maximal CPET along with spirometry and multiple breath washout indices were examined. HRCT scans were performed and scored using Bhalla score.

Results: Mean ΔVE/ΔVCO showed no significant differences among the three groups (P = .503). Mean VE discriminated significantly among the different groups (p < 0.001). Ventilation efficiency index did not correlate either with LCI or Bhalla score. However, VE together with ΔVE/ΔVCO slope could predict Bhalla score (r  = 0.869, P = .006).

Conclusion: No significant differences were found regarding ΔVE/ΔVCO slope levels between the three groups. Ventilation intercept (VE ) was elevated significantly as disease progresses reflecting increased dead space ventilation. CF patients retain their ventilation efficiency to exercise even as lung function deteriorates by adopting a higher respiratory rate along with increased dead space ventilation.
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http://dx.doi.org/10.1002/ppul.24438DOI Listing
October 2019

Two cases of myositis ossificans in children, after prolonged immobilization.

J Musculoskelet Neuronal Interact 2019 03;19(1):118-122

3rd Paediatric Dept, Hippokration Hospital, Aristotle University of Thessaloniki, Greece.

Myossitis ossificans (MO) is a benign disorder characterized by heterotopic bone formation in skeletal muscle. It is divided in three types, fibrodysplasia ossificans progressive (FOP), myositis ossificans circumscripta or traumatica (MOT) and myositis ossificans without a history of trauma (non traumatic or pseudomalignant MO). Myositis ossificans is extremely rare in children younger than 10 years. We present the clinical and radiological findings of two 5-year-old children with pseudomalignant MO due to prolonged immobilization. Plain x-ray films and CT scan with their characteristic findings of mature bone in the periphery of the lesion with smooth contour and well separated from the bone, enabled us to diagnose the lesion. To the best of our knowledge, no such cases have been reported in the literature.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454263PMC
March 2019

Chest wall lipoblastoma in a 3 year-old boy.

Respir Med Case Rep 2019 19;26:200-202. Epub 2019 Jan 19.

Paediatric Pulmonology Unit, 3rd Paediatric Dept, Aristotle University School of Medicine, Hippokration Hospital, Greece.

Background: Lipoblastoma is a rare, benign, fatty tissue tumor that occurs in infancy and early childhood. The most common tumor locations are the extremities and the torso. The location of this tumor in the chest wall and an intrathoracic extension is uncommon.

Case Report: We present a case of a 3-year-old boy with anterior chest wall lipoblastoma with an intrathoracic extension. Computed tomography was suggestive of lipoblastoma. The mass was completely excised through a right posterolateral thoracotomy. The histologic examination of the lesion confirmed the diagnosis of lipoblastoma.

Conclusion: Although extremely rare, chest wall lipoblastoma should be included in the differential diagnosis of thoracic mass in childhood.
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http://dx.doi.org/10.1016/j.rmcr.2019.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350110PMC
January 2019

A Case Report of Pulmonary Exacerbation after Initiation of Lumacaftor/Ivacaftor Therapy in a CF Female with Complicated Lung Disease.

Case Rep Pulmonol 2018 30;2018:8394370. Epub 2018 May 30.

3rd Paediatric Department, CF Unit, Hippokration General Hospital of Thessaloniki, Aristotle University of Thessaloniki, Greece.

Novel targeted treatments for Cystic Fibrosis give rise to new hope for an ever-growing number of CF patients with various mutations. However, very little evidence and guidelines exist to steer clinical decisions regarding patients whose illness takes an unexpected course. In such cases, the benefits and risks of discontinuing these treatments must be carefully and individually weighed, since their long-term effects remain mainly uncharted territory. In this report we document the case of a homozygous F508del CF patient with severe lung disease who presented with a pulmonary exacerbation shortly after the beginning of treatment with lumacaftor/ivacaftor and the complicated initial phase of therapy, which was followed by significant improvements.
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http://dx.doi.org/10.1155/2018/8394370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5998152PMC
May 2018

Efficacy and safety of the combination fluticasone propionate plus salmeterol in asthmatic preschoolers: An observational study.

J Asthma 2019 Jun 29;56(6):573-580. Epub 2018 Jun 29.

a Aristotle University of Thessaloniki , Greece, Paediatric Pulmonology Unit, Hippokration Hospital , Thessaloniki , Greece.

Background: Inhaled Corticosteroids (ICS) are the cornerstone of asthma management in pediatric patients. However, in some cases, asthma is not adequately controlled on ICS alone. Long-acting beta-agonists (LABA) are one of the available additional therapies but their use has rarely been studied among children younger than 5 years.

Objective: The aim of this observational study was to evaluate the efficacy and safety of the combination of fluticasone propionate and salmeterol (FP/SA) in asthmatic children younger than 5 years of age.

Methods: A retrospective study of 796 children under the age of 5 years (2.87 ± 1.22 years, 64.2% males), who were treated with FP/SA was conducted. Hospitalization rates, frequency of wheezing, exercise induced asthma, nocturnal wheeze and drug-related side-effects were recorded through children's medical records.

Results: The children had previously received short-acting β-agonists (73%), ICS (17%), montelukast (1%), and ICS with montelukast (2%). Mean duration of therapy with FP/SA was 12.45 ± 9.14 months. After adjusting for age, gender, and duration of treatment, a 89% reduction was recorded in annual hospitalization rates (from 27.13% before treatment to 3.01% after FP/SA therapy, p < 0.001), a 71% reduction in incidence of exercise-induced asthma (36.8% vs. after 10.6%, p < 0.001), a 81% reduction in nocturnal asthma (33.7% vs. after: 6.4%, p < 0.001), as well as in frequency of wheezing (p < 0.01),. No previous treatment carry-on effect was observed. No major drug-related side-effects occurred in the study group.

Conclusions: Combination therapy (FP/SA) is well-tolerated and highly effective in asthmatic children under the age of 5 years.
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http://dx.doi.org/10.1080/02770903.2018.1474923DOI Listing
June 2019

Lung clearance index (LCI) as a predictor of exercise limitation among CF patients.

Pediatr Pulmonol 2018 Jan 26;53(1):81-87. Epub 2017 Sep 26.

Paediatric Pulmonology and Cystic Fibrosis Unit, 3rd Paediatric Department, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Introduction: FEV is often considered the gold standard to monitor lung disease in cystic fibrosis (CF). Recently, there has been increasing interest in multiple breath washout (MBW) and cardiopulmonary exercise testing (CPET) as alternative or even more sensitive techniques. However, limited data exist on associations among the above methods.

Aim: To evaluate the correlations between outcome measures of MBW and CPET and to examine if ventilation inhomogeneity can predict exercise intolerance.

Subjects And Methods: Ninety-seven children and adults with CF (47 males, mean [range] age 14.9 (6.6; 26.7) years, mean FEV : 90.8% predicted, mean lung clearance index [LCI]: 11.4, and mean peak oxygen uptake [VO peak]: 82.4% predicted) performed spirometry, MBW, and CPET on the same day during their admission or outpatient visit.

Results: LCI, m /m , and m /m (P < 0.001) as well as VO peak%, breathing reserve (BR), minute ventilation (VE)/VO (P < 0.001), and VE/carbon dioxide release (VCO ) (P = 0.006) correlated significantly with FEV %. LCI, m /m , and m /m correlated with VO peak (P ≤ 0.001), VE (L/min) (P < 0.05), BR (P < 0.01), VE/VO (P < 0.001), and VE/VCO (P < 0.01). Multiple regression analysis showed that LCI could predict BR% (P < 0.001, r :0.272) and VE/VO (P < 0.001, r : 0.207) while LCI and FRC could predict VO peak% P < 0.001, r : 0.216) and VE/VCO (P < 0.001, r : 0.226).

Conclusion: Ventilation inhomogeneity as indicated by increased LCI is associated with less efficient ventilation during strenuous exercise and negatively impacts exercise capacity in CF.
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http://dx.doi.org/10.1002/ppul.23833DOI Listing
January 2018

Telephone monitoring and home visits significantly improved the quality of life, treatment adherence and lung function in children with cystic fibrosis.

Acta Paediatr 2017 11 13;106(11):1882. Epub 2017 Aug 13.

Paediatric Pulmonology and Cystic Fibrosis Unit, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

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http://dx.doi.org/10.1111/apa.13996DOI Listing
November 2017

A "real-life" study on height in prepubertal asthmatic children receiving inhaled steroids.

J Asthma 2018 04 31;55(4):437-442. Epub 2017 Jul 31.

a Paediatric Endocrinology Unit, 3rd Paediatric Dept, Hippokration Hospital , Aristotle University of Thessaloniki , Greece, Thessaloniki , Greece.

Introduction: Asthma is the most common chronic respiratory disease in children and inhaled corticosteroids (ICS) constitute the first line of treatment for these patients. However, the potential growth-inhibiting effect of ICS has often been a cause of concern for both caregivers as well as physicians, and there still remains conflict regarding their safety profile.

Objective: To assess whether the administration of ICS in low or medium doses is associated with height reduction in prepubertal children.

Methods: We performed a retrospective study to examine the association between ICS treatment and growth deceleration in children with mild persistent asthma. The comparison of height measurements every 6 months from 3 to 8 years of age was conducted among three groups of patients: patients not receiving ICS, patients being treated with low dose of ICS and patients being treated with medium dose of ICS (GINA Guidelines 2015).

Results: This study included 284 patients (198 male, 86 female) aged 3-8 years; 75 patients were not receiving ICS, 63 patients were on low-dose ICS and 146 patients were on medium-dose ICS. The measured height every 6 months did not differ significantly (p > 0.05) among the three groups while the difference remained stable (p > 0.05), even when we evaluated males and females separately.

Conclusions: In this "real-life" study we found that long-term treatment with ICS in low or medium doses is not associated with height reduction in prepubertal children with asthma.
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http://dx.doi.org/10.1080/02770903.2017.1336243DOI Listing
April 2018

Exercise responses are related to structural lung damage in CF pulmonary disease.

Pediatr Pulmonol 2016 09 12;51(9):914-20. Epub 2016 May 12.

3rd Pediatric Department, Paediatric Respiratory and CF Unit-Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece.

Introduction: Early detection of lung disease is a primary objective in monitoring patients with Cystic Fibrosis (CF); High-Resolution-Computed-Tomography (HRCT) assesses structural damage. Spirometry and cardiopulmonary exercise testing are used for functional evaluation of CF lung disease.

Aim: To evaluate the deterioration of exercise testing parameters over a 2-year period compared to the change of spirometry and HRCT parameters among CF patients.

Methods: Twenty-eight CF patients were evaluated with HRCT, spirometry, and exercise testing; 15 had two assessments with an interval of 2 years. Correlation analyses between Bhalla score parameters and functional measures were performed.

Results: Twenty-eight patients with CF (mean age 14.9 years, mean forced expiratory volume in 1 sec [FEV1 ] 83.2%) were evaluated. FEV1 was not found to change significantly in the 2-year period (P = 0.612). Both mean Bhalla score and mean peak oxygen consumption (VO2 peak %) deteriorated significantly (P = 0.014 and P = 0.026, respectively). VO2 peak and respiratory equivalents for O2 and CO2 at peak exercise were found to be significant predictors of Bhalla score (r = -0.477, P = 0.010; r = 0.461, P = 0.018; r = 0.402; P = 0.042, respectively). Anaerobic threshold was associated with changes in Bhalla score over the following 2 years.

Conclusions: Exercise testing is more sensitive than spirometry to detect structural changes in CF lungs. Pediatr Pulmonol. 2016; 51:914-920. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ppul.23474DOI Listing
September 2016

Pancreatic Cystosis in Two Adolescents with Cystic Fibrosis.

Case Rep Pediatr 2016 24;2016:5321785. Epub 2016 Mar 24.

Paediatric Pulmonology and CF Unit, 3rd Paediatric Department, Hippokration Hospital, Aristotle University of Thessaloniki, 49 Konstantinoupoleos street, 54642 Thessaloniki, Greece.

We present pancreatic cystosis in two adolescents with cystic fibrosis, a 13-year-old girl and an 18-year-old boy. In pancreatic cystosis, which is a rare manifestation of CF, the pancreatic parenchyma is replaced with multiple cysts of different sizes. Pancreatic cystosis is mainly an imaging based diagnosis and frequent follow-up should be recommended.
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http://dx.doi.org/10.1155/2016/5321785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823490PMC
April 2016

Validation study of the pediatric allergic rhinitis quality of life questionnaire.

Asian Pac J Allergy Immunol 2016 Jun;34(2):159-65

Paediatric Department, Hippokration Hospital, Aristotle University of Thessaloniki, Greece.

Background: The Paediatric Allergic Rhinitis Quality of Life Questionnaire (Ped-AR-QoL) is the first tool developed for the assessment of health-related quality of life (QoL) in Greek children with allergic rhinitis (AR).

Objective: The aim of the current study was to validate the child and parent forms of the Ped-AR-QoL in children aged 6-14 years-old who suffered from AR and were followed in a pediatric allergy clinic.

Methods: The Ped-AR-QoL, which was completed by 112 children and their parents, was correlated to the generic QoL questionnaire (Disabkids), which is already valid in Greece for children with chronic disorders, as well as with expert opinions on the severity of disease.

Results: The Ped-AR-QoL child and parent forms had very good internal consistency (α values of 0.797 and 0.872, respectively), while there was a moderate positive correlation of the disease-specific questionnaire with most of the subscales of the generic questionnaire. There has been a statistically significant association between the Ped-AR-QoL and the expert perception of disease severity.

Conclusions: The Ped-AR-QoL had very good reliability and convergent validity when compared with the generic Disabkids QoL. The significance of the association between the disease-specific questionnaire and the expert opinion is an important finding validating the questionnaire. The Ped-AR-QoL may become a helpful tool which can be used in everyday clinical practice by clinicians and it may also be used for assessing therapeutic interventions in clinical trials.
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http://dx.doi.org/10.12932/AP0651.34.2.2016DOI Listing
June 2016

Long-term outcome of parapneumonic effusions in children: Lung function and exercise tolerance.

Pediatr Pulmonol 2015 Jun 29;50(6):615-20. Epub 2014 Apr 29.

3rd Paediatric Dept, Paediatric Pulmonology Unit, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece.

Objectives: a: To evaluate the long-term outcome of parapneumonic effusions (PPE) in children regarding lung function and exercise tolerance, (b) to investigate the role of bronchial asthma in the outcome of PPE.

Methods: The design of the study included 51 children with PPE, at least 2 years after the initial infection. They were divided in two groups. Group A (38 children) consisted of children with PPE but without asthma prior initial infection. Group B (13 children) included children with PPE and asthma prior infection. Thirty-six children were taken as healthy controls (group C). All children performed spirometry and a maximal incremental cardiopulmonary exercise test on cycle ergometer.

Results: Children of both groups (A and B) showed statistically significant lower values in FVC%, FEV1%, and FEV1 /FVC compared to controls (group C). Children of group B had also significant lower FEF(25-75%) values compared to controls. Children of group B had significant lower FEV1 /FVC values compared to group A. All children of the three groups showed no differences in maximal exercise capacity (VO2max). Children of group A had higher respiratory equivalent to oxygen (VE/VO2) during exercise compared to healthy subjects.

Conclusions: There are small effects on lung function and exercise capacity in the long-term, among children with PPE, but of no clinical importance. Pre-existing bronchial asthma doesn't influence the outcome significantly.
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http://dx.doi.org/10.1002/ppul.23054DOI Listing
June 2015

Determinants of quality of life in children with asthma.

Pediatr Pulmonol 2013 Dec 8;48(12):1171-80. Epub 2013 Feb 8.

Pediatric Cardiosurgical Intensive Care Unit, "Onassis" Cardiac Surgery Center, Athens, Greece; Faculty of Nursing, National & Kapodistrian University of Athens, Athens, Greece.

Background: HRQoL in children with asthma depends on multiple factors, among which asthma severity and level of control are believed to play a vital role. The determinants of the connection between asthma severity and asthma control with quality of life remain unclear.

Aims: Primary aim of the study was to evaluate the HRQoL in children with asthma and to determine the factors that affect it.

Materials And Methods: In total 504 children and one of their parents were recruited during a regular follow up visit in an outpatient asthma clinic. The measures used were the DISABKIDS smiley measure (DSmM), chronic generic measure-long form (DCGM-37) and the Condition-specific modules for asthma along with a special form for collecting demographic and clinical characteristics.

Results: Three hundred fifteen children with mean age 5.35 years (Group A) and 189 with mean age 10.79 years (Group B), were recruited. Children with controlled asthma had significant higher mean score than the other asthma control groups (P < 0.001). Corticosteroid use, asthma severity, number of visits in doctor's office and lack of asthma control were significantly associated with the DCGM-37 scores as well as Impact Scale and Worry Scale. Lack of Asthma Control was the only factor that was associated with negative HRQoL in all the multiple regression models, controlling for the effect of the other covariates, in both age groups.

Conclusions: In conclusion, the evaluation of asthma HRQoL independently reflects the asthma control state and a dimension of its severity. These results highlight the need to modify asthma management strategy.
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http://dx.doi.org/10.1002/ppul.22768DOI Listing
December 2013

Drug-resistant tuberculosis in two children in Greece: report of the first extensively drug-resistant case.

Eur J Pediatr 2013 Apr 21;172(4):563-7. Epub 2012 Aug 21.

3rd Department of Pediatrics, School of Medicine, Aristotle University, Thessaloniki, Greece.

Extensively drug-resistant (XDR) tuberculosis (TB) represents a serious and growing problem in both endemic and non-endemic countries. We describe a 2.5-year-old girl with XDR-pulmonary TB and an 18-month-old boy with pre-XDR-central nervous system TB. Patients received individualized treatment with second-line anti-TB agents based on genotypic and phenotypic drug susceptibility testing results. Both children achieved culture conversion 3 months and 1 month after treatment initiation, respectively. The child with XDR-pulmonary TB showed evidence of cure while treatment adverse events were managed without treatment interruption. The child with pre-XDR-central nervous system TB after 6-month hospitalization with multiple infectious complications had a dismal end due to hepatic insufficiency possibly related to anti-TB treatment. This is the first report of children with pre-XDR and XDR TB in Greece, emphasizing the public health dimensions and management complexity of XDR TB.
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http://dx.doi.org/10.1007/s00431-012-1811-8DOI Listing
April 2013

Level of parent-asthmatic child agreement on health-related quality of life.

J Asthma 2011 Apr;48(3):286-97

Faculty of Nursing, National & Kapodistrian University of Athens, Goudi. 11517, Athens, Greece.

Background: Direct assessment of health-related quality of life (HRQοL) is necessary to understand the impact of a disease on patients' well-being and to evaluate clinical interventions. There is substantial debate in the literature on pediatric health outcomes concerning who is the most appropriate respondent when assessing children's HRQoL.

Objective: To evaluate the level of agreement between child self-reports and parent proxy-reports concerning HRQoL in children with asthma.

Methods: A total of 504 children with asthma and their parents who were referred to outpatient asthma clinic participated in this study. Subjects were divided into two age groups (4-7- and 8-14-year-olds). The DISABKIDS chronic generic measure-long form (DCGM-37), the DISABKIDS smiley measure (DSM), and the DISABKIDS condition-specific modules for asthma were used. The level of agreement between children and parents was evaluated using intra-class correlation coefficients and Bland-Altman analysis.

Results: A satisfactory level of agreement between younger children and their parents except those with severe asthma with both methods was observed; the level of agreement in the older ones was moderate with the exception of general subscale. Asthmatic children's mean HRQoL scores were significantly lower than their parents for all subscales, except children with severe asthma in the older group, who stated lower HRQoL than their parents in most of the domains except those of Impact and Worry that were in close agreement. Fathers' assessment of HRQoL score was closer to their children's self-assessment in both groups. Families with higher family income showed a greater level of agreement.

Conclusions: Our study illustrated that parents overestimate HRQoL of their children with asthma even though moderate agreement between child self-reports and parent proxy-reports on HRQoL was noticed. Fathers seem to be better proxy-reporters than mothers. Any evaluation of current approaches to measuring children's HRQoL needs to allow both parent and child to give their own perspective.
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http://dx.doi.org/10.3109/02770903.2011.555031DOI Listing
April 2011

Aspergillus and the paediatric lung.

Paediatr Respir Rev 2009 Dec 26;10(4):178-85. Epub 2009 Sep 26.

3rd Department of Paediatrics, Aristotle University, Hippokration Hospital, Konstantinoupoleos 49, GR-54642 Thessaloniki, Greece.

Aspergillus spp produce a wide range of saprophytic and invasive syndromes in the lungs, including allergic bronchopulmonary aspergillosis (ABPA), aspergilloma and invasive pulmonary aspergillosis (IPA). ABPA results from hypersensitivity to the fungus, and mainly affects patients with asthma or cystic fibrosis (CF). The treatment of choice consists of systemic corticosteroids and itraconazole. Aspergilloma is managed by observation or surgery. IPA is predominantly seen in patients with haematological malignancies, chronic granulomatous disease or immunosuppressive treatment. With the use of aggressive therapies for end-stage CF, such as heart-lung transplantation, the potential for a patient to convert from colonization or ABPA to IPA has increased. Suggestive clinical and radiological findings, supplemented with mycological data using serology and molecular biology, have enhanced the capacity to diagnose IPA in paediatric patients. While voriconazole is considered the first-line therapy in IPA, several other antifungal agents may be appropriate alternatives.
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http://dx.doi.org/10.1016/j.prrv.2009.06.006DOI Listing
December 2009

Cough affects quality of life in asthmatic children aged 8-14 more than other asthma symptoms.

Allergol Immunopathol (Madr) 2009 Mar-Apr;37(2):80-8

Faculty of Nursing, National and Kapodistrian University of Athens, Greece.

Background: Asthma may influence children's health-related quality of life (QoL) differently by various symptoms, at different severity. The primary aim of this study was to evaluate the QoL in children with asthma and describe the impact of each asthma symptom on the child's well-being at different severity levels.

Material And Methods: Two hundred randomly selected children and one of their parents who consulted an outpatient asthma clinic, participated in the study. Qol was assessed with DISABKIDS-Smiley measure for children aged 4-7 years and with DISABKIDS DCGM-37 and Asthma Module for children 8-14 year old.

Results: Most of the children suffered from mild or moderate persistent asthma. Children with uncontrolled asthma stated lower QoL compared to partly controlled or controlled in both age groups (p < 0.05 in all domains). Cough appeared to affect QoL of 8-14 year olds more than other symptoms, especially in girls. In younger children, sex (boys, p = 0.039), age (p = 0.045), proxy sex (father, p = 0.048), frequency of doctor visits (4-6 months, p = 0.001), use of beta-2 agonists (p = 0.007) and father's smoking habits (p = 0.015) were associated with the QoL of coughing children but no correlation between cough and QoL was detected. In the 8-14 year age group coughers reported lower QoL compared to their counterparts; moreover, cough was found to affect QoL more than other symptoms (p < 0.05 in all domains).

Conclusions: Cough has a direct effect on asthmatic children's QoL but there is still an obvious need for research to reveal all the determinats of this effect.
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http://dx.doi.org/10.1016/s0301-0546(09)71109-7DOI Listing
August 2009

Pediatric inflammatory myofibroblastic tumor of the trachea: a case report and review of the literature.

Pediatr Pulmonol 2008 Aug;43(8):831-5

Department of Pathology, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece.

Inflammatory myofibroblastic tumors (IMTs) are relatively rare entities of a distinct histologic appearance and benign clinical course. Although these lesions have been described in virtually every anatomic location, there are few documented reports with tracheal localization. We add to the short list of pediatric IMTs of the trachea, a 13-year-old boy that was referred to our pediatric respiratory unit for evaluation of his respiratory distress. In particular, we describe the clinical and pathologic features of this patient and present a review of all reported lesions in the available literature.
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http://dx.doi.org/10.1002/ppul.20869DOI Listing
August 2008

High resolution computed tomography of the chest in cystic fibrosis (CF): is simplification of scoring systems feasible?

Eur Radiol 2008 Mar 27;18(3):538-47. Epub 2007 Nov 27.

Department of Radiology, University Hospital of Alexandroupolis, Democritus University of Thrace, Dragana, 68100 Alexandroupolis, Greece.

The purpose of this study was to simplify HRCT scoring systems (SS) for CF by selecting representative HRCT parameters. Forty-two consecutive patients with CF underwent baseline and follow-up chest HRCT. Three radiologists evaluated 84 HRCTs employing five SS. "Simplified" HRCT SS were formed by selection of parameters exhibiting statistically significant relations with FEV1. Pulmonary function tests (PFTs) and nutrition (IBW%) were recorded. Regression analysis, Pearson correlation and T-test were used for statistical analysis. Three HRCT parameters were selected for the formation of "simplified" HRCT SS (severity of bronchiectasis, bronchial wall thickening, atelectasis-consolidation) using regression analysis. There was excellent correlation between each "simplified" and corresponding complete score (0.892 < r < 0.0967, p < 0.0001) or the remaining four complete scores (0.786 < r < 0.961, p < 0.0001). Strong correlation was found among the five "simplified" scores (0.803 < r < 0.997, p < 0.0001). Comparing baseline complete and "simplified" scores with corresponding follow-up ones, significant worsening was observed (p < 0.0001). PFTs and IBW% did not change significantly. HRCT scores correlated moderately with FVC and FEV1, but there was no correlation with FEF25-75 and IBW%. "Simplified" HRCT SS are as reliable as the complete ones and detect progression of lung disease earlier than clinical parameters. They are easy to use and could be adopted in clinical practice.
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http://dx.doi.org/10.1007/s00330-007-0810-zDOI Listing
March 2008

A Bayesian approach to copy-number-polymorphism analysis in nuclear pedigrees.

Am J Hum Genet 2007 Oct 8;81(4):808-12. Epub 2007 Aug 8.

School of Medicine and Biomedical Sciences, University of Sheffield, Sheffield, UK.

Segmental copy-number polymorphisms (CNPs) represent a significant component of human genetic variation and are likely to contribute to disease susceptibility. These potentially multiallelic and highly polymorphic systems present new challenges to family-based genetic-analysis tools that commonly assume codominant markers and allow for no genotyping error. The copy-number quantitation (CNP phenotype) represents the total number of segmental copies present in an individual and provides a means to infer, rather than to observe, the underlying allele segregation. We present an integrated approach to meet these challenges, in the form of a graphical model in which we infer the underlying CNP phenotype from the (single or replicate) quantitative measure within the analysis while assuming an allele-based system segregating through the pedigree. This approach can be readily applied to the study of any form of genetic measure, and the construction permits extension to a wide variety of hypothesis tests. We have implemented the basic model for use with nuclear families, and we illustrate its application through an analysis of the CNP located in gene CCL3L1 in 201 families with asthma.
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http://dx.doi.org/10.1086/520096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2227930PMC
October 2007

Atopic sensitization and the international variation of asthma symptom prevalence in children.

Am J Respir Crit Care Med 2007 Sep 15;176(6):565-74. Epub 2007 Jun 15.

Institute of Epidemiology, Ulm University, Helmholtzstrasse 22, D-89075 Ulm, Germany.

Rationale: Atopic sensitization has long been known to be related to asthma in children, but its role in determining asthma prevalence remains to be elucidated further.

Objectives: To investigate the role of atopic sensitization in the large international variation in the prevalence of childhood asthma.

Methods: Cross-sectional studies of random samples of 8- to 12-year-old children (n = 1,000 per center) were performed according to the standardized methodology of Phase Two of the International Study of Asthma and Allergy in Childhood (ISAAC). Thirty study centers in 22 countries worldwide participated and reflect a wide range of living conditions, from rural Africa to urban Europe. Data were collected by parental questionnaires (n = 54,439), skin prick tests (n = 31,759), and measurements of allergen-specific IgE levels in serum (n = 8,951). Economic development was assessed by gross national income per capita (GNI).

Measurements And Main Results: The prevalence of current wheeze (i.e., during the past year) ranged from 0.8% in Pichincha (Ecuador) to 25.6% in Uruguaiana (Brazil). The fraction of current wheeze attributable to atopic sensitization ranged from 0% in Ankara (Turkey) to 93.8% in Guangzhou (China). There were no correlations between prevalence rates of current wheeze and atopic sensitization, and only weak correlations of both with GNI. However, the fractions and prevalence rates of wheeze attributable to skin test reactivity correlated strongly with GNI (Spearman rank-order coefficient rho = 0.50, P = 0.006, and rho = 0.74, P < 0.0001, respectively). In addition, the strength of the association between current wheeze and skin test reactivity, assessed by odds ratios, increased with GNI (rho = 0.47, P = 0.01).

Conclusions: The link between atopic sensitization and asthma symptoms in children differs strongly between populations and increases with economic development.
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http://dx.doi.org/10.1164/rccm.200607-994OCDOI Listing
September 2007

Atypical CT findings of isolated pulmonary Langerhans cell histiocytosis in a 4-year-old boy.

J Thorac Imaging 2007 May;22(2):176-9

Department of Radiology, University Hospital of Alexandroupolis, Democritus University of Thrace, Dragana, Alexandroupolis, Greece.

A 4-year old boy was admitted to hospital with progressive respiratory failure. A chest roentgenogram revealed hyperinflated lungs and a diffuse reticular pattern. There was no smoking history in the family environment. A thin slice computed tomography of the lungs exhibited extended and diffuse cystic lung disease with no zonal predominance. An open lung biopsy showed pulmonary Langerhans cell histiocytosis. No other organs were involved. Despite treatment initiation the boy succumbed to his pulmonary insufficiency 3 weeks later. Isolated pulmonary Langerhans cell histiocytosis in children may have an unfavorable prognosis and in contrast with adults, it may present on computed tomography with lower lobe predominance and without sparing the lung bases or the anterior parts of middle lobe and lingula.
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http://dx.doi.org/10.1097/01.rti.0000213565.40667.8fDOI Listing
May 2007

Quantitative linkage genome scan for atopy in a large collection of Caucasian families.

Hum Genet 2007 Mar 14;121(1):83-92. Epub 2006 Nov 14.

Virginia Institute for Psychiatric and Behavioral Genetics, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, USA.

Quantitative phenotypes correlated with a complex disorder offer increased power to detect linkage in comparison to affected-unaffected classifications. Asthma is a complex disorder characterized by periods of bronchial obstruction and increased bronchial hyper reactivity. In childhood and early adulthood, asthma is frequently associated also with quantitative measures of atopy. Genome wide quantitative multipoint linkage analysis was conducted for serum IgE levels and percentage of positive skin prick test (SPT(per)) using three large groups of families originally ascertained for asthma. In this report, 438 and 429 asthma families were informative for linkage using IgE and SPT(per) which represents 690 independent families. Suggestive linkage (LOD > or = 2) was found on chromosomes 1, 3, and 8q with maximum LODs of 2.34 (IgE), 2.03 (SPT(per)), and 2.25 (IgE) near markers D1S1653, D3S2322-D3S1764, and D8S2324, respectively. The results from chromosomes 1 and 3 replicate previous reports of linkage. We also replicate linkage to 5q with peak LODs of 1.96 (SPT(per)) and 1.77 (IgE) at or near marker D5S1480. Our results provide further evidence implicating chromosomes 1, 3, and 5q. The current report represents one of the biggest genome scans so far reported for asthma related phenotypes. This study also demonstrates the utility of increased sample sizes and quantitative phenotypes in linkage analysis of complex disorders.
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http://dx.doi.org/10.1007/s00439-006-0285-zDOI Listing
March 2007

A genome-wide search for linkage to asthma phenotypes in the genetics of asthma international network families: evidence for a major susceptibility locus on chromosome 2p.

Eur J Hum Genet 2006 Mar;14(3):307-16

Genetics Research Glaxo SmithKline, Research Triangle Park, NC 27709, USA/Stevenage, UK. Sreekumar.

Asthma is a complex disease and the intricate interplay between genetic and environmental factors underlies the overall phenotype of the disease. Families with at least two siblings with asthma were collected from Europe, Australia and the US. A genome scan using a set of 364 families with a panel of 396 microsatellite markers was conducted. Nonparametric linkage analyses were conducted for asthma and three asthma-related phenotypes: bronchial hyper-reactivity (BHR), strict definition of asthma and atopic asthma. Nine chromosomal regions with LOD scores greater than 1.5 were identified (chromosomes 1q, 2p, 3q, 4p, 4q, 6q, 12q, 20p and 21). Linkage refinement analysis was performed for three BHR loci by genotyping single nucleotide polymorphisms at an average marker density of 1 cM. The LOD scores increased to 3.07 at chromosome 4p and 4.58 at chromosome 2p, while the chromosome 6p locus did not refine. The LOD score at the chromosome 2p locus is highly significant on a genome-wide basis. The refined locus covers a region with a physical size of 12.2 Mb. Taken together, these results provide evidence for a major asthma susceptibility locus on chromosome 2p.
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http://dx.doi.org/10.1038/sj.ejhg.5201532DOI Listing
March 2006

Loss of FEV1 in cystic fibrosis: correlation with HRCT features.

Eur Radiol 2002 Sep 19;12(9):2229-35. Epub 2002 Mar 19.

Department of Radiology, Ippokratio Hospital of Thessaloniki, 54642 Thessaloniki, Greece.

The purpose of this study was to determine which high-resolution computed tomography (HRCT) features in patients with cystic fibrosis are most strongly associated with functional impairment as expressed by forced expiratory volume in one second (FEV1). Forty-seven patients with cystic fibrosis underwent chest HRCT and had pulmonary function tests. The HRCT examinations were evaluated for 11 features scored using a modification of Bhalla system and FEV1 was recorded as percentage of the predicted value. Univariate and multivariate correlations between HRCT scores and FEV1 were performed. The most common HRCT feature was bronchiectasis (98%) followed by atelectasis-consolidation (81%), bronchial wall thickening (77%), tree-in-bud sign (74%), mucous plugging (72%) and mosaic perfusion pattern (47%). On univariate analysis the following features correlated strongly with FEV1: bronchial wall thickening ( p<0.0000001), tree-in-bud sign ( p<0.0000001), mucous plugging ( p<0.0000001), atelectasis-consolidation (p<0.0000001), thickening of interlobular septa ( p<0.0002), severity ( p<0.0002) and extent of bronchiectasis ( p<0.0002). On multivariate analysis bronchial wall thickening and atelectasis-consolidation were the strongest independent determinants of the FEV1. We found a regression equation between FEV1 and the two HRCT features: FEV1=constant variable+a multiplied by bronchial wall thickening+b multiplied by atelectasis-consolidation (a and b=regression coefficients, R(2)=0.48). The major morphological determinants of functional abnormality in cystic fibrosis, as expressed by the loss of FEV1, are bronchial wall thickening and atelectasis-consolidation.
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http://dx.doi.org/10.1007/s00330-002-1340-3DOI Listing
September 2002