Hellenic registry of patients with home mechanical ventilation (HR-HMV): profiling sleep Apnea-Hypopnea syndrome patients across Greece.

BACKGROUND: Chronic respiratory conditions are a prominent public health issue and thus, building a patient registry might facilitate both policy decision making and improvement of clinical management processes. Hellenic Registry of patients with Home Mechanical Ventilation (HR-HMV) was initiated in 2017 and a web-based platform is used to support patient data collection. Eighteen hospital departments (including sleep labs) across Greece participate in this initiative, focusing on recording data for both children and adult patients supported by mechanical ventilation at home, including patients with Sleep Apnea-Hypopnea Syndrome (SAHS) under Positive Airway Pressure (PAP) therapy. METHODS: The HR-HMV initiative ultimately aims to provide a database for evidence-based care and policy making in this specific domain. To this end, a web information system was developed and data were manually collected by clinics and hospital departments. Legal and privacy issues (such as General Data Protection Rule compliance and technical information security measures) have been considered while designing the web application. Based on the collected data, an exploratory statistical report of SAHS patients in Greece is presented. RESULTS: Eleven out of the eighteen participating clinics and hospital departments have contributed with data by the time of the current study. More than 5000 adult and children patient records have been collected so far, the vast majority of which (i.e., 4900 patients) diagnosed with SAHS. CONCLUSION: The development and maintenance of patient registries is a valuable tool for policy decision making, observational/epidemiological research and beyond (e.g., health technology assessment procedures). However, as all data collection and processing approaches, registries are also related with potential biases. Along these lines, strengths and limitations must be considered when interpreting the collected data, and continuous validation of the collected clinical data per se should be emphasized. Especially for Greece, where the lack of national registries is eminent, we argue that HR-HMV could be a useful tool for the development and the update of related policies regarding the healthcare services for patients with home mechanical ventilation support and SAHS patients, which could be useful for related initiatives at a European level as well.

Effects of a Long-Term Wearable Activity Tracker-Based Exercise Intervention on Cardiac Morphology and Function of Patients with Cystic Fibrosis.

Several studies have shown that patients with cystic fibrosis (CF), even at a young age, have pulmonary and cardiac abnormalities. The main complications are cardiac right ventricular (RV) systolic and/or diastolic dysfunction and pulmonary hypertension, which affects their prognosis. Exercise training (ET) is recommended in patients with CF as a therapeutic modality to improve physical fitness and health-related quality of life. However, questions remain regarding its optimal effective and safe dose and its effects on the patients' cardiac function. The study aimed to provide a wearable activity tracker (WAT)-based ET to promote physical activity in CF patients and assess its effects on cardiac morphology and function. Forty-two stable CF individuals (aged 16.8 ± 3.6 years) were randomly assigned to either the intervention (Group A) or the control group (Group B). Group A participated in a 1-year WAT-based ET program three times per week. All patients underwent a 6-min walking test (6-MWT) and an echocardiographic assessment focused mainly on RV anatomy and function at the baseline and the end of the study. RV systolic function was evaluated by measuring the tricuspid annular plane systolic excursion (TAPSE), the systolic tricuspid annular velocity (TVS'), the RV free-wall longitudinal strain (RVFWSL), and the right ventricular four-chamber longitudinal strain (RV4CSL). RV diastolic function was assessed using early (TVE) and late (TVA) diastolic transtricuspid flow velocity and their ratio TVE/A. Pulmonary artery systolic pressure (PASP) was also estimated. In Group A after ET, the 6MWT distance improved by 20.6% (p < 0.05), TVA decreased by 17% (p < 0.05), and TVE/A increased by 13.2% (p < 0.05). Moreover, TAPSE, TVS', RVFWSL, and RV4CSL increased by 8.3% (p < 0.05), 9.0% (p < 0.05), 13.7% (p < 0.05), and 26.7% (p < 0.05), respectively, while PASP decreased by 7.6% (p < 0.05). At the end of the study, there was a significant linear correlation between the number of steps and the PASP (r = −0.727, p < 0.01) as well as the indices of RV systolic function in Group A. In conclusion, WAT is a valuable tool for implementing an effective ET program in CF. Furthermore, ET has a positive effect on RV systolic and diastolic function.

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

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 beta2-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 ß2-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.

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

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.

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

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.

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

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.

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

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.

Mannitol Challenge to Assess Therapy Response in Asthmatic Children: An Interventional Cohort Study.

Bronchial provocation tests, such as the mannitol challenge, can be performed to identify and quantify the severity of bronchial hyperresponsiveness in asthmatic patients. Studies of the mannitol challenge as a monitoring tool in asthmatic children are limited. Our primary aim was to compare the bronchial hyperresponsiveness to mannitol in treatment-naive asthmatic children between baseline and three months after receiving the indicated asthma prophylaxis. Twenty-three asthmatic patients aged 4-16 years were analyzed in this prospective cohort study. All subjects underwent the mannitol challenge at baseline and after three months of treatment with budesonide ± formoterol. The difference in the provocative dose of mannitol to induce a 15% drop in FEV1 (PD15) between baseline and follow-up, as well as its association with the presence of exercise-induced or nocturnal asthma symptoms, were evaluated. The PD15 value increased significantly post-treatment (228.5 mg [4.50-458.15]; p = 0.04). Independently of the evaluation time point, the PD15 values were significantly lower in the presence of nocturnal asthma symptoms (490 mg [122-635] vs. 635 mg [635-635]; p = 0.03), whereas there was no association between the PD15 value and the presence of exercise-induced asthma (p = 0.73). These results suggest that bronchial hyperresponsiveness to mannitol may be a potential monitoring tool in the pediatric asthmatic population, reflecting therapy response in children receiving prophylactic treatment.

Low-frequency oscillometry indices to assess ventilation inhomogeneity in CF patients.

BACKGROUND: The utility of the forced oscillations technique (FOT) in cystic fibrosis (CF) remains uncertain. The aim of this study was to explore the ability of lower-frequency FOT indices, alone and after adjustment for the lung volume, to assess the extent of ventilation inhomogeneity in CF patients with varying disease severity. METHODS: Forty-five children, adolescents, and adults with CF (age 6.9-27 years) underwent spirometry, FOT, and nitrogen multiple-breath washout (N2-MBW) measurements. The respiratory resistance and reactance at 5 Hz (Rrs5 and Xrs5, respectively) were recorded, and a novel FOT index, the specific respiratory conductance (sGrs), was computed as the reciprocal of Rrs5 divided by the functional residual capacity. RESULTS: The sGrs correlated well with the lung clearance index (LCI) (Spearman's r: -.797), whereas the correlation of Rrs5 and Xrs5 with the LCI, albeit significant, was weaker (r: .643 and -.631, respectively). The sGrs emerged as the most robust predictor of LCI regardless of the severity of lung disease, as reflected by patients' age and lung function measurements. Most importantly, the relationship between sGrs and LCI remained unaffected by lung hyperinflation, as opposed to that of the LCI with the spirometric and standard FOT indices. CONCLUSIONS: In CF patients, the FOT indices at 5 Hz and the novel, volume-adjusted parameter sGrs, reflect the extent of lung involvement and the underlying ventilation inhomogeneity in a way comparable to N2-MBW. Future research should explore the role of lower-frequency FOT in assessing the severity and monitoring the progression of CF lung disease.

Physical Activity and Quality of Life among Patients with Cystic Fibrosis.

BACKGROUND: Physical activity (PA) improves exercise capacity, slows the decline in lung function, and enhances Quality of Life (QoL) in patients with cystic fibrosis (pwCF). OBJECTIVES: The study aimed to evaluate PA and QoL among children with CF compared to healthy controls; the secondary aim was to assess the correlation between PA, QoL, and lung function (FEV1). METHODS: Forty-five children and adolescents with CF and 45 age-matched controls completed two self-administered validated questionnaires: The Godin Leisure-Time Exercise Questionnaire (GLTEQ) and the DISABKIDS for QoL. Moreover, pwCF performed spirometry and multiple breath washout tests (MBW). In addition, weight, height, and BMI were recorded. The Godin Leisure-Time Exercise Questionnaire was used to evaluate physical activity; QOL was assessed using the DISABKIDS Questionnaire. The correlation of PA with QOL was assessed as well. RESULTS: Mean age of the CF population was 13.22 (±4.6) years, mean BMI 19.58 (±4.1) kg/m2, mean FEV1% 91.15 ± 20.46%, and mean LCI 10.68 ± 4.08. 68% of the CF group were active, 27% were medium active, 5% were sedentary, while 83% of the control group were active and 17% were medium active. PwCF with higher PA scores showed significantly higher emotional health (r2: 0.414, p: 0.006) and total QOL score (r2: 0.372; p: 0.014). The PA score showed no significant correlation with FEV1% or LCI. CONCLUSIONS: The children with CF showed satisfactory PA levels, which positively correlated to their QoL. More research is needed on the effect of increased levels of habitual physical activity to establish the decline in pulmonary function among pwCF.

Adherence to inhaled therapies over 4 years in people with cystic fibrosis.

BACKGROUND: This study examined the drug-specific and overall adherence of teenagers and adults with cystic fibrosis (CF) to inhaled therapies, to assess the degree of adherence, stability over a period of 4 years, and its association with health outcomes. METHODS: Fifty-five participants (30 women and 25 men) aged 14 years or older from two CF centers were enrolled in a retrospective review of inhaled medication adherence over 4 years. Adherence was assessed by the number of doses that were obtained by each participant based on the "e-prescription.gr" platform and the calculation of the medication possession ratio (MPR). RESULTS: The mean composite MPR (cMPR) for the entire research period was 0.75 ± 0.19. A total of 43.4% of participants showed a variance of adherence <25%. Participants with stable adherence had a significantly higher mean cMPR compared with those with variable adherence (0.86 ± 0.16 vs. 0.66 ± 0.17, p < 0.001). A statistically significant difference between groups of patients with different degrees of mean cMPR and mean weight was observed (p = 0.011). Patients with a mean cMPR ≥0.80 weighed significantly more than those with moderate and low adherence. In addition, mean weight correlated significantly with the mean cMPR (Β [95% confidence interval] = 14.845 [0.191-29.498], r = 0.269, p = 0.047). CONCLUSIONS: In our setting, the cMPR was easy to assess and showed that adherence was probably better than expected. The association of cMPR with weight should be further investigated. Stable adherence seemed to be related to high adherence. This observation could enhance our understanding of people with CF and their approach to treatment.

Pulmonary exacerbations, airway pathogens, and long-term course of lung clearance index in children and young adults with cystic fibrosis.

BACKGROUND: Pulmonary exacerbations (PEx), pathogens colonizing the respiratory tract, and patients' age are associated with progressive worsening of lung function among patients with cystic fibrosis (CF). However, the effect of these factors on longitudinal changes of Lung Clearance Index (LCI) remains unclear. AIM: To assess the role of age, different types of bronchial infection, and PEx on LCI deterioration. METHODS: We conducted a retrospective study assessing multiple-breath washout (MBW) and spirometry changes among CF patients evaluated at quarterly outpatient clinic visits over 8 years. MBW and spirometry were performed at each visit, sputum samples and/or cough swabs were obtained for culture, whereas respiratory symptoms and clinical examination findings were recorded. Patients who had ≥5 serial MBW measurements, one of which coincided with a pulmonary exacerbation, were reviewed. RESULTS: Seventy-six patients were included in the study: mean age of 10.61 years (range 1.75-23.75). A total of 1152 MBW tests and 1047 spirometry tests were performed. LCI was significantly higher among CF patients aged 11-15, 16-20, and over 20 years than those under 5 years of age; ΔLCI: 1.16 (confidence interval [CI] 0.43-1.90) and 3.25 (CI 2.33-4.17), respectively. Furthermore, LCI was significantly elevated in CF patients with positive cultures for Pseudomonas aeruginosa (0.52 LCI [CI -0.12 to 0.71]) and Stenotrophomonas Maltophilia (1.41 LCI [CI 0.61-2.21]). Moreover, increased values of LCI in CF patients were significantly associated with increased risk of PEx (odds ratio [OR] 1.19, CI [1.14-1.25], p < 0.001). CONCLUSION: LCI demonstrates a progression of lung disease and corresponds to changes in bacterial infections and PEx among patients with CF. LCI may be a valuable marker for tracking disease deterioration and may have a role in the routine clinical care of patients with CF.

Pulmonary medication adherence among children and adults with cystic fibrosis: Is there an association with disease severity?

BACKGROUND: Adherence to pulmonary medication is pivotal in delaying the progression of lung disease in cystic fibrosis (CF). Further exploring the consequences of poor adherence and its impact on disease severity may be valuable to personalize CF treatment strategy. AIM: To evaluate indicators of disease severity among children and adults with CF and investigate which of them are related to pulmonary medication adherence. METHODS: This is a retrospective cohort study. Data of children and adults followed up in one pediatric and one adult CF Unit were evaluated over 4 years. Disease severity was assessed by measuring body mass index (BMI), lung function, history of pulmonary exacerbations, and medication complexity. Adherence was assessed by calculating a 12-month medication possession ratio (MPR) for each pulmonary medication and then averaged for a composite MPR (cMPR) for each patient. Regression analysis was performed to explore the association of adherence with disease severity. RESULTS: Ninety-five patients were included in our study, 52 children and 43 adults. The overall cMPR was 0.74 (SD = 0.25); 0.68 (SD = 0.24) for children and 0.81 (SD = 0.24) for adults. Adults presented higher adherence, with overall mean cMPR 0.81 (SD = 0.24) compared to children with mean cMPR 0.68 (SD = 0.24) (p < 0.05, 95% CI = -0.27 to -0.03). Adherence was inversely related to FEV1 % predicted (ß = -0.002, 95% CI = -0.004 to 0, p = 0.023) and FVC% predicted (ß = -0.003, 95% CI = -0.005 to -0.001, p = 0.006) in regression analysis. Adherence was not found to be associated with BMI, history of exacerbations and medication complexity. The analysis of each medication showed that adherence to Dornase-alpha, Tobramycin and Colomycin was significantly related to specific disease severity indicators. CONCLUSION: An overall moderate to high level of adherence was found among our study population. Adults presented higher adherence compared to children. FEV1% and FVC% predicted were related to a significant decrease in adherence. Among our group of CF patients with an overall moderate to high level of adherence, adherence to pulmonary medication was inversely related to disease severity.

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

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.

Change in CF care during COVID-19 pandemic: Single-center experience in a middle-income setting.

INTRODUCTION: The coronavirus 2019 (COVID-19) pandemic has demanded care changes for patients with chronic disease. Patients with cystic fibrosis (CF) are considered at higher risk of developing severe manifestations in the case of SARS-CoV-2 infection, and a need for new ways of safer care delivery has been required to avoid transmission. OBJECTIVES: To assess the impact of the lockdown during the first wave of the COVID-19 pandemic and remote monitoring on patient's health status and daily maintenance therapy in a middle-income resource setting. METHODS: During the first wave of the pandemic period, we changed from regular clinic visits to telephone visit calls to monitor our patients' health condition and adherence to physiotherapy and physical exercise. RESULTS: A total of 120 patients or their caregivers have been contacted by telephone call visits over 10 weeks. During this period, 38 patients (28.33%) were identified to have pulmonary exacerbation; 89.5% were prescribed oral antibiotics, 3% were hospitalized to get iv antibiotics, and 8% of the patients presented other CF complications. Most of the patients did not change the frequency of the daily physiotherapy. Moreover, 71% of the patients who performed regular physical exercise changed the frequency and the type of exercise during the quarantine period. Interestingly, mean forced expiratory volume in 1 s and body weight increased significantly and after the lockdown period. CONCLUSIONS: During the COVID-19 pandemic, the implementation of telephone contact processes aiming for CF patients' appropriate care is of great importance. Further studies are needed to evaluate patient outcomes when transitioning from face-to-face clinics to telemedicine clinics.

The Fitter the Better? Cardiopulmonary Exercise Testing Can Predict Pulmonary Exacerbations in Cystic Fibrosis.

BACKGROUND: The role of cardiopulmonary exercise testing (CPET) in the assessment of prognosis in CF (cystic fibrosis) is crucial. However, as the overall survival of the disease becomes better, the need for examinations that can predict pulmonary exacerbations (PEx) and subsequent deterioration becomes evident. METHODS: Data from a 10-year follow up with CPET and spirometry of CF patients were used to evaluate whether CPET-derived parameters can be used as prognostic indexes for pulmonary exacerbations in patients with CF. Pulmonary exacerbations were recorded. We used a survival analysis through Cox Regression to assess the prognostic role of CPET parameters for PeX. CPET parameters and other variables such as sputum culture, age, and spirometry measurements were tested via multivariate cox models. RESULTS: During a 10-year period (2009-2019), 78 CF patients underwent CPET. Cox regression analysis revealed that VO2peak% (peak Oxygen Uptake predicted %) predicted (hazard ratio (HR), 0.988 (0.975, 1.000) p = 0.042) and PetCO2 (end-tidal CO2 at peak exercise) (HR 0.948 (0.913, 0.984) p = 0.005), while VE/VO2 and (respiratory equivalent for oxygen at peak exercise) (HR 1.032 (1.003, 1.062) p = 0.033) were significant predictors of pulmonary exacerbations in the short term after the CPET. Additionally, patients with VO2peak% predicted <60% had 4.5-times higher relative risk of having a PEx than those with higher exercise capacity. CONCLUSIONS: CPET can provide valuable information regarding upcoming pulmonary exacerbation in CF. Patients with VO2peak <60% are at great risk of subsequent deterioration. Regular follow up of CF patients with exercise testing can highlight their clinical image and direct therapeutic interventions.

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

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.

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.

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 (VO2max). The aim of the present study was to assess the prognostic value of hematological parameters of childhood obesity, as potential predictors of cardiorespiratory fitness (VO2max), 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 VO2max, using a cycle ergometer. The VO2max was negatively correlated with progressive strength to the BMIz (-0.656, p ≤ 0.001), hs-CRP (r = -0.341, p ≤ 0.002), glucose (r = -0.404, p ≤ 0.001) and insulin levels (r = -0.348, p ≤ 0.001), the homeostasis model assessment of insulin resistance (HOMA-IR) (r = -0.345, p ≤ 0.002), as well as to the leptin (r = -0.639, p ≤ 0.001) and fibrinogen concentrations (r = -0.520, p ≤ 0.001). The multivariate analysis revealed that only leptin and fibrinogen concentrations could predict the VO2max 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 VO2max 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, VO2max may be predicted from hematological parameters (leptin and fibrinogen), possibly bypassing more invasive methods.

Aspergillus and the paediatric lung.

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.