Search

Inert gas washout tests, performed using the single- or multiple-breath washout technique, were first described over 60 years ago. As measures of ventilation distribution inhomogeneity, they offer complementary information to standard lung function tests, such as spirometry, as well as improved feasibility across wider age ranges and improved sensitivity in the detection of early lung damage. These benefits have led to a resurgence of interest in these techniques from manufacturers, clinicians and researchers, yet detailed guidelines for washout equipment specifications, test performance and analysis are lacking. This manuscript provides recommendations about these aspects, applicable to both the paediatric and adult testing environment, whilst outlining the important principles that are essential for the reader to understand. These recommendations are evidence based, where possible, but in many places represent expert opinion from a working group with a large collective experience in the techniques discussed. Finally, the important issues that remain unanswered are highlighted. By addressing these important issues and directing future research, the hope is to facilitate the incorporation of these promising tests into routine clinical practice.

Advances in diagnostics and treatment of childhood cancer during the past few decades have substantially increased survival, resulting in a growing population of survivors of childhood cancer. Somatic and mental late effects of the cancer and the treatment may impact the quality of life (QoL). Previous reviews of QoL in survivors of childhood cancer have shown contradictory findings across studies and the majority of studies included have been based on data from North America and may not be directly comparable to a European setting. The aim of our study was to critically evaluate and summarise the latest evidence on the QoL of childhood cancer survivors in Europe and to identify survivors at particular risk. The eligible studies were published between 2008 and 2022, conducted in Europe and included participants who had survived at least 5 years after diagnosis of a childhood cancer. The main outcome of interest was QoL of survivors which was measured with validated qualitative and quantitative QoL questionnaires. A systematic literature search conducted in PubMed, EMBASE, PsycINFO and CINALH resulted in inclusion of 36 articles with a total of 14 342 survivors of childhood cancer. The majority of included studies found that childhood cancer survivors reported poorer QoL than comparisons. Female gender, treatment with haematopoietic stem cell transplantation and a brain tumour diagnosis were associated with lower QoL. With a growing population of childhood cancer survivors with many years ahead of them, targeted interventions and optimal follow‐up care are important to improve the QoL of survivors. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cell transplantation (HSCT) is currently the standard of care for many malignant and nonmalignant blood diseases. As several treatment-emerging acute toxicities are expected, optimal supportive measurements critically affect HSCT outcomes. The paucity of good clinical studies in supportive practices gives rise to the establishment of heterogeneous guidelines across the different centers, which hampers direct clinical comparison in multicentric studies. Aiming to harmonize the supportive care provided during the pediatric HSCT in Europe, the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) promoted dedicated workshops during the years 2017 and 2018. The present paper describes the resulting consensus on the management of sinusoidal obstructive syndrome, mucositis, enteral and parenteral nutrition, iron overload, and emesis during HSCT.

Background Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. Methods To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. Results There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. Conclusions These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk. [ABSTRACT FROM AUTHOR]

Background: Clinical management of primary ciliary dyskinesia (PCD) respiratory disease is currently based on improving mucociliary clearance and controlling respiratory infections, through the administration of antibiotics. Treatment practices in PCD are largely extrapolated from more common chronic respiratory disorders, particularly cystic fibrosis, but no randomized controlled trials (RCT) have ever evaluated efficacy and safety of any pharmacotherapeutics used in the treatment of PCD. Maintenance therapy, with the macrolide antibiotic azithromycin, is currently widely used in chronic respiratory diseases including PCD. In addition to its antibacterial properties, azithromycin is considered to have beneficial anti-inflammatory and anti-quorum-sensing properties. The aim of this study is to determine the efficacy of azithromycin maintenance therapy for 6 months on respiratory exacerbations in PCD. The secondary objectives are to evaluate the efficacy of azithromycin on lung function, ventilation inhomogeneity, hearing impairment, and symptoms (respiratory, sinus, ears and hearing) measured on a PCD-specific health-related quality of life instrument, and to assess the safety of azithromycin maintenance therapy in PCD.Methods: The BESTCILIA trial is a European multi-centre, double-blind, randomized, placebo-controlled, parallel group study. The intervention is tablets of azithromycin 250/500 mg according to body weight or placebo administered three times a week for 6 months. Subjects with a confirmed diagnosis of PCD, age 7-50 years, are eligible for inclusion. Chronic pulmonary infections with Gram-negative bacteria or any recent occurrence of non-tuberculous mycobacteria are exclusion criteria. The planned number of subjects to be included is 125. The trial has been approved by the Research Ethics Committees of the participating institutions.Discussion: We present a study protocol of an ongoing RCT, evaluating for the first time, the efficacy and safety of a pharmacotherapeutic treatment for patients with PCD. The RCT evaluates azithromycin maintenance therapy, a drug already commonly prescribed in other chronic respiratory disorders. Furthermore, the trial will utilize the Lung clearance index and new, PCD-specific quality of life instruments as outcome measures for PCD. Recruitment is hampered by frequent occurrence of Pseudomonas aeruginosa infection, exacerbations at enrolment, and the patients' perception of disease severity and necessity of additional management and treatment during trial participation.Trial Registration: EudraCT 2013-004664-58 (date of registration: 2014-04-08). [ABSTRACT FROM AUTHOR]

This statement summarizes the information available on specific exercise test protocols and outcome parameters used in patients with cystic fibrosis (CF) and provides expert consensus recommendations for protocol and performance of exercise tests and basic interpretation of results for clinicians. The conclusions were reached employing consensus meetings and a wide-band Delphi process. Although data on utility are currently limited, standardized exercise testing provides detailed information on physiological health, allows screening for exercise-related adverse reactions and enables exercise counselling. The Godfrey Cycle Ergometer Protocol with monitoring of oxygen saturation and ventilatory gas exchange is recommended for exercise testing in people 10 years and older. Cycle ergometry only with pulse oximetry using the Godfrey protocol or treadmill exercise with pulse oximetry - preferably with measurement of gas exchange - are second best options. Peak oxygen uptake, if assessed, and maximal work rate should be reported as the primary measure of exercise capacity. The final statement was reviewed by the European Cystic Fibrosis society and revised based on the comments received. The document was endorsed by the European Respiratory Society. © 2015 The Author(s) Published by S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

OBJECTIVE: The prevalence of lower limb deformities physiologically decreases after 5 years of age. It remains high in some tropical and subtropical regions where it has been associated with severe vitamin D deficiency, low calcium/milk intakes, malnutrition, and/or fluoride overexposure. Very little data is available in apparently healthy Caucasian children and adolescents. DESIGN: We evaluated the prevalence of genu varum/valgum and other clinical symptoms, and assessed vitamin D status and markers of calcium metabolism in 226 apparently healthy European full-time boarders (7–16 years) seen during winter–spring and fed a cereal-based diet with little access to meat, milk, and dairy products. A cohort of 71 white children and adolescents hospitalized for acute illness served as age-matched controls. RESULTS: Association studies showed a high prevalence of lower limb deformities (36%) and higher alkaline phosphate activities in the 21% of children and adolescent full-time boarders with serum 25-(OH)D levels ≤30 nmol/l, and low serum calcium in the 74% of boarders with 25-(OH)D levels ≤50 nmol/l, compared with boarders with higher vitamin D status. No such anomalies were found in the control cohort despite lower serum 25-(OH)D levels. CONCLUSIONS: Low 25-(OH)D levels, at least during winter–spring, combined with additional risk factors such as very low calcium/milk intakes and possibly digestive disorders, are associated with an increased risk of genu varum/valgum in European children and adolescents. Thus, dietary fortification, or supplementation with vitamin D, may be recommended, at least during the winter, to European children and adolescents with either none or insufficient calcium/dairy product intakes. [ABSTRACT FROM AUTHOR]

Introduction: Nutritional rickets has been described from at least 59 countries in the last 20 years. Its spectrum of causes differs in different regions of the world. Methods: We conducted a systematic review of articles on nutritional rickets from various geographical regions published in the last 20 years. We extracted information about the prevalence and causes of rickets. Results: Calcium deficiency is the major cause of rickets in Africa and some parts of tropical Asia, but is being recognised increasingly in other parts of the world. A resurgence of vitamin D deficiency has been observed in North America and Europe. Vitamin D-deficiency rickets usually presents in the 1st 18 months of life, whereas calcium deficiency typically presents after weaning and often after the 2nd year. Few studies of rickets in developing countries report values of 25(OH)D to permit distinguishing vitamin D from calcium deficiency. Conclusions: Rickets exists along a spectrum ranging from isolated vitamin D deficiency to isolated calcium deficiency. Along the spectrum, it is likely that relative deficiencies of calcium and vitamin D interact with genetic and/or environmental factors to stimulate the development of rickets. Vitamin D supplementation alone might not prevent or treat rickets in populations with limited calcium intake. [ABSTRACT FROM AUTHOR]

The Lung Clearance Index (LCI) is an index derived from washout recordings, able to detect early peripheral airway damage in subjects with cystic fibrosis (CF) with a greater sensitivity than spirometry. LCI is a marker of overall lung ventilation inhomogeneity; in fact, as pulmonary ventilation worsens, the number of tidal breaths and the expiratory volumes required to clear the lungs of a marker gas are increased, as documented by a greater value. In the field of CF, LCI allows indirect investigation of the small airways (< 2 mm) the site where, from a pathophysiologic point of view, the disease begins due to the defect of the CF transmembrane-conductance regulator (CFTR) protein. Infant pulmonary function changes seem to occur before clinically overt symptoms of lower respiratory illness occur. When performing the test, it is important to refer to the American Thoracic Society and European Respiratory Society consensus statements and apply a strict standardization. In Italy the first tests were carried out in 2014 for research purpose and now approximately 10 centers are collecting data and are experiencing a consistency in repeating exams. Currently in Italian centers children at pre-school age are the main target: in this population it is important to have a sensitive and feasible test, non-invasive, that can be performed at tidal volume without sedation, and requiring minimal cooperation and coordination, and that can be used longitudinally over time. Another target could be the transplanted subjects to detect early signs of lung function decline. The content of this paper captures the experience and discussions among some of the Italian centers where LCI is currently used for research and/or in clinical practice about the method and the need to have a common approach. The aim of this paper is not to describe the methodology of MBW, but to inform the pediatric community about the possible application of LCI in CF. [ABSTRACT FROM AUTHOR]