Cardiopulmonary Exercise Performance of Children Born Non-Extremely Preterm.

Data on exercise tolerance of children born non-extremely preterm are sparse. We aimed to explore the cardiopulmonary exercise testing (CPET) characteristics in this population. We studied 63 children (age 7-12 years) born at 290/7-366/7 weeks of gestation (34 were late preterm, 29 were preterm) and 63 age-matched, term-born controls. All performed spirometry and CPET (cycle ergometry). There were no differences in activity levels and spirometric parameters between the group of preterm-born children and controls. A peak oxygen uptake (VO2peak) of <80% was noted in 25.4% of the term-born and 49.2% of preterm-born children (p = 0.001). Term-born participants presented similar VO2peak to late-preterm children but higher than those born at <340/7 weeks of gestation (p = 0.002). Ventilatory limitation was noted in 4.8% of term and 7.9% of preterm participants, while only one preterm child presented cardiovascular limitation. Children born before 34 weeks of gestation had higher respiratory rates and smaller tidal volumes at maximum exercise, as well as lower oxygen uptake for the level of generated work. We conclude that school-age children born at 29-34 weeks of gestation may present decreased exercise performance attributed to an altered ventilatory response to exercise and impaired O2 utilization by their skeletal muscles rather than other cardiopulmonary limiting factors.

Novel Indices to Improve the Diagnostic Ability of Nocturnal Oximetry in Children with OSAS.

Nocturnal pulse oximetry (NOx) is an alternative diagnostic test for obstructive sleep apnea syndrome (OSAS) in childhood yet with variable diagnostic performance. Our aim was to apply advanced signal analysis to develop novel and more accurate NOx indices. We studied 45 children aged 3-10 years who underwent adenotonsillectomy for adenotonsillar hypertrophy and OSAS symptoms. Participants performed NOx before and three months after surgery, and the changes in McGill oximetry score (MOS), oxygen desaturation ≥3% index (ODI3), and the novel parameters-cumulative saturation area (CSA) and oxygen saturation sample entropy (SSE)-were assessed. There was a significant improvement (p < 0.001) in all NOx indices. When pre- and post-adenotonsillectomy NOx recordings were compared, the MOS had an area under the curve (AUC) of 0.811 with 63.2% sensitivity and 100% specificity at a cutoff >1. The AUC of ODI3 was 0.994, with 97.8% sensitivity and 91.1% specificity at a cutoff of >3.6 events per hour. The CSA and SSE had an AUC of 1.00, with 100% sensitivity and specificity at a cutoff of >293 and >0.99, respectively. We conclude that the herein-introduced indices-CSA and SSE-hold promise in improving the diagnostic ability of NOx in children suspected of OSAS.

Diverging trends of respiratory allergies and eczema in Greek schoolchildren: Six surveys during 1991-2018.

Background: The prevalence of childhood asthma, rhinoconjunctivitis, and eczema in the city of Patras, Greece, has been followed in four consecutive surveys since 1991. After a continuous rise in the prevalence of all three of these disorders, a plateau was reached for asthma between 2003 and 2008, whereas the prevalence of rhinoconjunctivitis and eczema continued to increase. Objective: To investigate these trends in the same population into the following decade. Methods: We repeated two methodologically identical cross-sectional parental questionnaire surveys in 2013 and 2018 among 8-9-year-old schoolchildren (N = 2554 and N = 2648, respectively). In 2018, spirometry and fractional exhaled nitric oxide (FeNO) measurements were also performed. Results: Current asthma (i.e., wheeze/asthma in the past 2 years) decreased from 6.9% in 2008 to 5.2% in 2013 and 4.3% in 2018 (p for trend < 0.001). The prevalence of lifetime ("ever had") rhinoconjunctivitis also declined (5.1% in 2008, 4.4% in 2013, 3.0% in 2018; p for trend < 0.001), whereas that of lifetime eczema increased (10.8%, 13.6%, and 16.1%, respectively; p for trend < 0.001). The relative risk of current asthma in children with ever-had rhinoconjundtivitis was 7.73 in 2008, 6.00 in 2013, and 6.69 in 2018, whereas the relative risk in those with ever-had eczema was 5.15, 2.80, and 2.22, respectively. Among children with asthma, those with rhinoconjunctivitis had lower forced expiratory volume in the first second of expiration and higher FeNO values than those with eczema. Conclusion: The prevalence of asthma and rhinoconjunctivitis declined during the past decade in Greek schoolchildren, whereas the prevalence of eczema continued to rise. Nevertheless, the relationship between rhinoconjunctivitis and asthma remained strong, whereas the association between eczema and asthma appears to have weakened.

Exercise Limitation in Children and Adolescents with Mild-to-Moderate Asthma.

BACKGROUND: Children with uncontrolled asthma are less tolerant to exercise due to ventilatory limitation, exercise-induced bronchoconstriction (EIB), or physical deconditioning. The contribution of these factors in children with controlled mild-to-moderate asthma is unknown. OBJECTIVE: To explore the underlying mechanisms of reduced exercise capacity in children with controlled mild-to-moderate asthma. METHODS: This was a cross-sectional study of 45 children and adolescents (age 8-18 years) with controlled mild-to-moderate asthma (asthma control test score 21-25) and 61 age-matched healthy controls. All participants completed a physical activity questionnaire and performed spirometry and cardiopulmonary exercise testing (CPET; maximal incremental protocol). Spirometric indices and CPET parameters were compared between the two groups. The effect of EIB (FEV1 decrease >10% post CPET), ventilatory limitation and physical deconditioning on maximum oxygen uptake (O2peak), was assessed by multivariable linear regression. RESULTS: 62.2% of children with asthma and 29.5% of controls (P = 0.002) were categorized as inactive. Reduced exercise capacity (O2peak <80%) was noted in 53.3% of asthmatics and 16.4% of controls (P < 0.001). EIB was documented in 11.1% of participants with asthma. Physical deconditioning was noted in 37.8% of children with asthma and in 14.8% of controls (P = 0.013). Physical deconditioning emerged as the only significant determinant of O2peak, irrespective of asthma diagnosis, body mass index, ventilatory limitation and EIB. CONCLUSION: Children with controlled mild-to-moderate asthma are less tolerant to strenuous exercise than their healthy peers. The decreased exercise capacity in this population should mainly be attributed to physical deconditioning, while the contribution of ventilatory limitation and EIB is rather small.

Changing trends in the prevalence of childhood asthma over 40 years in Greece.

BACKGROUND: A series of repeated questionnaire surveys among 8- to 9-year-old school children in the city of Patras, Greece, demonstrated a continuous rise in the prevalence of wheeze/asthma from 1978 to 2003, with a plateau between 2003 and 2008. We further investigated wheeze/asthma trends within the same environment over the last decade. METHODS: Two follow-up surveys were conducted in 2013 (N = 2554) and 2018 (N = 2648). Physician-diagnosed wheeze and asthma were analyzed in relation to their occurrence (recent-onset: within the last 2 years; noncurrent: before 2 years; persistent: both prior and within the last 2 years). In 2018, spirometry was also performed in participants reporting symptoms and in a sample of healthy controls. RESULTS: The prevalence of current wheeze/asthma declined from 6.9% in 2008% to 5.2% in 2013% and 4.3% in 2018. The persistent and noncurrent wheeze/asthma groups followed this overall trend (P-for-trend <0.001), while the prevalence of recent-onset wheeze/asthma remained unchanged (P-for-trend >0.05). Persistent and noncurrent wheezers were also more frequently diagnosed with asthma, in contrast to those with recent-onset wheeze. The FEV1 z-score was less than -1 in 32.1% of children with recent-onset and in 22.4% of those with persistent wheeze/asthma; both rates were higher than those of the Noncurrent wheeze/asthma group (7.1%; p < .05) and of healthy controls (3.5%; p < .001). CONCLUSIONS: The prevalence of childhood wheeze/asthma has declined significantly during the last decade in Greece. The reversing trend may in part be attributed to changing asthma perceptions among physicians and/or parents, especially in the case of younger children with troublesome respiratory symptoms.

Pediatric Pulmonary Function Testing in COVID-19 Pandemic and Beyond. A Position Statement From the Hellenic Pediatric Respiratory Society.

As the COVID-19 pandemic is still evolving, guidelines on pulmonary function testing that may dynamically adapt to sudden epidemiologic changes are required. This paper presents the recommendations of the Hellenic Pediatric Respiratory Society (HPRS) on pulmonary function testing in children and adolescents during the COVID-19 era. Following an extensive review of the relevant literature, we recommend that pulmonary function tests should be carried out after careful evaluation of the epidemiologic load, structured clinical screening of all candidates, and application of special protective measures to minimize the risk of viral cross infection. These principles have been integrated into a dynamic action plan that may readily adapt to the phase of the pandemic.

emm Types and clusters and macrolide resistance of pediatric group A streptococcal isolates in Central Greece during 2011-2017.

BACKGROUND: The surveillance of emm types and macrolide susceptibility of group A streptococcus (GAS) in various areas and time periods enhances the understanding of the epidemiology of GAS infections and may guide treatment strategies and the formulation of type-specific vaccines. Greece has emerged as a country with high macrolide use. However, studies suggest a gradual reduction in macrolide consumption after 2007. METHODS: During a 7-year period (2011-2017), 604 GAS isolates were recovered from consecutive children presenting with pharyngeal or nonpharyngeal infections in Central Greece; 517 viable isolates underwent molecular analysis, including emm typing. RESULTS: Isolates belonged to 20 different emm types (in decreasing order of prevalence: 1, 89, 4, 12, 28, 3, 75 and 6, accounting for 88.2% of total isolates). The emm types comprised 10 emm clusters (five most common clusters: E4, A-C3, E1, A-C4 and A-C5). The emm89 isolates were acapsular ('new clade'). Overall macrolide resistance rate was 15.4%, and cMLSB emerged as the predominant resistance phenotype (56.4%). The lowest annual resistance rates occurred in 2014 (13.1%), 2016 (5.5%) and 2017(8.0%) (P for trend = 0.002). Consumption of macrolide/lincosamide/streptogramin B declined by 22.6% during 2011-2017. Macrolide resistance and emm28 and emm77 types were associated (both P<0.001). The most frequently identified genetic lineages of macrolide-resistant GAS included emm28/ST52, emm77/ST63, emm12/ST36, emm89/ST101 and emm4/ST39. We estimated that 98.8% of the isolates belonged to emm types incorporated into a novel 30-valent M protein vaccine. CONCLUSIONS: In Central Greece during 2011-2017, the acapsular emm89 isolates comprised the second most prevalent type. Susceptibility testing and molecular analyses revealed decreasing GAS macrolide resistance rates, which may be attributed to the reduction in the consumption of macrolides and/or the reduced circulation of macrolide-resistant clones in recent years. Such data may provide valuable baseline information in targeting therapeutic intervention and the formulation of type-specific GAS vaccines.

Asthma: A Loss of Post-natal Homeostatic Control of Airways Smooth Muscle With Regression Toward a Pre-natal State.

The defining feature of asthma is loss of normal post-natal homeostatic control of airways smooth muscle (ASM). This is the key feature that distinguishes asthma from all other forms of respiratory disease. Failure to focus on impaired ASM homeostasis largely explains our failure to find a cure and contributes to the widespread excessive morbidity associated with the condition despite the presence of effective therapies. The mechanisms responsible for destabilizing the normal tight control of ASM and hence airways caliber in post-natal life are unknown but it is clear that atopic inflammation is neither necessary nor sufficient. Loss of homeostasis results in excessive ASM contraction which, in those with poor control, is manifest by variations in airflow resistance over short periods of time. During viral exacerbations, the ability to respond to bronchodilators is partially or almost completely lost, resulting in ASM being "locked down" in a contracted state. Corticosteroids appear to restore normal or near normal homeostasis in those with poor control and restore bronchodilator responsiveness during exacerbations. The mechanism of action of corticosteroids is unknown and the assumption that their action is solely due to "anti-inflammatory" effects needs to be challenged. ASM, in evolutionary terms, dates to the earliest land dwelling creatures that required muscle to empty primitive lungs. ASM appears very early in embryonic development and active peristalsis is essential for the formation of the lungs. However, in post-natal life its only role appears to be to maintain airways in a configuration that minimizes resistance to airflow and dead space. In health, significant constriction is actively prevented, presumably through classic negative feedback loops. Disruption of this robust homeostatic control can develop at any age and results in asthma. In order to develop a cure, we need to move from our current focus on immunology and inflammatory pathways to work that will lead to an understanding of the mechanisms that contribute to ASM stability in health and how this is disrupted to cause asthma. This requires a radical change in the focus of most of "asthma research."

The Forced Oscillation Technique in Paediatric Respiratory Practice.

The Forced Oscillation Technique (FOT) is a lung function modality based on the application of an external oscillatory signal in order to determine the mechanical response of the respiratory system. The method is in principal noninvasive and requires minimal patient cooperation, which makes it suitable for use in young paediatric patients. The FOT has been successfully applied in various paediatric respiratory disorders, such as asthma, cystic fibrosis, and chronic lung disease of prematurity, in order to assess airway obstruction, bronchodilator response, and airway responsiveness after bronchoprovocation challenge. This technique may be more sensitive than spirometry in identifying disturbances of peripheral airways and assessing the level of asthma control or the effectiveness of therapy at the long term. Further research is required to determine the exact role of the FOT in paediatric lung function testing and to incorporate the method in specific diagnostic and management algorithms.

Increased ß-glucuronidase activity in bronchoalveolar lavage fluid of children with bacterial lung infection: A case-control study.

BACKGROUND AND OBJECTIVE: ß-Glucuronidase is a lysosomal enzyme released into the extracellular fluid during inflammation. Increased ß-glucuronidase activity in the cerebrospinal and peritoneal fluid has been shown to be a useful marker of bacterial inflammation. We explored the role of ß-glucuronidase in the detection of bacterial infection in bronchoalveolar lavage fluid (BALF) of paediatric patients. METHODS: In this case-control study, % polymorphonuclear cell count (PMN%), ß-glucuronidase activity, interleukin-8 (IL-8), tumour necrosis factor-α (TNF-α) and elastase were measured in culture-positive (≥10(4) cfu/mL, C+) and -negative (C-) BALF samples obtained from children. RESULTS: A total of 92 BALF samples were analysed. The median ß-glucuronidase activity (measured in nanomoles of 4-methylumbelliferone (4-MU)/mL BALF/h) was 246.4 in C+ (interquartile range: 71.2-751) and 21.9 in C- (4.0-40.8) (P < 0.001). The levels of TNF-α and IL-8 were increased in C+ as compared with C- (5.4 (1.7-12.6) vs 0.7 (0.2-6.2) pg/mL, P < 0.001 and 288 (76-4300) vs 287 (89-1566) pg/mL, P = 0.042, respectively). Elastase level and PMN% did not differ significantly (50 (21-149) vs 26 (15-59) ng/mL, P = 0.051 and 20 (9-40) vs 18 (9-34) %, P = 0.674, respectively). The area under the curve of ß-glucuronidase activity (0.856, 95% confidence interval (CI): 0.767-0.920) was higher than that of TNF-α (0.718; 95% CI: 0.614-0.806; P = 0.040), IL-8 (0.623; 95% CI: 0.516-0.722; P = 0.001), elastase (0.645; 95% CI: 0.514-0.761; P = 0.008) and PMN% (0.526; 95 % CI: 0.418-0.632; P < 0.001). CONCLUSIONS: This study demonstrates a significant increase of ß-glucuronidase activity in BALF of children with culture-positive bacterial inflammation. In our population ß-glucuronidase activity showed superior predictive ability for bacterial lung infection than other markers of inflammation.

Investigating the associations between Mediterranean diet, physical activity and living environment with childhood asthma using path analysis.

OBJECTIVE: To investigate the role of the Mediterranean diet and physical activity with relation to living environment and childhood asthma. METHODS: 1125 children (529 boys), 10 to 12 years old were recruited either in an urban environment (Athens, n = 700) or rural environment (n = 425) in Greece. A path analytic model was developed to assess the causal relation between urban environment and asthma prevalence (standardized ISAAC questionnaire), through the mediation of the Mediterranean diet (evaluated by the KIDMED food frequency questionnaire) and physical activity (evaluated by the PALQ physical activity questionnaire). RESULTS: The proposed model had a very good fit (χ2/df ratio =1.05, RMSEA=0.007, 90% confidence interval: 0.01 to 0.046, p=0.97, CFI = 0.98). A significant total positive effect was found between urban environment and asthma symptoms (standardized beta= 0.09, p<0.001). Adherence to the Mediterranean diet was related negatively with asthma symptoms (standardized beta = -0.224, p<0.001). An inverse mediating effect of the Mediterranean diet was observed for the urban environment - asthma relation (standardized beta=-0.029, p<0.001) while physical activity had no significant contribution (p=0.62), adjusted for several confounders. CONCLUSIONS: The Mediterranean diet may protect against the harmful effect of urban environment on childhood asthma.

'They said it was bronchiolitis; is it going to turn into asthma doctor?'.

Acute bronchiolitis is a common paediatric disease of infancy. Its association with subsequent asthma development has puzzled clinicians and epidemiologists for decades. This article reviews the current state of knowledge regarding the role of acute bronchiolitis in the inception of asthma. There is little doubt that acute bronchiolitis is associated with an increased risk of recurrent wheezing throughout the primary school years although the direction of causality--i.e. whether bronchiolitis in infancy leads to asthma or it merely represents the first clinical presentation of predisposition to asthma--is uncertain. Existing evidence suggests that both host factors (e.g. prematurity, atopic predisposition) and acute viral infection characteristics (e.g. type of virus, severity) are operating in this relationship, perhaps with variable involvement in different individuals. Further clarification of these issues will help paediatricians provide evidence-based information regarding the long-term prognosis of this common disease to the families, and at the same time, it will facilitate prophylactic approaches and therapeutic strategies.

RespDoc: a new clinical decision support system for childhood asthma management based on Fraction of Exhaled Nitric Oxide (FeNO) measurements.

The use of Fraction of Exhaled Nitric Oxide (FeNO) for measurement of inflammation in the respiratory system is a good way to assess the level of asthma in children. In this paper we present a new Clinical Decision Support System (CDSS) for Childhood Asthma Management based on FeNO, which is named RespDoc. The core of RespDoc is a decision making algorithm and a patient's monitoring process that are extensively analyzed in the paper. The performance of RespDoc is tested through the process and assessment of archived patients' data.

Bacterial bronchitis caused by Streptococcus pneumoniae and nontypable Haemophilus influenzae in children: the impact of vaccination.

BACKGROUND: Protracted bacterial bronchitis is a major cause of persistent cough in childhood. The organisms most commonly isolated are nontypable Haemophilus influenzae and Streptococcus pneumoniae . There are no studies addressing typing of these organisms when recovered from the lower airways. METHODS: Isolates of these two organisms (identified in BAL samples from children undergoing routine investigation of a chronic cough thought to be attributable to a protracted bacterial bronchitis) were subject to typing. Samples were collected in Sheffield, England, and Athens, Greece. The majority of the children from Sheffield had received pneumococcal-conjugate vaccines 7 or 13 (PCV-7 or PCV-13) conjugate vaccine but only a minority of Greek children had received PCV-7. RESULTS: All 18 S pneumoniae isolates from Greek BAL samples are serotypes contained in PCV-13 while 10 are contained in PCV-7. In contrast, 28 of the 39 samples from Sheffield contained serotypes that are not included in PCV-13. All 26 of the nontypable H influenzae samples obtained in Sheffield produced distinct multilocus variable-number tandem repeat analysis profiles. There was a significant difference between children from Athens and Sheffield in the distribution of serotypes contained or not contained in the pneumococcal vaccine ( P = .04). More specifically, immunization with pneumococcal vaccine was related with isolation of S pneumoniae serotypes not included in the vaccine (OR, 0.021; CI, 0.003-0.115; P < .001). CONCLUSIONS: The data suggest that both vaccine and nonvaccine S pneumoniae serotypes may play a role in protracted bacterial bronchitis and provide some hints that serotype replacement may occur in response to the introduction of conjugate vaccines.

Physical activity and exercise-induced bronchoconstriction in Greek schoolchildren.

OBJECTIVE: To investigate the association between physical activity and exercise-induced bronchoconstriction (EIB) in an urban population sample of schoolchildren, taking into account potential confounders such as asthma symptoms and overweight. METHODS: Children aged 10-12 years answered validated questionnaires on physical activity (Physical Activity and Lifestyle Questionnaire) and asthma symptoms (ISAAC questionnaire), and were categorized according to their body mass index (BMI). EIB (FEV(1) decrease from baseline ≥13%) was assessed by a standardized free running Exercise Challenge Test (ECT). RESULTS: Six hundred seven children completed the ECT. There were no differences among asthma groups (diagnosed asthma, asthma-related symptoms not diagnosed as asthma, no asthma-related symptoms) regarding total daily energy expenditure and time spent in mild (1.1-2.9 metabolic equivalents-METs), moderate (3-6 METs), and vigorous (>6 METs) activities. Only overweight/obese EIB-positive children had shorter duration of vigorous activity as compared to their EIB-negative or non-overweight/obese EIB-positive peers. Total daily energy expenditure and duration of mild- and moderate-intensity activity were negatively associated with EIB independently of BMI status or asthma-related symptoms. CONCLUSIONS: Decreased levels of physical activity are associated with EIB irrespectively of BMI status and asthma-related symptoms. Longitudinal studies are needed to confirm the negative impact of sedentary lifestyle on the development of EIB suggested by these findings.

The association between leisure-time physical activities and asthma symptoms among 10- to 12-year-old children: the effect of living environment in the PANACEA study.

OBJECTIVE: This study evaluated the interrelationships of living environment, physical activity, lifestyle/dietary habits, and nutritional status on the prevalence of childhood asthma. METHODS: In a cross-sectional survey 1125 children (529 boys), 10 to 12 years old, were selected from 18 schools located in an urban environment (Athens, n = 700) and from 10 schools located in rural areas (n = 425) in Greece. RESULTS: Children living in Athens had higher likelihood of "ever had" asthma compared with children living in rural areas (odds ratio (OR) = 1.78, 95% confidence interval (CI) = 1.25-2.54), after adjusting for age and sex. After adjusting for age, sex, body mass index, and adherence to the Mediterranean diet (KIDMED score), leisure-time physical activity was inversely associated with "ever had" asthma. When stratifying by county of residence, a trend toward reduced asthma symptoms among children engaged in outdoor physical activities during their leisure time who reside in rural (but not urban) environment was observed (OR = 0.88, 95% CI = 0.77-1.01). CONCLUSIONS: The inverse relationship between asthma symptoms and leisure-time physical activity in the rural environment and the lack of an association between asthma symptoms and organized sports-related activities should draw the attention of public healthcare authorities. Their efforts should focus on the planning of a sustainable natural environment, which will promote the physical health of children and reduce the burden of childhood asthma.