The burden of sleep disordered breathing in children with sickle cell disease.

Children with sickle cell disease (SCD) have an increased risk of sleep disordered breathing (SDB) compared with the general pediatric population. There has been a growing research interest on this field in recent years, yet many questions regarding risk factors and clinical implications of SDB remain unclear. The aim of this review is to provide a concise narrative and systematic synthesis of the available evidence on the epidemiology, clinical presentation, complications, and management, of SDB in children with SCD. An electronic search was conducted on studies published from the 1st of January 2000 to the 31st of December 2020 in PubMed/Medline, Scopus, and Cochrane databases. All studies focusing on SDB in children with SCD aged from 0 to 20 years were included. Studies were eligible for inclusion if available in the English language. A quantitative synthesis of the included studies was performed. Only studies focusing on specific treatment outcomes were included in a meta-analytic process. A total of 190 papers were initially identified. After screening the title and abstract, 112 articles were evaluated for eligibility. At the end of the selection process, 62 studies were included in the analysis. Sleep disordered breathing is associated with worse neurological, neurocognitive, and cardiological outcomes, whereas the association with frequency or severity of vaso-occlusive pain events and acute chest syndrome was not clarified. Therapeutic interventions like adenotonsillectomy or oxygen supplementation may result in a significant increase in mean nocturnal oxygen saturation but effective clinical implications remain still unclear.

Lung function between 8 and 15 years of age in very preterm infants with fetal growth restriction.

BACKGROUND: The impact of intrauterine growth restriction (IUGR) on lung function in very preterm children is largely unknown as current evidence is mainly based on studies in children born small for gestational age but not necessarily with IUGR. METHODS: Spirometry, transfer factor of the lung for carbon monoxide (TLco), and lung clearance index (LCI) were cross-sectionally evaluated at 8.0-15.0 years of age in children born <32 weeks of gestation with IUGR (n = 28) and without IUGR (n = 67). Controls born at term (n = 67) were also included. RESULTS: Very preterm children with IUGR had lower mean forced expired volume in the first second (FEV1) z-score than those with normal fetal growth (∆ -0.66, 95% confidence interval (CI) -1.12, -0.19), but not significant differences in LCI (∆ +0.24, 95% CI -0.09, 0.56) and TLco z-score (∆ -0.11, 95% CI -0.44, 0.23). The frequency of bronchopulmonary dysplasia (BPD) in the two groups was, respectively, 43% and 10% (P = 0.003). IUGR was negatively associated with FEV1 (B = -0.66; P = 0.004), but the association lost significance (P = 0.05) when adjusting for BPD. CONCLUSIONS: IUGR has an impact on conducting airways function of very preterm children at school age, with part of this effect being mediated by BPD. Ventilation inhomogeneity and diffusing capacity, instead, were not affected. IMPACT: IUGR does not necessarily imply a low birthweight for gestational age (and vice versa). While a low birthweight is associated with worse respiratory outcomes, the impact of IUGR on lung function in premature children is largely unknown. IUGR affects conducting airways function in school-age children born <32 weeks with IUGR, but not ventilation inhomogeneity and diffusing capacity. The impact of IUGR on FEV1 seems mainly related to the higher risk of BPD in this group.

Beneficial effects of adenotonsillectomy in children with sickle cell disease.

Tonsillectomy and adenoidectomy (T&A) is frequently performed in children with sickle cell disease (SCD). Our aim was to evaluate the impact of this surgery on overnight oxygenation and rates of complications in these patients. Children with SCD who underwent T&A between 2008 and 2014 in two tertiary hospitals were retrospectively evaluated. Overnight oximetry and admission rates due to vaso-occlusive pain episodes (VOEs) and acute chest syndrome (ACS) in the year preceding and following the surgery were compared. 19 patients (10 males, 53%) with a median age of 6 years (range 3.5-8) were included. A significant increase of mean overnight arterial oxygen saturation measured by pulse oximetry (S pO2 ) (from 93±3.6% to 95.3±2.8%, p=0.001), nadir S pO2 (from 83.0±7.1% to 88±4.1%, p=0.004) and a reduction of 3% oxygen desaturation index (from a median value of 5.7 to 1.8, p=0.003) were shown. The mean annual rate of ACS decreased from 0.6±1.22 to 0.1±0.2 events per patient-year (p=0.003), while the mean cumulative rate of hospitalisations for all causes and the incidence of VOEs were not affected. T&A improved nocturnal oxygenation and was also associated with a reduction in the incidence of ACS at 1-year follow-up after surgery.

Comparison of pulse oximetry and earlobe blood gas with CO-oximetry in children with sickle cell disease: a retrospective review.

OBJECTIVES: To investigate the agreement between pulse oximetry (SpO2) and oxygen saturation (SaO2) measured by CO-oximetry on arterialised earlobe blood gas (EBG) in children and adolescents with sickle cell disease (SCD). DESIGN AND SETTING: We retrospectively reviewed 39 simultaneous and paired SaO2 EBG and SpO2 measurements from 33 ambulatory patients with SCD (32 subjects with Haemoglobin SS and one with Haemoglobin Sß+, 52% male, mean±SD age 11.0±3.6, age range 5-18). Measurements were performed between 2012 and 2015 when participants were asymptomatic. Hypoxaemia was defined as SaO2 ≤93%. A Bland-Altman analysis was performed to assess the accuracy of SpO2 as compared with EBG SaO2. RESULTS: The mean±SD SpO2 and SaO2 values in the same patients were, respectively, 93.6%±3.7% and 94.3%±2.9%. The bias SpO2-SaO2 was -0.7% (95% limits of agreement from -5.4% to 4.1%) and precision was 2.5%. In 9/39 (23%) cases, the difference in SpO2-SaO2 was greater than the expected error range ±2%, with SaO2 more often underestimated by SpO2 (6/9), especially at SpO2values ≤93%. Thirteen participants (33%) were hypoxaemic. The sensitivity of SpO2 for hypoxaemia was 100%, specificity 85% and positive predictive value 76%. CONCLUSIONS: Pulse oximetry was inaccurate in almost a quarter of measurements in ambulatory paediatric patients with SCD, especially at SpO2values ≤93%. In these cases, oxygen saturation can be confirmed through EBG CO-oximetry, which is easier to perform and less painful than traditional arterial blood sampling.

Limitations of regional ventilation inhomogeneity indices in children with cystic fibrosis.

BACKGROUND: Scond is a multiple breath washout (MBW) index that measures convection-dependent ventilation inhomogeneity (CDI) arising within conductive airways, but the calculation method is unreliable in subjects with advanced cystic fibrosis (CF) lung disease. A new CDI index, Scond *, has been proposed for use in adults with CF and moderate to severe ventilation inhomogeneity. We aimed to evaluate the most appropriate CDI index in children and adolescents with CF and various degrees of inhomogeneity, and from that the most appropriate diffusion-convection-interaction index (Sacin or Sacin *). METHODS: Scond , Sacin  and the alternative indices, Scond *, and Sacin * were retrospectively calculated in subjects with CF aged 3 to 18 years and age-matched controls, who underwent sulfur hexafluoride MBW between 2003 and 2015. The upper limit of normal was based on 95th percentile of the control population. RESULTS: One hundred and twenty-seven subjects with CF (44% male; mean age ± SD: 7.5 years ± 4.9) and 94 controls (53% male; 7.9 years ± 5.1) were included in the final analysis. All measures of ventilation inhomogeneity were significantly higher in children with CF. As predicted, Scond reached a maximum value at lung clearance index (LCI) values of approximately 9. In subjects with LCI ≥ 9 Scond * showed good correlation with LCI, whilst Scond had no relationship with LCI (Spearman rank correlation Scond */LCI, 0.49; P < .01; Scond /LCI, -0.068; P = .46). In subjects with mild disease (LCI < 9) Scond was more frequently abnormal than Scond * (37% vs 16%; P = .01). CONCLUSIONS: Scond and Sacin are sensitive indices of early regional inhomogeneity, but are of no value when LCI ≥ 9. In these subjects, Scond * & Sacin * are potential alternatives.

Regional ventilation inhomogeneity in survivors of extremely preterm birth.

INTRODUCTION: Survivors of extreme prematurity may have disrupted lung development. We hypothesized that the multiple breath washout (MBW) index Scond, which is intended to reflect ventilation inhomogeneity from the conducting airways, could be a sensitive marker of respiratory impairment in this group. METHODS: Spirometry, TLco, and MBW were cross-sectionally evaluated at 8 to 14 years of age in children born at <28 weeks between 2004 and 2010 in Udine, Italy. Age-matched controls born at term were also included. Bronchopulmonary dysplasia (BPD) was defined as oxygen-dependence at 36 weeks postmenstrual age. The limits of normal were the 5th percentile of the reference population (Global Lung Initiative) for spirometry and TLco and the 95th percentile of controls for Lung Clearance Index, Scond, and Sacin from MBW. RESULTS: Results were obtained in 47 extremely preterm children (53% boys, mean ± standard deviation age 11.3 ± 2.0 years, 40% with BPD) and 60 controls (50% boys, 11.6 ± 1.9 years). There were significant differences between preterm children and controls in all lung function outcomes, except for Sacin. Among children born <28 weeks, Scond tended to be frequently abnormal than FEV1 z-score (29% vs 14%, P = .06). At multivariable linear regression, in the preterm group, current asthma was significantly associated with a higher Scond (B = 0.019, 95% confidence interval, 0.000-0.038), whereas BPD was not. CONCLUSION: Almost a third of extremely preterm children at school age showed Scond alterations that affected also children without BPD. Longitudinal studies should clarify the prognostic meaning of Scond abnormalities in this group.

Nutrition and Lung Growth.

Experimental evidence from animal models and epidemiology studies has demonstrated that nutrition affects lung development and may have a lifelong impact on respiratory health. Chronic restriction of nutrients and/or oxygen during pregnancy causes structural changes in the airways and parenchyma that may result in abnormal lung function, which is tracked throughout life. Inadequate nutritional management in very premature infants hampers lung growth and may be a contributing factor in the pathogenesis of bronchopulmonary dysplasia. Recent evidence seems to indicate that infant and childhood malnutrition does not determine lung function impairment even in the presence of reduced lung size due to delayed body growth. This review will focus on the effects of malnutrition occurring at critical time periods such as pregnancy, early life, and childhood, on lung growth and long-term lung function.

Coeliac disease in infants: antibodies to deamidated gliadin peptide come first!

BACKGROUND: The onset of coeliac disease (CD) in the first year of life is uncommon and the diagnosis can be challenging due to the suboptimal sensitivity of tissue transglutaminase antibodies (tTG) at this age and the many other possible causes of malabsorption in infants. Antibodies to deamidated gliadin peptides (anti-DGPs), especially IgG, may appear earlier than IgA anti-tTG in very young children with CD. CASE PRESENTATION: We report here on an 8-month-old child who was evaluated for failure to thrive, constipation and developmental delay. The symptoms started following gluten introduction in the diet. Laboratory tests showed high fecal elastase concentration, normal serum IgA levels with positive IgG and IgA anti-DGPs, whereas anti-tTG were not detected. The duodenal biopsy revealed a complete villous atrophy (Marsh-Oberhuber 3C). The culture of biopsy fragments in the presence of gliadin peptides did not stimulate the production of IgA anti-endomysial antibodies. Genetic testing proved the child was positive for HLA-DQ2 (DQA1*05; DQB1*02) and HLA-DQ8 (DQA1*03, DQB1*0302). Having initiated the gluten-free diet, the symptoms disappeared and the infant experienced rapid catch-up growth with normalization of psychomotor development. CONCLUSIONS: This case report highlights the utility of anti-DGPs for screening infants with suspected CD. The pattern with positivity for IgG and IgA anti-DGPs only is rare in IgA-competent children with biopsy-proven CD. It could be explained in infancy as immaturity of the adaptive immune system.