Mycophenolate mofetil use is associated with reduced incidence of food allergy in liver transplanted children.

OBJECTIVES: The incidence of food allergy in children following liver transplantation is high and the pathogenesis is still not known. We aimed to identify risk factors for development of food allergies in liver transplant children. METHODS: 107 children and adolescents who underwent liver transplantation from 1999 to 2019 were included. Data were retrospectively collected from medical records included total and specific IgE, eosinophil cationic protein and eosinophil count 12 months after transplantation and at yearly follow up (median follow-up). RESULTS: 24/107 (22%) patients reported clinical food reactions. Median time from transplantation to debut of food allergy was 1.6 (IQR 0.6-3.3) years. Mycophenolate mofetil (MMF) was discontinued in 24/78 patients (31%) due to side effects. Children treated with MMF in addition to tacrolimus one year after transplantation reported less food allergy (12.5% vs. 37.8%, p=0.003) and sensitization to food allergens one year after transplantation (8.9% vs. 17.8%, p=0.02) than those not receiving MMF. Tacrolimus trough levels did not differ between the patients treated with MMF and those who were not. Treatment with MMF two years after transplantation was associated with less food allergy (p=0.001) and food sensitization (p=0.002), also when adjusted for age at transplantation (p=0.006 and p=0.03, respectively) or for use of basilixmab (p=0.015 and p=0.018, respectively). Basiliximab was also associated with less food allergy. CONCLUSIONS: Use of MMF one and two years after transplantation was associated with less food allergy and sensitization against food allergens. The effect of MMF was not due to reduced trough levels of of tacrolimus. An infographic is available for this article at: https://links.lww.com/MPG/C821.

The Physical Activity and Fitness in Childhood Cancer Survivors (PACCS) Study: Protocol for an International Mixed Methods Study.

BACKGROUND: Survivors of childhood cancer represent a growing population with a long life expectancy but high risks of treatment-induced morbidity and premature mortality. Regular physical activity (PA) may improve their long-term health; however, high-quality empirical knowledge is sparse. OBJECTIVE: The Physical Activity and Fitness in Childhood Cancer Survivors (PACCS) study comprises 4 work packages (WPs) aiming for the objective determination of PA and self-reported health behavior, fatigue, and quality of life (WP 1); physical fitness determination (WP 2); the evaluation of barriers to and facilitators of PA (WP 1 and 3); and the feasibility testing of an intervention to increase PA and physical fitness (WP 4). METHODS: The PACCS study will use a mixed methods design, combining patient-reported outcome measures and objective clinical and physiological assessments with qualitative data gathering methods. A total of 500 survivors of childhood cancer aged 9 to 18 years with ≥1 year after treatment completion will be recruited in follow-up care clinics in Norway, Denmark, Finland, Germany, and Switzerland. All participants will participate in WP 1, of which approximately 150, 40, and 30 will be recruited to WP 2, WP3, and WP 4, respectively. The reference material for WP 1 is available from existing studies, whereas WP 2 will recruit healthy controls. PA levels will be measured using ActiGraph accelerometers and self-reports. Validated questionnaires will be used to assess health behaviors, fatigue, and quality of life. Physical fitness will be measured by a cardiopulmonary exercise test, isometric muscle strength tests, and muscle power and endurance tests. Limiting factors will be identified via neurological, pulmonary, and cardiac evaluations and the assessment of body composition and muscle size. Semistructured, qualitative interviews, analyzed using systematic text condensation, will identify the perceived barriers to and facilitators of PA for survivors of childhood cancer. In WP 4, we will evaluate the feasibility of a 6-month personalized PA intervention with the involvement of local structures. RESULTS: Ethical approvals have been secured at all participating sites (Norwegian Regional Committee for Medical Research Ethics [2016/953 and 2018/739]; the Oslo University Hospital Data Protection Officer; equivalent institutions in Finland, Denmark [file H-19032270], Germany, and Switzerland [Ethics Committee of Northwestern and Central Switzerland, project ID: 2019-00410]). Data collection for WP 1 to 3 is complete. This will be completed by July 2022 for WP 4. Several publications are already in preparation, and 2 have been published. CONCLUSIONS: The PACCS study will generate high-quality knowledge that will contribute to the development of an evidence-based PA intervention for young survivors of childhood cancer to improve their long-term care and health. We will identify physiological, psychological, and social barriers to PA that can be targeted in interventions with immediate benefits for young survivors of childhood cancer in need of rehabilitation. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35838.

Cytokine profile in children with food allergy following liver transplantation.

BACKGROUND: LTX in children is associated with increased risk of food allergy, and the mechanisms underlying this are unknown. We wanted to study whether plasma cytokine profile differed in liver transplanted children, with and without food allergy, and whether it differed from untransplanted children with CLD. METHODS: Plasma cytokines, total and specific IgE in nine patients with food allergy were compared with 13 patients without food allergy following LTX, and also with seven untransplanted patients with CLD. RESULTS: No difference was found in the cytokine profile between liver transplanted patients with and without food allergy. Transplanted patients with food allergy having received a prescription of epinephrine had a significantly higher total IgE (2033 [234-2831] vs 10 [5-41] IU/L, P = .002) and MIP-1b (52 [37-96] vs 36 [32-39], P = .035) compared with transplanted patients without food allergy. Two patients with severe food allergy responded favorably to conversion from tacrolimus-based immunosuppression to MMF and corticosteroids with reduction in clinical symptoms, total IgE, specific IgE, IL-1ra, IL-4, RANTES, PDGF, MIP-1a, and TNFα. The transplantation group had higher levels of IL-1b, IL-5, IL-7, IL-13, GCSF, IFNγ, and MIP-1a compared with the CLD group. CONCLUSIONS: No overall difference was found in plasma cytokine profile between patients with and without food allergy. Patients with severe food allergy had significant elevation of MIP-1b. Discontinuation of tacrolimus reduced total and specific IgE and changed plasma cytokine profile. The plasma cytokine profile in liver transplanted children was different compared with children with CLD.

Asthma, Eczema, and Food Allergy in Children Following Liver Transplantation.

OBJECTIVES: To describe the prevalence and the relationship between asthma, eczema, food allergy, and rhinitis in children after liver transplantation. STUDY DESIGN: Children who were liver transplant recipients were investigated to assess whether the high prevalence of food allergies was accompanied by eczema, rhinitis, and asthma. Furthermore, we included 56 children with chronic liver disease to explore the risk of allergy, eczema, and asthma in this group. RESULTS: After liver transplantation, children had higher prevalence of allergic reactions to food as compared with children with chronic liver disease (P < .001). Current asthma (P = .04) and eczema (P < .02) were observed more frequently in transplanted children as compared with children with chronic liver disease. For transplanted children who had ever received tacrolimus the relative risk (RR) of asthma was 1.7 (95% CI, 1.2-2.4; P = .02) as compared with children with chronic liver disease. Transplanted children with asthma had higher rates of sensitization to food allergens than those without asthma (RR, 3.6; 95% CI, 1.3-10.3; P = .01). The most frequent food allergens associated with asthma in transplanted children were milk (RR for asthma, 3.9; 95% CI, 1.6-9.4; P < .01), eggs (RR, 2.9; 95% CI, 1.2-7.0; P = .03), and peanuts (RR, 3.7; 95% CI, 1.6-8.3; P < .01). Food allergies occurred earlier than asthma, at 1.5 years after transplantation (IQR, 0.5-3.0 years) vs 2.5 years after transplantation (IQR, 1.0-4.5 years; P < .05). Food allergies were also associated with eczema, but not with sensitization to aero-allergens or rhinitis. CONCLUSIONS: The high risk of food allergies in children who were liver transplant recipients was associated with eczema and asthma, but not rhinitis. The most frequent food allergens associated with asthma were milk, eggs, and peanuts.

Small effort, high impact: Focus on physical activity improves oxygen uptake (VO2peak ), quality of life, and mental health after pediatric renal transplantation.

This study estimates the effects on peak oxygen uptake (VO2 peak ), QoL, and mental health after the introduction of an adjusted post-transplant follow-up program, that is, early physiotherapy and focus on the importance of physical activity. VO2 peak was measured by a treadmill exercise test in 20 renal-transplanted children on the adjusted post-transplant follow-up and compared with a group of 22 patients investigated in a previously, before the implementation of our new follow-up routines. PedsQL and The Strengths and Difficulties Questionnaire (SDQ) were used to assess QoL and mental health in 45 patients on the new as compared to 32 patients on the previous follow-up strategy. The patients exposed to early physiotherapy and a higher focus on physical activity had significantly higher VO2 peak (44.3 vs 33.5 mL kg-1  min-1 , P = .031) in addition to improved QoL (P = .003) and mental health scores (P = .012). The cardiovascular risk profile was similar in both groups aside from significantly higher triglycerides in the present cohort. Small efforts as early physiotherapy and increased focus on physical activity after pediatric renal transplantation have significant impact on cardiorespiratory fitness, QoL, and mental health. The importance of physical activity should therefore be emphasized in follow-up programs.

Resolution of extensive severe bronchiectasis in an infant.

Bronchiectasis is, by definition, an irreversible condition. Following recent reports of reversible bronchiectasis in children, it has been suggested that the definition be broadened to include pre-bronchiectasis and transitional reversible states. We describe the case of a young infant who had extensive, severe bronchiectasis of unknown etiology that resolved following prolonged treatment with antibiotics and a tapering course of oral steroids. We suggest that the prolonged treatment may have played a role, perhaps by eradicating infection and thus enabling regeneration of bronchial anatomy.

The impact of shunt size on lung function in infants with univentricular heart physiology.

OBJECTIVES: To assess the relationship that shunt size, blood gases, and radiologic findings has on respiratory function in infants with univentricular heart physiology. SETTING: Cardiac catheter laboratory at Rikshospitalet University Hospital, Norway. PATIENTS: Fifteen infants with univentricular heart physiology admitted for cardiac catheterization. MEASUREMENTS: Lung function was measured by a fixed-orifice differential pressure flow sensor and mainstream volumetric capnography in 15 infants with univentricular heart arrangements during routine invasive assessment before the bidirectional cavopulmonary connection. Blood gases were measured from the indwelling catheters. Chest radiographs were assessed for heart size and pulmonary vasculature. Shunt size was assessed angiographically. MAIN RESULTS: Respiratory compliance was reduced in patients with a large surgical systemic-pulmonary arterial shunt (r = -0.67, r = 0.45, p = 0.03). Respiratory resistance was higher with increased heart size (r = 0.72, r = 0.52, p = 0.004). There was no association between arterial and end-tidal CO2 values. The arterial to end-tidal CO2 difference had an inverse relationship with the pulmonary to systemic shunt ratio (r = -0.38, r = 0.14, p = 0.015). CONCLUSION: A large surgical shunt size is related to stiffer lungs and a large heart is associated with a higher respiratory resistance. During mechanical ventilation of patients with univentricular heart physiology the end-tidal CO2 may be an unreliable substitute for arterial CO2 before the bidirectional cavopulmonary connection. We found a relationship between a decreased pulmonary to systemic shunt ratio and an increased arterial to end-tidal CO2 difference. This may indicate that a reason for the unreliability of end-tidal CO2 is an impaired gas exchange partially due to pulmonary hypoperfusion.

Differing lung function development in infants with univentricular hearts compared with healthy infants.

AIM: To compare the difference in lung function development of healthy controls and patients with univentricular hearts from birth prior to surgery and during the first year of life when cardiac shunt procedures and the cavopulmonary connection are required. METHODS: Tidal flow-volume measurements and single-occlusion tests were performed from birth serially up to 18 months of age on 28 unsedated spontaneously breathing infants with univentricular hearts and 58 healthy control infants. RESULTS: Infants with univentricular heart physiology had low tidal volumes, low compliance of the respiratory system and high respiratory rate at birth, which over time normalized, whereas the peak expiratory flow increased during the study period. The lung function measured at birth was predictive of later lung function measurements. CONCLUSION: The pattern of lung function development is different in the patients with univentricular hearts compared to healthy controls. Lung function measured at birth is predictive of later lung function.

Preoperative lung function in newborn infants with univentricular hearts compared with healthy controls.

AIM: To measure the difference in lung function between newborns with univentricular hearts and healthy controls and study associations between lung function and pulmonary blood flow and pulmonary vasculature markings. METHOD: Tidal flow-volume measurements and single occlusion tests were performed before surgery on 25 unsedated spontaneously breathing newborns with univentricular hearts recruited over a 3-year period. Seventy-five healthy control infants were measured. Pulmonary blood flow was graded according to the haemodynamic effect of the echocardiographically defined anatomy of the heart defect. Pulmonary vasculature was graded according to radiological markings. RESULTS: The infants with univentricular hearts had a lower mean tidal volume of 4.7 ml (CI 2.3, 7.2, p < 0.001) (n = 24) and a lower mean compliance of the respiratory system of 12.7 ml/kPa (CI 4.6, 20.8, p = 0.004) (n = 14). Pulmonary blood flow grading was associated with respiratory rate (r = 0.53, p < 0.001), tidal volume (r =-0.48, p < 0.001), compliance (r =-0.55, p < 0.001) and resistance (r =-0.31, p = 0.043). Pulmonary vasculature grading was associated with compliance (r =-0.68, p = 0.006), resistance (r =-0.69, p = 0.007) and the time constant (r =-0.62, p = 0.042). CONCLUSION: Newborns with univentricular hearts have reduced tidal volumes and reduced compliance of the respiratory system. The lung function abnormalities are associated with the degree of pulmonary blood flow and pulmonary vasculature markings.

Reduced pulmonary function in children with the Fontan circulation affects their exercise capacity.

Most children with functionally univentricular hearts nowadays are treated surgically by creating a total cavopulmonary connection. In the resulting Fontan circulation, the venous return and the pulmonary arterial bed are coupled in series, bypassing the heart. This gives the potential for interaction between the abnormal circulation and function of the lungs. In this study, we investigated the pattern of impairment of pulmonary function, and its relation to decreased exercise capacity. We performed spirometry in 33 (85 percent) of 39 eligible Norwegian children, aged from 8 to 16, with a total cavopulmonary connection, along with whole body plethysmography, the carbon monoxide single breath test, and a peak treadmill exercise test. The single breath test showed a mean corrected diffusing capacity of 66.5 percent of predicted, giving a z score of minus 2.88. The mean residual volume measured by whole body plethysmography was 146.8 percent, equivalent to a z score of 2.46, whereas the mean residual volume measured by the single breath test was 102.4 percent of predicted, this being the same as a z score of 0.43. The mean peak treadmill exercise test was 70.0 percent of predicted, equivalent with a z score of minus 3.07. Mean forced vital capacity was 85.7 percent of predicted, the equivalent z score being minus 0.92. Lung function correlated with the peak treadmill exercise test. We have shown, therefore, that children with the Fontan circulation have reduced diffusing capacity, possibly caused by the abnormal circulation through the lungs. The difference between residual volume measured by plethysmography and the single breath test implies trapping of air. The correlation of parameters for lung function with peak consumption of oxygen during exercise indicates that the abnormalities of pulmonary function may affect physical capacity.