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.

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.

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.