A systematic approach to transplanting non-resident, non-citizens in an established US pediatric lung transplant program.

Introduction: The Texas Children's Hospital Lung Transplant Program undertook consideration of its first non-resident, non-citizen for lung transplantation in 2011. Methods: Four referrals from the Royal Embassy of Saudi Arabia were received, and two patients were evaluated from 2011 to 2013. Results: After a suitable candidate and family was identified, the program adopted a systematic approach to ensure that all the necessary elements of pre-transplant care, informed consent, and post-transplant care could be effectively delivered. Conclusion: The use of hospital translation services and the development of a strong professional relationship with a well-trained pediatric respirologist in Saudi Arabia combined with an excellent early post-transplant clinical course provide lessons that may be of help to other transplant programs considering international patients as candidates for solid organ transplantation.

Haemodynamic characterisation and heart catheterisation complications in children with pulmonary hypertension: Insights from the Global TOPP Registry (tracking outcomes and practice in paediatric pulmonary hypertension).

BACKGROUND: The TOPP Registry has been designed to provide epidemiologic, diagnostic, clinical, and outcome data on children with pulmonary hypertension (PH) confirmed by heart catheterisation (HC). This study aims to identify important characteristics of the haemodynamic profile at diagnosis and HC complications of paediatric patients presenting with PH. METHODS AND RESULTS: HC data sets underwent a blinded review for confirmation of PH (defined as mean pulmonary arterial pressure ≥ 25 mmHg, pulmonary capillary wedge pressure ≤ 12 mmHg and pulmonary vascular resistance index [PVRI] of >3 WU × m(2)). Of 568 patients enrolled, 472 who fulfilled the inclusion criteria and had sufficient data from HC were analysed. A total of 908 diagnostic and follow-up HCs were performed and complications occurred in 5.9% of all HCs including five (0.6%) deaths. General anaesthesia (GA) was used in 53%, and conscious sedation in 47%. Complications at diagnosis were more likely to occur if GA was used (p=0.04) and with higher functional class (p=0.02). Mean cardiac index (CI) was within normal limits at diagnosis when analysed for the entire group (3.7 L/min/m(2); 95% confidence interval 3.4-4.1), as was right atrial pressure despite a severely increased PVRI (16.6 WU × m(2,) 95% confidence interval 15.6-17.76). However, 24% of the patients had a CI of <2.5L/min/m(2) at diagnosis. A progressive increase in PVRI and decrease in CI was observed with age (p<0.001). CONCLUSION: In TOPP, haemodynamic assessment was remarkable for preserved CI in the majority of patients despite severely elevated PVRI. HC-related complication incidence was 5.9%, and was associated with GA and higher functional class.

Clostridium difficile colitis in children following lung transplantation.

Risk factors for Clostridium difficile diarrhea are antibiotic exposure, hospitalization, extreme ages, and immunodeficiency. Patients with CF have a high rate of colonization with C. difficile. We performed a retrospective chart review of patients at Texas Children's Hospital who underwent lung transplantation since the inception of our program in October 2002 until October 2008. There were 78 pediatric lung transplants performed at our institution during the study period. Four patients developed six total episodes of CDC for an overall incidence of 5.4%. CF was the underlying diagnosis in all four patients, leading to an incidence of 8.9% in patients with CF. Two patients developed colitis within the first four months following transplant, and the other two patients developed colitis more than three yr after transplantation. All four patients required hospitalization, and three patients were managed medically while one patient underwent diverting ileostomy. One experienced renal insufficiency and subsequently expired. Overall survival was 75% among patients with CDC following lung transplantation. CDC causes significant morbidity and mortality in children with CF who have undergone lung transplantation.

Long-term impact of respiratory viral infection after pediatric lung transplantation.

To evaluate the epidemiology and to investigate the impact of RVI on chronic allograft rejection after pediatric lung transplantation, a retrospective study of pediatric lung transplant recipients from 2002 to 2007 was conducted. Association between RVI and continuous and categorical risk factors was assessed using Wilcoxon rank-sum tests and Fisher's exact tests, respectively. Association between risk factors and outcomes were assessed using Cox proportional hazards models. Fifty-five subjects were followed for a mean of 674 days (range 14-1790). Twenty-eight (51%) developed 51 RVI at a median of 144 days post-transplant (mean 246; range 1-1276); 41% of infections were diagnosed within 90 days. Twenty-five subjects developed 39 LRI, and eight subjects had 11 URI. Organisms recovered included rhinovirus (n = 14), adenovirus (n = 10), parainfluenza (n = 10), influenza (n = 5), and RSV (n = 4). Three subjects expired secondary to their RVI (two adenovirus, one RSV). Younger age and prior CMV infection were risks for RVI (HR 2.4 95% CI 1.1-5.3 and 17.0; 3.0-96.2, respectively). RVI was not associated with the development of chronic allograft rejection (p = 0.25) or death during the study period. RVI occurs in the majority of pediatric lung transplant recipients, but was not associated with mortality or chronic allograft rejection.

Respiratory viral infections within one year after pediatric lung transplant.

To characterize epidemiology and risk factors for respiratory viral infections (RVI) in pediatric lung transplant recipients within the first post-transplant year, a retrospective multicenter study of pediatric lung transplant recipients from 1988 to 2005 was conducted at 14 centers in the United States and Europe. Data were recorded for 1 year post transplant. Associations between RVI and continuous and categorical risk factors were assessed using Wilcoxon's rank-sum and chi(2) tests, respectively. Associations between time to RVI and risk factors or survival were assessed by multivariable Cox proportional hazards models. Of 576 subjects, 79 subjects (14%) had 101 RVI in the first year post transplant. Subjects with RVI were younger than those without RVI (median ages 9.7, 13; P<0.01). Viruses detected included adenovirus (n=25), influenza (n=9), respiratory syncytial virus (n=21), parainfluenza virus (n=19), enterovirus (n=4), and rhinovirus (n=22). In a multivariable model for time to first RVI, etiology other than cystic fibrosis (CF), younger age, and no induction therapy were independently associated with risk of RVI. Cytomegalovirus serostatus and acute rejection were not associated with RVI. RVI was independently associated with decreased 12-month survival (hazard ratio 2.6, 95% confidence interval 1.6-4.4). RVI commonly occurs after pediatric lung transplantation with risk factors including younger age and non-CF diagnosis. RVI is associated with decreased 1-year survival.

Mycobacterium abscessus in cystic fibrosis lung transplant recipients: report of 2 cases and risk for recurrence.

Mycobacterium abscessus is increasingly recognized as an important pathogen in some individuals with advancing lung disease related to cystic fibrosis (CF). Because of its resistance to antimicrobial agents and virulence, its presence in the lungs of potential lung transplant recipients can be problematic. We present 2 cases of individuals with CF in whom M. abscessus was present in the preoperative sputum cultures. The organism manifested different degrees of invasiveness in the 2 cases after transplantation with different outcomes, suggesting an approach to future candidates for lung transplantation that may be of clinical significance to their physicians and surgeons.

Lung transplantation in a patient with a thrombophilic disorder.

The prothrombin G20210A mutation has been associated with an increased risk of graft failure in renal transplant recipients. Little is known about the potential effect of this mutation on lung transplant recipients. We report the case of bilateral lung transplantation in a patient with cystic fibrosis who was heterozygous for the G20210A mutation of the prothrombin gene.

Clinical, radiological and pathological features of ABCA3 mutations in children.

BACKGROUND: Mutations in the ABCA3 gene can result in fatal surfactant deficiency in term newborn infants and chronic interstitial lung disease in older children. Previous studies on ABCA3 mutations have focused primarily on the genetic abnormalities and reported limited clinical information about the resultant disease. A study was undertaken to analyse systematically the clinical presentation, pulmonary function, diagnostic imaging, pathological features and outcomes of children with ABCA3 mutations. METHODS: The records of nine children with ABCA3 mutations evaluated at Texas Children's Hospital between 1992 and 2005 were reviewed and their current clinical status updated. Previous diagnostic imaging studies and lung biopsy specimens were re-examined. The results of DNA analyses were confirmed. RESULTS: Age at symptom onset ranged from birth to 4 years. Cough, crackles, failure to thrive and clubbing were frequent findings. Mean lung function was low but tended to remain static. CT scans commonly revealed ground-glass opacification, septal thickening, parenchymal cysts and pectus excavatum. Histopathological patterns included pulmonary alveolar proteinosis, desquamative interstitial pneumonitis and non-specific interstitial pneumonitis, and varied with age. Dense abnormalities of lamellar bodies, characteristic of ABCA3 mutations, were seen by electron microscopy in all adequate specimens. Outcomes varied with the age at which the severity of lung disease warranted open lung biopsy, and some patients have had prolonged survival without lung transplantation. CONCLUSIONS: The presentation and course of interstitial lung disease due to ABCA3 mutations are variable, and open lung biopsy and genetic testing are warranted early in the evaluation of children with a consistent clinical picture.

American Society of Transplantation executive summary on pediatric lung transplantation.

Lung transplantation in children poses distinctly different challenges from those seen in the adult population. This consensus statement reviews the experience in the field of pediatric lung transplantation and highlights areas that deserve further investigation.

Oxygen therapy for cystic fibrosis.

BACKGROUND: The most serious complications of cystic fibrosis (CF) relate to respiratory insufficiency. Oxygen supplementation therapy has been a standard of care for individuals with chronic lung diseases associated with hypoxemia for decades. It is common for physicians to prescribe oxygen therapy for people with CF when hypoxemia occurs. However, it is unclear if empiric evidence is available to provide indications for this therapy with its financial costs and often profound impact on lifestyle. OBJECTIVES: To assess whether oxygen therapy improves the longevity or quality of life of individuals with CF. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search of Group's Trials Register: April 2005. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials comparing oxygen, administered at any concentration, by any route, in people with documented CF for any time period. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. MAIN RESULTS: Nine published studies (149 participants) are included in this review, of which only one examined long-term oxygen therapy (28 participants). There was no statistically significant improvement in survival, lung, or cardiac health. Four studies examined the effect of oxygen supplementation during sleep by polysomnography. Although oxygenation improved, there were no demonstrable improvements in qualitative sleep parameters and modest hypoventilation was noted. In three studies, oxygen supplementation was evaluated during exercise. Hypoxemia was prevented, but mild hypercapnia resulted. Work performance was not improved, as measured in one study, but was improved in a second study. Furthermore, in two studies, exercise duration was enhanced by oxygen supplementation. In the study examining the impact of oxygen supplementation after exercise, recovery time was enhanced. AUTHORS' CONCLUSIONS: There are no published data to guide the prescription of chronic oxygen supplementation to people with advanced lung disease due to CF. Short-term oxygen therapy during sleep and exercise improves oxygenation but is associated with modest and probably clinically inconsequential hypercapnia. During exercise, there are improvements in exercise duration and peak performance. There is a need for larger, well-designed clinical trials to assess the benefits of long-term oxygen therapy in people with CF administered continuously or during exercise or sleep or both.

Paediatric lung transplantation.

Since 1990, lung transplantation has been performed in infants, children and adolescents in small numbers, and the numbers, in comparison with adult transplants, remain small today. The indications for lung transplantation are similar in childhood when compared with adults, but the disease entities are distinct. In children, severe pulmonary vascular disease is most commonly associated with developmental abnormalities or congenital heart disease, as opposed to idiopathic pulmonary hypertension. Cystic fibrosis is the dominant indication for lung transplantation in older childhood and adolescence. The operative approach to lung transplantation in early life differs from that in adults, in that cardiopulmonary bypass is more likely to be utilised and bilateral lung transplantation is strongly preferred to single lung transplantation. Living donor lung transplantation is proportionately more common in children and adolescents than in adults. Post-transplant complications related to viral infection and post-transplant lymphoproliferative disease are more common and more likely to be severe and life-threatening. Bronchiolitis obliterans is the most important complication after paediatric lung transplantation and limits both the quality of life and duration of survival, as in adults.

Surfactant proteins: role in lung physiology and disease in early life.

Pulmonary surfactant is an amalgam of proteins and phospholipids which serves to maintain a low surface tension within the alveolar regions of the lungs during changes in lung volume. Recently, two of the surfactant proteins--A and D--have been characterised within the collectin family and found to play important roles in the non-specific host defence of the lung. The field of surfactant biology has attracted the attention of physiologists, biochemists, molecular biologists and clinical scientists in an effort to describe the nature and role of pulmonary surfactant in health and disease. This paper will review the history and content of discoveries in the field of surfactant biology together with pulmonary diseases related to surfactant deficiency or dysfunction.

High incidence of posttransplant lymphoproliferative disease in pediatric patients with cystic fibrosis.

A major cause of morbidity and mortality following lung transplantation is posttransplant lymphoproliferative disease (PTLD). In a retrospective cohort analysis of pediatric patients, we evaluated the risk factors associated with PTLD in 128 first-time lung transplant recipients from 1990 to 1997. The greatest risk factor for PTLD was a diagnosis of cystic fibrosis (CF). Of the 16 patients in our analysis who had PTLD, 13 had a diagnosis of CF (odds ratio [OR]: 5.8; confidence interval 95% [CI]: 1.6 to 21.4). Because of the high frequency of PTLD in patients with CF (13 of 61; 23%), we performed a retrospective cohort analysis in which patients with CF and PTLD were designated as cases and patients with CF and without PTLD served as controls. In patients with CF, the only risk factor associated with PTLD was two or more episodes of acute rejection within 3 mo after transplantation (OR: 11.0; 95% CI: 2.7 to 55.7). Age, recipient Epstein-Barr virus or cytomegalovirus status, induction with antilymphocyte globulin or antithymocyte globulin (ATG), or use of ATG or OKT3 for acute rejection episodes were not risk factors for PTLD. The high frequency of PTLD in the subgroup of patients with two or more episodes of graft rejection within 2 mo after lung transplantation was unexpected, and warrants further investigation in prospective clinical studies and basic laboratories.

Intestinal obstruction after lung transplantation in children with cystic fibrosis.

BACKGROUND/PURPOSE: Distal intestinal obstruction syndrome (DIOS) occurs in 15% of patients with cystic fibrosis (CF). The authors reviewed their experience to determine the incidence, risk factors, and natural history of adhesive intestinal obstruction and DIOS after lung transplantation. METHODS: Eighty-three bilateral transplants were performed in 70 CF patients between January 1990 and September 1998. All were on pancreatic enzymes preoperatively, and none had preoperative bowel preparation. Fifty-six patients (80%) had prior gastrostomy (n = 54) or jejunostomy (n = 2). Eighteen patients (25.7%) had a previous laparotomy for meconium ileus (n = 8), fundoplication (n = 4), liver transplant (n = 1), jejunal atresia (n = 1), Janeway gastrostomy takedown (n = 1), pyloromyotomy (n = 1), free air (n = 1), or appendectomy (n = 1). RESULTS: After lung transplantation, 7 patients (10%) required laparotomy for bowel obstruction (6 during the same hospitalization, and 1 during a subsequent hospitalization). The causes of obstruction were adhesions only (n = 1), DIOS only (n = 2), and a combination of DIOS and adhesions (n = 4). Adhesiolysis was performed in the 5 patients with adhesions, and a small bowel resection was also performed in 1 patient. DIOS was treated by milking secretions distally without an enterotomy (n = 3) with an enterotomy and primary closure (n = 1) or with an end ileostomy and mucus fistula (n = 2). Five had recurrent DIOS early postoperatively. One resolved with intestinal lavage, 2 were treated successfully with hypaque disimpaction, and 2 underwent reoperation; 1 required an ileostomy. The most important risk factor for posttransplant obstruction was a previous major abdominal operation. Obstruction occurred in 7 of 18 (39%) who had undergone a prior laparotomy versus 0 of 52 who had not (P < .001, chi2). CONCLUSIONS: (1) The incidence of intestinal obstruction is high after lung transplantation in children with CF. (2) Previous laparotomy is a significant risk factor. (3) Recurrent obstruction after surgery for this condition is common. (4) Preventive measures such as pretransplant bowel preparation and early postoperative bowel lavage may be beneficial in these patients.

Neurologic complications of pediatric lung transplantation.

OBJECTIVE: To report neurologic complications in a large population of pediatric lung transplantation patients. METHODS: A retrospective review of the first 135 patients to undergo lung transplantation at St. Louis Children's Hospital from July 1990 to December 1997. RESULTS: Sixty-one (45%) patients had neurologic complications. The most common presenting symptoms were seizures (27%), followed by encephalopathy, headache, depression, and focal neurologic deficits. Cyclosporine toxicity (7%) and hypoxia-ischemia (7%) constituted the most commonly identified etiologies, followed by stroke, metabolic, and infectious causes. Risk factor analysis found that patients with interstitial lung disease had a higher frequency of hypoxic-ischemic events and patients with seizures had significantly elevated trough cyclosporine levels. Patients with stroke and hypoxia had a poor neurologic prognosis, whereas patients with cyclosporine toxicity uniformly had a good outcome. CONCLUSIONS: Neurologic complications occur frequently after lung transplantation in pediatric patients, with seizures being the most common presenting symptom. Except in patients with stroke and hypoxia, prognosis is generally favorable. Seizures not accompanied by an irreversible structural etiology are unlikely to require long-term treatment with antiepileptic medications. Cyclosporine neurotoxicity typically resolves without requiring discontinuation of immunosuppressive therapy.

Lung transplantation in very young infants.

INTRODUCTION: Established successes with adult lung transplantation have laid the foundation for extension of this therapeutic modality to infants and children dying of end-stage pulmonary disease. The purpose of this report is to convey our experience with 19 infants undergoing lung transplantation before the age of 6 months. METHODS: Six patients with predominantly pulmonary vascular disease and 13 patients with primarily pulmonary parenchymal disease have undergone bilateral sequential lung transplantation at our institution since 1990. Mean age at transplant was 104 +/- 44 days, and mean weight was 4.9 +/- 1.6 kg. RESULTS: Although early mortality (32%, 6/19) was higher than that previously reported for older pediatric age groups, long-term survival was similar (44% at a maximum follow-up of 6 years). Although anastomotic complications and infections occurred at a rate approximating that seen in older pediatric age groups, episodes of acute rejection appear to occur with decreased frequency. Similarly, at a mean follow-up of 3 years, only 2 (15%) of 13 long-term survivors have evidence of bronchiolitis obliterans. The functional residual capacity, as measured on infant pulmonary function tests, has gradually increased as the children have grown, suggesting that lung growth is occurring. CONCLUSIONS: Bilateral lung transplantation is a viable alternative in infants dying of end-stage pulmonary disease. Efforts directed toward avoiding the complications that lead to early posttransplant mortality combined with the seemingly lower incidence of early and late rejection may provide long-term results better than those in other age groups.

Depilation in a 6-month-Old with hypertrichosis: A case report.

Hypertrichosis in the pediatric age group can be troubling to both patients and parents. There is no well-established method for managing this problem in young children. We describe the successful use of a cream depilatory agent for removal of excess hair from the face and body of a 6-month-old girl. Excellent cosmetic results were obtained. The risks and benefits of the use of depilatory cream in young patients are analyzed. Other options for hair removal in children are also reviewed.

Growth of lungs after transplantation in infants and in children younger than 3 years of age.

We report serial measurements of lung volume and airflow in small children after lung transplantation. We expected that immature lungs could grow and develop normal volumes after transplantation, despite denervation and immunosuppression. At predetermined intervals, functional residual capacity (FRC) and forced expiratory flow were measured 86 times in 23 recipients younger than 3 yr of age (age at transplant, 13.2 +/- 8.4 mo; range, 2 to 30 mo). FRC was measured using open-circuit N2 washout. Maximal flow at FRC by rapid thoracoabdominal compression was used to distinguish between infants with and those without airflow obstruction. The slope of FRC (in milliliters) versus body length (in centimeters) for all 23 recipients studied was 8.63. For those children without obstruction (flow at FRC >/= 0.9 FRC/s, n = 16), the slope of FRC versus length was 6.61. The coefficient of variation for FRC measurements for all infants was 3.90 +/- 2.80% (range, 0.3 to 16.9%). We conclude that in the absence of significant airflow obstruction the volume of transplanted immature lungs increases at a rate similar to that reported in normal infants.

Lung retransplantation in children.

BACKGROUND: Early primary graft failure due to reperfusion injury may occur in up to 10% of all patients undergoing lung transplantation. Late graft failure in the form of bronchiolitis obliterans progressively increases in frequency as posttransplantation follow-up increases. In both situations, the degree of pulmonary dysfunction may worsen and result in the death of the recipient. The only treatment in many instances is retransplantation. The results in adults are reasonably well established. METHODS: We reviewed our experience in children. Of the 136 transplant procedures performed to date in children, 14 have been retransplantations. Six patients required retransplantation for early primary graft failure and 8 underwent retransplantation for bronchiolitis obliterans. RESULTS: There were three early and three late deaths. The actuarial survival at 2 years is 58%. The retransplant procedures were more complex than the primary transplant operations as evidenced by the longer time on cardiopulmonary bypass (199 +/- 71 versus 150 +/- 41 minutes; p < 0.01) and the greater volume of blood transfused (1,303 +/- 936 versus 570 +/- 300 mL; p < 0.01). Two of the long-term survivors who received transplants for bronchiolitis obliterans have subsequently had development of this same condition and 1 died secondary to this. In four instances living related donors were used for the retransplant procedure. The most striking difference in these procedures compared with those transplantations performed with cadaveric donors was the shorter donor lung ischemic times (99.5 and 123.3 minutes for the two lungs for living related donors and 251 and 293 minutes for the first and second lung for the cadaveric donors; p < 0.01). CONCLUSIONS: We believe that lung retransplantation in children is a reasonable therapy to offer in the circumstance of severe graft dysfunction. In the older child, the option of living donor transplantation offers advantages that might offset of the overall higher risk of this procedure.