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Background Although transbronchial biopsy (TBB) is the definitive method for diagnosing graft dysfunction after pediatric lung transplantation, concern over procedural complications has limited its use. We reviewed our institutional experience with clinically indicated TBB to determine its safety and efficacy with emphasis on how biopsy findings altered management. Methods A retrospective chart review was done of 61 pediatric lung transplantation patients undergoing 179 TBB procedures. Data were collected on pre-TBB symptoms, pulmonary function testing, and imaging studies. The prebiopsy diagnosis was noted and compared with the findings from TBB to see how frequently treatment changed after biopsy. Results Age at TBB ranged from 2 months to 20 years, with an average of 3 biopsies per patient. There was no procedure-related mortality. The incidence of complications was 9% and included important bleeding with spontaneous resolution in 6% and pneumothorax in 3%. The usual indication for TBB was a change in the chest roentgenogram, frequently accompanied by a decrease in flows on spirometry. The TBB specimens were adequate for pathologic analysis 92% of the time, and a specific pathologic diagnosis could be made in 54% of cases. The findings from TBB altered the clinical management of the patient 64% of the time. Conclusions In pediatric lung transplant recipients presenting with graft dysfunction, TBB is a low-risk diagnostic procedure that yields clinically useful information in a majority of cases. In our experience, the findings from TBB altered medical treatment in 64% of patients. Treatment was most often changed in the group diagnosed with rejection as the probable cause of graft dysfunction.

Bordetella bronchiseptica are small, pleomorphic Gram-negative coccobacilli which are commensal organisms in the upper respiratory tract of many wild and domestic animals ('kennel cough' in dogs). While it is common for health care providers to ask about exposure to ill family/friends, most do not routinely inquire about the health or immunization status of household pets. We report two cases of B. bronchiseptica pneumonia in lung transplant recipients [cystic fibrosis (CF); ages 10 and 15 yr; one male] who contracted B. bronchiseptica from pet dogs. We compared their course and outcome to four children (two CF, one congenital heart disease and one Duchenne's muscular dystrophy; four males, age range 6 months to 14 yr) with B. bronchiseptica cultured from the respiratory tract. Two of the four patients also acquired their illnesses from pet dogs and two from unknown sources. One lung transplant recipient expired from progressive respiratory failure. We conclude that B. bronchiseptica can cause serious infections in both immunosuppressed and immunocompetent children. We speculate that a detailed history of exposure to ill pets (particularly dogs), and the immunization status of all pets should be included in the routine evaluation of all pediatric transplant recipients.

Post-lung transplant bronchiolitis obliterans syndrome (BOS) is defined as an unexplained fall in forced expiratory volume in 1 s (FEV 1 ) ≥20% of baseline (B). There have been reports in adults that FEF 25-75% (> 30% decline from B) is more sensitive than FEV 1 for the early diagnosis of BOS. Yet, it is not known if other pulmonary function test (PFT) parameters - forced expiratory flow rates at 25-75% of vital capacity (FEF 25-75% ) and maximal expiratory flow rate at 80% (V max80% ), 70% (V max70% ) and 60% (V max60% ) - are more sensitive indicators for early diagnosis of BOS than FEV 1 in post-lung transplant children. We reviewed serial PFTs of 18 patients (ages 14.1 ± 3.7 yr, 50% female) who had lung transplantation at our institution from 1993 to 1999, and who met the criteria for BOS diagnosis. There was no significant difference in post-transplant days when decline in FEV 1 ≥20% of B, FEF 25-75% > 30% of B, and V max80% , V max70% and V max60% from normal occurred (635 ± 431. 551 ± 422 and 454 ± 287 days, respectively; p = 0.4). However, a decline in FEV 1 was the first abnormality in only 39% of the patients, while a decline in FEF 25-75% and V max at specific lung volume were the first abnormality in 78% and 56% of the patients, respectively. The earliest signs of BOS would be missed in 61% of patients if FEV 1 was the primary parameter used for the diagnosis. In order to improve the sensitivity of the diagnosis of post-lung transplant BOS: we speculate that the diagnosis should be based on decreases in FEF 25-75% rather than on FEV 1 .

Cystic fibrosis pulmonary disease is assessed by pulmonary function tests, arterial blood gases, and chest X-rays, but the correlation with lung pathology is unknown. We reviewed the clinical findings and lung pathology of 21 cystic fibrosis patients who had lung transplant. Pulmonary function tests, Brasfield scores, arterial blood gases, and age were correlated with lung pathology. All patients had severe Brasfield scores (9.0 +/- 3.2), airways obstruction (FEV1 25.6 +/- 5.6% predicted, FEF(25-75%) 11.0 +/- 4.5% predicted), and hyperinflation (residual volume [RV] 341.8 +/- 75.8% predicted). All patients were hypoxemic (PO2 64.2 +/- 8.2 mm Hg), and 5 of 21 (24%) were hypercapneic (PCO2 > 50 mm Hg). Pulmonary function tests and Brasfield scores were within a narrow range, and did not allow correlation with lung pathology. Small airway density (airways < 2 mm/cm2) decreased with increasing age. There were no differences in small airways inflammation and fibrous narrowing between the hypercapneic and nonhypercapneic patients, but the percent of smallest airways (airways < 0.35 mm) was significantly lower in the hypercapneic group. We conclude that there is significant correlation between airway pathology and increased age and CO2 retention. We speculate that decreased small airway density in older patients and the decreased proportion of smallest airways in hypercapneic patients is caused by increased dilatation of small airways.

The degree of pleural scarring complicating cystic fibrosis (CF) lung disease is thought to impact on the outcome of adult lung transplantation. This has not been previously studied in the pediatric population. We studied all patients undergoing lung transplantation at Children's Hospital Los Angeles from 1993 through 2000. Operative times, grade of pleural scarring, blood product transfusion requirements, and perioperative mortality were compared for patients with cystic fibrosis (35) versus those without this diagnosis (11). Patients with CF were slightly older (14.7 ± 3.8 vs 10.6 ± 5.6 years; P = 0.01) but had similar weights (34.8 ± 8.7 vs 34.4 ± 12.3 kg). The degree of pleural scarring was greater in the CF group but was only severe in four patients. Scarring did not impact on operative times (237 ± 46 vs 219 ± 39 minutes; P = 0.22) or cardiopulmonary bypass times (127 ± 40 vs 133 ± 49 minutes). Total perioperative blood requirements for the two groups were similar (35.6 ± 14.9 vs 42.8 ± 76.7 cm3/kg; P = 0.82). Pleural scarring in the pediatric CF patients undergoing lung transplantation is only severe in a minority of patients. It does not increase duration of operation nor blood transfusion requirements. CT scanning is consequently unnecessary in the preoperative workup of CF patients being evaluated for transplantation. CF patients undergoing transplantation have perioperative outcomes similar to those of noncystic patients.

Aspergillus has been noted to be the most common species of filamentous fungus isolated from the airways of lung transplantation (Tx) patients. In general, the bronchi are colonized asymptomatically with Aspergillus but this places such a patient population at greater risk of invasive infection. Other filamentous fungal species may also assume importance in this patient population. Here we report the post-transplant isolation of Paecilomyces variotii from the airways of a pediatric patient with cystic fibrosis (CF) who underwent bilateral living-donor lobar lung Tx. This is the first report of isolation of P. variotii in the pediatric lung Tx population. The isolation of filamentous fungi, such as Paecilomyces, with variable in vitro susceptibility to currently available antifungal agents further complicates the approach to post-transplant antifungal therapy in patients with lung Tx.

Long-term survival in lung transplant is limited by bronchiolitis obliterans (BOS). We compared outcomes in pediatric living donor bilateral lobar (LL) vs cadaveric lung transplant (CL).Children were studied who had LL or CL with at least 1 year follow-up. Data collected included acute rejection episodes, pulmonary function tests (PFT), BOS, and survival. Mean age was 13.36+/-3.16 years in LL and 12.00+/-4.19 years in CL patients (p = 0.37, ns).There was no difference in rejection (p = 0.41, ns). CL had rejection earlier (2.48+/-3.84 months) than LL (13.60+/-10.74 months; p = 0.02). There was no difference in 12 month PFT. But at 24 months, LL had greater forced expiratory volume in 1 second (FEV1) (p = 0.001) and FEF25-71% (p = 0.01) than CL. BOS was found in 0/14 LL vs 9/11 (82%) CL after 1 year (p = 0.04). After 2 years, 0/8 LL and 6/7 (86%) CL had BOS (p0.05). LL had 85% survival vs 79% for CL at 12 months. At 24 months, LL survival was 77% vs 67% for CL.Pediatric LL had less BOS and better pulmonary function than CL. As BOS is a determinant of long-term outcome, we believe LL is the preferred lung transplant method for children.

Background Posttransplant lymphoproliferative disease (PTLD) is a serious complication in transplant recipients. Abdominal PTLD has been reported, but the prognosis remains undefined. The purpose of this study was to identify the incidence, predisposing factors, and outcome of abdominal PTLD in pediatric cardiothoracic transplant patients. Methods Retrospective chart review of 134 transplant patients (50 heart, 77 lung, 7 heart/lung) at our institution (1995-2005). Results Posttransplant lymphoproliferative disease was diagnosed in 14 patients. Most were Epstein-Barr virus naive initially, but all had seroconverted when diagnosed with PTLD. Eight had abdominal involvement; 4 required surgical interventions—1 for intussusception and for bowel perforation, 2 for bowel perforation, and 1 for tumor debulking. All had lifelong follow-up, with an average follow-up of 3 years. Of 8 patients with abdominal PTLD, 4 died of complications related to PTLD, whereas 1 of 6 patients with extraabdominal PTLD died of PTLD. Conclusions Epstein-Barr virus infection after transplantation is a major risk factor for PTLD. Pediatric patients with PTLD who present with abdominal involvement are more likely to die of PTLD than those without abdominal disease. Delay in diagnosis may contribute to the high mortality. Therefore, prompt evaluation and surveillance for possible abdominal PTLD may decrease mortality associated with this devastating problem.

Living lobar lung transplantation places two donors at risk for each recipient. We examined the perioperative outcomes associated with the 253 donor lobectomies performed at our institution during our first decade of living lobar lung transplantation. There have been no perioperative or long-term deaths. 80.2% of donors (n = 203) had no perioperative complications, while fifty (19.8%) had one or more complication. The incidence of intraoperative complications was 3.6%. Complications requiring reoperation occurred in 3.2% of donors. 15.0% of donors had other perioperative complications; the most serious were two donors who developed pulmonary artery thrombosis, while the most common was the need for an additional thoracostomy tube or a thoracostomy tube for >/=14 d for persistent air leaks and/or drainage. Right-sided donors were more likely to have a perioperative complication than left-sided donors (odd ratio 2.02, p = 0.04), probably secondary to right lower and middle lobe anatomy. This experience has shown donor lobectomy to be associated with a relatively low morbidity and no mortality, and is important if this procedure is to be considered an option at more pulmonary transplant centers, given continued organ shortages and differences in philosophical and ethical acceptance of live

Bordetella bronchiseptica are small, pleomorphic Gram-negative coccobacilli which are commensal organisms in the upper respiratory tract of many wild and domestic animals ('kennel cough' in dogs). While it is common for health care providers to ask about exposure to ill family/friends, most do not routinely inquire about the health or immunization status of household pets. We report two cases of B. bronchiseptica pneumonia in lung transplant recipients [cystic fibrosis (CF); ages 10 and 15 yr; one male] who contracted B. bronchiseptica from pet dogs. We compared their course and outcome to four children (two CF, one congenital heart disease and one Duchenne's muscular dystrophy; four males, age range 6 months to 14 yr) with B. bronchiseptica cultured from the respiratory tract. Two of the four patients also acquired their illnesses from pet dogs and two from unknown sources. One lung transplant recipient expired from progressive respiratory failure. We conclude that B. bronchiseptica can cause serious infections in both immunosuppressed and immunocompetent children. We speculate that a detailed history of exposure to ill pets (particularly dogs), and the immunization status of all pets should be included in the routine evaluation of all pediatric transplant recipients.

Post-lung transplant bronchiolitis obliterans syndrome (BOS) is defined as an unexplained fall in forced expiratory volume in 1 s (FEV1)or=20% of baseline (B). There have been reports in adults that FEF25-75% (30% decline from B) is more sensitive than FEV1 for the early diagnosis of BOS. Yet, it is not known if other pulmonary function test (PFT) parameters - forced expiratory flow rates at 25-75% of vital capacity (FEF25-75%) and maximal expiratory flow rate at 80% (Vmax80%), 70% (Vmax70%) and 60% (Vmax60%) - are more sensitive indicators for early diagnosis of BOS than FEV1 in post-lung transplant children. We reviewed serial PFTs of 18 patients (ages 14.1 +/- 3.7 yr, 50% female) who had lung transplantation at our institution from 1993 to 1999, and who met the criteria for BOS diagnosis. There was no significant difference in post-transplant days when decline in FEV1or=20% of B, FEF25-75%30% of B, and Vmax80%, Vmax70% and Vmax60% from normal occurred (635 +/- 431, 551 +/- 422 and 454 +/- 287 days, respectively; p = 0.4). However, a decline in FEV1 was the first abnormality in only 39% of the patients, while a decline in FEF25-75% and Vmax at specific lung volume were the first abnormality in 78% and 56% of the patients, respectively. The earliest signs of BOS would be missed in 61% of patients if FEV1 was the primary parameter used for the diagnosis. In order to improve the sensitivity of the diagnosis of post-lung transplant BOS; we speculate that the diagnosis should be based on decreases in FEF25-75% rather than on FEV1.

Background Heart-lung transplant (HLT) is indicated in select children with end-stage cardiopulmonary disease. We sought to determine whether previous thoracic surgery increases peri-operative morbidity and mortality. Methods Retrospective data were analyzed using unpaired Student's t -test and Fisher's exact test. Results are reported as mean ± SD. Peri-operative mortality was defined as death at ≤30 days post-transplant. Results From August 1993 through April 2001, 13 patients (mean age 7.9 ± 5.3 years; 9 girls, 4 boys) underwent HLT at our center. Eight of 13 (62%) had previous thoracic surgery and 5 of 13 (38%) did not. Interval of last surgery to transplant date was 45.5 ± 26.4 months (range 6 to 79 months). We compared HLT patients who had previous thoracic surgery to HLT recipients who did not. There was no significant difference in weight (18.6 ± 14.3 vs 36.5 ± 20.7 kg, p = 0.09), age (6.5 ± 4.5 vs 10.2 ± 6.1 years, p = 0.23) or duration of intubation (14.1 ± 12.9 vs 17.0 ± 30.3 days, p = 0.83). There were no caval or tracheal anastomotic stenoses in either group. There was no significant difference in blood products transfused ≤48 hours after HLT: packed red blood cells ( p = 0.16); fresh frozen plasma ( p = 0.13); platelets ( p = 0.59), and cryoprecipitate ( p = 0.27). There was no difference in cardiopulmonary bypass time (129.3 ± 48.2 vs 160.6 ± 73.9 minutes, p 0.39); post-operative diaphragm dysfunction (4 of 8 vs 0 of 5, p = 0.1); re-exploration for bleeding (2 of 8 vs 1 of 5, p = 1.0); or peri-operative mortality (2 of 8 vs 0 of 5, p = 0.48). Conclusions We conclude that previous thoracic surgery in HLT recipients does not significantly increase blood product transfusion, cardiopulmonary bypass time or peri-operative mortality.

Lung volume increases after living donor lobar lung transplantation (LD) in children. The mechanism responsible for this increase may be alveolarization (lung growth) or alveolar dilation. The diffusing capacity of the lung for carbon monoxide adjusted for lung volume (DLco/VA) should decrease if alveolar dilation occurs, but not if lung growth occurs. Pulmonary function tests were measured 1-12 months after transplant in 20 children receiving LD transplants and in 11 children receiving cadaveric whole lung transplantation (CL). One month after transplant there were no differences between LD and CL recipients in age, gender, or height. Compared to the first month after transplant, height increased at 6-12 months after LD (p < 0.05), and only at 12 months after CL (p = 0.02). Total lung capacity (TLC) showed an 11-22% increase at 3-12 months after LD, and an 11-14% increase at 6-12 months after CL. DLco/VA showed an 11-17% decrease at 3-12 months after LD. However, in recipients of CL, DLco/VA showed a transient decrease of 10% at 3-6 months post-transplant, but was not significantly lower at 9-12 months. LD recipients had lower DLco/VA values than CL recipients at 6-12 months after transplant (p < 0.05). We conclude that following LD, lung volume increases, but DLco/VA decreases. We speculate that alveolar dilation, rather than alveolarization, is the primary mechanism of increased lung volume in children following LD.

Bilateral living donor lobar lung transplantation is a treatment option for selected children and adults with end-stage lung disease. Careful donor evaluation, skilled intraoperative management and surgical technique, and diligent immediate postoperative care and follow-up all contribute to better outcomes. Although medical management of whole lung transplant recipients in the immediate postoperative period is similar to that of lobar lung transplant recipients, there are specific differences. Anatomical distinctions, such as the entire cardiac output flowing to 2 lobes instead of 5, and thoracic space issues with simultaneous mechanical ventilation and chest tube suction, contribute to these differences. Early postoperative care, including initial postoperative stabilization, ventilation, fluid management, rejection/infection surveillance and prophylaxis, and beginning rehabilitation, can be adapted to ensure successful outcomes in these patients.

What psychosocial issues do adolescent cystic fibrosis (CF) patients experience after undergoing lung transplantation (Tx)? The aim of this study was to determine, using an ethnographic study design, the common themes and emotional responses in post-lung transplant adolescent CF patients of the Cardiothoracic Transplant Clinic at the Childrens Hospital Los Angeles. Nineteen CF lung transplant recipients were studied (eight males, 11 females: mean age at time of transplant, 15.7 ± 2.7 yr). The mean time interval from Tx to interview was 25.4 months (range 1–58 months). Sixteen patients had living donor lobar lung Tx while three patients received cadaveric lungs. A series of 25 questions was used to assess the psychosocial impact of Tx, and a semi-structured interview focused on the following five domains: lifestyle, family functioning, social functioning, body image, and psychological functioning. The major themes identified by patients included: a strong desire to set and attain meaningful long-range goals, the need to control as many aspects of their lives as possible while dealing with parental over-protectiveness, and the adjustment to a new lifestyle. Common emotional responses included manageable fear/anxiety of lung rejection and uncertainty of the future, impatience with disruptions of daily routines caused by post-transplant medical management and its effect on the attainment of set goals, and frustration with parental over-protectiveness. In general, patients reported a positive outlook on life, with greater emphasis on sought-after goals as well as inter-personal relationships. This study demonstrates that adolescent CF transplant recipients develop long-term goals and plans for independence. By identifying and anticipating the emotional needs of this population, health care providers can assist patients in improving the quality of their lives from a physiological, as well as a psychological, viewpoint.

Objective: Since development of a living donor bilateral lobar transplantation protocol for patients with cystic fibrosis, our indications have expanded to include recipients with other diagnoses. Methods: We report on our experience in eight patients with primary pulmonary hypertension, postchemotherapy pulmonary fibrosis, bronchopulmonary dysplasia, idiopathic pulmonary fibrosis, and obliterative bronchiolitis. The average age of the eight patients was 19.1 years (range 9 to 40). The mean preoperative carbon dioxide tension for the four patients who did not have primary pulmonary hypertension was 92 mm Hg (range 64 to 120 mm Hg), and the two patients with pulmonary fibrosis were intubated (one on high-frequency jet ventilation). Each recipient received a right lower lobe ( n = 7) or middle lobe ( n = 1) and a left lower lobe ( n = 8) from a total of 16 donors representing various combinations of the recipient's family ( n = 15) and an unrelated friend ( n = 1). Results: With an average follow-up of 1 year the overall survival is 75%. For the five patients followed up for at least 1 year, mean forced vital capacity was 80.6%, forced expiratory volume in 1 second was 75.6%, mid-forced expiratory flow was 64%, and diffusing lung capacity corrected for alveolar volume was 73% of predicted. For those patients with primary pulmonary hypertension, preoperative hemodynamics revealed mean pressures as follows: blood pressure 84.8 mm Hg, right atrial pressure 7.8 mm Hg, pulmonary artery pressure 71.3 mm Hg, pulmonary capillary wedge pressure 9.5 mm Hg, cardiac index 2.9 L/min per square meter, and pulmonary vascular resistance index 22.8 Wood units. Postoperative hemodynamics revealed a mean blood pressure of 84.3 mm Hg, right atrial pressure of 2.7 mm Hg, pulmonary artery pressure of 16 mm Hg, pulmonary capillary wedge pressure of 7.3 mm Hg, cardiac index of 4.2 L/min per square meter, and pulmonary vascular resistance index of 1.9 Wood units. Conclusions: Early results of living-donor bilateral lobar transplantation for diseases other than cystic fibrosis have resulted in satisfactory survival and pulmonary function. Additionally, patients with severe primary pulmonary hypertension have had dramatic normalization of their hemodynamics despite the limited amount of lung tissue transplanted. We believe that the data from this small cohort experience compares favorably with our larger series with cystic fibrosis and supports an expanded role for living-donor lobar transplantation in patients with alternate indications. (J Thorac Cardiovasc Surg 1997;114:917-22)

After correction for other risk factors non-adherence pre-transplant was the most important predictor of adherence related death. Older age and diagnosis of CF were also independent predictors. By secondary analysis adolescents (AAT 14 yrs) were at highest risk. Conclusion Non-adherence is a common cause of death in children following heart or lung transplantation, particularly in adolescents and in children with CF.

Objective: Living-donor lobar lung transplantation offers an alternative for patients with a life expectancy of less than a few months. We report on our intermediate results with respect to recipient survival, complications, pulmonary function, and hemodynamic reserve. Methods: Thirty-eight living-donor lobar lung transplants were performed in 27 adult and 10 pediatric patients for cystic fibrosis (32), pulmonary hypertension (two), pulmonary fibrosis (one), viral bronchiolitis (one), bronchopulmonary dysplasia (one), and posttransplantation obliterative bronchiolitis (one). Seventy-six donors underwent donor lobectomies. Results: There were 14 deaths among the 37 patients, with an average follow-up of 14 months. Predominant cause of death was infection, consistent with the large percentage of patients with cystic fibrosis in our population. The overall incidence of rejection was 0.07 episodes/patient-month, representing 0.8 episodes/patient. Postoperative pulmonary function testing generally showed a steady improvement that plateaued by postoperative months 9 to 12. Fourteen patients who were followed up for at least 1 year underwent right heart catheterization; pressures and pulmonary vascular resistances were within normal ranges. Bronchiolitis obliterans was definitively diagnosed in three patients. Among the 76 donors, complications in the postoperative period included postpericardiotomy syndrome (three), atrial fibrillation (one), and surgical reexploration (three). Conclusions: We believe that these data support an expanded role for living-donor lobar lung transplantation. Our intermediate data are encouraging with respect to the functional outcome and survival of these critically ill patients, who would have died without this option. (J Thorac Cardiovasc Surg 1996;112:1284-91)

Objective Living lobar lung transplantation was developed as a procedure for patients considered too ill to await cadaveric transplantation. Methods One hundred twenty-eight living lobar lung transplantations were performed in 123 patients between 1993 and 2003. Eighty-four patients were adults (age, 27 ± 7.7 years), and 39 were pediatric patients (age, 13.9 ± 2.9 years). Results The primary indication for transplantation was cystic fibrosis (84%). At the time of transplantation, 67.5% of patients were hospitalized, and 17.9% were intubated. One-, 3-, and 5-year actuarial survival among living lobar recipients was 70%, 54%, and 45%, respectively. There was no difference in actuarial survival between adult and pediatric living lobar recipients ( P = .65). There were 63 deaths among living lobar recipients, with infection being the predominant cause (53.4%), followed by obliterative bronchiolitis (12.7%) and primary graft dysfunction (7.9%). The overall incidence of acute rejection was 0.8 episodes per patient. Seventy-eight percent of rejection episodes were unilateral. Age, sex, indication, donor relationship, preoperative hospitalization status, use of preoperative steroids, and HLA-A, HLA-B, and HLA-DR typing did not influence survival. However, patients on ventilators preoperatively had significantly worse outcomes (odds ratio, 3.06, P = .03; Kaplan-Meier P = .002), and those undergoing retransplantation had an increased risk of death (odds ratio, 2.50). Conclusion These results support the continued use of living lobar lung transplantation in patients deemed unable to await a cadaveric transplantation. We consider patients undergoing retransplantations and intubated patients to be at significantly high risk because of the poor outcomes in these populations.