Neuroendocrine Cell Hyperplasia of Infancy. Clinical Score and Comorbidities.

Rationale: Neuroendocrine cell hyperplasia of infancy (NEHI) is an important form of children's interstitial and diffuse lung disease for which the diagnostic strategy has evolved. The prevalence of comorbidities in NEHI that may influence treatment has not been previously assessed.Objectives: To evaluate a previously unpublished NEHI clinical score for assistance in diagnosis of NEHI and to assess comorbidities in NEHI.Methods: We performed a retrospective chart review of 199 deidentified patients with NEHI from 11 centers. Data were collected in a centralized Research Electronic Data Capture registry and we performed descriptive statistics.Results: The majority of patients with NEHI were male (66%). The sensitivity of the NEHI Clinical Score was 87% (95% confidence interval [CI], 0.82-0.91) for all patients from included centers and 93% (95% CI, 0.86-0.97) for those with complete scores (e.g., no missing data). Findings were similar when we limited the population to the 75 patients diagnosed by lung biopsy (87%; 95% CI, 0.77-0.93). Of those patients evaluated for comorbidities, 51% had gastroesophageal reflux, 35% had aspiration or were at risk for aspiration, and 17% had evidence of immune system abnormalities.Conclusions: The NEHI Clinical Score is a sensitive tool for clinically evaluating NEHI; however, its specificity has not yet been addressed. Clinicians should consider evaluating patients with NEHI for comorbidities, including gastroesophageal reflux, aspiration, and immune system abnormalities, because these can contribute to the child's clinical picture and may influence clinical course and treatment.

Postinfectious Bronchiolitis Obliterans in Children: Diagnostic Workup and Therapeutic Options: A Workshop Report.

Bronchiolitis obliterans (BO) is a rare, chronic form of obstructive lung disease, often initiated with injury of the bronchiolar epithelium followed by an inflammatory response and progressive fibrosis of small airways resulting in nonuniform luminal obliteration or narrowing. The term BO comprises a group of diseases with different underlying etiologies, courses, and characteristics. Among the better recognized inciting stimuli leading to BO are airway pathogens such as adenovirus and mycoplasma, which, in a small percentage of infected children, will result in progressive fixed airflow obstruction, an entity referred to as postinfectious bronchiolitis obliterans (PIBO). The present knowledge on BO in general is reasonably well developed, in part because of the relatively high incidence in patients who have undergone lung transplantation or bone marrow transplant recipients who have had graft-versus-host disease in the posttransplant period. The cellular and molecular pathways involved in PIBO, while assumed to be similar, have not been adequately elucidated. Since 2016, an international consortium of experts with an interest in PIBO assembles on a regular basis in Geisenheim, Germany, to discuss key areas in PIBO which include diagnostic workup, treatment strategies, and research fields.

Perception of Pulmonary Function in Children with Asthma and Cystic Fibrosis.

Background: Under-perception of pulmonary dysfunction may delay appropriate treatment, while over-perception may result in unnecessary treatments. Objectives: To evaluate the ability of patients with asthma or cystic fibrosis and their subspecialty caregivers to assess changes in lung function based on their subjective clinical impressions. Methods: Patients were asked to qualitatively describe how they felt compared to their prior visit (same/better/worse) and to quantitatively estimate their forced expiratory volume in 1 s (FEV1) after being reminded of their FEV1 at the prior visit. Providers made similar estimates based on history and physical examination and knowledge of prior FEV1. After adjusting for relevant clinical covariates, lung function estimates were categorized as accurate (±5% of measured FEV1), overestimated (>5% above measured), and underestimated (>5% below measured). Results: One hundred nine patients estimated FEV1 on 179 occasions. Concordance between patient qualitative assessment and FEV1-based categories was low (κ = 0.08); 44% of patients reported feeling better than the FEV1-based category showed. Quantitatively, 56% of patient estimates were accurate, 18% were underestimated, and 26% overestimated; accuracy improved with age (odds ratio = 1.16, P = 0.01). Concordance between provider qualitative assessments and FEV1-based category was moderate (κ = 0.35); about 19% said their patient looked better than the FEV1-based category showed. Quantitatively, 65% of provider estimates were accurate, 16% were underestimated, and 19% were overestimated; accuracy improved with years of experience. Conclusions: Patients' and providers' perceptions of lung function were low to moderately accurate. Relying on subjective impression may place patients at risk for unnecessary treatments or increased morbidity. These findings highlight the importance of objective lung function assessment.

Airway microbiota across age and disease spectrum in cystic fibrosis.

Our objectives were to characterise the microbiota in cystic fibrosis (CF) bronchoalveolar lavage fluid (BALF), and determine its relationship to inflammation and disease status.BALF from paediatric and adult CF patients and paediatric disease controls undergoing clinically indicated bronchoscopy was analysed for total bacterial load and for microbiota by 16S rDNA sequencing.We examined 191 BALF samples (146 CF and 45 disease controls) from 13 CF centres. In CF patients aged <2 years, nontraditional taxa (e.gStreptococcus, Prevotella and Veillonella) constituted ∼50% of the microbiota, whereas in CF patients aged ≥6 years, traditional CF taxa (e.gPseudomonas, Staphylococcus and Stenotrophomonas) predominated. Sequencing detected a dominant taxon not traditionally associated with CF (e.gStreptococcus or Prevotella) in 20% of CF BALF and identified bacteria in 24% of culture-negative BALF. Microbial diversity and relative abundance of Streptococcus, Prevotella and Veillonella were inversely associated with airway inflammation. Microbiota communities were distinct in CF compared with disease controls, but did not differ based on pulmonary exacerbation status in CF.The CF microbiota detected in BALF differs with age. In CF patients aged <2 years, Streptococcus predominates, whereas classic CF pathogens predominate in most older children and adults.

A novel surfactant protein C gene mutation associated with progressive respiratory failure in infancy.

Mutations of the Surfactant Protein C (SPC) gene (SFTPC) have been associated with childhood interstitial lung disease (chILD) with variable age of onset, severity of lung disease, and outcomes. We report a novel mutation in SFTPC [c.435G->A, p.(Gln145)] that was associated with onset of symptoms in early infancy, progressive respiratory failure with need for prolonged mechanical ventilatory support, and eventual lung transplant at 1 year of age. While the mutation was not predicted to alter the amino acid sequence of the SP-C precursor protein, analysis of SP-C transcripts demonstrated skipping of exon 4. Because of limited data about the outcomes of infants with SFTPC mutations, we conducted a systematic review of all the SFTPC mutations reported in the literature in order to define their presenting features, clinical and radiologic features, and outcomes. Further advances in our understanding of chILD and creation of an international registry will help to track these patients and their outcomes. Pediatr Pulmonol. 2017;52:57-68. © 2016 Wiley Periodicals, Inc.

Antiinflammatory effects of bromodomain and extraterminal domain inhibition in cystic fibrosis lung inflammation.

Significant morbidity in cystic fibrosis (CF) results from chronic lung inflammation, most commonly due to Pseudomonas aeruginosa infection. Recent data suggest that IL-17 contributes to pathological inflammation in the setting of abnormal mucosal immunity, and type 17 immunity-driven inflammatory responses may represent a target to block aberrant inflammation in CF. Indeed, transcriptomic analysis of the airway epithelium from CF patients undergoing clinical bronchoscopy revealed upregulation of IL-17 downstream signature genes, implicating a substantial contribution of IL-17-mediated immunity in CF lungs. Bromodomain and extraterminal domain (BET) chromatin modulators can regulate T cell responses, specifically Th17-mediated inflammation, by mechanisms that include bromodomain-dependent inhibition of acetylated histones at the IL17 locus. Here, we show that, in vitro, BET inhibition potently suppressed Th17 cell responses in explanted CF tissue and inhibited IL-17-driven chemokine production in human bronchial epithelial cells. In an acute P. aeruginosa lung infection murine model, BET inhibition decreased inflammation, without exacerbating infection, suggesting that BET inhibition may be a potential therapeutic target in patients with CF.

Site of Bronchoalveolar Lavage Via Flexible Bronchoscopy and Fluid Return in Children.

BACKGROUND: Despite its widespread use as a diagnostic tool, the procedure for bronchoalveolar lavage (BAL) via flexible bronchoscopy is not standardized in children. Our objective was to examine the dissimilarities in fluid return between the different lobes in children undergoing flexible bronchoscopies with BAL. METHODS: We conducted a review of all pediatric flexible bronchoscopies with BAL conducted at a single institution over a 2-year period. Our predictor of interest was the site of the BAL. Our outcome of interest was the percent of fluid return. We used 1-way analysis of variance with subsequent pairwise comparisons for unadjusted analyses and multivariable linear regression for adjusted analyses. RESULTS: We identified 529 procedures that met prespecified criteria. The mean (SD) percent of fluid return was 52.1 (14.4) for the right middle lobe, 50.7 (16.0) for the lingula (LIN), 50.5 (18.6) for the right or left upper lobes other than LIN (R/L-UL), and 42.2 (18.7) for the right or left lower lobes (R/L-LL). The R/L-LL had significantly lower fluid return when compared with each of the other lobes (P<0.05 for all pairwise comparisons); in contrast, there was no significant difference in fluid return between the other lobes. In our main analysis adjusting for potential confounders, performing the BAL in the right middle lobe, LIN, or R/L-UL increased the fluid return by 11.1% [95% confidence interval (CI), 6.2-16.1], 9.5% (95% CI, 3.2-15.8), and 8.7% (95% CI, 0.9-16.5%), respectively, when compared with the R/L-LL. CONCLUSION: Our results suggest that the lower lobes provide the lowest BAL fluid return in children, whereas the other lobes seem to perform similarly.

Subjective and Objective Assessments of Flow-Volume Curve Configuration in Children and Young Adults.

RATIONALE: Analysis of maximal expiratory flow-volume curves (MEFVCs) allows for determination of airway obstruction, but quantitative methods to describe these curves are not commonly used. OBJECTIVES: We sought to determine the variability in MEFVC concavity assessment by pulmonary physicians, whether objective indices of concavity can be substituted for subjective expert impression, and whether MEFVC concavity correlates with clinical outcomes. METHODS: A survey of 37 MEFVCs (plus 3 duplicates) was sent to pulmonologists for quantitative assessment of MEFVC concavity. Objective indices (ß-angle, ratio forced expiratory flow at 50% of total lung volume to peak expiratory flow rate [FEF50/PEFR], ratio of maximum mid-expiratory flow to FVC [MMEF/FVC], kmax, and averaged flow-volume second derivatives) were calculated for each MEFVC and were correlated with the mean expert score. Both the mean expert scores and the best-performing index were then correlated with hospitalizations. MEASUREMENTS AND MAIN RESULTS: Ninety-two respondents provided usable data. There was substantial variability in concavity scores between subjects, but strong intrasubject reliability. Mean expert score did not differ by physician years of experience. Several indices (ß-angle, FEF50/PEFR, FEV1/FVC, MMEF/FVC, FEF50, and forced expiratory flow between 25 and 75% of total lung volume) correlated strongly with mean expert scores. A new variable (ß-MMEF) was constructed using coefficients from stepwise linear regression and accurately predicted the mean expert score (R(2) = 0.96). Mean expert score and ß-MMEF showed similar odds ratios for hospitalization (2.13 and 2.32, respectively) with identical positive (∼71%) and negative (87%) predictive values. The ß-MMEF was also associated with hospitalizations in two independent cohorts of children with asthma and cystic fibrosis. CONCLUSIONS: The ß-MMEF is an objective measure of maximal expiratory flow-volume curve concavity and highly correlates with expert impression. Both the mean expert score for expiratory curve concavity and the ß-MMEF were associated with increased risk of subsequent hospitalization. The ß-MMEF may be a useful biomarker for disease severity in asthma and cystic fibrosis.

Diffuse Lung Disease in Biopsied Children 2 to 18 Years of Age. Application of the chILD Classification Scheme.

RATIONALE: Children's Interstitial and Diffuse Lung Disease (chILD) is a heterogeneous group of disorders that is challenging to categorize. In previous study, a classification scheme was successfully applied to children 0 to 2 years of age who underwent lung biopsies for chILD. This classification scheme has not been evaluated in children 2 to 18 years of age. OBJECTIVES: This multicenter interdisciplinary study sought to describe the spectrum of biopsy-proven chILD in North America and to apply a previously reported classification scheme in children 2 to 18 years of age. Mortality and risk factors for mortality were also assessed. METHODS: Patients 2 to 18 years of age who underwent lung biopsies for diffuse lung disease from 12 North American institutions were included. Demographic and clinical data were collected and described. The lung biopsies were reviewed by pediatric lung pathologists with expertise in diffuse lung disease and were classified by the chILD classification scheme. Logistic regression was used to determine risk factors for mortality. MEASUREMENTS AND MAIN RESULTS: A total of 191 cases were included in the final analysis. Number of biopsies varied by center (5-49 biopsies; mean, 15.8) and by age (2-18 yr; mean, 10.6 yr). The most common classification category in this cohort was Disorders of the Immunocompromised Host (40.8%), and the least common was Disorders of Infancy (4.7%). Immunocompromised patients suffered the highest mortality (52.8%). Additional associations with mortality included mechanical ventilation, worse clinical status at time of biopsy, tachypnea, hemoptysis, and crackles. Pulmonary hypertension was found to be a risk factor for mortality but only in the immunocompetent patients. CONCLUSIONS: In patients 2 to 18 years of age who underwent lung biopsies for diffuse lung disease, there were far fewer diagnoses prevalent in infancy and more overlap with adult diagnoses. Immunocompromised patients with diffuse lung disease who underwent lung biopsies had less than 50% survival at time of last follow-up.

Surfactant Administration During Pediatric Extracorporeal Membrane Oxygenation.

Administering surfactant during pediatric extracorporeal membrane oxygenation (ECMO) may influence important clinical variables but has been insufficiently described. Ninety-six courses of ECMO from our center were retrospectively assessed, and 89 surfactant doses were identified during 37 ECMO courses. Surfactant administration was associated with a respiratory indication for ECMO and increased durations of ECMO and positive pressure ventilation. Hospital survival was 64.9% (24) in surfactant-treated ECMO courses and 72.9% (43) otherwise (p = 0.41). Dynamic compliance of the respiratory system (Cdyn; shown as least squares mean [standard error] in ml/cm H2O/kg by mixed-effects modeling) increased significantly from 0.34 (0.03) before surfactant to 0.40 (0.03) within 12 hours (p = 0.023) and to 0.45 (0.03) within 24 hours (p < 0.001) of surfactant administration. Other mechanical ventilator parameters, ECMO settings, and arterial blood gas results did not differ significantly after surfactant administration. Among surfactant recipients, significantly increased Cdyn was observed in the nonsurgical group (n = 20) but not in the cardiac surgery group (n = 17). In conclusion, respiratory system compliance is increased after surfactant administration and noncardiac surgical patients may preferentially benefit from this therapy. Surfactant administration was associated with longer durations of mechanical support, but not with unfavorable mortality.

Comparison of two aspiration techniques of bronchoalveolar lavage in children.

BACKGROUND: Although bronchoalveolar lavage (BAL) via flexible bronchoscopy is an essential diagnostic tool, its technique is not standardized in children. Our objective was to compare two different aspiration techniques of BAL in children (continuous wall suction vs. handheld syringe suction) in regards to the percentage of fluid recovered and the odds of performing a technically acceptable procedure (i.e., >40% of volume return). METHODS: We conducted a review of all pediatric flexible bronchoscopies with BAL conducted at our institution over a 2-year period. To minimize the differences between groups at baseline and reduce the possibility of bias, we used one-to-one propensity score (PS) caliper matching with no replacement for statistical analyses. RESULTS: We identified 539 procedures that met pre-specified criteria. There were considerable covariate imbalances between procedures in the handheld syringe group (n = 147) and those in the continuous wall group (n = 392); however, these imbalances were substantially reduced after the PS matching. In the matched sample (n = 236), children in the handheld syringe group had ∼7% higher volume return (95% CI = 3.4-11.0, P < 0.001) from BAL and threefold higher odds (95% CI = 1.5-8.6, P = 0.002) of performing a technically acceptable procedure. CONCLUSIONS: Our results suggest that handheld syringe suction offers a higher percentage of volume return from BAL and increases the odds of performing a technically acceptable procedure in children when compared to continuous wall suction.

An official American Thoracic Society clinical practice guideline: classification, evaluation, and management of childhood interstitial lung disease in infancy.

BACKGROUND: There is growing recognition and understanding of the entities that cause interstitial lung disease (ILD) in infants. These entities are distinct from those that cause ILD in older children and adults. METHODS: A multidisciplinary panel was convened to develop evidence-based guidelines on the classification, diagnosis, and management of ILD in children, focusing on neonates and infants under 2 years of age. Recommendations were formulated using a systematic approach. Outcomes considered important included the accuracy of the diagnostic evaluation, complications of delayed or incorrect diagnosis, psychosocial complications affecting the patient's or family's quality of life, and death. RESULTS: No controlled clinical trials were identified. Therefore, observational evidence and clinical experience informed judgments. These guidelines: (1) describe the clinical characteristics of neonates and infants (<2 yr of age) with diffuse lung disease (DLD); (2) list the common causes of DLD that should be eliminated during the evaluation of neonates and infants with DLD; (3) recommend methods for further clinical investigation of the remaining infants, who are regarded as having "childhood ILD syndrome"; (4) describe a new pathologic classification scheme of DLD in infants; (5) outline supportive and continuing care; and (6) suggest areas for future research. CONCLUSIONS: After common causes of DLD are excluded, neonates and infants with childhood ILD syndrome should be evaluated by a knowledgeable subspecialist. The evaluation may include echocardiography, controlled ventilation high-resolution computed tomography, infant pulmonary function testing, bronchoscopy with bronchoalveolar lavage, genetic testing, and/or lung biopsy. Preventive care, family education, and support are essential.

Radiation exposure from diagnostic imaging in the pediatric intensive care unit.

OBJECTIVE: To determine the range of radiation exposure from diagnostic imaging in children requiring mechanical ventilation. DESIGN: Prospective, observational. SETTING: Tertiary pediatric critical care unit. PATIENTS: We enrolled pediatric critical care unit patients requiring mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thoracic radiation exposure while the patient was in the pediatric critical care unit was measured using a small, radiolucent dosimeter secured to the anterior chest wall. Demographic data, diagnoses, and number and type of radiographic procedures were recorded. Differences between exposures by admission diagnoses were analyzed by rank sum test. Relationships between exposure and risk factors were assessed using multiple linear regression and Pearson correlation. Sixty-nine subjects were enrolled over a 175-day period. Subjects experienced a mean (± SD) of 11 ± 11 days of mechanical ventilation during which they underwent a mean of 14 ± 16 chest radiographs and 5 ± 4 other plain films. Subjects who had only plain radiographic studies (CXR group) had a median thoracic exposure of 1.02 (range, 0.13-28.26) mGy and a median daily exposure of 0.16 (range, 0.02-1.99) mGy/day. Subjects who had computed tomography and/or fluoroscopy studies in addition to plain radiographs (CXR+ group) had a median total thoracic exposure of 3.71 (range, 0.77-33.41) mGy and median daily exposure of 0.37 (range, 0.04-3.71) mGy/day, both of which were significantly higher than for subjects in the CXR group. There was no significant difference in average daily exposures according to admission diagnoses and daily exposure could not be predicted from a combination of variables, including age, body mass index, gender, or length of stay. Total number of radiologic studies was correlated, as expected, with duration of ventilation (r = 0.941, p < .0001). Exposure was significantly higher in patients who underwent computed tomography scans or fluoroscopy studies than in patients who only had plain radiography. CONCLUSIONS: Ventilated pediatric intensive care unit patients experienced an average daily thoracic radiation exposure above background environmental exposure and exposure varied widely, but exposures would not be expected to cause acute or chronic toxicity. Overall patient exposures were less than that received from 1 yr of natural background radiation.

Elevated sweat chloride concentration in children without cystic fibrosis who are receiving topiramate therapy.

BACKGROUND: Topiramate, which is used as an anticonvulsant and for migraine prophylaxis in children, causes oligohydrosis as a side-effect, but its effect on sweat chloride concentrations has not been studied systematically. METHODS: Twenty-one children receiving topiramate and 20 healthy controls with no signs or symptoms of pulmonary or gastrointestinal disease and a negative family history for cystic fibrosis (CF) underwent bilateral pilocarpine iontophoresis and sweat collection via Macroduct® system. RESULTS: Adequate samples (>15 µl volume) were obtained from 17/19 topiramate subjects (89%), and 19/20 (95%) controls. The mean sweat chloride concentration was 37.7 ± 18.8 mmol/L for patients receiving topiramate, and 15.9 ± 6.9 mmol/L for controls (p = 0.0001). The mean sweat volume was 29.1 ± 17.4 µl for patients receiving topiramate, and 41.2 ± 17.5 µl for controls (p = 0.037). Overall 8/17 (47%) of patients on topiramate with a measurable sweat chloride had either an intermediate (>40 mmol/L but <60 mmol/L) or elevated (>60 mmol/L) sweat chloride test result, while 0/19 control subjects had elevated sweat chloride (p = 0.0008). Further analysis of the in vitro activity of topiramate on cultured human bronchial epithelial cells in modified Ussing chambers showed no differences in chloride conductance measured in cells exposed to 10 or 50 µg/ml of topiramate when compared to non-exposed cells. CONCLUSIONS: This is the first report of a medication affecting sweat chloride values and shows that topiramate therapy can cause elevated sweat chloride concentrations in the absence of clinical manifestations of CF.

Feasibility of laparoscopic Nissen fundoplication after pediatric lung or heart-lung transplantation: should this be the standard?

BACKGROUND: Five-year graft survival in the pediatric lung transplant (LTxp) population is less than 50%, with obliterative bronchiolitis (OB) the leading cause of death at 1, 3, and 5 years post-transplant. Bronchiolitis obliterans syndrome (BOS), defined using spirometry values, is the clinical surrogate for the histological diagnosis of obliterative bronchiolitis. Surgical correction of documented gastroesophageal reflux disease (GERD) has been proposed as a means to potentially delay the onset of BOS and prolong allograft survival in adults before or after lung transplantation but only one such study exists in children. We have examined the safety and possible benefits of laparoscopic antireflux surgery in pediatric patients following lung (LTxp) and heart-lung transplantation (HLTxp). METHODS: An Institutional Review Board (IRB)-approved retrospective chart review was performed to evaluate the outcomes and complications of laparoscopic antireflux surgery in pediatric lung and heart-lung transplant patients. Spirometry data were collected for BOS staging using BOS criteria for children. RESULTS: Twenty-five lung and heart-lung transplants were performed between January 2003 and July 2009. Eleven transplant recipients, including six double-lung and five heart-lung (HLTxp), with a median age of 11.7 years (range 5.1-18.4 years), underwent a total of 12 laparoscopic Nissen fundoplications at a median of 427 days after transplant (range 51-2310 days). GERD was determined based upon clinical impression, pH probe study, gastric emptying study, and/or esophagram in all patients. Three patients already had a gastrostomy tube in place and two had one placed at the time of fundoplication. There were no conversions to open surgery, 30-day readmissions, or 30-day mortalities. Complications included one exploratory laparoscopy for free air 6 days after laparoscopic Nissen fundoplication for a gastric perforation that had spontaneously sealed. Another patient required a revision laparoscopic Nissen 822 days following the initial fundoplication for a paraesophageal hernia and recurrent GERD. The average length of hospital stay was 4.4 ± 1.7 days. Nine of the 12 fundoplications were performed in patients with baseline spirometry values prior to fundoplication and who could also complete spirometry reliably. One of these nine operations was associated with improvement in BOS stage 6 months after fundoplication; seven were associated with no change in BOS stage; and one was associated with a decline in BOS stage. CONCLUSION: It is feasible to perform laparoscopic Nissen fundoplication in pediatric lung and heart-lung transplant recipients without mortality or significant morbidity for the treatment of GERD. The real effect on pulmonary function cannot be assessed due to our small sample size and lack of reproducible spirometry in our younger patients. Additional studies are needed to elucidate the relationship between antireflux surgery and the potential for improving pulmonary allograft function and survival in children which has been previously observed in adult patients.

Lung transplantation for cystic fibrosis.

Lung transplantation is a complex, high-risk, potentially life-saving therapy for the end-stage lung disease of cystic fibrosis (CF). The decision to pursue transplantation involves comparing the likelihood of survival with and without transplantation as well as assessing the effect of wait-listing and transplantation on the patient's quality of life. Although recent population-based analyses of the US lung allocation system for the CF population have raised controversies about the survival benefits of transplantation, studies from the United Kingdom and Canada have suggested a definite survival advantage for those receiving transplants. In response to these and other controversies, leaders in transplantation and CF met together in Lansdowne, Virginia, to consider the state of the art in lung transplantation for CF in an international context, focusing on advances in surgical technique, measurement of outcomes, use of prognostic criteria, variations in local control over listing, and prioritization among the United States, Canada, the United Kingdom, and The Netherlands, patient adherence before and after transplantation and other issues in the broader context of lung transplantation. Finally, the conference members carefully considered how efforts to improve outcomes for lung transplantation for CF lung disease might best be studied. This Roundtable seeks to communicate the substance of our discussions.

Kidney after nonrenal transplantation-the impact of alemtuzumab induction.

BACKGROUND: Calcineurin inhibitor nephrotoxicity in nonrenal allograft recipients can lead to end-stage renal disease and the need for kidney transplantation. We sought to evaluate the role of alemtuzumab induction in this population. PATIENTS AND METHODS: We evaluated 144 patients undergoing kidney transplantation after nonrenal transplantation between May 18, 1998, and October 8, 2007. Seventy-two patients transplanted between January 15, 2003, and October 8, 2007, received alemtuzumab induction and continued their pretransplant immunosuppression. Seventy-two patients transplanted between May 18, 1998, and July 21, 2007, did not receive alemtuzumab induction, but received additional steroids and maintenance immunosuppression. Donor and recipient demographics were comparable. RESULTS: Overall, 1- and 3-year patient survival and renal function were comparable between the two groups. One- and 3-year graft survival was 93.0% and 75.3% in the alemtuzumab group and 83.3% and 68.7% in the no alemtuzumab group, respectively (P=0.051). The incidence of acute rejection was lower in the alemtuzumab group, 15.3%, than in the no alemtuzumab group, 41.7% (P=0.0001). The incidence of delayed graft function was lower in the alemtuzumab group, 9.7%, than in the no alemtuzumab group, 25.0% (P=0.003). The incidence of viral complications was comparable. CONCLUSION: Alemtuzumab induction with simple resumption of baseline immunosuppression in patients undergoing kidney transplantation after nonrenal transplantation represents a reasonable immunosuppressive strategy.

Comparative analysis of chest tube thoracostomy and video-assisted thoracoscopic surgery in empyema and parapneumonic effusion associated with pneumonia in children.

BACKGROUND: Controversy exists regarding the optimal management strategy for children having empyema or parapneumonic effusion as a complication of pneumonia. We hypothesized that video-assisted thoracoscopic surgery (VATS)-assisted drainage of pleural fluid and debridement of the pleural space is superior to a chest tube alone in the management of these patients. We further identified predictive factors-namely, presentation, radiographic findings, antibiotic usage, and pleural fluid features-that could predict the need for VATS rather than primary chest tube drainage. METHODS: Forty-nine pediatric patients with pneumonia complicated by parapneumonic effusion or empyema treated at the Children's Hospital of Pittsburgh (1997-2003) were divided into three groups according to the therapy instituted: Primary chest tube, chest tube followed by VATS, or primary VATS. The groups were analyzed in terms of demographics and outcome, as judged by pleural fluid analysis and hospital resource utilization. Demographic and outcome data were compared among groups using one-way analysis of variance and the Student t-test. RESULTS: All groups were similar with respect to demographics and initial antibiotic usage. Patients undergoing primary VATS had a higher initial temperature, whereas radiographic findings of mediastinal shift and air bronchograms were more likely to be found in patients who underwent primary chest tube placement. Patients undergoing primary VATS demonstrated a significantly shorter total stay and lower hospital charges than the other groups. Forty percent of children started on chest tube therapy failed even with subsequent VATS, necessitating a significantly longer hospital course (18 +/- 3 vs. 11 +/- 0.8 days; p < 0.05) and higher hospital charges ($50,000 +/- 7,000 vs. $29,000 +/- 1000) than those having primary VATS. CONCLUSIONS: Patients treated by primary VATS had a shorter stay and lower hospital charges than patients treated by chest tube and antibiotic therapy alone. There were no demographic, physiologic, laboratory, or chest radiographic data that predicted the selection of VATS as an initial treatment. These data suggest a strategy of primary VATS as first-line treatment in the management of empyema or parapneumonic effusion as a complication of pneumonia in pediatric patients.