Relationship between insulin-like growth factor I, dehydroepiandrosterone sulfate and proresorptive cytokines and bone density in cystic fibrosis.

INTRODUCTION: Patients with cystic fibrosis (CF) are known to be at risk for early osteoporosis, and the mechanisms that mediate bone loss are still being delineated. The aim of the present investigation was to investigate if a correlation exists in these patients between skeletal measurements by dual-energy x-ray absorptiometry (DXA) and two anabolic factors, dehydroepiandrosterone (DHEA) and insulin-like growth factor I (IGF-I), and proresorptive factors such as the cytokines interleukin-1beta, tumor necrosis factor alpha, and interleukin-6. METHODS: We studied 32 outpatients (18 females; mean age: 26.2+/-7.9 years) at a tertiary care medical center. The subjects had venous samples obtained, underwent anthropometric and bone mineral density (BMD) measurements, and completed a health survey. Serum IGF-I concentrations were below the age-adjusted mean in 78% of the participants, and DHEA sulfate (DHEAS) concentrations were low in 72%. Serum concentrations of all cytokines were on the low side of normal; nonetheless, there was a modest inverse correlation between IL-1beta and BMD at all sites. RESULTS: In univariate analyses, IGF-I and DHEAS were significant correlates of BMD or bone mineral content. In final multivariate models controlling for anthropometric and other variables of relevance to bone density, only IGF-I was identified as a significant independent skeletal predictor. While alterations in DHEAS, IGF-I, and specific cytokines may contribute to skeletal deficits in patients with CF, of these factors a low IGF-I concentration appears to be most strongly correlated with BMD. CONCLUSIONS: These findings may have therapeutic implications for enhancing bone density in these patients.

Ultrase MT12 and Ultrase MT20 in the treatment of exocrine pancreatic insufficiency in cystic fibrosis: safety and efficacy.

BACKGROUND: Cystic fibrosis causes exocrine pancreatic insufficiency, leading to malabsorption. Supplemental pancreatic enzyme therapy alleviates the concomitant malnutrition experienced by cystic fibrosis patients. It is recognized that patients experience variations in clinical response to different brands of enzymes. This has prompted the US Food and Drug Administration to require that enzyme supplements be subjected to New Drug Applications. AIM: To investigate the safety and efficacy of supplemental pancreatic enzyme therapy in cystic fibrosis subjects. METHODS: We compared two doses of one formulation of enteric-coated pancreatic enzymes: Ultrase MT12 (12,000 lipase units per capsule) and Ultrase MT20 (20,000 lipase units per capsule), to placebo in two separate safety and efficacy studies. RESULTS: Mean total fat, protein and carbohydrate intake did not differ significantly between the groups. A significant difference in both fat and protein absorption occurred with the enzyme therapy groups. The Ultrase MT12 and Ultrase MT20 groups experienced a mean fat and protein absorption 79.4% and 83.8%, and 87.3% and 88.6%, respectively. No adverse events related to study drug were reported. CONCLUSIONS: This study further supports the use of enzymes to treat pancreatic insufficiency in cystic fibrosis. Excellent fat and protein absorption was achieved with minimal adverse events and safe doses.

A two-year randomized, placebo-controlled trial of dornase alfa in young patients with cystic fibrosis with mild lung function abnormalities.

OBJECTIVE: Our objective was to determine whether long-term treatment of young patients with cystic fibrosis (CF) with dornase alfa maintains lung function and reduces respiratory tract exacerbations. STUDY DESIGN: This was a 96-week, randomized, double-blind, placebo-controlled trial involving 49 CF centers. Inclusion criteria were age 6 to 10 years and forced vital capacity > or = 85% predicted. Patients were excluded for hospitalization for complications of CF within 2 months and use of dornase alfa within 6 months. Patients were treated with dornase alfa 2.5 mg or placebo once daily with a jet nebulizer and a compressor. RESULTS: Patients were randomized, 239 to dornase alfa and 235 to placebo. At baseline the mean age was 8.4 years, the mean forced expiratory volume in 1 second 95% predicted, the mean forced expiratory flow, midexpiratory phase 85% predicted, and the mean forced vital capacity 102% predicted. At 96 weeks the treatment benefit for dornase alfa compared with placebo in percent predicted (mean +/- SE) was 3.2 +/- 1.2 for forced expiratory volume in 1 second (P =.006), 7.9 +/- 2.3 for forced expiratory flow between 25% and 75% of vital capacity (P =.0008), and 0.7 +/- 1.0 for forced vital capacity (P =.51). The risk of respiratory tract exacerbation was reduced by 34% in patients who received dornase alfa (relative risk 0.66, P =.048). There was no statistically significant difference between the groups in changes in weight-for-age percentile. Adverse event profiles for the treatment groups were similar. CONCLUSIONS: Treatment of young patients with CF with dornase alfa maintains lung function and reduces the risk of exacerbations over a 96-week period.

Functional antibody activity elicited by fractional doses of Haemophilus influenzae type b conjugate vaccine (polyribosylribitol phosphate-tetanus toxoid conjugate).

We evaluated the functional activities of antibodies, serum bactericidal activity (SBA), and immunoglobulin G (IgG) antibody avidity indices, using sodium thiocyanate (NaSCN) elution, elicited after vaccination with fractional doses of the Haemophilus influenzae type b conjugate (polyribosylribitol phosphate [PRP] conjugated to tetanus toxoid [PRP-T]) vaccine. A cohort of 600 infants from the Dominican Republic were randomized to receive one of three regimens of the PRP-T vaccine at ages 2, 4, and 6 months: full doses (10 microg of PRP antigen), one-half doses (5.0 microg), and one-third doses (3.3 microg) (J. Fernandez et al., Am. J. Trop. Med. Hyg. 62:485-490, 2000). Sixty serum samples, collected at age 7 months, with > or =2.0 microg of anti-PRP IgG per ml were randomly selected for avidity determinations. Geometric mean IgG concentrations were 13, 14, and 17 microg/ml for infants who received the full-dose (n = 19), one-half-dose (n = 19), and one-third-dose (n = 22) regimens, respectively. SBA geometric mean titers (1/dilution) were 85.0, 82.0, and 76.1 in sera from infants receiving the full-, one-half-, and one-third-dose regimens, respectively. Avidity indices (mean +/- standard error weighted average of NaSCN molar concentration x serum dilution factor) were 71.9 +/- 9.4, 123.6 +/- 26.8, and 150.9 +/- 24.9 for the full-, one-half-, and one-third-dose regimens, respectively. Upon comparison, the only significant difference (P = 0.024) found was a greater avidity index for sera from infants receiving the one-third-dose regimen than for sera from infants receiving the the full-dose regimen. We conclude that fractional doses elicit similar functional antibody activities in infants with > or = 2 microg of anti-PRP IgG per ml, corresponding to 89, 90, and 97% of infants receiving three doses of either the full concentration or one-half or one-third of the labeled concentration, respectively. This approach offers an alternative strategy for the prevention of H. influenzae type b disease in countries with limited resources.

Respiratory diseases in the first year of life in children born to HIV-1-infected women.

Our objective was to describe the respiratory complications, clinical findings, and chest radiographic changes in the first year of life in infected and uninfected children born to HIV-1-infected women. We prospectively followed a cohort of 600 infants born to HIV-1-infected women from birth to 12 months in a multicenter study. Of these, 93 infants (15.5%) were HIV-1-infected, 463 were uninfected, and 44 were of unknown status prior to death or loss to follow-up. The cumulative incidence ( +/- SE) of an initial pneumonia episode at 12 months was 24.1 +/- 4.7% in HIV-1-infected children compared to 1.4 +/- 0.6% in HIV-1-uninfected children (P < 0.001). The rate of Pneumocystis carinii pneumonia (PCP) was 9.5 per 100 child-years. The HIV-1 RNA load was not higher in the group that developed pneumonia in the first year vs. those who did not. Children who developed lower respiratory tract infections or PCP had increased rates of decline of CD4 cell counts during the first 6 months of life. Lower maternal CD4 cell counts were associated with higher rates of pneumonia, and upper and lower respiratory tract infections. The rates of upper respiratory tract infection and bronchiolitis/reactive airway disease in infected children were not significantly different than in uninfected children. At 12 months, significantly more HIV-1-infected than uninfected children had tachypnea and chest radiographs with nodular and reticular densities. There was no relationship between cytomegalovirus infection in the first year of life and radiographic changes or occurrences of pneumonia. In conclusion, despite a low incidence of PCP, rates of pneumonia remain high in HIV-infected children in the first year of life. The incidence of pneumonia in uninfected infants born to HIV-1-infected mothers is low. Chest X-ray abnormalities and tachypnea suggest that subacute disease is present in infected infants. Further follow-up is warranted to determine its nature.

Forced expiratory flow in uninfected infants and children born to HIV-infected mothers.

The Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV (P(2)C(2) HIV) Study is a multicenter study examining pulmonary and cardiac outcomes in offspring of HIV-infected mothers. This portion of the P(2)C(2) study tests the hypothesis that infants exposed to, but uninfected by, maternal HIV have normal maximal expiratory flow at functional residual capacity (V'max,(FRC)). We obtained 500 measurements of V'max,(FRC) by rapid thoracic compression in 285 children ages 6-30 mo in five U.S. centers. The data were compared with those from a healthy cohort of children described elsewhere. V'max,(FRC) rose with height in a linear relationship. The slope of the regression line in the exposed infants did not differ statistically from the slope in the comparison group, but the intercept was about 20% lower (p < 0.001). Height and weight were comparable in the two cohorts, and the differences between intercepts persisted after adjusting for birth weight and gestational age. However, maternal HIV infection cannot be assumed to be the cause as the cohorts may have differed in other variables, such as socioeconomic status and frequency of maternal smoking and drug use. Also, measurements varied substantially within and between our five centers, probably in part because of different racial and ethnic distributions. In summary, maternal HIV infection probably has only a modest effect, if any, on maximal expiratory flow at functional residual capacity in uninfected infants.

Thoracoabdominal compression and respiratory system compliance in HIV-infected infants.

The thoracoabdominal compression technique (TAC) is used to measure expiratory flow in infants. We investigated whether TAC caused a change in total thoracic compliance (Crs), resistance (Rrs), and respiratory system time constant (Trs). We studied 41 infants (mean age, 12.4 mo; SD, 7.5) from five centers studying longitudinal lung and cardiovascular function of infants from HIV-infected mothers. We measured Crs, Rrs, and Trs before and after TAC. Changes in Crs, Rrs, and Trs after TAC were not dependent on the length of time since TAC. Crs and Trs were reduced after TAC, p = 0.013 and p = 0.003, respectively, whereas Rrs did not change. When compared with uninfected infants, HIV-infected infants had a larger post-pre TAC percent decline in Crs (p = 0.003) and a post-pre TAC rise in mean Rrs (p = 0.03). These differences remained significant after adjusting for sex and age. When performing infant pulmonary function testing, TAC itself produces a temporary decrease in Crs and Trs that is more significant in infants at risk for abnormal lung volume or compliance. Therefore, the sequence of performing the infant lung function parameters should be the same each time the testing is repeated with TAC as the last parameter tested at each testing session.

Epidemiologic study of cystic fibrosis: design and implementation of a prospective, multicenter, observational study of patients with cystic fibrosis in the U.S. and Canada.

Cystic fibrosis (CF) is a complex illness characterized by chronic lung infection leading to deterioration in function and respiratory failure in over 85% of patients. An understanding of the risk factors for that progression and the interaction of these factors with current therapeutic strategies should materially improve the prevention of this progressive lung disease. The Epidemiologic Study of Cystic Fibrosis (ESCF) was therefore designed as a multicenter, longitudinal, observational study to prospectively collect detailed clinical, therapeutic, microbiologic, and lung function data from a large number of CF treatment sites in the U.S. and Canada. The ESCF also serves an important role as a phase-IV study of dornase alfa. To be eligible for enrollment, subjects must have the diagnosis of CF and receive the majority of their care at an ESCF site. In this paper, the authors present the ESCF study design in detail. Further, enrollment data collected at 194 study sites in 18,411 subjects enrolled from December 1, 1993 to December 31, 1995 are presented in summary form. This comprehensive study is unique in the detail of clinical data collected regarding patient monitoring and therapeutic practices in CF care. Two companion articles present data regarding practice patterns in cystic fibrosis care, including data on resource utilization and prescribing practices.

Cystic fibrosis: predictors of accelerated decline and distribution of disease in 230 patients.

OBJECTIVE: The purpose of this study was to determine predictors of accelerated deterioration in radiographic manifestations of cystic fibrosis. The incidence and distribution of focally accentuated disease were also studied. MATERIALS AND METHODS: From 230 patients, 3038 chest radiographs were scored using the Brasfield system. Scores were plotted against age, and a single age-based severity curve was created. Specific observations (at least one episode in the first 5 years of life of air trapping, linear markings, nodular cystic lesions, or large lesions) were assessed to determine predictors of accelerated decline in scores compared with the aggregate scores plotted in the age-based severity curve. Specific observations were noted as present or absent and graded as to severity. A specific observation was counted as present if seen on at least one occasion. (The number of occasions on which the observation was made did not affect statistical analysis.) We also evaluated the distribution of lung disease by assessing the severity and nature of disease through specific lobar distribution. RESULTS: Males showed a slightly greater rate of radiologic decline. Early development of air trapping or bronchiectasis was associated with an accelerated rate of decline over time. Lobe-dominant disease occurred in one third of all images and in two thirds of the patients. It varied with age in its incidence, location, and etiology. CONCLUSION: Hyperinflation or bronchiectasis that occurs before age 5 is associated with accelerated radiographic deterioration. The incidence and location of lobe-dominant disease varied with age in these patients.

Cystic fibrosis: a system for assessing and predicting progression.

OBJECTIVE: This study presents a radiography-based database scoring changes over time in a large population of patients with cystic fibrosis. The purpose of this database is to provide comparison for groups of patients undergoing experimental treatment to assess effect of the treatment. The data may also be used to compare individuals with their age-matched cohorts with cystic fibrosis. MATERIALS AND METHODS: From 230 patients, 3038 chest radiographs were scored using the Brasfield system. The scores from radiographs from all the patients were individually plotted for age, and a single age-based severity curve was created. The age-based severity curve was compared with similar curves derived from pulmonary function studies of a subset of the same patient population. RESULTS: We found high inter- and intraobserver reliability. The difference between the observers averaged 1.3 Brasfield points, the scale of which ranges up to 25 points. The age-based severity curve was presented as mean Brasfield scores versus age (birth to > 30 years) plotted with 95% confidence limits; the curve was also plotted in percentiles. The rate of decline of this curve was similar to the decline of pulmonary function studies in this patient population. CONCLUSION: The age-based curve, a structural anatomic parameter, differs from pulmonary function studies, which are functional. Thus the age-based severity curve provides an additional, independent basis for comparison between groups and individuals. It may be used for the initial assessment of lung disease and for gauging and predicting the rate of decline. The curve may be used as a long-range outcome criterion to evaluate new treatments in groups of patients with cystic fibrosis.

End-of-life care in cystic fibrosis.

OBJECTIVE: End-of-life clinical care in cystic fibrosis (CF) differs substantially from terminal care in childhood cancer. To examine this difference, we reviewed the medical care of a cohort of CF patients treated at Children's Hospital, Boston, to document the use of preventive, therapeutic, and palliative care in the month preceding death. PATIENTS: We reviewed the medical records of 44 patients older than 5 years who died of CF-related respiratory failure for the years 1984 to 1993. RESULTS: Thirty-eight patients (86%) received opiates for the treatment of severe dyspnea and pain; the duration of opiate use varied from less than 1 hour to greater than 1 month. The dose of opiates varied from less than 5 mg per hour to greater than 30 mg per hour. Thirty-three patients (75%) continued to receive intravenous antibiotics in the last 12 hours of life; 32 (72%) continued to receive preventive or therapeutic oral medications in the last 12 hours of life. All patients were designated as do not resuscitate at the time of death; 43 of the patients died in the hospital with 1 patient dying at home under hospice care. CONCLUSIONS: The model of comfort care developed in childhood cancer does not adequately describe the combination of preventive, therapeutic, and palliative care given at the end of life for CF at our institution. The majority of CF patients continued to receive intravenous antibiotics and/or oral vitamin preparations while being treated with opiates for terminal pain and dyspnea. Small doses of opiates seem to be effective in the treatment of the pain and dyspnea at the end of life in CF.

Safety of repeated intermittent courses of aerosolized recombinant human deoxyribonuclease in patients with cystic fibrosis.

OBJECTIVES: To determine the effect of repeated doses of aerosolized recombinant human deoxyribonuclease (rhDNase) on the development of anti-rhDNase antibodies, acute allergic reactions, and pulmonary function in patients with cystic fibrosis. DESIGN: A multicenter, open-label study in which 184 patients received 10 mg aerosolized rhDNase twice a day for 14 days followed by a 14-day washout period for a total of 6 treatment cycles. Serial determinations of anti-rhDNase antibodies and pulmonary functions were performed. RESULTS: Detectable anti-rhDNase antibodies developed in 16 (8.7%) patients. These patients had no changes in their symptoms from the time they entered the trial. Antibodies detected were all of the IgG isotype. Increases in both forced expired volume in 1 second and forced vital capacity were noted from the beginning to the end of each cycle of treatment returning to baseline during the off-treatment period of each cycle. Seropositivity to rhDNase was not associated with allergic reactions and had no relationship on improvement in pulmonary function. CONCLUSIONS: Development of anti-rhDNase antibodies occurred in a small number of patients and was not associated with side effects. Intermittent administration of rhDNase for 24 weeks to patients with cystic fibrosis was well tolerated and was not associated with anaphylaxis in any patient. Pulmonary function improved significantly during the 14-day cycles while rhDNase was administered and returned to baseline when rhDNase was discontinued.

Inhibition of neutrophil elastase in CF sputum by L-658,758.

Elastases in cystic fibrosis (CF) pulmonary fluids damage lung tissue and perpetuate cycles of infection, inflammation and injury. Elastases from three different sources may be present in CF airways: neutrophils, macrophages and Pseudomonas. We measured how well the cephalosporin-based antielastase L-658,758 blocks the activity of human neutrophil elastase (NE), human proteinase-3, human macrophage metalloelastase, mouse macrophage metalloelastase and Pseudomonas aeruginosa elastase. We also examined the ability of L-658,758 to block elastases in CF sputum in vitro. Sputum samples from adult CF patients were fractionated to obtain the aqueous sol phase. These were then studied individually or pooled. Elastinolytic activity, which ranged from 3.2 microg elastin degraded/ml sol/min to 26.3 microg elastin degraded/ml sol/min, was measurable in every individual sol sample and in the pooled sol. L-658,758 effectively inhibited elastinolysis by NE, proteinase-3 and the pooled sol but did not inhibit the activity of the metalloelastases, human and mouse macrophage metalloelastase and Pseudomonas elastase. Secretory leukoprotease inhibitor, which inhibited NE but did not inhibit proteinase-3, blocked 90% of sol elastinolytic activity; this suggests that the majority of this activity in the pooled sol derived from NE. L-658,758 was an effective inhibitor of sol elastase, blocking more than 97% of elastinolytic activity in the individual sol samples. We conclude that L-658,758 is an effective inhibitor of NE, proteinase-3 and CF sputum sol elastase.

Chronic pain in cystic fibrosis.

OBJECTIVE: The objective of this study was to examine the incidence and therapy of chronic pain in a group of older patients with cystic fibrosis (CF). PATIENTS: We identified two groups of patients followed at the CF Center at Children's Hospital (Boston); the first group consisted of all patients above the age of 5 years who died between 1984 and 1993, and the second was a cohort of 23 additional CF patients who had been referred to the Pain Treatment Service. DESIGN: Medical charts were reviewed for the etiology and therapy of all pain episodes requiring medical intervention. RESULTS: The incidence of chronic pain in this population increased sharply in the last 6 months of life. Headaches (55% of patients) and chest pain (65%) were frequently reported, although back pain (19%), abdominal pain (19%), and limb pain (16%) were also reported. In patients with headache, the main etiologies were hypercarbia or hypoxia, migraine, and sinusitis. The majority of chest pain was musculoskeletal, with pleuritis, pneumothorax, and rib fracture also reported as the cause of chest pain. INTERVENTIONS: A variety of nonpharmacological and pharmacological therapies were reported. Forty-one patients (53%) had pain severe enough to require opioid treatment, and 10 patients (13%) received opioids for more than 3 months. In eight patients with more severe pain, regional analgesia was found to be particularly effective. CONCLUSIONS: Chronic pain is a common problem in CF, particularly as the patient population ages. When administered with caution, opioids have proven to be effective and safe in this population; regional anesthesia can be used to preserve pulmonary toilet while adequately treating severe pain.

The effect of the absence of abdominal muscles on pulmonary function and exercise.

In order to determine the long-term sequelae of prune belly syndrome (PBS) and whether the absence of abdominal wall musculature impairs exercise performance we studied nine patients 6 to 31 yr of age with PBS. Conventional spirometry, lung volumes, DLCO, and respiratory muscle strength were measured. A progressive 1-min incremental exercise test was performed on a cycle ergometer, and relative abdominal and chest wall displacements were measured by respiratory inductive plethysmography (RIP). Mean values of TLC, FRC, and RV were 94 +/- 12, 88 +/- 13, and 94 +/- 41%, respectively. Mean values of PEFR, FEV1, and FEF25-75 were 83 +/- 24, 92 +/- 23, and 83 +/- 28%, respectively. Maximal expiratory pressures were significantly reduced in seven of nine patients, with marked reduction in four (>3 SD below the mean). Percent predicted maximal VO2 achieved, % maximal work, and % maximal heart rate were 79 +/- 13, 78 +/- 14, and 87 +/- 2%, respectively. All seven subjects with absent abdominal musculature had paradoxical motion of the abdomen during quiet respiration in the erect or sitting position and while exercising. These subjects had synchronous breathing at rest in the supine position. Although the etiology of the relatively low work rates and VO2 achieved was multifactorial, we speculate that the abdominal paradox in these subjects necessitates abnormally large rib cage displacements during exercise, which may be a significant contributing factor to exercise limitation in some of these subjects.

Actin filaments mediate DNA fiber formation in chronic inflammatory airway disease.

Purulent sputum from patients with chronic obstructive pulmonary disease has long been known to contain large DNA-rich fibers believed to impede airway drainage. We present a novel approach to study sputum structure using fluorescence microscopy to confirm the presence of large DNA-rich fibers and visualize for the first time filamentous actin in all sputum samples examined from patients with cystic fibrosis and chronic bronchitis. Both actin and DNA co-localize in the filaments previously identified as DNA alone. Treatment of sputum samples with recombinant human DNase I or the actin-filament-severing protein, gelsolin, both previously found to decrease viscosity, dissolves the sputum fiber bundles. Purified human DNA does not form large fibers alone in vitro but does so in the presence of filamentous actin, and these fiber bundles dissolve when treated with either gelsolin or DNase I. These findings implicate actin-DNA interactions in the pathogenesis of airway disease and identify both polymers as targets for therapy.

Prospective evaluation by computed tomography and pulmonary function tests of children with mediastinal masses.

BACKGROUND: Our ability to predict respiratory compromise during general anesthesia in a child with an anterior mediastinal mass is limited. Two prior reports have found a correlation between adequacy of ventilation during general anesthesia and the tracheal cross-sectional area obtained from computed tomograms (computed tomography [CT] scans). These and other reports have suggested that pulmonary function tests may provide additional information regarding anesthetic risks, but no studies have evaluated the extent of respiratory compromise in children with an anterior mediastinal mass. METHODS: We prospectively evaluated 31 children with mediastinal masses before 34 surgical procedures. At each evaluation the tracheal area (as a percent of the predicted area on the basis of age and gender) was determined by CT. Pulmonary function tests were performed in the sitting and supine positions. The eleven children with either a tracheal area or peak expiratory flow rate (PEFR) of less than 50% of predicted received only a local anesthetic; the majority of children above these levels (17 of 22) received a general anesthetic. RESULTS: Eleven of 31 patients had significant pulmonary restriction as defined by total lung capacity of less than 75% of predicted. Eight patients had a PEFR in the supine position of less than 50% of predicted. PEFR was lower in the supine than the upright position in all patients (median value of decrease, 12%). In 28 of 34 evaluations the child had a tracheal area greater than 50% of predicted, a criterion proposed for safe utilization of general anesthesia. This latter guideline, however, did not identify all patients with significant impairment of pulmonary function; five patients had a PEFR of less than 50% of predicted but tracheal areas of greater than 50% of predicted. All children were administered anesthetics uneventfully with these guidelines. CONCLUSIONS: Although the tracheal area can be accurately measured with the CT scan, this does not identify all children with mediastinal masses and abnormal pulmonary function. A large mass may produce significant restrictive impairment and hence reduction in PEFR by the intrathoracic volume it occupies and yet not cause tracheal compression. It may also reduce the PEFR by narrowing the bronchi distal to the carina. Currently no CT standards exist for measuring bronchial areas in children. Our study did not evaluate whether impaired pulmonary function as measured by PEFR would be predictive of respiratory collapse during general anesthesia because all were excluded and operated on under local anesthesia. General anesthesia was well tolerated in children with tracheal area and PEFR greater than 50% of predicted. Pulmonary function tests in children with anterior mediastinal masses may add valuable information to the anatomic evaluation obtained by CT scan.