Response of vascular endothelial growth factor and angiogenesis-related genes to stepwise increases in inspired oxygen in neonatal rat lungs.

BACKGROUND: Bronchopulmonary dysplasia is an inflammatory lung disease that afflicts preterm infants requiring supplemental oxygen and is associated with impaired pulmonary angiogenesis. We tested the hypothesis that there is a critical threshold of inspired O2 (FiO2) that alters pulmonary angiogenesis. METHODS: Within 2-6 h of birth, rat pups were exposed to 10%, 21%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% FiO2 for 2 h. Mixed arterial-venous blood gases, serum and pulmonary levels of vascular endothelial growth factor (VEGF) and soluble VEGF receptor-1, and pulmonary angiogenesis gene profiles were determined. RESULTS: PO2 increased with hyperoxia from 35.6 ± 5.0 (range: 31.5-39.8) at 10% O2 to 108.5 ± 25.0 (range: 82.2-134.8) at 100% O2. PO2 at 21% O2 was 42.4 ± 7.3 (range: 36.8-48.1). Lung VEGF levels declined at 40%-100%. The critical PO2 associated with decreased lung VEGF was 66 mm Hg, achieved with a FiO2 of 0.4. PO2 was inversely correlated with VEGF levels in the lungs (R = -0.377; P < 0.008). Antiangiogenesis genes were robustly upregulated at 70%, predominantly in males. Data are reported as mean ± SD. CONCLUSIONS: A critical threshold of FiO2 affecting angiogenesis exists in immature lungs. Exposure of preterm lungs to >40% inspired O2, even for 2 h, may result in abnormal expression of biomarkers regulating lung angiogenesis.

A prospective appraisal of pulmonary hypertension in children with sickle cell disease.

OBJECTIVES: Pulmonary hypertension (PHT) is a life-threatening complication of sickle cell disease that occurs in 20% to 40% of adults. Measurement of maximal tricuspid regurgitant jet velocity (TRV) by echocardiography provides a noninvasive screening tool; TRV values > or =2.5 m/s are correlated with PHT and increased mortality. Our objective was to estimate the prevalence of PHT in our pediatric sickle cell population and its possible association with various clinical and laboratory findings, including obstructive sleep apnea and/or pulmonary dysfunction. STUDY DESIGN: Eligible children had measurement of the TRV. Clinical data were collected, including detailed history with a standardized sleep apnea questionnaire; those with suggestive histories had polysomonography. Pulmonary function was assessed using whole body plethysmography. RESULTS: Of 48 subjects (79% homozygous sickle cell anemia; median age 12 y; 11 receiving chronic transfusion) enrolled in the study, 4 (8.3%) had TRV >2.5 m/s; all had homozygous sickle cell anemia and 1 was receiving hydroxyurea after 3 years of transfusion for secondary stroke prevention. Subjects with elevated TRV had higher indirect bilirubin levels; we found no association between elevated TRV and obstructive apnea or pulmonary function abnormalities. CONCLUSIONS: Elevation of TRV was relatively uncommon in our pediatric patients as compared with prevalence reported in adults and may be associated with increased hemolysis. There was no association with obstructive sleep apnea or abnormal pulmonary function.

Pulmonary dysfunction and sleep apnea in morbid obesity.

The interplay between obesity and respiratory function has implications on lung functions, sleep disordered breathing and asthma. Severe obesity can restrict lung functions in childhood, but the extent of obstructive disease due to obesity in childhood is not clear. Obesity is clearly linked to the increased incidence of sleep disordered breathing in childhood. Most obese children with sleep disordered breathing have tonsillo-adenoidal hypertrophy contributing to sleep apnea. The presence of sleep apnea is a consideration in recommending bariatric surgery in the appropriate setting. Obese children with asthma tend to have more symptoms of asthma. Obese children, particularly girls, have a greater likelihood of developing asthma later in life. Further investigations of the various interactions between obesity and respiratory function are currently needed. Obesity is on the rise in US, reflected in the 3 times higher prevalence of overweight (body mass index > 95th percentile) in children 6 to 19 years of age (1). The prevalence of morbid or severe obesity, defined as a body mass index (BMI) of 40 or more in adults (2), has also increased from 2.9%, in the years 1988-1994, to 4.7% in the years 1999-2000 (3). In children, severe obesity has been defined as a BMI standard deviation score > 2.5 (4). The interactions between morbid obesity and the respiratory system have become more relevant today and can be broadly discussed in relation to lung functions and exercise capacity; sleep disordered breathing; and asthma.

The prevalence of metabolic syndrome in inner city obese African-American youth.

BACKGROUND: In children and adolescents, obesity increases the risk of metabolic syndrome (MS). OBJECTIVE: We examined the prevalence of MS among obese and morbidly obese children and adolescents referred to an obesity clinic in a university-based hospital center. DESIGN/METHODS: A total of 194 obese (BMI > 95%) children and adolescents were evaluated. Fasting glucose, insulin, lipid panel, BMI, blood pressures were obtained. Main outcome measures were prevalence of components of MS by modified National Cholesterol Education Program (NCEP or Adult Treatment Panel 111 (ATP 111), with MS defined as > or = 3 components. RESULTS: There were 113 females (58%) and 81 males (42%); mean age of the cohort was 11.9 years (range: 3.4-18.8 years). One hundred seventy four (90%) of the cohort were African-American, 14 (7%) were Hispanic and 6 (3%) were others. Mean BMI z- score was 2.5 and ranged from 1.7 to 4.8. Thirty five percent of the total cohort had MS. Among the morbidly obese patients (BMI z-score > 2.5), the prevalence of the MS increased to 44%. Impaired fasting glucose (5.8 %), impaired glucose tolerance (6.5%) and silent diabetes mellitus (2.4%) were also identified. CONCLUSIONS: One third of obese patients referred to a hospital-based obesity center had the MS and nearly half of morbidly obese children and adolescents had MS.

The Downstart Program: a hospital-based pediatric healthy lifestyle program for obese and morbidly obese minority youth.

Although obesity affects all cultures, ethnic groups and social strata, this disorder affects African Americans, Hispanics and the poor at a disproportionate rate. The Downstart Pediatric Healthy Lifestyle Program was developed to provide a multi-disciplinary behavioral modification program for inner city families in Brooklyn, New York interested in leading a healthier, more active lifestyle. The Downstart Program uses a four-pronged approach of medical evaluation, exercise, nutritional education and lifestyle modification. A psychological evaluation is performed to determine the individual's ability and readiness to participate in group activities. Baseline physical fitness, flexibility and muscle strength are measured, followed by a twice-weekly karate/martial arts/dance program, incorporating principles established by the President's Council on Exercise. Nutritional and behavioral modification aspects of the program consist of weekly education about food groups, portion control, goal setting and appropriate rewards for attaining goals. Our preliminary results indicate that the Downstart Program may be a viable intervention for weight loss. Further study is needed to improve strategies for motivating patients and means and criteria for assessing long-term effects on health and lifestyle.

The familial aggregation of pediatric obstructive sleep apnea syndrome.

OBJECTIVE: To determine the role of genetic mechanisms in the development of pediatric obstructive sleep apnea syndrome (OSAS). DESIGN: Genetic-epidemiologic survey of families of index children with laboratory-confirmed OSAS. SETTING: Tertiary care academic medical center. PARTICIPANTS: Six-hundred nap polysomnograms performed in our institution's pediatric sleep laboratory over a 6-year period (1994-2000) were reviewed, and the 497 children who tested positive for OSAS were selected. A caretaker of 200 of these index patients was contacted, and 115 were enrolled in the study. INTERVENTION AND MAIN OUTCOME MEASURE: Questionnaire-type telephone interviews were conducted with the current caretakers of the index patients to assess the distribution of sleep-disordered breathing in the first-degree relatives. RESULTS: Data were collected for 445 first-degree relatives (256 adults and 189 children) of the 115 index patients. Habitual snoring was found in 194 (43.6%) of the family members, while symptoms highly suggestive of OSAS (nighttime "gasping for air" or "cessation of breathing") were found in 91(20.4%). Sixty-eight (26.6%) of the adult first-degree relatives and 23 (12.2%) of the pediatric first-degree relatives had symptoms highly suggestive of OSAS. Of the 115 index children, 50 (43.5%) had at least 1 relative with symptoms highly suggestive of OSAS; 6 (1.3%) of the first-degree relatives had sleep study results positive for OSAS, 4 (0.9%) were using nasal continuous positive airway pressure, and 21 (4.7%) had prior surgery for the treatment of OSAS. CONCLUSION: Considering the established prevalence of OSAS in the general population (2%-4%), the results of this study support a familial basis for this disorder.

Allergen sensitivity and asthma severity at an inner city asthma center.

The objective of this study was to examine the relationship of allergen sensitivity to asthma symptoms among inner-city asthmatics seen at our Brooklyn, NY, asthma center. We hypothesized that asthma severity would increase for adults and children with increased cockroach and dust mite allergen sensitivity. Data were gathered from retrospective chart review for all patients who were treated at the center with a diagnosis of asthma and had undergone skin-prick testing (SPT) for allergen sensitivity during 1998 (pediatric, n = 79; adult, n = 29). Asthma severity (determined by National Heart, Lung and Blood Institute [NHLBI] asthma severity class) was examined in relation to allergen sensitivity. Allergen sensitivity was measured by percent positive to skin-prick testing as well as by relative mean diameter of skin prick test wheals. For adults, mite sensitivity prevalence was 61% and cockroach sensitivity prevalence was 41%. For children, mite sensitivity prevalence was 49%; cockroach sensitivity prevalence was 42%. For adults, asthma severity correlated significantly with sensitivity to Cladosporium, tree, and grass as measured by percent positive skin tests and by increasing mean diameter of skin test wheals. There was a significant correlation with severity for adult dust mite sensitivity only as measured by increasing mean wheal diameter. Ragweed sensitivity showed a significant correlation with severity only as measured by percent positive skin tests. There was a significant positive association for adults between increasing asthma severity and total number of allergen sensitivities per subject. There was no significant correlation for children between asthma severity and total number of allergen sensitivities per subject. Among children, no specific allergen sensitization showed a significant positive association with asthma severity. By both measures of allergen sensitization, there was a significant negative association for children between Cladosporium and asthma severity. Among our inner-city asthmatic population significant correlation between mite sensitivity and asthma severity was found only in adults. No significant association was seen with cockroach. However, outdoor allergen sensitivity (Cladosporidium, tree, ragweed, and grass) significantly correlated with asthma for adults in this inner city population.

Clinical assessment of pediatric obstructive sleep apnea.

OBJECTIVE: To determine whether children with a clinical assessment suggestive of obstructive sleep apnea (OSA) but with negative polysomnography (PSG) have improvement in their clinical assessment score after tonsillectomy and adenoidectomy (T&A) as compared with similar children who do not undergo surgery. METHODS: In a prospective, randomized, investigator-blinded, controlled trial, 59 otherwise healthy children (mean age: 6.3 years [3.0]; 31 boys, 28 girls) with a clinical diagnosis of OSA (clinical assessment score 40) were recruited from the pediatric otolaryngology and pediatric pulmonary private offices and clinics of a tertiary care, academic medical center. A standardized assessment was performed on all patients, including history, physical examination, voice recording, tape recording of breathing during sleep, lateral neck radiograph, echocardiogram, and PSG. A clinical assessment score was assigned. Children with positive PSG (n = 27) were scheduled for T&A, whereas children with negative PSG (n = 29) were randomized to T&A (n = 15) or no surgery (n = 14). Children were reassessed in an identical manner at a planned 6-month follow-up. RESULTS: Follow-up was available for 21 patients with positive PSG, 11 patients with negative PSG randomized to T&A, and 9 nonsurgery patients. In the randomized subjects, the median reduction in clinical assessment score was 49 (range: 32-61) for the T&A patients as compared with 8 (range: -9 to 29) for the nonsurgery patients. Nine (82%) of the T&A patients were asymptomatic (clinical assessment score <20) compared with 2 (22%) of the nonsurgery patients. CONCLUSION: Children with a positive clinical assessment of OSA but negative PSG have significant improvement after T&A as compared with observation alone, thus validating the clinician's role in diagnosing upper airway obstruction.