Low-level environmental tobacco smoke exposure and inflammatory biomarkers in children with asthma.

OBJECTIVE: The effects of low-level environmental tobacco smoke (ETS) exposure, on asthma control, lung function and inflammatory biomarkers in children with asthma have not been well studied. The objective of the study was to assess ETS exposure in school-age children with asthma whose parents either deny smoking or only smoke outside the home, and to assess the impact of low-level ETS exposure on asthma control, spirometry and inflammatory biomarkers. METHODS: Forty patients age 8-18 years with well-controlled, mild-to-moderate persistent asthma treated with either inhaled corticosteroids (ICS) or montelukast were enrolled. Subjects completed an age-appropriate Asthma Control Test and a smoke exposure questionnaire, and exhaled nitric oxide (FeNO), spirometry, urinary cotinine and leukotriene E(4) (LTE(4)) were measured. ETS-exposed and unexposed groups were compared. RESULTS: Only one parent reported smoking in the home, yet 28 (70%) subjects had urinary cotinine levels ≥1 ng/ml, suggesting ETS exposure. Seven subjects (18%) had FeNO levels >25parts per billion, six of whom were in the ETS-exposed group. In the ICS-treated subjects, but not in the montelukast-treated subjects, ETS exposure was associated with higher urinary LTE(4), p = 0.04, but had no effect on asthma control, forced expiratory volume in 1 s or FeNO. CONCLUSIONS: A majority of school-age children with persistent asthma may be exposed to ETS, as measured by urinary cotinine, even if their parents insist they don't smoke in the home. Urinary LTE(4) was higher in the ETS-exposed children treated with ICS, but not in children treated with montelukast.

ALOX5 polymorphism associates with increased leukotriene production and reduced lung function and asthma control in children with poorly controlled asthma.

BACKGROUND: Identification of risk factors for reduced asthma control could improve the understanding and treatment of asthma. A promoter polymorphism in the 5-lipoxygenase gene affects gene expression and response to asthma therapy, but its impact on disease control remains unclear. OBJECTIVE: We sought to determine if the ALOX5 promoter SP1 tandem repeat polymorphism was associated with changes in cysteinyl leukotriene production, lung function, airway inflammation and asthma control score. METHODS: We analysed 270 children, 6- to 17-years old, with poorly controlled asthma enrolled in a 6-month clinical trial (NCT00604851). In secondary analysis, we associated the ALOX5 promoter SP1 tandem repeat polymorphism genotype (rs59439148) with asthma outcomes using both additive and recessive genetic models. We evaluated FEV1 percent predicted, symptom control, exhaled nitric oxide and urinary LTE4 levels. RESULTS: Of all children, 14.8% (40/270) (and 28% (38/135) of African Americans) carried two non-5-repeat variant alleles of rs59439148. Children who were homozygous for variant alleles had significantly higher urinary LTE4 levels (38 vs. 30 nmol/mol creatinine, P = 0.0134), significantly worse FEV1% predicted (84 vs. 91, P = 0.017) and a trend towards worse asthma control. FEV1% predicted values were significantly negatively correlated with urinary LTE4 (r = -0.192, P = 0.009). CONCLUSION AND CLINICAL RELEVANCE: Carrying two copies of a minor variant ALOX5 promoter SP1 tandem repeat allele contributes to increased cysLT exposure as determined by urinary LTE4 levels, reduced lung function and potentially worse asthma control. ALOX5 promoter SP1 tandem repeat genotype may be a risk factor for worse asthma outcomes.

Cold air inhalation challenge in the diagnosis of asthma in children.

A study was designed to determine the usefulness of cold air inhalation challenge testing in children with asthma and to determine the magnitude and duration of the response. A total of 17 children with asthma, mean age 11.7 years (range 6 to 16 years) and eight nonasthmatic children, mean age 11.5 years (range 7 to 15 years) were studied. The average response to isocapneic hyperventilation with cold air in the asthmatic children was a decrease in vital capacity of 10%, a decrease in forced expiratory volume in 1 second (FEV1) of 19%, a decrease in peak flow rate (PFR) of 24%, and a decrease in maximal midexpiratory flow rate (MMFR) of 36%. This was significantly different from the response to the same level of hyperventilation with warm, fully saturated air. The response to isocapneic hyperventilation with cold air in nonasthmatic children was significantly different from the asthmatic children's response with a mean decrease in vital capacity of 0.9%, a decrease in forced expiratory volume in 1 second of 2.5%, a decrease in peak flow rate of 7%, and a decrease in maximal midexpiratory flow rate of 10%. The response in the asthmatic children occurred four to eight minutes after challenge and resolved in eight to 12 minutes. Although the response was highly significant, none of the children developed respiratory distress. It was concluded that isocapneic hyperventilation with cold air is a safe and simple test for diagnosing asthma in children.

Spontaneous pneumothorax in children with AIDS.

The incidence of pneumothorax in HIV-infected children has not been reported. In adults with AIDS, pneumothorax has been described exclusively in association with Pneumocystis carinii pneumonia (PCP). We report the cases of three children with AIDS, one with lymphoid interstitial pneumonitis (LIP) without evidence of PCP and two with PCP, all of whom developed spontaneous pneumothorax (SP). On presentation, none of the children had any risk factors for the development of pneumothorax, but all had radiographic evidence of subpleural cystic lesions and bilateral pleural adhesions. None of the patients responded to conservative medical management, which included chest tube thoracostomy and chemical pleurodesis. Two patients underwent pleurectomy that resulted in resolution of the pneumothorax. Both patients with PCP who developed pneumothorax died, but the patient with LIP and SP has had no recurrences of any serious respiratory problems 3 years after pleurectomy and excision of the intrathoracic cysts.

Evidence of airway obstruction in children with idiopathic scoliosis.

Restrictive pulmonary function abnormalities are reported in children and adolescents with idiopathic scoliosis. We hypothesized that spirometry alone, without more extensive testing, including the measurement of lung volumes, is inadequate in characterizing lung function in these children and may miss obstructive abnormalities including significant gas trapping. To examine this hypothesis, we reviewed the pulmonary function tests of 44 children (36 female, 8 male) between the ages of 10 and 18 years with idiopathic scoliosis prior to surgical correction. Spirometry, measurements of lung volumes with both plethysmographic and helium dilution techniques, and bronchodilator response were analyzed for evidence of reversible airway obstruction and gas trapping. Eighteen of 44 (41%) subjects had significant restriction. Only 3 (7%) subjects met standard criteria for airflow obstruction. However, 20 (46%) subjects had an elevated total gas volume by plethysmography-functional residual capacity by helium dilution ratio indicative of moderate or severe gas trapping, 10 (23%) subjects showed mild gas trapping, 8 (18%) subjects had a ratio suggestive of gas trapping, and only 6 (14%) subjects were normal. Additionally, significant improvement in airway mechanics was noted after bronchodilator administration. Specific conductance improved in all subjects, with a mean increase of 62% +/- 8.0 (p<0.001). The residual volume-total lung capacity ratio and total gas volume by plethysmography also decreased significantly (mean decrease, 22.5% +/- 3.0 and 15% +/- 1.0, respectively, p<0.001) in response to inhaled bronchodilators. In conclusion, although restrictive defects are commonly present in children with idiopathic scoliosis, significant gas trapping and responses to bronchodilators also commonly occur. These abnormalities may be missed without extensive pulmonary function testing.

Urokinase in the management of complicated parapneumonic effusions in children.

OBJECTIVE: Use of intrapleural fibrinolytic agents in the management of complicated parapneumonic effusions has been widely reported in adults. Such agents promote drainage of fluid through the thoracostomy tube and may obviate surgery. Both streptokinase and urokinase have been used for this purpose, but there are few reports of their use in the children. The objective of this study was to evaluate the role of intrapleural urokinase in the management of complicated parapneumonic effusions in children. METHODS: We reviewed the hospital course of nine children, ages 6 months to 6 years, with complicated parapneumonic effusions who received intrapleural urokinase after failing to respond to I.V. antibiotics and closed-tube thoracostomy drainage. Four subjects had additional thoroscopic adhesiolysis before intrapleural instillation of urokinase; 20,000 IU of diluted urokinase was instilled three times a day via the thoracostomy tube for 3 days. RESULTS: Eight subjects responded to 3 days of urokinase instillation, with increased thoracostomy tube drainage and clinical resolution of symptoms. The remaining subject responded to a second course of instillation. Two subjects needed oral analgesic for transient chest pain. All subjects tolerated the procedure well. No bleeding, fever, anaphylaxis, or allergic reactions were noted. The coagulation parameters remained unchanged. CONCLUSION: Intrapleural instillation of urokinase appears to be a useful and safe adjunct in the management of complicated parapneumonic effusions in children. Its use may be considered in potential decortication patients in an effort to prevent surgery and possibly shorten hospitalization.

Nebulized lidocaine administered to infants and children undergoing flexible bronchoscopy.

STUDY OBJECTIVES: The purpose of this study was to evaluate the safety and efficacy of nebulized lidocaine hydrochloride as a topical anesthetic for use during flexible bronchoscopy in infants and children. DESIGN: This was a prospective, randomized, double-blind study. PATIENTS: Twenty consecutive patients scheduled for flexible bronchoscopy who were not intubated and had no known cardiac or hepatic disease comprised the study group. INTERVENTIONS: The patients were randomized to receive either 8 mg/kg or 4 mg/kg of nebulized 2% lidocaine by face mask prior to bronchoscopy. SETTING: The study took place in a bronchoscopy suite at an academic medical center. MEASUREMENTS: To determine systemic absorption, serum lidocaine levels were obtained. To assess efficacy of nebulized lidocaine as a topical anesthetic, changes in heart rate and blood pressure were recorded, and the bronchoscopist (who did not know the lidocaine dose used) rated the ease of passage of the bronchoscope through nose, vocal cords, trachea, bronchi, and all sites overall, and the degree of cough. RESULTS: Nebulized lidocaine was safe, was well-tolerated, and provided adequate anesthesia for half of the patients. The serum lidocaine levels were much lower than the levels in the toxic range. There was a trend toward easier passage of the bronchoscope in the high-dose group at all sites noted previously that were evaluated. CONCLUSION: Nebulized lidocaine in doses up to 8 mg/kg appears to be safe and moderately effective as a topical anesthetic for flexible bronchoscopy in infants and children. The serum levels were remarkably low. Fifty percent of the subjects required no supplemental lidocaine.

Forced expiratory maneuvers in children aged 3 to 5 years.

There is no consensus about reproducibility and reliability of spirometry in young children. We evaluated forced expiratory maneuvers from 98 children aged 3 to 5 years with a variety of respiratory disorders before and after bronchodilator treatment. Forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1) were analyzed for reproducibility by the American Thoracic Society criteria and for reliability based on the coefficient of variation (CV%). Over 90% of the patients cooperated, however, while 95% could exhale for at least 1 second, very few generated an FEV1 on all 6 "best" efforts. This clearly improved with age. Of all patients nearly 60% performed reproducible pre- and postbronchodilator sets of FVC but only 32% performed reproducible sets of FEV1. Based on the CV%, those patients who could reproducibly perform an FVC and FEV1 did it quite reliably (mean CV%, 9.38 and 7.01 for FVC and FEV1, respectively). We conclude that while some very young children can perform spirometry, reliability of performance cannot be assumed in this age group.

Effects of administration of aerosolized recombinant human deoxyribonuclease on resting energy expenditure in patients with cystic fibrosis.

By improving pulmonary function in patients with cystic fibrosis (CF), recombinant human deoxyribonuclease (rhDNase) may affect resting energy expenditure (REE). To examine this hypothesis, we measured REE by indirect calorimetry in seven patients with CF before (day 0) and 2 weeks after (day 15) administration of aerosolized rhDNase. Baseline REE was higher in all patients than predicted for age, sex, and weight (mean +/- SEM 128 +/- 4.9%; range, 116-147%). After 2 weeks of aerosolized rhDNase, mean forced vital capacity (FVC) (in % of predicted values) improved significantly from 54.1 +/- 2.2 to 66.3 +/- 4.2% (mean improvement, 12.3%; 95% CI, 2.8, 21; P < 0.05) and REE decreased by 11.0% (95% CI 3.2, 17.5; P < 0.05). In addition, the larger the improvement in FVC in response to rhDNase the greater the decrease in energy expenditure (r - 0.88). The REE decreased in all patients who had an increase in FVC and remained unchanged in two patients who had no change in FVC. We conclude that patients with CF whose lung function improve in response to aerosolized rhDNase have an acute and proportionate reduction in their resting energy expenditure.

Inspiratory flow limitation in children with bronchopulmonary dysplasia.

The objective of this study was to compare pulmonary function tests of children with bronchopulmonary dysplasia (BPD) and asthma, and to evaluate children with BPD for evidence of upper airway obstruction. This is a case-control retrospective study of pulmonary function tests (PFTs) of 11 children with BPD between 5 and 8 years of age who were followed by pediatric pulmonologists, and of 32 age- and height-matched children with asthma. The median forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF) were significantly lower in the BPD group (0.86 L, 0.79 L, 120 L/min) than in the asthmatic group (1.34 L, 1.21 L, 155 L/min; P = 0.002, P = 0.007, P = 0.004, respectively). Both groups were equally hyperinflated (median thoracic gas volume 155% of predicted values in the BPD compared to 152% predicted in the asthma group; P = 0.67), and both groups showed decreases in air-trapping after a bronchodilator. The ratios of forced expiratory flow at 50% of the FVC to forced inspiratory flow at 50% of the FVC (FEF50%/FIF50%) and FEV1 to PEF (FEV1/PEF) were used to assess upper airway obstruction and were higher in children with BPD than asthma (P = 0.0001 and P = 0.035, respectively). We conclude that pulmonary function of children with BPD who are still symptomatic after 5 years of age is different from age-matched children with asthma, and the children with BPD demonstrate significant inspiratory flow limitations.

Video-assisted thoracoscopy in the management of recurrent spontaneous pneumothorax in the pediatric population.

BACKGROUND AND OBJECTIVES: The purpose of the present study was to evaluate the application of video-assisted thoracoscopy in the management of recurrent spontaneous pneumothorax in the pediatric population. PATIENTS AND METHODS: Between 1995 and 1997, four patients with recurrent spontaneous pneumothorax were treated. Ages varied from 14 to 17 years. There were three males and one female. Two patients had spontaneous pneumothorax twice, and the other two had it three times. Three patients had primary spontaneous pneumothorax, and the fourth one had spontaneous pneumothorax secondary to cystic fibrosis. Computerized tomography of the chest demonstrated blebs in two patients, and in the other two it was suggestive of apical blebs but not definitive. All patients had failed treatment by tube thoracostomy. Video-assisted thoracoscopy demonstrated blebs in all patients. Removal was easily accomplished with an endoscopic automatic stapling device. The procedure was completed with mechanical pleurodesis, multiple intercostal blocks and intrapleural bupivacaine for control of pain. RESULTS: All patients had a quick and uneventful recovery. Follow-up ranged from one to three years. There were no complications or subsequent recurrences of the pneumothorax. CONCLUSIONS: Video-assisted thoracoscopy is a safe and effective technique in recurrent spontaneous pneumothorax. It allows for accurate identification and removal of the blebs, with quick recovery, minimal discomfort and good cosmetic results.

Hypoelectrolytemia, hypovolemia, and alkalosis in cystic fibrosis with wood-burning stove in winter.

Hypoelectrolytemia, alkalosis, and shock were present in an infant subsequently diagnosed as having cystic fibrosis (CF). Environmental temperature control was poorly maintained by a wood-burning stove in winter and contributed to the process of fluid and electrolyte loss. Pediatricians must consider CF and other processes when electrolytes and fluid are lost during environmental heat excess.

Effect of vasodilators at rest and during exercise in young adults with cystic fibrosis and chronic cor pulmonale.

Six clinically stable patients with cystic fibrosis (24 to 31 yr of age) and severe pulmonary impairment, right ventricular hypertrophy, and previous right-sided heart failure underwent cardiac catheterization to assess the hemodynamic effects of oxygen (fraction of inspired O2, 0.31, 0.50), phentolamine (5 mg intravenously), hydralazine (0.33 mg/kg intravenously), and nifedipine (20 mg sublingually). Measurements during dynamic exercise were also obtained before and after hydralazine therapy. Studies after 5 to 8 wk of continuous, orally administered hydralazine therapy were performed in 3 patients. The resting mean pulmonary artery pressure was 31 +/- 4 mmHg. At rest, only oxygen was a selective pulmonary vasodilator, decreasing pulmonary artery pressure and pulmonary vascular resistance in all patients. Systemic arterial pressure and resistance were not significantly changed. Phentolamine, hydralazine, and nifedipine did not alter pulmonary artery pressure or selectively affect the pulmonary vascular bed, reducing both calculated pulmonary and systemic vascular resistance, the latter to a similar or greater degree. Hydralazine and nifedipine significantly increased cardiac index and decreased systemic arterial pressure. Nifedipine mildly decreased systemic oxygenation. During exercise, the mean pulmonary artery pressure increased to 51 +/- 15 mmHg. Hydralazine increased systemic and mixed venous oxygenation both at rest and during exercise but did not alter the elevation in pulmonary artery pressure observed during exercise. After orally administered hydralazine therapy, oxygen delivery and cardiac index remained increased in 2 patients. These data support the use of oxygen but not of the other agents in patients with cystic fibrosis and chronic cor pulmonale unless the ability of hydralazine to increase oxygen delivery is determined to improve prognosis.

Patterns of gastroesophageal reflux (GER) in patients with apparent life-threatening events.

The incidence and temporal patterns of gastroesophageal reflux (GER) in infants presenting with an apparent life-threatening event (ALTE) was compared with GER characteristics of infants evaluated for persistent emesis, utilizing continuous 24 h intraesophageal pH monitoring. These data indicate that the incidence of significant GER was similar in both groups, despite the absence of a clinical vomiting history in 46% of ALTE patients. Furthermore, infants with ALTE demonstrate a significantly higher incidence of sleep reflux when compared with control infants presenting with vomiting alone (27 vs. 0%, p less than 0.001). Awake GER beyond the first two postprandial hours was not observed in either study group. Monitoring results, therefore, indicate that significant GER is common in infants with ALTE; and these infants manifest an apparently unique pattern of GER distinct from that observed in age-matched controls with GER alone. Possible relationships between GER in ALTE patients and the development/onset of apneic episodes are discussed.

Gastroesophageal reflux-induced hypoxemia in infants with apparent life-threatening event(s).

To evaluate relationships between gastroesophageal reflux (GER) and the development and onset of apparent life-threatening event(s) (ALTE), 16 infants presenting with ALTE and 6 control subjects manifesting clinical GER alone were studied using prolonged, esophageal pH monitoring in conjunction with simultaneous pulse oximetry and transthoracic impedance pneumocardiography. Despite the absence of a clinical vomiting history in 14 of 16 patients with ALTE, the incidence of GER was similar in both groups (patients with ALTE vs control subjects, 95% vs 100%). Significant arterial oxygen desaturation (less than 90% for greater than 3 minutes) was monitored during 60 episodes in 14 of 16 infants with ALTE, compared with no episodes of reduced arterial oxygen saturation in control subjects. Fifty-four of 60 of these desaturation events commenced within 3.9 +/- 0.4 minutes (mean +/- SD) of onset of a drop in esophageal pH to less than 4.0. Linear regression analysis indicates a significant correlation between duration of esophageal acidification and length of individual hypoxemic episodes (r = .39). Pneumocardiograms were normal in all patients. These data suggest that unsuspected GER is common in infants presenting with ALTE and, in these patients, GER may be directly associated with reflex hypoxemic episodes. Prolonged intraesophageal pH monitoring, performed simultaneously with evaluation for apnea, should be considered in all infants presenting with ALTE.

Aerosolized recombinant human DNase in hospitalized cystic fibrosis patients with acute pulmonary exacerbations.

The goal of this study was to evaluate the safety and efficacy of recombinant human DNase (rhDNase) in hospitalized patients with cystic fibrosis (CF) experiencing acute pulmonary exacerbations. Eighty patients with documented CF were enrolled at 11 CF centers when admitted for antibiotic therapy. Patients were at least 5 yr old with a forced vital capacity (FVC) > or = 35% of predicted and an oxygen saturation > or = 90% on a fraction of inspired oxygen (FIO2) < 0.5. Patients were randomized to receive rhDNase 2.5 mg in 2.5 ml excipient twice a day (n = 43) or 2.5 ml excipient alone twice daily (n = 37) along with conventional treatment for exacerbations. Administration of rhDNase was not associated with acute adverse events or deaths, and no patients experienced allergic or anaphylactic reactions. Although forced expiratory volume in one second (FEV1) and FVC improved in both treatment groups during the double-blind period, there were no statistically significant differences in the mean change from baseline in FEV1 or FVC between the two groups. rhDNase therapy is safe and well tolerated in CF patients with acute exacerbations requiring hospitalization, but the study did not demonstrate a statistically significant therapeutic effect of rhDNase when added to a regimen of antibiotics and chest physical therapy.