Howard Eigen

A multicenter study of alternate-day prednisone therapy in patients with cystic fibrosis☆☆☆★

The purpose of this study was to evaluate the efficacy and safety of alternate-day prednisone therapy in treating patients with mild-to-moderate cystic fibrosis during a 4-year period. In 15 North American cystic fibrosis centers, we screened 320 patients and enrolled 285 patients from April 1986 to December 1987. Patients were randomly assigned to take prednisone, 1 mg/kg per dose or 2 mg/kg per dose, or a matching placebo given on alternate days. Lung function, clinical status, hospitalizations, growth, and steroid side effects were monitored. During the first 24 months the percentage of the predicted forced vital capacity was greater in the 1 mg/kg group (p < 0.0001) and the 2 mg/kg group (p < 0.01) when each was compared with placebo. Patients in the 1 mg/kg group had a higher percentage of predicted forced vital capacity than placebo patients during the entire 48 months (p < 0.0025), but only in the group of patients who were colonized with Pseudomonas aeruginosa at baseline. For 48 months, the 1 mg/kg group had a higher percentage of predicted forced expiratory volume in 1 second than patients given placebo (p < 0.02). The prednisone-treated groups had a reduction in serum IgG concentrations (1 mg/kg vs placebo, p < 0.007; 2 mg/kg vs placebo, p < 0.003). From 6 months onward, height z scores fell in the 2 mg/kg group compared with those given placebo (p < 0.001). For the 1 mg/kg group, height z scores were lower from 24 months. An excess of abnormalities in glucose metabolism was seen in the 2 mg/kg group compared with the placebo group (p < 0.005). Our findings suggest a role for alternate-day prednisone therapy at a dose of 1 mg/kg in patients with mild to moderate cystic fibrosis. The benefit of improved lung function appears to outweigh the potential for adverse effects when the treatment period is less than 24 months.

Spirometry centile charts for young Caucasian children: The asthma UK collaborative initiative

RATIONALE Advances in spirometry measurement techniques have made it possible to obtain measurements in children as young as 3 years of age; however, in practice, application remains limited by the lack of appropriate reference data for young children, which are often based on limited population-specific samples. OBJECTIVES We aimed to build on previous models by collating existing reference data in young children (aged 3-7 yr), to produce updated prediction equations that span the preschool years and that are also linked to established reference equations for older children and adults. METHODS The Asthma UK Collaborative Initiative was established to collate lung function data from healthy young children aged 3 to 7 years. Collaborators included researchers with access to pulmonary function test data in healthy preschool children. Spirometry centiles were created using the LMS (lambda, micro, sigma) method and extend previously published equations down to 3 years of age. MEASUREMENTS AND MAIN RESULTS The Asthma UK centile charts for spirometry are based on the largest sample of healthy young Caucasian children aged 3-7 years (n = 3,777) from 15 centers across 11 countries and provide a continuous reference with a smooth transition into adolescence and adulthood. These equations improve existing pediatric equations by considering the between-subject variability to define a more appropriate age-dependent lower limit of normal. The collated data set reflects a variety of equipment, measurement protocols, and population characteristics and may be generalizable across different populations. CONCLUSIONS We present prediction equations for spirometry for preschool children and provide a foundation that will facilitate continued updating.

Gastroesophageal reflux in infants and children-comparative accuracy of diagnostic methods*

To assess the diagnostic accuracy of methods employed for detection of gastroesophageal reflux, 30 infants and children with symptoms of GER were evaluated by upper gastrointestinal series, gastroesophageal scintiscan, measurement of mean resting lower esophageal sphincter pressure, esophageal intraluminal PH measurement (acid reflux test), and endoscopy. Fifteen control patients were also evaluated by the above studies. GER was demonstrated by UGI in 15 and by GE scintiscan in 17 study patients. LESP less than 15 mm Hg was noted in 12 and a positive acid reflux test was obtained in 29 study patients. Esophagitis was detected in two (of 30) study patients radiographically and in 15 (of 21) study patients by upper gastrointestinal endoscopy. Pulmonary aspiration of gastric contents was not detected by the radionuclide method. None of the 15 control patients had GER demonstrated with any of the above methods. These studies indicate that (1) the acid reflux test correlates most closely with symptoms of GER; (2) THE GE scintiscan is complementary to the UGI in the diagnosis of GER, i.e., the combination increases sensitivity; (3) normal LESP does not necessarily exclude GER; and (4) endoscopy is superior to the UGI in detecting the presence of esophagitis.

TNF-α, IL-8, soluble ICAM-1, and neutrophils in sputum of cystic fibrosis patients

The cytokines tumor necrosis factor‐α (TNF‐α), interleukin‐8 (IL‐8), and intercellular adhesion molecule‐1 (ICAM‐1) have important roles in regulating neutrophil migration and the inflammatory response. To determine whether the concentration of these cytokines and soluble ICAM‐1 (sICAM‐1) in sputum was increased in patients with cystic fibrosis during acute exacerbations, we conducted (1) a cross‐sectional study of 40 patients, 22 who were clinically well and 18 with acute pulmonary exacerbations; and (2) an 11 months longitudinal study of 16 patients. Significant differences in clinical scores, pulmonary function, and sputum neutrophil density were found between the acutely ill and the well group. There was a strong linear relationship (P < 0.0005) between TNF‐α and IL‐8 concentrations in sputum, but no association between clinical status and cytokine concentrations. The concentration of sICAM‐1 was lower in acutely ill compared with well patients in the cross‐sectional study. Recovery of exogenous IL‐8 added to sputum was complete, while recovery of TNF‐α averaged 70%. Recovery of exogenous sICAM‐1 was only 43%, and the recoveries were lower in sputum samples from acutely ill patients than those from stable patients (P = 0.018). These data indicate that in cystic fibrosis patients, sputum concentrations of TNF‐α and IL‐8 are not increased during acute exacerbations of pulmonary inflammation. Pediatr Pulmonol. 1996; 21:11–19.

Predictability and consequences of spontaneous extubation in a pediatric ICU.

To determine the incidence of, and the factors contributing to spontaneous extubation (SE), we followed prospectively all intubated children admitted to a pediatric ICU. Eleven potential risk factors were monitored and scored twice daily for 8 consecutive months. Using data from the first 204 patient admissions, we evaluated the risk factors by orthogonal discriminant analysis and found that four factors (patient age, amount of secretions, endotracheal tube slippage, and state of consciousness), when considered together, had good discriminating power for SE vs. intentional extubation. We tested this method on the next 45 patient admissions and identified all seven spontaneously extubated patients as high risk. Analysis of covariance revealed successful discrimination between low-risk and high-risk patients for up to three days after patient admission. Overall, the incidence of SE was 13% (33 of 249). The effect of extubation on gas exchange was the same for spontaneously and intentionally extubated patients. No morbidity or deaths were attributed to SE. Standard ventilator low-pressure alarms did not reliably signal the presence of SE, nor did upper extremity restraints keep patients from extubating themselves.

Intra-abdominal complications of cystic fibrosis.

In recent years patients with cystic fibrosis (CF) have experienced longterm survival and have demonstrated a number of intra-abdominal complications. This report evaluates the intra-abdominal complications seen in 69 of 189 children with cystic fibrosis from 1972 to 1983. Forty-one patients were boys and twenty-eight girls. Complications occurred in 36 neonates, with meconium ileus (MI) noted in 33 and giant cystic meconium peritonitis (GCMP) in 3. Meconium ileus equivalent occurred in seven older children presenting with bowel obstruction. In addition, rectal prolapse occurred in 12, inguinal hernia in 10, intussusception in 3, cholelithiasis in 3, GE reflux in 4, stress ulcer in 1 and appendicitis in 1. Three infants with GCMP survived resection and enterostomy. Infants with MI were divided into simple (15) or complicated (18) cases. Nonoperative therapy using gastrografin enema was successful in three of eight with simple MI. Operative enterotomy and irrigation was successful in three cases while resection and enterostomy was done in nine. MI was complicated by atresia, volvulus and/or perforation in 18 cases requiring resection and anastomosis or enterostomy. Survival for MI was 86% compared to 36% in 25 MI patients treated in the previous two decades. Meconium ileus equivalent was successfully managed using gastrografin enema in five of seven children. Only 3 of 12 children with rectal prolapse required repair. Two cases of intussusception were reduced while one required resection. Three of 10 children had hernia recurrence due to chronic pulmonary problems.(ABSTRACT TRUNCATED AT 250 WORDS)

COMMON PLEURAL EFFUSIONS IN CHILDREN

The evaluation of pleural effusions in children differ from that of the adult in cause, symptom presentation, character of the fluid, techniques for diagnosis, treatment or management, and prognosis. These similarities and differences are reviewed with emphasis on the treatment of empyema.

Pediatric pulmonary function testing in asthma

Pulmonary function testing is an important tool in the management of asthma. Lung function can be readily assessed in both the office and patients home. This article reviews spirometry, peak flow meters, and bronchial challenge testing. Their interpretation and clinical use are presented as well.

Lower respiratory illness in infants and young children with cystic fibrosis

The purpose of our study was to assess the effect on pulmonary function of adding intravenous hydrocortisone to the standard treatment of infants with cystic fibrosis (CF) hospitalized for lower respiratory illnesses (LRI). Twenty CF infants were randomized and received 10 days of hydrocortisone (10 mg/kg/day) or placebo in addition to standard treatment with intravenous antibiotics, chest physiotherapy, and an aerosolized‐agonist with cromolyn. Functional residual capacity (FRC) and forced expiratory flows (V′max, FRC) were measured on admission, on Day 10 of hospitalization, and as outpatients 1–2 months following hospital discharge. Pulmonary function values were adjusted for differences in body length and expressed as Z‐scores.

Pulmonary function abnormalities in survivors of near drowning

To determine the pulmonary status of children surviving near-drowning accidents, we studied the pulmonary function of ten asymptomatic children 6 months to 8.5 years (mean 3.3 years) after the accident. All ten children had normal FEF max, FVC, FEV1/FVC, FEF 50%, FRC, and RV/TLC. However, six patients had an elevated VisoV and five of these had a reduced delta Vmax 50%, indicating peripheral airway disease. Seventy percent of the patients had bronchial hyperactivity. Only one patient had completely normal pulmonary function. These results indicate that near drowning results in large and small airway dysfunction in children with no predisposition to lung disease, which may be present years after the initial insult. Such children may be at increased risk of developing chronic lung disease, especially if exposed to known airway irritants such as cigarette smoke.