Recurrent pneumonia in children and its relationship to bronchial hyperreactivity.

To determine what conditions are most likely to cause persistent or recurrent pneumonia (PRP) in children, the records of 81 children referred to James Whitcomb Riley Hospital for Children for evaluation of PRP were reviewed. Twenty patients had an apparent underlying cause that predisposed them to PRP. Of the 61 remaining patients (mean age 3.8 years) without any apparent cause for PRP, 49% had a history of allergy or family history of asthma, 31% patients had a history of wheezing and 18% were wheezing during their initial visit. No patient had an elevated sweat chloride determination or immunoglobulin deficiency. Of the 12 patients who were able to be recalled for pulmonary function testing, three had airflow obstruction that responded to an inhaled bronchodilator (isoproterenol). Of the nine patients with normal function, eight responded to methacholine with a decrease from base line in the one-second forced expiratory volume of greater than 20%. In all, 92% of those tested had bronchial hyperreactivity. These results indicate that asthma is a common cause of PRP in children and that PRP may occur as the initial symptom even in the absence of wheezing.

Changing feeding trends as a cause of electrolyte depletion in infants with cystic fibrosis.

Between June 1979 and June 1980, 16 infants with cystic fibrosis (CF) were cared for at the James Whitcomb Riley Hospital for Children. Five of these children (average age 5.8 months) had a total of eight episodes of electrolyte depletion, with six episodes unassociated with high environmental temperature, fever, or significant gastrointestinal symptoms. Their primary symptoms were poor weight gain and anorexia. According to their dietary records, these five infants, at the time of their initial presentation, had an average electrolyte intake of 8 mEq of sodium, 12 mEq of potassium, and 10 mEq of chloride per day. All infants had been fed either standard infant formula or breast milk. Infant feeding surveys indicate that the estimated average sodium intake of 6-month-old infants has decreased from 45 mEq/day in 1965 to 15 mEq/day since 1977 when manufacturers stopped adding salt to baby foods. In addition, since 1971 the percentage of infants 6 months age receiving breast milk or standard infant formula rather than cow's milk, which is higher in sodium content, has increased from 33% to 72%. This decreased salt intake places the infant with CF at greater risk for electrolyte depletion than in the past. It is expected that a larger percentage of infants with CF will have electrolyte depletion as their initial symptom especially during periods of increased sweating or when electrolyte losses are experienced during gastrointestinal illnesses. CF should be suspected in any infant with electrolyte depletion, and infants known to have CF need daily salt supplementation. Serum electrolytes should be measured if the infant is experiencing weight loss or anorexia, particularly during periods of excessive salt losses.

Isolated pulmonary leukemic relapse following successful bone marrow transplant in a child with acute lymphoblastic leukemia.

Leukemic relapse and interstitial pneumonitis are common complications for leukemic patients following bone marrow transplantation. We present the case of a successful bone marrow transplantation patient who developed an interstitial infiltrate on chest roentgenogram 212 days post-transplant that was diagnosed by open lung biopsy and found to be a leukemic relapse of the lung parenchyma. No extrapulmonary sites were involved and the infiltrate cleared in three weeks with systemic chemotherapy. Pulmonary function tests continued to demonstrate restrictive disease. The patient remained in remission for nine months following pulmonary relapse on systemic chemotherapy. This patient illustrates an unusual site of leukemic relapse and the importance of open lung biopsy in the diagnosis of the immunosuppressed patient with a pulmonary infiltrate.

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.

Bronchoscopy for aspirated foreign bodies in children. Experience in 131 cases.

One hundred thirty-one children underwent rigid bronchoscopy under general anesthesia for suspected aspirated foreign bodies. There were 79 boys and 52 girls, with a mean age of 2.1 years. Physical examination showed decreased breath sounds (n = 130) and wheezing (n = 119) over the affected site. Chest roentgenograms were diagnostic or suggestive of aspirated foreign bodies in 127 cases (97%). Radiopaque lesions were noted on roentgenograms in ten cases. Four infants had a preoperative hypoxic arrest. Two patients had negative results of bronchoscopy (1.5%). Extraction of the aspirated foreign body was carried out at laryngoscopy in two patients and by forceps under direct vision at bronchoscopy in 97 patients. A Fogarty catheter was used in 12 cases. Postendoscopic complications included fever (n = 27), pulmonary infiltrate (n = 11), ventilatory support (n = 4), and pneumothorax (n = 2). Rigid bronchoscopy for aspirated foreign body in children is a safe, effective, and sometimes life-saving procedure. Morbidity is low and mortality is zero.

Role strain in couples with and without a child with a chronic illness: associations with marital satisfaction, intimacy, and daily mood.

This study examined marital role strain in 33 couples caring for a child with cystic fibrosis (CF) and 33 couples with a healthy child. The relationship between role strain, marital satisfaction, and psychological distress was tested. Couples completed a structured interview, questionnaires, a card sort procedure, and 4 daily diaries assessing activities and mood. Couples in the CF versus comparison group reported greater role strain on measures of role conflict, child-care tasks, and exchanges of affection. They also spent less time in recreational activities, but no reliable group differences were found in marital satisfaction or depression. Regression analyses indicated that role strain was related to marital satisfaction and depression and that recreation time accounted for additional variance. Path analysis suggested that recreation mediated the negative relationship between role strain and distress. The importance of using a contextual, process-oriented approach is discussed.

Isozymes of ribonuclease in human serum and urine. II. A survey of patients with cystic fibrosis.

A comparison of serum and urine RNase isozymes from CF patients, heterozygotes, and control subjects demonstrated that the major RNase isozymes are not abnormal in CF. Some preliminary evidence indicated that RNase activity of the pancreatic extracts administered to CF patients may appear in the urine and result in a slightly different urine isozyme pattern. In addition, the mean serum RNase activities of the CF patients and heterozygotes were significantly greater than the mean activity of the controls, but there was much overlap in values between the groups.

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.

Absence of long term pulmonary sequelae after mild meconium aspiration syndrome.

To assess residual damage from meconium aspiration syndrome (MAS), we studied 12 children, ages 6 to 9 years, an average of 7.4 years after injury. Our sample consisted of mildly affected patients, only one having required intubation and mechanical ventilation in the acute phase of illness. In each child we measured FVC, FEV1, PEFR, MMEFR, VisoV, lung volumes by plethysmography, DLCO and calculated FEV1/FVC and RV/TLC. Methacholine bronchial challenge was performed and the PD20 was calculated. These results were compared with those obtained from a group of 12 normal children studied in our laboratory. No significant difference was found for pulmonary function parameters studied, except for VisoV which was greater in MAS patients than normals (P less than 0.02). Given the inherent high degree of variability with VisoV, we were not able to ascribe this isolated finding to be indicative of small airway disease in these asymptomatic patients. We conclude that patients with mild to moderate initial insult from MAS show an absence of pulmonary sequelae when tested at an average of 7.4 years of age.

Airway responsiveness in infants following bronchiolitis.

Airway responsiveness to inhaled methacholine was assessed in 18 infants, 4 and 10 months old, following bronchiolitis. Pulmonary function was measured from partial expiratory flow-volume curves generated by the rapid compression technique. Sleeping infants inhaled increasing concentrations of methacholine until maximal expiratory flows at functional residual capacity (VmaxFRC) decreased by 30% or 2.5 mg/mL was inhaled. Airway responsiveness was quantitated by: 1) the threshold concentration (log TC) required to decrease VmaxFRC by 2 standard deviations from baseline; 2) the concentration required to decrease VmaxFRC by 30% (log PC30); and 3) the slope of the dose-response curve between TC and PC30 (log SPC30). At both the first and second evaluation, the bronchiolitic infants had lower baseline VmaxFRC (% pred.) than 24 control infants. In addition, the bronchiolitic infants had heightened airway responsiveness compared to controls, demonstrating lower values for logTC and logPC30 and steeper slopes to their dose-response curves (logSPC30). After accounting for the relationship between airway responsiveness and age, the occurrence of bronchiolitis was found to be a significant independent factor 10 months but not 4 months following bronchiolitis. The bronchiolitic infants did not demonstrate the decline in airway responsiveness with increasing age that occurs in normal infants. We conclude that infants exhibit heightened airway responsiveness following bronchiolitis.

Longitudinal evaluation of pulmonary function in infants and very young children with cystic fibrosis.

Thirty-two infants with cystic fibrosis (CF) had pulmonary function testing and chest radiographs at the time of diagnosis and on average 1 year later, when they had no acute respiratory symptoms. At diagnosis, 14 of 32 infants had respiratory symptoms (RESP) and 18 did not have respiratory symptoms (NRESP). There were no significant differences in age, weight, or length between the RESP and NRESP groups. At diagnosis, the RESP group had significantly lower forced expiratory flows compared to the NRESP group (41 +/- 32% vs. 98 +/- 48% predicted); however, there were no significant differences in functional residual capacity or chest radiographic scores. Between diagnosis and follow-up, the NRESP group had no significant change in pulmonary function but a decline in chest roentgenographic (CXR) scores (22 +/- 2 to 21 +/- 2). For infants in the RESP group, there were no significant changes in FRC or CXR score. Maximal expiratory flow at functional residual capacity (Vmax FRC) rose from diagnosis to 1 year follow-up (41 +/- 32% to 74 +/- 27% predicted; P < 0.002); however, at follow-up flows for the RESP group remained significantly lower than flows for the NRESP group (74% vs. 113% predicted; P < 0.0005). For the 32 infants with CF, there was significant correlation between percent predicted Vmax FRC at follow-up and at diagnosis (r = 0.47; P < 0.02). Those infants with lower percent predicted flows at diagnosis were more likely to have lower percent predicted flows 1 year later.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of maximal expiratory flows to evaluate central airways obstruction in infants.

Partial expiratory flow-volume (PEFV) curves obtained by the rapid compression technique were employed to assess airway function in three infants with three different lesions of the central airways (vascular ring, congenital tracheal stenosis, subglottic polyp). Preoperatively, all three demonstrated severe flow limitation with a relatively constant forced expiratory flow over the tidal volume range. Postoperatively the PEFV curves changed to a normal convex shape, and the maximal expiratory flows at functional residual capacity (VmaxFRC) returned to normal. The PEFV curve adds to our physiologic assessment of the severity of the central airway obstruction in infants and to the efficacy of our therapeutic intervention.

Effectiveness and safety of small vs. large doses of enteric coated pancreatic enzymes in reducing steatorrhea in children with cystic fibrosis: a prospective randomized study.

Among cystic fibrosis (CF) centers, usual doses of enteric coated (EC) pancreatic enzymes vary from one to six capsules per meal based upon arbitrary criteria for stool and growth patterns. Large doses of non-EC enzymes are associated with increased serum urate (SU) and urinary uric acid (UUA) but data are unavailable for EC enzymes. This study compared the effectiveness and safety of a relatively large dose (patient's usual dose) versus a small dose (1/4 usual dose) of EC enzymes in nine nourished children with CF, regarding decreasing fecal fat and stool nitrogen losses and maintaining normal SU and UUA concentrations. A crossover study design randomly assigned large or small doses to two consecutive 7 day treatment periods within each child. Large doses of EC enzymes reduced steatorrhea and increased SU and UUA. SU was normal with both treatments and UUA was normal, i.e., 17 of 18 values were between the 10th and 95th percentiles for healthy children eating a normal diet. When fat excretion was greater than 10% with small doses of EC enzymes, large doses resulted in reduced fat excretion and normal UUA. These data suggest that large doses of EC enzymes reduce steatorrhea and are safe in patients who have malabsorbtion with small doses.

Bronchodilator responsiveness in infants with bronchiolitis.

We evaluated 34 infants with bronchiolitis, (17 of both genders; mean age, 4.6 mos; ranges, 0.7-14.5 mos). The 20 inpatients were significantly younger than the 14 outpatients (2.6 vs. 8.2 months, P < 0.05), and more females were inpatients. Forced expiratory flows at functional residual capacity (VmaxFRC) were obtained at baseline, after aerosolized normal saline (NS), and metaproterenol (0.025 mL/kg in 2 mL NS). Flows were expressed as Z-scores, the difference between the measured and predicted flows, divided by the standard deviation for the predicted value. At baseline, outpatients were more obstructed than inpatients (-1.64 vs. -0.95, P < 0.05), infants > 2 months old were more obstructed than infants < or = 2 months old (-1.54 vs. -0.80, P < 0.05), and males more than females (-1.45 vs. -1.02, P < 0.05). Following NS the whole group had a small but significant decrease in Z-scores (-1.23 to -1.31, P < 0.05). Following metaproterenol, the younger infants had significantly (P < 0.05) higher Z-scores compared to baseline and NS (-0.80 vs. -0.86 vs. -0.59). However, no significant changes occurred in older infants. Females also had an increased flow after metaproterenol and were less obstructed than after NS (-1.11 vs. -0.86, P < 0.015). In males no increased flows occurred after metaproterenol (-1.45 vs. -1.48). Bronchodilator responsiveness did not relate to severity of airway obstruction, history of family asthma, allergy, or passive smoke exposure. We conclude that inhaled metaproterenol improves airway function in a subgroup of infants with bronchiolitis, but the subgroup could not clearly be identified because age and gender were confounding factors.

Infants with cystic fibrosis: pulmonary function at diagnosis.

Meconium ileus (MEC), failure to thrive (FTT), and a combination of FTT and pulmonary symptoms (COMB) are the most frequent symptoms of cystic fibrosis (CF) at the time of diagnosis. The purpose of this study was to compare to normal controls (NC) the pulmonary function of CF infants at the time of diagnosis, when grouped by these symptoms. The measurements of pulmonary function included oxygen saturation (SaO2), functional residual capacity (FRC), mixing index (MI), total respiratory system compliance (Crs), and maximal flow at FRC (VmaxFRC). Compared to NC (n = 33), the MEC group (n = 5) had a higher MI (54 vs. 42%) and no difference in SaO2, Crs or VmaxFRC. There were no significant differences between FTT (n = 8) and NC groups although there was a tendency for Crs to be lower in the FTT group (5.1 vs. 6.8 ml/cm H2O). When compared to all other groups, the COMB group (n = 11) had significantly lower SaO2, MI, Crs, and VmaxFRC. The normal lung function in the MEC group is consistent with the normal anatomy reported in CF infants dying secondary to meconium ileus. Longitudinal evaluation of the infants in this study, following initiation of care as patients with a diagnosis of CF, may allow us to determine whether symptoms at diagnosis remain an important determinant of lung function in infancy.

Lower respiratory illness in infants and young children with cystic fibrosis: evaluation of treatment with intravenous hydrocortisone.

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 beta-agonist with cromolyn. Functional residual capacity (FRC) and forced expiratory flows (V'mak,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. Upon admission flows were decreased, and FRC was increased in both groups; there were no differences between the groups. The change in pulmonary function from admission to Day 10 of hospitalization was not different for the two groups. From admission to outpatient follow-up after hospitalization, there was a significant increase in flows for the steroid group, but not for the placebo group. In addition, the direction of change in FRC was significantly different for the two groups; the steroid group had a small decrease in FRC, while the placebo group had a small increase in FRC. These findings suggest that the addition of intravenous hydrocortisone to the standard treatment of CF infants hospitalized for a LRI may produce a greater or a more sustained improvement in lung function following hospitalization.

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

The cytokines tumor necrosis factor-alpha (TNF-alpha), 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-alpha 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-alpha 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-alpha and IL-8 are not increased during acute exacerbations of pulmonary inflammation.

Magnetic resonance imaging of inflammatory lung disorders: preliminary studies in children.

Magnetic resonance(MR) scans were performed on 14 children with a variety of inflammatory disorders of the lungs. MR successfully identified disease in all of the children and accurately localized the disease within the lung fields. In patients with pneumonia and lung abscesses the acute inflammation was associated with a marked increase in signal intensity on T2 when compared with T1 weighted images. One patient with an inflammatory pseudotumor demonstrated a smaller increase in signal intensity on T2 weighted images than was seen in acute pneumonia. Abscess cavities were well identified along with the wall thickness. In patients with diffuse lung disease (diffuse histoplasmosis, miliary tuberculosis, Letterer-Siwe disease, and allergic alveolitis), each disease appeared different on the MR images. These preliminary studies indicate that magnetic resonance imaging is effective for identifying pulmonary disease in children and may improve the radiologist's ability to differentiate pulmonary disorders.

Effect of smaller droplet size of dornase alfa on lung function in mild cystic fibrosis. Dornase Alfa Nebulizer Group.

Aerosolized recombinant human DNase (dornase alfa) reduces mucus viscoelasticity in vitro and improves pulmonary function in patients with cystic fibrosis (CF). We postulated that if dornase alfa could be delivered more peripherally to small airways in the lung in the form of smaller aerosol droplets in patients with early airway obstruction, the increase in pulmonary function from baseline might be improved. CF patients (n = 749) with mild lung disease (baseline forced vital capacity > or = 70% predicted) were randomly assigned to receive dornase alfa 2.5 mg daily for 2 weeks by one of two nebulizer systems: 1) the Medic-Aid Durable SideStream nebulizer powered by the MobilAire Compressor (SS/MA) producing a droplet size with a mass median aerodynamic diameter (MMAD) of 2.1 microm; or 2) the Hudson T Up-draft nebulizer with a DeVilbiss Pulmo-Aide compressor (HT/PA) with an MMAD of 4.9 microm. Spirometry was performed at baseline and following 14 days of treatment. Dornase alfa delivered by both nebulizer systems produced small but statistically significant improvements in pulmonary function compared with baseline. There was a trend (P = 0.06) toward greater improvement in forced expiratory flow in 1 s in the SS/MA group (4.3%) compared with the HT/PA group (2.5%). These results indicate that the short-term spirometric response to dornase alfa is influenced in part by the physical characteristics of the aerosol in patients with mild lung disease. We speculate that this may be true for other therapeutic aerosols, and it appears that localization of disease in the lung plays a role in the response to inhaled agents.

Effectiveness of enteric coated pancreatic enzymes given before meals in reducing steatorrhea in children with cystic fibrosis.

In vitro data indicate that length of enzyme incubation with food critically affects enzyme dissolution and presumably effectiveness. This study compared the effectiveness of enteric coated (EC) pancreatic enzymes given before meals with those given during meals (15 minutes after beginning of meal) in reducing steatorrhea in well-nourished children with cystic fibrosis. Eight children (6 years 11 months old to 14 years 7 months old) were studied in the General Clinical Research Center at Indiana University Hospital, Indianapolis. A crossover study design randomly assigned enzymes before or during meals during two consecutive 7-day treatment periods for each child. No difference in fat excretion was documented for the total group when the children who took enzymes before meals were compared with those who took enzymes during meals. However, a stepwise multiple regression analysis of the difference (before minus during) in fat excretion on sex, age, enzyme number, and treatment order documented a positive correlation of age with fat excretion (r = .83). Mean fat excretion in younger children (less than 10 years old) decreased significantly when enzymes were given before meals (7.14 +/- 1.95%) rather than during meals (9.92 +/- 1.61%) (P = .004). The difference in fat excretion (mean = 2.78 +/- 0.55%, range = 1.4% to 4%) translates into a half to one full year's growth potential. Younger children with cystic fibrosis may benefit clinically from taking EC enzymes before meals.