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This study tested the efficacy of the Cystic Fibrosis Family Education Program, a cystic fibrosis self-management program, on improving participants' knowledge, self-efficacy, self-management behavior, health, and quality of life. A quasi-experimental pretest-posttest nonequivalent comparison group design was employed. Participants made up 104 patient-primary caregiver dyads from the intervention site cystic fibrosis center and 95 from the usual care comparison center. The intervention, a self-paced print curriculum based on social cognitive theory, targeted behavioral capability, self-efficacy, and outcome expectations and was implemented as an integral part of medical care. Parents, early childhood, middle childhood, and adolescents received separate materials on respiratory, nutrition and malabsorption, communication, and coping issues. Significant intervention effects were found on the knowledge scores for caregivers, adolescents, and children; caregiver and adolescent total self-management scores; Child Behavior Checklist total score; one parent coping scale score; the modified NIH score; NIH pulmonary factor 1; and the Brasfield total score. Significant interaction effects were evident in the self-efficacy scores for caregivers and children. [ABSTRACT FROM AUTHOR]

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Background: The nationwide decline in pediatric admissions to community hospitals threatens the sustainability of small pediatric residency programs. Little is known about the response of small programs to this challenge., Objectives: We report on the design and evaluation of an innovative, collaborative model for pediatric inpatient training between an academic community medical center and a children's hospital., Methods: We describe the operational, academic, and financial features of the model. Outcome measures include patient volume and subspecialty mix, resident and faculty perceptions as reported in an anonymous survey, and Accreditation Council for Graduate Medical Education Residency Review Committee (RRC) review., Results: In 2003, Albert Einstein Medical Center (Einstein) closed its pediatric inpatient unit and established an independent teaching service at St Christopher's Hospital for Children (St Christopher's) in Philadelphia, Pennsylvania. Under the new model, patient volume and subspecialty mix more than tripled. Einstein residents and faculty identified 5 major strengths: level of responsibility and decision making, caring for medically complex children, quality of teaching, teamwork, and opportunity to participate in academic activities at a children's hospital. St Christopher's leadership reported increased volume, no disruption of their residency program, and no dilution of clinical teaching material. The Einstein program was reaccredited by the RRC in 2006 for 2 years and in 2009 for 4 years., Conclusion: A collaborative model for inpatient training was successful in maintaining a community hospital-based pediatric residency program. Positive outcomes were documented for the residency program, the parent community hospital, and the collaborating children's hospital.

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The clinical characteristics most relevant to the decision to treat for a pulmonary exacerbation with antibiotics in cystic fibrosis patients were determined. Variables including age, increased cough frequency and sputum production, new crackles and wheezing, asthma, symptomatic sinusitis, hemoptysis, decreased lung function, weight loss, and new acquisition of Pseudomonas aeruginosa were collected in a large prospective multicenter database (Epidemiologic Study of Cystic Fibrosis). During a 12-month baseline period, data from 11692 patients were compared with data collected during the subsequent 6-month study period. Because pulmonary function assessments were unavailable for patients <6 years of age, separate analyses were done for those <6 and >or=6 years of age. The outcome of interest was any antibiotic treatment in the 6-month study period reported as indicated for an exacerbation. Characteristics with the most discriminatory power were determined using stepwise multiple logistic regression. For patients <6 years of age, the strongest independent associations with treatment for a pulmonary exacerbation were new crackles, increased cough frequency, decline in weight, and increased sputum production. For those patients >or=6 years of age, the strongest independent associations were a relative decrease in percent predicted forced expired volume in 1 sec, increased cough frequency, new crackles, and hemoptysis. The presence of three or more of these key characteristics was strongly associated with the occurrence of a treated exacerbation. The reproducibility of the model over time was confirmed by application to a subsequent set of data. This model has potential for use as an outcome measure in clinical trials, and to assist in treatment decisions for individual patients., (Copyright 2004 Wiely-Liss, Inc.)

Chiari type I malformation is characterized by herniation of the cerebellar tonsils through the foramen magnum. An association between Chiari type I malformation and cystic fibrosis (CF) has not previously been established. We report on five children and adolescents with CF in whom Chiari type I malformations were diagnosed. Three patients were 17-18 years old at time of diagnosis, one was 3 years old, and one was 10 months of age. All patients were followed at the Cystic Fibrosis Center at St. Christopher's Hospital for Children and were diagnosed with the malformations between June 1988 and June 1997. Over this same period, 400 CF patients 18 years or younger were followed routinely. All patients had the diagnosis of Chiari type I confirmed by brain-stem MRI. Neurologic findings included swallowing dysfunction, syncopal episodes, numbness of extremities, recurrent vomiting, and headaches. No two patients had the same presenting neurologic findings. Our data suggest that Chiari type I malformation is more common in CF than in the general population. The possibility of Chiari type I malformation should be included in the differential diagnosis of unexplained neurologic complaints in patients with CF., (Copyright 2000 Wiley-Liss, Inc.)

The number of patients with cystic fibrosis (CF) whose sputum culture has yielded Stenotrophomonas maltophilia has increased in the last 5 years at St. Christopher's Hospital for Children. We conducted a case-control study to determine risk factors for recovery of S. maltophilia in respiratory secretions from patients with CF. We reviewed the outpatient and inpatient records of patients colonized with S. maltophilia between 1993 and 1997, and of age-matched (at time of initial recovery of S. maltophilia) control patients with CF who had never had a positive sputum culture for S. maltophilia. Variables included age at time of CF diagnosis, gender, severity of CF (based on Shwachman-Kulczycki (S-K) scores and spirometry), frequency of hospitalizations, use of oral, intravenous, or inhaled antibiotics, and use of oral or inhaled corticosteroids in the 2 years prior to the first isolation of S. maltophilia from respiratory secretions. Statistical methods included stepwise logistic regression to determine risk factors for acquisition of S. maltophilia. During the study period, 58 patients with CF had a positive sputum or deep throat culture for S. maltophilia. The distribution of S. maltophilia acquisition by year increased from 7 patients in 1993 (incidence, 2.8%) to 16 in 1997 (incidence, 6.2%). Patients positive for S. maltophilia were found to have significantly worse growth parameters, S-K score, and spirometric values than S. maltophilia-negative CF controls (P < 0.05). Stepwise logistic regression demonstrated that treatment with long-term antibiotics (P = 0.0016) and number of days of intravenous antibiotic therapy (P = 0.035) were significant risk factors for S. maltophilia colonization in our group of CF patients. We conclude that patients with CF whose respiratory secretions yield S. maltophilia have an overall worse clinical status at the time of initial S. maltophilia isolation than noncolonized patients, and that preceding treatment with antibiotics may have predisposed them to the acquisition of this bacterium in their respiratory secretions., (Copyright 2000 Wiley-Liss, Inc.)

Cystic fibrosis (CF) is a chronic, progressive, genetic disease caused by flawed ion transport across epithelial membranes due to a genetic mutation. Most therapeutic efforts are centred on the main clinical manifestations of the disease: progressive destructive airway disease and pancreatic insufficiency. Most individuals with CF succumb to lung disease. The present-day therapeutic armamentarium includes agents that have been used for many decades, some of which have experienced transformations in their formulation or mode of administration thanks to the introduction of new manufacturing technologies. The development of new therapies involves new conceptual approaches, based on recent understanding of the disease. These therapies await proof of concept or clinical experimentation before being accepted as useful means to arrest the progression of the disease. In this article we will review therapeutic agents introduced into the clinical arsenal in the last 20 years, as well as experimental therapies under active investigation.

This report characterizes patterns of evaluation and monitoring of the health status of patients with cystic fibrosis (CF) as observed in the Epidemiologic Study of Cystic Fibrosis (ESCF), and compares these practices to published guidelines. All patients (18,411) who enrolled in ESCF at 194 study sites in the United States and Canada from December 1, 1993 to December 31, 1995 were considered for study. Patients enrolled before January 1, 1995 with >/=1 healthcare encounters during 1995 (12,631) were included in the analysis. Patients enrolled after January 1, 1995 (5,266), or who died (354), withdrew from the study (128), or were lost to follow-up (21) were excluded. Frequency of encounters (outpatient and hospital), spirometry, respiratory tract cultures, and chest radiographs were recorded during a 1-year period (1995) and analyzed by gender, age, severity of lung disease, and presence of any Pseudomonas species in the respiratory tract. The 12,631 patients had 53,024 outpatient visits. In 57.5% of patients, the recommended criteria of >/=4 total visits per year were met. Only 27.4% of all patients had >/=4 routine visits; 3.1% had only sick visits, and 59.0% had no sick visits. One third (34.6%) were hospitalized at least once, for a total of 8,561 hospitalizations. Older patients with lower pulmonary function and Pseudomonas in their respiratory tract had fewer routine visits and more sick visits, and were hospitalized more than were younger patients. In three fourths (75.8%) of patients the recommended criterion of two spirometry assessments per year was met, whereas in 79.3% the criterion of one culture was met, and in 68.3% the criterion of one radiograph/year was met. We conclude that in the majority of CF patients, the recommended criteria for routine evaluation and monitoring were met. However, in a rather substantial number they were not. An increase in the utilization of healthcare resources was observed in patients with more severe disease. This information will help to establish benchmarks for future quality assessment programs., (Copyright 1999 Wiley-Liss, Inc.)

This report describes the prescribing pattern of therapeutic interventions in the management of patients with cystic fibrosis (CF), as observed in the Epidemiologic Study of Cystic Fibrosis (ESCF). Use of 20 therapies by 12,622 patients was recorded from each health care encounter (53,024 outpatient visits and 8,561 hospitalizations) during a 1-year period (1995), and analyzed by gender, age, severity of lung disease, and presence of any Pseudomonas species in the respiratory tract. The percentage of patients using the following pulmonary therapies was observed (in descending order): airway clearance techniques (88.2%); inhaled bronchodilators (82.2%); oral antibiotics (excluding quinolones) (68. 2%); dornase alfa (52.9%); intravenous antibiotics (34.4%); oral quinolones (34.4%); inhaled antibiotics (34.3%); mast cell stabilizers (29.5%); inhaled corticosteroids (25.9%); oral corticosteroids (17.1%); oral bronchodilators (16.2%); oxygen (8. 1%); inhaled mucolytic agent acetyl cysteine (6.5%); and diuretics (1.4%). The percentage of patients using nutritional therapies was: pancreatic enzymes (96%); oral nutritional supplements (31.1%); enteral nutrition (7.3%); and parenteral nutrition (0.7%). The percentage of patients using other therapies was: nonsteroidal anti-inflammatory drugs (7.9%); and insulin or oral hypoglycemic agents (6.1%). The general trend was for therapies to be used more by older patients, those with lower pulmonary function, and by those with Pseudomonas in their respiratory tract. Exceptions to this trend occurred for airway clearance, oral antibiotics, mast cell stabilizers, and pancreatic enzymes. Four therapies (oral nutritional supplements, parenteral nutrition, diuretics, and pancreatic enzymes) were used more by males than females. However, there was no gender difference for this group of therapies on pulmonary or nutritional status., (Copyright 1999 Wiley-Liss, Inc.)

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., (Copyright 1999 Wiley-Liss, Inc.)

Unlabelled: In older children with cystic fibrosis (CF), well-documented improvements in lung function occur during hospitalization for treatment of pulmonary exacerbations., Objectives: (1) To test the hypothesis that improvement in lung function occurs in infants and toddlers hospitalized because of CF pulmonary exacerbations. (2) To compare changes in lung function measured during forced expiratory flow and tidal breathing., Study Design: Seventeen infants and toddlers with CF were evaluated at the beginning and end of hospitalization by the rapid thoracic compression technique to yield maximal flow at forced residual capacity. Tidal mechanics were measured by the esophageal balloon technique to yield lung conductance and compliance., Results: Lung function improved during the course of hospitalization. The greatest change was observed in measurements of maximal flow at functional residual capacity (.VmaxFRC), increasing from 38.5% +/- 6% predicted (mean +/- SEM) to 59.8% +/- 6% at the end (p < 0.005). Lung conductance (GL) increased from 60% +/- 6% to 78% +/- 8% (p < 0.02); lung compliance (CL) increased from 66% +/- 5% to 75% +/- 5% (p < 0.03). The degree of improvement of .VmaxFRC, GL, and CL was related to baseline measurements; those with poorer pulmonary function at baseline had the greatest degree of improvement during hospitalization., Conclusion: Assessments of airflow obstruction from measurements of .VmaxFRC and GL do not necessarily demonstrate similar findings in a given infant with CF, perhaps because these two techniques measure different physiologic properties. Changes in .VmaxFRC may best reflect the predominant pathophysiology of lung disease in infants and toddlers with CF.

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.

Purpose: Fibrosing colonopathy is a newly described entity seen in children with cystic fibrosis. The radiological hallmarks are foreshortening of the right colon with varying degrees of stricture formation. High-dose enzyme therapy has been implicated as the cause of this process. The purpose of this study is to review the author's experience with evaluation and treatment of these patients., Methods: There are currently 380 patients being treated at our CF center. Fifty-five of these patients have been treated with high-dose enzyme therapy (> 5,000 units of lipase/kg). The medical records of these patients, who are at risk for developing fibrosing colonopathy, were reviewed for the presence of recurrent abdominal complaints, and the work-up and treatment of these symptoms., Results: Chronic complaints of abdominal pain, distension, change in bowel habits, or failure to thrive were present in 24 of the 55 patients treated with high-dose enzymes. So far, 18 of these 24 patients have been evaluated by contrast enema. Thirteen of eighteen have been found to have fibrosing colonopathy characterized by foreshortening and strictures of the colon. Additional findings included focal strictures of the right colon (7 of 13), long segment strictures (5 of 13), and total colonic involvement (1 of 13). Nine patients with the most severe symptoms have undergone colon resection, including five segmental right colectomies, three extended colectomies (ileo-sigmoid anastomosis), and one subtotal colectomy with end-ileostomy. Pathological evaluation has shown submucosal fibrosis, destruction of the muscularis mucosa, and eosinophilia. No postoperative complications or deaths occurred. All nine postoperative patients have noted marked symptomatic improvement. Contrast enema follow-up results are available for six patients, and have documented no recurrent strictures to date. Three of four nonoperative patients have less severe symptoms and are currently being treated conservatively. The other family has refused surgery and the patient is being treated symptomatically., Conclusion: High-dose lipase replacement has been implicated as the etiology for FC and was present in all of our patients. Our cystic fibrosis center now routinely limits lipase to 2,500 U/kg per dose. We recommend the use of the contrast enemas to evaluate at-risk patients who have chronic abdominal complaints or who present with recurrent bowel obstruction. Colon resection should be performed in those with clinically and radiographically significant strictures with the expectation of a good outcome.

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.

Interstitial lung diseases (ILD) are disorders of the lower respiratory tract, characterized by chronic inflammation of the lung parenchyma, varying degree of fibrosis, derangement of the alveolar walls and loss of the functional alveolar capillary units. ILD are relatively uncommon in children. Most of the interstitial lung diseases have no known etiology. In children, common diseases associated with ILD include viral respiratory tract infections (RSV, parainfluenza, etc.), gastroesophageal reflux, idiopathic pulmonary fibrosis, pulmonary hemosiderosis, eosinophilic pneumonia, pneumonitis associated with AIDS, etc. Chronic inflammation of the alveoli (alveolitis), the initial injury in ILD, and several mediators released from inflammatory cells (eosinophils, neutrophils and macrophages) can cause fibrosis and derangement of alveolar walls. Dyspnea and a non-productive cough are the cardinal symptoms of ILD. Other findings include chest pain, hemoptysis and weight loss. Clubbing of fingers occur in approximately 50 per cent of cases. Diagnosis is based on a combination of history, clinical findings, radiographic findings, pulmonary function tests and histologic findings. Open lung biopsy has been very helpful in providing information regarding the extent and nature of the damage, prognosis and response to therapy. There are 3 main aspects in the treatment of ILD. The most important step is to identify and eliminate the cause. The second is suppression of the inflammation. The third is supportive and symptomatic treatment. Corticosteroids are the drugs commonly used for suppression of inflammation. Immunosuppressive drugs (azathioprine, cyclophosphamide) have also been tried. Lung transplantation and heart transplantation have been successfully achieved in selected patients. The results of therapy should be regularly monitored by clinical symptoms, chest radiographs and serial pulmonary function studies.

Objective: The purpose of this review is to familiarize the reader with the genetic aspects, clinical manifestations, diagnostic techniques and management of the primary ciliary dyskinesia syndrome. Further, this article illustrates some unusual features of this syndrome and discusses some speculative hypotheses concerning its pathogenesis and clinical presentation., Data Sources: The bibliography includes references in English as well as some references of historical interest in German. Both human and veterinary literature are quoted. Sources included computerized bibliographic searches of recent literature and reviews of literature., Study Selection: Selection of papers was made based on their historic importance in the definition and characterization of the disease, and on reviews of large bodies of novel or interesting information. Some review papers were not included to avoid repetition., Results: Although the incidence of primary ciliary dyskinesia is low, the inclusion of this condition in the differential diagnosis of chronic and recurrent sinobronchial disease in children and older individuals is very common. Primary ciliary dyskinesia should be suspected in individuals who present chronic respiratory symptoms already in the neonatal period, develop profuse, chronic mucopurulent rhinorrhea, and chronic otitis media and sinusitis. Chronic cough, obstructive lung disease, and bronchorrhea associated with the aforementioned manifestations should also make clinicians suspect this syndrome. Male sterility is almost universally present and situs inversus is present in 50% of affected persons. The diagnosis of primary ciliary dyskinesia is clinical and is confirmed by studies of ciliary motility and ultrastructure of the respiratory mucosa. Management is directed to microbial suppression by frequent antibiotic administration, and to clearing of retained secretions., Conclusions: The diagnosis of primary ciliary dyskinesia requires familiarity with the clinical picture and the specific techniques of identification. Although the basic mechanism of disease is known, the molecular genetics of primary ciliary dyskinesia and the causes for the phenotypic variability remain to be explained. Future research should be directed to the identification of the gene(s) responsible for the manifestations of the disease and to effective methods of activation, in vivo, of dysfunctional cilia.

Continuous positive airway pressure (CPAP) has been used in the treatment of infants with tracheobronchomalacia (TBM). However, the effects of CPAP on lung mechanics in these infants are unknown. We hypothesized that CPAP prevents airway collapse and improves forced exhalation. We studied respiratory mechanics of nine infants (age 15 +/- 3 mo, SEM) with acquired TBM documented by bronchoscopy, during quiet respiration and forced exhalation, using the esophageal balloon and rapid thoracic compression techniques, respectively. Measurements were made when infants received no CPAP and repeated when 5 and 8 cm H2O CPAP were applied to the airway opening via a modified Mapleson anesthesia circuit. Expiratory resistance (RL), midexpiratory tidal flow (VE50), and maximal flow at functional residual capacity (Vmax FRC) were compared at each level of CPAP. Vmax FRC increased threefold from baseline to 8 cm H2O CPAP (p < 0.005). In contrast, there was no difference in expiratory RL or in VE50 at any level of CPAP. These data suggest that in infants with acquired TBM, assessments of forced expiratory flow reflect the amount of CPAP necessary to prevent airway collapse during forced exhalation better than can measurements of tidal mechanics.

Objective: To determine whether nosocomial transmission of Pseudomonas cepacia occurred at a hospital with endemic P cepacia infection of patients with cystic fibrosis., Design: Two retrospective case-control studies., Setting: A large pediatric cystic fibrosis center., Participants: To assess risk factors for acquisition of P cepacia, 18 cases, defined as any patient with cystic fibrosis with first documented isolation of P cepacia in 1988 or 1989, were compared with 18 matched P cepacia-negative controls with cystic fibrosis. To assess potential modes of nosocomial P cepacia transmission, 14 cases with a hospitalization(s) between their last P cepacia-negative culture and first P cepacia-positive culture were compared with 14 hospitalized P cepacia-negative controls with cystic fibrosis., Methods: Handwiping cultures (N = 68) and selective environmental cultures were performed., Main Results: Cases tended to be more likely than controls to have been hospitalized at the cystic fibrosis center in the 3 months before their first P cepacia-positive culture (P = .08). In addition, cases tended to be more likely than hospitalized controls with cystic fibrosis to have had a P cepacia-positive roommate (P = .06) before becoming colonized with P cepacia organisms. Pseudomonas cepacia was cultured from the hands of two individuals: a P cepacia-colonized patient who had just undergone chest physiotherapy and consequent coughing and the investigator who shook the P cepacia-positive patient's hand after the patient's procedure., Conclusions: These results suggest that in this cystic fibrosis center, hospitalization is a risk factor for P cepacia acquisition and that person-to-person transmission of P cepacia may occur in the hospital via hand contact.

Twenty-one stable hospitalized cystic fibrosis patients with malabsorption syndrome participated in an open-label crossover clinical trial to evaluate the efficacy of two-period dosing regimens of a pancreatic microtablet enzyme preparation in the treatment of steatorrhea. Standard dosing consisted of 500 U lipase/kg body weight/meal, 250 U lipase/kg body weight/snack; high dosing consisted of 1,500 U lipase/kg body weight/meal, 750 U lipase/kg body weight/snack. Doses were determined by units of lipase/kg body weight to provide dosing consistency among patients of varying size. Each patient was on a regular diet of approximately 100 g of fat per day. Two separate, 72-h stool collections were performed between markers. A significant difference in mean percentage fat absorbed between the standard dose and the high dose was found (86% versus 91%, p < 0.05). Subjects were then stratified into two groups, based on the grams of fecal fat eliminated (GFFE) as follows: Group 1 with < or = 7 GFFE/24 h on both dosages (n = 7) and Group 2 with > 7 GFFE/24 h on either dose (n = 14). A significant difference (p < 0.05) between Group 1 (96%) and Group 2 (88%) was noted in the percentage fat absorbed while on the high dose. Fat absorption improved from 81% to 88%, (p < 0.05) in Group 2. During the study period, the adverse reactions of constipation or elevated serum uric acid levels were not observed. The increased doses of pancreatic enzymes resulted in improved correction of steatorrhea.

We examined measurement properties of the NIH Clinical Score for Cystic Fibrosis (CF) as an index of disease status. This score is being employed as a research tool for defining study populations and as an outcome measure, yet there are no published data on its reliability or how its items contribute to the overall measure of disease status. Criteria for scoring some items in the original index lack specificity. In this study, we used a modified score to have more clearly specified criteria, while retaining the original weightings and structure. For 200 patients with CF in two centers, we analyzed the total NIH Score and its subscores for internal consistency, interrater reliability, and factor analysis. Internal consistency indicates how inter-related the items are. The pulmonary subscore and overall score had fairly high internal consistency. However, the general subscore had low internal consistency, suggesting that the items are not measuring a single element of disease status and should not be added. Factor analysis provides additional information on the underlying structure and relationships among items. Five factors (groups of items) were identified accounting for 85% of the consistent variance of 14 items. These factors were designated by items accounting for most of their variance: general pulmonary, weight, disability, psychosocial, and acute infiltrate. While inter-rater reliability for the overall index was high, individual items showed less agreement. The results indicate that most of the variability in the NIH Score is attributable to pulmonary items in the first factor. The analyses suggest a new scoring structure for the NIH Score; the general subscore items do not contribute to the reliability or account for significant variance. Therefore, they will likely require further refinement or be eliminated.

Health care to military dependents with cystic fibrosis (CF) may be compromised by lack of consistency. Civilian centers provide an alternative for care. A reliable count of dependents with CF is unknown. We surveyed 196 military treatment facilities (MTFs) to obtain data on dependents with CF and compared it with data from the National CF Registry. Seventy-seven percent of the MTFs responded and 143 patients were identified. Registry data identified 373 CHAMPUS patients at 82 civilian centers. There were 284 patients in the Registry only and 54 patients in the MTF survey only. Eighty-nine patients were identified through both data sources. A total of 427 patients were identified. Under current CHAMPUS reorganization plans, MTFs will serve as "gateways" for funding of specialized civilian care. Thus, the influx of these and other chronically ill children into the MTF may tax the resources and capabilities of these facilities.

Bronchiolitis is an acute inflammation of the airways. In infancy, it usually results from viral infection, with RSV the most common agent. The clinical syndrome is characterized by symptoms of lower respiratory tract infection and obstruction. In most patients, the duration of illness is 1 week, but bronchiolitis can cause serious morbidity in patients with pre-existing cardiopulmonary disease. In addition, patients may be left with serious sequelae, including PBAR and OB. RSV causes direct damage to airways, but an exaggerated host immune response may contribute to the pathogenesis of airway obstruction in bronchiolitis. The mainstays of therapy include oxygen supplementation and fluid resuscitation, and other modalities remain controversial. There are no studies to support the use of corticosteroids alone in the treatment of bronchiolitis, but several recent reports demonstrate the value of bronchodilator therapy in some patients. Antiviral agents such as ribavirin show great promise in a therapy for bronchiolitis. In addition, ribavirin may modify some aspects of the immune response during acute infection with RSV, and therefore may play a role in the prevention of long-term sequelae.

Chronic endobronchial bacterial infection evokes purulent airway secretions in patients with CF. The viscoelastic properties of these secretions is primarily due to the presence of polymerized DNA from degenerating leukocytes. Recombinant human DNase I (rhDNase) reduces the viscosity of CF sputum in vitro. To test the hypothesis that rhDNase would improve pulmonary function in children and adults with CF, we compared the efficacy and safety of 10-day administration of three doses of aerosolized rhDNase (0.6, 2.5, or 10.0 mg twice daily) in 181 outpatients using a randomized, placebo-controlled parallel design. Forced vital capacity (FVC) improved 10 to 12% (p < 0.05 to 0.001), and forced expiratory volume in one second (FEV1) improved 10 to 15% (p < 0.001) across all doses of rhDNase compared with placebo. The magnitude of effect was dose dependent for both FVC and FEV1 through study Day 21 (p < 0.001). rhDNase was associated with a decreased perception of dyspnea and an improved perception of well-being. No patients developed detectable anti-rhDNase antibodies or bronchial reactivity to rhDNase. Some patients experienced mild upper airway irritation, but no major adverse events were reported. Administration for 10 days of aerosolized rhDNase to pediatric and adult outpatients with CF improves lung function and is well tolerated. Although all three doses were efficacious, the greatest improvement in FEV1 and FEV1/FVC ratio was demonstrated in the 2.5 and 10.0 mg rhDNase treatment groups.

Background: Direct aerosol delivery of aminoglycosides such as tobramycin to the lower airways of patients with cystic fibrosis may control infection with Pseudomonas aeruginosa and improve pulmonary function, with low systemic toxicity. We conducted a randomized crossover study to evaluate the safety and efficacy of aerosolized tobramycin in patients with cystic fibrosis and P. aeruginosa infections., Methods: Seventy-one patients with stable pulmonary status were recruited from seven U.S. centers for the treatment of cystic fibrosis and randomly assigned to one of two crossover regimens. Group 1 received 600 mg of aerosolized tobramycin for 28 days, followed by half-strength physiologic saline (placebo) for two 28-day period. Group 2 received placebo for 28 days, followed by tobramycin for two 28-day periods. Pulmonary function, the density of P. aeruginosa in sputum, ototoxicity, nephrotoxicity, and the emergence of tobramycin-resistant P. aeruginosa were monitored., Results: In the first 28-day period, treatment with tobramycin was associated with an increase in the percentage of the value predicted for forced expiratory volume in one second (9.7 percentage points higher than the value for placebo; P < 0.001), forced vital capacity (6.2 percentage points higher than the value for placebo; P = 0.014), and forced expiratory flow at the midportion of the vital capacity (13.0 percentage points higher than the value for placebo; P < 0.001). A decrease in the density of P. aeruginosa in sputum by a factor of 100 (P < 0.001) was found during all periods of tobramycin administration. Neither ototoxicity nor nephrotoxicity was detected. The frequency of the emergence of tobramycin-resistant bacteria was similar during both tobramycin and placebo administration., Conclusions: The short-term aerosol administration of a high dose of tobramycin in patients with clinically stable cystic fibrosis is an efficacious and safe treatment for endobronchial infection with P. aeruginosa.

Further delineation of a generalized bone dysplasia which we call spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type is presented. This dwarfing condition has several serious complications, with the most common cause of death being spinal cord damage secondary to atlantoaxial instability. It is a heritable condition with an autosomal recessive mode of transmission. Radiologic diagnostic criteria are developed on the basis of studies in 8 patients with the oldest being between 4 and 5 years old. The condition is clinically and radiographically apparent neonatally or in early infancy, and it is probable that all or almost all affected individuals will come to medical attention in the age range screened by this study.

Sipid mediators of inflammation have been implicated in the pathogenesis of Pseudomonas aeruginosa (PA) related pulmonary damage in patients with cystic fibrosis. We studied the role of these mediators in a rat model of PA endobronchitis using essential fatty acid deficient (EFAD) animals. Whole blood from EFAD animals produced significantly less leukotriene B4 (LTB4) and hydroxyheptadecatrienoic acid when stimulated ex vivo than did whole blood from control animals (p less than 0.005). Similarly, lung lavage fluid from EFAD animals infected with PA contained less LTB4 and thromboxane B2 (TXB2) than that from control animals. Despite these differences, cellular infiltration of airways in response to PA infection was virtually identical in animals from the regular diet and the EFAD groups. Both EFAD and control animals had a significant increase in white blood cells (WBC) in lung lavage fluid at 1, 3 and 6 days following infection with PA when compared to animals receiving sterile beads. Localized areas of consolidation and nodularity were grossly evident in the lungs of all PA infected animals irrespective of their ability to generate the lipid inflammatory mediators. Microscopic examination of lung sections demonstrated similar changes in all infected animals. We conclude that LTB4 and TXB2 production occurs early in the course of PA pulmonary infection in rats. This early rise in lipid mediators is temporally associated with an influx of WBC into the airways. However, attenuation of eicosanoid production by use of an EFAD diet does not lead to a reduction in the inflammatory response to PA infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Transition from pediatric to adult health care is fraught with difficulties. On the one hand, the adult care system is not properly prepared to receive patients who are survivors of the so-called childhood disorders. On the other hand, patients and families have difficulty leaving the protective environment created by pediatric caregivers, who in turn may have mixed feelings about letting the patients go. Normalization of development and social adaptation for chronically ill adolescents, however, should include a change in the environment in which health care is received. This article examines some of the issues surrounding transition and transfer from pediatric to adult health care systems and propose some avenues toward implementation of such programs.

The computed tomographic (CT) appearances of a thymolipoma are described in a 5 1/2-year-old girl. The location and CT appearances of the tumor appear to be specific for the diagnosis of thymolipoma.

We obtained maximal partial expiratory flow-volume (PEFV) curves using the rapid compression technique in three infants with intrathoracic tracheomalacia. Maximum flows were quantitated at functional residual capacity (VmaxFRC). Studies were performed at baseline, after inhalation of methacholine (MCh) and after inhalation of albuterol. At baseline, all three patients had significantly lower than normal VmaxFRC values, and two patients displayed expiratory flow limitation during tidal breathing. VmaxFRC improved significantly after MCh administration, but fell back toward or below baseline after albuterol. Additionally, the ratio of forced to tidal flows at mid-tidal volume (Vmid(forced/tidal), a reflection of expiratory flow reserve, increased after MCh administration and decreased after albuterol. Two patients also received oral bethanechol: 2.9 mg/M2, q 8 hr for 10 days, after which PEFV curves were repeated. Both Vmax FRC and Vmid(forced/tidal) were increased over baseline after bethanechol administration, but decreased after albuterol. These results suggest that in patients with abnormally collapsible tracheae, stimulation of tracheal smooth muscle can improve airway stability, thereby increasing forced expiratory flows. Additionally, relaxation of airway smooth muscle by bronchodilators can have the opposite effect and exacerbate obstruction.

Pulmonary hypertension is a relatively common complication of chronic lung disease in children that can cause diminished right ventricular performance (RVP) and, eventually, cor pulmonale and heart failure. Since oxygen may decrease pulmonary artery pressure in these patients, we questioned whether RVP would also improve concomitantly. We evaluated the effect of oxygen on RVP in two young hypoxemic patients by radionuclide angiography. A child with bronchopulmonary dysplasia and cor pulmonale who was not clinically in heart failure had acutely better RVP while breathing oxygen and a further improvement after continuous oxygen therapy for 1 year. In a young adult with cystic fibrosis who was suspected of being in heart failure RVP acutely improved when the FIO2 was increased. We conclude that oxygen may improve RVP in hypoxemic patients and speculate that the observation of such improvement may be valuable for the early detection of patients who can benefit from long-term oxygen therapy.

Possible mechanisms of transmission of Pseudomonas cepacia in hospitalized patients with cystic fibrosis were examined. Twelve patients were colonized with P. cepacia prior to admission (group 1), and 15 patients were not (group 2). Daily contact occurred between both groups. Sputum cultures were obtained from all patients at admission and discharge, and 3 and 6 months after discharge in group 2 patients. Environmental cultures included cough plates, settle plates, spirometry tubing, stethoscopes, sinks, wall outlets, and hands of patients, physicians, nurses, and respiratory therapists. Specimens were plated on a P. cepacia-selective medium. All group 1 patients remained colonized with P. cepacia at discharge. None of the group 2 patients acquired P. cepacia during hospitalization or follow-up. P. cepacia was recovered from three of 151 environmental cultures; two of these were presumably patient related. P. cepacia contamination of pulmonary function equipment, wall outlets, hands, and stethoscopes was not documented. We conclude that transient aerosol environmental contamination is uncommon and restricted to the immediate patient environment.

The medical records of 142 patients with cystic fibrosis were reviewed. The patient group included 78 males and 64 females; three patients were black. Periods of observation ranged from two to 25 years (mean, 14.5 years). The analysis focused on clinical evaluation at age 18 years and included information gained at an earlier age. Evaluation at age 18 years was based on Shwachman and Kulczycki's (S-K) scoring system, Brasfield chest roentgenographic scoring system, pulmonary function measurements, height-adjusted weight percentile, sputum bacteriologic results, number of hospitalizations for treatment of pulmonary infections prior to the age of 18 years, time of onset of clubbing, and frequency of complications. There were no significant differences between the sexes in clinical features. Median survival from the time of diagnosis to the conclusion of the study period (1955 to 1984) was 22 years for females and 25 years for males (NS). Median length of survival beyond the age of 18 years was eight years for females and 12 years for males (NS). Stepwise logistic regression and Cox regression analysis applied to 11 variables identified the S-K clinical score at 18 years of age as the best predictor of survival to the age of 23 years. The median durations of survival after the age of 18 years for patients with clinical scores of 30 to 49, 50 to 64, and 65 to 75 at age 18 were five, seven and a half, and 12 years, respectively (p less than 0.0001). Low clinical score, low weight percentile, and Pseudomonas cepacia colonization of the lower respiratory tract at the age of 18 years indicated a poor prognosis. On the other hand, high clinical score, good weight percentile, and colonization with Staphylococcus aureus alone were likely to be found in patients with mild disease and an increased likelihood of long-term survival with preserved pancreatic function.

Abnormalities of the interaction between alpha 2-macroglobulin and proteases have been suspected in cystic fibrosis. We measured the binding activity for trypsin of alpha 2-macroglobulin in 65 patients with cystic fibrosis, 41 obligate heterozygotes for cystic fibrosis, 18 children with asthma, 21 adult patients with chronic obstructive pulmonary disease, and 21 healthy control subjects. The assay was based on the observation that, once it is bound to alpha 2-macroglobulin, trypsin is no longer inhibited by soybean trypsin inhibitor. The bound trypsin retains activity against synthetic substrates such as N-alpha-benzoyl-arginine-p-nitroanilide. We found a moderately increased molar binding ratio of trypsin to alpha 2-macroglobulin in all patient groups and heterozygotes compared to healthy control subjects. The absolute concentration of alpha 1-macroglobulin was related to age rather than to the disease of the patient. Our data argue against a defect in protease-binding activity of alpha 2-macroglobulin in cystic fibrosis. The moderately increased binding activity observed could have been related to a structural difference in alpha 2-macroglobulin or to binding of ligands. This finding however, was not unique to patients with cystic fibrosis; the binding activity was increased in heterozygotes and in patients with other pulmonary diseases.

A 9-year-old with immunodeficiency developed a severe, diffuse respiratory illness that necessitated mechanical ventilation. Open lung biopsy revealed Respiratory Syncytial Virus (RSV) as the sole pathogen. RSV detection should be included in the differential diagnosis of diffuse lung disease in an immunocompromised child.