Immunohistologic quantification of Pseudomonas aeruginosa in the tracheobronchial tree from patients with cystic fibrosis.

Pseudomonas aeruginosa has been recognized as a pathogen of major importance in the patient with cystic fibrosis (CF). However, no information is available regarding the histologic quantification of P. aeruginosa organisms in the CF tracheobronchial tree. We retrieved all formalin-fixed paraffin-embedded lung blocks from 20 consecutive autopsies of cystic fibrosis patients. Serial histologic sections were made and stained by three methods: hematoxylin and eosin, immunoperoxidase with anti-P. aeruginosa rabbit serum as the primary antibody, and immunoperoxidase with normal rabbit serum as the primary antibody. By studying the hematoxylin and eosin section, we classified five areas in the lung as bronchi, large bronchioles, small bronchioles, bronchioloectatic areas, and abscess/airways with destroyed epithelium. The areas stained by an anti-P. aeruginosa immunoperoxidase method were examined under high-power magnification, and the bacteria within random fields were counted. Pseudomonas aeruginosa organisms were identified in 14 of 20 cases, including 13 of 16 cases in which P. aeruginosa was specifically cultured at autopsy. Quantification of organisms within the lumens of all five airway types showed that the bacterial density in cystic fibrosis airways is highest in bronchi.

A novel mutation in the cystic fibrosis gene in patients with pulmonary disease but normal sweat chloride concentrations.

BACKGROUND: Many patients with chronic pulmonary disease similar to that seen in cystic fibrosis have normal (or nondiagnostic) sweat chloride values. It has been difficult to make the diagnosis of cystic fibrosis in these patients because no associated mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene has been identified. METHODS: We evaluated 23 patients with pulmonary disease characteristic of cystic fibrosis but with sweat chloride concentrations in the normal range. Mutations in the CFTR gene were sought by direct sequencing of polymerase chain reaction-amplified nasal epithelial messenger RNA and by testing the functioning of affected epithelium. RESULTS: A cytidine phosphate guanosine dinucleotide C-to-T point mutation in intron 19 of the CFTR gene, termed 3849 + 10 kb C to T, was identified in 13 patients from eight unrelated families. This mutation was found in patients from three different ethnic groups with three different extended haplotypes. The mutation leads to the creation of a partially active splice site in intron 19 and to the insertion into most CFTR transcripts of a new 84-base-pair "exon," containing an in-frame stop codon, between exons 19 and 20. Normally spliced transcripts were also detected at a level approximately 8 percent of that found in normal subjects. This mutation is associated with abnormal nasal epithelial and sweat acinar epithelial function. CONCLUSIONS: We have identified a point mutation in intron 19 of CFTR and abnormal epithelial function in patients who have cystic fibrosis-like lung disease but normal sweat chloride values. The identification of this mutation indicates that this syndrome is a form of cystic fibrosis. Screening for the mutation should prove diagnostically useful in this population of patients.

Stability and change in the psychological adjustment of mothers of children and adolescents with cystic fibrosis and sickle cell disease.

Found moderate stability in the classification of maternal adjustment in two longitudinal studies of mothers of children and adolescents with cystic fibrosis and sickle cell disease. In terms of the transactional stress and coping model, stable poor maternal adjustment was associated with higher levels of appraisal of daily stress and palliative coping and low levels of family supportiveness. With initial levels of maternal adjustment, demographic parameters, and follow-up interval controlled, concurrent levels of daily stress accounted for significant portions of variance in maternal adjustment at follow-up for both illness groups. In addition, illness severity, child psychological adjustment, and family conflict added significant increments to maternal adjustment at follow-up in the cystic fibrosis group. Findings are discussed in terms of a basis for subsequent intervention studies to enhance the adjustment of mothers of children with chronic illness.

Change over a 12-month period in the psychological adjustment of children and adolescents with cystic fibrosis.

Found that group rates of mother-reported and child-reported adjustment problems remained relatively constant over initial and 12-month follow-up assessment points. However, there was less stability in the classification of the adjustment of individuals, in specific behavior problem patterns and diagnoses, and in child-reported adjustment than in mother-reported adjustment. With initial level of child adjustment controlled, children's perceptions of self-worth accounted for a significant increment in child-reported symptoms and mother-reported adjustment at follow-up. Maternal distress also accounted for a significant increment in child-reported symptoms. These findings add support for the role of maternal adjustment and child self-worth in the adjustment of children with cystic fibrosis.

Allergic bronchopulmonary aspergillosis in patients with cystic fibrosis.

In order to determine the incidence of allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis (CF), we reviewed the records of 236 patients followed up at the Duke CF Center. Sixty patients (25 percent) had colonies of Aspergillus fumigatus. These patients were older and had more severe disease as assessed by lower Shwachman-Kulczycki (S-K) scores than the patients who did not have evidence of A fumigatus. In 15 of the patients with A fumigatus (6.5 percent of the total population), the diagnosis was ABPA. Age and S-K scores were not significantly different from those of the patients with A fumigatus without ABPA. Diagnostic features of the affected patients included wheezing refractory to bronchodilator therapy, persistent pulmonary infiltrates, peripheral eosinophilia, positive skin reactivity to an A fumigatus antigen and elevated total serum IgE levels. Steroid therapy was started for all patients, and clinical improvement was noted within 1 month as evidenced by decreased symptoms and weight gain. Chest x-ray films usually showed improvement. Vital capacity improved in all but two patients. Total IgE did not consistently decrease in response to therapy. Although the diagnosis of ABPA may be difficult to establish, ABPA commonly is associated with CF. Most patients respond to steroid therapy; however, the effect of therapy on the course of the disease is difficult to assess.

Psychological adjustment of children with cystic fibrosis: the role of child cognitive processes and maternal adjustment.

Found 60% of children 7-12 years old with cystic fibrosis to have a parent-reported behavior problem and 62% met the criteria for a DSM-III diagnosis based on a structured clinical interview with the child. Mixed internal and external behavior problem patterns and diagnoses of anxiety and oppositional disorder were most frequent. Support was provided for the hypothesized psycho-social/mediational roles of child perception of self-worth and maternal anxiety in child adjustment. Together, the variables of the transactional stress and coping model accounted for 39 and 43% of the variance in mother-reported internalizing and externalizing behavior problems and for 68% of the variance in child-reported problems.

Long-term outcome of pediatric sarcoidosis with emphasis on pulmonary status.

Sixty-one pediatric and adolescent patients (age < or = 16 years) with sarcoidosis proved by biopsy specimen were identified during the period 1957 to 1976; 19 patients with elapsed time from diagnosis of 8 to 35 years (mean, 21 years) were reexamined in 1985. Age at onset of disease ranged from 4 to 16 years (mean, 12.5 years). Sex distribution was equal; 68 percent of individuals were black. At follow-up, clinical evaluation, chest roentgenograms, pulmonary function tests, electrocardiograms (ECGs), echocardiograms (ECHO), and angiotensin-converting enzyme (ACE) activity were performed on each subject. In addition, complete blood cell counts, erythrocyte sedimentation rates, serum calcium, immunoglobulin levels, B- and T-cell enumerations, and intradermal skin tests for delayed hypersensitivity were also obtained. Although all initial pediatric chest roentgenograms were abnormal, at follow-up only 37 percent were abnormal. Pulmonary function test results were available for ten children, and 90 percent were decreased. In 1985, 68 percent of the adults had abnormal lung function; furthermore, eight patients had reduced diffusing capacities, one had hypoxemia, and two had elevated ACE activity. Specific abnormalities were noted on two ECGs and 12 ECHOs. One individual had an elevated sedimentation rate, while another had an increased serum calcium level. Six patients had elevated IgA values, two had elevated IgM values, and two had depressed IgM values; IgG values were normal in all subjects. B- and T-cell percentages were unremarkable in all patients tested. Four individuals were anergic to skin test antigens. Long-term pulmonary morbidity was observed in four patients; in addition, one of these and four others suffered nonpulmonary sequelae. These results are in agreement with those of other investigators, but insufficient data still exist on the long-term effects of sarcoidosis on the pediatric host.

Stress, coping, and family functioning in the psychological adjustment of mothers of children and adolescents with cystic fibrosis.

Assessed the role of illness parameters, demographic parameters, and hypothesized psychosocial/mediational processes in the psychological adjustment of 68 mothers of children and adolescents (7-17 years of age) with cystic fibrosis. Together the illness and demographic parameters accounted for only 13-15% of the variance in maternal adjustment. However, the hypothesized mediational processes accounted for 35-40% increment in the variance in maternal adjustment. More specifically, maternal adjustment was associated with lower levels of perceived daily stress, less use of palliative coping methods, and family functioning characterized by high levels of supportiveness.

Coexisting endogenous lipoid pneumonia, cholesterol granulomas, and pulmonary alveolar proteinosis in a pediatric population: a clinical, radiographic, and pathologic correlation.

Benign pulmonary diseases that have been associated with the accumulation of endogenous lipids within the alveoli, bronchioles, and interstitial tissues include endogenous lipoid pneumonia (ELP), pulmonary alveolar proteinosis (PAP), pulmonary interstitial and intra-alveolar cholesterol granulomas (PICG), various xanthomatous lesions, and malakoplakia. In ELP, fat-filled finely vacuolated macrophages fill the alveoli. In PAP, the aveoli become filled with cholesterol and periodic acid-Schiff (PAS)-positive acellular debris. In PICG, cholesterol esters are released from degenerating macrophages and, as organization occurs, the cholesterol is deposited in the form of acicular clefts within the interstitium. These morphologically distinct presentations of endogenous lipid deposition within the lung have long been thought to represent unique disease processes but several authors now postulate a possible relationship between these entities. We report here on the clinical, radiographic, and morphologic findings in eight pediatric patients with diverse primary disease processes who were subsequently found to have varying and often coexisting degrees of ELP, PAP, and PICG.

The role of biomedical and psychosocial processes in the intellectual and academic functioning of children and adolescents with cystic fibrosis.

This study found intellectual and academic functioning of 76 children and adolescents with cystic fibrosis to be normally distributed. Intellectual functioning was related inversely to age, and both intellectual and academic functioning were related directly to socioeconomic status. Medical status did not add a significant increment in the amount of variance in intellectual and academic functioning accounted for by age and socioeconomic status.

Ultrastructural morphology of the lung in cystic fibrosis.

Cystic fibrosis (CF) is the most common lethal genetic disease among Caucasians, with much of the morbidity and most of the mortality related to pulmonary complications. The underlying defect in this disease has yet to be precisely defined, so it is somewhat surprising that a comprehensive study of the ultrastructural morphology of the lung in CF has not heretofore been reported. We used transmission electron microscopy to examine the small airways in 15 patients who had died of CF, and compared the findings with 15 disease controls with non-CF chronic airways disease and 15 patients with normal lung morphology. The lung parenchyma was also examined ultrastructurally in 7 patients with CF, 4 disease controls, and 4 normal lung cases. In addition, the literature regarding the ultrastructural morphology of the large airways in CF was reviewed. Patients with CF showed non-specific ciliary abnormalities, hyperplasia of mucous cells, increased numbers of pulmonary neuroendocrine and indeterminate cells, degeneration and sloughing of epithelial cells, and colonization of bacteria of the mucous layer of the small airways when compared with normal controls. Alveoli showed non-specific injury and regeneration of type II pneumocytes. However, these changes were all similar to those observed in the disease controls. Specifically, no cellular or subcellular ultrastructural abnormality unique to CF was observed. It is probable that the most useful ultrastructural approach to the lung in CF in future studies will involve X-ray microanalytical studies of ionic composition using cryotechniques.

Risk factors for the development of posterior subcapsular cataracts in patients with cystic fibrosis and allergic bronchopulmonary aspergillosis treated with corticosteroids.

Posterior subcapsular cataracts (PSCC) occur in a high percentage of patients treated with long-term systemic corticosteroids (Naumann Gott, Apple DJ, eds: Pathology of the Eye. New York: Springer-Verlag, 1986). Fifteen patients with cystic fibrosis treated at Duke University Medical Center between January 1982 and October 1987 required prednisone for treatment of allergic bronchopulmonary aspergillosis (ABPA). Two of these patients (13.3%) were noted to have PSCC during prednisone therapy. We retrospectively examined factors associated with steroid administration that may have been predictive of the development of PSCC in these patients including: 1) steroid therapy for longer than 2 years, 2) steroid dose of 10 mg/day or greater for longer than 6 months, 3) steroid dose of 40 mg/day or greater for longer than 2 months, and 4) change in linear growth pattern during steroid therapy. None of these factors predicted the risk of developing PSCC. Therefore, we recommend that all patients with cystic fibrosis who receive steroids for the treatment of a concomitant condition such as ABPA should undergo careful examination for opacities of the ocular lens at each clinical visit regardless of the duration or dose of steroids.