Cystic fibrosis in three children with bronchopulmonary dysplasia.

Cystic fibrosis (CF) and bronchopulmonary dysplasia (BPD) are two common causes of chronic lung disease in children. Patients with BPD or CF often have recurrent respiratory symptoms, failure to thrive, and/or metabolic alkalosis during infancy and childhood. Thus, recognizing the diagnosis of CF in an infant with BPD can be difficult. We present three infants with both BPD and CF. The infants shared a history of respiratory distress and prolonged oxygen requirements. All three also had difficulty gaining weight, even after pancreatic enzyme supplementation was instituted. Metabolic alkalosis was observed in two infants. Previous studies in children with CF suggest that early diagnosis may impact both lung health and nutritional status. A high index of suspicion is necessary for clinicians to identify these children early and intervene with appropriate therapy.

Airway complications following pediatric lung and heart-lung transplantation.

Obstruction at the airway anastomosis is a recognized complication of adult heart-lung transplantation (HLT) and lung transplantation (LT). Data for pediatric transplantation have been scarce. We reviewed our experience in pediatric HLT and LT to determine the frequency of airway complications and to document the therapeutic modalities used for their treatment. Fifty-three patients (median age: 13.8 yr; range: 1.3 to 28.2 yr) underwent HLT (n = 25), SLT (n = 3), DLT (n = 25), or repeat DLT (n = 3) and survived for more than 72 h. Major anastomotic airway complications requiring intervention affected one of the 25 HLT (4%) and seven of the 28 LT (SLT + DLT) patients (25%) (p = 0.05). Four patients with granulation tissue occluding the airway were treated with forceps resection, laser ablation, or balloon dilatation. Three patients with fibrotic strictures received silicone stents, laser ablation, or balloon dilatation. Two patients with bronchomalacia or diffuse stricture below the anastomosis underwent metal stent placement. Five of seven patients who were treated for anastomotic complications had satisfactory relief of airway obstruction. As compared with previously studied adults, pediatric heart-lung transplant recipients had the same or a lower frequency, and pediatric lung transplant recipients had a higher frequency of major anastomotic airway complications. A variety of treatment modalities were necessary to achieve adequate relief of airway obstruction.

Stimulation of Cl(-) secretion by chlorzoxazone.

We previously demonstrated that 1-ethyl-2-benzimidazolone (1-EBIO) directly activates basolateral membrane calcium-activated K(+) channels (K(Ca)), thereby stimulating Cl(-) secretion across several epithelia. In our pursuit to identify potent modulators of Cl(-) secretion that may be useful to overcome the Cl(-) secretory defect in cystic fibrosis (CF), we have identified chlorzoxazone [5-chloro-2(3H)-benzoxazolone], a clinically used centrally acting muscle relaxant, as a stimulator of Cl(-) secretion in several epithelial cell types, including T84, Calu-3, and human bronchial epithelium. The Cl(-) secretory response induced by chlorzoxazone was blocked by charybdotoxin (CTX), a known blocker of K(Ca). In nystatin-permeabilized monolayers, chlorzoxazone stimulated a basolateral membrane I(K), which was inhibited by CTX and also stimulated an apical I(Cl) that was inhibited by glibenclamide, indicating that the G(Cl) responsible for this I(Cl) may be cystic fibrosis transmembrane conductance regulator (CFTR). In membrane vesicles prepared from T84 cells, chlorzoxazone stimulated (86)Rb(+) uptake in a CTX-sensitive manner. In excised, inside-out patches, chlorzoxazone activated an inwardly-rectifying K(+) channel, which was inhibited by CTX. 6-Hydroxychlorzoxazone, the major metabolite of chlorzoxazone, did not activate K(Ca), whereas zoxazolamine (2-amino-5-chlorzoxazole) showed a similar response profile as chlorzoxazone. In normal human nasal epithelium, chlorzoxazone elicited hyperpolarization of the potential difference that was similar in magnitude to isoproterenol. However, in the nasal epithelium of CF patients with the DeltaF508 mutation of CFTR, there was no detectable Cl(-) secretory response to chlorzoxazone. These studies demonstrate that chlorzoxazone stimulates transepithelial Cl(-) secretion in normal airway epithelium in vitro and in vivo, and suggest that stimulation requires functional CFTR in the epithelia.

Comparison of Flutter device and chest physical therapy in the treatment of cystic fibrosis pulmonary exacerbation.

Chest physiotherapy (CPT) is recommended for the clearance of bronchial secretions in the management of patients with cystic fibrosis (CF). The Flutter valve (Scandipharm, Birmingham, AL) has been introduced as an alternative method to CPT for airway mucus clearance. The objective of this study was to compare the short-term effects of CPT and the Flutter valve on pulmonary function and exercise tolerance in patients with cystic fibrosis. Twenty-three patients, 5 to 21 years of age, were randomized to receive one of two interventions: CPT or the Flutter valve, upon admission to the hospital for a 2-week treatment of pulmonary exacerbation. Pulmonary function testing (PFTs) and the 6-min walk test were performed on admission, day 7, and day 14 of hospitalization. Data analysis indicated no significant differences between the two groups on admission. Both groups showed improvement in pulmonary function test results, but the Flutter group had a higher mean forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV(1)) compared to the CPT group after 1 week of intervention. Both groups continued to improve during the 2-week intervention, with no significant difference in FVC or FEV(1) between groups by the end of 2 weeks. Mean forced expiratory flow rate between 25-75% of vital capacity (FEF(25-75)), 6-min walk distance, and resting arterial oxyhemoglobin saturation (SaO(2)) showed little change by day 7, but improved significantly (P< 0.05) by day 14 of hospitalization in both groups, with no significant difference between groups. This study demonstrated that patients using the Flutter device had better pulmonary function after 1 week of therapy and similar improvement in pulmonary function and exercise tolerance compared to CPT after 2 weeks of therapy, suggesting that Flutter valve therapy is an acceptable alternative to standard CPT during in-hospital care of patients with CF.

Non-aspergillus allergic bronchopulmonary mycosis in a pediatric patient with cystic fibrosis.

This article describes a child with cystic fibrosis (CF) and allergic bronchopulmonary mycosis caused by Tricosporon beigelii. An 11-year-old boy with CF failed to respond to conventional treatment for a pulmonary exacerbation. Bronchial washings contained copious budding yeast forms, subsequently identified as T beigelii. Total serum immunoglobulin E was elevated and precipitating antibodies to T beigelii were positive. Together these findings support the diagnosis of allergic bronchopulmonary mycosis. The patient improved with antifungal therapy and systemic glucocorticoid therapy. The pathologic potential of yeast in the airways of patients with CF is unclear. The diagnosis of non-Aspergillus allergic bronchopulmonary mycosis requires a high degree of suspicion and has potentially important implications for the management of patients with CF.

MUC1 and other sialoglycoconjugates inhibit adenovirus-mediated gene transfer to epithelial cells.

Recombinant adenoviruses are currently being evaluated as gene transfer vectors for the treatment of airway diseases. Recent evidence indicates that gene transfer to differentiated airway epithelial cells is inefficient. We hypothesized that apical membrane glycoconjugates, such as the transmembrane mucin MUC1, reduce the efficiency of adenovirus-mediated gene transfer. To address this, studies were performed in primary bronchial epithelial and Madin Darby canine kidney (MDCK) cells transduced to express human MUC1. Colocalization of MUC1 and an adenoviral lacZ transgene in the bronchial epithelial cells revealed that at several multiplicities of infection, the percentage of cells expressing lacZ was five-fold less in MUC1-expressing cells. Moreover, lacZ expression was three- to eight-fold lower in MUC1-expressing than in control MDCK cells, demonstrating that MUC1 interferes with gene transfer and is not merely a phenotypic marker of a cell that is refractory to adenovirus infection. Neuraminidase pretreatment of cells to remove sialic acid residues prior to viral adsorption increased the efficiency of gene transfer two- to five-fold in human airway and MDCK cells, and in a xenograft model of human airway. This effect was also observed in cultured cells that do not express MUC1, suggesting that other sialylated glycoconjugates impact on the efficiency of gene transfer. An inhibitory effect of negatively charged glycoconjugates on adenovirus binding was further supported by the finding that adsorption of adenovirus with a polycation significantly increased gene transfer efficiency. These data demonstrate for the first time that sialoglycoconjugates on epithelial cells reduce the efficiency of adenovirus-mediated gene transfer.

MR evaluation of right pulmonary agenesis and vascular airway compression in pediatric patients.

OBJECTIVE: The purpose of this study was to evaluate the spectrum of airway and vascular anomalies in agenesis of the right lung and to assess the role of imaging in defining the anatomy. CONCLUSION: Symptomatic children with right lung agenesis often have anatomic distortion of the airway with vascular compression, and occasionally they have intrinsic airway stenosis. MR imaging most accurately defines the entire spectrum of airway and vascular anatomic abnormalities. Precise delineation of the anatomy is essential in patient management and surgical planning.

Polycations increase the efficiency of adenovirus-mediated gene transfer to epithelial and endothelial cells in vitro.

Recombinant adenoviruses are being developed for gene therapy for cystic fibrosis and other lung diseases, and for prevention and treatment of vascular thrombosis. A major limitation to the clinical utility of adenoviruses is the low efficiency of gene transfer achieved in vivo. In addition, little is known about the initial interactions between adenoviruses and the target cell. To address the hypothesis that the negative charge presented by membrane glycoproteins reduces the efficiency of adenovirus-mediated gene transfer, primary cultures of human airway, Madin-Darby canine kidney cells, an immortalized cystic fibrosis airway epithelial cell line, and primary cultures of sheep pulmonary artery endothelium were infected with recombinant adenovirus containing the E. coli lacZ reporter gene (Ad2 beta gal2) in the presence of various polyions. For each cell type, adsorption of Ad2 beta gal2 in the presence of the polycations polybrene, protamine, DEAE-dextran, and poly-L-lysine significantly increased the percentage of cells that express lacZ. The polyanion heparin did not significantly alter gene transfer efficiency, but completely abrogated the effects of polycations. These data provide evidence that negatively charged moieties on the cell surface reduce the efficiency of adenovirus-mediated gene transfer, and that alteration of the charge interaction between adenoviruses and the cell surface may improve the potential clinical application of these vectors.

Young adults' knowledge, attitudes, and behavior about abortions in young women.

OBJECTIVE: To document opinions and decision-making strategies of young adults regarding abortions for young women. METHODS: Eighty-nine male and 215 female college students completed a questionnaire on abortion during routine visits to their university health center. RESULTS: Among the salient findings, most respondents took a pro-abortion stance for girls under 18 in cases of rape (92% of students), incest (90%), or danger to the girl's health (90%). A much lower priority was given for abortion in cases of fetal abnormalities (55% of students), economic hardship (51%), or for girls who were married (55%). Abortion was considered acceptable regardless of circumstances by 46% of students and never a good idea by 18%. The outcome of unplanned pregnancies for minors should be decided by the girl (90% of students), partner (55%), parents (29%), and state or federal law (8%). Abortions for minors should require parental notification (45%) or consent (33%). Although only one student felt illegal abortions were safe, 19% would seek this kind of abortion and 4% of females would try to cause their own miscarriage if abortions were outlawed in the United States. CONCLUSIONS: The vast majority of young adults believed that girls under 18 should retain the right to decide the outcome of their pregnancy and should not be subjected to governmental restrictions. The highest priority for abortion was given to girls who had been victimized or whose health was at risk. Although nearly all respondents are aware of the hazards of criminal abortions, many would resort to such unsafe practices if legal alternatives were no longer available.