Diagnosis of tracheal injury in mechanically ventilated premature infants by flexible bronchoscopy. A pilot study.

Flexible bronchoscopy (FB) is uniquely suited for the study of large airway lesions in the ventilated premature infant. However, no standardized clinical scoring system of distal tracheal injury exists and the adverse consequences of FB in ventilated premature infants are not well described. Using a prototype Olympus fiberoptic ultrathin bronchoscope with a directable tip and an outer diameter of 2.2 mm, we serially scored distal tracheal injury in conventionally ventilated premature infants on the basis of mucosal and obstructive changes observed at bronchoscopy. In addition, we prospectively evaluated the incidence of adverse cardiovascular and pulmonary effects during, immediately after, and within 1 h of FB. We performed 21 FBs in eight conventionally ventilated premature infants with birth weight of 1,239 +/- 438 g and gestational age of 30 +/- 3 weeks. The carina and mainstem bronchi were easily visualized in all infants using the prototype bronchoscope. During the first several days of life, moderate-to-severe distal tracheal mucosal injury occurred frequently, while moderate-to-severe obstructive injury occurred infrequently. Distal mucosal injury appeared to improve during the fourth week of life. Mild distal obstructive injury began to appear during the second week of life. Adverse consequences of FB observed in our patient population included transient hypoxemia and bradycardia during FB, changes in systolic blood pressure immediately and within 1 h after FB, and emesis immediately after FB. Serious adverse cardiovascular or pulmonary effects were not observed. We conclude that FB can be performed safely with appropriate monitoring and is a useful tool in the clinical assessment and serial evaluation of distal tracheal injury in ventilated premature infants. We speculate that moderate-to-severe distal tracheal mucosal injury may be associated with the development of later obstructive injury. On the basis of this preliminary study, further prospective investigations of tracheal injury in ventilated premature infants appear to be warranted.

High fever after flexible bronchoscopy and bronchoalveolar lavage in noncritically ill immunocompetent children.

Flexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) have been applied increasingly to the evaluation of pulmonary disease in children. Although several complications have been reported following FB and BAL, high fever after BAL in immunocompetent children has not previously been reported. To determine the frequency, clinical characteristics, and outcome of these complications in children who developed high fever post-BAL, we retrospectively reviewed all bronchoscopic procedures done on an outpatient basis between August 1995 and July 1997. We identified 78 immunocompetent noncritically ill children who had undergone FB and BAL as an outpatient procedure for evaluation of underlying pulmonary disease, of whom 13 (17%) developed temperature (T) higher than or equal to 39 degrees C (fever group). The 13 patients in the fever group had a median age of 10 (range, 4-48) months and a reported T of 39.4 degrees C (39.1-40.6 degrees C) occurring 7.5 (4-12) hr after BAL. To determine if there were differences in clinical or BAL fluid (BALF) characteristics, we compared each child in the fever group to two children in the nonfever group, based upon primary indications and age. There were no differences in demographic or clinical characteristics between the two groups. Lymphocyte concentrations in BALF were significantly reduced in the fever group (P = 0.03). An abnormal BALF cell differential (defined as one or more of the following: neutrophils >10%, lymphocytes >30%, or eosinophils >1%) was significantly more common in the fever group (P = 0.008, odds ratio 3.6). We conclude that high fever is a frequent adverse event following BAL in noncritically ill immunocompetent children with underlying pulmonary disease. Pre-BAL clinical characteristics are not associated with development of high fever. However, the finding of an abnormal BALF cell differential is strongly associated with development of high fever post-BAL.

Pediatric flexible airway endoscopy--the light in the tunnel.

Flexible airway endoscopy (FAE) allows direct visualization and functional assessment of the larynx and central airways and access to lung lavage fluid and biopsy specimens for culture and diagnostic studies. Recently, FAE has been utilized in children for diagnosis and therapy of airway and pulmonary disorders. Pediatric FAE differs significantly from adult FAE in regards to anatomy and physiology of the central airways, indications, sedation and monitoring, common diagnostic findings, and therapeutic options. This review will focus upon clinical utility of pediatric FAE with emphasis upon diagnostic and therapeutic applications and limitations of this relatively new invasive technology.

Effects of maternal dexamethasone on expression of SP-A, SP-B, and SP-C in the fetal rat lung.

Prenatal administration of glucocorticoids has been shown to enhance surfactant production in the fetus. Since the surfactant proteins play an important role in surfactant function and secretion, we wished to determine the effects of maternal glucocorticoid administration on their fetal expression and appearance. Daily dexamethasone (DEX) (1 mg/kg/day) or 0.9% saline was administered to timed-pregnant rats on gestational days 14 through 16 or on day 16 with sacrifice on day 17 (term day 22), and on gestational days 14 through 18, or days 16 through 18, or day 18 with sacrifice on day 19. SP-A content was determined in lung homogenates from treated and control male and female fetal rats by an enzyme-linked in lung homogenates from treated and control male and female fetal rats by an enzyme-linked immunosorbent assay. The abundance of mRNAs for SP-A, SP-B, and SP-C per fixed amount of total cellular RNA was also determined in lungs from treated and control male and female fetal rats by Northern blot analysis. In litters sacrificed on day 17, DEX administered on days 14 through 16 and on day 16 resulted in significant increases in SP-A content. Expression of SP-A mRNA, which was not detectable in control fetuses on day 17, became clearly apparent after either 1 or 3 d of DEX treatment. The abundance of mRNAs for SP-B and SP-C also increased in day-17 fetuses after either 1 or 3 d of DEX treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Ontogeny of surfactant apoproteins in the rat.

Content of the 26-38-kD surfactant apoprotein (SP-A) was determined in lung homogenates from fetal (17-21 d gestation), postnatal (1-28 d of life), and adult male and female rats by a double sandwich ELISA. Expression of mRNA for SP-A as well as the hydrophobic apoproteins, SP-B and SP-C, were also determined in lung homogenates from fetal and adult rats of both sexes by Northern blot analysis. SP-A was undetectable in fetal lungs on d 17 (day of birth = d 22) and barely detectable on d 18. On d 19 there was a 3- to 4-fold increase in SP-A content above d 18 levels. Between d 19 and 21 SP-A content significantly increased another 6- to 9-fold. SP-A content on the day of birth was not significantly different from that seen on gestational d 21. SP-A content decreased 35-40% between the day of birth and postnatal d 7. After the second postnatal week SP-A content gradually increased, reaching adult levels after d 28. No sex differences in SP-A content were observed during fetal or postnatal lung maturation. SP-A mRNA was first detected in fetal lungs on d 18 and increased in relative abundance until d 21, but remained below adult levels. Developmental changes in fetal lung SP-A content closely paralleled changes in fetal expression of SP-A mRNA. SP-B mRNA was also first detected on d 18, then increased in relative abundance to adult levels by d 20. SP-C mRNA was clearly detectable on d 17, then increased in relative abundance to adult levels by d 20-21. Unlike surfactant phospholipids, there are no apparent sex differences in the expression of any of the surfactant apoproteins during late gestation. The differences observed during fetal lung maturation in the time of onset and changes in relative abundance among the three apoprotein mRNA imply that their genes may be differentially regulated in the developing rat lung.

Clinical utility of flexible bronchoscopy and bronchoalveolar lavage in young children with recurrent wheezing.

OBJECTIVE: The objective of this study was to determine in young children with recurrent wheezing poorly responsive to bronchodilator therapy whether flexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) provide clinically useful information, whether age-specific differences are present in bronchoscopic and BAL fluid (BALF) findings, and whether differential cellular analysis of BALF is useful in suggesting an infectious or inflammatory process. DESIGN: This was a retrospective case series with descriptive and analytical components. The study population included children referred to a large tertiary care children's hospital subspecialty service for further evaluation of recurrent wheezing. Clinical and demographic data and findings of FB and BALF studies were collected from chart review. For purposes of data analysis patients were divided into 0- to 6-, 7- to 12-, and 13- to 18-month age groups. RESULTS: Thirty otherwise healthy children, 0 to 18 months of age with recurrent wheezing, who had undergone FB were identified; and 28 were found to have positive diagnostic findings. Airway abnormalities were found in 17 (57%) and tended to be more common in the 0- to 6-month age group. In the 27 who also had BAL performed, 3 (11%) had a positive bacterial culture, 9 (33%) a positive viral culture, and 5 (19%) an elevated lipid-laden macrophage index suggesting aspiration. Differential cellular analysis was abnormal in 11 (41%), a finding that was significantly associated with a positive bacterial culture, a positive viral culture, or an elevated lipid-laden macrophage index. CONCLUSIONS: In this population of young children with recurrent wheezing poorly responsive to bronchodilator therapy, FB and BAL yielded useful diagnostic findings in most children studied. In addition, in the presence of an infectious or inflammatory process, differential cellular analysis of BALF revealed an increased percentage of neutrophils.

Developmental changes of fetal rat lung Na-K-ATPase after maternal treatment with dexamethasone.

Late in gestation, the prenatal fetal alveolar epithelium switches from fluid secretion to resorption of salt and water via apical sodium channels and basal Na-K-ATPase. The amounts of lung sodium pump activity protein and mRNA increase in the lung just before birth. Because maternal glucocorticoids (GC) may promote maturation of the alveolar epithelium and augment fetal surfactant apoprotein levels, we hypothesized that GC increase the fetal lung Na-K-ATPase alpha- and beta-subunit gene expression in development. Timed-pregnant Sprague-Dawley rats were injected daily with intraperitoneal dexamethasone (1 mg/kg) or saline for 1, 3, or 5 days before death at fetal day (FD) 17 or 19. Maternal GC treatment altered the fetal lung wet to dry weight, decreasing it at FD17 and increasing it at FD19. Northern analysis of total lung RNA for the alpha1- and beta1-pump subunits demonstrated differential regulation of the mRNA in response to GC. At FD17, beta1-mRNA increased after 1 (FD16) or 3 days (FD14-FD16) of GC treatment, whereas alpha1-mRNA was not altered. There were accompanying increases in beta1-, but not alpha1-, protein. At FD19, GC treatment for 5 days (FD14-FD18) increased beta1- and decreased alpha1-mRNA levels, but treatment for 1 (FD18) or 3 days (FD16-FD18) had no effect. In all groups, the alpha1-Na-K-ATPase protein was predominantly on the basolateral surface of airspace epithelium by immunofluorescence. In summary, maternal dexamethasone differentially affected the fetal lung mRNA levels of the two sodium pump subunits in a complex manner, with increased beta1-mRNA levels dependent on duration of treatment and fetal age.

Blastomycosis in children.

Infections due to Blastomyces dermatitidis are not commonly encountered in children and adolescents. Knowledge of the diagnosis and treatment of this disease is largely based upon experience with adult patients. We recently reviewed our experience with blastomycosis to evaluate the difficulties in diagnosis and treatment of this disease in the pediatric population. Ten patients with blastomycosis were identified during our review, and five had pulmonary disease alone. Of these five patients, four required open-lung biopsy for diagnosis, even though three had previously undergone bronchoalveolar lavage. The response to treatment with the oral azole antifungal agents (ketoconazole, fluconazole, and itraconazole) was limited, and the agent with the greatest success remains amphotericin B. Until more data are available, amphotericin B should be used for complicated and life-threatening cases of blastomycosis. If oral azole agents are used for non-life-threatening cases, patients should be followed closely, and if clinical deterioration occurs or serum levels of medications are not adequate, then amphotericin B should be substituted for the oral azole agent.