Faculty Bibliography

The association between gastroesophageal reflux (GER) and upper airway obstruction in children is recognized but not well understood. Our objective was to determine if the creation of a model of upper airway obstruction in dogs would cause GER and to determine if the GER is related to intrathoracic pressure changes. Five dogs underwent evaluation with esophageal manometry and pH probe at baseline and 1 week after creation of an upper airway obstruction. Airway obstruction was created by placement of a fenestrated cuffed tracheostomy tube, which was then capped and the cuff was inflated, requiring the animals to breathe via the fenestrations. The negative inspiratory pressure (Pes) (+/- SD) increased from 11.8 +/- 4.8 cm H(2)O at baseline to 17.6 +/- 4.9 cm H(2)O 1 week after creation of an airway obstruction (p = .029). None of the dogs had GER at baseline with a reflux index (RI) value of 0.0; however, 1 week after creation of airway obstruction, three out of five dogs had GER, with a mean RI value of 21.2 +/- 21.2. There was a significant (p = .023) correlation (r = .928) of the changes in Pes and RI values following airway obstruction. Upper airway obstruction (UAO) does cause GER in this canine model. Severity of GER is significantly correlated with Pes changes.

Mycoplasma pneumoniae (Mp) infection is associated with asthma exacerbation in children. We hypothesized that Mp infection may cause airway inflammation by inducing the release of cytokines by respiratory epithelial cells. The levels of chemokines interleukin-8 (IL-8) and released upon activation, normal t cell expressed and secreted (RANTES) released by nasal epithelial cell (NEC) cultures established from asthmatic and nonasthmatic children were measured by ELISA at 4, 24, 48, and 72 hr after cells were inoculated with Mp, and were compared with baseline release of these factors. The presence of MP on apical membranes of NEC after infection was confirmed by transmission electron microscopy, and adherence was shown to be inhibited by erythromycin. Mp infection did not alter NEC release of IL-8 or RANTES at any time point. In contrast, tumor necrosis factor alpha (TNF-alpha) stimulated increased IL-8 at all time points, and respiratory syncytial virus (RSV) infection stimulated RANTES release at 48 and 72 hr by NEC. These results were not significantly different between NEC from asthmatic and nonasthmatic children. As a comparison, peripheral blood mononuclear cells from normal human volunteers were also incubated with Mp and had significantly increased release of IL-2, IL-6, and TNF-alpha. We conclude that Mp, unlike viral pathogens such as RSV, is unlikely to directly stimulate early airway surface cytokine responses via mechanisms involving epithelial cells. We speculate that the chronic presence of mononuclear cells at the airway surface of asthmatics provides a target for Mp-triggered cytokine production.

The presence of lipids in alveolar macrophages has been used clinically as an indicator of aspiration, a process associated with increased lung inflammation in animal models. The hypothesis is that the quantity of lipids in alveolar macrophages, measured as lipid-laden index (LLI), would correlate with lung inflammation in paediatric patients. Children with chronic respiratory symptoms (21 cystic fibrosis (CF), 24 non-CF) underwent flexible bronchoscopy with bronchoalveolar lavage (BAL) and 24-h intraoesophageal pH monitoring for clinical indications. Total cell counts, number and per cent of neutrophils and macrophages, and LLI were determined in the bronchoalveolar lavage fluids (BALF) from all children. BALF were also obtained from eight healthy, young nonsmoking adults for comparison. LLI in non-CF children were 6.9 +/- 3.5 (mean +/- SEM) which were higher than LLI in healthy adults (1.0 +/- 0.4), (p=0.045). Children with CF had very high LLIs (19.2 +/- 4.5) compared with both healthy adults (p=0.014) and children without CF (p=0.045). LLI did not correlate with airway inflammation in any group. LLI in children with abnormal pH probes had a tendency to be higher than in children with normal pH probes, but the difference was not significant (p=0.098). It is concluded that the lipid-laden index was significantly elevated in children with chronic respiratory symptoms compared with healthy adults, and in children with cystic fibrosis compared with those who have other chronic respiratory conditions. However, the lipid-laden index did not correlate with the quantity of bronchoalveolar lavage fluid inflammation. The lipid-laden index in children may, in part, reflect processes other than aspiration, such as airways obstruction.

We describe an 11-year-old girl with cystic fibrosis (CF) who presented with respiratory failure and Burkholderia cepacia bacteremia (cepacia syndrome). She survived her illness after aggressive treatment with parenteral antibiotics and corticosteroids. We speculate that treatment with corticosteroids may decrease the influx of proinflammatory cytokines and neutrophil-induced inflammation, with resulting improvement in the outcome of cepacia syndrome in CF patients.