Faculty Bibliography

OBJECTIVES: Protracted bacterial bronchitis is defined as the presence of more than 4 weeks of chronic wet cough that resolves with appropriate antibiotic therapy, in the absence of alternative diagnoses. The diagnosis of protracted bacterial bronchitis is not readily accepted within the pediatric community, however, and data on the incidence of bacterial bronchitis in children are deficient. The objective of this study was to determine the frequency of bacterial bronchitis in children with chronic wet cough and to analyze their bronchoscopic findings. METHODS: We performed a retrospective review of charts of children who presented with chronic wet cough, unresponsive to therapy, before referral to the pediatric pulmonary clinic. RESULTS: A total of 197 charts and bronchoscopy reports were analyzed. Of 109 children who were 0 to 3 years of age, 33 (30.3%) had laryngomalacia and/or tracheomalacia. The bronchoscopy showed purulent bronchitis in 56% (110) cases and nonpurulent bronchitis in 44% (87). The bronchoalveolar lavage bacterial cultures were positive in 46% (91) of the children and showed nontypable Haemophilus influenzae (49%), Streptococcus pneumoniae (20%), Moraxella catarrhalis (17%), Staphylococcus aureus (12%), and Klebsiella pneumoniae in 1 patient. The chi(2) analysis demonstrated that positive bacterial cultures occurred more frequently in children with purulent bronchitis (74, 69.8%) than in children with nonpurulent bronchitis (19, 19.8%) (P < .001). CONCLUSIONS: Children who present with chronic wet cough are often found to have evidence of purulent bronchitis on bronchoscopy. This finding is often indicative of a bacterial lower airway infection in these children.

The causal relationship between gastroesophageal reflux (GER) and respiratory disorders is not well understood. Previous experimental studies that investigated this relationship were performed in anesthetized animals and used artificial acidification of esophagus for simulation of GER. In this study, we investigated the impact of GER on intrapleural pressures (IPP) in conscious, unanesthetized dogs. After the induction of appropriate anesthesia, 5 purpose-bred mongrel dogs underwent reflux-creating surgery (partial cardiomyectomy). The presence of GER was confirmed by determining the reflux index (RI) and the duration of longest reflux episode (DLRE) after 24-h intraesophageal pH-metry. IP was monitored before and after cardiomyectomy using a subcutaneously placed telemetric implant with its pressure-sensor catheter tip inserted into the pleural space. Partial cardiomyectomy resulted in a significant increase in RI from a preoperative mean value of 0.38 +/- 0.21 to 7.52 +/- 2.56%, and DLRE from 1.22 +/- 1.12 to 36.80 +/- 12.71 min, as recorded by the proximal sensor of the pH probe. A similar trend was observed at the distal sensor. After cardiomyectomy, the negative inspiratory IPP significantly increased from 17.2 +/- 7.9 to 28.4 +/- 9.7 mm Hg. A similar effect was observed in the negative expiratory IPP. The negative inspiratory IPP had a significant correlation with both RI (R = 0.932) and DLRE (R = 0.899). Cardiomyectomy causes GER, the severity of which correlates with negative inspiratory IPP in a dog model. The suggested model allows for the investigation of the pathologic association of GER with respiratory disorders in conscious animals.

Introduction: Children with asthma and allergic rhinitis are often treated with a combination of inhaled and nasal corticosteroids. Safety data on this combination treatment in children are not available. This study evaluates adrenal function in children receiving combination therapy with nasal and inhaled corticosteroid using a low-dose adrenocorticotropin (ACTH) test. Methods: Twelve children aged 6–12 years with severe asthma and allergic rhinitis were given combination therapy with high-dose inhaled HFA-beclomethasone dipropionate (HFA-BDP) (320 micro-g/day for fi rst 2 months and 160 micro-g/day thereafter) and fl unisolide nasal spray (116 micro-g/day). A low-dose ACTH test was performed before treatment and 6 months later. Results: There was no significant change (mean plus/minus SD) in both baseline (7.78 plus/minus 5.34 before treatment and 7.53 plus/minus 4.02 after treatment, p = 0.42) and stimulated (22.58 ± 6.97 before treatment and 19.2 plus/minus 3.53, p = 0.09 after treatment) cortisol levels. Conclusion: Combination therapy with high-dose HFA-BDP and fl unisolide nasal spray did not cause suppression of adrenal function in pediatric patients with severe asthma and allergic rhinitis

Laryngeal exposure to acid and aspiration of gastric contents may lead to severe respiratory disorders. This study utilizes the canine model of Gastroesophageal reflux (GER) to identify whether lower esophageal dysfunction is associated with upper and lower airway pathology. MATERIALS AND METHODS: Five mongrel dogs underwent GER-creating surgery (partial cardiomyectomy). Laryngeal reflux finding score (RFS), lipid-laden macrophage index (LLMI) and BAL fluid cell differential were obtained before and after surgery. RESULTS: Partial cardiomyectomy in dogs significantly increased the Reflux index (RI) from 0.38 +/- 0.21% to 7.56 +/- 2.89% (P = 0.048), the duration of the longest reflux episode (DLRE) from 1.22 +/- 1.19 min to 66.2 +/- 42.03 min postoperatively (P = 0.049) and the total number of episodes in 24 hr from 2.06 +/- 1.03 to a postoperative value of 19.24 +/- 4.79. There was no statistically significant change in values for RFS, LLMI, and BAL fluid cell differential after the induction of GER. CONCLUSIONS: Acid reflux to the proximal esophagus of this animal model did not cause laryngeal exposure to acid or aspiration of gastric content. The results of this study suggest that presence of GER, secondary to lower esophageal dysfunction is not necessarily associated with upper and lower airway pathology.

BACKGROUND: Monitoring of intrapleural pressure (IPP) is used for evaluation of lung function in a number of pathophysiological conditions. We describe a telemetric method of non-invasive monitoring of the IPP in conscious animals intermittently or continuously for a prolonged period of time. MATERIALS AND METHODS: After IACUC approval, six mongrel dogs were used for the study. After sedation, each dog was intubated and anesthetized using 0.5% Isoflurane. A telemetric implant model TL11M2-D70-PCT from Data Science International was secured subcutaneously. The pressure sensor tip of the catheter from the implant was inserted into the pleural space, and the catheter was secured with sutures. The IPP signals were recorded at a sampling rate of 100 points/second for 30 to 60 min daily for 4 days. From these recordings, the total mean negative IPP (mmHg), and the total mean negative IPP for a standard time of 30 min were calculated. In addition, the actual inspiratory and expiratory pressures were also measured from stable recording of the IPP waveforms. RESULTS: In six dogs, the total mean +/- SD negative IPP was -10.8 +/- 10.6 mmHg. After normalizing with respect to acquisition time it was -13.2 +/- 11.2 mmHg/min. The actual inspiratory pressure was -19.7 +/- 15.3, and the expiratory pressure was -11.0 +/- 12.9. CONCLUSIONS: Our study demonstrates that telemetric monitoring of IPP can be performed reliably and non-invasively in conscious experimental animals. The values for IPP in our study are compatible with the results of other investigators who used different methods of IPP measurement. Further work may show this method to be helpful in understanding the pathophysiology of various breathing disorders

BACKGROUND: The quantity of lipids in alveolar macrophages is used clinically as an indicator of aspiration, which is associated with increased lung inflammation. This is determined in the macrophages obtained from bronchoalveolar lavage (BAL) and is expressed as lipid-laden macrophage index (LLMI). Although there is ample data on LLMI in human subjects, there is no published data pertaining to the baseline measures of the LLMI in canines, which are extensively used for experimental studies on gastroesophageal reflex (GER) and airway diseases. Primary aim of the present study was to collect data pertaining to the cytology and LLMI in BAL fluids obtained from healthy dogs. MATERIALS AND METHODS: Eight dogs underwent a bronchoscopy with BAL collection, and esophageal pH monitoring to determine the reflux index (RI). The BAL fluid was processed and reviewed under a microscope to determine the proportions of the various cell types and the LLMI. RESULTS: The median RI among the subjects was found to be 0.6 (0.0, 1.2). The BAL cytology analysis showed 77.5% (71.0, 83.5) macrophages, 21.0 (13.0, 24.5) lymphocytes and 2.5 (1.5, 5.0) neutrophils. The median LLMI was found to be 156 (111, 208). CONCLUSIONS: Although the differential cell counts in the dogs' BAL fluid was comparable to that of other experimental animals and humans, the LLMI was distinctly higher than the corresponding value reported for other species. As LLMI is a valuable modality for evaluation of intrapulmonary pathophysiology, these data on LLMI can be used as a species-specific standard for canine subjects used for experimental studies on GER and airway diseases.

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.