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The effect of serial in vivo passage on the expression of virulence and DNA stability of an infectious laryngotracheitis virus strain of low virulence.

The effect of 35 serial passages in vivo on an infectious laryngotracheitis virus strain of low virulence was examined in terms of effect on virulence and DNA stability. Within 3 passages in live chickens there was evidence of increasing respiratory distress. Severe respiratory distress (with death in some cases) was observed after the 6th passage, except when there appeared to be a transient decline in pathogenicity following short term storage of the virus inoculum at -70 degrees C. Restriction endonuclease analysis of viral DNA derived from the original inoculum and the final passage did not reveal any genomic alteration. It is postulated that there is a potential for live ILTV vaccines to cause outbreaks of clinical disease in the event of inadequate or incomplete vaccination procedures.

Animals↗

Ozone-induced inflammation and altered ventilation in genetically susceptible mice: a comparison of acute and subacute exposures.

We have examined whether the effects of acute (2 ppm/3 h) and subacute (0.3 ppm/72 h) ozone (O3) exposures on airways are mutually predictive. Inbred C57BL/6J (susceptible) and C3H/HeJ (resistant) mice are differentially responsive to inflammation induced by the 2 exposures. Breeding experiments and cosegregation analysis indicated that 2 separate genes control inflammatory responses: Inf (acute), Inf-2 (subacute). The genetic model was also used to examine the effects of both exposures on the magnitude and pattern of breathing. Results imply that mechanisms that control susceptibility to the 2 exposures are not the same, and that one response is not necessarily predictive of the other.

Animals↗

Racemic epinephrine in the treatment of laryngotracheitis: can we identify children for outpatient therapy?

The purpose of this study was to identify a cohort of children with laryngotracheitis (croup) who may be safely discharged from the emergency department (ED) after treatment with nebulized racemic epinephrine (RE), corticosteroids, and prolonged observation. Consecutive children (younger than 13 years of age) presenting to the ED with the diagnosis of laryngotracheitis were evaluated prospectively according to a croup scoring system. Sixty-one patients (4 to 108 months of age) with persistent inspiratory stridor at rest after 20 minutes of mist therapy who received nebulized RE (0.05) mL/kg of a 2.25% solution) and intramuscular dexamethasone (0.6 mg/kg) were enrolled in the study. Patients were observed in the ED while croup scores were assessed at 15, 60, 120, and 180 minutes. Croup scores were significantly improved (analysis of variance, P < .01) throughout the observation period in 31 patients (51%) who were discharged from the ED. Only one patient returned within 48 hours for further cool mist therapy. The maximum benefit from RE therapy was seen at 60 minutes. If a child had persistent resting stridor or a croup score greater than 2 at that time, hospitalization was inevitable. The 30 patients admitted to the hospital were younger (19.1 v 27.8 months) and had higher pretreatment croup scores (5.7 v 4.1). This was the first prospective study to identify a subset of children who have received RE to be safely discharged home after observation in the ED.

Administration, Inhalation↗

Hydrogen peroxide-induced epithelial damage increases terbutaline transport in guinea-pig tracheal wall: implications for drug delivery.

An isolated vagus nerve-tracheal tube preparation from guinea-pig was treated intraluminally with hydrogen peroxide (H2O2) at various concentrations. Exposure to, 100 mmol/L H2O2 for 20 min was chosen for further experiments since it appeared to cause selective damage to the epithelium. Thus the subepithelial layers of the tracheal wall appeared intact as judged by light microscopic examination. The response to nerve stimulation (increase in intratracheal pressure) was attenuated by only about 20%. Terbutaline administration into the tracheal lumen caused a concentration-dependent inhibition of the response to nerve stimulation. In tracheal preparations pretreated with 100 mmol/L H2O2 there was a 20-fold decrease in the EC50 for terbutaline. The EC50 for terbutaline added to the external medium was not changed by the H2O2 pretreatment. The efflux of 3H-terbutaline from the tracheal lumen into the external medium was three times higher in H2O2-treated than in control preparations. It is concluded that in the H2O2-damaged epithelium the absorption of terbutaline is enhanced resulting in a better availability of the drug in the smooth muscle layer after intraluminal administration.

Animals↗

Airway obstruction secondary to tracheobronchial involvement of asymptomatic undiagnosed Crohn's disease in a pediatric patient.

Tracheal involvement in Crohn's disease is extremely rare and can present with airway obstruction in any age group, including the pediatric patient. We describe the case of a 9-year-old female who presented with a 2-week history of intermittent stridor, resolving temporarily with the administration of systemic steroids. The patient denied any abdominal complaints and was otherwise healthy. Bronchoscopy revealed progressive tracheal inflammation necessitating an urgent tracheotomy. Subsequent laboratory investigation confirmed the diagnosis of Crohn's disease. This is the first reported case of previously undiagnosed Crohn's disease presenting with airway manifestations.

Airway Obstruction↗

Production of pro-inflammatory polypeptides by airway mucous glands and its potential significance.

Burn patients often develop respiratory distress and ARDS several days after injury. An ovine model allows experimental study of this problem. In sheep the injury is characterized by intense acute inflammation in the trachea and bronchi from 3 to 48h after injury, with accumulation of neutrophils, fibrin and other plasma proteins, and mucus in airway lumens. We have carried out immunostaining for multiple cytokines in this model, including interleukin-8 (IL-8), Interleukin-1 beta (IL-1beta), interleukin-1 alpha (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha), and vascular endothelial growth factor (VEGF). All of these show intense immunostaining in airway mucous glands. IL-1beta and VEGF show substantial constitutive staining in the serous cells of mucous glands, while IL-8, IL-1alpha, and TNF-alpha show substantially increased expression after injury. This pattern of expression of cytokines in mucous glands, and the apparent release of cytokines into the lumen after injury, are considered potentially highly significant in the progression of injury in this model. In addition, a proinflammatory function of mucous glands might prove to be important in chronic lung diseases such as chronic bronchitis and asthma.

Animals↗

Angiogenesis in mice with chronic airway inflammation: strain-dependent differences.

Chronic inflammation is associated with blood vessel proliferation and enlargement and changes in vessel phenotype. We sought to determine whether these changes represent different types of angiogenesis and whether they are stimulus dependent. Chronic airway inflammation, produced by infection with Mycoplasma pulmonis, was compared in strains of mice known to be resistant (C57BL/6) or susceptible (C3H). Tracheal vascularity, assessed in whole mounts after Lycopersicon esculentum lectin staining, increased in both strains at 1, 2, 4, and 8 weeks after infection, but the type of vascular remodeling was different. The number of vessels doubled in tracheas of C57BL/6 mice, with corresponding increases of capillaries and venules. In contrast, neither the number nor the length of vessels changed in C3H mice. Instead, vessel diameter and endothelial cell number doubled, and the proportion of venules doubled with a corresponding decrease of capillaries. Although the infection had no effect on baseline plasma leakage, in both strains it potentiated the leakage produced by substance P. We conclude that the same stimulus can result in blood vessel proliferation or enlargement, depending on the host response. Endothelial cells proliferate in both cases, but in one case new capillaries form whereas in the other capillaries convert to venules.

Animals↗

Tracheal replacement with cryopreserved tracheal allograft: experiment in dogs.

BACKGROUND: It has been difficult to perform tracheal allotransplantation without immunosuppression. To determine whether cryopreserved trachea can be used in tracheal replacement, we evaluated the viability of cryopreserved tracheal allografts in a canine model of immunosuppressant-free transplantation. METHODS: Cryopreserved tracheal allografts, which had been frozen to -80 degrees C in a programmed freezer and then stored in liquid nitrogen (-196 degrees C) (group 1, n = 6), fresh tracheal autografts (group 2, n = 5), and fresh tracheal allografts (group 3, n = 4) were transplanted into the thoracic segment of the trachea using an omental flap without immunosuppressive agents. RESULTS: All dogs in groups 1 and 2 survived, but in group 3, all 4 died of airway obstruction between 1 month and 2 months after operation. Histologically, the cryopreserved allografts displayed normal epithelium and cartilage, but the fresh allografts showed chronic inflammatory changes, no epithelium, and no cartilage. CONCLUSIONS: Cryopreserved tracheal allografts maintain their structural integrity after transplantation. The cryopreservation process seems to reduce the allogenic response of the trachea in canine models. Therefore, we believe the cryopreserved tracheal allograft is an excellent choice for tracheal replacement.

Airway Obstruction↗

Bronchopulmonary inflammation and airway smooth muscle hyperresponsiveness induced by nitrogen dioxide in guinea pigs.

We investigated whether acute exposure to nitrogen dioxide (NO2) causes major inflammatory responses (inflammatory cell recruitment, oedema and smooth muscle hyperresponsiveness) in guinea pig airways. Anaesthetised guinea pigs were exposed to 18 ppm NO2 or air for 4 h through a tracheal cannula. Bronchoalveolar lavage was performed and airway microvascular permeability and in vitro bronchial smooth muscle responsiveness were measured. Exposure to NO2 induced a significant increase in eosinophils and neutrophils in bronchoalveolar lavage fluid, microvascular leakage in the trachea and main bronchi (but not in peripheral airways), and a significant in vitro hyperresponsiveness to acetylcholine, electrical field stimulation, and neurokinin A, but not to histamine. Thus, this study shows that in vivo exposure to high concentrations of NO2 induces major inflammatory responses in guinea pig airways that mimic acute bronchitis induced by exposure to irritant gases in man.

Acetylcholine↗

Comparison of the effects of infectious bronchitis and infectious laryngotracheitis on the chicken respiratory tract.

In infectious bronchitis (IB) virus infection of the chicken the upper and lower respiratory tracts were damaged, but infectious laryngotracheitis (ILT) virus caused lesions only in the upper respiratory tract. Secondary infection with Escherichia coli was apparent in the trachea of birds inoculated with either virus but was more striking in those given IB virus. Serum alpha 1-acid glycoprotein, an acute-phase protein, occurred in higher concentrations in chickens inoculated with IB virus than in those given ILT virus.

Animals↗

Necrotizing tracheobronchitis: a new indication for emergency bronchoscopy in the neonate.

Necrotizing tracheobronchitis (NTB) is a recently recognized cause of tracheal obstruction in the mechanically ventilated neonate. This process involves inflammation and necrosis of the mucosa of the distal trachea and mainstem bronchi. The sloughing of this material into the tracheal lumen results in plugging and acute respiratory distress. We documented this diagnosis in 19 infants. Four were diagnosed at autopsy. Fifteen had emergency bronchoscopy performed in the neonatal intensive care unit with removal of the obstructing debris. Ten of these 15 neonates survived (66.7%). The diagnosis of necrotizing tracheobronchitis should be suspected in those neonates requiring positive pressure ventilation in whom a sudden unexplained increase in ventilatory requirements develops. This is often associated with hypercarbia and a history of high-peak inspiratory pressures with or without hypoxia. Emergency bronchoscopy in these neonates is necessary both for diagnosis and treatment of the necrotizing tracheobronchitis.

Bronchitis↗

Treatment of neonatal necrotizing tracheobronchitis with extracorporeal membrane oxygenation and bronchoscopy.

Necrotizing tracheobronchitis has recently been described as a complication of mechanical ventilation of newborns with respiratory failure. Despite the use of bronchoscopy, 45% of the reported patients to date have died. In this study, we report the use of extracorporeal membrane oxygenation (ECMO) to stabilize two patients with necrotizing tracheobronchitis. While supported by bypass, both patients underwent prolonged bronchoscopies with removal of extensive amounts of tracheal debris. ECMO provided efficient oxygenation in the face of near total airway occlusion, and permitted far more extensive bronchoscopic debridement and lavage than would have been possible if the lungs were required for oxygenation. In addition, ECMO provided a period of lung "rest" during which ventilator settings were reduced, thus minimizing further barotrauma and allowing for lung and airway healing. Both patients recovered without significant respiratory sequelae. ECMO and bronchoscopy are effective forms of therapy for patients with life-threatening necrotizing tracheobronchitis when conventional modalities of treatment have failed.

Bronchitis↗

Diffuse necrotizing tracheobronchitis: an acute and chronic disease.

Necrotizing tracheobronchitis (NTB) is characterized by acute episodes of airway obstruction, hypercarbia, and lack of chest movement in mechanically ventilated neonates. Emergency bronchoscopic removal of necrotic tissue is essential for survival. Although postmortem lesions extend into smaller bronchi, survivors have not demonstrated residual tracheobronchial abnormalities. Two infants were treated successfully for NTB but succumbed to diffuse tracheobronchial strictures with progressive pulmonary hyperinflation. A third neonate with esophageal atresia and left pulmonary agenesis developed NTB. Despite initial postbronchoscopic improvement, the infant died at age 6 weeks with diffuse obstructing NTB. All three infants required endotracheal intubation and mechanical ventilation. High-frequency jet ventilation was not used. Tracheal cultures for fungi, bacteria and viruses were negative. Successful treatment of NTB may be followed acutely by recurrence of NTB and chronically by diffuse tracheobronchial strictures and emphysema.

Acute Disease↗

Laryngotracheobronchitis as a complication of measles during an urban epidemic.

OBJECTIVE: To evaluate demographic and clinical correlates of laryngotracheobronchitis (LTB) as a complication of measles during a community-wide epidemic. DESIGN: Retrospective review of medical records. SETTING: Childrens Hospital Los Angeles, a large urban pediatric facility, during a regional epidemic of measles studied January through June 1990. PATIENTS: All patients identified at our hospital who met Centers for Disease Control criteria for measles. MEASUREMENTS AND RESULTS: Of 440 patients with measles, 82 also had LTB (18.6%). Patients in whom LTB developed were significantly younger (mean +/- SD: 14.7 +/- 8.2 months) than the cohort (24.8 +/- 30.1 months) (p less than 0.001) and more likely to require hospitalization (91.5%) than the cohort (44.3%) (p less than 0.001). Thirteen patients (17.3%) required intensive care, including 9 (11%) who required endotracheal intubation for a mean of 8.3 +/- 7.1 days. Pulmonary function testing of five patients with an endotracheal tube in place, including three not clinically assessed as having pneumonia, indicated the presence of concomitant lower respiratory tract disease. CONCLUSION: Laryngotracheobronchitis was a frequent and often severe complication of measles. The likelihood that LTB would develop was inversely related to age, generally required inpatient care, and necessitated endotracheal intubation in severely affected patients.

Adolescent↗