The Tricky Trachea: Tracheitis and Mediastinitis Treated With Infliximab and Steroids in a Patient With Ulcerative Colitis.

Pulmonary extra-intestinal manifestations of inflammatory bowel disease are rare, comprising 0.21% to 0.4% of the inflammatory bowel disease population. Common symptoms include cough, chest pain, and dyspnea. Abnormal pulmonary function tests are common in these patients, with restrictive, obstructive, and diffusion capacity defects. CT scanning remains the most sensitive imaging technique to detect abnormalities. Pulmonary manifestations are diverse and include airway, parenchymal, and pleural disease. Large airway disease predominates, particularly bronchiectasis. Upper airway disease is rare but concerning for the development of acute airway compromise. To our knowledge, there are no reports of concurrent mediastinitis with tracheitis in the setting of inflammatory bowel disease. We present a case of a patient with ulcerative proctitis who experienced the development of inflammatory tracheitis and mediastinitis. Her disease responded to systemic steroids and biologic therapy. In addition to our case, we reviewed the literature and provide an approach to pulmonary complications as extra-intestinal manifestation of inflammatory bowel disease.

Pulmonary Manifestations of Inflammatory Bowel Disease.

Pulmonary manifestations of inflammatory bowel disease are increasingly recognized in patients with ulcerative colitis and Crohn's disease. Most commonly, incidental abnormalities are noted on chest imaging or pulmonary function tests. Although clinically significant pulmonary disease is less common, it can carry significant morbidity for patients. We review the presenting symptoms, workup, and management for several of the more common forms of inflammatory bowel disease-related pulmonary disease. Increased awareness of the spectrum of extraintestinal inflammatory bowel disease will help providers more readily recognize this phenomenon in their own patients and more comprehensively address the protean sequelae of inflammatory bowel disease.

Invasive Aspergillus Pseudomembranous and Obstructive Tracheo-bronchitis in an Immuno-competent Patient.

A 19 year female, presented with life threatening haemoptysis and cough with minimum expectoration for 3 months. Bronchoscopy showed multiple nodules in airway. The direct microscopy and culture of sputum revealed fungal elements and Aspergillus flavus respectively. Serum Galactomannan was positive. Thus diagnosis of invasive aspergillus tracheo-bronchitis made. She responded to voriconazole. Aspergillus tracheo-bronchitis is a rare form of invasive pulmonary aspergillosis in immuno-competent host. Aspergillus spp in respiratory samples should not be routinely discarded as colonization.

[SOME CLINICAL AND CYTOKINE FEATURES OF THE CLINICAL COURSE OF RECURRENT RESPIRATORY SYSTEM DISEASES IN CHILDREN WITH THE TOXOCARIASIS INVASION].

The aim of the present study was to analyze clinical and cytokine features of recurrent respiratory system diseases in children with toxocariasis. 50 children aged 1 to 17 years (mean age - 10±5 years) with recurrent current of respiratory system disorders were studied. During the survey such clinical manifestations of the respiratory system disorders as obstructive bronchitis (50%), bronchial asthma (30%), pneumonia (10%) and laryngotracheitis (10%) have been revealed. Statistical analysis of the results was performed using the software package STATISTICA 6.1 (SNANSOFT). We have shown that the disorders of respiratory system in case of toxocariasis invasion often occur with severe intoxication and bronchial obstruction syndromes, temperature reaction, respiratory insufficiency and hepatomegaly. A prolonged course of the disease has been noted. "Inflammatory" indicators of general blood analysis, such as leukocytosis and increased of ESR have been recorded in patients with respiratory system disorders in children with T.canis infection significantly more often, significant "allergic" laboratory changes were in the form of eosinophilia. High average levels of pro-inflammatory IL-6, as well as low levels of IL 5 have been determined in children suffering from the respiratory system disorders and with toxocariasis invasion in the anamnesis. The obtained findings require further study.

An unusual case of invasive Aspergillus ulcerative tracheobronchitis without involvement of lung parenchyma in a post-renal transplant patient.

We present the case of a 54-year-old male, who presented with respiratory complaints four months after he underwent renal transplantation. Bronchoscopy showed ulcerated mucosa of the left main bronchus and computed tomography (CT) of the thorax showed foci of air within the bronchial wall. A biopsy from the lesion showed septate fungal hyphae, dichotomously branching at acute angles. A locally invasive Aspergillus ulcerative tracheobronchitis with no parenchymal involvement is an important cause of tracheobronchitis in post-renal transplant patients. An early diagnosis and institution of appropriate treatment can improve the outcome. A combination treatment of caspofungin and voriconazole can be considered if patient is not responding to voriconazole alone.

SLC26A9-mediated chloride secretion prevents mucus obstruction in airway inflammation.

Asthma is a chronic condition with unknown pathogenesis, and recent evidence suggests that enhanced airway epithelial chloride (Cl-) secretion plays a role in the disease. However, the molecular mechanism underlying Cl- secretion and its relevance in asthma pathophysiology remain unknown. To determine the role of the solute carrier family 26, member 9 (SLC26A9) Cl- channel in asthma, we induced Th2-mediated inflammation via IL-13 treatment in wild-type and Slc26a9-deficient mice and compared the effects on airway ion transport, morphology, and mucus content. We found that IL-13 treatment increased Cl- secretion in the airways of wild-type but not Slc26a9-deficient mice. While IL-13-induced mucus overproduction was similar in both strains, treated Slc26a9-deficient mice exhibited airway mucus obstruction, which did not occur in wild-type controls. In a study involving healthy children and asthmatics, a polymorphism in the 3' UTR of SLC26A9 that reduced protein expression in vitro was associated with asthma. Our data demonstrate that the SLC26A9 Cl- channel is activated in airway inflammation and suggest that SLC26A9-mediated Cl- secretion is essential for preventing airway obstruction in allergic airway disease. These results indicate that SLC26A9 may serve as a therapeutic target for airway diseases associated with mucus plugging.

Effects of clarithromycin and dexamethasone on mucus production in isografted rat trachea.

OBJECTIVES: The purpose of this study was to develop an animal model for the study of mucus overproduction and to assess the effect of a 14-membered macrolide antibiotic and a glucocorticoid on lipopolysaccharide (LPS)-induced mucus production. METHODS: Tracheas from donor rats were homografted to recipient rats for 4 weeks, and the usefulness of this tracheal homograft model in the study of mucus production was examined. RESULTS: Oral administration of clarithromycin (CAM) to recipient rats for 4 weeks significantly reduced LPS-induced mucus production in the homografted trachea. Dexamethasone administered for 4 weeks also significantly reduced the mucus volume in LPS-treated homografted trachea compared with that in the control rats. The implanted trachea containing control medium was not histologically different from normal trachea. When the medium instilled into the implanted trachea contained 1 µg/ml LPS, the volume and spinability of mucus produced in the tracheal lumen were significantly increased compared to those in the trachea instilled with control medium. Goblet cell metaplasia was also observed in the implanted trachea containing LPS. CONCLUSIONS: The present study shows that LPS-administered homografted trachea is a good animal model of chronic hypersecretory diseases of the upper and lower airways. CAM and dexamethasone could be treatment choices in such hypersecretory diseases.

Bacterial tracheitis--not always primary.

A child presented with features of bacterial tracheitis with complete response to therapy. He presented with a recurrence one week later. A foreign body in the tracheal wall was diagnosed and removed by bronchoscopy. Tracheal intubation for airway management and tracheal toileting are not enough in bacterial tracheitis; bronchoscopy should be considered to diagnose any underlying cause.

Inflammatory response of tracheobronchial epithelial cells to endotoxin.

Respiratory epithelial cells play a crucial role in the inflammatory response in endotoxin-induced lung injury, an experimental model for acute lung injury. To determine the role of epithelial cells in the upper respiratory compartment in the inflammatory response to endotoxin, we exposed tracheobronchial epithelial cells (TBEC) to lipopolysaccharide (LPS). Expression of inflammatory mediators was analyzed, and the biological implications were assessed using chemotaxis and adherence assays. Epithelial cell necrosis and apoptosis were determined to identify LPS-induced cell damage. Treatment of TBEC with LPS induced enhanced protein expression of cytokines and chemokines (increases of 235-654%, P < 0.05), with increased chemotactic activity regarding neutrophil recruitment. Expression of the intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was enhanced by 52-101% (P < 0.0001). This upregulation led to increased adhesion of neutrophils, with >95% adherence to TBEC after LPS stimulation, which could be blocked by either ICAM-1 (69%) or VCAM-1 antibodies (55%) (P < 0.05). Enhanced neutrophil-induced necrosis of TBEC was observed when TBEC were exposed to LPS. Reduced neutrophil adherence by ICAM-1 or VCAM-1 antibodies resulted in significantly lower TBEC death (52 and 34%, respectively, P < 0.05). Therefore, tight adherence of neutrophils to TBEC appears to promote epithelial cell killing. In addition to indirect effector cell-induced TBEC death, direct LPS-induced cell damage was seen with increased apoptosis rate in LPS-stimulated TBEC (36% increase of caspase-3, P < 0.01). These data provide evidence that LPS induces TBEC killing in a necrosis- and apoptosis-dependent manner.

Bacterial tracheitis reexamined: is there a less severe manifestation?

OBJECTIVE: Bacterial tracheitis (BT) is a condition that can cause fatal airway obstruction. We evaluated our experience with BT over a 10-year period. STUDY DESIGN: Retrospective review of patients treated for BT between 1991 and 2001. RESULTS: Ninety-four cases were evaluated. The mean patient age was 7.9 years. At presentation, 60% were afebrile, and the mean WBC count was 10.8 x 10(3)/mm3 . Only 53% of patients required intubation. Younger children were more likely to require this intervention. S. aureus was the most commonly cultured bacteria, while isolation of M. catarrhalis was associated with a higher intubation rate. A pathologic virus was isolated in 64% of the 34 cultures performed. Only 9 patients were described as "toxic," and 6 presented in respiratory extremis. There were no deaths. CONCLUSION AND SIGNIFICANCE: A subset of patients with tracheal membranes has a less severe clinical appearance. Nonetheless, these patients require debridement and aggressive medical treatment. We propose that the term "exudative tracheitis" (ET) better describes this entity. Older patients who are less systemically ill and rapidly respond to local and systemic therapy are characteristic of ET. EBM RATING: C.

Inhibition of the TNF-pathway: use of infliximab and etanercept as remission-inducing agents in cases of therapy-resistant chronic inflammatory disorders.

OBJECTIVE: To examine the potential of the two tumour necrosis factor (TNF) inhibitors infliximab and etanercept as remission-inducing agents in chronic therapy-resistant inflammatory disorders of immune or non-immune pathogenesis. METHODS: 14 patients with adult Still's disease/macrophage activation syndrome (4), Wegener's disease (3), Behçet's disease (3), keratoscleritis (1), lymphomatous tracheo-bronchitis (1) Cogan's syndrome (1), and rapidly destructive crystal arthropathy (1) were treated with infliximab (n = 10) and etanercept (n = 4). All patients showed organ-threatening progression of their diseases with resistance to conventional immunosuppressive medication. Therapeutic benefit was assessed clinically and by documenting organ-specific functional and morphological alterations. Side effects were compared with the data of our clinic's rheumatoid arthritis (RA) patients treated by TNF inhibitors. RESULTS: A rapid and dramatic beneficial effect was documented in 9 patients and a moderate one in 5. Best responses (clinical and laboratory parameters) were seen in patients with macrophage activation syndrome/adult Still's disease and Behçet's disease, while the results were less impressive in those with Wegener's disease, Cogan's syndrome, idiopathic cerato-scleritis and lymphomatous tracheobronchitis. In all cases immunosuppressive agents and systemic glucocorticoids could be reduced or discontinued. CONCLUSIONS: TNF inhibition may be highly effective in patients with severe, therapy-resistant chronic inflammatory disorders.

Tracheobronchial involvement with Crohn's disease.

We report the case of a young woman with Crohn's disease of the bowel who presented with a purulent tracheobronchitis and life-threatening upper airway obstruction. Fibreoptic bronchoscopy demonstrated severe tracheal and upper bronchial pseudotumours and stenosis. The role of recent discontinuation of corticosteroids, for quiescent inflammatory bowel disease, in the development of endobronchial disease and the dramatic response in airway patency after reintroduction of prednisolone in this rare complication of Crohn's disease are discussed.

Eosinophilic tracheobronchitis and airway cough hypersensitivity in chronic non-productive cough.

BACKGROUND: We have shown that some patients presenting with chronic bronchodilator-resistant non-productive cough have global atopic tendency and airway cough hypersensitivity without non-specific bronchial hyperresponsiveness, abbreviated as atopic cough. The cough is successfully treated with histamine H1-antagonists and/or glucocorticoids. OBJECTIVE: This prospective study was conducted to elucidate the histological feature of atopic cough. METHODS: Tracheal and bronchial mucosa obtained by transbronchoscopic biopsy and bronchoalveolar lavage (BAL) cell component were studied with special emphasis on eosinophils in eight non-smokers diagnosed with atopic cough, all of whom had increased sensitivity of cough response to inhaled capsaicin, normal lung function and bronchial responsiveness to methacholine and normal chest roentgenogram. Their cough completely resolved on histamine H1-antagonists and/or glucocorticoids. Transbronchoscopic tracheal and bronchial biopsy and BAL were also performed in healthy non-smokers as a control. RESULTS: A small number of eosinophils was detected in subepithelium of trachea in six of seven patients and in subepithelium of bronchi in seven of eight cough patients. The numbers of eosinophils in subepithelium of trachea and bronchi were significantly increased in the patients compared with control subjects. There was no BAL eosinophilia in any patients. CONCLUSION: It is concluded that eosinophilic tracheobronchitis and cough hypersensitivity are pathological and physiological characteristics of atopic cough.

Tissue macrophages associated with angiogenesis in chronic airway inflammation in rats.

Angiogenesis is a feature of chronic inflammation produced by Mycoplasma pulmonis infection of the respiratory tract. The mechanism of this angiogenesis is unknown, but cellular growth factors and matrix remodeling proteases produced by inflammatory cells are likely to be involved. The goal of this study was to determine the relationship between changes in the number, shape, and distribution of ED2-immunoreactive macrophages and the development of angiogenesis in the tracheal mucosa of Wistar rats after M. pulmonis infection. In pathogen-free rats, ED2-positive cells were scattered in the airway mucosa (261 +/- 42 cells/mm2 of surface, mean +/- SE). Most cells were irregularly shaped and had moderate ED2 immunoreactivity. No lymphoid tissue was present. The number of ED2-positive cells increased rapidly after infection, was 120% above baseline at 1 wk, and remained significantly increased throughout the 4-wk study (P < 0.05). Angiogenesis was first detected at 2 wk, and at 3 wk the vessel length density was nearly 8-fold the pathogen-free value. At 3 and 4 wk, focal sites of angiogenesis coincided with discrete clusters of round, strongly immunoreactive ED2-positive cells (1,340 +/- 124 cells/mm2) in polyp-like collections of mucosal lymphoid tissue. The close association of distinctive ED2-positive cells with angiogenic blood vessels suggests a relationship between a subset of tissue macrophages and the angiogenesis associated with M. pulmonis infection. The time course of the changes indicates that the initial influx of ED2-positive macrophages precedes the angiogenesis, and the rounding of the cells parallels the growth of new vessels.

Involvement of gicerin, a cell adhesion molecule, in tracheal development and regeneration.

Gicerin is a novel cell adhesion protein that belongs to the immunoglobulin superfamily. Gicerin protein adheres to neurite outgrowth factor, an extracellular matrix protein in the laminin family, and also exhibits homophilic adhesion. In the present study, we investigated the involvement of gicerin and neurite outgrowth factor in tracheal development and regeneration. In an early embryonic stage, gicerin protein was highly expressed in tracheal epithelial cells, but not in loosely arranged mesenchymal cells. During development, mesenchymal cells become condensed around the tracheal epithelium and then differentiate into muscle and cartilage; high levels of gicerin expression were observed in these cells. In the later embryonic and posthatching stages, no gicerin expression was detected in tracheal epithelium or cartilage. In addition, expression of gicerin increased transiently in the tracheal epithelium during the regeneration after tracheitis induced by the infectious bronchitis virus. Furthermore, a polyclonal antibody against gicerin inhibited the epithelial regeneration in tracheal organ cultures. These findings suggest that glcerin plays an important role in both tracheal development and regeneration.

Traqueítis bacteriana

La traqueítis bacteriana es una entidad potencialmente fatal que ha reaparecido en la última década con inusitado auge. A propósito de su detección en nuestro servicio decidimos realizar un estudio retrospectivo en el Hospital Universitario de la Misericordia de Santa Fe de Bogotá entre enero de 1990 y julio de 1994. Se revisaron 88 historias de pacientes con diagnósticos clínico sugestivo de traqueítis bacteriana pero sólo 13 pacientes cumplieron con el requisito de confirmación endoscópica del diagnóstico para ser considerados en el presente trabajo. La edad osciló entre 1 y 7 años, predominando el sexo masculino. Existió antecedente de infección respiratoria previa en el 54 por ciento, los síntomas más frecuentes fueron fiebre, tos perruna y dificultad respiratoria; los hemogramas mostraron leucocitosis, neutrofilia y aumento de la VSG. En la endoscopia se observó exudado traqueal, membranas purunlentas y úlceras; en solo cultivo se aisló Staphylococcus aureus. El 62 por ciento requirió permeabilizar la vía aérea, 3 con traqueostomía y 5 con tubo orotraqueal. El 46 por ciento se manejó con oxacilina y todos evolucionaron satisfactoriamente.

Gastropharyngeal reflux in infants and children. A pharyngeal pH monitoring study.

Gastroesophageal reflux has been shown to play an important role in chronic and acute inflammatory disorders of the airway. In particular, gastroesophageal reflux has been suggested to be the cause of pharyngolaryngeal problems, according to the literature, at any age. However, to our knowledge, the presence of acid in the pharynx in pathological cases has not yet been proved. A series of eight patients (aged 2 months to 7.5 years) with recurrent acute laryngotracheitis underwent a two-channel pH monitoring for 23 to 24 hours. One pH probe was placed in the lower esophagus, the other in the pharynx, at the level of the epiglottis. Acid gastroesophagopharyngeal reflux was demonstrated in every patient. A significant difference with a series of six control subjects was noted in terms of esophageal and pharyngeal pH monitoring. The most significant item is the total time the pH in the pharynx was below 6. Despite the limited number of patients, this study suggests the role of gastroesophageal reflux in recurrent laryngotracheitis in infants and children.

Inhibition of neutral endopeptidase potentiates neurogenic inflammation in the rat trachea.

The present study was performed to determine whether neurogenic inflammation in the rat trachea can be exaggerated by inhibiting neutral endopeptidase, an enzyme that degrades tachykinins that are believed to mediate neurogenic inflammation. Neurogenic inflammation was produced by antidromic electrical stimulation of one vagus nerve (2.5 Hz, 1 ms, 5 V for 5 min) in the presence of atropine or by an intravenous injection of capsaicin (100 micrograms/kg). Neutrophils that adhered to the endothelium of venules were visualized and counted in tracheal whole mounts that were stained by a histochemical reaction for myeloperoxidase. Neural inflammation increased the number of adherent neutrophils. Pretreatment with the neutral endopeptidase inhibitor phosphoramidon (1.0 or 2.5 mg/kg iv) increased neutrophil adhesion induced by neural inflammation. As assessed by the amount of extravasation of Monastral blue pigment, neural inflammation also increased vascular permeability, and this change was potentiated by phosphoramidon. These results are consistent with the concept that neuropeptides released from sensory nerves in the tracheal mucosa cause neutrophils to adhere to venules and increase vascular permeability and that these effects are modulated by neutral endopeptidase.