Tracheal collapsibility in adults is dynamic over time.

BACKGROUND: Tracheal collapse is a weakness of the tracheal wall leading to expiratory central airway collapse of more than 50% compared to inspiration. It has previously been discussed whether the collapsibility of the greater airways is a stable or a dynamic condition. Indeed, other well-known lung diseases such as asthma are characterized by dynamic changes with respect to pulmonary function indices. There are several different morphologies of the trachea related to collapsibility such as the crescent type and the saber-sheath type both involving the tracheal cartilage and excess dynamic airway collapse only involving the posterior membranous part of the trachea. Is the morphology of the trachea important for the course of the disease? The effect or adverse effects of inhaled corticosteroids are thought to play a role in the increasing incidence of the excess tracheal collapse. In this pilot study, we hypothesized that the excess collapsibility of the tracheal wall is dynamic. METHODS: We prospectively examined 20 patients with excessive tracheal collapse on previous CT scans performed primarily due to bronchiectasis. A repeat CT scan was performed in order to evaluate the collapsibility. Before the repeat scan, patients were trained in maximal inspiration, expiration and breathholding. CT was performed in full inspiration and at end-expiration. Image assessment was performed on a dedicated CT workstation using standard lung window display settings. The percentage expiratory collapse based on cross sectional areas from carina to the thoracic inlet was calculated. Pulmonary function tests were performed and analysed in accordance with the American Thoracic Society and the European Respiratory Society guidelines. RESULTS: Repeat CT scan were performed after 24 month +/- 7.2. Six of the 20 participants (30%) were males. Mean age was 67 +/- 11.3 years. Mean FEV1 was 83% of predicted, FVC 96.6 % of predicted and FEV1/FVC-ratio 71%. In 45% of the patients tracheal expiratory collapse improved (by more than 10%) based on percentage change in cross sectional areas in expiration compared to inspiration. 35% of patients showed disease progression with increased collapse and in 20% the collapsibility remained unchanged. CONCLUSION: We demonstrate that the collapsibility in a large fraction of the patients had actually improved at the follow up examination. We do not find any dependency of the change in collapsibility on the morphology of the trachea after end expiration, use of corticosteroid, or recurrent infections. In addition, no correlation between the changes in collapse and changes in the pulmonary function tests and the symptoms is observed.

Anticoagulant rodenticide toxicosis causing tracheal collapse in 4 small breed dogs.

OBJECTIVE: To describe 4 cases of tracheal narrowing attributed to tracheal mucosal hemorrhage caused by anticoagulant rodenticide toxicity in breeds predisposed to tracheal collapse. CASE SUMMARY: Over the years 2005-2014, 4 dogs were presented for respiratory distress secondary to diffuse tracheal narrowing. All dogs had possible anticoagulant rodenticide ingestion and prolonged prothrombin time. All dogs received fresh-frozen plasma transfusions, vitamin K1 supplementation, and supportive care. Tracheal narrowing improved on follow-up radiographs in 3 of 4 patients. One of 4 did not have follow-up radiographs performed. All dogs survived. NEW OR UNIQUE INFORMATION PROVIDED: Anticoagulant rodenticide toxicity causing clinical signs consistent with tracheal collapse is a rare but recognized phenomenon that has not been previously reported in breeds prone to tracheal collapse.

Tracheobronchopathy From Inhaled Corticosteroids.

Inhaled corticosteroids (ICSs) have become the mainstay of asthma control. They are also recommended as an add-on therapy to long-acting beta agonists and anticholinergics in moderate to severe COPD with recurrent exacerbations. Ultimately this clinical practice has led to the widespread use of ICSs, which are supported by a more favorable side effect profile than that of systemic steroids.

Iatrogenic tracheal laceration in the setting of chronic steroids.

We report the case of a 71-year-old woman with end-stage chronic obstructive pulmonary disease who presented with a 10-cm tracheal laceration from a presumed traumatic intubation in the setting of respiratory distress and chronic obstructive pulmonary disease exacerbation and subsequently developed significant subcutaneous emphysema along her neck and mediastinum in addition to her peritoneum and mesentery. We were successfully able to treat this patient conservatively up until the time that tracheostomy was warranted. We discuss and review tracheobronchial injuries with respect to etiology, risk factors, and management and hope to benefit health care providers managing airways in patients at risk for tracheal injury.

Tracheobronchial calcifications in children.

BACKGROUND: Tracheobronchial calcifications are considered a rare radiologic finding in children. Our clinical experience indicates that this finding is not infrequently seen among children with prosthetic heart valves who have been treated with warfarin sodium. OBJECTIVE: We hypothesized that calcifications of the tracheobronchial tree are more common than previously reported in this patient population. MATERIALS AND METHODS: We reviewed the medical records and imaging studies of children who underwent cardiac valve replacement at our institution to estimate the prevalence. RESULTS: Tracheobronchial calcifications were identified on chest radiographs in 6 out of 17 children (35%), indicating that this imaging finding might be frequently overlooked. CONCLUSION: All children positive for tracheobronchial calcifications had been anticoagulated with warfarin sodium between the time of surgery and development of positive imaging findings. Our findings suggest that tracheobronchial calcifications are not uncommon in children treated with warfarin. Further investigation is necessary to determine wether there is a cause-effect relationship in these children.

Mediastinal infusion with tracheal necrosis: an unusual complication of Port-a-cath devices.

The Port-a-cath (PAC) is a catheter totally implanted under the skin. It is commonly used in oncology for permanent venous access. It provides a more simple way to infuse chemotherapies, antibiotics or parenteral nutrition, while offering improved comfort to patients. The usual complications of these devices (infections and catheter obstructions) are well documented. More exceptional events are catheter fractures with systemic migration, and endopleural perfusions due to a wrong positioning of the catheter. Since 1998, 10 cases of mediastinal infusion of cytotoxics have been reported. Surgical management was necessary in only two cases. We are reporting the case of a 57-year-old female suffering from a multimetastatic sigmoid adenocarcinoma. A mediastinal infusion of Folfiri and bevacizumab with a tracheal necrosis complicated the PAC use and required a latissimus dorsi myoplasty to fill up the tracheo-bronchial defect.

Efficiency of lornoxicam in lung and trachea injury caused by peroxynitrite.

Peroxynitrite is involved in the pathogenesis of pulmonary diseases such as asthma, occupational pulmonary diseases and acute respiratory distress syndrome (ARDS) due to excessive production of nitric oxide or superoxide or both. Lornoxicam, a new oxicam derivative, is a potent anti-inflammatory agent. In this study, we evaluated the role of lornoxicam in a peroxynitrite-induced pulmonary and tracheal injury model by measuring myeloperoxidase (MPO) activity, malondialdehyde (MDA) and 3-nitrotyrosine (3-NT) levels in lung tissue and bronco-alveolar lavage fluid. The study protocol was based on three experimental groups as treatment (T), control (C) and peroxynitrite (P). Each group was subdivided into three subgroups as 2nd, 24th and 48th hour groups. P and T groups were injected intratracheal peroxynitrite. The T group received intraperitoneal lornoxicam before and 24h after peroxynitrite installation. Tissue and serum MDA, MPO values and tissue 3-NT value of the treatment and control groups were found significantly lower than the peroxynitrite group at the 2nd, 24th and 48th hours (p<0.05). Similarly, values obtained from bronco-alveolar lavage fluid examination in the control and treatment groups were significantly less than those in the peroxynitrite group (p<0.01). Therefore, Lornoxicam has been found to be effective in attenuating peroxynitrite induced pulmonary and tracheal injury in rats.

Dipeptidyl peptidase IV deficiency increases susceptibility to angiotensin-converting enzyme inhibitor-induced peritracheal edema.

BACKGROUND: Serum dipeptidyl peptidase IV (DPPIV) activity is decreased in some individuals with ACE inhibitor-associated angioedema. ACE and DPPIV degrade substance P, an edema-forming peptide. The contribution of impaired degradation of substance P by DPPIV to the pathogenesis of ACE inhibitor-associated angioedema is unknown. OBJECTIVES: We sought to determine whether DPPIV deficiency results in increased edema formation during ACE inhibition. We also sought to develop an animal model using magnetic resonance imaging to quantify ACE inhibitor-induced edema. METHODS: The effect of genetic DPPIV deficiency on peritracheal edema was assessed in F344 rats after treatment with saline, captopril (2.5 mg/kg), or captopril plus the neurokinin receptor antagonist spantide (100 mug/kg) by using serial T2-weighted magnetic resonance imaging. RESULTS: Serum dipeptidyl peptidase activity was dramatically decreased in DPPIV-deficient rats (P < .001). The volume of peritracheal edema was significantly greater in captopril-treated DPPIV-deficient rats than in saline-treated DPPIV-deficient rats (P = .001), saline-treated rats of the normal substrain (P < .001), or captopril-treated rats of the normal substrain (P = .001). Cotreatment with spantide attenuated peritracheal edema in captopril-treated DPPIV-deficient rats (P = .005 vs captopril-treated DPPIV-deficient rats and P = .57 vs saline-treated DPPIV-deficient rats). CONCLUSIONS: DPPIV deficiency predisposes to peritracheal edema formation when ACE is inhibited through a neurokinin receptor-dependent mechanism. Magnetic resonance imaging is useful for modeling ACE inhibitor-associated angioedema in rats. CLINICAL IMPLICATIONS: Genetic or environmental factors that decrease DPPIV activity might increase the risk of ACE inhibitor-associated angioedema.

Adriamycin mouse model: a variable but reproducible model of tracheo-oesophageal malformations.

A spectrum of tracheo-oesophageal malformations is seen in humans: oesophageal atresia, tracheal agenesis and laryngotracheo-oesophageal clefts. They are thought to share a common but unknown aetiology. These birth defects are frequently associated with other VACTERL anomalies. The adriamycin rat model (ARM) has proved to be a valuable model of the VACTERL anomalies, illustrating the dysmorphogenesis of oesophageal atresia and tracheal agenesis. As organogenesis relies on temporaspatially co-ordinated signalling systems, the next step would be to study the molecular pathogenesis of tracheo-oesophageal malformations. However, the mouse is the foremost mammal studied by developmental biologists, offering an expanding wealth of knowledge and scientific research techniques with which to investigate these anomalies. A limited dose response analysis of the teratogenicity of adriamycin in the mouse has identified a dose and timing of injections that produced tracheo-oesophageal malformations and other VACTERL anomalies. A clear account of the types and variability of the tracheo-oesophageal malformations produced by this dose is essential in order to be able to plan and interpret any future investigations of early gestation fetuses. CBA/Ca mice were accurately time-mated (n = 10). Nine dams received intraperitoneal injections of adriamycin (6 mg/kg) and one control dam received saline injections, on days 7 and 8. Fetuses were harvested on day 18, near term. Tracheo-oesophageal malformations were examined by dissecting microscope and serial transverse sections. Results are reported in the standard teratological manner as mean percentage per litter (+/-SEM). The resorption rate of the adriamycin treated fetuses was 50.4%. There were 29 adriamycin treated fetuses for inspection. Tracheo-oesophageal malformations were found in 29.2% (+/-10.3), affecting five out of nine litters. Oesophageal atresia occurred in 15.6% (+/-8.1), laryngotracheo-oesophageal cleft in 10.4% (+/-7) and tracheal agenesis in 3.1% (+/-3.1). All of these malformations occurred with a tracheo-oesophageal fistula. Unlike the ARM, the AMM can produce fetuses with complete laryngotracheo-oesophageal cleft as well as oesophageal atresia or tracheal agenesis. Their occurrence was found to be reproducible but variable. These are important considerations when planning and interpreting experiments using this model.

Tracheobronchomalacia and air trapping after mustard gas exposure.

RATIONALE: Mustard gas primarily affects the eyes, skin, and particularly the respiratory tract. Tracheobronchomalacia (TBM) and air trapping are often observed in high-resolution computerized tomography (HRCT) scans of the chest of mustard gas-exposed patients. OBJECTIVES: To examine the frequency and severity of TBM in a group of Iranian wartime mustard gas-exposed victims, and to investigate the correlation between TBM and air trapping in these cases. MATERIALS AND METHODS: Chest HRCT films obtained from 300 randomly selected subjects who had been exposed to mustard gas 15.5 yr previously were reviewed to determine the existence of TBM and air trapping. The HRCT films of a healthy control group were also analyzed for comparison. RESULTS: Out of 300 reviewed cases, 13 had TBM. From these 13 TBM cases, 11 (85%) showed air trapping with mean score of 5.5. In the control group, 5 (25%) of 20 subjects showed air trapping, with mean score of 0.6. The total air trapping was significantly higher in the TBM group (p < 0.001). There was an association between the severity of tracheomalacia and air trapping in the TBM group (p = 0.01, r = 0.69), but no association was observed between severity of bronchomalacia and air trapping. CONCLUSION: The results show that air trapping and TBM are correlated, both as long-term sequelae in mustard gas-exposed cases. Because air trapping is highly suggestive of bronchiolitis obliterans, we conclude that both bronchiolitis obliterans and TBM are caused by a single underlying process affecting small and large airways, respectively, in this group of patients.

In vivo differentiation potential of tracheal basal cells: evidence for multipotent and unipotent subpopulations.

The composition of the conducting airway epithelium varies significantly along the proximal to distal axis, with that of the tracheal epithelium exhibiting the greatest complexity. A number of progenitor cells have been proposed to contribute to the maintenance of this cellular diversity both in the steady state and in response to injury. However, individual roles for each progenitor cell type are poorly defined in vivo. The present study was undertaken to investigate the hypothesis that basal cells represent a multipotent progenitor cell type for renewal of the injured tracheal epithelium. To understand their contribution to epithelial repair, mice were exposed to naphthalene to induce airway injury and depletion of the secretory cell progenitor pool. Injury resulted in a rapid induction of cytokeratin 14 (K14) expression among the majority of GSI-B4-reactive cells and associated hyperplasia of basal cells. Restoration of depleted secretory cells occurred after 6 days of recovery and was associated with regression of the basal cell hyperplasia, suggesting a progenitor-progeny relationship. Multipotent differentiation of basal cells was confirmed using a bitransgenic ligand-regulated Cre-loxP reporter approach in which expression of a ubiquitously expressed LacZ reporter was activated within K14-expressing progenitor cells during airway repair. With the use of this approach, it was determined that K14-expressing cells include subsets capable of either multipotent or unipotent differentiation in vivo. We conclude that basal cells have the capacity for restoration of a fully differentiated epithelium.

Mouse strain modulates the role of the ciliated cell in acute tracheobronchial airway injury-distal airways.

Understanding cellular repair mechanisms in vivo has been advanced through the use of well-defined injury and repair models and their application to knockout and transgenic animals, primarily mice generated in a variety of background strains. However, little is known concerning the effect that mouse strain itself has on the interpretation and comparability of observations when the strain used for genetic manipulation is not the strain used to develop the model. We compared acute bronchiolar injury and repair in three strains of mice used in knockout mouse development (C57BL/6, 129/TerSv, and 129/SvEv) to the model strain (Swiss Webster) after treatment with the same dose of naphthalene and sacrificed at 1, 2, 4, 7, and 14 days after treatment. Extent of Clara cell toxicity and exfoliation was identical in the distal airways of all strains. There were significant strain-related differences in ciliated cell squamation, initiation and duration of proliferation, epithelial differentiation, and time to completion of epithelial repair. We conclude that ciliated cells play a prominent role in repair of distal airway injury, but that all phases of the repair process differ by strain. In addition, our findings reinforce that control animals must be of the same strain, ideally litter mates, when transgenic or knockout mice are used for the study of airway repair processes and mechanisms.

[Fatal toxic respiratory epitheliolysis. Subacute tracheo-bronchial desquamation in Stevens-Johnson syndrome]. / Epithéliolyse respiratoire toxique fatale. Desquamation suraiguë trachéo-bronchique lors d'un syndrome de Stevens-Johnson.

Acute bronchial mucosal sloughing related to Toxic Epidermal Necrolysis (Lyell syndrome) is widely reported in literature. On the contrary severe respiratory involvement is rare in post-infectious or toxic Epitheliolysis (Stevens-Johnson syndrome). There is no well-known predictive sign of bronchial epithelium involvement. An 18-year-old patient was admitted for Stevens-Johnson syndrome related to sulfasalazine (salazosulfapyridine). There were no respiratory signs. An acute respiratory failure occurred 36 hours after from admission due to an obstructive and desquamative necrosis of the tracheobronchial epithelium. We purpose that a fiberoptic laryngoscopy should be performed even in non-dyspneic patients suffering from Stevens-Johnson syndrome if hypersecretion is present. Fiberoptic bronchoscopy can be helpful in these cases.