Airway Defects Research Articles

Current Perspectives in Mesenchymal Stromal Cell Therapies for Airway Tissue Defects.

Lung cancer is the leading cause of cancer death and respiratory diseases are the third cause of death in industrialized countries; for this reason the airways and cardiopulmonary system have been the focus of extensive investigation, in particular of the new emerging branch of regenerative medicine. Mesenchymal stromal cells (MSCs) are a population of undifferentiated multipotent adult cells that naturally reside within the human body, which can differentiate into osteogenic, chondrogenic, and adipogenic lineages when cultured in specific inducing media. MSCs have the ability to migrate and engraft at sites of inflammation and injury in response to cytokines, chemokines, and growth factors at a wound site and they can exert local reparative effects through transdifferentiation and differentiation into specific cell types or via the paracrine secretion of soluble factors with anti-inflammatory and wound-healing activities. Experimental and clinical evidence exists regarding MSCs efficacy in airway defects restoration; although clinical MSCs use, in the daily practice, is not yet completely reached for airway diseases, we can argue that MSCs do not represent any more merely an experimental approach to airway tissue defects restoration but they can be considered as a “salvage” therapeutic tool in very selected patients and diseases.

Thyroid ala perichondrial flaps for subglottic reconstruction.

Techniques available for reconstruction of the cricotracheal region in adults are currently suboptimal. We sought to 1) understand the anatomic basis for the thyroid ala perichondrial flap, 2) describe the technique of harvesting and intraluminal placement, and 3) learn the limitations of defects for which it can be used. Cadaveric anatomical study. In fresh cadaveric specimens, the perichondrium of the outer layer of the thyroid cartilage was elevated by tracing the superior, medial, and lateral borders of each thyroid cartilage ala. The inferiorly based flap was then placed into the airway through the cricothyroid membrane. The extent of coverage was measured. A total of 10 flaps were performed (6 male and 4 female). The average length of thyroid perichondrial flaps obtained was 1.67 cm. All flaps were able to completely cover the cricoid cartilage and extended to but did not cover the first tracheal ring. Once placed intraluminally, the flaps extended 2.4 cm below the vocal cords. Using both flaps enabled coverage of the entire anterior 180 degrees of the airway lumen in all specimens. There were no significant differences in male/female or right-sided/left-sided flaps. The thyroid ala perichondrial flap is technically feasible and can provide coverage of anterior airway defects up to approximately 2.4 cm below the true vocal cords. This flap could enable transfer of vascularized tissue to aid in cricotracheal reconstruction.

Disorders of haemostasis in patients with acute necrotising pancreatitis

Our objective was to investigate the capacity of a pumpless extracorporeal lung membrane (iLA) (Novalung; Novalung GmbH, Hechingen, Germany) to provide adequate respiratory support and the impact on morbidity/mortality during complex airway reconstruction.Only patients unable to be ventilated via conventional intubation were eligible for the study. A larynx mask or orotracheal tubes were placed above the airway defect and the iLA was attached via femoral vessels (arteriovenous), providing extracorporeal gas exchange, apneic hyperoxygenation, and total tubeless airway reconstruction. Haptoglobulin, plasmin–antiplasmin complex, P-selectin activation, and interleukin 6 were measured before, during, and after iLA use and 72 hours postoperatively.Fifteen consecutive patients (age, 42 ± 17 years) underwent elective (n = 7) or emergency (n = 8) reconstruction of the airway owing to a variety of disorders or defects. The iLA was left in place for 185 ± 61 minutes, diverted 1.70 ± 0.48 L/min of the cardiac output, and provided an arteriovenous carbon dioxide removal and oxygen transfer of 173 ± 94 and 144 ± 83 mL/min, respectively. The arterial oxygen tension/inspired oxygen fraction (314 ± 31 mm Hg), and arterial carbon dioxide tension (40 ± 6 mm Hg) remained stable throughout the entire operations. The following procedures were performed: redo slide tracheoplasties (n = 3), redo tracheoesophageal fistula repair (n = 1), sleeve lobectomies (n = 2), main carina reconstructions (n = 7), and anastomotic stenting and myocutaneous coverages (n = 2). Three patients required prolonged (9 ± 2 days) postoperative iLA support. Two (13%) patients died during the hospital stay. The use of iLA was associated with significant (P < .05) but clinically nonrelevant and yet nonpathologic increases of haptoglobulin (hemolysis), plasmin–antiplasmin complex (coagulation activation), and P-selectin activation (platelet activation). Data normalized within 48 hours postoperatively.Data suggest that iLA provides complete intraoperative respiratory support in patients who cannot receive conventional intubation/ventilation without relevant effects on cellular trauma, coagulatory response, and inflammatory response.

Phosphorylation of protein Tau by GSK3β prolongs survival of bigenic Tau.P301L × GSK3β mice by delaying brainstem tauopathy

Tau.P301L transgenic mice suffer precocious mortality between ages 8 and 11 months, resulting from upper airway defects caused by tauopathy in autonomic brainstem circuits that control breathing (Dutschmann et al., 2010). In individual mice, the clinical phenotype evolves progressively and rapidly (3–6weeks) from clasping, over general motor impairment to severe reduction in body-weight into the terminal phase that announces imminent death (<3days). Surprisingly, co-expression of GSK3β with Tau.P301L significantly prolonged survival of bigenic biGT mice (Terwel et al., 2008), which we here assign to delayed development of brainstem tauopathy. Eventually, brainstem tauopathy became as prominent in old biGT mice in the specified brainstem nuclei as in the parental Tau.P301L mice, resulting in similar clinical deterioration and terminal phase preceding death, although at later age. Biochemically, in both genotypes the pathway to neurofibrillary tangles and neuropil threads was similar: phosphorylation of protein Tau and formation of soluble oligomers and insoluble aggregates, ending in the typical tangles and threads of tauopathy. The extra GSK3β activity led to expected increased phosphorylation of protein Tau, particularly at residues S262 and S396, which we must conclude to delay the aggregation of protein Tau in the brainstem of aging biGT mice. The unexpected, paradoxical alleviation of the brainstem problems in biGT mice allowed them to grow older and thereby develop more severe tauopathy in forebrain than Tau.P301L mice, which succumb at younger age.

Repair of Tracheal Aspergillosis Perforation Causing Tension Pneumothorax

Tracheobronchial aspergillosis is a rare entity mainly observed in immune-compromised patients or those who have undergone transplantation. It may cause airway ulcerations or bleeding. We report the case ofa 17-year-old patient receiving chemotherapy foracute lymphoblastic leukemia who presented withright-sided tension pneumothorax. Chest tube drainage revealed a massive air leak without reexpansion of the lung, and bronchoscopy showed a15-× 15-mm defect of the distal trachea related to aspergillosis infection. The defect was closed by an intrathoracic transposition of a pedicled latissimus dorsi muscle flap, which was sutured into the debrided defect followed by temporary endotracheal stenting and antifungal medication.

A case for early bronchoscopic airway assessment after disc battery ingestion

Disc battery ingestion in children is becoming increasingly common with the proliferation of small battery-powered electronic devices. In the case of esophageal impaction, the likelihood and severity of complications are proportionate to the time between ingestion and removal. Tracheo-esophageal fistulae (TOF) are a recognized complication and can be life-threatening. We describe an interesting case of disc battery ingestion with delayed recognition of a TOF. We document the tracheal mucosal healing process of a large airway defect and describe the role of bronchoscopy in guiding the timing of surgical intervention. This case highlights the important role of early bronchoscopic assessment in management of these patients.

ARMC4 Mutations Cause Primary Ciliary Dyskinesia with Randomization of Left/Right Body Asymmetry

The motive forces for ciliary movement are generated by large multiprotein complexes referred to as outer dynein arms (ODAs), which are preassembled in the cytoplasm prior to transport to the ciliary axonemal compartment. In humans, defects in structural components, docking complexes, or cytoplasmic assembly factors can cause primary ciliary dyskinesia (PCD), a disorder characterized by chronic airway disease and defects in laterality. By using combined high resolution copy-number variant and mutation analysis, we identified ARMC4 mutations in twelve PCD individuals whose cells showed reduced numbers of ODAs and severely impaired ciliary beating. Transient suppression in zebrafish and analysis of an ENU mouse mutant confirmed in both model organisms that ARMC4 is critical for left-right patterning. We demonstrate that ARMC4 is an axonemal protein that is necessary for proper targeting and anchoring of ODAs.

Jagged1 is the major regulator of notch‐dependent cell fate in proximal airways

The Notch signaling pathway plays complex roles in developing lungs, including regulation of proximodistal fates, airway cell specification and differentiation. However, the specific Notch-mediated signals involved in lung development remain unclear. Here we report that Jagged1 is expressed in a subset of bronchial and bronchiolar epithelial cells, where it controls proximal airway cell fate and differentiation. In agreement with previous studies involving disruption of all Notch signaling, we found that deletion of Jagged1 in airway epithelium increased the number of ciliated cells at the expense of Clara cells, a phenotype associated with downregulation of Hes1. Deletion of Jagged1 also led to an increased number of pulmonary neuroendocrine cells (PNEC), suggesting that Jagged1/Notch signaling inhibits PNEC cell fate. As expected, Jagged1 deletion did not affect alveolar cell differentiation, although alveolar septation was impaired, likely an indirect effect of proximal airway defects. Finally, in the postnatal lung, Jagged1 deletion induced mucous metaplasia, accompanied by downregulation of Hes1 and Hes5. Our results demonstrate that Jagged1-mediated Notch signaling regulates multiple cell fate decisions as well as differentiation in the respiratory system to coordinate lung development and to maintain a balance of airway cell types in adult life.

Osteocutaneous radial forearm reconstruction of large partial cricotracheal defects

Single-stage procedures for reconstruction of large cricotracheal defects have been limited in success and malignant immature teratomas in the larynx of an adult have never been reported. This was a case report and literature review. A 27-year-old man presented with 2 weeks of new-onset stridor and was found to have a mass obstructing 80% of the subglottis and trachea. He underwent a noncircumferential partial cricotracheal resection with a resultant 7-cm luminal defect, followed by osteocutaneous radial forearm flap semi-rigid reconstruction. A novel technique was used to allow a functional and patent airway, which may be applied to other partial luminal reconstructive defects. Postoperatively, the patient was decannulated and has good speech quality and swallowing function. This work was performed at the Henry Ford Health System. This project was reviewed and was granted full approval by the Henry Ford Health System Institutional Review Board. This is the first reported case of malignant immature teratoma to involve the larynx, trachea, and recurrent laryngeal nerve in an adult patient, and the first single-stage technique described to use free tissue transfer without prefabrication for a 7-cm airway defect.

Non-circumferential tracheal resection with muscle flap reconstruction for adenoid cystic carcinoma

Circumferential airway resection with primary anastomosis has been widely adopted as a treatment for adenoid cystic carcinoma (ACC) of the trachea. However, carinal resection is a complicated procedure with high mortality and morbidity rates. We describe a technique of non-circumferential tracheal resection performed to treat ACC arising from the lower membranous trachea adjacent to the carina. The tumor was resected while preserving the tracheo-carinal cartilage. A silicone Y-stent was placed at the bifurcation to ensure airway patency before closing the defect. The airway defect, measuring 4×2.5cm, was closed using an autologous pericardial patch and pedicled latissimus dorsi muscle flap. These procedures were technically easy, and no postoperative airway complication occurred.

The pumpless extracorporeal lung membrane provides complete respiratory support during complex airway reconstructions without inducing cellular trauma or a coagulatory and inflammatory response

Our objective was to investigate the capacity of a pumpless extracorporeal lung membrane (iLA) (Novalung; Novalung GmbH, Hechingen, Germany) to provide adequate respiratory support and the impact on morbidity/mortality during complex airway reconstruction. Only patients unable to be ventilated via conventional intubation were eligible for the study. A larynx mask or orotracheal tubes were placed above the airway defect and the iLA was attached via femoral vessels (arteriovenous), providing extracorporeal gas exchange, apneic hyperoxygenation, and total tubeless airway reconstruction. Haptoglobulin, plasmin-antiplasmin complex, P-selectin activation, and interleukin 6 were measured before, during, and after iLA use and 72 hours postoperatively. Fifteen consecutive patients (age, 42±17 years) underwent elective (n=7) or emergency (n=8) reconstruction of the airway owing to a variety of disorders or defects. The iLA was left in place for 185±61 minutes, diverted 1.70±0.48 L/min of the cardiac output, and provided an arteriovenous carbon dioxide removal and oxygen transfer of 173±94 and 144±83 mL/min, respectively. The arterial oxygen tension/inspired oxygen fraction (314±31 mm Hg), and arterial carbon dioxide tension (40±6 mm Hg) remained stable throughout the entire operations. The following procedures were performed: redo slide tracheoplasties (n=3), redo tracheoesophageal fistula repair (n=1), sleeve lobectomies (n=2), main carina reconstructions (n=7), and anastomotic stenting and myocutaneous coverages (n=2). Three patients required prolonged (9±2 days) postoperative iLA support. Two (13%) patients died during the hospital stay. The use of iLA was associated with significant (P<.05) but clinically nonrelevant and yet nonpathologic increases of haptoglobulin (hemolysis), plasmin-antiplasmin complex (coagulation activation), and P-selectin activation (platelet activation). Data normalized within 48 hours postoperatively. Data suggest that iLA provides complete intraoperative respiratory support in patients who cannot receive conventional intubation/ventilation without relevant effects on cellular trauma, coagulatory response, and inflammatory response.

Tracheobronchial reconstructions with bronchoplastic closure: An alternative method in treatment of bronchogenic carcinoma involving the carina or tracheobronchial angle

Our objective was to summarize our experience with tracheobronchial reconstructions using bronchoplastic closure for airway defects after noncircumferential resections of bronchogenic carcinoma involving the carina or tracheobronchial angle. From January 1990 to December 2005, all patients who underwent tracheobronchial reconstructions with bronchoplastic closure for bronchogenic carcinoma involving the carina or tracheobronchial angle were included. The clinical data for patients were collected retrospectively, including demographic characteristics, occurrences of postoperative complications, and survival. A total of 40 patients were eligible, including 23 who had right pneumonectomies, 6 who had right upper lobectomies, and 11 who had left pneumonectomies, associated with lower lateral wall of the trachea resections or with partial carinal resections for centrally localized tumors. The airway defects ranged from 0.5×2 cm to 2×4 cm and involved up to 50% of the airway circumference. Microscopic residual disease was found postoperatively at the bronchial margin in 20% (8/40). Of 40 patients, 2 (5.0%) had pulmonary atelectasis develop, 2 (5.0%) arrhythmia, 2 (5.0%) bronchopleural fistula, and 1 (2.5%) airway stenosis after operation. Thirty-day mortality was 2.5% (1/40). Median survival for 40 patients was 18.5 months with a cumulative survival of 72.2%, 26.6%, and 21.3% at 1, 3, and 5 years, respectively. Tracheobronchial reconstruction using bronchoplastic closure might be a reasonable option for closing massive central airway defects for advanced bronchogenic carcinoma involving the tracheobronchial angle or carina, avoiding tracheal sleeve pneumonectomy with limited excision of the lateral wall of the trachea or carina.

Effect of Myrtol standardized on mucus hypersecretion and clearance of Pseudomonas aeruginosa in a rat model of chronic obstructive pulmonary disease

This study aimed to investigate the effect of Myrtol standardized (GeloMyrtol forte) in the treatment of chronic obstructive pulmonary disease (COPD) in an animal model. A total of 93 experimental rats were randomly divided into 6 groups: control (n = 6), exposure to cigarette smoke (CS, n = 6), CS plus Myrtol standardized treatment (CS + M, n = 6), Pseudomonas aeruginosa (PA) infection (PA, n = 25), CS + PA (n = 25), and CS + PA + M (n = 25). For all 62 CS rats, they were exposed to cigarette smoke for a period of 12 weeks. During this time period the 31 CS + M rats (CS + M; CS + PA + M) received 300 mg/kg/day Myrtol standardized intragastrically always 30 min prior to smoke exposure. For CS + PA and CS + PA + M rats, intratracheal PA inoculation was performed after the 12 weeks of smoke exposure. All intratracheal PA inoculations were followed by a post-infection examination at 6, 12, 24, 48 and 72 h in each 5 rats. All study animals were euthanized and their lungs were excised; the left lung was homogenized for determination of bacterial load and measurements of TNF-alpha and IL-6, the right lungs were preserved for histo- and immunohistochemical examinations (e. g. MUC5AC). The lungs from CS rats were pathologically similar to those of COPD patients with the characteristics of goblet cell metaplasia and MUC5AC hypersecretion. CS animals had a significantly greater number of MUC5AC positive cells in the bronchial epithelial cells, and significantly increased expression levels of TNF-alpha and IL-6 after PA infection. However, the administration of Myrtol standardized significantly (p = 0.002) attenuated MUC5AC hypersecretion, measured as integrity optical density (IOD), in CS + M rats (45.98 +/- 6.25) as compared to CS alone (65.55 +/- 11.18) rats. The same applies at different time points between CS + PA rats (65.15 +/- 11.94, 75.88 +/- 7.42, 81.2 +/- 6.49, 75.14 +/- 6.85 and 67.32 +/- 10.61, respectively) and CS + PA + M rats (47.08 +/- 4.78, 54.22 +/- 6.59, 65.4 +/- 6.12, 59.98 +/- 4.96 and 48.43 +/- 7.29, respectively). Similar effects were found in the production of IL-6 and TNF-alpha in the CS + PA + M lungs. Similarly the bacterial load of 10,980 +/- 4,253 CFU in CS + PA + M was significantly lower compared to 42,400 +/- 3,296 CFU in CS + PA lungs after 72 h PA infection. In conclusion, this experimental study demonstrates a significant therapeutic effect of Myrtol standardized in treating common pathological conditions, such as airway mucus hypersecretion and defect of mucociliary functions in COPD.

RETRACTED: Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study

Tracheal tumours can be surgically resected but most are an inoperable size at the time of diagnosis; therefore, new therapeutic options are needed. We report the clinical transplantation of the tracheobronchial airway with a stem-cell-seeded bioartificial nanocomposite. A 36-year-old male patient, previously treated with debulking surgery and radiation therapy, presented with recurrent primary cancer of the distal trachea and main bronchi. After complete tumour resection, the airway was replaced with a tailored bioartificial nanocomposite previously seeded with autologous bone-marrow mononuclear cells via a bioreactor for 36 h. Postoperative granulocyte colony-stimulating factor filgrastim (10 μg/kg) and epoetin beta (40,000 UI) were given over 14 days. We undertook flow cytometry, scanning electron microscopy, confocal microscopy epigenetics, multiplex, miRNA, and gene expression analyses. We noted an extracellular matrix-like coating and proliferating cells including a CD105+ subpopulation in the scaffold after the reseeding and bioreactor process. There were no major complications, and the patient was asymptomatic and tumour free 5 months after transplantation. The bioartificial nanocomposite has patent anastomoses, lined with a vascularised neomucosa, and was partly covered by nearly healthy epithelium. Postoperatively, we detected a mobilisation of peripheral cells displaying increased mesenchymal stromal cell phenotype, and upregulation of epoetin receptors, antiapoptotic genes, and miR-34 and miR-449 biomarkers. These findings, together with increased levels of regenerative-associated plasma factors, strongly suggest stem-cell homing and cell-mediated wound repair, extracellular matrix remodelling, and neovascularisation of the graft. Tailor-made bioartificial scaffolds can be used to replace complex airway defects. The bioreactor reseeding process and pharmacological-induced site-specific and graft-specific regeneration and tissue protection are key factors for successful clinical outcome. European Commission, Knut and Alice Wallenberg Foundation, Swedish Research Council, StratRegen, Vinnova Foundation, Radiumhemmet, Clinigene EU Network of Excellence, Swedish Cancer Society, Centre for Biosciences (The Live Cell imaging Unit), and UCL Business.

Age-Related Impairment of Ultrasonic Vocalization in Tau.P301L Mice: Possible Implication for Progressive Language Disorders

BackgroundTauopathies, including Alzheimer's Disease, are the most frequent neurodegenerative diseases in elderly people and cause various cognitive, behavioural and motor defects, but also progressive language disorders. For communication and social interactions, mice produce ultrasonic vocalization (USV) via expiratory airflow through the larynx. We examined USV of Tau.P301L mice, a mouse model for tauopathy expressing human mutant tau protein and developing cognitive, motor and upper airway defects.Methodology/Principal FindingsAt age 4–5 months, Tau.P301L mice had normal USV, normal expiratory airflow and no brainstem tauopathy. At age 8–10 months, Tau.P301L mice presented impaired USV, reduced expiratory airflow and severe tauopathy in the periaqueductal gray, Kolliker-Fuse and retroambiguus nuclei. Tauopathy in these nuclei that control upper airway function and vocalization correlates well with the USV impairment of old Tau.P301L mice.ConclusionsIn a mouse model for tauopathy, we report for the first time an age-related impairment of USV that correlates with tauopathy in midbrain and brainstem areas controlling vocalization. The vocalization disorder of old Tau.P301L mice could be, at least in part, reminiscent of language disorders of elderly suffering tauopathy.

Thyroid Perichondrial Flaps for Sub‐Glottic Reconstruction

Objective: Techniques available for reconstruction of the crico-tracheal region in adults are currently suboptimal. We sought to 1) Understand the anatomic basis for the thyroid perichondrial flap, 2) Describe the technique of harvesting and intraluminal placement, and 3) Learn the limitations of defects for which it can be used. Method: In fresh cadaveric specimens, the perichondrium of the outer layer of the thyroid cartilage was elevated by tracing the superior, medial and lateral borders of each thyroid cartilage ala. The inferiorly based flap was then placed into the airway through the cricothyroid membrane. The extent of coverage was measured. Results: Current results are limited to female cadaveric measurements only. The extent of thyroid perichondrial flaps were 1.7 and 1.8 cm on the right and left respectively. The flaps were able to completely cover the cricoid cartilage and extended to but did not cover the first tracheal ring. Once placed intraluminally the flaps extended 2.5 and 2.6 cm below the true vocal cords on the right and left respectively. Using both flaps enabled coverage of the entire anterior 180 degrees of the airway lumen. Conclusion: The thyroid perichondrial flap is technically feasible and can provide coverage of anterior airway defects up to approximately 2.5 cm below the true vocal cords. This flap could enable transfer of vascularized tissue to aid in crico-tracheal reconstruction. Further work in male cadavers as well as animal studies are in progress.

Raphé tauopathy alters serotonin metabolism and breathing activity in terminal Tau.P301L mice: Possible implications for tauopathies and Alzheimer's disease

Tauopathies, including Alzheimer's disease are the most frequent neurodegenerative disorders in elderly people. Patients develop cognitive and behaviour defects induced by the tauopathy in the forebrain, but most also display early brainstem tauopathy, with oro-pharyngeal and serotoninergic (5-HT) defects. We studied these aspects in Tau.P301L mice, that express human mutant tau protein and develop tauopathy first in hindbrain, with cognitive, motor and upper airway defects from 7 to 8 months onwards, until premature death before age 12 months. Using plethysmography, immunohistochemistry and biochemistry, we examined the respiratory and 5-HT systems of aging Tau.P301L and control mice. At 8 months, Tau.P301L mice developed upper airway dysfunction but retained normal respiratory rhythm and normal respiratory regulations. In the following weeks, Tau.P301L mice entered terminal stages with reduced body weight, progressive limb clasping and lethargy. Compared to age 8 months, terminal Tau.P301L mice showed aggravated upper airway dysfunction, abnormal respiratory rhythm and abnormal respiratory regulations. In addition, they showed severe tauopathy in Kolliker-Fuse, raphé obscurus and raphé magnus nuclei but not in medullary respiratory-related areas. Although the raphé tauopathy concerned mainly non-5-HT neurons, the 5-HT metabolism of terminal Tau.P301L mice was altered. We propose that the progressive raphé tauopathy affects the 5-HT metabolism, which affects the 5-HT modulation of the respiratory network and therefore the breathing pattern. Then, 5-HT deficits contribute to the moribund phenotype of Tau.P301L mice, and possibly in patients suffering from tauopathies, including Alzheimer's disease.

The ENaC-overexpressing mouse as a model of cystic fibrosis lung disease

Chronic lung disease remains the major cause of morbidity and mortality of cystic fibrosis (CF) patients. Cftr mutant mice developed severe intestinal obstruction, but did not exhibit the characteristic CF ion transport defects (i.e. deficient cAMP-dependent Cl − secretion and increased Na + absorption) in the lower airways, and failed to develop CF-like lung disease. These observations led to the generation of transgenic mice with airway-specific overexpression of the epithelial Na + channel (ENaC) as an alternative approach to mimic CF ion transport pathophysiology in the lung. Studies of the phenotype of βENaC-transgenic mice demonstrated that increased airway Na + absorption causes airway surface liquid (ASL) depletion, reduced mucus transport and a spontaneous CF-like lung disease with airway mucus obstruction and chronic airway inflammation. Here, we summarize approaches that can be applied for studies of the complex in vivo pathogenesis and preclinical evaluation of novel therapeutic strategies in this model of CF lung disease.

Kergin Pneumonectomy: A Rare Procedure

We have evaluated our cases of "Kergin" pneumonectomy in which a bronchial flap of the medial part of the right main stem bronchus was created during right pneumonectomy and was turned upward to cover the lateral airway defect at the level of the carina. Five male patients with a mean age of 53.6 underwent "Kergin" pneumonectomy due to nonsmall cell carcinoma arising from right upper lobe entrance, which does not allow a classical pneumonectomy. Postoperative pathology stagings were stage IIB in 1 patient and stage IIIA in 4 patients. Any operative mortality or short-term complication was not observed. Two of the patients died in the second year of follow-up. "Kergin" pneumonectomy is a rarely performed procedure with acceptable morbidity and mortality and good lung cancer resection. Actually, our current report of five cases will be one of the largest series of "Kergin" pneumonectomy.

Tissue-engineered airway and “in situ tissue engineering”

Since the 1980s, tissue engineering has become one of the major areas of endeavor in medical research, applying the principles of biology and engineering to the development of functional substitutes for damaged tissue. Using this technology, various attempts have been made to create and apply a tissue-engineered prosthetic trachea, or airway. In addition to the conventional tissue engineering approach, a new substantially different concept has been advocated in Japan since 2000. This is "in situ tissue engineering," where a tissue is created not in vitro but in vivo, exploiting the potential of the living body for wound healing. An artificial trachea created by in situ tissue engineering has already been applied in human patients for reconstruction of airway defects, and promising results have been obtained. This article reviews recent progress in the relatively new field of airway reconstruction employing tissue engineering.