A 70-Year-Old Man With Cough and Recurrent Respiratory Infections.

CASE PRESENTATION: A 70-year-old man was referred for evaluation of recurrent respiratory infections requiring antibiotics and chronic cough over 3 years. Two months prior to presentation, he started to develop blood-tinged sputum but not frank hemoptysis. He otherwise denied any fever, chills, night sweats, or weight loss. He had dyspnea during the respiratory infections but not otherwise. His medical history was significant for chronic rhinitis without sinusitis and a low serum IgM level. He was a never smoker and a farmer but otherwise had no significant or specific exposures or travel history. His family history was significant for alpha-1 antitrypsin deficiency in his mother.

Descending Aortopexy and Posterior Tracheopexy for Severe Tracheomalacia and Left Mainstem Bronchomalacia.

Posterior descending aortopexy can relieve posterior intrusion of the left mainstem bronchus that may limit the effectiveness of posterior tracheobronchopexy. We review outcomes of patients undergoing both descending aortopexy and posterior tracheopexy for severe tracheobronchomalacia with posterior intrusion and left mainstem compression to determine if there were resolution of clinical symptoms and bronchoscopic evidence of improvement in airway collapse. All patients who underwent both descending aortopexy and posterior tracheopexy from October 2012 to October 2016 were retrospectively reviewed. Clinical symptoms, tracheomalacia scores based on standardized dynamic airway evaluation by anatomical region, and persistent airway intrusion requiring reoperation were collected. Data were analyzed by Wald and Wilcoxon signed-rank tests. Thirty-two patients underwent descending aortopexy and posterior tracheopexy at median age of 18 months (interquartile range 6-40 months). Median follow-up was 3 months (interquartile range 1-7 months). There were statistically significant improvements in clinical symptoms postoperatively, including cough, noisy breathing, prolonged and recurrent respiratory infections, ventilator dependence, blue spells, and brief resolved unexplained events (all P < 0.001), as well as exercise intolerance (P = 0.033), transient respiratory distress requiring positive pressure (P = 0.003), and oxygen dependence (P = 0.007). Total tracheomalacia scores improved significantly (P < 0.001), with significant segmental improvements in the middle (P = 0.003) and lower (P < 0.001) trachea, and right (P = 0.011) and left (P < 0.001) mainstem bronchi. Two patients (6%) had persistent airway intrusion requiring reoperation with anterior aortopexy or tracheopexy. Descending aortopexy and posterior tracheopexy are effective in treating severe tracheobronchomalacia and left mainstem intrusion with significant improvements in clinical symptoms and degree of airway collapse on bronchoscopy.

Computed tomographic bronchial collapsibility values over 50% may be detected in healthy dogs.

Bronchomalacia and bronchial collapse are important causes of chronic coughing in dogs. The current reference standard diagnostic tests for these problems are flexible bronchoscopy and biopsy. Previous human studies have also supported inspiration/expiration computed tomography (CT) as a diagnostic test. The current prospective, pilot study aimed to determine whether inspiration/expiration CT is also a feasible test for quantifying bronchial collapsibility in dogs. Thoracic CT images were acquired using a 64-row multidetector CT for 10 healthy Beagle dogs during maximal inspiration and expiration. For each scan, one observer measured transverse sectional areas of the mainstem and lobar bronchi, and the dorsal and ventral segmental bronchi of the left cranial lobar bronchus. Diameters for each bronchus were also measured in transverse, sagittal, and dorsal planes. Bronchial collapsibility (%) was calculated as the difference between inspiration/expiration transverse sectional areas divided by the inspiration transverse sectional areas. Mean bronchial collapsibility of all bronchi was 38.20 ± 15.17%. A collapsibility of over 50% was found in the dorsal (n = 7) and ventral (n = 4) segmental bronchi of the left cranial lobar bronchus, and the left caudal (n = 5) and right middle (n = 2) lobar bronchus. Bronchial collapsibility measurements were greater in the dorsal and ventral segmental bronchi of the left cranial lobar bronchus and the left caudal lobar bronchus (P < 0.001). Findings supported inspiration/expiration CT as a modality to noninvasively assess bronchial collapse in dogs and a bronchial collapsibility value greater than 50% for detecting pathologic bronchial collapse in clinically affected dogs.

Laryngomalacia, Tracheomalacia and Bronchomalacia.

Airway malacia can occur in the larynx (larygomalacia), trachea (tracheomalacia), or bronchi (bronchomalacia). As a group these are the most common congenital abnormalities of the pediatric airway and are characterized by increased airway compliance, resulting in excessive dynamic collapse during the respiratory cycle. While a diagnosis can be suspected based on clinical history and physical examination, definitive evaluation is based of nasopharyngolaryngoscopy and/or bronchoscopy. Observation and conservative management are typically all that are required. However, surgical intervention can be necessary in the most severe cases, and can result in significant improvement in symptoms.

Post-pneumonectomy and post-lobectomy syndromes: case series and review of the literature.

The post-pneumonectomy syndrome is a rare complication consisting of rotation and herniation of the mediastinal structures, the remaining lung and the respective bronchi, into the contralateral hemithorax. This situation may produce symptomatic airway obstruction and varies in its presentation and severity. We describe one case of right and one of left pneumonectomy syndrome as well as one case of post-lobectomy syndrome. We review the literature on the pathophysiology, the clinical, radiological and bronchoscopic characteristics of this rare entity and discuss all available therapeutic alternatives.

Chitayat syndrome: hyperphalangism, characteristic facies, hallux valgus and bronchomalacia results from a recurrent c.266A>G p.(Tyr89Cys) variant in the ERF gene.

BACKGROUND: In 1993, Chitayat et al., reported a newborn with hyperphalangism, facial anomalies, and bronchomalacia. We identified three additional families with similar findings. Features include bilateral accessory phalanx resulting in shortened index fingers; hallux valgus; distinctive face; respiratory compromise. OBJECTIVES: To identify the genetic aetiology of Chitayat syndrome and identify a unifying cause for this specific form of hyperphalangism. METHODS: Through ongoing collaboration, we had collected patients with strikingly-similar phenotype. Trio-based exome sequencing was first performed in Patient 2 through Deciphering Developmental Disorders study. Proband-only exome sequencing had previously been independently performed in Patient 4. Following identification of a candidate gene variant in Patient 2, the same variant was subsequently confirmed from exome data in Patient 4. Sanger sequencing was used to validate this variant in Patients 1, 3; confirm paternal inheritance in Patient 5. RESULTS: A recurrent, novel variant NM_006494.2:c.266A>G p.(Tyr89Cys) in ERF was identified in five affected individuals: de novo (patient 1, 2 and 3) and inherited from an affected father (patient 4 and 5). p.Tyr89Cys is an aromatic polar neutral to polar neutral amino acid substitution, at a highly conserved position and lies within the functionally important ETS-domain of the protein. The recurrent ERF c.266A>C p.(Tyr89Cys) variant causes Chitayat syndrome. DISCUSSION: ERF variants have previously been associated with complex craniosynostosis. In contrast, none of the patients with the c.266A>G p.(Tyr89Cys) variant have craniosynostosis. CONCLUSIONS: We report the molecular aetiology of Chitayat syndrome and discuss potential mechanisms for this distinctive phenotype associated with the p.Tyr89Cys substitution in ERF.

Transplant Pulmonary Interventions: Translating Lung Transplant Interventions to Nontransplant Patients.

Roughly 10% of lung transplant recipients experience airway complications. Although the incidence has decreased dramatically since the first lung transplants were performed in the 1960s, airway complications have continued to adversely affect outcomes. Bronchoscopic interventions such as balloon dilation, airway stenting, and endobronchial electrocautery play an important role in ameliorating the morbidity and mortality associated with these complications. This review describes the array of bronchoscopic interventions used to treat airway complications after lung transplant and how these techniques can be used in nontransplant settings as well.

Traqueobroncomalacia / Tracheobronchomalacia

A 10-years-old girl with recurrent wheezing was diagnosed as asthmatic. Her spirometry showed variable central airway intrathoracic obstruction. The bronchoscopy confirmed the presence of bronchomalacia.

Se presenta el caso de una paciente de edad escolar, quien por sibilancias recurrentes se trataba como asmática. Al realizar espirometría forzada se detectó un compromiso variable de vía central intratorácica. La fibrobroncoscopía confirmó la presencia de broncomalacia.

The first tissue-engineered airway transplantation: 5-year follow-up results.

BACKGROUND: In 2008, the first transplantation of a tissue-engineered trachea in a human being was done to replace an end-staged left main bronchus with malacia in a 30-year-old woman. We report 5 year follow-up results. METHODS: The patient was followed up approximately every 3 months with multidetector CT scan and bronchoscopic assessment. We obtained mucosal biopsy samples every 6 months for histological, immunohistochemical, and electron microscopy assessment. We also assessed quality of life, respiratory function, cough reflex test, and production and specificity of recipient antibodies against donor human leucocyte antigen. FINDINGS: By 12 months after transplantation, a progressive cicatricial stenosis had developed in the native trachea close to the tissue-engineered trachea anastomosis, which needed repeated endoluminal stenting. However, the tissue-engineered trachea itself remained open over its entire length, well vascularised, completely re-cellularised with respiratory epithelium, and had normal ciliary function and mucus clearance. Lung function and cough reflex were normal. No stem-cell-related teratoma formed and no anti-donor antibodies developed. Aside from intermittent bronchoscopic interventions, the patient had a normal social and working life. INTERPRETATION: These clinical results provide evidence that a tissue-engineering strategy including decellularisation of a human trachea, autologous epithelial and stem-cell culture and differentiation, and cell-scaffold seeding with a bioreactor is safe and promising. FUNDING: European Commission, Knut and Alice Wallenberg Foundation, Swedish Research Council, ALF Medicine.

Bronchomalacia in dogs with myxomatous mitral valve degeneration.

BACKGROUND: Cough in the geriatric small breed dog with myxomatous mitral valve degeneration (MMVD), a large left atrium, and absence of heart failure often is attributed to compression of the left mainstem bronchus by the left atrium. Studies investigating this syndrome are lacking in dogs. HYPOTHESIS: Airway collapse is independent of left atrial enlargement. ANIMALS: A total of 16 dogs presenting with chronic cough in the absence of congestive heart failure. Group 1 dogs (n = 10) had moderate-to-severe left atrial enlargement based on an echocardiographically calculated left atrial:aortic surface area [LA:Ao(a)] > 6. Group 2 dogs (n = 6) had no to mild left atrial enlargement [LA:Ao(a) ≤ 6]. METHODS: Dogs were prospectively evaluated. CBC, biochemistry, urinalysis, cervical and thoracic radiographs, fluoroscopy, echocardiography, and bronchoscopy were performed. Bronchoscopic abnormalities were compared between groups using Fisher's Exact Test. P < .05 was considered significant. RESULTS: Fluoroscopy identified airway collapse in both groups. Bronchoscopic evidence of airway collapse >50% was observed in multiple bronchi with no difference between groups. All dogs had inflammation on airway cytology with respiratory infection in 1 dog in group 2. Left atrial size was interpreted radiographically as enlarged in 9 of 10 group 1 dog and in 2 of 6 group 2 dogs. VHS was above normal in both groups of dogs regardless of echocardiographic evidence of cardiomegaly. CONCLUSIONS: Results failed to identify an association between left atrial enlargement and airway collapse in dogs with MMVD, but did suggest that airway inflammation is common in dogs with airway collapse.

Treatment of airway complications following lung transplantation.

OBJECTIVE: To describe our experience in airway complications following lung transplant and to suggest a management algorithm, using different tools from the Interventional Pulmonology armamentarium. METHOD: Retrospective chart review of all airway complications following lung transplant from January 1999 to July 2007. RESULTS: During that period 223 patients underwent lung transplantation, with a total of 345 anastomoses in the airway. Seventy anastomoses (20.23%) had complications requiring endoscopic treatment. The total number of endoscopic interventions were 631 in 52 patients. Thirty three patients had a combination of bronchial stenosis and bronchomalacia. Eighteen patients had bronchial stenosis only and 1 patient had dehiscence of the anastomosis. Balloon dilation was most commonly transiently effective and ultimately 47 patients required stent placement. The most common complication associated with the use of stent was granulation tissue formation, seen in 57.3% of patients. After stent placement, the forced expiratory volume in 1(st) second (FEV(1)) improved significantly. CONCLUSION: Airway complications after lung transplant are frequent. Balloon dilation was effective only in a few patients with bronchial stenosis, although the majority ultimately needed a stent. Airway repermeabilization after stent placement improved FEV(1). Based on our experience, we propose a management algorithm for airway complications after lung transplant.

Bronchial collapsibility at forced expiration in healthy volunteers: assessment with multidetector CT.

PURPOSE: To assess forced-expiratory bronchial collapsibility in healthy volunteers by using multidetector computed tomography (CT) and to compare the results with the current diagnostic criterion for bronchomalacia. MATERIALS AND METHODS: The institutional review board approved this HIPAA-compliant study. Following informed consent, 51 healthy volunteers with normal pulmonary function and no history of smoking were imaged by using a 64-detector row scanner with spirometric monitoring at total lung capacity and during forced exhalation. The total study population (in whom both main bronchi were imaged) included 25 men and 26 women (mean age, 50 years). Each scan was analyzed at a workstation by a fellowship-trained thoracic radiologist. Cross-sectional area measurements were obtained from end-inspiratory and forced-expiratory CT images for the right main bronchus (RMB), left main bronchus, (LMB), and bronchus intermedius (BI), and the mean percentage of expiratory collapse was calculated for each bronchus. The number of participants who exceeded the current diagnostic threshold level (>50% expiratory reduction in cross-sectional area) for bronchomalacia was calculated. Comparisons of airway dimensions and airway collapse according to bronchial segment and sex were made by using repeated-measures analysis of variance. RESULTS: Mean percentage of expiratory collapse was 66.9% ± 19.0 (standard deviation) for the RMB and 61.4% ± 16.7 for the LMB. Thirty-seven (73%) of 51 participants exceeded the diagnostic threshold level for bronchomalacia. Significant differences were observed in mean percentage of expiratory collapse between the RMB (66.9% ± 19.0) and LMB (61.4% ± 16.7) (P = .0005). Among a subgroup of 37 participants in whom the BI was also imaged, the mean percentage of expiratory collapse was 61.8% ± 22.8, and 27 (73%) participants exceeded the diagnostic threshold level for bronchomalacia. CONCLUSION: Healthy volunteers demonstrate a wide range of forced-expiratory bronchial collapse, frequently exceeding the current diagnostic threshold level for bronchomalacia.

Clinical experience with a new removable tracheobronchial stent in the management of airway complications after lung transplantation.

BACKGROUND: Airway complications are among the most challenging problems after lung transplantation. This article describes the use of a new tracheobronchial stent that can be placed and removed easily by flexible bronchoscopy. METHODS: A retrospective review was done of 24 consecutive patients requiring tracheobronchial stent placement after lung transplantation. A new self-expanding hybrid nitinol stent was used, and changes in airway diameter and spirometry were assessed. Stent related complications were recorded. RESULTS: Between February 2007 and April 2008, 24 patients underwent stent placement, and 49 stents were placed for 36 anastomoses at risk. Indications included bronchial stenosis in 12, bronchomalacia in 12, bronchial stenosis plus bronchomalacia in 20, and partial bronchial dehiscence in 5. Adjunctive procedures included electrocautery in 1, balloon dilatation in 7, and electrocautery plus balloon dilatation in 4. The average degree of stenosis decreased from 80% to 20%. After stent placement, the average increase was 0.28 liters in forced vital capacity and 0.44 liters in forced expiratory volume in 1 second. Complications included granulation tissue formation in 10 stents, migration in 9, thick mucus formation in 2, and fracture in 3. CONCLUSION: Airway complications in lung transplant patients were effectively palliated. Our complication rate with this new stent is comparable with other airway stents. This stent has the advantage of easy removability during flexible bronchoscopy if complications from the stent outweigh the benefits of palliation.

Clinical transplantation of a tissue-engineered airway.

BACKGROUND: The loss of a normal airway is devastating. Attempts to replace large airways have met with serious problems. Prerequisites for a tissue-engineered replacement are a suitable matrix, cells, ideal mechanical properties, and the absence of antigenicity. We aimed to bioengineer tubular tracheal matrices, using a tissue-engineering protocol, and to assess the application of this technology in a patient with end-stage airway disease. METHODS: We removed cells and MHC antigens from a human donor trachea, which was then readily colonised by epithelial cells and mesenchymal stem-cell-derived chondrocytes that had been cultured from cells taken from the recipient (a 30-year old woman with end-stage bronchomalacia). This graft was then used to replace the recipient's left main bronchus. FINDINGS: The graft immediately provided the recipient with a functional airway, improved her quality of life, and had a normal appearance and mechanical properties at 4 months. The patient had no anti-donor antibodies and was not on immunosuppressive drugs. INTERPRETATION: The results show that we can produce a cellular, tissue-engineered airway with mechanical properties that allow normal functioning, and which is free from the risks of rejection. The findings suggest that autologous cells combined with appropriate biomaterials might provide successful treatment for patients with serious clinical disorders.