Effect of Prenatal versus Postnatal Vitamin D Deficiency on Pulmonary Structure and Function in Mice.

Epidemiologic studies have linked gestational vitamin D deficiency to respiratory diseases, although mechanisms have not been defined. We hypothesized that antenatal vitamin D deficiency would impair airway development and alveolarization in a mouse model. We studied the effect of antenatal vitamin D deficiency by inducing it in pregnant mice and then compared lung development and function in their offspring to littermate controls. Postnatal vitamin D deficiency and sufficiency models from each group were also studied. We developed a novel tracheal ultrasound imaging technique to measure tracheal diameter in vivo. Histological analysis estimated tracheal cartilage total area and thickness. We found that vitamin D-deficient pups had reduced tracheal diameter with decreased tracheal cartilage minimal width. Vitamin D deficiency increased airway resistance and reduced lung compliance, and led to alveolar simplification. Postnatal vitamin D supplementation improved lung function and radial alveolar count, a parameter of alveolar development, but did not correct tracheal narrowing. We conclude that antenatal vitamin D deficiency impairs airway and alveolar development and limits lung function. Reduced tracheal diameter, cartilage irregularity, and alveolar simplification in vitamin D-deficient mice may contribute to increased airways resistance and diminished lung compliance. Vitamin D supplementation after birth improved lung function and, potentially, alveolar simplification, but did not improve defective tracheal structure. This mouse model offers insight into the mechanisms of vitamin D deficiency-associated lung disease and provides an in vivo model for investigating preclinical preventive and therapeutic strategies.

Tracheal damage.

Tracheal damage. Blunt/penetrating trauma and inhalation injuries to the trachea can result in acute airway compromise, with life-threatening implications. Early assessment, identification, and prompt and appropriate management are of paramount importance in order to reduce patient morbidity and mortality. Signs and symptoms of these injuries are specific and sometimes subtle, and their seriousness may be obscured by other injuries. Diagnosis can therefore be challenging, requiring a high index of suspicion. Indeed, diagnosis and treatment are often delayed, resulting in attempted surgical repair months or even years after injury. Laryngoscopy, flexible and/or rigid bronchoscopy and computed tomography of the chest are the procedures of choice for a definitive diagnosis. Airway control and appropriate ventilation represent the key aspects of emergency management. Definitive treatment depends on the site and the extent of injury. Surgery, involving primary repair with direct suture or resection and end-to-end anastomosis, is the treatment of choice for patients suffering from tracheal injuries. A conservative approach must be considered for the paediatric population and selected patients with mainly iatrogenic damage. We present a review of the incidence, mechanisms of injury, clinical presentations, diagnosis, initial airway management, anaesthetic considerations and definitive treatment in the case of tracheal damage from blunt/penetrating trauma and inhalation injuries.

Respiratory motion variability of primary tumors and lymph nodes during radiotherapy of locally advanced non-small-cell lung cancers.

BACKGROUND AND PURPOSE: The need for target adjustment due to respiratory motion variation and the value of carina as a motion surrogate is evaluated for locally advanced non-small-cell lung cancer. MATERIAL AND METHODS: Using weekly 4D CTs (with audio-visual biofeedback) of 12 patients, respiratory motion variation of primary tumors (PT), lymph nodes (LN) and carina (C) were determined. RESULTS: Mean (SD) 3D respiratory motion ranges of PT, LN and C were 4 (3), 5 (3) and 5 (3) mm. PT and LN (p = 0.003), and LN and C motion range were correlated (p = 0.03). Only 20 %/5 % of all scans had variations >3 mm/5 mm. Large respiratory motion range on the initial scan was associated with larger during-treatment variations for PT (p = 0.03) and LN (p = 0.001). Mean (SD) 3D relative displacements of PT-C, LN-C and PT-LN were each 6 (2) mm. Variations of displacements >3 mm/5 mm were observed in 28 %/6 % of scans for PT-LN, 20 %/9 % for PT-C, and 20 %/8 % for LN-C. CONCLUSIONS: Motion reassessment is recommended in patients with large initial motion range. Relative motion-related displacements between PT and LN were larger than PT and LN motion alone. Both PT and C appear to be comparable surrogates for LN respiratory motion.

Hyperbaric oxygen therapy for the treatment of anastomotic complications after tracheal resection and reconstruction.

OBJECTIVE: Failure of anastomotic healing is a rare but serious complication of laryngotracheal resection. Treatment options include reoperation, tracheostomy, or T-tube placement. Hyperbaric oxygen therapy (HBOT) is the delivery of 100% O2 at pressures greater than 1 atm, and has been shown to enhance wound healing after tracheal resection in animal models. To date, there have been no reports describing its usefulness in humans after tracheal resection. METHODS: Five consecutive patients with varying degrees of failed anastomotic healing, from necrotic cartilage to partial separation identified by bronchoscopy were treated with HBOT. HBOT was administered for 90 minutes via a hyperbaric chamber pressurized to 2 atm with 100% oxygen. Patients were treated with daily or twice daily HBOT. Four of 5 patients had buttressing of the anastomosis by strap muscle at the initial surgery. RESULTS: All patients had evidence of anastomotic healing on bronchoscopy. None of the patients in this series required tracheostomy, T-tube, or reoperation after initiation of HBOT. On average it took 9.6 days for healing to occur (5-14 days). The size of the anastomotic defect ranged between 3 and 13 mm. One patient required bilateral tympanostomy tubes for inner ear discomfort and experienced blurry vision as complications of HBOT. One patient developed tracheal stenosis from granulation tissue that required bronchoscopic debridement. CONCLUSIONS: In select patients with anastomotic complications after tracheal resection, HBOT may aid in healing and avoid tracheostomy. Future investigations are necessary to further define the benefits of HBOT in the management of airway anastomotic complications.

Verification of a commercial implementation of the Macro-Monte-Carlo electron dose calculation algorithm using the virtual accelerator approach.

In this work, the accuracy of the implementation of the Macro Monte Carlo electron dose calculation algorithm into the radiation therapy treatment planning system Eclipse is evaluated. This implementation - called eMC - uses a particle source based on the Rotterdam Initial Phase-Space model. A three-dimensional comparison of eMC calculated dose to dose distributions resulting from full treatment head simulations with the Monte Carlo code package EGSnrc is performed using the 'virtual accelerator' approach. Calculated dose distributions are compared for a homogeneous tissue equivalent phantom and a water phantom with air and bone inhomogeneities. The performance of the eMC algorithm in both phantoms can be considered acceptable within the 2%/2 mm Gamma index criterion. A systematic underestimation of dose by the eMC algorithm within the air inhomogeneity is found.

Palliative airway stenting performed under radiological guidance and local anesthesia.

PURPOSE: To assess the effectiveness of airway stenting performed exclusively under radiological guidance for the palliation of malignant tracheobronchial strictures. METHODS: We report our experience in 16 patients with malignant tracheobronchial stricture treated by insertion of 20 Ultraflex self-expandable metal stents performed under fluoroscopic guidance only. Three patients presented dysphagia grade IV due to esophageal malignant infiltration; they therefore underwent combined airway and esophageal stenting. All the procedures were performed under conscious sedation in the radiological room; average procedure time was around 10 min, but the airway impediment never lasted more than 40 sec. RESULTS: We obtained an overall technical success in 16 cases (100%) and clinical success in 14 patients (88%). All prostheses were successfully placed without procedural complications. Rapid clinical improvement with symptom relief and normalization of respiratory function was obtained in 14 cases. Two patients died within 48 hr from causes unrelated to stent placement. Two cases (13%) of migration were observed; they were successfully treated with another stent. Tumor overgrowth developed in other 2 patients (13%); however, no further treatment was possible because of extensive laryngeal infiltration. CONCLUSIONS: Tracheobronchial recanalization with self-expandable metal stents is a safe and effective palliative treatment for malignant strictures. Airway stenting performed exclusively under fluoroscopic view was rapid and well tolerated.

Safety and efficiency of metered dose inhaler delivery of salbutamol in the intubated rabbit.

OBJECTIVE: To determine the safety and efficiency of metered dose inhaler salbutamol delivered to the intubated rabbit. DESIGN: Prospective, comparative, five-group laboratory investigation. SETTING: Animal laboratory, Department of Nuclear Medicine. SUBJECTS: A total of 30 adult, anesthetized New Zealand White rabbits. INTERVENTIONS: Three groups of rabbits underwent tracheal intubation through a tracheostomy and received 5 puffs of 99mTcO4 salbutamol delivered at the elbow connector (group 1) or via a catheter with its distal tip positioned at the midpoint (group 2) or bevel of the endotracheal tube (group 3). No intervention was provided for the rabbits in the fourth group. A fifth group underwent tracheal intubation through the mouth and received salbutamol (5 puffs) delivered at the bevel of the endotracheal tube. MEASUREMENTS: Delivery efficiency was expressed as the ratio of radioactivity emitted from lungs and trachea to the total radioactivity of the administered dose. Histopathologic injury scores were assigned to each trachea or lung specimen. MAIN RESULTS: Delivery efficiency was 30 times greater in groups 3 and 5 (full catheter) than in group 1 (elbow). The injury scores were similar in all groups. CONCLUSION: We conclude that the increased efficiency obtained by administration of metered dose inhaler salbutamol at the distal tip of endotracheal tube is not necessarily associated with increased epithelial injury.

The feasibility of high dose iodine 131 treatment as an alternative to surgery in patients with a very large goiter: effect on thyroid function and size and pulmonary function.

Some patients with very large goiters (>150 mL) are not candidates for surgery. We evaluated the feasibility of high dose 131I in such patients. Twenty-three patients (2 men and 21 women; median age, 67 yr; range, 42-86 yr) with very large goiter (8 toxic) were treated with calculated high dose 131I [median, 2281 megabecquerels (61.6 mCi); range, 988-4620 megabecquerels (26.7-124.9 mCi)]. During the 12-month observation period, goiter reduction and tracheal anatomy were monitored by magnetic resonance imaging, and the respiratory capacity was monitored by pulmonary function tests. Five patients (22%) developed hypothyroidism. Thyroid volumes were at baseline, after 1 week, and after 1 yr [mean +/- SEM, 311 +/- 28, 314 +/- 26 (P = NS), and 215 +/- 26 (P < 0.01) mL]. The relative changes 1 week after therapy ranged from -14.1% to 15.3%. After 1 yr the mean size was reduced by 33.9% (range, 13.5-61.4%). Only the initial goiter size showed a significant negative correlation to the percent reduction. The smallest cross-sectional area of the trachea decreased 9.2% within 1 week after treatment, but eventually emerged with a 17.9% larger area [mean +/- SEM, 84.3 +/- 4.8, 75.5 +/- 5.1 (P < 0.01), and 98.2 +/- 6.0 (P < 0.01) mm2]. The inspiratory parameter, FIF50%, improved after an initial insignificant decline [baseline therapy, after 1 week, after 3 months, and after 1 yr (mean +/- SEM), 2.37 +/- 0.24, 2.20 +/- 0.21 (P = NS), 2.51 +/- 0.23 (P = NS), and 2.76 +/- 0.25 (P = 0.01) L/s]. FIF50% correlated significantly with the smallest cross-sectional tracheal area (baseline, 1 week, and 1 yr: r = 0.74; P < 0.001, r = 0.63; P < 0.005, and r = 0.46; P < 0.05). Changes in tracheal anatomy did not correlate with changes in either lung dynamics or goiter size. In conclusion, very large goiters can be reduced by a third, on the average, with high dose 131I therapy without any initial clinically significant tracheal compression. Tracheal cross-sectional area as well as pulmonary inspiratory capacity improve. No serious adverse effects are seen.

Insertion of a self-expandable endotracheal metal stent using topical anaesthesia and a fibreoptic bronchoscope: a comfortable way to offer palliation.

A self-expandable stent was used to obtain prolonged relief of stridor resulting from tracheal obstruction by extrinsic tumour compression despite prior external irradiation. The stent was inserted in an easy and comfortable procedure with fibreoptic bronchoscopy under local anaesthesia.

CT quantitation of tracheal cross-sectional area as a guide to the surgical and anesthetic management of children with anterior mediastinal masses.

Pediatric patients presenting with anterior mediastinal masses between January 1980 and November 1988 were reviewed to assess the correlation between tracheal cross-sectional area and anesthetic risks. Forty-two patients had evaluable computed tomography (CT) scans and underwent a surgical procedure. Thirty-four patients had Hodgkin's disease, six had non-Hodgkin's lymphoma, and two had mediastinal teratoma. Tracheal cross-sectional areas were greater than 75% of expected in 19 cases, greater than 50% to 75% in 16 cases, greater than 25% to 50% in five cases, and less than or equal to 25% in two cases. The presence or extent of symptoms did not correlate well with the degree of tracheal narrowing shown by CT scan except for orthopnea. Local anesthesia was used primarily in patients with significant tracheal narrowing (tracheal size was less than or equal to 56% in 5 of 6 patients). General anesthesia with spontaneous ventilation by mask was performed in four patients with tracheal areas of 33%, 73%, 76%, and 98% of expected. General endotracheal anesthesia was utilized in the remaining 32 patients, only three of whom had tracheal areas of less than 50% of expected (down to 30%, 26%, and 24% of expected) and one received preoperative radiotherapy (26%). None of these 32 patients had symptoms of orthopnea or dyspnea at rest, and only one had dyspnea on exertion. All tolerated anesthesia without difficulty. No patient in this series suffered respiratory or cardiovascular collapse during surgery. Adequate biopsy material was obtained in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Radiographic tracheal diameter measurements in acute infectious croup: an objective scoring system.

The percentage of change in tracheal diameter (TD% change), as assessed by an objective radiological measurement, was used along with a simple subjective clinical score to assess response to therapy in upper airway obstruction in 14 patients with acute infectious croup. Studies were performed on the 14 patients, each of whom was randomly assigned to one of two treatment groups: distilled water or racemic epinephrine (RE), both being nebulized and delivered by manual IPPB. The objective radiological assessment and the subjective clinical score both confirmed that RE is significantly (p less than 0.005) more effective than distilled water in the acute relief of upper airway obstruction. The more precise radiological assessment may be of value in determining objectively better drug therapy for infectious croup.