Bronchoscopic Instillation Research Articles

Bronchoscopic topical steroid instillation in prevention of tracheal stenosis

Corrosive acid poisoning commonly results in chemical injuries to respiratory and upper gastrointestinal tract. Corrosive mucosal erosion of the larynx and trachea may occur if the patient aspirates acid. We successfully used local anti-inflammatory action of dexamethasone instilled through a fiber-optic bronchoscope for regression of mucosal edema and prevention of subsequent development of stricture in a young female.

Proteomic Analysis of Human Bronchoalveolar Lavage Fluid after Subsgemental Exposure

The analysis of airway fluid, as sampled by bronchoalveolar lavage (BAL), provides a minimally invasive route to interrogate lung biology in health and disease. Here, we used immunodepletion, coupled with gel- and label-free LC-MS/MS, for quantitation of the BAL fluid (BALF) proteome in samples recovered from human subjects following bronchoscopic instillation of saline, lipopolysaccharide (LPS) or house dust mite antigen into three distinct lung subsegments. Among more than 200 unique proteins quantified across nine samples, neutrophil granule-derived and acute phase proteins were most highly enriched in the LPS-exposed lobes. Of these, peptidoglycan response protein 1 was validated and confirmed as a novel marker of neutrophilic inflammation. Compared to a prior transcriptomic analysis of airway cells in this same cohort, the BALF proteome revealed a novel set of response factors. Independent of exposure, the enrichment of tracheal-expressed proteins in right lower lung lobes suggests a potential for constitutive intralobar variability in the BALF proteome; sampling of multiple lung subsegments also appears to aid in the identification of protein signatures that differentiate individuals at baseline. Collectively, this proof-of-concept study validates a robust workflow for BALF proteomics and demonstrates the complementary nature of proteomic and genomic techniques for investigating airway (patho)physiology.

Iatrogenic Tracheal Ruptures: Review of the Literature and Personal Experience on 11 Cases

Objective: Iatrogenic tracheal rupture is a rare, but life-threatening complication of orotracheal intubation. In this retrospective study, etiology, and diagnostic and therapeutic approaches for iatrogenic tracheal ruptures were reviewed. Method: Eleven patients (6 males and 5 females) were diagnosed and treated for iatrogenic tracheal rupture in our clinic. The laceration occurred after orotracheal intubation in 7 cases, and during percutaneous tracheostomy and emergency tracheostomy in the other four cases, respectively. Diagnosis was made during thoracic surgery in 5 cases. The remaining cases were diagnosed in the post-operative period; the most common symptoms were mediastinal and subcutenous emphysema and pneumothorax. Results: The diagnosis was confirmed by bronchoscopy in all cases. The lacerations were longitudinal, 1-7 cm in length and were located in the distal membranous trachea. While ruptures detected intraoperatively were repaired during the surgery, the others were treated conservatively. No mortality was observed among cases treated surgically. However, three of the cases treated conservatively died (50%), and the cause of death was the underlying disease requiring intubation. Conclusion: We are in the opinion that primary disease is a determinant of patient outcome. Except cases identified during surgery, emergency surgical interventions should be preferred in patients, in whom ventilation cannot be achieved. On the other hand, bronchoscopic fibrin glue instillation should additively be applied to conservative treatment of tracheal lacerations.

Establishment and evaluation of a Chinese rhesus model of tuberculosis

To establish and evaluate the Chinese rhesus model of tuberculosis. Twelve Chinese rhesus macaques, randomly divided into 3 groups, were inoculated with 2 different doses of Mycobacterium tuberculosis H(37) Rv strain via both bronchoscopic and intratracheal instillation into the lungs. Clinical observation and laboratory examinations were performed, including erythrocyte sedimentation rate, C-reactive protein, tuberculin skin test and X-ray examination. Histopathological assessments were performed in the 24th week postinfection. Statistical analysis was performed by ANOVA in the 3 groups. After infection all the animals manifested fever, weight lose, lack of appetite, coughing and other symptoms of tuberculosis. The temperature gradually increased and reached a peak [(40.1 ± 0.2)°C] at the 8th week postinfection. The weight decreased significantly at 24th week postinfection (-5.5 ± 5.6)%. Erythrocyte sedimentation rate elevated significantly at the 6th to 8th week postinfection (36 ± 40) mm/1 h. C-reactive protein was significantly increased at the 6th to 24th week after infection (75.8 ± 49.8) mg/L. The positive rate of tuberculin skin test was 100%. In Group I (bronchoscopic instillation, 20 CFU) the disease developed slowly, and the main manifestation of chest X-ray was patchy shadows. In group II (bronchoscopic instillation, 100 CFU) and group III (intratracheal instillation, 100 CFU) the disease developed rapidly, and the main manifestation of chest X-ray was patchy and nodular lesions during the 4th to the 12th week postinfection, but became large patchy and consolidation lesions during the 12th to the 24th week postinfection. Tuberculosis granuloma and caseous necrosis, similar to the pathological changes of human tuberculosis, were found in the lungs, mediastinal lymph nodes, kidney and spleen. The results of acid-fast stain were positive. The most serious pathological manifestations were observed in group II, followed by group III and group I. The highest bacterial load of the right lung was seen in group II, followed by group I and group III. A chinese rhesus model of tuberculosis was successfully developed via both bronchoscopic and intratracheal instillation. Their clinical manifestations, disease progression and pathological changes were similar to human primary tuberculosis and hematogenous disseminated tuberculosis.

Bipolarishawaiiensisas etiologic agent of allergic bronchopulmonary mycosis: first case in a paediatric patient

Allergic bronchopulmonary mycosis (ABPM) is a worldwide hypersensitivity lung disease of multiple etiologies with Aspergillus fumigatus as the most common etiologic agent. We report the first instance of Bipolaris hawaiiensis causing ABPM in a paediatric patient. A six-year-old girl presented in June 2009 with productive cough, exertional dyspnoea, occasional wheezing, restricted air entry in left infra-scapular and infra-axillary areas, 7% eosinophils (absolute count 540/mm(3)) and total IgE 1051.3 IU/m in the sera. Bronchoscopy revealed narrowing of left main bronchus and mucoid impaction of the left lower lobe segmental bronchi. Cytological examination of BAL revealed few eosinophils, Charcot-Leyden crystals and mucus embedded hyphae. Examination of KOH wet mounts of repeated sputum and BAL specimens revealed septate, brownish hyphae and culture of the specimens resulted in the isolation of multiple colonies of a fungus later identified as B. hawaiiensis based on phenotypic characters and sequencing of internal transcribed spacer and D1/D2 regions of rDNA. In addition, (1-3)-β-D-glucan was demonstrated in serum (316 pg/ml) by Fungitell kit, supportive of fungal infection/colonization. Histopathologic studies of a bronchial biopsy revealed necrotic debris, macrophage aggregates, lymphocytes, polymorphs and PAS positive hypae. The patient was administered oral itraconazole for 12 weeks, intravenous liposomal amphotericin B for one month, weekly bronchoscopic suctioning and voriconazole instillation, resulting in reduced mucopurulent secretions and considerable clinical improvement. A serum sample collected on 5 November demonstrated precipitins against antigens of the B. hawaiiensis isolate. In March 2010, intradermal skin testing revealed a strong, type I hypersensitivity (induration diam-12 mm) against B. hawaiiensis. The patient relapsed with wheezing and difficulty in respiration in April 2010. Considering the positive type I cutaneous hypersensitivity, the aforementioned laboratory and clinical observations, the patient was finally diagnosed as having ABPM and was successfully treated with oral prednisone. A high index of clinical suspicion with requisite investigations is crucial for early diagnosis and appropriate therapy of ABPM in order to prevent the late sequelae of irreversible broncho-pulmonary damage.

Reply to Leoncini

We appreciate the great interest expressed by Leoncini [1] in our report on tracheal lacerations after endotracheal intubation [2]. The recent experience with 23 tracheal lacerations reported by the author from San Martino Hospital in Genoa [3] seems to be an external validation of our morphological classification. Indeed, Leoncini is right in taking into account the clinical condition of the patients and we fully agree with him; however, we would like to stress that it has been clearly stated in our article [2] that the bronchoscopic findings determine further treatment provided that (1) the patient has stable vital signs, (2) pneumothorax has been resolved and (3) adequate respiratory status has been achieved (spontaneous or mechanical). On the other hand, we believe that the most important take-home message from our article is that the depth, and not the length, of tracheal injury represents the most important factor for the evaluation of such difficult patients. Furthermore, preventing of mediastinitis is a key goal of thoracic surgeons dealing with postintubation-tracheal lacerations, and we do not agree with Leoncini’s statement that if mediastinitis is not present, a conservative management can be accomplished. A wait-and-see policy, in the presence of a level IIIA lesion (complete laceration of the tracheal wall with an oesophageal or mediastinal soft-tissue hernia without oesophageal injury or mediastinitis), could be acceptable only if the physicians have a great experience in dealing with such patients, but could be a disaster if clinicians are not ready to detect any minimal clinical change because in the presence of clear signs of mediastinitis, the mortality is very high (40—50%) [4]. The last sentence of Dr Leoncini’s letter deserves a word of caution: time to diagnosis is very important. In our experience, diagnosis and treatment took place within 24 h of sustaining injury. Delayed diagnosis is not at all a favorable factor, except in the presence of level I injury (mucosal or submucosal tracheal involvement without mediastinal emphysema and without perioesophageal injury), which easily resolves spontaneously. In an attempt to provide correct guidelines for the management of tracheal injuries, we would like to stress the importance of broad-spectrum antibiotic therapy and parenteral nutrition. The role of bronchoscopic instillation of fibrin glue (Tissucol, Baxter Healthcare, Deerfield, MA, USA), routinely performed in our Unit to promote tissue sealing and regeneration of tracheal lacerations, has not yet been clearly understood and needs further investigations. References

Lentiviral airway gene transfer in lungs of mice and sheep: successes and challenges

Persistent airway gene expression can be achieved in mouse nasal airway using a vesicular stomatitis virus glycoprotein pseudotyped lentiviral (LV) gene vector in combination with lysophosphatidylcholine (LPC) pretreatment. We have now examined the acute in vivo effects of this combination single-dose method for airway LV gene transfer in mouse and sheep lung. Mouse and sheep lungs were exposed to LPC followed 1 h later with the LV vector. Lungs were processed 7 days later using X-gal detection to measure beta-gal gene expression and identify transduced cell types. In mouse ciliated conducting airways, LPC pretreatment produced extensive gene transfer that extended from the tracheal dosing site into the bronchi and lower airways. Gene expression was present in both terminally differentiated surface cells and in basal cells. Without LPC pretreatment, transduction was limited to the dosing site. In sheep lung, small-volume bronchoscopic instillation delivery produced localized and low-level transduction near the dosing site. Gene expression was again present in surface and basal cells. Neither alterations in LPC dose parameters, nor larger vector volumes increased the level of transduction. These findings are the first to confirm the applicability of LPC pretreatment in the production of extensive lentiviral gene transfer in mouse lung airways. However, improved methodologies to increase transduction efficiency are required for adult sheep lung. The results suggest that continued in vivo development of LPC-enhanced lentiviral gene transfer is needed in the lungs of large animals to establish effective lentiviral gene transfer techniques suited to the treatment of airway disease.

Bronchoscopic instillation of activated recombinant factor VII to treat diffuse alveolar hemorrhage in a child

Pediatric PulmonologyVolume 45, Issue 4 p. 411-411 Letter to the Editor Bronchoscopic instillation of activated recombinant factor VII to treat diffuse alveolar hemorrhage in a child Andrew A. Colin MD, Corresponding Author Andrew A. Colin MD [email protected] Division of Pediatric Pulmonology, University of Miami, Miami, FloridaDivision of Pediatric Pulmonology, Miller School of Medicine, University of Miami, 1580 NW 10th Avenue, Room 125, Miami, FL 33136.Search for more papers by this authorMitra Shafieian MD, Mitra Shafieian MD Division of Pediatric Pulmonology, University of Miami, Miami, FloridaSearch for more papers by this authorMartin Andreansky MD, PhD, Martin Andreansky MD, PhD Division of Pediatric Hematology/Oncology, University of Miami, Miami, FloridaSearch for more papers by this author Andrew A. Colin MD, Corresponding Author Andrew A. Colin MD [email protected] Division of Pediatric Pulmonology, University of Miami, Miami, FloridaDivision of Pediatric Pulmonology, Miller School of Medicine, University of Miami, 1580 NW 10th Avenue, Room 125, Miami, FL 33136.Search for more papers by this authorMitra Shafieian MD, Mitra Shafieian MD Division of Pediatric Pulmonology, University of Miami, Miami, FloridaSearch for more papers by this authorMartin Andreansky MD, PhD, Martin Andreansky MD, PhD Division of Pediatric Hematology/Oncology, University of Miami, Miami, FloridaSearch for more papers by this author First published: 24 February 2010 https://doi.org/10.1002/ppul.21178Citations: 13AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume45, Issue4April 2010Pages 411-411 RelatedInformation

Endoscopic Sealing of Bronchopleural Fistulas with Submucosal Injection of a Tissue Expander: A Novel Technique

The occurrence of a bronchopleural fistula (BPF) continues to represent a challenging management problem, and is associated with high morbidity and mortality. A novel and successful technique that uses submucosal injection of a tissue expander for bronchoscopic occlusion of BPFs has been designed. This method may be used either alone or in combination with bronchoscopic instillation of n-butyl-cyanoacrylate glue. The occlusion technique is described, with a presentation of two patients who were successfully treated with this method. The submucosal injection of a tissue expander is an effective, economical and minimally invasive technique for managing BPFs.

Activation of coagulation and inhibition of fibrinolysis in the human lung on bronchial instillation of lipoteichoic acid and lipopolysaccharide*

Pneumonia is characterized by an acute inflammatory response in the lung, which is frequently associated with changes in coagulation and fibrinolysis in the bronchoalveolar space. Here, we compared the effects of lipoteichoic acid (LTA), a major cell wall component of Gram-positive bacteria, and lipopolysaccharide (LPS), in the human bronchoalveolar space. Controlled in vivo volunteer study. Clinical research unit. Twenty-three healthy nonsmoking male volunteers. Sterile saline was instilled into a lung subsegment followed by bronchoscopic instillation of either LTA (Staphylococcus aureus, at a dose of 4, 20, or 100 ng/kg body weight) or LPS (Escherichia coli, 4 ng/kg body weight) into the contralateral lung. Bronchoalveolar lavage fluid was obtained 6 hours thereafter. Bronchial instillation of LTA- or LPS-activated bronchoalveolar coagulation, as reflected by increases in the levels of thrombin-antithrombin complexes, d-dimer, and soluble tissue factor. Concurrently, LTA and LPS inhibited anticoagulant mechanisms, as indicated by reductions in antithrombin, Protein C, and Activated Protein C concentrations together with elevated levels of soluble thrombomodulin. Both LTA and LPS administration was associated with an inhibition of pulmonary fibrinolysis, as measured by a reduction in plasminogen activator activity and elevated levels of plasminogen activator inhibitor type I. This study is the first to describe the effects of LTA on hemostasis in humans, demonstrating that LTA induces similar changes in the human bronchoalveolar space as LPS, characterized by activation of coagulation with concurrent inhibition of anticoagulant and fibrinolytic pathways.

Surfactant as salvage therapy in life threatening primary graft dysfunction in lung transplantation

Impaired surfactant activity may contribute to primary graft dysfunction after lung transplantation. We assessed the role of surfactant treatment in lung transplant recipients with severe life threatening primary lung graft dysfunction. Five patients after lung transplantation: 4 after single-lung transplantation, for emphysema (n=3) or idiopathic pulmonary fibrosis (n=1), and 1 patient after double-lung transplantation for cystic fibrosis. All had severe life threatening primary graft dysfunction that failed to respond to conventional measures. Treatment consisted of bronchoscopic instillation of mammalian surfactant, 20-90cc, at 3 (n=1) or 7 days (n=4) after transplantation. There was a significant improvement in the ratio of partial arterial oxygen tension (PaO(2)) to fractional concentration of oxygen in inspired gas (FIO(2)), from a mean of 98.8+/-21.7 to 236.8+/-52.3 mmHg (p=0.0006), within hours of treatment. All were eventually discharged home and showed a satisfactory FEV(1) (44-67% predicted) at the 6-month follow-up. All patients were still alive 6 months or more after transplantation. Surfactant treatment improves oxygenation and may be life saving in patients with primary lung graft dysfunction.

Treatment of lobar atelectasis with bronchoscopically administered recombinant human deoxyribonuclease in cystic fibrosis?

Recombinant human deoxyribonuclease (rhDNase) reduces sputum viscosity and improves pulmonary function in cystic fibrosis (CF). The objective of this study was to describe our experience in which rhDNase (Pulmozyme; Roche, Basel, Switzerland) was administered by bronchoscopic instillation into atelectatic lobes in five adults with CF. We found this method successful in treating lobar atelectasis, which was resistant to conventional therapy with antibiotics and physiotherapy. In all but one of the cases we described, administration of DNase in this manner resulted in a radiographic and clinical improvement of the atelectasis. We recommend that respiratory physicians consider this as a second line treatment in the management of atelectasis.

Resolution of Severe Ischemia–Reperfusion Injury Post–Lung Transplantation After Administration of Endobronchial Surfactant

Ischemia-reperfusion injury (IRI) is a prominent cause of primary graft failure after lung transplantation and is associated with an altered surfactant profile. Experimental animal studies have found that replacement with exogenous surfactant administered via fiber-optic bronchoscopy (FOB) enhanced recovery from IRI with improved pulmonary compliance and gas exchange after lung transplantation. We report our clinical experience with FOB instillation of surfactant in severe IRI after human lung transplantation. This study is a retrospective review of 106 consecutive lung or heart-lung transplants performed at a single institution. Severe IRI was defined as diffuse roentgenographic alveolar infiltrates, worsening hypoxemia and decreased lung compliance within 72 hours of lung transplantation. One vial of surfactant (20 mg/ml phospholipid) was instilled into each segmental bronchus upon diagnosis of IRI. Six patients (5 bilateral sequential and 1 re-do heart-lung transplant), mean age 46 years, were diagnosed with IRI and surfactant was administered at a mean of 37 hours (range 2.3 to 98) post-transplant. Mean graft ischemia time was 376 minutes (range 187 to 625) and cardiopulmonary bypass time 174 minutes (range 0 to 210). Mean Pao(2) [mm Hg]/Fio(2) ratio before and 48 hours after surfactant instillation was 70 and 223, respectively. Significant resolution of radiologic infiltrates was evident in all cases within 24 hours. Successful extubation occurred at a mean of 13.5 days and survival is presently 100% at 19 months (range 3 to 54). Bronchoscopic instillation of surfactant improves oxygenation and prognosis after severe IRI in lung transplant recipients. It represents a cost-effective, relatively non-invasive therapeutic alternative to extracorporeal membrane oxygenation.

Monocytic/Macrophagic Pneumonitis after Intrabronchial Deposition of Vascular Endothelial Growth Factor in Neonatal Lambs

Preterm and young neonates are prone to inadequate surfactant production and are susceptible to respiratory distress syndrome characterized by alveolar damage and hyaline-membrane formation. Glucocorticoid therapy is commonly used in preterm and young infants to enhance lung maturation and surfactant synthesis. Recently, vascular endothelial growth factor (VEGF) was suggested to be a novel therapeutic agent for lung maturation that lacked adverse effects in mice. The purpose of this study was to assess the safety of incremental concentration (0.0005, 0.005, and 0.05 mg/ml) and duration (16, 24, and 32 hours) of recombinant human VEGF after bronchoscopic instillation (10 ml) in neonatal lambs. High-dose VEGF caused locally extensive plum-red consolidation that was microscopically characterized by interstitial and alveolar infiltrates of cells that were morphologically and phenotypically (CD68+) consistent with monocytes/macrophages. T cells (CD3+) and B cells (CD79+) were located primarily in bronchus/bronchiole-associated lymphoid tissue and were not consistently altered by treatment with VEGF. The dose of VEGF had significant effects on both gross lesions (P < .0047) and microscopic monocyte/macrophage recruitment scores (P < .0001). Thus, the VEGF dose instilled into the lung greatly influenced cellular recruitment and lesion development. The post-dosing interval of VEGF in this study had minor impact (no statistical significance) on cellular recruitment. This study showed that airway deposition of VEGF in the neonatal lamb induces monocyte/macrophage recruitment to the lung and high doses can cause severe lesions. The cellular recruitment suggests further research is needed to define dosages that are efficacious in enhancing lung maturation while minimizing potential adverse effects.

Functional and genomic changes induced by alveolar transmigration in human neutrophils

Although the accumulation of neutrophils in the lungs and airways is common to many inflammatory lung diseases, including acute lung injury, the alterations that neutrophils undergo as they leave the peripheral circulation and migrate into the lungs have not been well characterized. Human volunteers were exposed to endotoxin by bronchoscopic instillation. The resulting air space neutrophil accumulation and peripheral blood neutrophils were isolated 16 h later, compared with circulating neutrophils isolated before or after to the pulmonary endotoxin exposure, and compared with circulating neutrophils exposed to endotoxin in vitro. Microarray analysis was performed on air space, circulatory, and in vitro endotoxin-stimulated neutrophils. Functional analysis included the determination of neutrophil apoptosis, chemotaxis, release of cytokines and growth factors, and superoxide anion release. Dramatic gene expression differences were apparent between air space and circulating neutrophils: approximately 15% of expressed genes have altered expression levels, including broad increases in inflammatory- and chemotaxis-related genes, as well as antiapoptotic and IKK-activating pathways. Functional analysis of air space compared with circulating neutrophils showed increased superoxide release, diminished apoptosis, decreased IL-8-induced chemotaxis, and a pattern of IL-8, macrophage inflammatory protein-1beta, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha release different from either unstimulated or LPS-stimulated circulating neutrophils. Many of these changes are not elicited by in vitro treatment with endotoxin. Limited differences were detected between circulating neutrophils isolated before and 16 h after pulmonary endotoxin instillation. These results suggest that neutrophils sequestered in the lung become fundamentally different from those resident in the circulation, and this difference is distinct from in vitro activation with endotoxin.

Resident Th1-Like Effector Memory Cells in Pulmonary Recall Responses toMycobacterium tuberculosis

We recently described a model of Th1 recall responses based on segmental antigen challenge with purified protein derivative of Mycobacterium tuberculosis (PPD). Bronchoscopic instillation of 0.5 tuberculin units of PPD resulted in localized lymphocytic inflammation in PPD-positive subjects only. Recruited lymphocytes were predominantly CD4+ and were enriched for cells capable of PPD-specific interferon (IFN)-gamma production. In the current study, we investigated the mechanisms by which this localized recall response is mobilized. Bronchoscopic PPD challenge of skin test-positive subjects resulted in the production of CXCR3 ligands IFN-gamma-inducible protein (IP)-10 and monokine induced by IFN-gamma (Mig), but not of CCR5 ligands macrophage inflammatory protein-1alpha and regulated-upon activation, normal T-cell expressed and secreted, whereas skin test-negative subjects produced none of these chemokines. Baseline bronchoalveolar lavage (BAL) cells of skin test-positive subjects produced IP-10 and Mig in response to in vitro stimulation as well. Because IP-10 and Mig are IFN-gamma-inducible chemokines, these findings suggested that chemokine responses to PPD were facilitated by resident memory cells of the lung. Further studies confirmed that baseline BAL lymphocytes of PPD-positive subjects produce IFN-gamma in response to PPD, and that, compared with peripheral blood, BAL cells are preferentially enriched for PPD-specific lymphocytes. This IFN-gamma production is predominantly a function of CD4+ T cells that display the CD45RO+/CCR7- surface phenotype characteristic of effector memory cells.

Common anti-inflammatory and diverse smooth muscle cell effects of AAV-mediated angiopoietin-1 and -2 expression in rat cardiac allografts

improved pulmonary compliance and gas exchange after lung transplantation. Aim: We report our clinical experience of FOB instillation of surfactant in severe RI after human lung transplantation. Methods: Retrospective review of 92 consecuetive lung or heart lung transplants performed at a single institution. Severe RI was defined as diffuse roentgenographic alveolar infiltrates, worsening hypoxaemia and decreased lung compliance within 72 hours of lung transplantation. One 5 ml vial of surfactant (Beractant Bovine Lung Extract, Abbott, Australasia Ptd. Ltd, 20mg/ml phospholipid) was instilled into each segmental bronchus upon diaqnosis of RI. Results: Five patients (all bilateral sequential) of mean age 49 years were diagnosed with RI and surfactant administered at a mean of 42 hours (range 2.3–98) post transplant. Mean graft ischaemic time was 414 minutes (range 232–625) and cardiopulmonary bypass time 167 minutes (range 0–210). Mean oxygen index (PaO2mmHg/FiO2) pre and 48 hours post surfactant was 70 and 223 respectively. Significant resolution of radiological infiltrates was evident in all cases within 24 hours. Successful extubation occurred at a mean of 15.8 days and survival is 100% at 16.2 months (range 1–49). Conclusions: Bronchoscopic instillation of surfactant improves oxygenation and prognosis following severe RI in lung transplant recipients. It represents a non-invasive therapeutic alternative to extra corporeal membrane oxygenation to significantly improve clinical outcome in RI.

Experimental Mycobacterium tuberculosis infection of cynomolgus macaques closely resembles the various manifestations of human M. tuberculosis infection.

Nonhuman primates were used to develop an animal model that closely mimics human Mycobacterium tuberculosis infection. Cynomolgus macaques were infected with low doses of virulent M. tuberculosis via bronchoscopic instillation into the lung. All monkeys were successfully infected, based on tuberculin skin test conversion and peripheral immune responses to M. tuberculosis antigens. Progression of infection in the 17 monkeys studied was variable. Active-chronic infection, observed in 50 to 60% of monkeys, was characterized by clear signs of infection or disease on serial thoracic radiographs and in other tests and was typified by eventual progression to advanced disease. Approximately 40% of monkeys did not progress to disease in the 15 to 20 months of study, although they were clearly infected initially. These monkeys had clinical characteristics of latent tuberculosis in humans. Low-dose infection of cynomolgus macaques appears to represent the full spectrum of human M. tuberculosis infection and will be an excellent model for the study of pathogenesis and immunology of this infection. In addition, this model will provide an opportunity to study the latent M. tuberculosis infection observed in approximately 90% of all infected humans.

Closure of a Postoperative Bronchopleural Fistula with Bronchoscopic Instillation of n-butyl-2-cyanoacrylate (Histoacryl(R))

Bronchopleural fistula(BPF) occurs as a postoperative complication in 2 to 5 percent of pulmonary resection. The detection of BPF is generally difficult and various diagnostic methods have been utilized to identify the site of the fistula in order to treat it adequately. Closure of these BPF can be surgical intervention or bronchoscopic application of various sealing agents. We report an experience with use of bronchoscopic instillation of n-butyl-2-cyanoacrylate() for closure of a postpneumonectomy BPF.

Utilización de fibrinógeno-trombina por vía endoscópica en el tratamiento de la hemoptisis masiva

We assessed the efficacy of fibrinogen-thrombin instillation through the fiberoptic bronchoscope to treat massive hemoptysis in patients to whom embolization of bronchial arteries was not available, was contraindicated or had failed. The fibrinogen-thrombin solution used was Tissucol, which in addition to 2% fibrinogen and 4 U/ml of thrombin, also contained factor XIII an aprotinin. The fibrinogen-thrombin solution was instilled with the aid of the Duplojec system and a 70 cm x 2 mm 4-way catheter. In 53 of the 628 fiberoptic bronchoscopies performed during the study, the indication was hemoptysis > or = 150 ml/12 h. Of these, bronchoscopic instillation of fibrinogen-thrombin was indicated in 5 cases because bronchial artery embolization was impossible. The point of bleeding was located by bronchoscopy in all cases and fibrinogen-thrombin instillation controlled hemoptysis immediately and throughout the follow-up period, which ranged 4 to 10 months. Morning expectoration of blood (< 10 ml) was observed in only 1 patient in the 3 days after treatment. The mean time taken for bronchoscopic exploration was 3 minutes (range, 2-7). In all cases fiberoptic bronchoscopy was performed without complications that might have required the procedure to be suspended. We conclude that the local use of fibrinogen-thrombin or fibrin glue instilled through the fiberoptic bronchoscope to the point of bleeding is a simple, fast and cheap way to control massive hemoptysis on a short and long-term basis.(ABSTRACT TRUNCATED AT 250 WORDS)