Search

Chronic lung allograft dysfunction (CLAD) is a major limitation to long-term success of lung transplantation. Restrictive allograft syndrome (RAS) is a recently discovered subtype of CLAD, showing distinct clinical, pathological and radiological features compared with the major CLAD subtype, bronchiolitis obliterans syndrome (BOS). Introduction of the novel CLAD classification system that differentiates CLAD into BOS and RAS has stimulated research activities aiming delineation of the underlying pathological mechanism in the 2 CLAD subtypes. Accumulating evidences suggest that BOS and RAS could be biologically distinct, indicating that optimal therapeutic strategy could be different. Further efforts in refinements in biologic profiling of BOS and RAS will lead to a better understanding of CLAD, as well as the development of personalized and targeted preventive therapies for underlying CLAD subtypes.

Sodium alginate is the main ingredient of the seaweed, and its water solution has moderate viscosity. The areas of the pleural defect and around the suture line were covered with polyglycolic acid felt by using 5% sodium alginate water solution in 41 patients who underwent pulmonary resection from November 2006 to April 2007. 28 patients were lung cancer, 6 patients were pulmonary metastasis, and 7 patients were pneumothorax. The duration of the postoperative air leakage was 0.7 days on average. Neither side effect nor complication was observed. This method is cheap, safe, and effective for prevention for postoperative pulmonary fistula.

Bortezomib is a proteasome inhibitor that can be effective in the treatment of refractory and relapsed multiple myeloma. Recently, severe pulmonary complications associated with bortezomib therapy have been reported in Japan. Because bortezomib has not yet been approved for general use in Japan and is imported by attending physicians on the request of patients, The Japanese Society of Hematology and The Japanese Society of Clinical Hematology sent urgent questionnaires to the councilors of both societies in order to explore the situation and details of pulmonary complications associated with bortezomib therapy. Clinical details were available for 46 patients who had been treated with personally imported bortezomib in Japan. Seven patients (15.2%), including 3 who died from respiratory failure, showed complications definitely or probably caused by bortezomib. Of the 7 patients, 6 had a prior history of stem cell transplantation (SCT), whereas only 14 of 39 patients without lung injury had received SCT treatment (p = 0.033 by Fischer's exact test). Multivariate analysis revealed that the concomitant use of corticosteroids might reduce the risk of lung injury (p = 0.024; odds ratio = 0.055) and that a previous SCT might increase the risk (p = 0.042; odds ratio = 13.140). We summarized these data from questionnaires for a limited Japanese cohort and therefore do not know the precise incidence of lung injury linked to fatal progression. Thus, future verification concerning these matters is warranted after the approval of bortezomib for use in Japan. Clinicians should be aware of the possibility of severe pulmonary complications associated with bortezomib therapy. Note that this report has the same contents as the article appeared in the International Journal of Hematology (vol. 84, p406-412, 2006) by permission of both the editorials of the Japanese Society of Hematology and the Japanese Society of Clinical Hematology, and should be considered as the Japanese translation of the article.

Background: The purpose of this study is to examine the effects of neutrophil elastase inhibitor on postoperative cytokine levels in patients after esophagectomy., Methods: Fifteen patients were divided into two groups; group 1: 9 patients receiving neutrophil elastase inhibitor (0.2 mg x kg(-1) x hr(-1) from the admission to ICU to extubation), group 2: 6 patients as a control. We measured neutrophil elastase activity, interleukin 1-beta, interleukin 6 and interleukin 8 preoperatively, just after the admission to ICU, and 24, 48 and 72 hours after the surgery., Results: There were significant differences in neutrophil elastase activity and interleukin 8 in group 1 24 hours after the surgery, compared with those in group 2. The time necessary for mechanical ventilation in group 1 was shorter than that in group 2 (group 1: 44.7 +/- 24.7 hrs, group 2: 112.8 +/- 90.3 hrs, P = 0.048)., Conclusions: The administration of neutrophil elastase inhibitor may be useful for patients after esophagectomy to reduce overexpression of plasma cytokine levels after surgery.

We investigated the comparative effectiveness of the seat and glue types of fibrin adhesive, to clarify which is more useful in preventing postoperative parenchymal air leaks after lung resection. One hundred sixteen patients received fibrin adhesive to prevent postoperative air leakage after lung resection carried out by the same surgeon. Ninety-two lobectomies and 24 partial resections were assessed. There were 29 patients with emphysematous lung. In the seat type group, an average of 2.6 postoperative days elapsed before chest drain removal. In the glue type, this average was 3.2 days, a significant difference. This difference was also evident in the lobectomy group. However, among emphysematous lung patients and the partial resection group, there was no apparent difference. Prolonged air leakage was seen in 2 patients with emphysematous lung, but no difference in terms of drug formation could be seen. The seated type of fibrin adhesive was more useful than the glue type in preventing postoperative air leaks, but in emphysematous lung patients, better surgical technique would seem to be the critical factor.

The pathophysiologic role of thrombin in the development of lung injury after the normothermic cardiopulumonary bypass (CPB) was studied in the rabbit model. A control group (group D) was subjected to the pericardiotomy without institution of CPB. Group A rabbits (n = 6) underwent left heart bypass (80 ml/kg/min) for 60 minutes without occlusion of the systemic or pulmonary artery and a succeeding reduced flow (20-30 ml/kg/min) for another 30 minutes, group B rabbits (n = 6) underwent complete CPB (80 ml/kg/min) for 60 minutes in the working mode with occlusion of the pulmonary arterial trunk and a succeeding reduced flow without occlusion of the pulmonary artery for another 30 minutes, group C rabbits (n = 6) underwent the same CPB technique as group B in conjunction with continuous intravenous infusion of argatroban (60 micrograms/kg/min), the specific thrombin inhibitor. In this group, infusion of argatroban was initiated 60 minutes prior to institution of CPB and terminated at the end of the experiment. We sacrificed rabbits four hours after the experiment began, and assessed not only morphometrically thrombus formation, leukocytic infiltration and luminal narrowing of small-sized pulmonary arteries but also immunohistochemically the expression of tissue factor (TF) and IL-1 beta, and physico-functionally respiratory index (RI) and pulmonary vascular resistance (PVR). Rabbits in group A showed multiple occurrence of lung thrombi, luminal narrowing of small arteries, and mild infiltration of macrophages and neutrophils positive for TF, and, in addition, their RI and PVR became mildly worse. In group B, all these morphological and physico-functional parameters became much worse than those observed in group A rabbits (p < .01). In contrast, argatroban treatment could significantly improve these parameters (p < .01). The expression of TF and IL-1 beta, however, was not significantly different in group A, B and C. These findings indicate that thrombin function intimately participates in the development of pulmonary ischemia-reperfusion injury during CPB. In addition, the anti-thrombin treatment would be an effective therapeutical tool for the prevention of not only activation of extrinsic coagulation pathway but also its sequential inflammatory and circulatory disturbance in ischemia-reperfusion injury of lung during CPB.

We report a case of 67-years-old male, who suffered right upper lobectomy for primary lung cancer. The upper-middle interlobar surface of right lung was incomplete interlobe. Many air leakages were noted in the cut surface of upper-middle interlobe during the sealing test. We sealed this cut surface of upper-middle interlobe by using the photopolymerized synthetic bioabsorbable hydrogel (Advaseal). Air leakage was not noted during the sealing test, and no leakage was not noted after operation. We have observed no biological toxicity (such as cytotoxicity, hemolytic toxicity, systemic toxicity or mutagenic toxicity) by using Advaseal. The new photopolymerized synthetic bioabsorbable hydrogel (Advaseal) is a effective sealant against pulmonary air leaks in the cut surface of the lung.

We analyzed postoperative early complications of primary lung cancer in 321 cases during 1982 to 1993 in our hospital, and assessed the prevention and the treatment against these complications. In order of frequency the complications are, paroxymal supraventricular tachcarida (10.6%), atelectasis due to sputum (6.9%), pulmonary fistula for more than seven days (4.7%), hoarseness of voice due to recurrent nerve palsy (4.0%), chylothorax (2.5%), gastrointestinal tract complications (2.2%), reoperation due to massive bleeding (1.2%), wound dehiscence (0.9%), bronchial fistula (0.6%), rupture of ascending aorta (0.3%) and myocardial infarction (0.3%). The two cases of bronchial fistula after pneumonectomy, and one of myocardial infarction after lobectomy through the median approach died of early complications. The operative indication for primary lung cancer is extended to the patients with higher age and lower pulmonary function; so we should be careful for the pre and postoperative prevention and the rapid and appropriate treatment against these postoperative early complications.

The incidence of perioperative complication and days of hospital stay were studied in 56 patients with funnel chest operation under inhalational anesthesia (18 cases), intravenous anesthesia (23 cases) and epidural anesthesia (15 cases). Perioperative complication occurred most frequently in the inhalational group and was followed by intravenous and epidural group. Postoperative hospitalization on an average was 21.4 days in the inhalational group, 21.9 days in the intravenous group and 16.7 days in the epidural group. It is said that postoperative pain leads to splinting of the chest, which can cause atelectasis and/or pneumonia. Severe postoperative pulmonary complication was reduced in the epidural groups. As a result, hospitalization in the epidural group was shorter than in other groups. This study suggests that epidural anesthesia is more advantageous for funnel chest operation because epidural anesthesia has protective action against arrhythmia and postoperative pulmonary complication.

Felt prepared from polyglycolide (PGA) polymer fibers was pasted with fibrin glue for prevention of postoperative pulmonary fistula, and its effects were evaluated. The subjects were 90 patients who underwent thoracotomy and were expected to develop air leakage between March 1990 and the end of 1993. The felt sheet was simply pasted in position in 67 patients, applied and fixed by suturing in 7, and sutured and pasted in 16. The duration of air leakage in the three groups were 4.6 +/- 4.1, 3.9 +/- 4.9, and 3.2 +/- 3.8 days, respectively. According to the surgical procedure employed, the duration of air leakage was 5.0 +/- 4.0 days in 41 patients who underwent pulmonary lobectomy, 5.0 +/- 4.3 days in 5 patients who underwent segmentectomym, 2.6 +/- 3.1 days in 26 cases who underwent partial pneumonectomy, and 4.9 +/- 4.0 days in the 14 cases who underwent bulla resection. In terms of disease, the leakage time was 4.6 +/- 4.2 days in patients with emphysema, 0.6 +/- 1.2 days in those with diffuse pulmonary fibrosis, 0.7 +/- 0.9 days in those with Infectious disease, 4.8 +/- 4.2 in those with lung cancer, 1.5 +/- 1.5 days in those with benign lung tumor, and 3.8 +/- 2.7 days in those with metastatic lung tumors. The procedure had no side-effect on liver or kidney function. No infection was observed even after decortication for empyema. The use of felt prevented excessive shrinking of the lung due to over-suturing. Therefore, intraoperative application of a PGA felt sheet was considered to be an effective method for prevention of pulmonary fistula.

Extended lymph node dissection in the neck and upper mediastinum often brings about postoperative pulmonary complications. Since September 1987, we have performed this type of lymph node dissection in 18 patients paying special attention to the preservation of tracheal proper sheath along with left bronchial artery and autonomic nerve branches. We compared their postoperative respiratory and circulatory outcomes with those of 17 patients in whom lymph node dissection was carried out without consideration for these aspects. Tracheal mucosal damage, respiratory functional parameters such as PaO2, AaDO2 and Qs/Qp and actual incidence of pneumonia significantly improved in recent cases undergoing meticulous dissection in the neck and upper mediastinum. However, neither circulatory dynamics nor incidences of recurrent nerve palsy and arrhythmia showed a significant improvement. The postoperative period required for reappearance of cough reflex was shorter in this group of patients, but the difference was not significant. The results indicated that pulmonary disorders occurring frequently after extended lymph node dissection for thoracic esophageal cancer was able to be well controlled by meticulous dissection procedure as mentioned above.

To clarify the prophylactic effect of epidural anesthesia with buprenorphine on postoperative pulmonary complications, the incidence of pulmonary complications after chest surgery was evaluated in 2 groups: the group that underwent epidural anesthesia, namely the test group, and the control group. Pulmonary complications were classified as follows: mild complications, sustained wheezing and/or small atelectasis-like shadows seen on chest x-rays. These improved by conventional methods except for bronchial toilet. Moderate complications included pneumonia and/or respiratory failure and/or atelectasis which needed bronchial toilet. There were 56 cases (58%) with no pulmonary complications in the control group and 89 cases (77%) in the test group. The number of patients with pulmonary complications were 40 (42%) in the control group and 27 (23%) in the test group, respectively (p less than 0.01). Those with mild or moderate complications were 25 (26%), 15 (16%) in the control group and 21 (18%), 6 (5%) in the test group, respectively. There was significant difference between no complication group and moderate complication group (p less than 0.01). These results show that epidural anesthesia is useful in preventing pulmonary complications after chest surgery.

Recently, the quality of life of a cancer patient has been extensively discussed. Especially, side effects of chemotherapy are major problems of cancer patients. Cardiotoxicity of adriamycin and pulmonary toxicity of bleomycin are not common side effects of chemotherapy, but they can be devastating, particularly, when they occur in a patient who has been cured of cancer. Therefore, we tried to demonstrate the efficacy of cardiac or pulmonary monitoring in early detection of the toxicity. In conclusion, now non-invasive and invasive standard methods of monitoring have yet to be convincingly established, because most methods are either of no predictive value or too sensitive. Moreover, to date an effective prophylaxis of cardiotoxicity or pulmonary toxicity is still lacking. Exact evaluation of risk factors and thorough cardiac or pulmonary monitoring are necessary in patients under chemotherapy.

Three of 254 patients with Eizenmenger's syndrome had complications, namely bleeding during and after surgery of open lung biopsy. Histopathologic study of the lung in patients suffering from complications revealed that destruction of the collateral vessels characterized by wide lumen and weak walls is responsible for the postoperative bleeding. Such complications can be prevented by using the TA stapler which cuts off the lung tissue with little or no damage to the other lung tissues.

A method of percutaneous intratracheal catheter (PITC) was studied for postoperative respiratory care and prevention of postoperative pulmonary complications. The oxygen was insufflated through the catheter persistently at 2-4 liters per minute. Successful results were obtained in 20 patients who were in poor pulmonary risk such as older age, major operation and pre-existing pulmonary insufficiency, revealing more effectiveness in oxygenation rather than other devices of oxygen supply. An experimental study was performed to evaluate its efficacy using dogs with respiratory impairment, which were designed by removal of 6 ribs of 5 cm in each from the left thoracic wall and bilateral division of phrenic nerves. The animals were maintained under the condition of spontaneous respiration with air-insufflation through the PITC. The following results were obtained. End-expiratory pressure (0.22 cm H2(0)/1 min) increased. Functional reserve capacity increased. Alveolar ventilation increased. Dead space to tidal volume ratio decreased. PaO2 and PaCO2 improved to the normal range. The immediate postoperative use of this method has been found most satisfactory in respiratory care and elimination of postoperative pulmonary complications.

In order to find a method to ameliorate pulmonary toxicity of peplomycin (PEP), microscopic changes of the lung following PEP administration and effect of anti-platelet aggregating agents on the toxicity was investigated in mice. When PEP was administered intravenously once a day for 7 days, microthrombi mainly composed of aggregated platelets and fibrin appeared in the capillaries of the lung in an early phase before severe pulmonary edematous lesions and fibrosis occurred. Combination therapy of anti-platelet aggregating agents such as phthalazinol, dipyridamole, ticlopidine and indomethacin suppressed these toxic changes. Especially, ticlopidine was the most effective and superior to prednisolone used clinically for amelioration of the toxicity. Microthrombi, preceding edematous lesions, were considered to be attributed to damages of endothelium by PEP, because PEP itself did not develop platelet aggregation in vitro and ex vivo. Therefore, the microthrombi are likely to produce congestion of pulmonary microcirculation leading to edematous lesions by increase of permeability, and to play significant roles in the development of pulmonary fibrosis in a late phase. Anti-platelet aggregating agents such as ticlopidine are concluded to ameliorate the lung toxicity by preventing microcirculation impairment with the microthrombus.

Current topics for occupational and environmental medicine and physiology in the U.S.A., especially in the National Institute for Occupational Safety and Health (NIOSH), and the University of California, San Francisco, are reviewed. Reduction of the rate for occupational lung diseases is one of the national objectives for occupational safety and health in the U.S.A., and NIOSH has rated it as the top disease of ten-leading work-related diseases and injuries. Current topics for occupational lung diseases--asbestosis, byssinosis, silicosis, coal worker's pneumoconiosis, lung cancer, and occupational asthma & hyperreactivity, and for pathophysiology of airway hyperreactiveness and pulmonary edema are discussed.