The purpose of this study is (1) The success rate of OK-432 pleurodesis after thoracic surgery that air leak over 48 hours (2)The side effects and treatments of OK-432 pleurodesis.

[Methods] This study was a prospective, randomized, open-label, controlled study to evaluate the effectiveness of OK-432 pleurodesis of persistent air Leak after pulmonary Resection. The adult patient have persistent air leak >48 hours after thoracic surgery, will randomized to OK-432 pleurodesis (OK-432 group) or normal saline pleurodesis (NS group). The trial will be conduct from May 25, 2015 to May 25, 2018 in the Department of Surgery at national Taiwan University Hospital, a medical center. The study protocol was approved by the hospitals' Institutional Review Boards. A total of 80 cases, the subjects will be the hospital thoracic surgery ward and received outpatient programs. Eligible Subjects : adults (minimum age> 20 years; maximum age ≦ 70 years old) patients with thoracic surgery and over48 hours of continuous air leak. The exclusion criteria include: penicillin allergy,primary pneumothorax, esophageal cancer, immune dysfunction, those who can not sign a consent form, and pregnant or lactating, other serious concomitant illness such as uremia or liver cirrhosis. Study steps: eligible Patients will randomize according to computer-generated random numbers, with 1:1 ratio in sequentially numbered, sealed envelopes by a study nurse who was masked to the study. Randomization envelopes were opened, and randomization was performed by the study nurse after informed consent was obtain. Eligible inpatients were randomized to the OK-432 group or the normal saline (NS) group，each group are 40 cases.

All subjects were observed by the physician who was masked to the study， about air leak stop time, chest tube removal time, discharge time, outpatient chest X-ray, pulmonary function tests as necessary. cases if persistent air leak more than seven days, the attending physician determines whether pleurodesis again or surgery or other medical treatment. Finally, the researcher who do not know groups will collection data by "air leak case record form" including diagnosis, surgical site，the start and end time of the surgery, the use of antibiotics, discomfort problems (pain , stomach discomfort, cough, fever> 38 ℃, allergic reactions and respiratory discomfort), postoperative air leak time, air leak stop time , chest tube removal time, discharge time, the data will be use SPSS20.0 version of the statistical software package, and T-test, pair T-test ，Anova ,linear correlation statistical methods for analysis.

Outcome measures: OK-432 success rate, OK-432 side effects, air leak time, chest tube remove time, length of hospital stay.

[Background and Objective] :Air leak produced after thoracic surgery is a common phenomenon.Prolonged chest tube placement can lead to empyema or infection, and extended hospitalization or even death. In 2010 many researchers reported that The incidence of lung resection produce air leak about 8-26% (Singhal et al., 2010), and even up to 50% (Mueller & Marzluf, 2014).How to effectively treatment is still not clear.The chemical pleurodesis is an effective option in management of air leak.There are several chemical agents for pleurodesis, such as tetracycline and minocycline, talc, Taurolidine, bleomycin, iodopovidone, picibanil (OK-432), silver nitrate, quinacrine. What kind of chemical agent effective remain controversial. A study evaluated after thoracoscopic operation for primary spontaneous pneumothorax the safety and efficacy of chemical pleurodesis with a comparison between minocycline and OK-432. The OK-432 pleurodesis (19 patients) as the primary treatment and the primary success rate was 95%.(How et al., 2014).Another retrospective case-control study examining post-isolated lobectomies and bilobectomies by thoracotomy of Persistent air leak，sclerosis (talc, bleomycin, minocycline, doxycycline)for the treatment of prolonged air leak was successful in 40 of 41 patients (the success rate of 97.6%) (Liberman et al., 2010). The prolonged air leaks after major pulmonary resection still no empirical treatment of clinical research.

Hypothesis: patients were persistent air leak after 48 hours chest surgery will perform OK-432 pleurodesis .The chest tube time can reduce and length of hospital stay. Extended applications can significantly reduce medical costs and manpower, and to explore OK -432 pleurodesis side effects and treatment.

Inclusion criteria:

• Patients were eligible for this study if they were more than 20 and less than 70 years old of age and under thoracic surgery that air leak lasting more than 48 hours form chest drainage bottles.

Exclusion criteria :

• penicillin allergy, primary pneumothorax, esophageal cancer, immune dysfunction, those who can not sign a consent form, and pregnant or lactating, other serious concomitant illness such as uremia or liver cirrhosis.