Gefitinib is regarded as a relatively safe agent for the treatment of an advanced non-small cell lung cancer (NSCLC). Pulmonary toxicity such as interstitial lung disease associated with gefitinib is uncommon with an estimated all time incidence around 1% worldwide. Moreover, a case of gefitinib associated with pulmonary cystic changes has not been reported yet. In this report we present a case of progressive multiple air cystic changes in both lungs in a patient with NSCLC and intrapulmonary metastases who underwent a gefitinib therapy.
Antineoplastic Agents/*adverse effects ; Brain Neoplasms/secondary ; Carcinoma, Non-Small-Cell Lung/*drug therapy/secondary ; Cysts/*chemically induced ; Female ; Humans ; Lung/pathology ; Lung Diseases/*chemically induced ; Lung Diseases, Interstitial ; Lung Neoplasms/*drug therapy ; Middle Aged ; Quinazolines/*adverse effects

OBJECTIVETo observe the phenomenon of pulmonary hemorrhage (PH) induced by exogenous endothelin-1 (exET-1) and the antagonizing effect of exogenous calcitonin gene-related peptide (exCGRP) in newborn rats.

METHODS(1) To study the exET-1 induced PH: 100 newborn Wistar rats were randomly assigned into control group (group A, n = 10) and experiment groups (20 rats in each of groups B, C, D and E and 10 in group F). Thirty microl of normal saline and different concentrations of exET-1 in saline (ranged from 2 x 10(-6) mol/L to 10 x 10(-6) mol/L) were dripped into the rats' trachea through intubation for control group and the experiment groups, respectively. (2) To study the antagonizing effect of calcitonin gene-related peptide against endothelin: 50 rats were randomly assigned into control group (group D(1), n = 10) and experiment groups D(2), D(3), D(4) and D(5) (10 rats in each group), and were treated with 30 microl of normal saline as control and 4 x 10(-6) mol/L exET-1 via tracheal dripping. Twenty microl of exCGRP (concentrations ranged from 6.7 x 10(-8) mol/L to 6.7 x 10(-6) mol/L) were given by dripping to rats in groups D(3) to D(5) 30 minutes after the administration of exET-1. (3) The rats were sacrificed 3 hours after the first tracheal dripping and the gross anatomical and histological (HE staining) changes in lungs were observed.

RESULTS(1) Following the treatment with exET-1, the rats showed cyanosis and dyspnea rapidly. The severity of respiratory symptoms varied in a dose dependent fashion with the concentrations of exET-1. The symptoms were relieved in the survived rats in about 30 minutes. The rats of all exET-1 treated groups presented with different degree of PH and group D (treated with 4 x 10(-6) mol/L of exET-1) had the highest incidence (diffuse PH 30%, focal PH 25%, spotty PH 25% and 80% in total), with a mortality of 20%. Rats in group E and F had lower incidence of PH (50% and 20%) but higher mortality (35% and 60%). (2) After the administration of different concentrations of exCGRP, the skin of the exET-1 treated rats turned ruddy rapidly with a significantly decreased incidence of PH and all the rats survived. The best protective effect was observed with the concentration of 6.7 x 10(-6) mol/L, and the incidence of PH was reduced to 20% (focal PH 10%, spotty PH 10%).

CONCLUSIONA significant increase of the endogenous ET-1 in hemorrhagic lung tissue caused by rewarming and reoxygenation following hypothermia and hypoxia had been confirmed. Administration of intratracheal exET-1 could induce pulmonary hemorrhage. This suggests that a significant increase of endogenous ET-1 in lung tissue may be one of the mechanisms in pathogenesis of PH caused by rewarming and reoxygenation following hypothermia and hypoxia. Endotracheal administration of exCGRP showed protective antagonizing effect against PH induced by exET-1. The authors speculate that the exCGRP has the potential to treat or even prevent PH caused by a significant increase of the endogenous ET-1.

Animals ; Animals, Newborn ; Calcitonin Gene-Related Peptide ; pharmacology ; Dose-Response Relationship, Drug ; Endothelin-1 ; toxicity ; Female ; Hemorrhage ; chemically induced ; prevention & control ; Lung ; drug effects ; pathology ; Lung Diseases ; chemically induced ; prevention & control ; Male ; Random Allocation ; Rats ; Rats, Wistar

PURPOSE: This study was undertaken to determine the effects of intratracheal administration of endotoxin on hyperoxia-induced lung injury in neonatal rats. MATERIALS AND METHODS: Newborn Sprague Dawley rat pups were divided into four experimental groups: normoxia control (NC), normoxia with endotoxin treatment (NE), hyperoxia control (HC), and hyperoxia with endotoxin treatment (HE) groups. In HC and HE, rat pups were subjected to 14 days of hyperoxia (> 95% oxygen) within 12 hours after birth. In endotoxin treated group (NE and HE), Escherichia coli endotoxin (0.5microgram in 0.03mL of saline) was given intratracheally at the 1st, 3rd and 5th postnatal day. Radial alveolar count (RAC), mean linear intercept (MLI), RAC/MLI ratios, and degree of fibrosis were measured to assess the changes in lung morphology. RESULTS: During the research period, survival rates in both HC and HE were notably reduced 7 days after endotoxin was administered, but body weight gain was considerably reduced only in HC. On day 14, significant arrest in alveolarization, as evidenced by the decrease of RAC and RAC/MLI ratio and increase of MLI as well as increased fibrosis, were noted in HC. Although slight but significant arrest in alveolarization and increased fibrosis score were observed in NE compared to NC, the hyperoxia-induced lung damage observed in HC was significantly improved in HE. CONCLUSION: This study suggests that intratracheal administration of endotoxin significantly attenuated hyperoxia-induced lung injury in neonatal rats.
Animals ; Animals, Newborn ; Body Weight ; Drug Administration Routes ; Endotoxins/*administration & dosage ; Hyperoxia/*complications ; Lung Diseases/*chemically induced/*etiology/pathology ; *Lung Injury ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the clinical, pathologic and radiologic features of amiodarone-induced lung injury.

METHODSThe clinical, pathologic and radiologic features, including treatment and follow-up information of three cases diagnosed as amiodarone-induced lung injury from October 2004 to October 2005 in the Peking Union Medical College Hospital were reviewed.

RESULTSAll the patients were males, with age ranging from 35 to 64 years. The duration of symptoms varied from 20 days to 3 years. All presented with cough. Worsening dyspnea and inspiratory crackles were noted in two patients. Computerized tomography showed bilateral patchy infiltration, ground-glass appearance and accentuation of bronchovascular markings. The most common pathologic manifestations included cellular interstitial pneumonia associated with intra-alveolar collections of macrophages and type II pneumocyte hyperplasia. Some of the macrophages contained finely vacuolated cytoplasm. An organizing pneumonia pattern was seen in one patient.

CONCLUSIONSAmiodarone-induced lung injury has characteristic pathologic features which may provide clues to diagnosis. Correlation with clinical and radiologic findings is also important.

Adult ; Amiodarone ; adverse effects ; Anti-Arrhythmia Agents ; adverse effects ; Biopsy ; Follow-Up Studies ; Glucocorticoids ; therapeutic use ; Humans ; Lung ; drug effects ; pathology ; radiation effects ; Lung Diseases, Interstitial ; chemically induced ; drug therapy ; pathology ; Lung Injury ; chemically induced ; drug therapy ; pathology ; Male ; Middle Aged ; Prednisone ; therapeutic use ; Pulmonary Alveoli ; drug effects ; pathology ; Retrospective Studies ; Tomography, X-Ray Computed

From 2006 to 2011, an outbreak of a particular type of childhood interstitial lung disease occurred in Korea. The condition was intractable and progressed to severe respiratory failure, with a high mortality rate. Moreover, in several familial cases, the disease affected young women and children simultaneously. Epidemiologic, animal, and post-interventional studies identified the cause as inhalation of humidifier disinfectants. Here, we report a 4-year-old girl who suffered from severe progressive respiratory failure. She could survive by 100 days of extracorporeal membrane oxygenation support and finally, underwent heart-lung transplantation. This is the first successful pediatric heart-lung transplantation carried out in Korea.
Child, Preschool ; Disinfectants/toxicity ; Extracorporeal Membrane Oxygenation ; Female ; Humans ; *Humidifiers ; Lung/drug effects/pathology ; Lung Diseases, Interstitial/*chemically induced/pathology/*therapy ; *Lung Transplantation ; Republic of Korea ; Respiratory Rate ; Retrospective Studies ; Thorax/diagnostic imaging ; Tomography, X-Ray Computed

OBJECTIVETo analyze the clinical features of interstitial pneumonitis (IP) associated with interferon therapy for chronic hepatitis C.

METHODSWe report the first case of IP in China resulting from pegylated interferon alpha-2a in combination with ribavirin for treatment of hepatitis C viral infection. A statistical analysis of the related literatures documenting such IP cases was performed using SPSS 11.5 software.

RESULTSOf the 22 patients reported to develop IP after interferon therapy alone or in combination with ribavirin, 83%, 72% and 56% of the patients had the symptoms of dyspnoea, dry cough and fever, respectively. Twenty of these cases presented with restrictive pulmonary functional impairment and/or hypoxemia, and diffuse infiltration on chest radiography and/or CT. Complications were documented in 71% of the cases within 12 weeks of the treatment. The majority (85%) of the patients had favorable prognoses with an average recovery time of 7.5 weeks. Compared with the patients with mild and moderate pulmonary function impairment, 8 patients with severe pulmonary functional impairment had early onset of IP during the interferon therapy (6.6 vs 14.1 weeks, P<0.05), and a higher rate of corticosteroid treatment (75% vs 54%, P>0.05).

CONCLUSIONIP is a rare pulmonary complication associated with IFN therapy, and patients with chronic hepatitis C should be followed up closely in the first 12 weeks of interferon therapy. Prompt discontinuation of medication is mandatory in the presence of IP, and corticosteroid therapy may not be essential for patients with mild or moderate pulmonary functional impairment under close monitoring. The severity of pulmonary damage is associated with the time of complication occurrence, and corticosteroids are required when obvious pulmonary toxicity occurs in early stage of the treatment (within 6 weeks) to reduce the pulmonary damage.

Adult ; Aged ; Female ; Hepatitis C, Chronic ; drug therapy ; Humans ; Interferon-alpha ; adverse effects ; therapeutic use ; Lung ; diagnostic imaging ; drug effects ; pathology ; physiopathology ; Lung Diseases, Interstitial ; chemically induced ; diagnostic imaging ; pathology ; physiopathology ; Male ; Middle Aged ; Time Factors ; Tomography, X-Ray Computed

OBJECTIVETo investigate the oxidative damage to lung tissue and peripherial blood in PM2.5-treated rats.

METHODSPM2.5 samples were collected using an auto-sampling instrument in summer and winter. Treated samples were endotracheally instilled into rats. Activity of reduced glutathione peroxidase (GSH-Px) and concentration of malondialdehyde (MDA) were used as oxidative damage biomarkers of lung tissue and peripheral blood detected with the biochemical method. DNA migration length (microm) and rate of tail were used as DNA damage biomarkers of lung tissue and peripheral blood detected with the biochemical method.

RESULTSThe activity of GSH-Px and the concentration of MDA in lung tissue significantly decreased after exposure to PM2.5 for 7-14 days. In peripheral blood, the concentration of MDA decreased, but the activity of GSH-Px increased 7 and 14 days after experiments. The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood. The DNA migration length (microm) and rate of tail in lung tissue and peripheral blood significantly increased 7 and 14 days after exposure to PM2.5. The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood.

CONCLUSIONPM2.5 has a definite oxidative effect on lung tissue and peripheral blood. The activity of GSH-Px and the concentration of MDA are valuable biomarkers of oxidative lung tissue damage induced by PM2.5. The DNA migration length (microm) and rate of tail are simple and valuable biomarkers of PM2.5-induced DNA damage in lung tissues and peripheral blood. The degree of DNA damage in peripheral blood can predict the degree of DNA damage in lung tissue.

Animals ; DNA Damage ; drug effects ; Drug Administration Routes ; Drug Administration Schedule ; Lung ; drug effects ; pathology ; Lung Diseases ; blood ; chemically induced ; pathology ; Male ; Oxidative Stress ; Particle Size ; Particulate Matter ; administration & dosage ; toxicity ; Rats ; Rats, Wistar ; Seasons

OBJECTIVETo observe the efficacy and the adverse effects of erlotinib in the treatment for advanced non-small cell lung cancer (NSCLC) in Chinese patients.

METHODSFrom November 2005 to March 2009, a total of 519 patients with unresectable, local advanced, relapsed or metastatic NSCLC were enrolled in the trial. All the patients were treated with erlotinib 150 mg/day until disease progression or intolerable toxicity or for other reasons. The response rate, time to disease progression, overall survival and toxicity were analyzed.

RESULTSOf these 519 patients, 1 case had complete response, 127 cases had partial response and 263 cases had stable disease, resulting in an overall response rate (CR + PR) of 26.7%, disease stable rate of 54.9% and disease control rate (CR + PR + SD) of 81.6%. The median time to progression was 6.44 months and median overall survival was 15.37 months. The major erlotinib treatment-related adverse events (AE) were mild (CTC AE 1/2), only 3 cases had severe adverse effect, 1 case had interstitial lung disease and died of respiratory failure.

CONCLUSIONThe study presents excellent response rates, time to progression and overall survival of erlotinib treatment for advanced NSCLC in Chinese patients, and its adverse events are tolerable.

Asian Continental Ancestry Group ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Diarrhea ; chemically induced ; Disease Progression ; Erlotinib Hydrochloride ; Exanthema ; chemically induced ; Female ; Follow-Up Studies ; Humans ; Lung Diseases, Interstitial ; chemically induced ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Protein Kinase Inhibitors ; adverse effects ; therapeutic use ; Quinazolines ; adverse effects ; therapeutic use ; Receptor, Epidermal Growth Factor ; adverse effects ; antagonists & inhibitors ; therapeutic use ; Remission Induction ; Survival Rate

Lansoprazole is an acid proton-pump inhibiting drug that is used for the treatment of duodenal or gastric ulcers, H. pylori infection, gastroesophageal reflux disease or Zollinger-Ellison syndrome. Although lansoprazole is well known for its gastrointestinal and dermatologic adverse effects, mild pulmonary symptoms are also known to develop from taking this drug. There have been no reports about lansoprazole-induced interstitial lung disease. We report here a case of lansoprazole-induced interstitial lung disease that developed in a 66-year-old man.
2-Pyridinylmethylsulfinylbenzimidazoles/*adverse effects ; Aged ; Anti-Ulcer Agents/*adverse effects ; Biopsy/methods ; Gastroesophageal Reflux/drug therapy ; Humans ; Lung/*pathology ; Lung Diseases, Interstitial/*chemically induced ; Male ; Thoracic Surgery, Video-Assisted ; Tomography, X-Ray Computed

Pulmonary toxicity is one of the most serious adverse effects associated with a quick course of vincristine, bleomycin, and cisplatin neoadjuvant chemotherapy (NAC-VBP). The aim of this study was to evaluate pulmonary toxicity related to a quick course NAC-VBP. A total of consecutive 61 patients, who underwent at most 3 cycles of NAC-VBP every 10 days in the International Federation of Gynecology and Obstetrics (FIGO) stage IB-IIB cervical cancer from 1995 to 2007, were retrospectively analyzed. Of the 61 study subjects, 7 (11.5%) were identified to have pulmonary toxicity and 2 (3.3%) died of pulmonary fibrosis progression despite aggressive treatment and the use of a multidisciplinary approach. No factor predisposing pulmonary toxicity was identified. Initial symptoms were non-specific, but bronchiolitis obliterans organizing pneumonia and interstitial pneumonitis were characteristic findings by high-resolution computed tomography of the chest. The benefit of steroid therapy was uncertain and was associated with steroid-induced diabetes mellitus requiring insulin therapy in two patients. Fatal pulmonary toxicity is a major concern of a quick course NAC-VBP. In conclusion, these patients require special monitoring for bleomycin-induced pulmonary toxicity.
Aged ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*adverse effects/therapeutic use ; Bleomycin/administration & dosage/*adverse effects/therapeutic use ; Cisplatin/administration & dosage/*adverse effects/therapeutic use ; Female ; Humans ; Lung Diseases/*chemically induced/pathology ; Middle Aged ; *Neoadjuvant Therapy ; Pulmonary Fibrosis/chemically induced/mortality/pathology ; Retrospective Studies ; Tomography, X-Ray Computed ; Uterine Cervical Neoplasms/complications/*drug therapy ; Vincristine/administration & dosage/*adverse effects/therapeutic use