Prognostic significance of initial platelet counts and fibrinogen level in advanced non-small cell lung cancer.

Thrombocytosis and coagulation systems activation are commonly associated with disease progression and are suggested poor prognostic factors in patients with malignancies. This study aimed to investigate the prevalence and prognostic significance of thrombocytosis and elevated fibrinogen levels in patients with advanced non-small cell lung cancer (NSCLC). Initial platelet counts and fibrinogen levels were reviewed in 854 patients with histologically proven NSCLC. Thrombocytosis was defined as platelet counts > 450 × 10(9)/L. A serum fibrinogen level > 4.5 g/L was considered high. At the time of diagnosis, initial platelet counts and serum fibrinogen levels were evaluated before treatment. Clinicopathologic data including histological type, tumor, node, metastasis (TNM) stage, performance status, treatment method, and survival time were evaluated. Initial thrombocytosis was found in 6.9% of patients, and elevated fibrinogen levels were found in 55.1% of patients. Patients with thrombocytosis had a significantly poorer prognosis than patients with normal platelet counts (P < 0.001). In multivariate survival analysis, thrombocytosis was an independent prognostic factor (P < 0.001). An elevated serum fibrinogen level was associated with poor prognosis (P < 0.001). In conclusion, initial thrombocytosis and a high fibrinogen level are independent factors for predicting poor prognosis in patients with advanced NSCLC.

Treatment response and adverse reactions in older tuberculosis patients with immunocompromising comorbidities.

PURPOSE: The aim of this study was to elucidate the effects of immunocompromising comorbidities on treatment response and adverse reactions in older tuberculosis (TB) patients. MATERIALS AND METHODS: The medical records of 182 patients older than 65 years with proven TB by positive culture of Mycobacterium tuberculosis and with available drug susceptibility tests were reviewed retrospectively. These patients were subsequently assigned to either the comorbidity group (n=78) or non-comorbidity group (n=104) depending on whether they had immunocompromising comorbidities. RESULTS: The mean durations of treatment were 9.9 ± 3.3 months in the comorbidity group and 9.3 ± 3.2 months in the non-comorbidity group (p=0.21). M. tuberculosis culture results converted to negative in most patients with available follow-up cultures at two months after treatment. The successful treatment rates were 94.9% and 98.9% in the comorbidity and non-comorbidity groups, respectively (p=0.30). The most common side effects of anti-TB treatment were skin rash/pruritus (13% in the comorbidity group vs. 11% in the non-comorbidity group, p=0.79), gastro-intestinal problems (14% vs. 9%, p=0.25) and hepatotoxicity (14% vs. 7%, p=0.09). CONCLUSION: The present study shows that the successful treatment rate for TB is high and that immunocompromising comorbidities have no effect on the response to treatment and adverse effects in older TB patients.

Clinical implication of microscopic anthracotic pigment in mediastinal staging of non-small cell lung cancer by endobronchial ultrasound-guided transbronchial needle aspiration.

Microscopic anthracotic pigment (MAP) is frequently observed in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimen in non-small cell lung cancer, but its clinical interpretation is not well-known. The aim of this study was to evaluate the clinical implication of MAP in mediastinal staging of non-small cell lung cancer. From May 2010 to July 2011, consecutive potentially operable non-small cell lung cancer patients who underwent EBUS-TBNA for mediastinal staging were recruited. Of the total 133 patients, 102 (76.7%) were male patients. Median age was 68 yr. Total 279 mediastinal lymph nodes were sampled by EBUS-TBNA; station 4R (100, 35.8%) and station 7 (86, 30.8%) were the most common sites. Malignant lymph nodes were 100 (35.8%). MAP was observed in 61 (21.7%) lymph nodes, and among them only 3 were malignant lymph nodes (P < 0.001). The lymph nodes with MAP were smaller (9.0 vs 10.8 mm, P = 0.001) and showed low standard uptake values on FDG-PET (4.4 vs 4.7, P = 0.256). In multivariate analysis, MAP was negatively associated with malignant lymph node (adjusted OR, 0.12; 95% CI, 0.03-0.42; P < 0.001). In potentially operable non-small cell lung cancer patients, MAP in endobronchial ultrasound-guided transbronchial needle aspiration specimens is strongly associated with benign mediastinal and hilar lymph nodes.

Prognosis for non-small cell lung cancer patients with brain metastases.

PURPOSE: Brain metastasis has a poor prognosis in patients with advanced non-small cell lung cancer (NSCLC). In this study, we evaluated the prognosis of NSCLC patients with brain metastases. METHODS: We analyzed a total of 313 NSCLC patients with brain metastasis. We compared the prognoses between a group of less than four (group A) and a group of more than four or equal to four (≥4) (group B) brain metastases. RESULTS: The median survival time was 334 days (group A, 164 patients, 52.4%) and 234 days (group B, 149 patients, 47.6%). Univariate analysis showed that the number of metastases, age at diagnosis of brain metastasis, smoking history, histologic type, and former stage of primary lung cancer before brain metastasis, had a significant influence. In addition, treatment for primary lung cancer lesions and brain metastasis also affected the overall survival (p < .0001). However, there was no difference in the overall survival between the two groups in the multivariate analysis. CONCLUSION: Our results show that the number of brain metastases, classified by group A (<4) or group B (≥4) did not influence the overall survival of NSCLC patients. However, the overall survival in group A was better than in group B when analyzed, except for local brain treatment modalities in sub-group analysis, suggesting that non-optimized local treatment strategies might cause an unexpected prognosis result in this retrospective study. We suggest that more prospective studies might be needed for the optimal standard treatment for brain metastasis.

Effects of consumer-centered u-health service for the knowledge, skill, and attitude of the patients with chronic obstructive pulmonary disease.

Through the use of ubiquitous health, or u-Health, services, medical information can be adapted and made accessible via computer and Internet to provide quality healthcare to anybody, any place, and any time. We developed and implemented u-Health services for patients with chronic obstructive pulmonary disease and studied their experiences with respect to their knowledge of chronic obstructive pulmonary disease and skill and attitude toward the u-Health devices. The u-Health services were composed of telemonitoring and teleconsultation supplemented with home visits. To determine its effectiveness, the u-Health service system was implemented for 2 years with 144 chronic obstructive pulmonary disease patients in a clinical experiment. The subjects were divided into three experimental groups, each provided with different services, compared before and after intervention, and among groups. The analysis of data gathered through the system suggested that u-Health services can support patients with chronic obstructive pulmonary disease, improve patients' knowledge about chronic obstructive pulmonary disease self-management, build u-Health device usage skills, and foster a positive attitude toward u-Health devices. The u-Health services for the chronic obstructive pulmonary disease patients were both feasible and effective from the patients' perspective.

Clinical features of patients on home oxygen therapy due to chronic respiratory failure at one university hospital.

BACKGROUND/AIMS: Home oxygen therapy (HOT) costs a great deal every year and demand for the service is growing. In Korea, health insurance has covered HOT since November 1, 2006. The objective of this study was to evaluate clinical features of patients who used long-term HOT due to chronic respiratory failure and to determine the appropriateness of oxygen prescriptions. METHODS: Between November 2006 and April 2010, patients prescribed long-term HOT were enrolled in the study at a tertiary university referral hospital and their medical records and telephone survey information were evaluated. In total, 340 patients were evaluated retrospectively. RESULTS: Regarding the initial indications for HOT, their mean PaO(2) was 49.8 mmHg and mean SpO(2) was 82.2%. Underlying diseases included chronic obstructive pulmonary disease (COPD, 19.8%), lung cancer (12.6%), and interstitial lung disease (11.2%). The admission rate within 1 year was 53.4% and the average number of admissions was 1.64/patient. Other underlying diseases for which oxygen was prescribed, despite not meeting the insurance coverage criteria, were lung cancer (36.6%) and interstitial pneumonia (16.6%). CONCLUSIONS: Home oxygen prescriptions have increased since health insurance coverage was extended. However, cases of oxygen prescriptions frequently do not meet the coverage criteria. It is important to discuss extending the coverage criteria to other disease groups, such as interstitial lung disease and lung cancer, in terms of cost-effectiveness. Further, physicians prescribing oxygen therapy should be educated regarding the criteria.

Positive tuberculin skin test or interferon-gamma release assay in patients with radiographic lesion suggesting old healed tuberculosis.

Radiographic lesions suggesting old healed tuberculosis (TB) is considered a risk factor for the subsequent development of active TB. The aim of this study was to estimate the positive rates of tuberculin skin test (TST) and interferon-gamma release assay (IGRA) in persons with old healed TB. Participants with lesions suggesting old healed TB on chest images and controls without such lesions were prospectively enrolled between January 1, 2010, and January 31, 2011. TST and the QuantiFERON-TB Gold In-Tube test (QFT-GIT) were performed. In total, 193 participants with old healed TB and 126 controls were recruited. The rates of positive TST and QFT-GIT among patients with old healed TB were 54.6% and 77.7%, respectively. The rates of positive TST and QFT-GIT among patients without old healed TB were 38.9% and 61.9%. Sixteen percent of participants with old healed TB showed negative results by both TST and QFT-GIT. The positive rate of TST waned among participants with old healed TB who were older than 60 yr, whereas QFT-GIT positivity was unaffected by age. The positive rates of TST and IGRA among participants with radiographic lesions suggesting old healed TB was higher than without those lesions. In addition, IGRA may be more accurate than TST for the detection of latent TB infection, especially in populations of individuals older than 60 yr.

Treatment response and long term follow-up results of nonspecific interstitial pneumonia.

The purpose of this study was to investigate the long-term clinical course of non-specific interstitial pneumonia (NSIP) and to determine which factors are associated with a response to steroid therapy and relapse. Thirty-five patients with pathologically proven NSIP were included. Clinical, radiological, and laboratory data were reviewed retrospectively. The male-to-female ratio was 7:28 (median age, 52 yr). Thirty (86%) patients responded to steroid therapy, and the median follow-up was 55.2 months (range, 15.9-102.0 months). Five patients (14%) showed sustained disease progression and three died despite treatment. In the five with sustained disease progression, NSIP was associated with various systemic conditions, and the seropositivity of fluorescent antinuclear antibody was significantly associated with a poor response to steroids (P = 0.028). The rate of relapse was 25%, but all relapsed patients improved after re-treatment. The initial dose of steroids was significantly low in the relapse group (P = 0.020). In conclusion, progression is associated with various systemic conditions in patients who show progression. A low dose of initial steroids is significantly associated with relapse.

Bacterial yield from quantitative cultures of bronchoalveolar lavage fluid in patients with pneumonia on antimicrobial therapy.

BACKGROUND/AIMS: Early diagnosis and appropriate antimicrobial choice are crucial when managing pneumonia patients, and quantitative culture of bronchoalveolar lavage (BAL) fluid is considered a useful method for identifying pneumonia pathogens. We evaluated the quantitative yield of BAL fluid bacterial cultures in patients being treated with antimicrobials and attempted to identify factors predictive of positive BAL cultures. METHODS: Patients over 18 years old and whose BAL fluid was subjected to quantitative culture to identify the organism causative of pneumonia between January 1, 2005, and December 31, 2009, were included. We reviewed the results of BAL fluid bacterial cultures and the clinical records, laboratory tests, and radiographic findings of the patients. RESULTS: BAL was performed on 340 patients with pneumonia. A positive BAL culture, defined as isolation of more than 10(4) colony forming units/mL bacteria, was documented in 18 (5.29%) patients. Of these, 9 bacteria isolated from 10 patients were classified as probable pathogens. The most frequently isolated bacteria were methicillin-resistant Staphylococcus aureus, Acinetobacter baumannii, and Pseudomonas aeruginosa. No independent predictive factor for positive BAL cultures was identified. CONCLUSIONS: The yield of quantitative BAL fluid bacterial culture in patients already on antimicrobials was low. Clinicians should be cautious when performing a BAL culture in patients with pneumonia who are already on antimicrobials.

Prognosis in patients having chronic obstructive pulmonary disease with significant coronary artery lesion angina.

BACKGROUND/AIMS: Many studies have investigated angina and its relationship with chronic obstructive pulmonary disease (COPD). However, angina was diagnosed only by noninvasive tests or only by clinical symptoms in most of these studies. The aim of this study was to compare the prognosis, including rate of hospitalization and death from significant coronary artery lesion and nonsignificant coronary artery lesion angina, in patients with COPD. METHODS: Patients with COPD who underwent coronary angiography (CAG) due to angina were reviewed retrospectively at a tertiary referral hospital. COPD is defined as post-bronchodilator forced expiratory volume in 1 sec/forced vital capacity (FEV(1)/FVC) of < 70%. A significant coronary lesion is defined as at least 50% diameter stenosis of one major epicardial artery in CAG. RESULTS: In total, 113 patients were enrolled. Mean follow-up duration was 39 ± 21 months. Of the patients, 52 (46%) had mild COPD and 48 (42%) had moderate COPD. Sixty-nine (61%) patients had significant stenosis in CAG. The death rate in the follow-up period was 2.21 per 100 patient-years. No significant difference was observed among the all-cause mortality rate, admission rate, or intensive care unit admission rate in patients who had COPD with or without significant coronary artery disease. Pneumonia or acute exacerbation of COPD was the most common cause of admission. CONCLUSIONS: In patients having COPD with angina who underwent CAG, no significant difference was observed in mortality or admission events depending on the presence of a significant coronary artery lesion during the 2-year follow-up period.

Quantification of galantamine in human plasma by validated liquid chromatography-tandem mass spectrometry using glimepride as an internal standard: application to bioavailability studies in 32 healthy Korean subjects.

A simple, rapid and selective liquid chromatography method coupled with tandem mass spectrometry is developed and validated for the quantification of galantamine in human plasma using a commercially available compound, glimepride, as an internal standard (IS). Following simple one-step liquid-liquid extraction by ethyl acetate, the analytes are separated using an isocratic mobile phase consisting of acetonitrile and 0.01M ammonium acetate (95/5, v/v) on a reverse-phase C18 column and analyzed by tandem mass spectrometry in the multiple reaction monitoring mode using the transitions of respective (M + H)(+) ions, m/z 288.22 → 213.20 and m/z 491.17 → 352.30 for the quantification of galantamine and IS, respectively. The standard calibration curves show good linearity within the range of 4 to 240 ng/mL (r(2) = 0.9996, 1/x(2) weighting). The lower limit of quantification is 4 ng/mL. The retention times of galantamine and IS are 1.1 and 0.71 min, which showsthe high throughput potential of the proposed method. In addition, no significant metabolic compounds are found to interfere with the analysis. Acceptable precision and accuracy are obtained for the concentrations over the standard curve range. The validated method is successfully applied for pharmacokinetic and bioequivalence studies of 24 mg of a galantamine hydrobromide capsule in 32 healthy Korean subjects.

Prognostic factors for non-small cell lung cancer with bone metastasis at the time of diagnosis.

INTRODUCTION: The skeletal system is one of the most common distant sites of metastatic non-small cell lung cancer (NSCLC) which may lead to skeletal-related event (SRE). The purpose of this study was to assess the frequency of SRE and the prognostic factors of overall survival (OS) in patients presenting bone metastasis in NSCLC. METHODS: Two hundred and twenty NSCLC patients with skeletal metastases at the time of diagnosis between January 2000 and August 2007 were investigated retrospectively. RESULTS: Forty-seven of 110 patients (43%) without a SRE at the time of diagnosis experienced their first SRE during the follow-up. Patients with squamous cell carcinoma had a 1.8-times higher risk of short OS [95% confidence interval (CI) 1.11-2.84, p=0.016], compared with patients with non-squamous cell carcinoma, and patients treated with EGFR TKIs achieved a 50% protective effect in OS compared with patients not treated with them (95% CI 0.32-0.80, p=0.004). Patients with ECOG performance status 0-1 and single bone metastasis had a 1.8-times (95% CI 1.13-2.60, p=0.003) and 2.4-times (95% CI 1.26-4.46, p=0.008) longer OS than patients with performance status≥2 and two or more bone metastases, respectively. CONCLUSION: Our study demonstrated that the frequency of SRE was common and single bone metastasis, good performance status (ECOG 0, 1), EGFR TKI treatment had good prognosis and histology of squamous cell carcinoma had bad prognosis.

Differential sensitivities to tyrosine kinase inhibitors in NSCLC harboring EGFR mutation and ALK translocation.

Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) translocations in non-small cell lung cancer (NSCLC) are mutually exclusive. However, several exceptional cases harboring both genetic alterations have been reported. In this study, a total of 444 patients with lung adenocarcinoma were examined for their EGFR and ALK status at Seoul National University Hospital between July 2008 and September 2011. EGFR mutations and ALK translocations were detected in 228 (51.4%) and 34 (7.7%) patients, respectively. Four patients (0.9%) had both genetic alterations and three underwent curative surgery. One patient who received both EGFR tyrosine kinase and ALK inhibitors, separately showed an objective response to the ALK inhibitor alone. Considering our and previous studies, patients harboring both EGFR mutation and ALK translocation showed differential sensitivities to both targeted therapies, suggesting a variable dependence on EGFR and ALK oncogenes.

Prognostic effect of age on survival of patients with stage I adenocarcinoma of the lung.

AIMS AND BACKGROUND: It is still unclear whether age is an independent prognostic factor in patients with stage I NSCLC. METHODS: Five hundred and sixty-nine patients with stage I adenocarinoma who underwent surgical resection as first treatment were included. The effect on overall survival of age, gender, smoking habits, Charlson comorbidity index score (CCIS), type of surgery, tumor size and lymphatic or blood vessel invasion was analyzed. RESULTS: When the patients were divided into four groups according to quartiles of age, distributions of gender, smoking habit, CCIS, histology, blood vessel invasion and adjuvant chemotherapy were significantly different among the four groups. Age, gender, smoking habit, CCIS, tumor size and lymphatic and blood vessel invasion were significantly associated with overall survival of the patients in Kaplan-Meier analysis (logrank, P <0.001, P <0.001, P = 0.029, P <0.001, P = 0.001, P = 0.001 and P = 0.007, respectively). Moreover, the highest quartile of age (over 68 years old) was a prominent determinant for a worse prognosis after adjustment for the confounding variables using a Cox proportional hazard model (adjusted hazard ratio = 2.735, 95% confidence interval = 1.623-4.608, P <0.001). CONCLUSIONS: The findings suggest that age is an important determinant of overall survival in patients with stage I adenocarcinoma. Therefore, age should be considered in classifying the patients into groups of higher or lower risk for death as well as in designing clinical trials.

EGFR mutations as a predictive marker of cytotoxic chemotherapy.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) are important predictive markers for the response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Whether EGFR mutations can also predict the clinical outcomes in NSCLC patients receiving chemotherapy has not yet been established. METHODS: We included 217 locally advanced/metastatic NSCLC cases in our study cohort. Each patient had received platinum doublet chemotherapy as a first line treatment, and had been screened for an EGFR mutation. RESULTS: The subject cohort comprised 80 EGFR wild type and 137 EGFR-mutated lung cancer patients. Gemcitabine-based and taxane-based regimens were administered in 131 (60.4%) and 86 (39.6%) cases, respectively. Among the patients with a wild type EGFR, there was no significant difference in the response rate (RR), disease control rate (DCR), or progression-free survival (PFS) between gemcitabine-based and taxane-based therapies. Among the patients with EGFR mutations, no difference in RR was observed between gemcitabine-based and taxane-based treatments. On the other hand, the DCR and PFS associated with taxane-based therapy were superior when compared with the gemcitabine-based treatments. When we analyzed patients with an EGFR exon 19 deletion, the PFS of the taxane treated cases was better than that of the gemcitabine treated cases (5.3 months vs 3.7 months, P=0.012). CONCLUSIONS: Our current data indicate that lung cancer patients with EGFR-mutations had longer PFS with taxane than gemcitabine when receiving a platinum-based doublet regimen. The predictive meaning of EGFR mutations for cytotoxic chemotherapy should be further investigated.

Vitamin D deficiency and changes in serum vitamin D levels with treatment among tuberculosis patients in South Korea.

BACKGROUND AND OBJECTIVE: Vitamin D deficiency has been reported to be associated with the development of active tuberculosis (TB), but many discrepancies exist among studies. The aims of this study were to compare the frequency of vitamin D deficiency in a Korean population of TB patients and control subjects, and to monitor the changes in vitamin D levels during TB treatment. METHODS: Patients with newly diagnosed TB were prospectively enrolled. In addition, healthy volunteers or patients with diseases other than TB were enrolled as controls. Baseline serum 25-hydroxyvitamin D (25-OHD) levels were measured in both groups and compared. In the TB patients, measurements of serum 25-OHD were repeated 1 month after the initiation of treatment and again after completion of treatment. RESULTS: In total, 116 patients with TB and 86 control subjects were recruited. The median 25-OHD concentration was not different in TB patients at diagnosis (13.9 ng/mL; interquartile range (IQR) 8.80-21.8) compared with control subjects (13.2 ng/mL; IQR 9.6-19.3) (P = 0.97). The frequency of vitamin D deficiency (≤ 10 ng/mL) was also not different in TB patients (36.2%) compared with controls (27.3%) (P = 0.21). In TB patients, the median 25-OHD concentration decreased significantly during treatment, to 12.5 ng/mL at 1 month and 11.0 ng/mL on completion of treatment (P = 0.01). CONCLUSIONS: Vitamin D levels do not appear to be associated with the development of TB in the Korean population. The median 25-OHD concentration decreased after treatment for TB.

Quantification of nimesulide in human plasma by high-performance liquid chromatography with ultraviolet detector (HPLC-UV): application to pharmacokinetic studies in 28 healthy Korean subjects.

Nimesulide is a selective COX-2 inhibitor that is as effective as the classical non-acidic nonsteroidal anti-inflammatory drugs in the relief of various pain and inflammatory conditions, but is better tolerated with lower incidences of adverse effects than other drugs. After oral dose of 100 mg nimesulide to western subjects, a mean maximal concentration (C(max)) of 2.86 ∼ 6.5 µg/mL was reached at 1.22 ∼ 2.75 h and mean t(1/2ß) of 1.8 ∼ 4.74 h. This study developed a robust method for quantification of nimesulide for the pharmacokinetics and suitability of its dosage in Korea and compared its suitability with other racial populations. Nimesulide and internal standard were extracted from acidified samples with methyl tert-butyl ether and analyzed by high-performance liquid chromatography with ultraviolet detection (HPLC-UV). The 28 healthy volunteers took 2 tablets of 100 mg nimesulide and blood concentrations were analyzed during the 24 h post dose. Several pharmacokinetic parameters were represented: AUC(0-infinity) = 113.0 mg-h/mL, C(max) = 12.06 mg/mL, time for maximal concentrations (T(max)) = 3.19 h and t(1/2ß) = 4.51 h. These were different from those of western populations as follows: AUC was 14.5% and C(max) was 28% that of of Korean subjects and T(max) and t(1/2ß) were also different. The validated HPLC-UV method was successfully applied for the pharmacokinetic studies of nimesulide in Korean subjects. Because the pharmacokinetics of nimesulide were different from western populations, its dosage regimen needs to be adjusted for Koreans.

Outcome of patients with connective tissue disease requiring intensive care for respiratory failure.

Occasionally acute respiratory failure (ARF) develops in patients with connective tissue disease (CTD), but the etiologies of ARF in these patients are not fully elucidated. The objective of this study is to find out the causes of ARF leading to intensive care unit (ICU) admission in these patients and to assess their clinical outcome. The medical records of 1,870 consecutive patients admitted to the ICU in Seoul National University Hospital since January 2005-September 2008 were reviewed. A total of 66 patients with CTD were analyzed. The median age was 58 years, and 45 patients were women. The median length of ICU stay was 16 days with a median duration of mechanical ventilation support of 15 days. The distribution of underlying CTD was 17 patients with systemic lupus erythematosus; 15 with rheumatoid arthritis; 14 with systemic vasculitis; and nine with polymyositis-dermatomyositis. Pneumonia was the leading cause of ARF in 24 patients (36%). We could not identify the cause of ARF in 14. Other causes of ARF were acute pulmonary edema for nine patients, diffuse alveolar hemorrhage for eight and Pneumocystis pneumonia for four. Forty-one patients (62%) died during admission, and the mortality rate was the lowest in those with acute pulmonary edema. Use of norepinephrine was statistically higher in nonsurvivors. We could identify the cause of ARF leading to ICU admission in at least 80% of patients with CTD. However, these patients still showed a high mortality rate regardless of etiology. Their survival might be influenced by hemodynamic status.

The clinical implications of bronchoscopy in hemoptysis patients with no explainable lesions in computed tomography.

INTRODUCTION: Hemoptysis is observed frequently in patients, although chest computed tomography (CT) shows no explainable lesion as the cause of hemoptysis. However, the clinical course of these patients has not been reported fully. METHODS: This study included patients who visited Seoul National University Hospital and Seoul National University Bundang Hospital to be treated for hemoptysis from January 2003 through October 2009 and who had no lesion causing hemoptysis in chest CT. We retrospectively analyzed their bronchoscopic and clinical findings. RESULTS: A total of 228 patients were included, and the mean follow-up duration was 781 days. All patients underwent bronchoscopy. The bronchoscopic findings of 191 patients (83.8%) were negative for hemoptysis and showed the possible causes of bleeding in 37 patients (16.2%). Forty-three of the 191 patients with negative bronchoscopic findings had oronasopharyngeal problems or were using anticoagulants. After excluding these 43 patients, hemoptysis recurred in 29 (19.6%) of the remaining patients. Thirteen of the patients whose bronchoscopic findings identified the possible causes of bleeding (35.1%) experienced recurrence. Only one patient (0.4%) was diagnosed with lung cancer by the initial bronchoscopy, and no patient developed malignancy during the follow-up period. CONCLUSION: The recurrence rate was higher in the patients with positive findings than in the patients with negative findings on bronchoscopy. Although about 20% of patients with negative bronchoscopy findings experienced recurrence, the clinical course of those in whom recurrent bleeding occurred was usually benign.

Adverse pulmonary reactions associated with the use of monoclonal antibodies in cancer patients.

BACKGROUND: The incidence and clinical characteristics of adverse pulmonary reactions resulting from anticancer monoclonal antibody (mAbs) therapy have not been well described. We determined the incidence and clinical characteristics of adverse pulmonary reactions in patients treated with anticancer chemotherapy including mAbs. METHODS: A retrospective cohort study was performed including patients who were treated with a chemotherapeutic regimen that included rituximab, trastuzumab, cetuximab, or bevacizumab at Seoul National University Hospital between January 1, 2004 and December 31, 2008. Rates of adverse pulmonary reactions classified as non-infectious and infectious complications were compared with those among patients treated with comparable regimens without mAbs. RESULTS: In total, 1078 patients were included (418 for rituximab, 329 for trastuzumab, 122 for cetuximab, 209 for bevacizumab). Adverse pulmonary reactions were identified in 36 patients (3.5%) and the incidence differed among agents: cetuximab (9%), rituximab (5.3%), trastuzumab (0.6%), bevacizumab (0.5%). Infectious pulmonary complications occurred in 28 patients, and eight patients experienced non-infectious pulmonary complications, most commonly interstitial lung disease (6 patients). In a multivariate analysis, low serum albumin level was associated with the development of pulmonary complications. The incidence of overall adverse pulmonary reactions did not differ between the mAbs users and the 1012 patients treated with comparable regimens other than mAbs (3.5% vs. 2.8%, P=0.53). CONCLUSIONS: Infectious and non-infectious adverse pulmonary reactions occur in patients with cancer who are administered a regimen including mAbs. Clinicians should be alert for the possibility of pulmonary adverse reactions, particularly among patients with low serum albumin levels.