Relationship between the cellular composition of sputum and the cytologic diagnosis of lung cancer

In 410 patients with either a primary or a metastatic malignant lung process, the cellular composition of the sputum specimens was analyzed in relation to the diagnostic accuracy of sputum cytology and in relation to anamnestic and clinical patient characteristics. In patients with primary lung cancer, sputum samples with true-positive cytologic diagnoses contained significantly more cells from the deeper airways, such as alveolar macrophages and bronchial columnar cells, than did sputum specimens with a false-negative diagnosis, even though these cell types were present in both types of specimens. In sputum samples from patients with metastatic lung malignancies, differences in cellular composition of specimens with true-positive and false-negative diagnoses were not significant.     

Diagnostic significance of "severe dysplasia" in sputum cytology

The diagnostic significance of a cytologic diagnosis of "severe dysplasia" on sputum samples was assessed. In a group of 46 patients with diagnoses of severe dysplasia, follow-up showed no malignancy of the lung in 25 patients (54%) and a malignant process in 21 patients (46%). These groups were compared to 52 patients with correct negative and 202 patients with correct positive sputum diagnoses. Of the patient characteristics investigated, age, previous sputum production, vital capacity and low forced expiratory volume were not significantly related to a sputum cytodiagnosis of severe dysplasia. In contrast, severe dyspnea showed a significantly higher frequency in patients with a sputum cytodiagnosis of severe dysplasia, but without an underlying malignant lung process. Follow-up disclosed a malignant tumor in 10 of 13 patients with disease; the presence of severely dysplastic cells in sputum specimens from such patients should be considered a warning signal for an underlying malignant lung process. Since severe dysplasia should be considered a premalignant epithelial lesion, patients with sputum cytodiagnoses of severe dysplasia should undergo bronchoscopy, with multiple bronchial brushings of all areas showing suspicious mucosal changes, together with segmental bronchial washings. In case a malignant process cannot be located, sputum examinations should be repeated at three-month intervals.     

Relationship between patient characteristics and the sputum cytologic diagnosis of lung cancer

In 421 patients with a malignant lung process, from whom samples of sputum of satisfactory quality were received, patient characteristics relevant to the cytologic diagnosis of malignancy were investigated. In patients with primary lung cancer, the presence of blood in the sputum was highly significant from the point of view of its association with a correct positive cytologic diagnosis on sputum. The same relationship was noted in patients with metastatic lung cancer. In patients producing bloody sputum, the examination of at least three sputum samples gave a proportion of correct positive diagnoses of 0.88 in primary lung cancer patients and of 0.77 in patients with metastatic lung disease. Furthermore, a high sensitivity of the sputum cytology diagnosis of malignancy was found in primary lung cancer patients with low forced expiratory volume values (less than 50% of the vital capacity), with large tumors (greater than 24 mm in diameter) and with squamous-cell cancers. A central location of the tumor correlated with significantly better cytodiagnostic results in patients with both primary and metastatic cancers.     

Fine needle aspiration biopsy versus sputum and bronchial material in the diagnosis of lung cancer. A comparative study of 168 patients

A group of 168 consecutive lung cancer patients in whom a definitive diagnosis of primary lung cancer was established either in a conventional cytologic specimen of sputum or bronchial material or in a specimen obtained by fine needle aspiration (FNA) biopsy was reviewed to compare the relative accuracies between the modalities of sputum and bronchial material on one hand versus FNA cytology on the other in the diagnosis of lung cancer. The patients included in the study were selected from a total of 1,093 patients who had been diagnosed and treated for lung cancer at Duke University Medical Center over the five-year period of January 1, 1980, through December 31, 1984. In 325 (29.8%) of the 1,093 patients, a definitive cancer diagnosis was established from histopathologic study alone, without any cytologic diagnoses. In 420 patients (38.4%), both histologic and cytologic material had been interpreted as being conclusively diagnostic for lung cancer. In 348 patients (31.8%), a cytologic diagnosis of lung cancer was made without a histologic confirmation. Thus, in a total of 768 (70.3%) of the 1,093 cases, a definitive cytologic diagnosis of cancer had been made. Of these 768 patients, 168 had been evaluated by both conventional respiratory cytologic methods (examination of sputum and bronchial material) and with FNA biopsy cytology. In 9 patients (5.4%), only conventional respiratory cytologic specimens were conclusively diagnostic for cancer. In 122 patients (72.6%), only the FNA biopsy specimen was diagnostic. In 37 patients (22.0%), both conventional respiratory specimens and FNA specimens yielded a definitive lung cancer diagnosis. The FNA specimen was the only positive cytologic specimen in 90.2% of large cell undifferentiated carcinomas, 79.5% of adenocarcinomas, 66.7% of small cell undifferentiated carcinomas and 58.2% of squamous cell carcinomas. In 26.5% of the patients, a diagnosis of cancer could have been established on conventional cytologic specimens, without the necessity of proceeding to percutaneous FNA biopsy. From this study, it is concluded that the techniques of conventional respiratory cytology and FNA biopsy cytology are complementary in the diagnosis of lung cancer. While the percentage of lung cancers diagnosed by FNA biopsy cytology alone is much greater than that obtained by conventional respiratory cytology alone, more than one-fourth of these cancers could be detected by the less invasive techniques of sputum collection and bronchoscopy.     

Bronchial brushing during fiberoptic bronchoscopy for the cytodiagnosis of lung cancer: comparison with sputum and bronchial washings.

In a study of 50 cases of bronchogenic carcinoma in which brushings and washings during fiberoptic bronchoscopy, as well as sputum cytopathologic examinations were performed in the same patients, accuracy rates were respectively: 76 per cent, 76 per cent and 56 per cent. The main cytologic differences setting brush apart from wash and sputum specimens referred to the arrangement of tumor cells as well as the distribution of chromatin within their nuclei. These differences appeared related to cell degeneration which was minimal in brush materials and maximum in sputum specimens. Only six cases were assigned a different cell type of bronchogenic carcinoma when brush cytopathologic diagnoses were compared with results obtained by biopsy or lobectomy specimens. Our findings are consistent with the view that the brush technique is very accurate for the cytodiagnosis of lung cancer and becomes also rather specific once cytologic characteristics of the fresher samples obtained become familiar to the cytopathologist. Non-observance of the special characteristics of these better preserved cellular samples is the major pitfall as to diagnosing, cell typing and judging degree of differentiation of bronchogenic carcinoma in brush cytology specimens.     

Proliferating activity, DNA ploidy changes of lung cancer cells before and after chemotherapy

To assess proliferating activity, DNA ploidy changes of lung cancer cells before and after chemotherapy, we performed a flow cytometry analysis (FC) using fresh bronchoscopy specimens from 38 patients with lung cancer. Among 33 males and 5 females, squamous cell carcinoma (NSLC) was recognized in 12 males, 15 males had small cell lung cancer (SCLC) and 6 males had lung cancer with no histological type (LC) defined. Three women had SCLC, 1 had NSCLC and one had LC. Control consisted of 11 COPD patients. The percentage of diploid cells was significantly lower and cells with hypoploid cells were significantly higher in study group before treatment. High percentage of G2M cells characterised NSCLC and LC groups, whether high number of S phase cells characterised NSCLC and SCLC group before treatment. The treatment lowered percentage of G2M cells in NSCLC and CA group, whether diploid, hypoploid and S phase cells did not differ than those from before treatment.     

纤维支气管镜吸痰联合肺泡灌洗在肺癌术后合并肺部感染患者中的临床应用价值

目的:探讨纤维支气管镜吸痰联合肺泡灌洗在肺癌术后合并肺部感染患者中的临床应用价值。方法:选择2017年1月-2020年12月间来江苏省人民医院接受治疗的82例肺癌术后合并肺部感染患者,根据随机数字表法分为对照组(纤维支气管镜吸痰、常规治疗)和研究组(纤维支气管镜吸痰、常规治疗、肺泡灌洗),各41例,对照组给予常规抗感染加纤维支气管镜吸痰治疗,研究组在对照组基础上结合肺泡灌洗治疗,观察两组疗效,对比两组呼吸功能、生活质量和外周血辅助性T细胞17(Th17细胞)/调节性T细胞(Treg)变化。结果:研究组的临床总有效率优于对照组(P<0.05)。治疗1周后,两组气道阻力(Raw)、气道峰压(PIP)、呼吸做功(WOB)降低,且研究组低于对照组(P<0.05)。治疗1周后,两组Th17细胞占单个核细胞百分比、白介素-6(IL-6)、白介素-17(IL-17)降低,且研究组低于对照组(P<0.05),治疗1周后,两组Treg细胞占单个核细胞百分比、白介素-10(IL-10)升高,且研究组高于对照组(P<0.05)。治疗1周后,两组社会/家庭状况、生理状况、与医生的关系、功能状况、附加的关注情况、情感状况等领域评分升高,且研究组高于对照组(P<0.05)。结论:纤维支气管镜吸痰联合肺泡灌洗可促进肺癌术后合并肺部感染患者呼吸功能改善,调节外周血Th17细胞/Treg细胞失衡,促进生活质量提高。     

Lung Cancer—Improved Cytologic Detection by Inducing Production of Sputum

The principle of producing bronchial lavage by deposition of large amounts of heated aerosol has resulted in a significantly greater yield of positive cytologic diagnosis of bronchogenic carcinoma than with repeated “volunteer” specimens of sputum. Positive pressure plus bronchodilators augments greater sputum volume.Using this technique, cases in which results of bronchoscopy and aspiration biopsy were negative for malignant change, were diagnosed cytologically.Application of this technique can sometimes detect early lung carcinoma before roentgenographic changes are detectable. Positive tests in clinically far advanced disease may prevent unnecessary surgical intervention.The simplicity of the technique, the freedom from adverse reactions, and its wide acceptance by the subjects tested, make it valuable in the diagnosis of lung cancer.     

Patients' & Healthcare Professionals' Values Regarding True- & False-Positive Diagnosis when Colorectal Cancer Screening by CT Colonography: Discrete Choice Experiment

Purpose

To establish the relative weighting given by patients and healthcare professionals to gains in diagnostic sensitivity versus loss of specificity when using CT colonography (CTC) for colorectal cancer screening.

Materials and Methods

Following ethical approval and informed consent, 75 patients and 50 healthcare professionals undertook a discrete choice experiment in which they chose between “standard” CTC and “enhanced” CTC that raised diagnostic sensitivity 10% for either cancer or polyps in exchange for varying levels of specificity. We established the relative increase in false-positive diagnoses participants traded for an increase in true-positive diagnoses.

Results

Data from 122 participants were analysed. There were 30 (25%) non-traders for the cancer scenario and 20 (16%) for the polyp scenario. For cancer, the 10% gain in sensitivity was traded up to a median 45% (IQR 25 to >85) drop in specificity, equating to 2250 (IQR 1250 to >4250) additional false-positives per additional true-positive cancer, at 0.2% prevalence. For polyps, the figure was 15% (IQR 7.5 to 55), equating to 6 (IQR 3 to 22) additional false-positives per additional true-positive polyp, at 25% prevalence. Tipping points were significantly higher for patients than professionals for both cancer (85 vs 25, p<0.001) and polyps (55 vs 15, p<0.001). Patients were willing to pay significantly more for increased sensitivity for cancer (p = 0.021).

Conclusion

When screening for colorectal cancer, patients and professionals believe gains in true-positive diagnoses are worth much more than the negative consequences of a corresponding rise in false-positives. Evaluation of screening tests should account for this.     

Use of neostigmine to increase the rate of lung cancer detection by sputum cytology

Neostigmine induction was investigated as a method for increasing the rate of detection of lung cancer in respiratory cytology samples. Eleven patients with dry and essentially nonproductive cough were given neostigmine, 15 mg by mouth or 0.5 mg by hypodermic injection. The quality of sputum produced was increased in all cases; the sputum was also more easily expectorated. Eight patients suspected of having lung cancer had previously negative cytologic examinations of sputum obtained by conventional methods. Following the administration of neostigmine, malignant cells indicating squamous-cell carcinoma were found in the sputum samples of three of these patients while dysplastic cells were detected in the samples from two patients. It is postulated that neostigmine intake may increase the excretion of mucous glands in the bronchial submucosa as well as the bronchial epithelium itself.     

A novel method of sputum processing for cytologic diagnosis of lung cancer

OBJECTIVE: To compare the diagnostic sensitivity and cytologic findings of the sputum-processing method with those of the traditional sputum smear method. STUDY DESIGN: From May to December 2001, 300 consecutive sputum samples were collected from 168 patients suspected of having lung cancer in the Chest Department, Taipei Veterans General Hospital. After the sputum smear method, the remaining sputum material was processed by homogenization, filtration and fixation. All the slides were stained with Papanicolaou stain and reviewed by 2 cytologists. RESULTS: Of the 300 sputum samples, 141 from 79 patients were finally diagnosed as lung malignancies. The mean number of sputum samples was 1.78 per patient. Among the 79 patients, 46 had peripheral lung malignancies (58.2%). The overall diagnostic sensitivities of sputum smear and sputum-processing methods were 29% and 31%, respectively (P = .776). Tumor location and cell types did not change the difference significantly; however, among patients with small cell lung cancer, there was a higher detection rate with the sputum-processing method (50% vs. 20%, P = .350). Eight patients with negative results with the sputum smear had positive results with the sputum-processing method (8 of 79 = 10.1%). Microscopic morphologic differences between the 2 methods were described. CONCLUSION: There was no significant difference in diagnostic sensitivity between the sputum smear and sputum-processing methods. However, the sputum-processing method may play a role in patients with small cell lung carcinoma.     

Pneumocystis carinii pneumonia: detection of parasites in sputum and bronchoalveolar lavage fluid by monoclonal antibodies.

Diagnosis of pneumocystis pneumonia is based on identifying Pneumocystis carinii cytochemically in material from the lung. The silver methenamine staining methods most commonly used are technically difficult and lack specificity. The diagnostic value of immunocytological identification of the parasite was evaluated by using mouse monoclonal antibody 3F6, specific for human pneumocystis, to identify P carinii in bronchoalveolar lavage fluid and sputum by immunofluorescence and was compared with that of other variables. Bronchoalveolar lavage was performed on 25 patients positive for HIV antibody with clinically suspected pneumocystis pneumonia and 40 patients negative for HIV antibody who presented with interstitial disorders of the lung. Lavage fluid showed pneumocystis only in the patients positive for antibody, the parasite being detected in 19 by immunofluorescence and in 17 by a modified silver methenamine staining method. Chest x ray films obtained at the time of bronchoscopy showed interstitial or alveolar shadowing in 17 of the 19 patients, but clinical symptoms and the presence of antibodies to pneumocystis did not seem to be predictive. Sputum samples were collected during 43 episodes of clinically suspected pneumocystis pneumonia in patients positive for HIV antibody. Pneumocystis was detected consistently more commonly by immunofluorescence than the silver strain in sputum collected routinely and induced by inhalation of saline. In 17 patients bronchoalveolar lavage followed sputum collection, and the sensitivity of detection of pneumocystis in immunofluorescence in sputum compared with lavage fluid was 57% (8/14). Immunofluorescence was suitable for specimens fixed in ethanol and seemed highly specific and more sensitive than the standard cytochemical methods for identifying pneumocystis.     

Elevated Levels of the Complement Activation Product C4d in Bronchial Fluids for the Diagnosis of Lung Cancer

Molecular markers in bronchial fluids may contribute to the diagnosis of lung cancer. We previously observed a significant increase of C4d-containing complement degradation fragments in bronchoalveolar lavage (BAL) supernatants from lung cancer patients in a cohort of 50 cases and 22 controls (CUN cohort). The present study was designed to determine the diagnostic performance of these complement fragments (hereinafter jointly referred as C4d) in bronchial fluids. C4d levels were determined in BAL supernatants from two independent cohorts: the CU cohort (25 cases and 26 controls) and the HUVR cohort (60 cases and 98 controls). A series of spontaneous sputum samples from 68 patients with lung cancer and 10 controls was also used (LCCCIO cohort). Total protein content, complement C4, complement C5a, and CYFRA 21-1 were also measured in all cohorts. C4d levels were significantly increased in BAL samples from lung cancer patients. The area under the ROC curve was 0.82 (95%CI = 0.71–0.94) and 0.67 (95%CI = 0.58–0.76) for the CU and HUVR cohorts, respectively. In addition, unlike the other markers, C4d levels in BAL samples were highly consistent across the CUN, CU and HUVR cohorts. Interestingly, C4d test markedly increased the sensitivity of bronchoscopy in the two cohorts in which cytological data were available (CUN and HUVR cohorts). Finally, in the LCCCIO cohort, C4d levels were higher in sputum supernatants from patients with lung cancer (area under the ROC curve: 0.7; 95%CI = 0.56–0.83). In conclusion, C4d is consistently elevated in bronchial fluids from lung cancer patients and may be used to improve the diagnosis of the disease.     

Cytologic diagnosis of pulmonary carcinoma on bronchoscopic brushing material

The material obtained by brushing procedures under visual control from 370 consecutive patients with histologically confirmed primary carcinoma of the lung who underwent bronchoscopy was examined cytologically. The sputum of 276 of these patients was also investigated. The overall sensitivity of the bronchoscopically obtained cytology was 0.67; however, the values were 0.78 and 0.28, respectively, for the cases with and without visible lesions of the bronchi. Sputum examination enhanced the sensitivity to 0.79 overall and to 0.84 and 0.61, respectively, for the two groups, with a greater benefit for the group with negative bronchoscopy. The overall cytologic typing accuracy for 252 cases was 0.66, with a range of 0.19 to 0.86, depending on the histologic type. Typing failures were essentially related to adenocarcinomas and large-cell carcinomas.     

The Adventures and Times of Eosilred,Prince of Elfour: A Bloodtime Story: Part IV

Eighty patients with carcinoma of the lung have been treated at the Nova Scotia Sanatorium since 1940; in 15, coexisting active pulmonary tuberculosis was present. No characteristic clinical or roentgenological findings indicated that the tuberculous individual also had lung cancer. In four cases cancer was not diagnosed until the lung was examined by the pathologist. In the others a considerable interval elapsed before carcinoma was suspected.Only four patients with known cancer were considered suitable for thoracotomy. In three, an attempt at curative resection was made. One survived over seven years before accidental death; one is alive less than one year after operation; the third died as a result of the surgery. Bronchogenic carcinoma should be suspected in every tuberculous patient over the age of 50; diagnostic investigations should include bronchoscopy and cytological studies of bronchial secretion and sputum. Suspicion of carcinoma in any such patient constitutes an indication for early resection of the tuberculous disease.     

百令胶囊联合罗氟司特治疗老年支气管哮喘的效果及对免疫功能的影响

目的:研究百令胶囊联合罗氟司特治疗老年支气管哮喘的效果及对免疫功能的影响。方法:选择2018年3月~2019年3月我院第六派驻门诊部收治的110例老年支气管哮喘患者,随机分为两组,每组各55例。对照组患者口服罗氟司特片,每次500 mg,每天1次。观察组患者联合服用百令胶囊,每次5粒,每天3次。比较两组的临床控制率,治疗前后两组诱导痰中炎症因子、中性粒细胞、呼出气一氧化氮(fractional exhaled nitric oxide,FeNO)水平和免疫功能的变化。结果:治疗后,观察组的临床控制率为70.91%(39/55),明显高于对照组[40.00%(22/55)](P<0.05);两组的CD4+、CD4+/CD8+和CD3+均较治疗前明显升高,且观察组的CD4+、CD4+/CD8+和CD3+明显高于对照组(P<0.05);两组患者诱导痰中中性粒细胞绝对值、中性粒细胞百分比、白细胞介素-4(interleukin-4,IL-4)、FeNO、白细胞介素-17(interleukin-17,IL-17)均较治疗前明显降低(P<0.05),诱导痰中的干扰素-γ(Interferon gamma,IFN-γ)均较治疗前明显升高(P<0.05),且观察组诱导痰中的组中性粒细胞绝对值、中性粒细胞百分比、IL-4、FeNO、IL-17明显低于对照组(P<0.05),诱导痰中的IFN-γ均明显高于对照组(P<0.05)。结论:百令胶囊联合罗氟司特对老年支气管哮喘患者具有显著的疗效,其机制可能与抑制中性粒细胞的激活、调节T淋巴细胞亚群的平衡和抑制相关炎症因子的释放相关。     

Culture Conversion Rate at 2 Months of Treatment According to Diagnostic Methods among Patients with Culture-Positive Pulmonary Tuberculosis

Introduction

The culture-negative conversion rate of sputum after 2 months of treatment in patients with pulmonary tuberculosis (TB) is used as a reliable surrogate marker for relapse after completion of treatment. We hypothesized that culture conversion of sputum at 2 months of anti-TB treatment and the time to culture conversion are different among pulmonary TB patients who are diagnosed using different methods.

Methods

Culture-confirmed pulmonary TB patients who were diagnosed between 1 January, 2011 and 31 December, 2012 were classified into three groups based on the diagnostic method that prompted treatment initiation: positive acid-fast bacilli (AFB) staining of sputum (smear-positive group), negative AFB staining, but Mycobacterium tuberculosis was cultured from sputum (culture-positive group), and positive AFB staining, positive polymerase chain reaction (PCR) for M. tuberculosis, or culture of M. tuberculosis from a bronchoscopic specimen (bronchoscopy group). Rates of negative mycobacterial culture conversion at 2 months of anti-TB treatment and the time to negative culture conversion of sputum were compared among the three groups.

Results

A total of 203 patients with culture-confirmed pulmonary TB were included in the final analysis. TB patients in the culture-positive group (94.1%) and the bronchoscopy group (97.6%) showed a higher culture conversion rate at 2 months of treatment than those in the smear-positive group (78.7%, P = 0.001). Additionally, the time to culture conversion was longer in the smear-positive group (median, 40 days) than in the culture-positive (median, 19 days; P = 0.009) and bronchoscopy groups (median, 29 days; P = 0.004).

Conclusions

The higher culture conversion rate at 2 months and the shorter time to culture conversion among pulmonary TB patients with a negative AFB smear suggests the feasibility of shortening treatment duration and isolation in these patients.     

VEGF and IL-18 in induced sputum of lung cancer patients

Cytokines are key players in the biological processes of malignant tumors and special interest has been focused on cytokines exerting tumor and anti-tumor properties, such as vascular endothelial growth factor (VEGF) and Interleukin-18 (IL-18). Aim of this study was to assess IL-18 and VEGF levels in induced sputum of lung cancer patients at diagnosis, and assess their possible association with the histological type of cancer, the stage and the overall patient survival. Seventy six patients with a diagnosis of lung cancer were recruited and were followed up for 48months. Thirteen healthy smokers and 16 healthy non-smokers were used as control groups. VEGF and IL-18 were measured by ELISA in sputum supernatants at the time of diagnosis. Lung cancer patients had significantly higher baseline IL-18 and VEGF levels compared to healthy controls (p<0.001). No difference was found in IL-18 and VEGF levels between the various stages in non-small cell lung cancer (NSCLC) and between limited and extended small cell lung cancer (SCLC). However, the ratio of VEGF/IL-18 was significantly higher in NSCLC compared to SCLC patients (p=0.018). In extended SCLC overall survival was inversely associated with baseline sputum VEGF levels (p=0.034) and estimated mortality risk was 1.14 (95% CI 1.006-1.283) for an increase of 100pg/ml in VEGF levels. Such association was not found regarding baseline IL-18 levels. VEGF levels in induced sputum may have a prognostic role in the survival of SCLC. The ratio VEGF/IL-18 in induced sputum differs between NSCLC and SCLC, indicating differences in angiogenesis mechanisms and/or immunological response in these two major histological types of lung cancer.     

Efficacy and pattern of use of sputum cytology as a diagnostic test

Sputum cytology is regarded by many clinicians as a noninvasive, cheap and simple test for the diagnosis of bronchogenic carcinoma. Since the introduction of fibre-optic bronchoscopy and more easily obtained bronchial biopsies reliance on sputum cytology has diminished. However, in Edinburgh it was perceived that sputum samples were still being sent as well as, rather than instead of, bronchoscopic specimens. This retrospective study was undertaken to determine whether or not cytological examination of sputum is an efficient and sensitive test in the investigation of patients with suspected bronchogenic carcinoma. It demonstrated that the Lothian University Hospitals NHS Trust Pathology Directorate receives many sputa from departments not specializing in respiratory disease when there is no indication for the test. In addition, we have shown that the absolute sensitivity of the test is only 5% and that when there is a strong clinical suspicion of bronchogenic carcinoma the results of sputum cytology do not play a significant role in the management of the patient. We recommend that sputum cytology is restricted to those patients under the care of Respiratory Units in whom bronchoscopy is inappropriate or unsuccessful.     

Autoantibodies against tumor-associated antigens in sputum as biomarkers for lung cancer

Tumor antigens (TAs) can initiate host immune responses and produce TA-associated autoantibody (TAAbs), potential cancer biomarkers. Sputum is directly generated from the upper and lower airways, and thus can be used as a surrogate sample for the diagnosis of lung cancer based on molecular analysis. To develop sputum TAAb biomarkers for the early detection of lung cancer, the leading cause of cancer death, we probed a protein microarray containing more than 9,000 antigens with sputum supernatants of a discovery set of 30 lung cancer patients and 30 cancer-free smokers. Twenty-eight TAs with higher reactivity in sputum of lung cancer cases vs. controls were identified. The diagnostic significance of TAAbs against the TAs was determined by enzyme-linked immunosorbent assays (ELISAs) in sputum of the discovery set and additional 166 lung cancer patients and 213 cancer-free smokers (validation set). Three sputum TAAbs against DDX6, ENO1, and 14–3-3ζ were developed as a biomarker panel with 81% sensitivity and 83% specificity for diagnosis of lung cancer, regardless of stages, locations, and histological types of lung tumors. This study provides the first evidence that sputum TAAbs could be used as biomarkers for the early detection of lung cancer.