OBJECTIVE: Cigarette smoking exacerbates the progression of pulmonary tuberculosis (TB). The role of tertiary lymphoid structures (TLS) in chronic lung diseases has gained attention; however, it remains unclear whether smoking-exacerbated lung damage in TB is associated with TLS. This study aimed to analyze the characteristics of pulmonary TLS in smokers with TB and to explore the possible role of TLS in smoking-related lung injury in TB. METHODS: Lung tissues from 36 male patients (18 smokers and 18 non-smokers) who underwent surgical resection for pulmonary TB were included in this study. Pathological and immunohistological analyses were conducted to evaluate the quantity of TLS, and chest computed tomography (CT) was used to assess the severity of lung lesions. The correlation between the TLS quantity and TB lesion severity scores was analyzed. The immune cells and chemokines involved in TLS formation were also evaluated and compared between smokers and non-smokers. RESULTS: Smoker patients with TB had significantly higher TLS than non-smokers ( P < 0.001). The TLS quantity in both the lung parenchyma and peribronchial regions correlated with TB lesion severity on chest CT (parenchyma: r = 0.5767; peribronchial: r = 0.7373; both P < 0.001). Immunohistochemical analysis showed increased B cells, T cells, and C-X-C motif chemokine ligand 13 (CXCL13) expression in smoker patients with TB ( P < 0.001). CONCLUSION Smoker TB patients exhibited increased pulmonary TLS, which was associated with exacerbated lung lesions on chest CT, suggesting that cigarette smoking may exacerbate lung damage by promoting TLS formation.
Humans ; Male ; Tuberculosis, Pulmonary/immunology* ; Middle Aged ; Tertiary Lymphoid Structures/pathology* ; Adult ; Lung/pathology* ; Smoking/adverse effects* ; Smokers ; Aged ; Tomography, X-Ray Computed

PURPOSE: Severe asthma and asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) are difficult to control and are often associated with poor clinical outcomes. However, much is not understood regarding the diagnosis and treatment of severe asthma and ACOS. To evaluate the current perceptions of severe asthma and COPD among asthma and COPD specialists, we designed an e-mail and internet-based questionnaire survey. METHODS: Subjects were selected based on clinical specialty from among the members of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Academy of Tuberculosis and Respiratory Diseases. Of 432 subjects who received an e-mail invitation to the survey, 95 subjects, including 58 allergists and 37 pulmonologists, responded and submitted their answers online. RESULTS: The specialists estimated that the percentage of severe cases among total asthma patients in their practice was 13.9%±11.0%. Asthma aggravation by stepping down treatment was the most common subtype, followed by frequent exacerbation, uncontrolled asthma despite higher treatment steps, and serious exacerbation. ACOS was estimated to account for 20.7% of asthma, 38.0% of severe asthma, and 30.1% of COPD cases. A history of smoking, persistently low forced expiratory volume in 1 second (FEV1), and low FEV1 variation were most frequently classified as the major criteria for the diagnosis of ACOS among asthma patients. Among COPD patients, the highly selected major criteria for ACOS were high FEV1 variation, positive bronchodilator response, a personal history of allergies and positive airway hyperresponsiveness. Allergists and pulmonologists showed different assessments and opinions on asthma phenotyping, percentage, and diagnostic criteria for ACOS. CONCLUSIONS: Specialists had diverse perceptions and clinical practices regarding severe asthma and ACOS patients. This heterogeneity must be considered in future studies and strategy development for severe asthma and ACOS.
Allergy and Immunology ; Asthma* ; Diagnosis ; Electronic Mail ; Forced Expiratory Volume ; Humans ; Hypersensitivity ; Lung Diseases, Obstructive ; Population Characteristics ; Pulmonary Disease, Chronic Obstructive ; Smoke ; Smoking ; Specialization* ; Tuberculosis

OBJECTIVE: To evaluate the relative factors influencing olfactory dysfunction in patients with chronic rhinosinusitis (CRS). METHOD: Visual analogue scale (VAS) was applied to measure the severity of olfactory dysfunction of 270 patients with CRS. Patients were divided into two groups, one was that the quality of life (QOL) of patients was affected by olfactory dysfunction (VAS > 5), the other was that without QOL affected by olfactory dysfunction (VAS ≤ 5). The association between age, gender, nasal polyps, allergic rhinitis, smoking history, early nasal surgery history and other clinical factors, and serum total IgE level, peripheral blood eosinophil count, peripheral blood mononuclear cell count and olfactory dysfunction was analyzed. RESULT: The number of patients with nasal polyps, allergic rhinitis, previous nasal surgeries, the level of serum total IgE, and the severity of edema were significantly increased in patients with impaired QOL associated with olfactory dysfunction (P < 0.05). Sex distribution, age, smoking history, deviation of nasal septum, eosinophil and mononuclear cell count did no statistically differ between the groups with and without impaired QOL associated with olfactory dysfunctions (P > 0.05). Serum total IgE increased (OR = 1.003, P < 0.01) and severe edema (OR = 2.483, P < 0.01) were the risk factors for the impairment of olfactory function, more notably for edema; whereas previous nasal surgeries was a protective factor (OR = 0.408, P < 0.01). CONCLUSION Sever edema and increased serum total IgE are risk factors, whereas previous nasal surgeries history is a protective factor for the olfactory dysfunction.
Chronic Disease ; Female ; Humans ; Leukocytes, Mononuclear ; Male ; Nasal Polyps ; Olfaction Disorders ; etiology ; Quality of Life ; Rhinitis ; complications ; immunology ; Rhinitis, Allergic ; complications ; immunology ; Risk Factors ; Sinusitis ; complications ; immunology ; Smell ; Smoking ; adverse effects

Tobacco smoking is a global healthcare problem that poses a substantial and costly health burden. Nicotine is the major constituent responsible for the addiction to tobacco. Current strategies helping tobacco smokers have limited utility in increasing rates of smoking cessation, consequently indicating the need for alternative therapies. A novel therapeutic method is vaccination against nicotine. Nicotine vaccine can generate specific antibodies that can sequester nicotine from cigarette smoke in the blood, and prevent its access to the brain and minimize positive reinforcing effects, which may help smokers to stop smoking. The vaccine will have great potential for the treatment of nicotine addiction and for relapse prevention. Here we will review the current status of vaccines against nicotine addiction and discuss the problems associated with the development of nicotine vaccines.
Clinical Trials as Topic ; Humans ; Nicotine ; antagonists & inhibitors ; immunology ; Smoking ; immunology ; therapy ; Smoking Cessation ; methods ; Tobacco Use Disorder ; immunology ; therapy ; Vaccination ; methods ; Vaccines ; therapeutic use

BACKGROUNDCigarette smoke induces an acute but persisting inflammation in peripheral blood and airway in chronic obstructive pulmonary disease (COPD), and CD8(+) Tc-lymphocytes are considered as a key role in this process. We aimed to investigate the Tc-lymphocytes immunodeviation in system and local airway of COPD patients and changes of the immunodeviation after short-term smoking cessation.

METHODSPeripheral blood (PB) and bronchoalveolar lavage fluid (BALF) were collected from 42 patients (14 COPD patients, 16 smokers with normal lung function and 12 nonsmokers), while PB and induced sputum (IS) were obtained from other 19 patients (10 quitting smokers and 9 continuing smokers) at baseline and follow-up respectively of 4-week smoking cessation. Percentages of CD8(+) Tc-lymphocytes (%CD3(+)) and Tc1/Tc2 ratios were measured by flow cytometry.

RESULTSPercentages of CD8(+) Tc-lymphocytes were higher in COPD patients than those in smokers and nonsmokers in both PB and BALF. Tc1/Tc2 ratio in PB and in BALF from COPD patients was greater than that from smokers and nonsmokers and negatively correlated with FEV1 %pre. When comparing the ratios between PB and BALF, significantly positive correlation was found in COPD patients. Furthermore, after 4-week smoking cessation, percentages of CD8(+) Tc-lymphocytes in PB and IS in quitting smokers were decreased compared to that in baseline and continuing smokers, whereas Tc1/Tc2 ratios were not influenced.

CONCLUSIONSCD8(+) Tc1-trend immunodeviation profiles occurred in both system and local airway of COPD patients. This exceptional immunodeviation could not be relieved by short-term smoking cessation.

Aged ; Bronchoalveolar Lavage Fluid ; immunology ; CD8-Positive T-Lymphocytes ; immunology ; Female ; Humans ; Lung ; physiopathology ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; immunology ; physiopathology ; Smoking Cessation ; Time Factors

Asthma ; drug therapy ; epidemiology ; etiology ; China ; epidemiology ; Cluster Analysis ; Humans ; Phenotype ; Pulmonary Eosinophilia ; etiology ; Smoking ; adverse effects ; Th2 Cells ; immunology

OBJECTIVEImprovement in lung function was reported after acupuncture treatment of chronic obstructive pulmonary disease (COPD), but little is known about the underlying mechanisms. Because an immune response imbalance could be seen in COPD, we hypothesize that electroacupuncture (EA) may play a role in regulating inflammatory cytokines and contribute to lung protection in a rat model of smoke-induced COPD.

METHODSA COPD model using male Sprague-Dawley rats exposed to cigarette smoke was established. The rats were randomly divided into four groups (control, sham, COPD, and COPD plus EA), and COPD model was evaluated by measuring pulmonary pathological changes and lung function. EA was applied to the acupuncture point Zusanli (ST36) for 30 min/d for 14 d in sham and COPD rats. Bronchoalveolar lavage fluid (BALF) was used to measure levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and malonaldehyde (MDA).

RESULTSCompared with the control rats, COPD rats had significant changes in lung resistance (RL) and lung compliance (CL) (both P<0.01), bronchi and bronchiole airway obstruction (P<0.01), and levels of MDA, TNF-α, and IL-1β (P<0.01). There were no significant differences between the control and the sham groups. Compared with the COPD rats, the COPD plus EA rats had decreased RL and increased CL (both P<0.05), and reduced bronchi and bronchiole airway obstruction (P<0.05, P<0.01, respectively), while levels of TNF-α, IL-1β, and MDA in BALF were lowered (P<0.05 and P<0.01, respectively). However, TNF-α and IL-1β levels of the EA group rats remained higher than those of the control group (P<0.05).

CONCLUSIONEA at ST36 can reduce lung injury in a COPD rat model, and beneficial effects may be related to down-regulation of inflammatory cytokines. The anti-inflammatory and antioxidant effects may prolong the clinical benefit of EA.

Acupuncture Points ; Animals ; Bronchoalveolar Lavage Fluid ; immunology ; Disease Models, Animal ; Electroacupuncture ; Humans ; Interleukin-1beta ; immunology ; Male ; Pulmonary Disease, Chronic Obstructive ; etiology ; immunology ; therapy ; Rats ; Rats, Sprague-Dawley ; Smoking ; adverse effects ; Tumor Necrosis Factor-alpha ; immunology

Telomerase play a key role in the maintenance of telomere length and chromosome integrity. We have evaluated the association between telomerase activity and the risk of lung cancer in peripheral blood. Telomerase activity in peripheral blood mononuclear cells was measured by a PCR-designed telomeric repeat amplification protocol in 63 lung cancer patients and 190 healthy controls that were matched for age, gender, and smoking status. Telomerase activity was significantly lower in the lung cancer patients than in controls (mean +/- standard deviation; 1.32 +/- 1.65 vs 2.60 +/- 3.09, P < 1 x 10(-4)). When telomerase activity was categorized into quartiles based on telomerase activity in the controls, the risk of lung cancer increased as telomerase activity reduced (Ptrend = 1 x 10(-4)). Moreover, when the subjects were categorized based on the median value of telomerase activity, subjects with low telomerase activity were at a significantly increased risk of lung cancer compared to subjects with high telomerase activity (adjusted odds ratio = 3.05, 95% confidence interval = 1.60-5.82, P = 7 x 10-4). These findings suggest that telomerase activity may affect telomere maintenance, thereby contributing to susceptibility to lung cancer.
Age Factors ; Aged ; Case-Control Studies ; Female ; Humans ; Leukocytes, Mononuclear/enzymology/immunology ; Lung Neoplasms/*enzymology/*etiology ; Male ; Middle Aged ; Odds Ratio ; Risk Factors ; Sex Factors ; Smoking ; Telomerase/*blood

BACKGROUNDChronic obstructive pulmonary disease (COPD) is a progressive disease associated with a cellular inflammatory response mostly concerned with cigarette smoking. Chemokine receptors CCR1/5 play an important role in the inflammatory cells recruitment in the lung of COPD patients. The aim of this study was to determine the impact of cigarette smoking on the expression of CCR1/5 on inflammatory cells in induced sputum, and the relationship between the receptors expression and COPD severity.

METHODSDifferential cells in induced sputum were counted and the optical densities of CCR1 and CCR5 on inflammatory cells in induced sputum from COPD patients (n = 29), healthy smokers (n = 11), and nonsmokers (n = 6) were measured using immunocytochemistry. Concentrations of CCL3, the ligand of CCR1/5, in supernatant of induced sputum were detected by enzyme-linked immunosorbent assay.

RESULTSThe expressions of CCR1 and CCR5 on inflammatory cells in healthy smokers were significantly higher than those in nonsmokers, and the expression of CCR1 in patients with COPD was significantly increased when compared with nonsmokers but not healthy smokers. The expressions of CCR1 and CCR5 on inflammatory cells in severe and very severe COPD patients were higher compared with mild and moderate COPD patients. CCL3 level was positively correlated with the total cell counts in induced sputum and smoking history, and negatively correlated with percentage of predicted FEV(1).

CONCLUSIONSCigarette smoking could increase the expression of CCR1 on the inflammatory cells. Both CCR1 and CCR5 expressions on the inflammatory cells in induced sputum could be associated with COPD severity.

Adult ; Aged ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; immunology ; metabolism ; Receptors, CCR1 ; metabolism ; Receptors, CCR5 ; metabolism ; Smoking ; adverse effects ; Sputum ; cytology ; immunology

BACKGROUNDSmoking causes frequent asthma attacks, leading to a rapid decline in lung function in patients with asthma, and it can also reduce the therapeutic effect of glucocorticoids in patients with asthma. Therefore, the present study aimed to investigate the effect of cigarette smoke on the expression of myeloid differentiation factor 88 (MyD88) in marrow dendritic cells (DCs) in asthmatic rats, and to explore the molecular mechanism of cigarette smoke exposure on asthma by DCs.

METHODSForty Wistar rats were randomly divided into the following groups: control, smoke exposure, asthma, and asthma combined with smoke exposure. The animal model was established, and then rat bone marrow-derived DCs were collected. Additionally, rat spleen lymphocytes and bone marrow-derived DCs were cultured together for mixed lymphocyte responses. Interferon (IFN)-gamma and interleukin (IL)-4, IL-10, and IL-12 expressions were determined by enzyme-linked immunosorbent assay (ELISA). MyD88 expression was determined by Western blotting. The proliferation of lymphocytes was examined with methyl thiazolyl tetrazolium (MTT) colorimetric assay.

RESULTSMyD88 expression was decreased in the asthma combined with smoke exposure group compared to the asthma group (P < 0.01), and IL-10 and IL-12 expressions were decreased in the asthma combined with smoke exposure group compared to control group (P < 0.01). In addition, DCs stimulating activity on allogeneic lymphocytes were significantly decreased in the smoke exposure combined with asthma group compared to the control and asthma groups (P < 0.01). After allogeneic mixed lymphocyte responses, IL-4 expression was increased and IFN-gamma was decreased in the asthma group and the asthma combined with smoke exposure group compared to control group (P < 0.01). IL-4 expression was increased and IFN-gamma was decreased in the asthma combined with smoke exposure group compared to the asthma group (P < 0.01). The study also showed that MyD88 expression was positively correlated with IL-12 and IFN-gamma expressions and the activity of lymphocytes (P < 0.01), and negatively correlated with IL-4 expression (P < 0.01).

CONCLUSIONSSmoking aggravates asthma by weankening immunological mechanism. MyD88-dependent pathways may play a role in the immunological balance and activation of lymphocytes.

Animals ; Asthma ; immunology ; metabolism ; Bone Marrow Cells ; cytology ; metabolism ; Dendritic Cells ; drug effects ; metabolism ; Lymphocyte Activation ; drug effects ; Male ; Myeloid Differentiation Factor 88 ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Smoking ; adverse effects