Neutrophil chemokines in bronchoalveolar lavage fluid and leukocyte-conditioned medium from nonsmokers and smokers

Polymorphonuclear neutrophils (PMN) have been implicated in the pathogenesis of emphysema. The chemokines interleukin-8(IL-8), growth-related oncogene (GRO-alpha) and extractable nuclear antigen (ENA)-78 may be involved in the increased numbers of PMN in smokers' airspaces. The levels of these cytokines in bronchoalveolar lavage fluid (BALF) and bronchoalveolar lavage leukocyte conditioned medium (LCM), along with BALF PMN numbers in 12 smokers who abstained for 12 h (chronic smoking) or continued to smoke until I h before study (acute smoking) and seven nonsmokers were compared. Neutrophils in BALF increased in acute (1.96+/-0.53%, 0.99+/-0.32x10(6) cells) compared with chronic smokers (0.59+/-0.25%, 0.61+/-0.24x10(6) cells, p<0.05 nonsmokers) and nonsmokers (0.79+/-0.29%, 0.05+/-0.01x 10(6) cells, p<0.05). There were no differences in IL-8 or GRO-alpha in BALF between smokers and nonsmokers. ENA-78 levels were lower in smokers (p=0.006). There was no difference in IL-8, GRO-alpha or ENA-78 in LCM from unstimulated cells in smokers versus nonsmokers. After stimulation with lipopolysaccharide (LPS) 10 ng mL(-1), IL-8 release in acute smokers (p=0.04) and GRO-alpha release in smokers (p=0.009) were significantly higher than in nonsmokers. Following stimulation with LPS 100 ng.mL(-1), GRO-alpha release was higher in smokers (p=0.03) and increased further in acute smokers (p=0.02 versus nonsmokers, p=0.04 versus chronic smokers) and ENA-78 release increased in smokers (p=0.02 versus non-smokers). In conclusion, influx of polymorphonuclear neutrophils into smokers' airspaces is an acute phenomenon and neutrophil chemokine release from mixed bronchoalveolar lavage leukocytes is influenced by cigarette smoking and endotoxins.     

Alveolar macrophage release of tumor necrosis factor-alpha in chronic alcoholics without liver disease

Alcohol is an immunosuppressive drug, and chronic abuse has been associated with increased susceptibility to a variety of infections, including bacterial pneumonia and tuberculosis. Alveolar macrophages are the resident phagocytes of the lung and play a central role in lung host defenses against infection ranging from direct antibacterial activity to the release of proinflammatory cytokines such as tumor necrosis factor-alpha (TNFalpha). TNFalpha, in particular, plays a key role in the development of the early inflammatory response. In this study, we investigated the effects of chronic alcohol consumption on alveolar macrophage release of TNFalpha in vitro. We prospectively studied lipopolysaccharide (LPS)-stimulated release of TNFalpha from alveolar macrophages obtained from bronchoalveolar lavage fluid (BALF) in 22 alcoholic (18 smokers, 4 nonsmokers) and 7 nondrinking healthy volunteers (3 smokers, 4 nonsmokers). The total number of cells recovered by bronchoalveolar lavage (BAL) and their differential distribution were not significantly different in alcoholics versus controls (43 +/- 8 x 10(6) and 39 +/- 13 x 10(6), respectively). However, the total number of cells recovered from BALF was significantly higher in smokers (51 +/- 8 x 10(6)) than in nonsmokers (19 +/- 5 x 10(6)). Spontaneous (basal) release of TNFalpha by alveolar macrophages was the same in alcoholics and controls. In contrast, LPS-stimulated release of TNFalpha was significantly suppressed in alcoholics compared with that of controls (1343 +/- 271 vs. 3806 +/- 926 U TNF/ml/10(6) cells, respectively, p < 0.015). When controlled for smoking, LPS-stimulated TNFalpha production was suppressed in alcoholic nonsmokers (563 +/- 413 U TNF/ml/10(6)) compared with control nonsmokers (5113 +/- 1264 U TNF/ml/10(6)). LPS-stimulated TNFalpha production was also less in control smokers (2063 +/- 386 U TNF/ml/10(6) cells) than in control nonsmokers (5113 +/- 1264 U TNF/ml/10(6) cells). There was no difference in TNFalpha production between smoking alcoholics and smoking control subjects. We conclude that chronic alcohol consumption significantly suppresses LPS-stimulated alveolar macrophage production of TNFalpha. This effect is obscured if the subject also smokes. Because TNFalpha production is an important element in host defense, this may explain, in part, the susceptibility of chronic alcohol abusers to a variety of infections.     

Alveolar lining fluid regulates mononuclear phagocyte 5-lipoxygenase metabolism

The lung clearance of technetium-99m diethylenetriamine penta-acetic acid (99mTc-DTPA) is a measure of respiratory epithelial permeability. Many factors may contribute to the wide range of normal values, including the method of correction for background activity. The aim of this study was to compare three methods of analysis, including their repeatability. 99mTc-DTPA lung clearance imaging was performed on eight nonsmokers (age 32+/-2 yrs, forced expiratory volume in one second (FEV1) 102.8+/-3.3% predicted yrs, mean+/-SEM and seven smokers (age 46+/-4 yrs, p<0.01, versus nonsmokers; FEV1 88.9+/-8.9%, p<0.05 versus nonsmokers) on two occasions each. The smokers were asked to refrain from smoking for 12 h. An uncorrected analysis was compared with two methods corrected for recirculating background activity using an intravenous correction and inter-renal and shoulder background regions of interest. The uncorrected method gave higher mean values for 50% lung clearance of 99mTc-DTPA (t50) values than the inter-renal (p<0.001) and shoulder (p<0.001) methods of correction in nonsmokers and the inter-renal method gave lower values than the shoulder-corrected method (p<0.05). In smokers there was no difference. There were no differences in mean t50 values obtained on two separate visits. There was no difference in the repeatability of the three methods of analysis. The three methods of analysis produced comparable results with no differences in repeatability.     

Bronchial reactivity, lung function, and serum immunoglobulin E in smoking-discordant monozygotic twins

Smokers with chronic bronchitis and/or chronic obstructive pulmonary disease (COPD) have been reported to have an increased bronchial reactivity (BR). It has been discussed whether increased BR is a risk factor for the development of COPD in smokers. We studied 10 monozygotic twin pairs who were discordant for tobacco smoking by means of histamine provocation tests, lung function tests, and serum samples for total IgE. The smokers had a mild obstructive ventilatory impairment, with FEV1 significantly lower than that of the partner both when it was determined from the flow-volume loops (3.2 +/- 1.0 L for smokers and 3.4 +/- 0.8 L for nonsmokers) and by the Vitalograph spirometer (3.5 +/- 1.0 L for smokers and 3.8 +/- 0.8 L for nonsmokers). Forced midexpiratory flow (FEF25-75%) and forced expiratory flow at 75 to 85% of vital capacity (FEF75-85%) were both significantly lower in the smokers (p < 0.05). The alveolar plateau phase N2-delta test and lung clearing index in the multibreath nitrogen washout test were both significantly affected in the smokers (p < 0.05 and p < 0.01, respectively). We found no significant difference in histamine reactivity between smokers and nonsmokers and no correlation between differences in reactivity and differences in lung function within pairs. Total serum IgE was significantly higher in the smokers than in their nonsmoking siblings. These data suggest that obstructive ventilatory impairment and raised serum IgE are earlier and more constant manifestations of tobacco smoking than increased bronchial reactivity. Thus, bronchial hyperreactivity does not seem to be a major risk factor for the development of early airways obstruction in smokers.     

Effects of cigarette smoking on solid and liquid intragastric distribution and gastric emptying

BACKGROUND: The acute effects of cigarette smoking on gastric emptying are controversial, whereas its effects on the intragastric distribution of solids and liquids are not established. METHODS: Dual isotope gastric scintigraphy was performed in 15 habitual smokers (studied twice, either sham smoking or actively smoking) and in 15 age- and sex-matched nonsmokers. RESULTS: Acute smoking was associated with an increased prevalence of episodes of retrograde intragastric movement of solids (3 of 15 sham subjects vs. 12 of 15 actively smoking subjects; P < 0.01) and of liquids (0 of 15 vs. 7 of 15; P < 0.01) from distal to proximal stomach. Fundal half-emptying time (T1/2) for liquids was also prolonged by smoking (43 +/- 19 minutes sham vs. 125 +/- 216 minutes active; P < 0.05). Acute smoking delayed solid lag time (13 +/- 6 minutes sham vs. 32 +/- 18 active; P < 0.05) and liquid T1/2 (46 +/- 21 vs. 90 +/- 50 minutes; P < 0.05). In the nonsmokers, such episodes of proximal intragastric redistribution did not occur, and intragastric and overall emptying parameters did not differ significantly from those of habitual sham smokers. CONCLUSIONS: Acute cigarette smoking produces excessive antrofundal redistribution of both solid and liquid contents and delays solid and liquid gastric emptying.     

Elevated levels of cytokeratin 19 in the bronchoalveolar lavage fluid of patients with chronic airway inflammatory diseases--a specific marker for bronchial epithelial injury

Cytokeratin 19 (CK19) is a specific cytoskeletal structure of simple epithelia, including bronchial epithelial cells (BEC). Since CK19 is released from injured bronchial epithelium, we investigated the levels of CK19 fragments in the bronchoalveolar lavage fluid (BALF) of eight patients with chronic airway inflammatory diseases (CAID) using an enzyme-linked immunosorbent assay (ELISA). Included in our test group were four cases of chronic bronchitis, three cases of bronchiectasis, and one case of diffuse panbronchiolitis. There were also 15 control subjects (five asymptomatic smokers and 10 nonsmokers). BALF from the nonsmokers as well as from the asymptomatic smokers contained few CK19 fragments (0.2 +/- 0.2 and 1.9 +/- 0.8 pg/ml, respectively). In contrast, significantly high levels of CK19 were present in the BALF of patients with CAID (21.7 +/- 5.7 pg/ml; p < 0.01 versus nonsmoking controls). In addition, CK19 fragment concentrations in BALF correlated significantly with the number of neutrophils (r = 0.722, p < 0.01) but not with the numbers of macrophages or lymphocytes in BALF. BALF from patients with CAID contained high levels of neutrophil elastase (NE) activity, suggesting that NE might be an important stimulus for the release of CK19 from BEC. To prove this, we incubated BET-1A cells, a human immortalized bronchial epithelial cell line, both in the absence and the presence of inflammatory mediators (including NE, tumor necrosis factor-alpha [TNF-alpha], and hydrogen peroxide). We then measured the concentration of CK19 fragments in the culture supernatants with ELISA. BET-1A cells released CK19 fragments into their culture supernatants after treatment with NE but not after treatment with TNF or hydrogen peroxide. Further, we demonstrated that CK19 cleaved by NE could not be detected by ELISA. Our results suggest that CK19 measurement in BALF is useful for assessing the presence of bronchial epithelial injuries.     

Establishment of xenografts and cell lines from well-differentiated human thyroid carcinoma

OBJECTIVE: To investigate the acute effect of cigarette smoking on glucose tolerance, insulin sensitivity, serum lipids, blood pressure, and heart rate. RESEARCH DESIGN AND METHODS: This nonrandomized experimental control trial in a tertiary care center included 20 healthy chronic smokers and 20 age-, sex-, and BMI-matched healthy volunteers. Two oral glucose tolerance tests (OGTTs) were performed on each subject. Three cigarettes were smoked during the first 30 min in one of the tests. Serum glucose, insulin, and C-peptide levels were measured every 30 min; the area under the curve (AUC) and the insulin sensitivity index (ISI) were calculated; serum total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels were measured at 0 and 180 min; and blood pressure and heart rate were recorded every 5 min throughout 180 min. RESULTS: Smoking acutely impaired glucose tolerance: the AUC for glucose in smokers was 25.5 +/- 1.03 mmol/l (mean +/- SE) (95% CI 22.9-28) during the smoking OGTT and 21.8 +/- 0.85 mmol/l (CI 19.2-24.3) in the control OGTT (P < 0.01); in nonsmokers, it was 19.7 +/- 0.3 mmol/l (CI 18.8-20.5) in the smoking OGTT and 18.7 +/- 0.35 mmol/l (CI 17.8-19.5) in the control OGTT (P < 0.05). Smoking acutely increased serum insulin and C-peptide levels and decreased ISI only in smokers: ISI in smokers was 55 +/- 2.8 (CI 47.4-62.6) in the control OGTT and 43 +/- 2.7 (CI 35.4-50.6) in the smoking OGTT (P < 0.05). Smoking acutely caused a rise of serum total cholesterol levels in both groups and increased LDL cholesterol and triglyceride serum levels significantly only in smokers (P < 0.05). A significant rise of blood pressure and heart rate while smoking was present in all the subjects. CONCLUSIONS: Smoking acutely impaired glucose tolerance and insulin sensitivity, enhanced serum cholesterol and triglyceride levels, and raised blood pressure and heart rate. These findings support the pathogenetic role of cigarette smoking on cardiovascular risk factors.     

Effects of tobacco smoking and abstinence on middle latency auditory evoked potentials

OBJECTIVE: To evaluate the effects of tobacco cigarette smoking and overnight abstinence on middle latency auditory evoked potentials among smokers and nonsmokers. METHODS: Groups of 9 to 10 adult male and female nonsmokers and smokers participated in the study. Each person volunteered for two laboratory sessions conducted in the early afternoon on 2 separate days. Smokers abstained from tobacco products 6 to 15 hours before the abstinent session and maintained their usual smoking behavior before the smoking session. The nonsmokers had a similar laboratory experience but sham smoked by means of inhaling air. Middle latency auditory evoked potentials were recorded from Cz to both ears as reference. RESULT: The latencies of the Na and Pa potentials during the smoking session were significantly (p < 0.01) shorter than those in abstinent smokers and nonsmokers. After smoking, peak-to-trough amplitudes for the V-Na, Na-Pa, and Pa-Nb potentials were larger than those after abstinence and significantly larger than those among nonsmokers. CONCLUSIONS: The shorter latencies of the middle latency brain wave components in the smoking session suggest faster processing of sensory information after cigarette smoking. Larger Pa amplitudes after cigarette smoking suggest a higher arousal level than that among partially abstinent smokers and nonsmokers.     

In vivo quantitation of epithelial lining fluid in dog lung

We used an original saturation bronchoalveolar lavage (SBAL) technique (Eur. Respir. J. 1995;8[Suppl. 19]398S) to quantitate lung epithelial lining fluid volume (VELF) in dogs in two separate experiments: control and after oleic-acid-induced injury. We confirmed the hypothesis that 99mTc-DTPA, infused at constant plasma activity, reaches equilibrium with epithelial lining fluid after 90 min. We performed eight sequential lavages 215 min after beginning the infusion of 99mTc-DTPA. 99mTc-DTPA activity (Qn) in the lavage fluid increased linearly with time, suggesting transport from the plasma into the alveoli during lavage. We extrapolated Qn to time zero (Q0), when 99mTc-DTPA was not affected by lavage. VELF was calculated from: VELF = Q0/Cp, (Cp: 99mTc-DTPA mean plasma activity). 125I-albumin was used as a nondiffusible alveolar indicator to measure the fluid volume present in the lavaged segment (Vt,n). Vt,n plateaud for n >= 4. VELF/Vt,n(n = 5,8) was 1.7 +/- 0.4 and 25.0 +/- 4.4% (p < 0.05) in control and injury experiments, respectively. SBAL allowed reliable measurements of VELF and detection of alveolar edema fluid in the injured lung.     

Molecular cloning of a mutated HOXB7 cDNA encoding a truncated transactivating homeodomain-containing protein

Bronchial infections are common in smokers and seem to be related to the presence of chronic bronchitis (CB). Why only some smokers develop repeated bronchial infections is not known. The aim of this study was to screen for immunological changes associated with disease in patients with CB and recurrent infectious exacerbations compared to asymptomatic smokers. Sixteen smokers with stable CB and recurrent infectious exacerbations, and 18 asymptomatic smokers, all without any immunomodulating treatment, underwent bronchoscopy and bronchoalveolar lavage (BAL). Smoking history and current smoking status were comparable. Serum levels of immunoglobulin (Ig)A, IgM, IgG and IgG subclasses were measured. Blood and BAL lymphocyte phenotypes and proliferative responses of peripheral blood mononuclear cells (PBMCs) to various stimulators were analysed. Unstimulated and tetanus toxoid-stimulated production of cytokines in PBMC cultures was measured. Natural killer (NK-) cell activity was analysed. A significantly (p<0.05) lower level of IgG3 was found in the CB group, and a significantly (p<0.01) higher proliferative response of PBMCs was found in the CB group after stimulation with diphtheria toxoid. Detectable levels of interleukin (IL)-6, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma, but not of IL-2, IL-4 or transforming growth factor-beta2, were found in supernatants from cultured cells in both study groups. Stimulated TNF-alpha production was significantly (p<0.05) higher in the CB group. NK-cell activity did not differ significantly between the study groups. There were no major differences between the groups in lymphocyte subpopulations in blood or BAL. In conclusion, no major alterations in the analysed indices of cell-mediated and humoral immunity were found in patients with chronic bronchitis prone to recurrent infectious exacerbations when compared with asymptomatic smoking controls.     

Cigarette smoking is associated with increased human monocyte adhesion to endothelial cells: reversibility with oral L-arginine but not vitamin C

OBJECTIVES: This study sought to assess the effect of cigarette smoking on adhesion of human monocytes to human endothelial cells and to measure the effect of L-arginine and vitamin C supplementation on this interaction. BACKGROUND: Cigarette smoking has been associated with abnormal endothelial function and increased leukocyte adhesion to endothelium, both key early events in atherogenesis. Supplementation with both oral L-arginine (the physiologic substrate for nitric oxide) and vitamin C (an aqueous phase antioxidant) may improve endothelial function; however, their benefit in cigarette smokers is not known. METHODS: Serum was collected from eight smokers (mean [+/-SD] age 33 +/- 5 years) with no other coronary risk factors and eight age- and gender-matched lifelong nonsmokers. The serum was added to confluent monolayers of human umbilical vein endothelial cells and incubated for 24 h. Human monocytes obtained by counterflow centrifugation elutriation were then added to these monolayers for 1 h, and adhesion then was measured by light microscopy. To assess reversibility, monocyte/ endothelial cell adhesion was then measured for each subject 2 h after 2 g of oral vitamin C and 2 h after 7 g of oral L-arginine. RESULTS: In smokers compared with control subjects, monocyte/ endothelial cell adhesion was increased (46.4 +/- 4.5% vs. 27.0 +/- 5.2%, p < 0.001), endothelial expression of intercellular adhesion molecule (ICAM)-1 was increased (0.31 +/- 0.02 vs. 0.22 +/- 0.03, p = 0.004), and vitamin C levels were reduced (33.7 +/- 24.1 vs. 53.4 +/- 11.5 mumol/liter, p = 0.028). After oral L-arginine, monocyte/ endothelial cell adhesion was reduced in smokers (from 46.4 +/- 4.5% to 35.1 +/- 4.0%, p = 0.002), as was endothelial cell expression of ICAM-1 (from 0.31 +/- 0.02 to 0.27 +/- 0.01, p = 0.001). After vitamin C, there was no significant change in monocyte/ endothelial cell adhesion or ICAM-1 expression from baseline in the smokers despite an increase in vitamin C levels (to 115 +/- 7 mumol/liter). CONCLUSIONS: Cigarette smoking is associated with increased monocyte-endothelial cell adhesion when endothelial cells are exposed to serum from healthy young adults. This abnormality is acutely reversible by oral L-arginine but not by vitamin C.     

Abnormal mucosal glycoprotein synthesis in inflammatory bowel diseases is not related to cigarette smoking

Patients with ulcerative colitis are usually non- or ex-smokers in contrast to Crohn's disease where smoking is common. Abnormalities of quantity and quality of intestinal mucus have been postulated in the pathogenesis of these diseases. It is possible that smoking habit may exert its effects via changes in mucus in inflammatory bowel disease. We have therefore studied incorporation of N-acetylglucosamine into synthesized colonic mucin in explants from 85 controls with normal colonoscopic appearances and histology, including 27 smokers and 58 nonsmokers, 36 patients with ulcerative colitis and 19 with ileocolonic Crohn's disease over 24 h in tissue culture. Incorporation of N-acetylglucosamine into normal explants was 31.3 +/- (SD) 7.1 dpm/microgram biopsy protein, incorporation was increased in patients with active Crohn's disease (mean 41.2 +/- (SD) 10.4 dpm/microgram biopsy protein, p = 0.003), decreased in inactive ulcerative colitis (mean 24.1 +/- 7.8 dpm/microgram biopsy protein, p = 0.0006) but normal in active ulcerative colitis (mean 35.0 +/- 13.8 dpm/microgram biopsy protein, p = 0.44). No significant relationship was found between cigarette smoking habits and mucus synthesis in controls with normal mucosa (nonsmokers, n = 58, mean 31.0 +/- (SD) 7.52 dpm/microgram biopsy protein; smokers, n = 27, mean 31.8 +/- (SD) 6.1 dpm/microgram biopsy protein, p = 0.9). This study shows that mucus glycoprotein synthesis is reduced in inactive ulcerative colitis, rising to normal levels in active disease and that synthesis is increased in Crohn's disease. There is no effect of smoking on mucus synthesis by control biopsies suggesting that the differences seen in inflammatory bowel disease are not related to cigarette smoking.     

Persistent airway hyperresponsiveness and histologic alterations after chronic antigen challenge in cats

We studied the effect of chronic immune sensitization on the airway reactivity and associated cytologic and histologic alterations in initially nonatopic cats, a species that spontaneously develops idiopathic asthma. Seven cats were sensitized by intramuscular injection of Ascaris suum antigen (AA) for 4 wk, and four other cats served as sham controls. Airway sensitization was demonstrated by an increased response to nebulized AA in sensitized animals (RL = 45.9 +/- 6.1 cm H2O/L/s, versus a baseline response of 24.7 +/- 1.5 cm H2O/L/s, p < 0.01), and hyperresponsiveness was demonstrated by an increased response to acetylcholine (ACh)-challenge 24 h after AA (approximately 1.0 log decrease in PD200, p < 0.01). The number of eosinophils in the sensitized animals' bronchoalveolar lavage (BAL) fluid increased 12-fold (p < 0.01 versus control) in response to AA challenge; 32 +/- 5% of the BAL eosinophils had a specific density < 1.050, versus 8 +/- 2% prior to AA challenge (p < 0.05). There was no change in airway reactivity, eosinophil recovery, or density in the control group 24 h after sham challenge with saline. The same seven sensitized cats further received nebulized AA three times weekly for 4 to 6 wk, after which BAL samples were again obtained and ACh dose-response curves generated 72 h after the final administration of nebulized AA. Airway hyperresponsiveness increased (approximately 1.5 log decrease in PD200, p < 0.001) and the number of eosinophils recovered in BAL fluid was increased 11-fold (p < 0.05). Necropsy specimens demonstrated bronchoconstriction in AA-challenged animals but not controls; luminal narrowing was accompanied by: (1) a 29.0 +/- 0.34% increase in smooth-muscle thickness (p < 0.05); (2) goblet-cell and submucosal-gland hypertrophy and hyperplasia; and (3) epithelial erosion and eosinophilic infiltration. We demonstrate in nonhuman species persistent airway hyperreactivity associated with a complete constellation of histologic changes in epithelium, smooth muscle, and mucus glands, and cytologic changes in BAL fluid, all induced by immune sensitization. Our data suggest that chronic immune sensitization per se could be a salient factor in causing many of the changes associated with chronic bronchial asthma.     

Respiratory response to cigarette smoking among adolescent smokers: a pilot study

BACKGROUND: Because cigarette smoking affects the respiratory system earlier than many other systems of the human body, an attempt was made to identify objective and subjective respiratory problems among adolescent smokers. METHODS: Two studies based on a pulmonary function test (PFT), respiratory symptom assessment, and other smoking-related variables were undertaken. Study 1 involved cigarette smokers (N = 18, 22% males, mean age 18.7 years) from a freshman college class who participated in an acute smoking experiment that involved performing a PFT before and after smoking a single cigarette. Study 2 was performed on a combined group of vocational-technical high school students and freshman college students (N = 44, 48% males, mean age 17.8 years) where PFT parameters, respiratory symptoms, and smoking-related health vulnerability were assessed among smokers vs nonsmokers. RESULTS: In Study 1, the average reduction across PFT parameters was 4.4% and the mean estimated lung age increased from 27.15 to 29.84 years. In Study 2, a consistent trend toward reduction of PFT values among smokers vs nonsmokers was observed; the mean forced expiratory volume in 1 sec/forced vital capacity ratio (90.51% vs 94.59%), peak expiratory flow rate (80.32% vs 92.06%), and flow rate of 50% of forced vital capacity (88.39% vs 102.81%) differed significantly. Significant differences in respiratory symptoms were also observed among smokers vs nonsmokers. CONCLUSIONS: The beginning of respiratory health disorders can be identified among adolescent smokers. These findings might provide important clues on how to improve outcomes from health care provider-based adolescent smoking cessation counseling.     

The role of neutrophils in the pathogenesis of idiopathic pulmonary fibrosis

STUDY OBJECTIVES: The prognostic value of the neutrophil count in BAL fluid (BALF) has been controversial. The role of neutrophils in this inflammatory lung disease, therefore, was evaluated in this study by additional measures. MATERIALS AND METHODS: We performed BAL in 22 patients with idiopathic pulmonary fibrosis (IPF) diagnosed by open lung biopsy specimen. Percent polymorphonuclear leukocyte (PMN) in BALF and absolute neutrophil counts were compared with those of normal nonsmokers. Elastase complexed to alpha-1-proteinase inhibitor (alpha1-PI) in plasma and BALF was measured as a marker of elastase burden, and neutrophil distribution in 22 lung tissues was observed by immunohistochemistry using antineutrophil elastase antibody. RESULTS: Percent PMN and absolute neutrophil counts in BALF did not increase in patients with IPF as compared with normal nonsmokers (n=15); the plasma elastase-alpha1-PI complex value (mean+/-SE) of patients with IPF (668.5+/-112.4 ng/mL) was significantly high as compared with that of normal nonsmokers (130.3+/-21.3, p<0.001). In addition, the BALF elastase-alpha1-PI complex value (mean+/-SE) of patients with IPF was also significantly high (333.1+/-87.0 ng/mg albumin) as compared with that of normal nonsmokers (83.1+/-29.3 ng/mg albumin, p<0.05). Immunohistochemistry demonstrated considerable numbers of neutrophils infiltrating the lung parenchyma in biopsy specimens obtained by open lung biopsy. CONCLUSIONS: These results suggested that although the neutrophil count in BALF could not represent the distribution of neutrophil in the lung, high levels of neutrophil elastase were demonstrated in lung parenchyma and also in both BALF and sera. Therefore, neutrophils might indeed play an important role in the pathogenesis of IPF.     

Effect of dietary protein and environmental temperature on growth performance and water consumption of male broiler chickens

The purpose of this study was to investigate whether smokers outside buildings with work-place smoking bans smoke "harder" than those smoking in social settings. An unobtrusive random observational study of smokers followed by structured interview was used, with 143 smokers taking smoking breaks outside their office buildings and 113 smokers in social settings. The main outcome measurements were number of puffs per cigarette and cigarette smoking duration. The mean number of puffs per cigarette for the office building group was 18.7% greater than that for the social settings group (10.7 +/- 3.2 vs. 8.7 +/- 2.7, t = 5.58, df = 253, p < 0.001); 74.8% of smokers outside offices took more than the mean number of puffs for the group compared to 42.5% of smokers in social settings (chi 2 df 1 = 26.31, p < 0.0001). Mean cigarette smoking duration was 30.4% shorter for the work-place group than the social settings group (3.9 +/- 1.2 minutes vs. 5.6 +/- 2.6 minutes). Of smokers outside offices, 55.2% had a cigarette smoking duration between 3 and 4.59 minutes, while 53.1% of smokers in social settings took > or = 5 minutes to smoke the observed cigarette (chi 2 df 2 = 31.55, p < 0.0001). Smokers who scored at the 75th percentile on the Fagerstrom Tolerance Scale took a mean 9.5 +/- 2.6 puffs per cigarette compared to 9.3 +/- 2.7 puffs by those who scored in the 25th percentile on the scale (t = 0.34, df = 145, p = 0.73). Regardless of degree of nicotine dependency, smokers leaving work-stations to smoke outside buildings smoked their cigarettes nearly 19% "harder" than cigarettes smoked in social settings. The individual and public health benefits of reduced smoking frequency engendered by work-place smoking bans may be lessened by policies which allow smokers to take smoking breaks.     

Citation for the Distinguished Physician Award of the Endocrine Society to Dr. John P. Bilezikian

OBJECTIVE: To elucidate the molecular mechanism of smoking cessation and its relationship to body weight gain, the effects of smoking on the serum levels of leptin were studied in Japanese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The serum levels of leptin after an overnight fast in 37 adult male Japanese patients with type 2 diabetes (17 smokers and 20 nonsmokers) were assayed using radioimmunoassay. In addition, the serum leptin levels in four nondiabetic smokers were measured before and 2 weeks after quitting smoking. RESULTS: Smokers and nonsmokers did not differ in age, BMI, or levels of blood glucose and fasting insulin but did differ in HDL cholesterol levels (1.07 +/- 0.18 vs. 1.32 +/- 0.24 mmol/l for smokers and nonsmokers, respectively, P = 0.002). The mean serum leptin level of smokers did not differ from that of nonsmokers (3.8 +/- 1.9 vs. 3.8 +/- 1.6 ng/ml). The leptin level correlated with the fasting insulin level and BMI (r = 0.55 and 0.56, P < 0.001 and 0.001, respectively). The leptin levels in four heavy smokers showed no change after the subjects quit smoking (3.3 +/- 1.0 vs. 3.8 +/- 1.8 ng/ml, before and after quitting, respectively). CONCLUSIONS: Because smoking did not affect the leptin levels, the effects of quitting smoking on the fuel metabolism appear to be due to some other factors.     

Glutathione depletion in epithelial lining fluid of lung allograft patients

The lower respiratory tract is protected against reactive oxygen species (ROS) by a complex antioxidant system. In the epithelial lining fluid (ELF), glutathione (L-alpha-glutamyl-L-cysteinylglycine, GSH) is essential for adequate protection of pneumocytes from potential toxicity mediated by extracellular hydrogen peroxide (H2O2). We assessed the concentration of total GSH in bronchoalveolar lavage fluid (BALF) in lung allograft patients in the absence and presence of acute rejection. Bronchoalveolar lavage (BAL) and biopsies were performed concurrently on 36 occasions in 17 patients who had undergone lung transplantation. BALF samples were divided into two groups on the basis of presence or absence of acute lung rejection on transbronchial biopsy. Seven BALF samples were obtained from control subjects for comparison. The BALF data demonstrated significantly lymphocyte recruitment and evidence of lung injury during acute rejection episodes. Transplant allografts without rejection showed significant depletion of total GSH in the ELF as compared with that of normal volunteers (94.0 +/- 9.7 microM versus 302.6 +/- 40.8 microM, p < 0.01). Transplant allografts with acute rejection had a slightly higher GSH concentration in their ELF (179.8 +/- 34.7), but this was still lower than control values. The deficiency of total GSH in the alveolar fluid may predispose lung allografts to extracellular H2O2-mediated toxicity.     

Occupation and smoking in college graduates.

The results of a study of 895 members of the Harvard Class of 1946, 13 years after graduation, with respect to the association of occupation and smoking behavior, indicate statistically significant differentiations between smokers and nonsmokers; between cigarette, cigar, and pipe smokers; and in accordance with degree or rate of cigarette smoking. The significance of these findings appears to relate to the influence of personality and constitution on smoking behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acute effects of cigarette smoking on fetal cardiovascular and uterine Doppler parameters

The purpose of this study was to assess the effects of smoking one cigarette (nicotine mean 0.63 +/- 0.17 mg) on uterine- and foetal cardiovascular Doppler parameters in healthy pregnant smokers. All pregnancies (n = 16; mean gestational age: 36 +/- 4 weeks) had been uneventful and all foetuses were appropriate for gestational age with normal baseline Doppler parameters and normal foetal outcome (birthweight: 3254 +/- 340 grams). Measurements, performed immediately before and after smoking, included pulsatility index (PI) of umbilical artery (UA), middle cerebral artery (MCA), foetal descending aorta and uterine artery as well as maternal and foetal heart rate. The ratio of UA/MCA PI was used to assess centralisation. Changes in foetal cardiac output were determined by: time-velocity integral times heart rate, at aortic and pulmonary valve level. Foetal heart rate (p < 0.0005, paired t-test) and maternal heart rate (p < 0.05) increased significantly. All other parameters did not change significantly. However, in one additional woman with labile hypertension and increased baseline uterine artery PI (1.9), smoking of one cigarette caused a substantial rise in uterine artery PI to 3.25 ten minutes after smoking. Middle cerebral artery PI decreased from 2.2 to 1.18 with an unchanged cardiac output and umbilical artery PI raising the UA/MCA PI ratio from 0.51 to 0.81, suggesting a brain sparing effect. Smoking of one cigarette raised maternal and foetal heart rate. There was no evidence of other cardiovascular effects or centralisation in healthy foetuses of normal pregnancies, but this might not be true in foetus of pathologic pregnancies.