Interleukin-16-producing NK cells and T-cells in the blood of tobacco smokers with and without COPD.

BACKGROUND: Long-term exposure to tobacco smoke causes local inflammation in the airways that involves not only innate immune cells, including NK cells, but also adaptive immune cells such as cytotoxic (CD8+) and helper (CD4+) T-cells. We have previously demonstrated that long-term tobacco smoking increases extracellular concentration of the CD4+-recruiting cytokine interleukin (IL)-16 locally in the airways. Here, we hypothesized that tobacco smoking alters IL-16 biology at the systemic level and that this effect involves oxygen free radicals (OFR). METHODS: We quantified extracellular IL-16 protein (ELISA) and intracellular IL-16 in NK cells, T-cells, B-cells, and monocytes (flow cytometry) in blood samples from long-term tobacco smokers with and without chronic obstructive pulmonary disease (COPD) and in never-smokers. NK cells from healthy blood donors were stimulated with water-soluble tobacco smoke components (cigarette smoke extract) with or without an OFR scavenger (glutathione) in vitro and followed by quantification of IL-16 protein. RESULTS: The extracellular concentrations of IL-16 protein in blood did not display any substantial differences between groups. Notably, intracellular IL-16 protein was detected in all types of blood leukocytes. All long-term smokers displayed a decrease in this IL-16 among NK cells, irrespective of COPD status. Further, both NK and CD4+ T-cell concentrations displayed a negative correlation with pack-years. Moreover, cigarette smoke extract caused release of IL-16 protein from NK cells in vitro, and this was not affected by glutathione, in contrast to the decrease in intracellular IL-16, which was prevented by this drug. CONCLUSION: Long-term exposure to tobacco smoke does not markedly alter extracellular concentrations of IL-16 protein in blood. However, it does decrease the intracellular IL-16 concentrations in blood NK cells, the latter effect involving OFR. Thus, long-term tobacco smoking exerts an impact at the systemic level that involves NK cells; innate immune cells that are critical for host defense against viruses and tumors - conditions that are overrepresented among smokers.

Impaired peripheral airway function in adults following repair of esophageal atresia.

BACKGROUND: Esophageal atresia (EA) often leads to persistent symptoms and impaired respiratory function in adulthood. The role of peripheral airways in this impairment has not been previously investigated. Furthermore, asthma-like symptoms are common in these patients. PURPOSE: The purpose of this study was to investigate pulmonary outcome, including possible peripheral airway dysfunction, perhaps missed by conventional pulmonary function tests and to see if the diagnosis asthma was accurate. METHODS: Twenty eight patients operated for EA in Gothenburg 1968-1983 answered a questionnaire regarding respiratory symptoms and underwent pulmonary function tests. Peripheral airway function was measured by multiple breath washout. RESULTS: 22/28 (79%) patients had a history of respiratory symptoms. Abnormal peripheral airway function was found in 17 (61%) patients, while only 6 (21%) patients displayed values indicating central obstruction. Nine patients had restrictive disease. Airway hyperresponsiveness was frequent and associated with atopy and airway inflammation. However, respiratory symptoms or doctor-diagnosed asthma did not correlate with any specific lung function test abnormality. CONCLUSION: Different lung function abnormalities are present in EA survivors, and peripheral airway disease is common. Classical asthma seems to be difficult to diagnose in this patient group. Given the high prevalence of respiratory morbidity, long-term follow-up of pulmonary function, including peripheral airway function, is warranted.

Respiratory symptoms and peripheral airways disease in a cross-sectional study on a random population sample.

OBJECTIVES: Respiratory symptoms are associated with spirometry results but more strongly with smoking history, suggesting that alterations in the lung other than those revealed by spirometry contribute to cause symptoms. Smoking may cause obstruction of peripheral airways that is poorly detected by spirometry. The slope of phase III of the single-breath nitrogen (N(2)) test detects smoking-induced alterations in smokers before spirometry is impaired. The aim of the present investigation was to study the association between respiratory symptoms and the slope of phase III adjusting for spirometry results and smoking history. DESIGN: Single-centre retrospective cross-sectional study. SETTING: University hospital in Gothenburg, Sweden. PARTICIPANTS: A random population sample of 430 elderly men. METHODS: The presence of seven different respiratory symptoms were analysed by a multiple logistic regression model in relation to spirometry results, smoking history (pack-years) and the slope of phase III in a population sample of 430 elderly men, age span 50-67 years. Furthermore, smoking normalised values of the slope of phase III were calculated and differences between subjects reporting/not reporting symptoms were tested. RESULTS: The presence of some cough symptoms was significantly associated with a steep slope of phase III also when adjusting for spirometry results and smoking history. Furthermore, smoking normalised slope of phase III was significantly steeper among subjects with cough symptoms compared to those without cough symptoms. CONCLUSIONS: Cough symptoms may be an effect of abnormalities in peripheral airways at least among elderly men.

A realistic validation study of a new nitrogen multiple-breath washout system.

BACKGROUND: For reliable assessment of ventilation inhomogeneity, multiple-breath washout (MBW) systems should be realistically validated. We describe a new lung model for in vitro validation under physiological conditions and the assessment of a new nitrogen (N(2))MBW system. METHODS: The N(2)MBW setup indirectly measures the N(2) fraction (F(N2)) from main-stream carbon dioxide (CO(2)) and side-stream oxygen (O(2)) signals: F(N2) = 1-F(O2)-F(CO2)-F(Argon). For in vitro N(2)MBW, a double chamber plastic lung model was filled with water, heated to 37°C, and ventilated at various lung volumes, respiratory rates, and F(CO2). In vivo N(2)MBW was undertaken in triplets on two occasions in 30 healthy adults. Primary N(2)MBW outcome was functional residual capacity (FRC). We assessed in vitro error (√[difference](2)) between measured and model FRC (100-4174 mL), and error between tests of in vivo FRC, lung clearance index (LCI), and normalized phase III slope indices (S(acin) and S(cond)). RESULTS: The model generated 145 FRCs under BTPS conditions and various breathing patterns. Mean (SD) error was 2.3 (1.7)%. In 500 to 4174 mL FRCs, 121 (98%) of FRCs were within 5%. In 100 to 400 mL FRCs, the error was better than 7%. In vivo FRC error between tests was 10.1 (8.2)%. LCI was the most reproducible ventilation inhomogeneity index. CONCLUSION: The lung model generates lung volumes under the conditions encountered during clinical MBW testing and enables realistic validation of MBW systems. The new N(2)MBW system reliably measures lung volumes and delivers reproducible LCI values.

Prediction of BOS by the single-breath nitrogen test in double lung transplant recipients.

BACKGROUND: The present study analyses the ability of the alveolar slope of the single-breath nitrogen washout test (N2-slope) to diagnose and predict the development of the bronchiolitis obliterans syndrome (BOS). METHODS: We present a retrospective analysis of 61 consecutive bilateral lung or heart-lung transplant recipients who were followed at regular control visits during a three year follow-up. The operating characteristics of the N2-slope to diagnose BOS and potential BOS (BOS 0-p) and to predict BOS were determined based on cut off values of 95% specificity. RESULTS: The sensitivity of the N2-slope to identify BOS was 96%, and BOS 0-p 100%. The predictive ability to predict BOS with a N2-slope > 478% of the predicted normal was 56%, and if combined with a coincident FEV1 < 90% of the basal value, the predictive ability was 75%. CONCLUSIONS: The predictive ability of either the N2-slope or of FEV1 to diagnose BOS is limited but the combination of the two appears useful. Follow-up protocols of bilateral lung and heart-lung transplant recipients should consider including tests sensitive to obstruction of the peripheral airways.

Cardiac function in relation to rhythm outcome after intraoperative epicardial left atrial cryoablation.

OBJECTIVES: To assess the effects of intraoperative left atrial epicardial cryoablation on rhythm and atrial and ventricular function. DESIGN: Thirty five patients with coronary artery disease and documented atrial fibrillation underwent coronary artery bypass surgery and concomitant cryoablation. An age and gender matched control group of 35 patients with atrial fibrillation underwent bypass surgery alone. Echocardiography was performed 9 ? 32 days before and 22 ? 6 months after surgery. RESULTS: The proportion of patients in sinus rhythm at follow-up was 63% and 34% (p = 0.04) in the cryoablation and control groups, respectively. In patients with sinus rhythm both before surgery and at follow-up, the left atrial area increased (p = 0.002) and the mitral annular excursion during atrial contraction decreased (p = 0.01) after cryoablation. The mitral flow velocity during atrial systole decreased after cryoablation (p = 0.002). The LV diameter increased (p = 0.03) and the left ventricular ejection fraction (LVEF) decreased (p = 0.03) in cryoablated but not in control patients. Continued deterioration was seen in patients with atrial fibrillation both pre- and postoperatively. CONCLUSIONS: At long-term follow-up, a significantly higher proportion of patients was in sinus rhythm in the cryoablation than in the control group. The atrial and ventricular function had decreased at follow-up two years after surgery. This decrease was small and occurred within or close to the reference values in patients with sinus rhythm at follow-up, while patients remaining in atrial fibrillation showed a significant continued deterioration. Some subgroups were small, and the findings, although statistically significant, should be interpreted with caution.

Left ventricular diastolic function and right atrial size are important rhythm outcome predictors after intraoperative ablation for atrial fibrillation.

BACKGROUND: Left ventricular (LV) diastolic function and right atrial (RA) size are not routinely included in preoperative echocardiographic examination in patients undergoing cardiac surgery with concomitant ablation for atrial fibrillation (AF). OBJECTIVE: To investigate the role of echocardiographic variables including LV diastolic function and RA area in long-term rhythm outcome prediction, in patients with documented AF undergoing intraoperative ablation concomitant to coronary artery bypass grafting (CABG). METHODS: Thirty-five consecutive patients, scheduled for CABG, and with a history of paroxysmal or permanent AF for 8.5 ± 11.3 years (mean ± SD) (median 5.8 years), were included in this prospective study. Echocardiography was performed prior to and 2.3 ± 0.4 years after the surgical procedure. RESULTS: Both LA and RA areas, LV diastolic function, paroxysmal AF, and sinus rhythm (SR) preoperatively were associated with SR at long-term follow-up. In the multivariate analysis, RA area (P = 0.004), and decreased LV diastolic function preoperatively, measured as the maximal LV long-axis relaxation velocity (P = 0.02), predicted SR at follow-up. CONCLUSIONS: RA size and LV diastolic function may be important variables in prediction of long-term rhythm outcome after intraoperative ablation for AF.

Short-term sinus rhythm predicts long-term sinus rhythm and clinical improvement after intraoperative ablation of atrial fibrillation.

AIMS: Our aim was to compare the long-term effects on rhythm and quality of life (QoL) after left atrial epicardial radiofrequency (RF) ablation vs. no ablation in patients undergoing cardiac surgery. METHODS AND RESULTS: Thirty-nine patients with ECG documented atrial fibrillation (AF) scheduled for coronary artery bypass grafting (CABG) with or without concomitant valve surgery were consecutively elected for epicardial RF ablation. Thirty-nine age- and gender-matched patients scheduled for CABG with or without concomitant valve surgery only and with documented AF served as controls. The follow-up after ablation was 32 +/- 11 months. The percentage of patients in sinus rhythm (SR) at long-term follow-up was 62 vs. 33% (P = 0.03) after ablation and no ablation, respectively. SR at 3 months was highly predictive of that at 32 months (sensitivity 95%, positive predictive value 86%). Long-term SR was associated with better QoL, fewer symptoms, higher ejection fraction, and smaller left and right atria than AF. CONCLUSION: SR at 3 months was highly predictive of long-term SR that was associated with clinical improvement when compared with patients still in AF. AF at 3 months did not preclude a later stabilization to SR.

COPD 'diagnosis' based on spirometric reference equations.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is suspected if the ratio between forced expired volume in 1 s (FEV(1)) and forced vital capacity is below 0.7 after bronchodilatation, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD). As this ratio varies with age and gender, the lower limit of normality (LLN) of appropriate reference equations appears more adequate. OBJECTIVES: To study the prevalences of suspected COPD according to the GOLD criterion and various reference equations in a well-defined population sample. METHODS: Spirometries obtained in a random population sample of 598 men, 50 or 60 years of age, were analysed. The prevalences of suspected COPD were calculated according to the GOLD criterion and the LLNs of four Nordic and two European reference equations. RESULTS: The GOLD criterion resulted in prevalences of COPD of 9.3% and 23.7% in the 50- and 60-year-old never-smokers, respectively. Depending on the reference equation, the calculated prevalences of COPD varied between 9.3% and 23.4% and 12.0% and 39.1% among all of the 50- and 60-year-old men, respectively. CONCLUSIONS: The GOLD criterion is inadequate because of substantial overestimation in 60-year-old never-smokers. LLNs of the various reference equations are unreliable because of obvious lack of consistency. Spirometric criteria for airway obstruction, and suspicion of COPD, therefore need to be revised.

High tidal end expiratory flow--an index of dynamic hyperinflation?

Dynamic hyperinflation is considered an important mechanism behind shortness of breath and reduced exercise capacity in chronic obstructive pulmonary disease (COPD) patients. Prevailing methods to assess dynamic hyperinflation are crude because of the large normal variation of both functional residual capacity and inspiratory capacity (IC). In the present study, we hypothesized that expiratory flow on a relatively high level near the end of tidal expiration is an indication of dynamic hyperinflation. A method to measure tidal end expiratory flow (TEEF), i.e. the flow between 0.6 s and 0.04 s before start of inspiration is presented and evaluated in 15 healthy subjects and 16 COPD patients. The COPD patients had more than twice as high TEEF values compared with the healthy subjects (45.4 +/- 23.8 and 20.4 +/- 7.3 ml s(-1) respectively; mean +/- SD; P = 0.0002, for TEEF at 0.4 s before start of inspiration). TEEF values correlated to IC, e.g. TEEF at 0.4 s before start of inspiration expressed as a fraction of mean expiratory flow, correlated to IC (% pred.) (r = 0.74; P<0.0001). These results justifies further testing of the relationship between TEEF and dynamic hyperinflation.

QRS aberration during atrial fibrillation at rest and during exercise. Effect of a selective potassium channel blocking agent.

This study assesses the occurrence of and identifies clinical characteristics associated with the development of aberrant conduction during infusion of the I(kr)-blocker almokalant. Class III drugs may induce aberrant conduction by prolongation of cardiac repolarization, especially during atrial fibrillation (AF). Ninety-two patients with AF received a 6-hour almokalant infusion, aiming at conversion to sinus rhythm (SR). Fiftyfive of the patients received an identical infusion during SR. During almokalant infusion, the number of patients with intermittent QRS aberration during AF increased, from 21% to 80% at rest, and was further increased to 89% during exercise, with predominantly left, and sequential bilateral, bundle branch aberrancy. Patients with aberrant conduction showed signs of more advanced myocardial disease. Predictors of the development of QRS aberration were female gender, arrhythmia duration, and decreased left ventricular ejection fraction, while use of calcium antagonists decreased the probability. No patient showed aberration during regular SR. Twenty-one patients experienced aberrantly conducted supraventricular premature beats. In conclusion, aberrant conduction is common during infusion of the I(kr)-blocker almokalant during AF, and seems to be more frequent in females and in patients with more advanced myocardial disease.