Airway Reactance Predicts Static Lung Hyperinflation in Severe Asthma.

BACKGROUND AND OBJECTIVES: Background: Static lung hyperinflation (SLH) measured using body plethysmography in patients with asthma is associated with poor outcomes. The severity of SLH may be associated with small airway dysfunction (SAD), which can be measured using impulse oscillometry (IOS). Objective: This study aims to determine the correlation between SLH and SAD in patients with severe asthma and assess the improvement in SLH and SAD with treatment. METHODS: We analyzed data from patients who were enrolled in the Taiwan Severe Asthma Registry, which comprises a prospective observational cohort. Plethysmography and IOS were performed regularly. The relationship between spirometry and IOS parameters was determined. Changes in the clinical outcomes in response to treatment were analyzed. RESULTS: Of 107 patients with severe asthma, 83 (77.6%) had SLH based on an increased residual volume to total lung capacity ratio (RV/ TLC). Most patients were older women with worse pulmonary function and SAD than those without SLH. SAD, defined as increased airway resistance/reactance, was significantly correlated with SLH. Airway reactance at 5 Hz (X5) ≤-0.21 kPa/(L/s) detected SLH with an area under the receiver operating characteristic curve of 0.84 (P<.0001; sensitivity, 85.2%; and specificity, 83.3%). After 12 months, patients who received add-on biologics (vs those who did not) had significantly reduced exacerbations, fractional exhaled nitric oxide level, and blood eosinophil counts, as well as improved forced expiratory volume in the first second, X5, and a trend toward reduced RV/TLC ratio. CONCLUSIONS: In severe asthma, airway reactance (X5) could be a novel parameter for assessing SLH.

Airway Reactance Predicts Static Lung Hyperinflation in Severe Asthma

Background: Static lung hyperinflation (SLH) measured using body plethysmography in patients with asthma is associated with poor outcomes. The severity of SLH may be associated with small airway dysfunction (SAD), which can be measured using impulse oscillometry (IOS). Objective: This study aims to determine the correlation between SLH and SAD in patients with severe asthma and assess the improvement in SLH and SAD with treatment. Methods: We analyzed data from patients who were enrolled in the Taiwan Severe Asthma Registry, which comprises a prospective observational cohort. Plethysmography and IOS were performed regularly. The relationship between spirometry and IOS parameters was determined. Changes in the clinical outcomes in response to treatment were analyzed. Results: Of 107 patients with severe asthma, 83 (77.6%) had SLH based on an increased residual volume to total lung capacity ratio (RV/TLC). Most patients were older women with worse pulmonary function and SAD than those without SLH. SAD, defined as increased airway resistance/reactance, was significantly correlated with SLH. Airway reactance at 5 Hz (X5) ≤−0.21 kPa/(L/s) detected SLH with an area under the receiver operating characteristic curve of 0.84 (P<.0001; sensitivity, 85.2%; and specificity, 83.3%). After 12 months, patients who received add-on biologics (vs those who did not) had significantly reduced exacerbations, fractional exhaled nitric oxide level, and blood eosinophil counts, as well as improved forced expiratory volume in the first second, X5, and a trend toward reduced RV/TLC ratio. Conclusion: In severe asthma, airway reactance (X5) could be a novel parameter for assessing SLH. (AU)

Antecedentes: En el asma bronquial, la hiperinsuflación pulmonar estática (SLH) medida mediante pletismografía corporal (Pleth) se asocia a un peor pronóstico. La gravedad de la SLH podría estar asociada con la disfunción de las vías respiratorias pequeñas (SAD), que puede medirse mediante la oscilometría de impulsos (IOS). Objetivo: Este estudio pretende determinar la correlación entre el SLH y la SAD en pacientes con asma grave, y la mejora de ambos parámetros en respuesta al tratamiento. Métodos: Se analizaron los datos de los pacientes que se inscribieron en el Registro de Asma Grave de Taiwán, una cohorte observacional prospectiva. Se realizaron periódicamente mediciones de Pleth e IOS. Se determinó la relación entre los parámetros espirométricos e IOS. Se analizaron los cambios en los parámetros clínicos y funcionales en respuesta al tratamiento. Resultados: De una muestra de 107 pacientes con asma grave, 83 (77,6%) presentaban SLH, definida mediante una relación volumen residual/capacidad pulmonar total (VR/CTP) aumentada. La mayoría de los pacientes eran mujeres de edad avanzada con peor función pulmonar y SAD, en comparación con los que no tenían SLH. El SAD por aumento de la resistencia/reactancia de las vías respiratorias se correlacionó significativamente con el SLH. La reactancia de las vías respiratorias a 5 Hz (X5) ≤-0,21 [kPa/(L/s)] detectó el SLH con un área bajo la curva ROC de 0,84 (p < 0,0001, sensibilidad = 85,2% y especificidad = 83,3%). Después de 12 meses, los pacientes que recibieron tratamiento biológico adicional presentaron una reducción significativa de las exacerbaciones, del nivel de óxido nítrico exhalado, del recuento de eosinófilos en sangre, una mejora del volumen espiratorio forzado en el primer segundo, de la X5, y una tendencia a la reducción del cociente RV/TLC en comparación con los que no recibieron tratamiento biológico... (AU)

Allergic rhinitis and risk of erectile dysfunction--a nationwide population-based study.

BACKGROUND: A growing body of evidence has disclosed that allergic rhinitis (AR) is a systemic inflammatory disease. Inflammatory mediators and cells involved in AR have also been reported to be implicated in the process of atherosclerosis, which is relevant to the occurrence of erectile dysfunction (ED). Our objective was to explore the relationship between AR and future ED events. METHODS: From 1 January 2000 to 31 December 2008, we identified male patients, who were aged 18-55 years and newly diagnosed with AR from the Taiwan National Health Insurance Research Database. A control cohort without AR, which was matched for age, comorbidities and medications, was selected for comparison. The two cohorts were followed up until 31 December 2009 and observed for occurrence of ED by registry of ED diagnosis in the database. RESULTS: Of the 128,118 sampled male patients (64,059 AR patients vs 64,059 matched controls), 1455 (1.16%) experienced ED during a mean follow-up period of 5.82 years, including 844 (1.32% of the AR patients) from the AR cohort and 611 (0.95%) from the controls. Kaplan-Meier analysis revealed a tendency of AR patients to develop ED (log-rank test, P < 0.001). After adjusting confounder variables by Cox regression, subjects with AR experienced a 1.37-fold (95% CI, 1.24-1.52; P < 0.001) increase in incident ED. The risk of ED was higher in cases with more frequent clinical visits for AR and in cases needing medication more than 4 weeks. CONCLUSIONS: Patients with AR appeared to be at higher risk of future ED, possibly in a severity-dependent manner.

Anti-inflammatory effects of salmeterol/fluticasone, tiotropium/fluticasone or tiotropium in COPD.

The anti-inflammatory effects of salmeterol/fluticasone (SFP), tiotropium/fluticasone (Tio+FP) and tiotropium (Tio) alone were investigated on the inflammatory cells and mediators in sputum induced from chronic obstructive pulmonary disease patients. Subjects were either newly diagnosed or had not taken any medication for 3 months prior to the study. Subjects (n = 99) were randomised (not double blinded) and received either SFP (100/1,000 microg daily), Tio+FP (18/1,000 microg daily) or Tio (18 microg daily) for 12 weeks. Induced sputum and serum C-reactive protein (CRP) were analysed prior to and at the end of treatment. The results showed that treatment with SFP caused a significant reduction in interleukin (IL)-8 and matrix metalloprotease (MMP)-9 in induced sputum, compared with treatment with Tio alone. There were no treatment differences between the SFP and Tio+FP groups in decreasing IL-8 and MMP-9 levels. The reduction in IL-8 showed significant association with the reduction in MMP-9. All treatment groups failed to significantly reduce the numbers of total cells, neutrophils, macrophages and eosinophils in induced sputum; in addition, there were no treatment differences in terms of improvement of forced expiratory volume in one second, forced vital capacity, CRP or quality of life between the three groups. The anti-inflammatory effects of salmeterol/fluticasone probably contribute to the clinical benefits seen in chronic obstructive pulmonary disease patients.

Total intravenous anesthesia using propofol and ketamine for ambulatory gynecologic laparoscopy.

Laparoscopy under total intravenous anesthesia (TIVA) with spontaneous respiration is a commonly encountered procedure in ambulatory gynecologic surgery. The purpose of this study was to evaluate the efficacy of TIVA using propofol and ketamine, compared with endotracheal inhalational general anesthesia (EIGA) for ambulatory gynecologic laparoscopy. Fifty-eight female patients, aged 17-48 years, were randomly allocated into two groups. Group 1 (TIVA) (n = 28) received propofol at the induction of anesthesia followed by propofol infusion for maintenance. Intravenous ketamine 0.5 mg/kg was administered before operation for anesthetic effect. Natural airway and spontaneous breathing were then maintained in patients. Group 2 (n = 30) received EIGA with isoflurane under controlled ventilation. We found that the two groups demonstrated similar trend characters of pH and PaCO2 during operation and in recovery room. The incidence of postoperative vomiting was higher in group 2 than in group 1 (30% vs. 7%; p < 0.05). The incidence of intraoperative arrhythmia was higher in group 2 than in group 1 (40% vs. 3%; p < 0.001). Furthermore, the incidence of sore throat was higher in group 2 than in group 1 (47% vs. 7%; p < 0.001). We conclude that TIVA with spontaneous respiration is suitable for ambulatory gynecologic laparoscopy.

Upgrading clinical decision support with published evidence: what can make the biggest difference?

BACKGROUND: To enhance clinical decision support, presented messages are increasingly supplemented with information from the medical literature. The goal of this study was to identify types of evidence that can lead to the biggest difference. METHODS: Seven versions of a questionnaire were mailed to randomly selected active family practice physicians and internists across the United States. They were asked about the perceived values of evidence from randomized controlled trials, locally developed recommendations, no evidence, cost-effectiveness studies, expert opinion, epidemiologic studies, and clinical studies. Analysis of variance and pairwise comparisons were used for statistical testing. RESULTS: Seventy-six (52%) physicians responded. On a Likert scale from one to six, randomized controlled clinical trial was the highest rated evidence (mean 5.07, SD +/- 1.14). Such evidence was significantly superior to locally developed recommendations and no evidence at all (P < .05). The interaction was also strong between the types of evidence and clinical areas (P = .0001). CONCLUSION: While most health care organizations present data without interpretation or simply try to enforce locally developed recommendations, such approaches appear to be inferior to techniques of reporting data with pertinent controlled evidence from the literature. Investigating physicians' perceptions is likely to benefit the design of computer generated messages.

Regional differences in mucosal hemodynamics in experimental colonic injury in rats.

In rat colon damaged by 10% acetic acid and by dinitrochlorobenzene, we test the following hypotheses: (1) mucosal hemodynamic changes are significantly different at the ulcer base, the ulcer margin, and the inflamed non-ulcer-bearing mucosa; and (2) these mucosal hemodynamic changes also vary with time after induction of the colonic injury. Mucosal hemodynamic changes were documented by reflectance spectrophotometry, and variations in gross mucosal morphology were confirmed by hematoxylin and eosin histologic sections. Results revealed that in the acute stage, the ulcer base, which was covered by necrotic debris, showed ischemia without congestion. The ulcer margin at the edge of the ulcer base showed ischemia with congestion. The nonulcerated mucosa, which appeared erythematous, showed increased perfusion. In the convalescent stage, all the altered perfusion patterns returned to normal. These observations offer plausible explanations for the variability in colonic perfusion observed in experimentally damaged colons.

Effects of cyclooxygenase and lipoxygenase inhibition on eicosanoids and healing of acetic acid colitis in rats.

Both cyclooxygenase products, such as prostaglandin (PG) E2, and lipoxygenase products, such as leukotriene (LT) B4, are increased in colitis and have potent proinflammatory actions. We studied effects of specific inhibitors of cyclooxygenase and 5-lipoxygenase on the healing of acetic acid colitis in rats. Acetic acid colitis was induced 24 hr before enzyme inhibition began. Four days after induction of colitis, the area of gross colonic mucosal damage was determined by image analysis. Eicosanoid content in the intestinal lumen was quantitated by radioimmunoassay following chromatographic purification. Under these conditions, indomethacin significantly retarded the healing of colonic lesions and inhibited PGE2 by > 90% compared to placebo-treated colitis rats. AA861 had no effect on the healing of lesions, although > 75% inhibition of leukotriene synthesis was demonstrated. These results suggest that inhibition of endogenous colonic prostaglandins can impair healing mechanisms in acute colitis even after inflammation has developed. In contrast, inhibition of leukotriene synthesis did not affect healing.

Superior mesenteric artery is more important than inferior mesenteric artery in maintaining colonic mucosal perfusion and integrity in rats.

Mucosal hemodynamics (by reflectance spectrophotometry) and mucosal damage (by histologic examination) following acute colonic ischemia were evaluated in different anatomic locations in the colon of anesthetized rats. The reflectance spectrophotometer provides an index of mucosal hemoglobin concentration (IHB) and an index of oxygen saturation of hemoglobin (ISO2). The patterns of ischemia without congestion (decreases IHB, decreases ISO2) during superior mesenteric artery occlusion, and ischemia with congestion (increases IHB, decreases ISO2) during portal vein occlusion, previously demonstrated in the stomach and duodenum, are also applicable to the colon. The significant linear correlations between changes (as percent of baseline) in IHB, ISO2, and hydrogen gas clearance suggest that changes in these indices are adequate indicators of changes in colonic mucosal perfusion. Superior mesenteric artery ligation produced significant reductions in both indices, and an increase in damage in the mucosa of the cecum, transverse colon, splenic flexure, and left colon, but not the rectum. Inferior mesenteric artery ligation produced only slight reduction in these indices and minimal damage only in the mucosa of the splenic flexure. These results support the hypothesis that the superior mesenteric artery is more important than the inferior mesenteric artery in maintaining colonic perfusion and colonic mucosal integrity in the rat.

Regional differences in gut blood flow and mucosal damage in response to ischemia and reperfusion.

Ischemia and reperfusion of the small intestine and colon in rats were produced by reversible occlusion (for 30 min and 1 or 3 h) of the superior mesenteric artery and the aorta above the inferior mesenteric artery. Despite a greater reduction of mucosal perfusion in the colon than in the small intestine with 30 min of ischemia, the depth of mucosal damage was significantly smaller in the former than in the latter. Thirty minutes of ischemia followed by 1 h of reperfusion induced an increase in polymorphonuclear leukocyte infiltration in both locations. Exacerbation of mucosal injury occurred only in the small intestine, suggesting that reperfusion injury is independent of polymorphonuclear leukocyte infiltration. Reperfusion after 1 or 3 h of ischemia did not exacerbate mucosal damage in either location. Allopurinol significantly diminished the exacerbation of injury after reperfusion in the small intestine. The protective effect of allopurinol, however, was neither associated with an improvement in perfusion nor a reduction in polymorphonuclear leukocyte infiltration. These data indicate that there is a window (30 min) of reperfusion injury in the small intestine, but there is no evidence of reperfusion injury in the colon.

Assessment of mucosal hemodynamics in normal human colon and patients with inflammatory bowel disease.

Reflectance spectrophotometry measures indices of mucosal hemoglobin concentration (IHB) and oxygen saturation (ISO2). In the rat colon, characteristic patterns of IHB and ISO2 are associated with ischemia with congestion (increased IHB and decreased ISO2) and ischemia without congestion (decreased IHB and decreased ISO2). Endoscopic measurements with acceptable interobserver variability was demonstrated in the canine stomach. In eight healthy subjects, endoscopic measurement in different areas of the colon and rectum revealed significantly lower IHB values in the splenic flexure. These observations are compatible with reduced flow and increased susceptibility to ischemic damage in this watershed area. The endoscopic measurements in 13 patients with active inflammatory bowel disease revealed an increase in IHB and ISO2 values in the involved areas, indicating an increase in mucosal blood flow. In six patients restudied when the disease remitted, these values returned to normal.

Design, construction, and analysis of a continuous-temperature infrared calibrator for temperature measurement using an infrared scanner.

A continuous-temperature infrared calibrator is designed and constructed for providing reference video signals in temperature measurement using an infrared scanner. The calibrator can be controlled for a wide range of temperature settings and to present a continuous span of reference signals for calibration purposes. Both analytical and experimental methods are used to evaluate the performance of the calibrator. Results show that the calibrator has a normal total emissivity of at least 0.984, which is about 1% lower than the predicted value. Methods to improve the emissivity of the calibrator are also discussed. The paper provides for analytical equations useful for parameters estimation in the future design of the calibrator.