Different Relationships between FENO and COPD Characteristics in Smokers and Ex-Smokers.

Exhaled nitric oxide (FENO) is a marker of type-2 inflammation in asthma and is used in its management. However, smokers and ex-smokers have lower FENO values, and the clinical use of FENO values in COPD patients is unclear. Therefore, we investigated if FENO had a relationship to different COPD characteristics in smoking and ex-smoking subjects. Patients with COPD (n = 533, 58% females) were investigated while in stable condition. Measurements of FENO50, blood cell counts, IgE sensitisation and lung function were performed. Medication reconciliation was used to establish medication usage. Smokers (n = 150) had lower FENO50 9 (8, 10) ppb (geometric mean, 95% confidence interval) than ex-smokers did (n = 383) 15 (14, 16) ppb, p < 0.001. FENO50 was not associated with blood eosinophil or neutrophil levels in smokers, but in ex-smokers significant associations were found (r = 0.23, p < 0.001) and (r = -0.18, p = 0.001), respectively. Lower FENO values were associated with lower FEV1% predicted in both smokers (r = 0.17, p = 0.040) and ex-smokers (r = 0.20, p < 0.001). Neither the smokers nor ex-smokers with reported asthma or IgE sensitisation were linked to an increase in FENO50. Ex-smokers treated with inhaled corticosteroids (ICS) had lower FENO50 14 (13, 15) ppb than non-treated ex-smokers 17 (15, 19) ppb, p = 0.024. This was not found in smokers (p = 0.325). FENO is associated with eosinophil inflammation and the use of ICS in ex-smoking COPD subjects, but not in smoking subjects suggesting that the value of FENO as an inflammatory marker is more limited in smoking subjects. The association found between low FENO values and low lung function requires further investigation.

Commonly used reference values underestimate oxygen uptake in healthy, 50-year-old Swedish women.

Cardiopulmonary exercise testing (CPET) is the gold standard among clinical exercise tests. It combines a conventional stress test with measurement of oxygen uptake (VO2 ) and CO2 production. No validated Swedish reference values exist, and reference values in women are generally understudied. Moreover, the importance of achieved respiratory exchange ratio (RER) and the significance of breathing reserve (BR) at peak exercise in healthy individuals are poorly understood. We compared VO2 at maximal load (peakVO2 ) and anaerobic threshold (VO2@AT ) in healthy Swedish individuals with commonly used reference values, taking gender into account. Further, we analysed maximal workload and peakVO2 with regard to peak RER and BR. In all, 181 healthy, 50-year-old individuals (91 women) performed CPET. PeakVO2 was best predicted using Jones et al. (100·5%), while SHIP reference values underestimated peakVO2 most: 112·5%. Furthermore, underestimation of peakVO2 in women was found for all studied reference values (P<0·001) and was largest for SHIP: women had 128% of predicted peakVO2 , while men had 104%. PeakVO2 was similar in subjects with peak RER of 1-1·1 and RER > 1·1 (2 328·7 versus 2 176·7 ml min-1 , P = 0·11). Lower BR (≤30%) related to significantly higher peakVO2 (P<0·001). In conclusion, peakVO2 was best predicted by Jones. All studied reference values underestimated oxygen uptake in women. No evidence for demanding RER > 1·1 in healthy individuals was found. A lowered BR is probably a normal response to higher workloads in healthy individuals.

Large Buffering Effect of the Duodenal Bulb in Duodenal Switch: a Wireless pH-Metric Study.

INTRODUCTION: Bariatric procedures result in massive weight loss, however, not without side effects. Gastric acid is known to cause marginal ulcers, situated in the small bowel just distal to the upper anastomosis. We have used the wireless BRAVO™ system to study the buffering effect of the duodenal bulb in duodenal switch (DS), a procedure in which the gastric sleeve produces a substantial amount of acid. METHODS: We placed a pre- and a postpyloric pH capsule in 15 DS-patients (seven men, 44 years, BMI 33) under endoscopic guidance and verified the correct location by fluoroscopy. Patients were asked to eat and drink at their leisure, and to register their meals for the next 24 h. RESULTS: All capsules but one could be successfully placed, without complications. Total registration time was 17.2 (1.3-24) hours prepyloric and 23.1 (1.2-24) hours postpyloric, with a corresponding pH of 2.66 (1.74-5.81) and 5.79 (4.75-7.58), p < 0.01. The difference in pH between the two locations was reduced from 3.55 before meals to 1.82 during meals, p < 0.01. Percentage of time with pH < 4 was 70.0 (19.9-92.0) and 13.0 (0.0-34.6) pre and postpylorically, demonstrating a large buffering effect. CONCLUSION: By this wireless pH-metric technique, we could demonstrate that the duodenal bulb had a large buffering effect, thus counteracting the large amount of gastric acid passing into the small bowel after duodenal switch. This physiologic effect could explain the low incidence of stomal ulcers.

Cardiac function after hematopoietic cell transplantation: an echocardiographic cross-sectional study in young adults treated in childhood.

BACKGROUND: Hematopoietic cell transplantation (HCT) including preparative regimens with chemotherapy and total body irradiation (TBI) is an accepted treatment for many malignant disorders but may have side-effects for several organs, including the cardiovascular system. The aim of this study was to study very long-term consequences on cardiac function after childhood HCT. PROCEDURE: Cardiac function was evaluated using echocardiography and levels of NT-proBNP and growth hormone (GHmax) in 18 patients, at a median of 18 years after HCT including TBI, and in 18 matched controls. RESULTS: Patients after HCT had cardiac dimensions, volumes, and left ventricular ejection fractions within normal range after correction for body size. However, compared with the control group, patients after HCT had significantly lower E/A ratio, as a measure of left ventricular diastolic function, significantly lower fractional shortening and mitral annular plane systolic excursion, as measures of left ventricular systolic function, significantly lower tricuspid annular plane systolic excursion, as a measure of right ventricular function, and significantly higher NT-proBNP, as a measure of total cardiac function. Also, pulmonary flow acceleration time was shorter in the group after HCT, indicating possible pulmonary involvement. Heart rate was significantly higher and GHmax significantly lower in patients after HCT. CONCLUSIONS: Almost two decades after HCT, including preparative regimens with TBI, cardiac function in patients was found to be within normal range. However, when compared with a healthy control group, patients after HCT showed lower systolic and diastolic left ventricular function as well as lower right ventricular function.

Exercise-induced dyspnea is a problem among the general adolescent population.

RATIONALE: Respiratory symptoms during exercise are common and might limit adolescents' ability to take part in physical activity. OBJECTIVE: To estimate the prevalence, determinants and consequences of exercise-induced dyspnea (EID) on daily life in a general population of 12-13 year old adolescents. METHODS: A letter was sent to the parents of all 12-13 year old adolescents in the city of Uppsala (n = 3838). Parents were asked to complete a questionnaire together with their child on EID, asthma and allergy, consequences for daily life (wheeze, day time- and nocturnal dyspnea) and physical activity. The response rate was 60% (n = 2309). RESULTS: Fourteen percent (n = 330) reported EID, i.e. had experienced an attack of shortness of breath that occurred after strenuous activity within the last 12 months. Female gender, ever-asthma and rhinitis were independently associated with an increased risk of EID. Ever-asthma was reported by 14.6% (n = 338), and 5.4% (n = 128) had both EID and ever-asthma. Sixty-one percent (n = 202) of the participants with EID did not have a diagnosis of asthma. In addition to rhinitis, participants with EID reported current wheeze and day-time as well as nocturnal dyspnea more often than the group without EID. No difference was found in the level of physical activity between participants with and without EID. CONCLUSION: Adolescents with undiagnosed exercise-induced dyspnea have respiratory symptoms and are affected in daily life but have the same level of physical activity as adolescents without exercise-induced respiratory symptoms.

Pulmonary function after autologous bone marrow transplantation in children: a long-term prospective study.

We performed serial pulmonary function tests (PFTs) consisting of spirometry and diffusing capacity in 26 children after BMT. The median follow-up was 10 years. The influence of total body irradiation (TBI) on long-term pulmonary function was of particular interest. In the 20 children who had received TBI, after an initial decrease the PFTs showed recovery, but the mean lung volumes were still significantly decreased 5 years after BMT at 10% below baseline. The proportions of children with restrictive impairment 5 and 10 years after BMT were 20 and 21%, respectively. Only one child was diagnosed with obstructive impairment. The proportions of children with isolated diffusing impairment at 5 and 10 years were 7/20 (35%) and 7/13 (54%), respectively. Six children had received chemotherapy only and showed isolated diffusing impairment as the only long-term sequela in 4/5 and 1/3 at 5 and 10 years. Our main finding was that there was little change in PFTs 1-10 years after BMT. TBI was associated with persistently decreased lung volumes in a proportion of patients, whereas chemotherapy also might have been of importance for the development of impaired gas exchange.

Delayed gastric emptying in patients with diffuse versus limited systemic sclerosis, unrelated to gastrointestinal symptoms and myoelectric gastric activity.

OBJECTIVE: To study the gastric function in patients with diffuse and limited systemic sclerosis (SSc) in relation to the degree of upper gastrointestinal symptoms. METHODS: Scintigraphic gastric emptying and recording of the myoelectric signals of the stomach were examined in 15 patients with diffuse SSc (dSSc), 13 patients with limited SSc (lSSc) and 15 healthy controls. The frequency of upper gastrointestinal symptoms was determined using a questionnaire. RESULTS: Patients with dSSc had slower gastric emptying (scintigraphic gastric half-emptying time median (Md) 103 min, range 75-447 min) than control subjects (Md 70 min, range 38-94) and patients with lSSc (Md 76 min, range 43-460). Electrogastrographic recordings did not differ between dSSc, lSSc or controls. Symptoms tended to be more abundant in dSSc patients than in lSSc patients, however, patients with a high frequency of symptoms did not differ from patients with low frequency of symptoms in gastric function, as measured with scintigraphic gastric emptying or electrogastrography (EGG). Neither EGG nor a thorough review of upper gastrointestinal symptoms could predict delayed gastric emptying. CONCLUSION: The higher prevalence of delayed gastric emptying in patients with dSSc in this study indicates a more severe involvement of the gastrointestinal tract in dSSc than in lSSc, and stresses the importance of differentiating between the subtypes of SSc patients. Since EGG dysrythmia did not correlate with gastric emptying we concluded that factors other than defective myoelectric signals might contribute to a disturbed gastric function.

Increased nitric oxide elimination from the airways after smoking cessation.

Smokers have been found to have low exhaled nitric oxide (NO) levels. The aim of the present study was to investigate where in the respiratory system the decrease in NO occurs, and whether this decrease was affected by smoking cessation. Measurements of exhaled NO were carried out in smokers (n=20) and non-smoking control subjects (n=30). In nine of the smokers, exhaled NO was analysed 1, 2 and 4 weeks after smoking cessation. The level of exhaled NO at a flow rate of 0.1 litre/s was significantly lower in smokers (4+/-2 p.p.b.) than in non-smokers (7+/-5 p.p.b.; P=0.007). A calculation of the contributions from different areas of the lung showed that the NO flux from the airways was significantly lower (14+/-10 compared with 36+/-26 nl/min; P=0.0001) and the alveolar fraction was significantly higher (2.1+/-0.8 compared with 1.5+/-0.9 p.p.b.; P=0.006) in smokers than in non-smokers. Nine smoking subjects refrained from smoking for 4 weeks, and this resulted in increased NO flux from the airways of 28+/-17 nl/min, which was no longer significantly different from controls. In conclusion, endogenous production of NO in the airways is decreased in smokers, but can be restored to normal values by 4 weeks after cessation of smoking. Smokers have an increased alveolar fraction of NO, and this might be a diagnostic sign of lung damage. Thus NO monitoring can be used to indicate improvements when a smoker decides to stop smoking.

Extended NO analysis applied to patients with COPD, allergic asthma and allergic rhinitis.

The recommended method to measure exhaled nitric oxide (NO) cannot reveal the source of NO production. We applied a model based on the classical Fick's first law of diffusion to partition NO in the lungs. The aim was to develop a simple and robust solution algorithm with a data quality control feature, and apply it to patients with known alterations in exhaled NO. Subjects with allergic rhinitis, allergic asthma, chronic obstructive pulmonary disease (COPD) smokers and controls were investigated. NO was measured at three expiratory flow rates. An iteration method was developed to partition NO. The airway tissue content of NO was increased in asthma, 144 +/- 80 ppb (P = 0.04) and decreased in smokers, 56 +/- 36 ppb (P = 0.02). There was no difference between subjects with rhinitis, 98 +/- 40 ppb and controls, 98 +/- 44 ppb. The airway transfer rate was increased in allergic asthma and allergic rhinitis, 12 +/- 4 vs. 12 +/- 5 ml sec(-1), compared to controls, 8 +/- 2 ml sec(-1) (P < 0.001). The alveolar levels were no different from controls, 2 +/- 1 ppb. In COPD the alveolar levels were increased, 4 +/- 2 ppb (P < 0.001). Extended NO analysis reveals from where in the respiratory system NO is generated. Hence, this new test can be added to the tools the physician has for the diagnosis and treatment of patients with respiratory disorders.

Investigation of the excluded stomach after Roux-en-Y gastric bypass.

BACKGROUND: One problem with Roux-en-Y gastric bypass (RYGBP) is that it leaves the bypassed segment not readily available for endoscopic or radiographic examinations. MATERIALS AND METHODS: Three males, 50, 54 and 64 years old, suffered from repeated, gastrointestinal bleeding of unknown origin requiring transfusion 1/2, 1 and 7 years after RYGBP. Access to the stomach was obtained by an ultrasound-guided percutaneous gastrostomy. RESULTS: We could perform endoscopy, barium studies and gastric acid output measurements through the gastrostomy. Histological gastritis, low acid output and absence of H. pylori infection were found. CONCLUSION: We were able to exclude severe gastric disease in our patients.

Inhaled mannitol shifts exhaled nitric oxide in opposite directions in asthmatics and healthy subjects.

We investigated if healthy subjects could release NO upon hyperosmolar challenge as a defence mechanism, and whether asthmatics with atopy showed an altered response. A plot of NO output versus flow rate was used to calculate the alveolar level and the NO-flux from the airways. The asthmatics had a higher NO output and this was due to an increased NO-flux from the airways, 86+/-30 nl min(-1) compared with control 21+/-2 nl min(-1) (P<0.05). The alveolar NO levels showed no difference. In response to a dry powder of mannitol the exhaled NO concentration decreased in asthmatics by 37+/-7%, but increased in the control by 9+/-4% (P<0.001). The FEV(1.0) decreased 13+/-2% and airway conductance 42+/-7% in asthmatics and in the controls 2+/-1% and 0+/-7%, respectively (P<0.001). We conclude that asthmatics have an altered response to mannitol challenge in regards to exhaled NO. This may result from down regulation of constitutive NO production as a result of high levels of NO flux from the airways.

Different airway responsiveness profiles in atopic asthma, nonatopic asthma, and Sjögren's syndrome. BHR Study Group. Bronchial hyperresponsiveness.

BACKGROUND: Different mechanisms may underlie bronchial hyperresponsiveness (BHR) in different diseases. The aim of this study was to investigate the bronchial responsiveness profile produced by three different challenge tests, methacholine, a direct stimulus, and two indirect stimuli, adenosine 5'-monophosphate (AMP) and cold air, in subjects with asthma and patients with Sjögren's syndrome. METHODS: The study population comprised 40 adult patients with asthma, 18 subjects with Sjögren's syndrome, and 20 controls. Blood samples were collected before each challenge for measurements of serum eosinophil peroxidase (S-EPO) and eosinophil cationic protein (S-ECP). The investigated subjects recorded peak expiratory flow and kept a symptom diary. RESULTS: Atopic subjects with asthma were significantly more hyperresponsive to AMP than nonatopic subjects with asthma (P=0.01) and subjects with Sjögren's syndrome (P=0.02). No difference was seen between atopic and nonatopic subjects with asthma in the case of challenges with methacholine or cold air. In atopic subjects with asthma, a significant correlation was found between challenges with methacholine and AMP (r=0.91, P=0.0001) and methacholine and cold air (r=0.83, P=0.004), but, in nonatopic subjects with asthma, no significant correlation was seen between methacholine and AMP or cold air challenges. In atopic subjects with asthma, the dose-response slope for AMP was correlated to S-EPO (r= -0.56; P = 0.01) and S-ECP (r= -0.51, P = 0.02), while no correlation between BHR and inflammation markers was found in the two other patient groups. CONCLUSIONS: The results of this study suggest that patients with asthma and subjects with Sjögren's syndrome display different bronchial responsiveness profiles for different challenge agents. Atopic subjects with asthma are more hyperresponsive to AMP than nonatopic subjects and patients with Sjögren's syndrome. More than one challenge may be required to detect different aspects of bronchial responsiveness.

Exhaled nitric oxide and its relationship to airway responsiveness and atopy in asthma. BHR-Study Group.

Exhaled nitric oxide (NO) has attracted increasing interest as a non-invasive marker of airway inflammation. The purpose of this study was to determine whether exhaled nitric oxide in subjects with asthma varied according to their atopic status and to examine its correlation with airway hyperresponsiveness and lung function measurements. Forty patients with asthma and 13 controls participated in the study. Nitric oxide was measured on three occasions with intervals of at least 3 days, using a chemiluminescence method. Airway responsiveness was assessed with methacholine challenge and lung function measurements were made. All subjects recorded peak expiratory flow and kept a symptom diary during a 17-day period. There was no significant difference in lung function measurements, peak expiratory flow or symptom score between the two asthma groups. Atopic patients with asthma had a significantly higher mean amount of exhaled NO than non-atopic subjects with asthma (162 +/- 68 vs. 113 +/- 55 nl min-1; P = 0.03) and the control group (88 +/- 52 nl min-1; P = 0.004). No significant difference was found in the amount of exhaled NO between non-atopic patients with asthma and the controls. In atopic subjects with asthma the mean exhaled NO was significantly correlated to the dose-response slope for methacholine (r = -0.52; P = 0.02), while no such correlation was found in the non-atopic group. In conclusion; in this study, atopic subjects with asthma had higher levels of exhaled NO than non-atopic subjects. Atopic status should be taken into account when measuring levels of exhaled NO in subjects with asthma.

Comparison of two methacholine challenge methods using Spira-2 or Mefar dosimeter.

Two bronchial challenge protocols with breath-actuated dosimeters, Spira Elektro-2 and Mefar, with similar cumulative dose steps were compared in 28 patients with mild to moderate asthma. Methacholine challenges were performed after two different protocols at the same time of day in random order 3 or 4 days apart. The provocative dose of methacholine producing a 20% fall in forced expiratory volume in 1 second (PD20) was lower when determined by Spira than with the Mefar dosimeter (P < 0.05). Transition equations calculated by linear regression analysis were: PD20mefar = exp10[0.897 + 0.678(logPD20spira)] (P < 0.05; r = 0.62) and PD20spira = exp10[0.759 + 0.559 (log PD20mefar)] (P < 0.05; r = 0.62). The slopes were calculated by regressing the percentage fall in FEV1 on log10 (dose) and transformed as slope = 100/(regression coefficient + 10). The mean slope (95% CI) for Spira was 3.1 (2.6-3.7) and for Mefar 4.4 (3.6-5.1) (P < 0.005). Regression equations calculated by linear regression analysis were: slope(mefar) = 2.126 + 0.712 slope(spira) (P < 0.05; r = 0.51) and slope(spira) = 1.551 + 0.365 slope(mefar) (P < 0.05; r = 0.51). In conclusion, PD20 was smaller and the decline in FEV1/log(dose) curve steeper using the Spira compared with the Mefar protocol. The dose-response curves should be validated and transition equations calculated when bronchial reactivity to inhaled agents is compared, even while using apparently similar well-standardized dosimeter methods.

Ozone-induced lung function decrements do not correlate with early airway inflammatory or antioxidant responses.

This study sought to clarify the early events occurring within the airways of healthy human subjects performing moderate intermittent exercise following ozone challenge. Thirteen healthy nonsmoking subjects were exposed in a single blinded, crossover control fashion to 0.2 parts per million (ppm) O3 and filtered air for 2 h, using a standard intermittent exercise and rest protocol. Lung function was assessed pre- and immediately post-exposure. Bronchoscopy was performed with endobronchial mucosal biopsies, bronchial wash (BW) and bronchoalveolar lavage (BAL) 1.5 h after the end of the exposure period. Respiratory tract lining fluid (RTLF) redox status was assessed by measuring a range of antioxidants and oxidative damage markers in BW and BAL fluid samples. There was a significant upregulation after O3 exposure in the expression of vascular endothelial P-selectin (p<0.005) and intercellular adhesion molecule-1 (p<0.005). This was associated with a 2-fold increase in submucosal mast cells (p<0.005) in biopsy samples, without evidence of neutrophilic inflammation, and a decrease in BAL fluid macrophage numbers (1.6-fold, p<0.005), with an activation of the remaining macrophage subset (2.5-fold increase in % human leukocyte antigen (HLA)-DR+ cells, p<0.005). In addition, exposure led to a 4.5-fold and 3.1-fold increase of reduced glutathione (GSH) concentrations, in BW and BAL fluid respectively (p<0.05), with alterations in urate and alpha-tocopherol plasma/RTLF partitioning ratios (p<0.05). Spirometry showed reductions in forced vital capacity (p<0.05) and forced expiratory volume in one second (p<0.01), with evidence of small airway narrowing using forced expiratory flow values (p<0.005). Evidence was found of O3-induced early adhesion molecule upregulation, increased submucosal mast cell numbers and alterations to the respiratory tract lining fluid redox status. No clear relationship was demonstrable between changes in these early markers and the lung function decrements observed. The results therefore indicate that the initial lung function decrements are not predictive of, or causally related to the O3-induced inflammatory events in normal human subjects.

Rapid effect of lansoprazole on intragastric pH: a crossover comparison with omeprazole.

BACKGROUND: The time to onset of acid inhibition is considered an important factor when treating patients with reflux symptoms. This study was therefore designed to investigate the effect of 30 mg lansoprazole and 20 mg omeprazole on gastric pH after single-dose administration. METHODS: The study was of a randomized, open-label, single-dose and two-way crossover design with a washout period of at least 7 days in between. Fifteen healthy adult male and female subjects were included. The subjects were intubated with a pH catheter. Intragastric pH was measured every 4th sec for 10 min before and during 8 h after drug administration. Blood samples, for determination of plasma concentrations of lansoprazole and omeprazole, were obtained on 10 occasions during 6 h after drug administration. The area under the curve (AUC), the elimination halflife (t1/2), and the peak concentration (Cmax) of the two drugs were calculated. RESULTS: All subjects completed the study without major complications. The mean pH (0-8 h) after drug administration was 2.9 for lansoprazole and 2.0 for omeprazole (P = 0.0058). A pH of more than 4 was reached for the first time after 130 min with lansoprazole and after 250 min with omeprazole. AUC was 4919 +/- 2526 nmol/l x h for lansoprazole and 1352 +/- 1120 nmol/l x h for omeprazole. CONCLUSION: Single-dose administration of 30 mg lansoprazole is followed by a rapid absorption of the drug and hence a more efficient acid suppression than after single-dose administration of 20 mg omeprazole in healthy volunteers.

Increased nitric oxide in expired air in patients with Sjögren's syndrome. BHR study group. Bronchial hyperresponsiveness.

Nitric oxide has an important role in the regulation of airway function and can have pro-inflammatory effects. Bronchial hyperresponsiveness (BHR) and respiratory symptoms are common in patients with Sjögren's syndrome (SS). The aim of this study was to determine whether patients with SS have an increased amount of exhaled NO and whether this NO correlates with respiratory symptoms and BHR. Exhaled NO was measured in 18 patients with SS and 13 normal subjects on three different occasions with intervals of at least 3 days using a chemiluminescence method. Airway responsiveness was assessed with methacholine provocation. Serum levels of myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO) were measured. Exhaled NO was significantly higher in patients with SS than in controls (147+/-82 versus 88+/-52 nL x min(-1); mean+/-SD; p=0.041). Exhaled NO was correlated with age (partial r=0.52, p=0.006) and serum HNL (partial r=0.46, p=0.014). There were no significant correlations between exhaled NO and respiratory symptoms, BHR or serum MPO, ECP or EPO. Disease duration was negatively associated with serum MPO (r=-0.47, p=0.043). In patients with SS, a positive correlation was found between symptom score and serum ECP (partial r=0.65, p=0.003) and EPO (partial r=0.62, p=0.004) and a negative correlation with age (partial r=-0.60, p=0.005). In conclusion, elevated levels of exhaled nitric oxide in patients with Sjögren's syndrome were demonstrated. The mechanism underlying this increase in exhaled nitric oxide in Sjögren's syndrome is not known.

Computed tomographic measurement of lung density changes in lung water with hemodialysis.

In 10 hemodialysis patients, with an ultrafiltration volume ranging from 1 to 4.5 liters per session, the lung density was measured by computed tomography (CT) and the lung volumes by total body plethysmography. From the CT numbers (difference in X-ray attenuation between lung and water, measured in Hounsfield units, HU), and by using a special computer program, quantitative estimates of the densities of normally inflated (pixels between -1,000 and -500 HU), poorly inflated (pixels between -500 and -100 HU) and noninflated lung tissue (pixels between -100 and +100 HU) were obtained. The sizes of the normally and poorly inflated areas were also measured. The results showed that, after dialysis, the normally inflated area was decreased in density and increased in size, and conversely, the size of the poorly inflated area was diminished but without change in density. This finding implied introduction of more gas into the lung. The above observation was reflected by the results of pulmonary function measurements, in that the total lung capacity and functional residual capacity were significantly increased after dialysis. In conclusion, changes in lung fluid (both intra- and extravascular) with hemodialysis can be measured quantitatively by the changes in lung density as estimated by the CT densitometry technique.

Intragastric pH after oral administration of single doses of ranitidine effervescent tablets, omeprazole capsules and famotidine fast-dissolving tablets to fasting healthy volunteers.

BACKGROUND: The therapeutic effect of drugs inhibiting acid production on acid-related discomforts is related to both the onset and duration of action of the drug. The effects on gastric pH by single oral doses of some acid-inhibiting drugs were investigated by measuring daytime (morning to lunch) intragastric pH in healthy volunteers. METHODS: This randomized, single-dose, 4-way crossover study included 15 healthy fasting subjects. Effervescent ranitidine tablets 150 and 300 mg, fast-dissolving famotidine tablets 20 mg and capsules of omeprazole 20 mg were administered. Measurements of intragastric pH were performed every 4 s for 10 min prior to drug administration and during the following 4 h. RESULTS: The effervescent ranitidine tablets (150 or 300 mg) produced similar changes in intragastric pH: following an immediate increase to about pH 5, intragastric pH decreased slightly over the next 10-20 min. Thereafter pH increased steadily, reaching pH 4 after 20-40 min and pH 6 after about 70 min. After famotidine, pH 4 was reached after 80 min, significantly slower than ranitidine. After omeprazole, pH 3 was never reached. Ranitidine 150 and 300 mg showed significantly larger integrated pH responses over the 4-h observation period, compared to famotidine (P = 0.0288 and 0.0074) or omeprazole (P < 0.001). CONCLUSIONS: After single-dose administration to healthy fasting volunteers), ranitidine effervescent tablets showed a significantly more rapid onset of action and a significantly larger integrated pH response compared to either famotidine 20 mg fast-dissolving tablets or omeprazole 20 mg capsules.

Lung density for assessment of hydration status in hemodialysis patients using the computed tomographic densitometry technique.

The density of the lung reflects the total mass of fluid, air, and dry lung tissue per unit volume of the lung. Lung density can be measured by evaluation of attenuation of an electron beam with computed tomography (CT). This technique has been shown to be sufficiently reliable and sensitive to distinguish normal from abnormal lung water. The aim of this study was to find out whether lung density properly reflects the hydration status in hemodialysis patients in comparison with other standard methods. Fourteen hemodialysis patients, with an ultrafiltration ranging from 0.3 to 4.5 liters per session, underwent CT measurements of lung density, ultrasonographic measurements of the diameter of the inferior vena cava after quiet expiration (IVCe) and quiet inspiration (IVCi), and measurements of the hematocrit and plasma levels of the biochemical hydration markers cyclic guanosine monophosphate (cGMP) and atrial natriuretic peptide (ANP). These measurements were performed before and 3.5 to 4 hours after termination of dialysis. Quantitative estimates of lung density were obtained within pixels with CT numbers ranging between -1000 and -100 Hounsfield Units (HU), and compared with normal data from 18 normal controls. In normal controls, the lung density ranged from -800 to -730 HU. In hemodialysis patients, lung density was significantly higher than normal before dialysis (-678 +/- 96 HU, P < 0.01) and significantly decreased after dialysis (-706 +/- 92 HU, P < 0.05), indicating a decrease in fluid content of the lung. The density was normalized in 5 patients. A significant correlation was found between lung density and IVCe both before and after dialysis (r = 0.8, P < 0.01 for both). Change in density was significantly correlated to amount of ultrafiltration (r = 0.67, P < 0.01) and percent change in blood volume (r = 0.63, P < 0.05), indicating that lung density is greatly affected by changes in the extracellular fluid volume, mainly the intravascular volume. In conclusion, lung water reflects the hydration status in hemodialysis patients and can be monitored by measuring the lung density by CT. Accordingly, normalization of lung density can help to achieve a proper dry weight in these patients.